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1. Simulating and Optimizing Preparative Protein Chromatography with ChromX

Author: Hahn, Tobias, Huuk, Thiemo, and Heuveline, Vincent
Abstract: Industrial purification of biomolecules is commonly based on a sequence of chromatographic processes, which are adapted slightly to new target components, as the time to market is crucial. To improve time and material efficiency, modeling is increasingly used to determine optimal operating conditions, thus providing new challenges for current and future bioengineers. At the Karlsruhe Institute of Technology (KIT), mechanistic modeling of protein chromatography has long been part of the curriculum of the Bioengineering master's degree program, supported by exercises using simulation software. Emphasis lies on nonlinear preparative chromatography, where the result strongly depends on the sample concentration. For undergraduate students to gain hands-on experience in model-based optimization, a three-week, in-depth laboratory course was designed on the purification of a ternary mixture of proteins using ion-exchange chromatography and mechanistic modeling. Students apply in-house software ChromX, which is made available for download, together with tutorials on numerics and practical applications. This article presents the working principle of ChromX and results of the laboratory course for undergraduate students.
Published: 2015
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2. Photonic Synthesis and Coating of High‐Entropy Oxide on Layered Ni‐Rich Cathode Particles

Author: Yanyan Cui, Yushu Tang, Jing Lin, Junbo Wang, Horst Hahn, Ben Breitung, Simon Schweidler, Torsten Brezesinski, and Miriam Botros
Subjects: cathodes, high‐entropy materials, Li1+x(Ni1−y−zCoyMnz)1−xO2 (NCM) coatings, Li‐ion batteries, photonic curings, Physics, QC1-999, Chemistry, QD1-999
Abstract: High‐entropy materials have drawn much attention as battery materials due to their distinctive properties. Lithiated high‐entropy oxide (Li0.33(MgCoNiCuZn)0.67O, LiHEO) exhibits both high lithium‐ion and electronic conductivity, making it a potential coating material for layered Ni‐rich oxide cathodes (Li1+x(Ni1−y−zCoyMnz)1−xO2, NCM or NMC) in conventional Li‐ion battery cells; however, high‐temperature synthesis limits its application. Therefore, a photonic curing strategy is used for synthesizing LiHEO and the non‐lithiated form (denoted as high‐entropy oxide [HEO]), and nanoscale coatings are successfully produced on LiNi0.85Co0.1Mn0.05O2 (NCM851005) particles. To one's knowledge, this is the first report on particle coating with high‐entropy materials using photonic curing. NCM851005 with LiHEO‐modified surface shows good cycling stability, with a capacity retention of 97% at 1 C rate after 200 cycles. The improvement in electrochemical performance is attributed to the conformal coating that prevents structural changes caused by the reaction between cathode material and liquid electrolyte. Compared to bare NCM851005, the coated material shows a significantly reduced tendency for intergranular cracking, successfully preventing electrolyte penetration and suppressing side reactions. Overall, photonic curing presents a novel cost‐ and energy‐efficient synthesis and coating procedure that paves the way for surface modification of any heat‐sensitive material for a wide range of applications.
Published: 2024
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3. A Microfluidic Paper-Based Lateral Flow Device for Quantitative ELISA

Author: Ashutosh Kumar, Cameron Hahn, Stephen Herchen, Alex Soucy, Ethan Carpio, Sophia Harper, Nassim Rahmani, Constantine Anagnostopoulos, and Mohammad Faghri
Subjects: lab-on-paper, microfluidic device, paper-based ELISA, multi-directional flow assay, point-of-care diagnostic, Physics, QC1-999, Microscopy, QH201-278.5, Microbiology, QR1-502, Chemistry, QD1-999
Abstract: This study presents an innovative lateral flow microfluidic paper-based analytical device (μPAD) designed for conducting quantitative paper-based enzyme-linked immunosorbent assays (p-ELISA), seamlessly executing conventional ELISA steps in a paper-based format. The p-ELISA device utilizes a passive fluidic circuit with functional elements such as a multi-bi-material cantilever (B-MaC) assembly, delay channels, and a buffer zone, all enclosed within housing for autonomous, sequential loading of critical reagents onto the detection zone. This novel approach not only demonstrates a rapid assay completion time of under 30 min, but also boasts reduced reagent requirements, minimal equipment needs, and broad applicability across clinical diagnostics and environmental surveillance. Through detailed descriptions of the design, materials, and fabrication methods for the multi-directional flow assay (MDFA), this manuscript highlights the device’s potential for complex biochemical analyses in a user-friendly and versatile format. Analytical performance evaluation, including a limit of detection (LOD) of 8.4 pM for Rabbit IgG, benchmarks the device’s efficacy compared to existing p-ELISA methodologies. This pioneering work lays the groundwork for future advancements in autonomous diagnostics, aiming to enhance global health outcomes through accessible and reliable testing solutions.
Published: 2024
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4. Introducing SpectraFit: An Open-Source Tool for Interactive Spectral Analysis

Author: Anselm W. Hahn, Joseph Zsombor-Pindera, Pierre Kennepohl, and Serena DeBeer
Subjects: Chemistry, QD1-999
Published: 2024
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5. Powering aircraft with 100 % sustainable aviation fuel reduces ice crystals in contrails

Author: R. S. Märkl, C. Voigt, D. Sauer, R. K. Dischl, S. Kaufmann, T. Harlaß, V. Hahn, A. Roiger, C. Weiß-Rehm, U. Burkhardt, U. Schumann, A. Marsing, M. Scheibe, A. Dörnbrack, C. Renard, M. Gauthier, P. Swann, P. Madden, D. Luff, R. Sallinen, T. Schripp, and P. Le Clercq
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: Powering aircraft by sustainable aviation fuels (SAFs) is a pathway to reduce the climate impact of aviation by lowering aviation lifecycle CO2 emissions and by reducing ice crystal numbers and radiative forcing from contrails. While the effect of SAF blends on contrails has been measured previously, here we present novel measurements on particle emission and contrails from 100 % SAF combustion. During the ECLIF3 (Emission and CLimate Impact of alternative Fuels) campaign, a collaboration between the Deutsches Zentrum für Luft- und Raumfahrt (DLR), Airbus, Rolls-Royce, and Neste, the DLR Falcon 20 research aircraft performed in situ measurements following an Airbus A350-941 source aircraft powered by Rolls-Royce Trent XWB-84 engines in 1 to 2 min old contrails at cruise altitudes. Apparent ice emission indices of 100 % HEFA-SPK (hydro-processed esters and fatty acids–synthetic paraffinic kerosene) were measured and compared to Jet A-1 fuel contrails at similar engine and ambient ice-supersaturated conditions within a single flight. A 56 % reduction in ice particle numbers per mass of burned fuel was measured for 100 % HEFA-SPK compared to Jet A-1 under engine cruise conditions. The measured 35 % reduction in soot particle numbers suggests reduced ice activation by the low-sulfur HEFA fuel. Contrail properties are consistently modeled with a contrail plume model. Global climate model simulations for the 2018 fleet conservatively estimate a 26 % decrease in contrail radiative forcing and stronger decreases for larger particle reductions. Our results indicate that higher hydrogen content fuels as well as clean engines with low particle emissions may lead to reduced climate forcing from contrails.
Published: 2024
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6. Factors Influencing Success in Physical Chemistry

Author: Hahn, Karen E. and Polik, William F.
Abstract: The factors correlating to the student success in physical chemistry courses are investigated. The influence of mathematics ability on student performance in class is examined.
Published: 2004

7. Improved Performance of High‐Entropy Disordered Rocksalt Oxyfluoride Cathode by Atomic Layer Deposition Coating for Li‐Ion Batteries

Author: Bei Zhou, Siyu An, David Kitsche, Sören L. Dreyer, Kai Wang, Xiaohui Huang, Jannik Thanner, Matteo Bianchini, Torsten Brezesinski, Ben Breitung, Horst Hahn, and Qingsong Wang
Subjects: atomic layer deposition, cathode–electrolyte interface, disordered rocksalt, lithium‐ion batteries, Physics, QC1-999, Chemistry, QD1-999
Abstract: Lithium‐excess cation‐disordered rocksalt materials are a promising class of transition metal‐based cathodes that exhibit high specific capacity and energy density. The exceptional performance is achieved through participation of anionic redox in addition to cationic redox reactions in the electrochemistry. However, anionic redox reactions accompanied by oxygen evolution, accelerated electrolyte breakdown, and structural evolution lead to voltage hysteresis and low initial Coulombic efficiency. Herein, an Al2O3 layer with varying thickness has been coated onto a high‐entropy disordered rocksalt oxyfluoride cathode through atomic layer deposition to enhance battery performance. The results indicate that the utilization of a uniform Al2O3 coating improves the capacity retention and rate capability of the cathode, with the performance being strongly dependent on the layer thickness. Further investigation into cathode–electrolyte interfacial reactions reveals that the thin protecting Al2O3 coating can reduce the decomposition of electrolyte on the cathode surface but cannot prevent bulk phase degradation during prolonged cycling. These findings highlight the need for optimized coating design on the disordered rocksalt cathode to improve battery performance.
Published: 2024
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8. Formation of CNHC∧Calkyl and CNHC∧Caryl κ2‑Chelate Complexes through Competitive sp3- and sp2‑CH Activations: An Experimental and Computational Study

Author: Matthias D. Böhme, Sebastian Termühlen, Patrick D. Dutschke, Alexander Hepp, and F. Ekkehardt Hahn
Subjects: Chemistry, QD1-999
Published: 2023
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9. Impact of Metal Ions on Cellular Functions: A Focus on Mesenchymal Stem/Stromal Cell Differentiation

Author: Kirsten Peters, Susanne Staehlke, Henrike Rebl, Anika Jonitz-Heincke, and Olga Hahn
Subjects: mesenchymal stem/stromal cells (MSCs), metal ions, metalloproteins, cell differentiation, oxidative stress, inflammation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Metals play a crucial role in the human body, especially as ions in metalloproteins. Essential metals, such as calcium, iron, and zinc are crucial for various physiological functions, but their interactions within biological networks are complex and not fully understood. Mesenchymal stem/stromal cells (MSCs) are essential for tissue regeneration due to their ability to differentiate into various cell types. This review article addresses the effects of physiological and unphysiological, but not directly toxic, metal ion concentrations, particularly concerning MSCs. Overloading or unbalancing of metal ion concentrations can significantly impair the function and differentiation capacity of MSCs. In addition, excessive or unbalanced metal ion concentrations can lead to oxidative stress, which can affect viability or inflammation. Data on the effects of metal ions on MSC differentiation are limited and often contradictory. Future research should, therefore, aim to clarify the mechanisms by which metal ions affect MSC differentiation, focusing on aspects such as metal ion interactions, ion concentrations, exposure duration, and other environmental conditions. Understanding these interactions could ultimately improve the design of biomaterials and implants to promote MSC-mediated tissue regeneration. It could also lead to the development of innovative therapeutic strategies in regenerative medicine.
Published: 2024
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10. miR-10a/b-5p-NCOR2 Regulates Insulin-Resistant Diabetes in Female Mice

Author: Se Eun Ha, Rajan Singh, Byungchang Jin, Gain Baek, Brian G. Jorgensen, Hannah Zogg, Sushmita Debnath, Hahn Sung Park, Hayeong Cho, Claudia Marie Watkins, Sumin Cho, Min-Seob Kim, Moon Young Lee, Tae Yang Yu, Jin Woo Jeong, and Seungil Ro
Subjects: microRNAs, diabetes mellitus, estrogen, pancreatic β-cells, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Gender and biological sex have distinct impacts on the pathogenesis of type 2 diabetes (T2D). Estrogen deficiency is known to predispose female mice to T2D. In our previous study, we found that a high-fat, high-sucrose diet (HFHSD) induces T2D in male mice through the miR-10b-5p/KLF11/KIT pathway, but not in females, highlighting hormonal disparities in T2D susceptibility. However, the underlying molecular mechanisms of this hormonal protection in females remain elusive. To address this knowledge gap, we utilized ovariectomized, estrogen-deficient female mice, fed them a HFHSD to induce T2D, and investigated the molecular mechanisms involved in estrogen-deficient diabetic female mice, relevant cell lines, and female T2D patients. Initially, female mice fed a HFHSD exhibited a delayed onset of T2D, but ovariectomy-induced estrogen deficiency promptly precipitated T2D without delay. Intriguingly, insulin (INS) was upregulated, while insulin receptor (INSR) and protein kinase B (AKT) were downregulated in these estrogen-deficient diabetic female mice, indicating insulin-resistant T2D. These dysregulations of INS, INSR, and AKT were mediated by a miR-10a/b-5p-NCOR2 axis. Treatment with miR-10a/b-5p effectively alleviated hyperglycemia in estrogen-deficient T2D female mice, while β-estradiol temporarily reduced hyperglycemia. Consistent with the murine findings, plasma samples from female T2D patients exhibited significant reductions in miR-10a/b-5p, estrogen, and INSR, but increased insulin levels. Our findings suggest that estrogen protects against insulin-resistant T2D in females through miR-10a/b-5p/NCOR2 pathway, indicating the potential therapeutic benefits of miR-10a/b-5p restoration in female T2D management.
Published: 2024
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11. Modeling Planar Electrodes and Zero‐Gap Membrane Electrode Assemblies for CO2 Electrolysis

Author: Dr. Victoria M. Ehlinger, Dr. Dong Un Lee, Dr. Tiras Y. Lin, Dr. Eric B. Duoss, Dr. Sarah E. Baker, Prof. Thomas F. Jaramillo, and Dr. Christopher Hahn
Subjects: Electrochemistry, Energy Conversion, Kinetics, Semiempirical Calculations, Sustainable Chemistry, Industrial electrochemistry, TP250-261, Chemistry, QD1-999
Abstract: Abstract Multiphysics modeling enables probing of conditions inside a CO2 electrolyzer that are difficult to measure, such as local concentrations and pH, as well as rapid testing of possible design changes. A one‐dimensional model for a zero‐gap membrane electrode assembly (MEA) CO2 electrolyzer was developed with the assumption that catalyst layers interact with the membrane ionomer such that the ionomer affects the underlying kinetics. The kinetics for bicarbonate reacting to form hydrogen are fit using a planar electrode model for silver with an ionomer coating. The MEA model results are validated against experimental studies for current density and product selectivity. Flooding of the cathode is modeled using saturation curves, and results show that blocked pores in the microporous layer play a significant role in limiting the mass transport at high potentials (>2.8 V). Sensitivity studies showed that CO Faradaic efficiency can be increased by decreasing catalyst layer thickness and porosity, and decreasing KHCO3 concentration.
Published: 2024
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12. Mortality Prediction by Kinetic Parameters of Lactate and S-Adenosylhomocysteine in a Cohort of Critically Ill Patients

Author: Jochen J. Schoettler, Kathrin Brohm, Sonani Mindt, Evelyn Jäger, Bianka Hahn, Tanja Fuderer, Holger A. Lindner, Verena Schneider-Lindner, Joerg Krebs, Michael Neumaier, Manfred Thiel, and Franz-Simon Centner
Subjects: organ dysfunction, lactate, s-adenosylhomocysteine, mortality prediction, critically ill patients, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death. We evaluated the performance of kinetic SAH parameters for mortality prediction compared with lactate parameters in a cohort of critically ill patients. For lactate and SAH, maxima and means as well as the normalized area scores were calculated for two periods: the first 24 h and the total study period of up to five days following ICU admission. Their performance in predicting in-hospital mortality were compared in 99 patients. All evaluated parameters of lactate and SAH were significantly higher in non-survivors compared with survivors. In univariate analysis, the predictive power for mortality of SAH was higher compared with lactate in all forms of application. Multivariable models containing SAH parameters demonstrated higher predictive values for mortality than models based on lactate parameters. The optimal models for mortality prediction incorporated both lactate and SAH parameters. Compared with lactate, SAH displayed stronger predictive power for mortality in static and dynamic application in critically ill patients.
Published: 2024
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13. The Immune Checkpoint BTLA in Oral Cancer: Expression Analysis and Its Correlation to Other Immune Modulators

Author: Jutta Ries, Leah Trumet, Alina Hahn, Lina Kunater, Rainer Lutz, Carol Geppert, Marco Kesting, and Manuel Weber
Subjects: BTLA, immune checkpoints, immune therapy, OSCC, oral squamous cell carcinoma, CD96, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: In oral squamous cell carcinoma (OSCC) tissues, an immunotolerant situation triggered by immune checkpoints (ICPs) can be observed. Immune checkpoint inhibitors (ICIs) against the PD1/PD-L axis are used with impressive success. However, the response rate is low and the development of acquired resistance to ICI treatment can be observed. Therefore, new treatment strategies especially involving immunological combination therapies need to be developed. The novel negative immune checkpoint BTLA has been suggested as a potential biomarker and target for antibody-based immunotherapy. Moreover, improved response rates could be displayed for tumor patients when antibodies directed against BTLA were used in combination with anti-PD1/PD-L1 therapies. The aim of the study was to check whether the immune checkpoint BTLA is overexpressed in OSCC tissues compared to healthy oral mucosa (NOM) and could be a potential diagnostic biomarker and immunological target in OSCC. In addition, correlation analyses with the expression of other checkpoints should clarify more precisely whether combination therapies are potentially useful for the treatment of OSCC. A total of 207 tissue samples divided into 2 groups were included in the study. The test group comprised 102 tissue samples of OSCC. Oral mucosal tissue from 105 healthy volunteers (NOM) served as the control group. The expression of two isoforms of BTLA (BTLA-1/2), as well as PD1, PD-L1/2 and CD96 was analyzed by RT-qPCR. Additionally, BTLA and CD96 proteins were detected by IHC. Expression levels were compared between the two groups, the relative differences were calculated, and statistical relevance was determined. Furthermore, the expression rates of the immune checkpoints were correlated to each other. BTLA expression was significantly increased in OSCC compared to NOM (pBTLA_1 = 0.003; pBTLA_2 = 0.0001, pIHC = 0.003). The expression of PD1, its ligands PD-L1 and PD-L2, as well as CD96, were also significantly increased in OSCC (p ≤ 0.001). There was a strong positive correlation between BTLA expression and that of the other checkpoints (p < 0.001; ρ ≥ 0.5). BTLA is overexpressed in OSCC and appears to be a relevant local immune checkpoint in OSCC. Thus, antibodies directed against BTLA could be potential candidates for immunotherapies, especially in combination with ICI against the PD1/PD-L axis and CD96.
Published: 2024
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14. Structure and properties of molybdenum oxide nitrides as model systems for selective oxidation catalysts

Author: Lerch Martin, Huber Manoup, Hahn Alexander HP, Schmidt-Zhang Peter, Kühn Sven, and Ressler Thorsten
Subjects: Chemistry, QD1-999
Abstract: Abstract Molybdenum oxide nitride (denoted as Mo(O,N)3) was obtained by ammonolysis of α-MoO3 with gaseous ammonia. Electronic and geometric structure, reducibility, and conductivity of Mo(O,N)3 were investigated by XRD, XAS, UV-Vis spectroscopy, and impedance measurements. Catalytic performance in selective propene oxidation was determined by online mass spectrometry und gas chromatography. Upon incorporation of nitrogen, Mo(O,N)3 maintained the characteristic layer structure of α-MoO3. XRD analysis showed an increased structural disorder in the layers while nitrogen is removed from the lattice of Mo(O,N)3 at temperatures above ~600 K. Compared to regular α-MoO3, Mo(O,N)3 exhibited a higher electronic and ionic conductivity and an onset of reduction in propene at lower temperatures. Surprisingly, α-MoO3 and Mo(O,N)3 exhibited no detectable differences in onset temperatures of propene oxidation and catalytic selectivity or activity. Apparently, the increased reducibility, oxygen mobility, and conductivity of Mo(O,N)3 compared to α-MoO3 had no effect on the catalytic behavior of the two catalysts. The results presented confirm the suitability of molybdenum oxide nitrides as model systems for studying bulk contributions to selective oxidation.
Published: 2011
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15. Cold Atmospheric Pressure Plasma-Activated Medium Modulates Cellular Functions of Human Mesenchymal Stem/Stromal Cells In Vitro

Author: Olga Hahn, Tawakalitu Okikiola Waheed, Kaarthik Sridharan, Thomas Huemerlehner, Susanne Staehlke, Mario Thürling, Lars Boeckmann, Mareike Meister, Kai Masur, and Kirsten Peters
Subjects: cold atmospheric pressure plasma, plasma-activated medium, mesenchymal stem/stromal cells, oxidative stress, metabolic activity, cell migration, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Cold atmospheric pressure plasma (CAP) offers a variety of therapeutic possibilities and induces the formation of reactive chemical species associated with oxidative stress. Mesenchymal stem/stromal cells (MSCs) play a central role in tissue regeneration, partly because of their antioxidant properties and ability to migrate into regenerating areas. During the therapeutic application, MSCs are directly exposed to the reactive species of CAP. Therefore, the investigation of CAP-induced effects on MSCs is essential. In this study, we quantified the amount of ROS due to the CAP activation of the culture medium. In addition, cell number, metabolic activity, stress signals, and migration were analyzed after the treatment of MSCs with a CAP-activated medium. CAP-activated media induced a significant increase in ROS but did not cause cytotoxic effects on MSCs when the treatment was singular and short-term (one day). This single treatment led to increased cell migration, an essential process in wound healing. In parallel, there was an increase in various cell stress proteins, indicating an adaptation to oxidative stress. Repeated treatments with the CAP-activated medium impaired the viability of the MSCs. The results shown here provide information on the influence of treatment frequency and intensity, which could be necessary for the therapeutic application of CAP.
Published: 2024
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16. Soluble NKG2DLs Are Elevated in Breast Cancer Patients and Associate with Disease Outcome

Author: Anna Seller, Christian M. Tegeler, Jonas Mauermann, Tatjana Schreiber, Ilona Hagelstein, Kai Liebel, André Koch, Jonas S. Heitmann, Sarah M. Greiner, Clara Hayn, Dominik Dannehl, Tobias Engler, Andreas D. Hartkopf, Markus Hahn, Sara Y. Brucker, Helmut R. Salih, and Melanie Märklin
Subjects: NKG2DL, serum marker, breast cancer, DCIS, survival, MIC, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.
Published: 2024
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17. Exploiting Hidden Information Leakages in Backward Privacy for Dynamic Searchable Symmetric Encryption

Author: Hyundo Yoon, Muncheon Yu, Changhee Hahn, Dongyoung Koo, and Junbeom Hur
Subjects: dynamic searchable encryption, information leakages, forward security, backward security, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract: Dynamic searchable symmetric encryption (DSSE) enables searches over encrypted data as well as data dynamics such as flexible data addition and deletion operations. A major security concern in DSSE is how to preserve forward and backward privacy, which are typically achieved by removing the linkability between the newly added data and previous queries, and between the deleted data and future queries, respectively. After information leakage types were formally defined for different levels of backward privacy (i.e., Type-I, II, III), many backward private DSSE schemes have been constructed under the definitions. However, we observed that the backward privacy can be violated by leveraging additional secondary leakage, which is typically leaked in specific constructions of schemes in spite of their theoretical guarantees. In this paper, in order to understand the security gap between the theoretical definitions and practical constructions, we conduct an in-depth analysis of the root cause for the secondary leakage, and demonstrate how it can be abused to violate Type-II backward privacy (e.g., the exposure of the deletion history) of DSSE constructions in practice. We then propose a novel Type-II backward private DSSE scheme based on Intel SGX, which is resilient to the secondary leakage abuse attack. According to the comparative analysis of our scheme with the state-of-the-art SGX-based DSSE schemes, Bunker-B (EuroSec’19) and SGX-SE1 (ACNS’20), our scheme shows higher efficiency in terms of the search latency with a negligible utility loss under the same security level (cf. Bunker-B) while showing similar efficiency with a higher security level (cf. SGX-SE1). Finally, we formally prove that our scheme guarantees Type-II backward privacy.
Published: 2024
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18. History of rape moderates the pathways from emotion dysregulation to alcohol and risky sex outcomes among college women

Author: Austin M. Hahn, Raluca M. Simons, Christine K. Hahn, and Jeffrey S. Simons
Subjects: Adult, Social Psychology, Adolescent, Universities, Sexual Behavior, Emotions, Protective factor, Alcohol, PsycINFO, Affect (psychology), Article, chemistry.chemical_compound, Young Adult, Risk-Taking, Alexithymia, Risky sexual behavior, Intervention (counseling), medicine, Humans, Emotional dysregulation, medicine.disease, Clinical Psychology, chemistry, Rape, Female, Psychology, Clinical psychology
Abstract: OBJECTIVE Affective and emotional dysregulation are consistently linked to greater alcohol use and related consequences, including risky sexual behavior. Moreover, these associations are even stronger among women with experiences of sexual assault. The current study tested affect, alexithymia, positive urgency, and negative urgency as predictors of alcohol use, alcohol-related consequences, and risky sexual behavior and the moderating impact of rape history on these associations among a sample of college women. METHOD Participants were 1,005 college women between the ages of 18 and 25. Approximately 20% of the sample (n = 204) reported a history of rape since age 14. RESULTS Positive and negative urgency statistically mediated the associations between negative affect and alexithymia and the alcohol and risky sex outcomes. Positive urgency was directly associated with alcohol use, while negative urgency was directly associated with alcohol-related consequences. Moreover, rape history moderated these associations, indicating that positive affect may be an important protective factor among women who have experienced rape. CONCLUSIONS The current study identified important unique risk and protective pathways that may increase or reduce women's risk for alcohol-related consequences and risky sexual behavior. Importantly, these pathways are comprised of constructs that are malleable and modifiable and can be targeted and changed through intervention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Published: 2023

19. Biomarker Rule-in or Rule-out in Patients With Acute Diseases for Validation of Acute Kidney Injury in the Emergency Department (BRAVA): A Multicenter Study Evaluating Urinary TIMP-2/IGFBP7

Author: Thiyapha Werayachankul, Win Sen Kuan, Paola Antonini, Sanjeeva Herath, Hahn Young Kim, Hyun Suk Yang, Phatthranit Phattharapornjaroen, Urmila Anandh, Kyeong Ryong Lee, Hanah Kim, Mui Teng Chua, Jong Won Kim, Salvatore Di Somma, Chagriya Kitiyakara, Anchalee Chittamma, Zoltan H. Endre, Horng Ruey Chua, Andrea R. Horvath, and Mina Hur
Subjects: Male, medicine.medical_specialty, Urinary system, Clinical Biochemistry, urologic and male genital diseases, chemistry.chemical_compound, Internal medicine, Intensive care, medicine, Humans, Prospective Studies, Aged, Tissue Inhibitor of Metalloproteinase-2, Creatinine, business.industry, Biochemistry (medical), Area under the curve, Acute kidney injury, General Medicine, Emergency department, Acute Kidney Injury, medicine.disease, United States, Insulin-Like Growth Factor Binding Proteins, chemistry, Acute Disease, Biomarker (medicine), Female, Emergency Service, Hospital, Risk assessment, business, Biomarkers
Abstract: Background Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED. Methods This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses. Results Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m)2/1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P=0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development (P Conclusions NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or ruling-out of AKI in the ED.
Published: 2022

20. PKCθ-mediated serine/threonine phosphorylations of FAK govern adhesion and protrusion dynamics within the lamellipodia of migrating breast cancer cells

Author: Sarah Gandarillas, Valérie Choesmel-Cadamuro, Nathalie Van Acker, Camille Franchet, Y Barreira, Christele Segura, Loïc Van Den Berghe, Carine Froment, Klaus M. Hahn, Jiaying Liu, Odile Burlet-Schiltz, Andrei V. Karginov, Xiaobo Wang, Georges Czaplicki, Karine Belguise, Florence Dalenc, and Lucie Chadelle
Subjects: Cancer Research, Cell, Mice, Nude, Breast Neoplasms, Protein Serine-Threonine Kinases, Article, Focal adhesion, Serine, Mice, Cell Movement, Cell Line, Tumor, Cell Adhesion, medicine, Animals, Humans, Pseudopodia, Phosphorylation, Cytoskeleton, Mice, Inbred BALB C, FERM domain, Chemistry, Kinase, Cell biology, medicine.anatomical_structure, Oncology, Protein Kinase C-theta, Focal Adhesion Kinase 1, MCF-7 Cells, Heterografts, Female, Lamellipodium
Abstract: The cytoskeleton and cell-matrix adhesions constitute a dynamic network that controls cellular behavior during development and cancer. The Focal Adhesion Kinase (FAK) is a central actor of these cell dynamics, promoting cell-matrix adhesion turnover and active membrane fluctuations. However, the initial steps leading to FAK activation and subsequent promotion of cell dynamics remain elusive. Here, we report that the serine/threonine kinase PKCθ participates in the initial steps of FAK activation. PKCθ, which is strongly expressed in aggressive human breast cancers, controls the dynamics of cell-matrix adhesions and active protrusions through direct FAK activation, thereby promoting cell invasion and lung metastases. Using various tools for in vitro and live cell studies, we precisely decipher the molecular mechanisms of FAK activation. PKCθ directly interacts with the FAK FERM domain to open FAK conformation through PKCθ’s specific V3 domain, while phosphorylating FAK at newly identified serine/threonine residues within nascent adhesions, inducing cell dynamics and aggressive behavior. This study thus places PKCθ-directed FAK opening and phosphorylations as an original mechanism controlling dynamic, migratory, and invasive abilities of aggressive breast cancer cells, further strengthening the emerging oncogenic function of PKCθ.
Published: 2022

21. A multi-functional microfluidic device compatible with widefield and light sheet microscopy

Author: Wesley R. Legant, Ana T. Nogueira, Yu Shi, Klaus M. Hahn, Ellen C. O’Shaughnessy, Regan P Moore, and Katelyn M Heath
Subjects: Microscopy, Fabrication, Materials science, business.industry, Microfluidics, Biomedical Engineering, Structured illumination microscopy, High resolution, Bioengineering, General Chemistry, Biochemistry, Article, Refractometry, chemistry.chemical_compound, Fluorinated ethylene propylene, chemistry, Lab-On-A-Chip Devices, Light sheet fluorescence microscopy, Optoelectronics, business, Refractive index, Lenses
Abstract: We present a microfluidic device compatible with high resolution light sheet and super-resolution microscopy. The device is a 150 μm thick chamber with a transparent fluorinated ethylene propylene (FEP) cover that has a similar refractive index (1.34) to water (1.33), making it compatible with top-down imaging used in light sheet microscopy. We provide a detailed fabrication protocol and characterize the optical performance of the device. We demonstrate that the device supports long-term imaging of cell growth and differentiation as well as the rapid addition and removal of reagents while simultaneously maintaining sterile culture conditions by physically isolating the sample from the dipping lenses used for imaging. Finally, we demonstrate that the device can be used for super-resolution imaging using lattice light sheet structured illumination microscopy (LLS-SIM) and DNA PAINT. We anticipate that FEP-based microfluidics, as shown here, will be broadly useful to researchers using light sheet microscopy due to the ability to switch reagents, image weakly adherent cells, maintain sterility, and physically isolate the specimen from the optics of the instruments.
Published: 2022

22. A BRCA1 Coiled-Coil Domain Variant Disrupting PALB2 Interaction Promotes the Development of Mammary Tumors and Confers a Targetable Defect in Homologous Recombination Repair

Author: Arnab Ray Chaudhuri, Jos Jonkers, Sjoerd Klarenbeek, Eline van der Burg, Bing Xia, Kerstin Hahn, Nicole S. Verkaik, Jeroen Essers, Haico van Attikum, Magdalena B. Rother, Colin Pritchard, Peter Bouwman, Hanneke van der Gulden, Chirantani Mukherjee, Emilia M. Pulver, Ivo J. Huijbers, Anne Paulien Drenth, Stefan J. Roobol, Roebi de Bruijn, Marieke van de Ven, Renske de Korte-Grimmerink, Maria Valeria Lattanzio, Gerarda van de Kamp, Dik C. van Gent, Molecular Genetics, Radiology & Nuclear Medicine, and Surgery
Subjects: Cancer Research, endocrine system diseases, Tumor suppressor gene, PALB2, Poly ADP ribose polymerase, Apoptosis, Mammary Neoplasms, Animal, missense variants affecting its PALB2-interacting coiled-coil, Biology, law.invention, Mice, chemistry.chemical_compound, breast cancer, Limited genomic instability, SDG 3 - Good Health and Well-being, law, Tumor Cells, Cultured, medicine, Animals, Missense mutation, Genomic position, Homologous Recombination, skin and connective tissue diseases, Cell Proliferation, BRCA2 Protein, Mice, Knockout, Cisplatin, BRCA1 Protein, Recombinational DNA Repair, Gene Expression Regulation, Neoplastic, Embryonic lethality, Oncology, chemistry, Cancer research, Suppressor, Female, Tumor Suppressor Protein p53, Fanconi Anemia Complementation Group N Protein, Homologous recombination, DNA, medicine.drug
Abstract: The BRCA1 tumor suppressor gene encodes a multidomain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks, which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, BRCA1 missense variants affecting its PALB2-interacting coiled-coil domain are considered variants of uncertain clinical significance (VUS). Using genetically engineered mice, we show here that a BRCA1 coiled-coil domain VUS, Brca1 p.L1363P, disrupts the interaction with PALB2 and leads to embryonic lethality. Brca1 p.L1363P led to a similar acceleration in the development of Trp53-deficient mammary tumors as Brca1 loss, but the tumors showed distinct histopathologic features, with more stable DNA copy number profiles in Brca1 p.L1363P tumors. Nevertheless, Brca1 p.L1363P mammary tumors were HRR incompetent and responsive to cisplatin and PARP inhibition. Overall, these results provide the first direct evidence that a BRCA1 missense variant outside of the RING and BRCT domains increases the risk of breast cancer. Significance: These findings reveal the importance of a patient-derived BRCA1 coiled-coil domain sequence variant in embryonic development, mammary tumor suppression, and therapy response. See related commentary by Mishra et al., p. 6080
Published: 2021

23. Sequencing of PD-1/L1 Inhibitors and Carboplatin Based Chemotherapy for Cisplatin Ineligible Metastatic Urothelial Carcinoma

Author: Vadim S. Koshkin, Bernadett Szabados, Daniel Castellano, Matthew D. Galsky, Petros Grivas, Lucia Carril-Ajuria, Min Y. Teo, Daniele Raggi, Guru Sonpavde, Parissa Alerasool, Thomas Powles, Lillian Werner, Jacob Gaines, Xiao X. Wei, Ravindran Kanesvaran, Joaquim Bellmunt, Jonathan E. Rosenberg, Andrea Necchi, Noah M. Hahn, Rana R. McKay, Laura Morrison, Pedro Isaacsson Velho, Wei, Xiao X, Werner, Lillian, Teo, Min Y, Rosenberg, Jonathan E, Koshkin, Vadim S, Grivas, Petro, Szabados, Bernadett, Morrison, Laura, Powles, Thoma, Carril-Ajuria, Lucia, Castellano, Daniel, Velho, Pedro Isaacsson, Hahn, Noah M, Mckay, Rana R, Raggi, Daniele, Necchi, Andrea, Kanesvaran, Ravindran, Alerasool, Parissa, Gaines, Jacob, Galsky, Matthew, Bellmunt, Joaquim, and Sonpavde, Guru
Subjects: Male, Metastatic Urothelial Carcinoma, Urology, medicine.medical_treatment, Antineoplastic Agents, carcinoma, History, 18th Century, urologic and male genital diseases, Article, programmed cell death 1 receptor, Carboplatin, chemistry.chemical_compound, Carcinoma, Humans, Medicine, In patient, Immune Checkpoint Inhibitors, Retrospective Studies, Cisplatin, Carcinoma, Transitional Cell, Chemotherapy, business.industry, medicine.disease, Programmed Cell Death 1 Receptor, First line treatment, Urinary Bladder Neoplasms, chemistry, transitional cell, carboplatin, Cancer research, Drug Therapy, Combination, Female, urinary bladder neoplasms, business, medicine.drug
Abstract: PURPOSE: Current first-line treatment options in patients with metastatic urothelial carcinoma (mUC) unfit to receive cisplatin-containing chemotherapy include PD-1/L1 inhibitors and carboplatin-containing chemotherapy. However, the optimal sequencing of these therapies remains unclear. MATERIAL AND METHODS: We conducted a multicenter retrospective analysis. Consecutive cisplatin-ineligible patients with mUC treated with first-line carboplatin-containing chemotherapy followed sequentially by second-line PD-1/L1 inhibitor, or the reverse order, were included. Patient demographics, objective response, time to treatment failure for first-line (TTF1) and second-line (TTF2) therapy, interval between end of first-line and initiation of second-line treatment (Interval(1L-2L)), and overall survival (OS) were collected. Multivariate analysis was conducted to examine the association of sequencing on OS. RESULTS: In this multicenter retrospective study, we identified 146 cisplatin-ineligible patients with mUC treated with first-line (1L) PD-1/L1 inhibitor therapy followed by second-line (2L) carboplatin-containing chemotherapy (Group 1, n=43) or the reverse sequence (Group 2, n=103). In the overall cohort, median age was 72, 76% were men, and 18% had liver metastasis. In both groups, objective response rates were higher with carboplatin-containing chemotherapy (45.6% 1L, 44.2% 2L) compared to PD-1/L1 inhibitors (9.3% 1L, 21.3% 2L). On multivariate analysis, treatment sequence was not associated with overall survival (HR 1.05, p=0.85). Site of metastasis was the only factor significantly associated with overall survival (p=0.002). CONCLUSIONS: In this biomarker-unselected cohort of cisplatin-ineligible patients with mUC, PD-1/L1 inhibitor followed by carboplatin-containing chemotherapy and the reverse sequence had comparable OS.
Published: 2021

24. Predicting the mechanical behavior of a polypropylene-based nonwoven using 3D microstructural simulation

Author: Siegfried Schmauder, Florian Keller, Friedemann J. Hahn, and Kai M. Hoess
Subjects: Polypropylene, chemistry.chemical_compound, Materials science, Polymers and Plastics, chemistry, Materials Science (miscellaneous), Composite material, General Agricultural and Biological Sciences, Industrial and Manufacturing Engineering
Published: 2021

25. TGF‐beta pathway inhibition as the therapeutic acceleration of diabetic bone regeneration

Author: Maxi von Glinski, Alexander Sogorski, Felix Reinkemeier, Mustafa Becerikli, Marius Drysch, Christoph Wallner, Mehran Dadras, Björn Behr, Stephan A. Hahn, Johannes Maximilian Wagner, and Marcus Lehnhardt
Subjects: Bone Regeneration, Angiogenesis, Chemistry, Regeneration (biology), Acceleration, Bone healing, Antibodies, Neutralizing, Mice, medicine.anatomical_structure, Osteogenesis, Transforming Growth Factor beta, Osteoclast, Gene expression, TGF beta signaling pathway, Diabetes Mellitus, Cancer research, medicine, Animals, Immunohistochemistry, Orthopedics and Sports Medicine, Bone regeneration
Abstract: Bone regeneration and fracture healing are impaired in diabetic patients due to defective functions of associated cells. Thus, the search for molecular causes and new treatment strategies are of particular clinical relevance. We investigated the gene expression profile of bones from type 2 diabetic (db- /db- ) mice and wild-type (wt) mice by comparative microarray analyses before and after placing tibial defects and examined the expression of several osteogenesis- and osteoclastogenesis-related markers by quantitative real-time polymerase chain reaction. In regenerating wt bones, pathways related to, for example, inhibition of matrix metalloproteases were activated, whereas in db- /db- bones activation of pathways related to, for example, osteoarthritis, transforming growth factor-beta (Tgfb), or hypoxia-inducible factor 1a were detected during regeneration. We defined the Tgfb pathway as a potential therapeutic target and locally applied a single dose (0.5 µg) of the Tgfb 1, 2, and 3 neutralizing antibody 1D11 on tibial defects in db- /db- mice (n = 7). Seven days postoperation, histological and immunohistochemical stainings were performed. Decreased bone regeneration, osteogenic differentiation, osteoclast invasion, and angiogenesis in db- /db- mice were significantly restored by local 1D11 application in comparison to the phosphate-buffered saline controls. Thus, local treatment of db- /db- bony defects with Tgfb neutralizing antibody 1D11 might be considered a good candidate for the successful acceleration of bone regeneration.
Published: 2021

26. Modeling Sympathetic Hyperactivity in Alzheimer’s Related Bone Loss

Author: Carisa A. DeKalb, Mariah S. Hahn, Ahmad S. Arabiyat, and Robert A. Culibrk
Subjects: medicine.medical_specialty, Sympathetic Nervous System, medicine.medical_treatment, Inflammation, In Vitro Techniques, PC12 Cells, Paracrine signalling, Alzheimer Disease, Bone Marrow, Internal medicine, medicine, Animals, Humans, Osteopontin, Interleukin 6, Aged, biology, Tumor Necrosis Factor-alpha, Chemistry, General Neuroscience, Mesenchymal stem cell, Mesenchymal Stem Cells, General Medicine, Coculture Techniques, Rats, Bone Diseases, Metabolic, Psychiatry and Mental health, Clinical Psychology, Endocrinology, Cytokine, medicine.anatomical_structure, biology.protein, Tumor necrosis factor alpha, Bone marrow, Inflammation Mediators, Geriatrics and Gerontology, medicine.symptom
Abstract: Background: A significant subset of patients with Alzheimer’s disease (AD) exhibit low bone mineral density and are therefore more fracture-prone, relative to their similarly aged neurotypical counterparts. In addition to chronic immune hyperactivity, behavioral dysregulation of effector peripheral sympathetic neurons—which densely innervate bone and potently modulate bone remodeling—is implicated in this pathological bone reformation. Objective: Thus, there exists a pressing need for a robust in vitro model which allows interrogation of the paracrine interactions between the putative mediators of AD-related osteopenia: sympathetic neurons (SNs) and mesenchymal stem cells (MSCs). Methods: Toward this end, activated SN-like PC12 cells and bone marrow derived MSCs were cultured in poly(ethylene glycol) diacrylate (PEGDA) hydrogels in the presence or absence of the AD-relevant inflammatory cytokine tumor necrosis factor alpha (TNF-α) under mono- and co-culture conditions. Results: PC12s and MSCs exposed separately to TNF-α displayed increased expression of pro-inflammatory mediators and decreased osteopontin (OPN), respectively. These data indicate that TNF-α was capable of inducing a dysregulated state in both cell types consistent with AD. Co-culture of TNF-α-activated PC12s and MSCs further exacerbated pathological behaviors in both cell types. Specifically, PC12s displayed increased secretion of interleukin 6 relative to TNF-α stimulated monoculture controls. Similarly, MSCs demonstrated a further reduction in osteogenic capacity relative to TNF-α stimulated monoculture controls, as illustrated by a significant decrease in OPN and collagen type I alpha I chain. Conclusion: Taken together, these data may indicate that dysregulated sympathetic activity may contribute to AD-related bone loss.
Published: 2021

27. Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events

Author: Christina D. Fang, Randall J. Lee, Rachel A. Gladstone, Kelsey Ogomori, Vivian Yang, Eric Vittinghoff, Byron K. Lee, Gregory M. Marcus, Emily Lee, Gregory Nah, Isaac R. Whitman, Edward P. Gerstenfeld, Shannon M Fan, Vasanth Vedantham, Henry H. Hsia, Jeffrey E. Olgin, Sean Joyce, Zian H. Tseng, Robin Fatch, Joshua D. Moss, Judith A. Hahn, and Melvin M. Scheinman
Subjects: Male, medicine.medical_specialty, Alcohol Drinking, Population, Alcohol abuse, Alcohol, Odds, chemistry.chemical_compound, Internal medicine, Atrial Fibrillation, Internal Medicine, Humans, Medicine, Prospective Studies, education, education.field_of_study, Cross-Over Studies, business.industry, Area under the curve, Atrial fibrillation, General Medicine, Odds ratio, Middle Aged, medicine.disease, chemistry, Ambulatory, Electrocardiography, Ambulatory, Blood Alcohol Content, Female, business
Abstract: BACKGROUND Patients' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event. OBJECTIVE To objectively ascertain whether alcohol consumption heightens risk for an AF episode. DESIGN A prospective, case-crossover analysis. SETTING Ambulatory persons in their natural environments. PARTICIPANTS Consenting patients with paroxysmal AF. MEASUREMENTS Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events. RESULTS Of 100 participants (mean age, 64 years [SD, 15]; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio [OR], 2.02 [95% CI, 1.38 to 3.17]) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 [CI, 1.63 to 7.89]) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 [CI, 1.04 to 1.83] per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 [CI, 1.06 to 1.22] per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours. LIMITATION Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population. CONCLUSION Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur. PRIMARY FUNDING SOURCE National Institute on Alcohol Abuse and Alcoholism.
Published: 2021

28. Reduced ice number concentrations in contrails from low-aromatic biofuel blends

Author: T. Bräuer, C. Voigt, D. Sauer, S. Kaufmann, V. Hahn, M. Scheibe, H. Schlager, F. Huber, P. Le Clercq, R. H. Moore, and B. E. Anderson
Subjects: Chemistry, Physics, QC1-999, QD1-999
Abstract: Sustainable aviation fuels can reduce contrail ice numbers and radiative forcing by contrail cirrus. We measured apparent ice emission indices for fuels with varying aromatic content at altitude ranges of 9.1–9.8 and 11.4–11.6 km. Measurement data were collected during the ECLIF II/NDMAX flight experiment in January 2018. The fuels varied in both aromatic quantity and type. Between a sustainable aviation fuel blend and a reference fuel Jet A-1, a maximum reduction in apparent ice emission indices of 40 % was found. We show vertical ice number and extinction distributions for three different fuels and calculate representative contrail optical depths. Optical depths of contrails (0.5–3 min in age) were reduced by 40 % to 52 % for a sustainable aviation fuel compared to the reference fuel. Our measurements suggest that sustainable aviation fuels result in reduced ice particle numbers, extinction coefficients, optical depth and climate impact from contrails.
Published: 2021

29. Effects of long-term exercise and a high-fat diet on synovial fluid metabolomics and joint structural phenotypes in mice: an integrated network analysis

Author: Albert Batushansky, A.K. Hahn, E.B. Prado Lopes, Timothy M. Griffin, Ronald K. June, and Rachel A. Rawle
Subjects: Leptin, medicine.medical_specialty, Metabolite, Interleukin-1beta, Biomedical Engineering, Osteoarthritis, Diet, High-Fat, Article, chemistry.chemical_compound, Chondrocytes, Metabolomics, Rheumatology, Physical Conditioning, Animal, Synovitis, Internal medicine, Glucose Intolerance, Synovial Fluid, Animals, Medicine, Synovial fluid, Orthopedics and Sports Medicine, Chemokine CCL2, Glucose tolerance test, medicine.diagnostic_test, business.industry, Cartilage, Interleukin-8, Hypertrophy, X-Ray Microtomography, medicine.disease, Stifle, Obesity, Interleukin-10, Mice, Inbred C57BL, Endocrinology, medicine.anatomical_structure, chemistry, business, Biomarkers
Abstract: Summary Objective To explore how systemic factors that modify knee osteoarthritis risk are connected to ‘whole-joint’ structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. Methods Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9–13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. Results High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1β and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. Conclusion Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.
Published: 2021

30. Reactivity of Ruthenium(II) Complexes Bearing Bis-NHC Ligands

Author: Alexander Hepp, Patrick D. Dutschke, Tobias Lübbering, and F. Ekkehardt Hahn
Subjects: chemistry.chemical_classification, Bearing (mechanical), Ethylene, Chemistry, Organic Chemistry, chemistry.chemical_element, Salt (chemistry), law.invention, Ruthenium, Inorganic Chemistry, chemistry.chemical_compound, law, Polymer chemistry, Reactivity (chemistry), Physical and Theoretical Chemistry, Methylene, Linker
Abstract: Bis-imidazolium salts bearing N-2-fluorobenzyl substituents and methylene, ethylene, or propylene linkers ([H2-4]Br2–[H2-6]Br2) and the bis-imidazolium salt [H2-8]Br2 featuring an ethylene linker a...
Published: 2021

31. Comparative Techno-Economic and Life Cycle Analysis of Water Oxidation and Hydrogen Oxidation at the Anode in a CO2 Electrolysis to Ethylene System

Author: Victor A. Beck, Sarah E. Baker, Christopher Hahn, Michael Stadermann, Jeremy T. Feaster, Roger D. Aines, Andrew A. Wong, Wenqin Li, Steven A. Hawks, Sneha A. Akhade, Joel B. Varley, Eric B. Duoss, and Jonathan T. Davis
Subjects: Electrolysis, Ethylene, Materials science, Renewable Energy, Sustainability and the Environment, Hydrogen oxidation, General Chemical Engineering, Techno economic, General Chemistry, law.invention, Anode, chemistry.chemical_compound, Chemical engineering, chemistry, law, Environmental Chemistry
Published: 2021

32. Making the Process of Enzyme Production in Solid-State Cultivation Cleaner and More Sustainable—Reuse of Raw Materials and a Syringe-Type Bioreactor Enter in the Scene

Author: Paula Cavion Costa, Eduardo Echer dos Reis, Willian Daniel Hahn Schneider, Roselei Claudete Fontana, Marli Camassola, and Laura Salgueiro de Carvalho
Subjects: Waste management, Renewable Energy, Sustainability and the Environment, Chemistry, General Chemical Engineering, Scientific method, Bioreactor, Solid-state, Environmental Chemistry, Production (economics), General Chemistry, Reuse, Raw material, Syringe
Published: 2021

33. Cyclic electron flow (CEF) and ascorbate pathway activity provide constitutive photoprotection for the photopsychrophile, Chlamydomonas sp. UWO 241 (renamed Chlamydomonas priscuii)

Author: Mark M. Hahn, Susanna D’Silva, Marina Cvetkovska, Isha Kalra, Devon Popson, Rachael M. Morgan-Kiss, and Sarah Stahl-Rommel
Subjects: Photoinhibition, biology, Chemistry, Chlamydomonas, Plant physiology, Cell Biology, Plant Science, General Medicine, Photosystem I, biology.organism_classification, Photosynthesis, Biochemistry, Acclimatization, Photoprotection, Biophysics, Psychrophile
Abstract: Under environmental stress, plants and algae employ a variety of strategies to protect the photosynthetic apparatus and maintain photostasis. To date, most studies on stress acclimation have focused on model organisms which possess limited to no tolerance to stressful extremes. We studied the ability of the Antarctic alga Chlamydomonas sp. UWO 241 (UWO 241) to acclimate to low temperature, high salinity or high light. UWO 241 maintained robust growth and photosynthetic activity at levels of temperature (2 °C) and salinity (700 mM NaCl) which were nonpermissive for a mesophilic sister species, Chlamydomonas raudensis SAG 49.72 (SAG 49.72). Acclimation in the mesophile involved classic mechanisms, including downregulation of light harvesting and shifts in excitation energy between photosystem I and II. In contrast, UWO 241 exhibited high rates of PSI-driven cyclic electron flow (CEF) and a larger capacity for nonphotochemical quenching (NPQ). Furthermore, UWO 241 exhibited constitutively high activity of two key ascorbate cycle enzymes, ascorbate peroxidase and glutathione reductase and maintained a large ascorbate pool. These results matched the ability of the psychrophile to maintain low ROS under short-term photoinhibition conditions. We conclude that tight control over photostasis and ROS levels are essential for photosynthetic life to flourish in a native habitat of permanent photooxidative stress. We propose to rename this organism Chlamydomonas priscuii.
Published: 2021

34. Lewis Acid Behavior of MoF5 and MoOF4: Syntheses and Characterization of MoF5(NCCH3), MoF5(NC5H5)n, and MoOF4(NC5H5)n (n = 1, 2)

Author: Michael Gerken, Stacey D. Wetmore, Janelle Bykowski, Nolan Hahn, René T. Boeré, and Douglas Turnbull
Subjects: 010405 organic chemistry, Chemistry, Dimer, Hexacoordinate, Nuclear magnetic resonance spectroscopy, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, law.invention, Adduct, Inorganic Chemistry, Crystallography, chemistry.chemical_compound, Pentagonal bipyramidal molecular geometry, law, Lewis acids and bases, Physical and Theoretical Chemistry, Electron paramagnetic resonance, Natural bond orbital
Abstract: The Lewis acid-base adducts MoF5(NC5H5)n and MoOF4(NC5H5)n (n = 1, 2) were synthesized from the reactions of MoF5 and MoOF4 with C5H5N and structurally characterized by X-ray crystallography. Whereas the crystal structures of MoF5(NC5H5)2 and MoOF4(NC5H5)2 are isomorphous containing pentagonal-bipyramidal molecules, the fluorido-bridged, heptacoordinate [MoF5(NC5H5)]2 dimer differs starkly from monomeric, hexacoordinate MoOF4(NC5H5). For the weaker Lewis base CH3CN, only the 1:1 adduct, MoF5(NCCH3), could be isolated. All adducts were characterized by Raman spectroscopy in conjunction with vibrational frequency calculations. Multinuclear NMR spectroscopy revealed an unprecedented isomerism of MoOF4(NC5H5)2 in solution, with the pyridyl ligands occupying adjacent or nonadjacent positions in the equatorial plane of the pentagonal bipyramid. Paramagnetic MoF5(NC5H5)2 was characterized by electron paramagnetic resonance (EPR) spectroscopy as a dispersion in solid adamantane as well as in a diamagnetic host lattice of MoOF4(NC5H5)2; EPR parameters were computed using ZORA with the BPW91 functional using relativistic all-electron wave functions for Mo and simulated using EasySpin. Density functional theory calculations (B3LYP) and natural bond orbital analyses were conducted to elucidate the distinctive bonding and structural properties of all adducts reported herein and explore fundamental differences observed in the Lewis acid behavior of MoF5 and MoOF4.
Published: 2021

35. STAT3 as a Potential Target for Tumor Suppressive Effects of 15-Deoxy-δ12,14-prostaglandin J2 in Triple Negative Breast Cancer

Author: Seong Hoon Kim, Xizhu Fang, Young-Joon Surh, Su-Jung Kim, Young-Il Hahn, and Nam-Chul Cho
Subjects: chemistry.chemical_compound, chemistry, Apoptosis, LNCaP, Cancer cell, Cancer research, Phosphorylation, Estrogen receptor, Tyrosine phosphorylation, Tyrosine, Triple-negative breast cancer
Abstract: STAT3 plays a prominent role in proliferation and survival of tumor cells. Thus, STAT3 has been considered to be a prime target for development of anti-cancer therapeutics. The electrophilic cyclopentenone prostaglandin,15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has been well recognized for its capability to modulate intracellular signaling pathways involved in cancer cell growth and progression. We previously reported that 15d-PGJ2 had potent cytotoxicity against harvey-ras transformed human mammary epithelial cells through direct interaction with STAT3. In this study, we have attempted to verify the inhibitory effects of 15d-PGJ2 on STAT3 signaling in human breast tumor cells. The triple negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468 displaying constitutive phosphorylation of STAT3 on the tyrosine 705 (Tyr705) residue, underwent apoptosis upon inhibition of STAT3 by 15d-PGJ2. In contrast, estrogen receptor positive MCF-7 breast cancer cells that do not exhibit elevated STAT3 phosphorylation were much less susceptible to 15d-PGJ2-induced apoptosis as assessed by PARP cleavage. Furthermore, 15d-PGJ2 inhibited interleukin-6-induced tyrosine phosphorylation of STAT3 in LNCaP cells. According to molecular docking studies, 15d-PGJ2 may preferentially bind to the cysteine 259 residue (Cys259) present in the coiled-coil domain of STAT3. Site-directed mutagenesis of STAT3 identified Cys259 to be the critical amino acid for the 15d-PGJ2-induced apoptosis as well as epithelial-to-mesenchymal transition. Taken together, these findings suggest STAT3 inactivation through direct chemical modification of its Cys259 as a potential therapeutic approach for treatment of triple negative breast cancer treatment.
Published: 2021

36. Effects of iloperidone on hERG 1A/3.1 heterotetrameric channels

Author: Bok Hee Choi, Hong Joon Lee, Sang June Hahn, and Jin-Sung Choi
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, biology, Chemistry, General Neuroscience, HEK 293 cells, hERG, Depolarization, Isoxazoles, Ether-A-Go-Go Potassium Channels, Cell membrane, Surface membrane, Iloperidone, HEK293 Cells, medicine.anatomical_structure, Piperidines, Potassium Channel Blockers, medicine, biology.protein, Biophysics, Humans, Repolarization, Biotinylation, cardiovascular diseases, Reversible inhibition, medicine.drug
Abstract: Objectives Iloperidone is an atypical antipsychotic drug that is widely used for the treatment of schizophrenia. hERG 3.1, alternatively spliced form of hERG 1A, is considered a potential target for an antipsychotic drug. The present study was designed to study the effects of iloperidone on hERG 1A/3.1 heterotetrameric channels. Methods The interactions of iloperidone with hERG 1A/3.1 heterotetrameric channels stably expressed in HEK cells were investigated using the whole-cell patch-clamp technique and western blot analysis. Results Iloperidone inhibited the hERG 1A/3.1 tail currents at -50 mV in a concentration-dependent manner with an IC50 value of 0.44 μM. The block of hERG 1A/3.1 currents by iloperidone was voltage-dependent and increased over a range of voltage for channel activation. However, the block by iloperidone was voltage-independent at more depolarized potentials where the channels were fully activated. A fast application of iloperidone inhibited the hERG 1A/3.1 current elicited by a 5-s depolarizing pulse to +60 mV to fully inactivate the hERG 1A/3.1 currents. Iloperidone also induced a rapid and reversible inhibition of hERG 1A/3.1 tail currents during repolarization. However, iloperidone had no effect on either hERG 1A or hERG 1A/3.1 channel trafficking to the cell membrane. Conclusions Our results indicated that iloperidone concentration-dependently inhibited hERG 1A/3.1 currents by preferentially interacting with the open states of channels, but not by the disruption of membrane trafficking or surface membrane expression of hERG 1A and hERG 1A/3.1 channel proteins.
Published: 2021

37. Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function

Author: Chang-Yun Cho, Isaac Park, Ji Seul Han, Jee Hyung Sohn, Yong Geun Jeon, Sangsoo Lim, Hyun-Woo Rhee, Sang Mun Han, Hahn Nahmgoong, Sun Kim, Yul Ji, and Jae Bum Kim
Subjects: Male, MAPK/ERK pathway, congenital, hereditary, and neonatal diseases and abnormalities, Antioxidant, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Mice, Transgenic, Glucosephosphate Dehydrogenase, medicine.disease_cause, Mice, Adipose Tissue, Brown, 3T3-L1 Cells, hemic and lymphatic diseases, parasitic diseases, Brown adipose tissue, Gene expression, Internal Medicine, medicine, Animals, Cells, Cultured, chemistry.chemical_classification, Mice, Inbred C3H, Reactive oxygen species, nutritional and metabolic diseases, Thermogenesis, Cell biology, Mice, Inbred C57BL, Cytosol, Adipocytes, Brown, medicine.anatomical_structure, chemistry, Reactive Oxygen Species, Oxidative stress
Abstract: Reactive oxygen species (ROS) are associated with various roles of brown adipocytes. Glucose-6-phosphate dehydrogenase (G6PD) controls cellular redox potentials by producing NADPH. Although G6PD upregulates cellular ROS levels in white adipocytes, the roles of G6PD in brown adipocytes remain elusive. Here, we found that G6PD defect in brown adipocytes impaired thermogenic function through excessive cytosolic ROS accumulation. Upon cold exposure, G6PD-deficient mutant (G6PDmut) mice exhibited cold intolerance and downregulated thermogenic gene expression in brown adipose tissue (BAT). In addition, G6PD-deficient brown adipocytes had increased cytosolic ROS levels, leading to ERK activation. In BAT of G6PDmut mice, administration of antioxidant restored the thermogenic activity by potentiating thermogenic gene expression and relieving ERK activation. Consistently, body temperature and thermogenic execution were rescued by ERK inhibition in cold-exposed G6PDmut mice. Taken together, these data suggest that G6PD in brown adipocytes would protect against cytosolic oxidative stress, leading to cold-induced thermogenesis.
Published: 2021

38. Nitrite reductase activity within an antiparallel de novo scaffold

Author: James E. Penner-Hahn, Vincent L. Pecoraro, Elizabeth C. Manickas, Karl J. Koebke, Alison G. Tebo, and Aniruddha Deb
Subjects: Coiled coil, Helix bundle, biology, Chemistry, Protein design, Active site, Antiparallel (biochemistry), Nitrite reductase, Biochemistry, Small molecule, Inorganic Chemistry, biology.protein, Biophysics, Binding site
Abstract: Copper nitrite reductase (CuNiR) is a copper enzyme that converts nitrite to nitric oxide and is an important part of the global nitrogen cycle in bacteria. The relatively simple CuHis3 binding site of the CuNiR active site has made it an enticing target for small molecule modeling and de novo protein design studies. We have previously reported symmetric CuNiR models within parallel three stranded coiled coil systems, with activities that span a range of three orders of magnitude. In this report, we investigate the same CuHis3 binding site within an antiparallel three helical bundle scaffold, which allows the design of asymmetric constructs. We determine that a simple CuHis3 binding site can be designed within this scaffold with enhanced activity relative to the comparable construct in parallel coiled coils. Incorporating more complex designs or repositioning this binding site can decrease this activity as much as 15 times. Comparing these constructs, we reaffirm a previous result in which a blue shift in the 1s to 4p transition energy determined by Cu(I) X-ray absorption spectroscopy is correlated with an enhanced activity within imidazole-based constructs. With this step and recent successful electron transfer site designs within this scaffold, we are one step closer to a fully functional de novo designed nitrite reductase.
Published: 2021

39. Cannabis Glandular Trichome Cell Walls Undergo Remodeling to Store Specialized Metabolites

Author: Shawn D. Mansfield, Michael G. Hahn, Samuel J. Livingston, Jonathan E. Page, Eun Jeong Annie Bae, Faride Unda, and A. Lacey Samuels
Subjects: 0106 biological sciences, Physiology, medicine.medical_treatment, Plant Science, Matrix (biology), 01 natural sciences, Epitope, Cell wall, 03 medical and health sciences, chemistry.chemical_compound, Cell Wall, Arabinogalactan, medicine, Extracellular, Cannabis, 030304 developmental biology, 0303 health sciences, Trichomes, Cell Biology, General Medicine, Trichome, Cell biology, Xyloglucan, chemistry, Cannabinoid, 010606 plant biology & botany
Abstract: The valuable cannabinoid and terpenoid metabolites of Cannabis sativa L. are produced by floral glandular trichomes. The trichomes consist of secretory disk cells, which produce the abundant lipidic metabolites, and an extracellular storage cavity. The mechanisms of apoplastic cavity formation to accumulate and store metabolites in cannabis glandular trichomes remain wholly unexplored. Here, we identify key wall components and how they change during cannabis trichome development. While glycome and monosaccharide analyses revealed that glandular trichomes have loosely bound xyloglucans and pectic polysaccharides, quantitative immunolabeling with wall-directed antibodies revealed precise spatiotemporal distributions of cell wall epitopes. An epidermal-like identity of early trichome walls matured into specialized wall domains over development. Cavity biogenesis was marked by separation of the subcuticular wall from the underlying surface wall in a homogalacturonan and α-1,5 arabinan epitope-rich zone and was associated with a reduction in fucosylated xyloglucan epitopes. As the cavity filled, a matrix with arabinogalactan and α-1,5 arabinan epitopes enclosed the metabolite droplets. At maturity, the disk cells’ apical wall facing the storage cavity accumulated rhamnogalacturonan-I epitopes near the plasma membrane. Together, these data indicate that cannabis glandular trichomes undergo spatiotemporal remodeling at specific wall subdomains to facilitate storage cavity formation and metabolite storage.
Published: 2021

40. Chemical Modifications of Ag Catalyst Surfaces with Imidazolium Ionomers Modulate H2 Evolution Rates during Electrochemical CO2 Reduction

Author: Siwei Liang, Sarah E. Baker, Sneha A. Akhade, Christopher Hahn, Thomas F. Jaramillo, Eric B. Duoss, Stephen E. Weitzner, Zhenan Bao, Kabir Abiose, David M. Koshy, Joel B. Varley, Adam Shugar, James S. Oakdale, and Jingwei Shi
Subjects: Steric effects, chemistry.chemical_classification, Chemistry, General Chemistry, Polymer, Electrochemistry, Ring (chemistry), Biochemistry, Catalysis, chemistry.chemical_compound, Colloid and Surface Chemistry, Chemical engineering, Density functional theory, Selectivity, Ionomer
Abstract: Bridging polymer design with catalyst surface science is a promising direction for tuning and optimizing electrochemical reactors that could impact long-term goals in energy and sustainability. Particularly, the interaction between inorganic catalyst surfaces and organic-based ionomers provides an avenue to both steer reaction selectivity and promote activity. Here, we studied the role of imidazolium-based ionomers for electrocatalytic CO2 reduction to CO (CO2R) on Ag surfaces and found that they produce no effect on CO2R activity yet strongly promote the competing hydrogen evolution reaction (HER). By examining the dependence of HER and CO2R rates on concentrations of CO2 and HCO3-, we developed a kinetic model that attributes HER promotion to intrinsic promotion of HCO3- reduction by imidazolium ionomers. We also show that varying the ionomer structure by changing substituents on the imidazolium ring modulates the HER promotion. This ionomer-structure dependence was analyzed via Taft steric parameters and density functional theory calculations, which suggest that steric bulk from functionalities on the imidazolium ring reduces access of the ionomer to both HCO3- and the Ag surface, thus limiting the promotional effect. Our results help develop design rules for ionomer-catalyst interactions in CO2R and motivate further work into precisely uncovering the interplay between primary and secondary coordination in determining electrocatalytic behavior.
Published: 2021

41. HE-LHC: The High-Energy Large Hadron Collider Future Circular Collider Conceptual Design Report Volume 4

Author: Pushpalatha C Bhat, B. Seeber, C. Pagliarone, Marco Statera, Victor P. Goncalves, Daria Astapovych, W. Bartmann, S. Iwamoto, M. Mentink, Alessandro Tricoli, E. R. Bielert, Laurent Chevalier, Patrick Koppenburg, Marco Calviani, C. Montag, P. Spiller, Jan Uythoven, P. Di Nezza, G. Guillermo Canton, B. Sailer, Markus Elsing, Sara Khatibi, Luca Vecchi, Luigi Palumbo, J. P. Penttinen, T. Podzorny, Maneesh Kumar, J. M. Rifflet, C. Kotnig, Jean Zinn-Justin, Christopher B. Verhaaren, A. Chernoded, Alessandro Bertarelli, L. M. Tkachenko, C. Koeberl, P. J. Mallon, M. Takeuchi, W. Venturini Delsolaro, G. Lamanna, S. Weinzierl, J. Gao, W. Kaabi, David D'Enterria, D. Barna, Paolo Castelnovo, Rajat Gupta, Oliver Boine-Frankenheim, Adarsh Pyarelal, Andreas Salzburger, Tessa Charles, M.E. Biagini, O. Panella, M. Stuart, A. Kollegger, V. Garcia Diaz, Olcay Bolukbasi, Maurizio Pierini, H. Aksakal, Tord Riemann, Abhishek M. Iyer, V. Shiltsev, D. Buttazzo, J. Blümlein, Prateek Agrawal, L. Sestini, Martin Bauer, Felicitas Pauss, S. Fiorendi, F. Bossu, Marco Nardecchia, C. Leonidopoulos, Wojciech Kotlarski, A. Saba, I. Bautista-Guzmán, W. Hillert, Giorgio Ambrosio, T. Lehtinen, Michael Andrew Parker, Silvia Taroni, Gian F. Giudice, Ph. Lebrun, Johann A. Briffa, T. Risselada, Giuseppe Lerner, A. Lechner, L. S. Miralles, M. Kuze, J. M. Valet, P. S. B. Dev, S. Holleis, Ph. Schwemling, M. Biglietti, S. Banerjee, Thomas Schörner-Sadenius, A. Sanz Ull, V. Tikhomirov, S. Savelyeva, Jiayin Gu, D. Zhou, Federico Ravotti, S. A. Bogacz, Daniele Mirarchi, R. Tomás García, Yann Coadou, F. Yu, Y. Cai, T. Lari, F. Holdener, D. Shwartz, C. Bhat, Ramesh Gupta, Markus Klute, E. Palmieri, P. Collier, Branislav Sitar, Yves Sirois, Livio Fanò, S. Rojas-Torres, E. Locci, Ruben Garcia Alia, I. Božović Jelisavić, R. Chehab, J. A. Aguilar-Saavedra, M. Pasquali, A. Di Cicco, Bernhard Auchmann, Klaus Heinemann, Alessia Tricomi, D. Lucchesi, B. Haerer, M. Morrone, Paolo Giacomelli, Sonia Carra, A. Senol, Ivan Koop, Luca Silvestrini, Anna Stakia, Heather Gray, E. Skordis, A. D. Kovalenko, Paul Langacker, R. Li, Bernardo Bordini, R. Rata, Arjan Verweij, Shehu S. AbdusSalam, Andrey Karyukhin, U. van Rienen, Gianluigi Arduini, Bernhard Holzer, S. A. Nikitin, S. S. Kozub, Satoshi Mishima, B. Di Micco, S. Izquierdo Bermudez, N. Pukhaeva, Nigel Watson, F. Prino, Jean-Michel Sallese, Sotirios Vlachos, Alessandro Vicini, A. Valassi, Daniel Treille, F. Dordei, A. M. Fernandez Navarro, B. Dziewit, Marcello Abbrescia, J. M. Hauptman, I. Chaikovska, Paolo Giubellino, Michael J. Baker, V.V. Kashikhin, Friedrich Lackner, Filippo Sala, A. Langner, D. Pulikowski, H. Eriksson, Matteo Turri, Andrea Wulzer, M. Aiba, Lisa Borgonovi, I. Morozov, V. Haurylavets, J. F. Croteau, S. Boselli, L. A. Gonzalez Gomez, Claudia Tambasco, F. Mahmoudi, Sébastien Descotes-Genon, A. Luciani, Pavel Piminov, M. Varasteh, T. Herzig, Sandra Aumon, Cristina Bernini, Joseph Bramante, Roberta Arnaldi, G. Zick, Daniel Schulte, R. Santoro, Anna Kulesza, I. Turk Cakir, M. Nonis, Silvia Posada Arias, Livia Soffi, T. Wojtoń, E. Cennini, Florian Bauer, B. Rousset, J.-L. Grenard, C. Neubüser, Frederic Derue, Loukas Gouskos, Rainer Wallny, G. Calderini, M. Merk, M. Mühlegger, Roberto Cimino, M. Ramsey-Musolf, P. Rebello Teles, Mario Galanti, Mikhail Shaposhnikov, A. Andreazza, Maria Vittoria Garzelli, Masaya Ishino, José W. F. Valle, Colin Bernet, G. Velev, Cristina Botta, E. Fischer, J. Malclés, Giuseppe Montenero, Tripurari Srivastava, E. Renner, Shahnam Gorgi Zadeh, D. Cantore-Cavalli, Paul Laycock, J. Komppula, Simon C. Hopkins, Helmut Burkhardt, Eric Lancon, I. Aichinger, Andre Sznajder, F. Bordry, Massimo Giovannozzi, Aidan Robson, Anna Giunta, A. Carvalho, S. Farinon, Daniel Wollmann, M. Fouaidy, Martti Raidal, R. Gerard, Giovanni Volpini, U. Niedermayer, A. Alekou, Alexander J.G. Lunt, Vincenzo Cavasinni, Andrzej Siodmok, U. Kaya, Matthias Schott, Marumi Kado, S. A. Arsenyev, José Zurita, John Osborne, Patrick Meade, Gianmarco Bovone, G. Li, Klaus Schlenga, Antti Stenvall, D. Duellmann, Werner Riegler, I. Garzia, Yasuyuki Okumura, G. Pikurs, F. Maltoni, Massimo Sorbi, M. Arzeo, B. Strauss, Y. W. Baek, Mauro Chiesa, K. Ilyina-Brunner, Javier L. Albacete, R. Farinelli, C. Pes, Nicolas Morange, S. M. Zernov, U. Wagner, Emmanuelle Perez, G. G. Da Silveira, J. Neundorf, Néstor Armesto, T. Hahn, Roman N. Lee, Roderik Bruce, B. Y. Sharkov, T. du Pree, G. Cibinetto, Evelin Meoni, R. Rinaldesi, James A. Ellison, Radim Slovak, Silvia Franchino, Mikko Laine, T. Pugnat, S. P. Das, Yuji Enari, Emanuela Barzi, Cihan Bayindir, R. Boels, Jana Faltova, M. Moreno Llácer, Scott A. Yost, Michael Spannowsky, Florian Burkart, Marcin Chrzaszcz, K. Suzuki, Luca Trentadue, S. Masciocchi, Gilad Perez, Steve Peggs, K. Sugita, Eleonora Belli, Carmine Senatore, K. Y. Oyulmaz, Aldo Deandrea, Irakli Minashvili, Desmond P. Barber, M. I. Martínez-Hernández, A. Apyan, S. Petracca, Mikael Chala, Urs Achim Wiedemann, T. Sian, Olivier Deschamps, R. Monge, G. Avrillaud, Jan Kieseler, Hubert Spiesberger, J. Maitre, G. D. Shirkov, M. Hofer, Emanuela Sirtori, Sinan Kuday, Kirill Skovpen, Sara Casalbuoni, Johann Usovitsch, N. Chen, G. Tejeda-Muñoz, F. Bellini, E. Chyhyrynets, Michael Stöger-Pollach, M. Vogel, J. G. Mendes Saraiva, A. Rivetti, M. Podeur, Luc Poggioli, V. A. Gromov, R. Sirvinskaite, S. B. Leith, Giancarlo D'Ambrosio, Tony Price, Philippe Mermod, Rabindra N. Mohapatra, T. Mitshuhashi, Koji Terashi, Leonel Ferreira, L. Vale Silva, N. Muchnoi, J. L. Stanyard, Thomas Marriott-Dodington, A. Andriatis, Oleg Solovyanov, A. Daljevec, A. Butterworth, S. Myers, D. Chanal, Tatiana Pieloni, M. Rodríguez-Cahuantzi, G. Nardini, D. Boscherini, Kazuhito Ohmi, James Molson, S. Kowalski, Christoph Haberstroh, Martin Aleksa, K. Kershaw, M. Mulder, Leonid Rivkin, G. Vorotnikov, Luigi Salvatore Esposito, J. Kalinowski, Michele Cascella, Francesco Giffoni, Alessandro Polini, Georges Azuelos, M. Prioli, Wolfgang Altmannshofer, S. K. Patra, H. J. He, J. J. Aguilera-Verdugo, Hannu Paukkunen, P. Chomaz, Shoji Asai, Nicolas Magnin, Gavin P. Salam, R. Wang, F. Avino, Alexander Romanenko, A. Rossi, Steve Muanza, Richard Ruiz, Dmitry Teytelman, S. Klöppel, S. Atieh, M. Mohammadi Najafabadi, L. Apolinario, Andrea Tesi, M. Maggiora, A. Falkowski, Janusz Gluza, M. Sauvain, Hamzeh Khanpour, S. Chance, Ansgar Denner, Ma. Greco, Andreas Papaefstathiou, Manuela Boscolo, Joydeep Chakrabortty, E. Franco, R. R. Bosley, G. Peón, Fred Olness, Simone Alioli, Andrea Gaddi, M. K. Sullivan, M. Segreti, M. Panareo, Florian Goertz, Z. G. Zhao, H. Chanal, O. Martin, P. Azzurri, Agnieszka Chmielinska, M. Kordiaczyńska, O. Brunner, J. Von Ahnen, Jose Santiago, K. Foraz, Y. Alexahin, Marcello Mannelli, Christian Schwanenberger, S. Ganjour, Simone Marzani, T. M. Taylor, S. Di Vita, J. Womersley, I. Karpov, Valentina Morretta, Saverio D'Auria, Patrick Draper, B. Hacışahinoğlu, E. Gorini, Andrew J. Long, S. La Mendola, G. Zevi Dell Porta, I. Abdyukhanov, M. Cobal, Luca Marzola, E. Rochepault, A. Kusina, German Rodrigo, R. Schmidt, Jan Steggemann, E. Premat, P. Slavich, F. Gianotti, P. Jarry, Ram Krishna Dewanjee, L. Felsberger, T. Martinez, A. Niemi, Jürgen Reuter, P. A. Bruckman de Renstrom, Ryu Sawada, J. T. Childers, Gelsomina Catalano, P. Barjhoux, O. R. Blanco-García, Pilar Hernández, H. Correia-Rodrigues, V. Ippolito, S. De Curtis, Juan Rojo, Ayberk Yilmaz, S. Baird, Morteza Khatiri Yanehsari, Enrico Scomparin, Daniel Appelö, J. Kozaczuk, Matthew Jones, B. Caiffi, C. Del Bo, Susanna Guiducci, Giuliano Panico, M. Knecht, J. Coupard, M. Ciuchini, H. Kritscher, Claire Gwenlan, P. Costa Pinto, Thibaut Lefèvre, N. Bellegarde, Christian Scheuerlein, P. Ferreira da Silva, M. Verducci, X. Ruan, H. Pikhartova, Juan M. O'Callaghan, Kazuro Furukawa, D. Saez de Jauregui, Maria Rescigno, Stephan Eisenhardt, Andrea Dainese, Z. Drásal, G. H. Corral, J. M. Camalich, John Ellis, E. Gabrielli, L. Rumyantsev, A. Caliskan, K. Brunner, K. Tang, P. Sopicki, J. Fan, Marcin Kucharczyk, S. Gorgi Zadeh, Carlos A. Salgado, Simone Bologna, Y. Muttoni, A. Chancé, Patrick Jenny, Mark Boland, G. Yang, G. Wilkinson, Roger J. Hernández-Pinto, M. Novák, Gennady Stupakov, E. Jensen, Lance D. Cooley, Torbjörn Sjöstrand, S. Su, Matthew Luzum, J. Casas, Per Osland, T. Robens, Oscar A. Sampayo, Evgeny Levichev, P. N. Ratoff, G. Rolandi, M. A. Valdivia Garcia, Anthony Keith Morley, L. van Riesen-Haupt, A. Sublet, M. A. Mazzoni, J.L. Gutierrez, A. Abramov, Abbas Kenan Ciftci, A. Provino, L. Delle Rose, John Fox, Barry M. Dillon, V. Smirnov, G. N. Taylor, Anke-Susanne Müller, C. Pira, Fulvio Piccinini, A. Faus-Golfe, Pietro Antonioli, S. Sanfilippo, Julien Cogan, A. Ribon, Andrew Hutton, Frank Zimmermann, Lev Dudko, Erez Etzion, J. Polinski, G. Bencivenni, M. Gil Costa, L. K. Gladilin, Yannis Papaphilippou, Michael Spira, Maria Paola Lombardo, M. Fiascaris, Darius A. Faroughy, S. O. Kara, Peter Braun-Munzinger, A. Wohlfahrt, A. A. Krasnov, S.A. Gourlay, W. Da Silva, Jacqueline Keintzel, Radja Boughezal, Renat Sadykov, L. R. Sulak, Valentin V. Khoze, T. Tydecks, S. Puławski, Daniel de Florian, Pedro Schwaller, A. Akay, Nicola Serra, Sukanta Dutta, Christophe Royon, Alessandro Ricci, A. Kuendig, C. G. Honorato, K. Kołodziej, L. Deniau, Michael Kramer, J. Ferradas Troitino, A. Arbey, A. M. Staśto, Marcel Demarteau, Ralph Aßmann, O. Grimm, D. Forkel-Wirth, Owain Rhodri Jones, A. M. Kolano, G. Chiarello, William Trischuk, Andrea Dell'Acqua, Elisabetta Gallo, H. Song, Frank Petriello, N. Ibarrola, C. Colldelram, A. I. Ryazanov, A. Meier, Phillip Allport, J. de Blas, S. Chattopadhyay, Massimo Florio, X. Jiang, Bertrand Baudouy, T. Otto, Tevong You, Christoph Englert, Roberto Pittau, G. M. Bilei, Matthew McCullough, N. S. Ramírez-Uribe, J. Charles, Amalia Ballarino, Federico Antinori, A. V. Kotwal, P. Le Guen, Berndt Müller, Chiara Roda, Xavier Buffat, D. K. Hong, Matthias Liepe, G. Gorine, V. A. Okorokov, D. Bozzini, N. Simand, Giuseppe Francesco Tartarelli, C. Marquet, R. Contino, A. M. Teixeira, R. Trant, Roberto Losito, M. Quispe, Valery I. Telnov, Helga Timko, D. Lissauer, Giulio Aielli, Giorgio Chiarelli, M. J. Baldwin, A. Winter, X. Sarasola, E. E. Boos, Aleandro Nisati, Cedric Garion, Monica D'Onofrio, S. M. Gascon-Shotkin, Daniele Barducci, G. Rosaz, Nathaniel Craig, L. D’Aloia Schwartzentruber, A. Falou, A. Henriques, Tobias Hurth, Michael Eisterer, Andreas Grau, Austin Ball, D. Delikaris, P. A. McIntosh, E. Graverini, Kadri Ozdemir, F. Valchkova, Marco Zanetti, Guenakh Mitselmakher, S. Albergo, Peter Levai, Caterina Vernieri, F. Stivanello, Michael Barnes, Henri Bachacou, Daniel Fournier, L. T. Wang, D. Boutin, S. Moretti, B. Riemann, Michael Murray, Aleksandr Azatov, C. T. A. Cook, Valentina Maria Cairo, J. B. De Vivie De Regie, H. Schmickler, M. Schenk, Georgios Voutsinas, André Schöning, S. G. Bondarenko, Giorgio Bellomo, Andrei Seryi, Jane Nachtman, Clement Helsens, E. De Lucia, Jakob Salfeld-Nebgen, Lorenzo Pezzotti, Z. Townsend, B. Dalena, Mogens Dam, Yasar Onel, Yi-Ming Zhong, B. Curé, A. A. Kolomiets, A. M. Valente-Feliciano, Laurette Ponce, David Olivier Jamin, P. Krkotic, Alexandre Louzguiti, Marina Putti, Holger Podlech, Petr Volkov, M. Angelucci, F. Duval, I. Hiekkanen, W. M. Yao, Giancarlo Ferrera, C. Lorin, Y. Dydyshka, Kurt R. Peters, Gergely Gabor Barnafoldi, V. Vysotsky, V. Arı, E. Pilicer, M. Chamizo-Llatas, G. Kuhlmann, Hans Quack, R. Valizadeh, Tiina Salmi, Thomas Kramer, Adam Jeff, A. Abada, J. M. Duval, J. Abelleira Fernandez, A. Leveratto, E. Tal Hod, X. Wu, Laurent Serin, Sarah Aull, Samuele Mariotto, A. Poiron, Sabine Riemann, P. Selva, V. I. Pantsyrny, Gianluca Valentino, K. Kahle, S. Aune, K. Potamianos, Eros Cazzato, M. Giovannetti, Petr Mandrik, S. Sidorov, F. Collamati, Simone Gilardoni, S. Bertolucci, Alexander V. Zlobin, Mehmet Sahin, Marco Delmastro, G. Aydın, A. Doblhammer, Alan S. Cornell, S. J. De Jong, M. Caccia, M. Lueckhof, P. Sollander, Mauro Taborelli, J. Shelton, Frank Gerigk, Robert Rimmer, Ayres Freitas, Pierluigi Bruzzone, Brajesh K. Singh, K. Keppel, N. Alipour Tehrani, C. Prasse, Louis Rinolfi, Emma Slade, W. Flieger, Alexey Dudarev, H. J. Yang, T. Köttig, L. Mether, C. Weiland, Andrea Malagoli, Sunghoon Jung, F. Conventi, I. Tropin, G. H. A. Viehhauser, Tomas Davidek, Y. O. Günaydin, Daniel Andreas Britzger, F. Toral, James John Brooke, R. Steerenberg, G. Morello, Mauro Migliorati, Alexej Grudiev, C. Tetrel, Wolfgang Höfle, J. V. Minervini, L. García Tabarés, V. Yermolchik, Claude Guyot, D. Guadagnoli, Giorgio Vallone, N. De Filippis, Oleksii Beznosov, P. Charitos, N. Schwerg, Ahmed Hammad, P. Manil, F. Niccoli, Lydia Iconomidou-Fayard, R. Aleksan, K. Hahn, P. Meridiani, Peter Skands, Tobias Golling, Lucio Rossi, G. Gobbi, Michael Hance, A. J. Barr, V. Del Duca, V. Guzey, M. Pont, Michele Selvaggi, Oliver Brüning, J. Barreiro Guimarães da Costa, A. Drago, Y. Zhang, Giovanni Punzi, Viktor Matveev, Anadi Canepa, Clemens Lange, B. L. Militsyn, Martijn Mulders, Max Klein, V. D’Auria, M. Mylona, Valeria Braccini, S. DasBakshi, David Calvet, Sophia Borowka, David Marzocca, S. Jadach, A. A. Pankov, Christophe Ochando, A. A. Tudora, I. Masina, Jure Zupan, A. Preinerstorfer, Benjamin Fuks, H. K. Soltveit, G. Rolando, E.E. Perepelkin, T. G. Rizzo, Saleh Sultansoy, Federico Roncarolo, K. Elsener, R. Q. Pan, P. Zhuang, David Attié, Jac Perez, K. Kravalis, F. Anulli, V. Ruhlmann-Kleider, S. Malvezzi, Steffen A. Bass, E. La Francesca, Heinz Pernegger, K. Grzanka, M. T. Tiirakari, Alberto Ventura, Alessandro Cerri, Marco Peruzzi, Eric Montesinos, O. Etisken, F. Grancagnolo, S. Kartal, H. Humer, Oliver Fischer, M. Primavera, Marco Toliman Lucchini, P. Vedrine, Felix Kling, M. Altınlı, Sergio Calatroni, C. Han, Olivier Leroy, R. T. D’Agnolo, N. Klinkenberg, A. Audurier, Tatsushi Nakamoto, Ali Bozbey, Bernd A. Kniehl, Carl J. Debono, I. P. J. Shipsey, Gregorio Bernardi, Paolo Nason, William James Fawcett, J. M. Jiménez, D. Denisov, M. Serluca, David Curtin, Arif Akhundov, M. García Pérez, Iacopo Vivarelli, Emanuele Bacchiocchi, Markus Zerlauth, Julia Hrdinka, F. Butin, F. Müller, D. Tikhonov, Jorg Wenninger, A. Kilic, Fabrizio Ferro, J. Tanaka, S. A. Antipov, Miroslav Atanasov, S. Kuttimalai, A. Y. Starikov, F. R. Blánquez, S. V. Furuseth, G. Gaudio, L. Malgeri, J. Curti, B. Turbiarz, S. Li, A. Romanov, Costas G. Papadopoulos, Brennan Goddard, Frank Krauss, Lidija Zivkovic, Toms Torims, Michaela Lackner, D. A. Lyubimtsev, G. Borghello, J. F. Grosse-Oetringhaus, A. Bogomyagkov, H. Duran Yildiz, N. Foppiani, Arthur Schaffer, J. Zhou, D. Liberati, Vincenzo Guidi, Naeem A. Tahir, M. Besançon, Daniel Schoerling, Joe Incandela, Giacomo Polesello, O. Cakir, I. Ruehl, Ruggero Vaglio, Z. 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Zurita, J, Işık Üniversitesi, Mühendislik Fakültesi, İnşaat Mühendisliği Bölümü, Işık University, Faculty of Engineering, Department of Civil Engineering, Bayındır, Cihan, Universitat Politècnica de Catalunya. Departament de Teoria del Senyal i Comunicacions, Universitat Politècnica de Catalunya. RF&MW - Grup de Recerca de sistemes, dispositius i materials de RF i microones, Abada A., Abbrescia M., AbdusSalam S.S., Abdyukhanov I., Abelleira Fernandez J., Abramov A., Aburaia M., Acar A.O., Adzic P.R., Agrawal P., Aguilar-Saavedra J.A., Aguilera-Verdugo J.J., Aiba M., Aichinger I., Aielli G., Akay A., Akhundov A., Aksakal H., Albacete J.L., Albergo S., Alekou A., Aleksa M., Aleksan R., Alemany Fernandez R.M., Alexahin Y., Alia R.G., Alioli S., Alipour Tehrani N., Allanach B.C., Allport P.P., Altinli M., Altmannshofer W., Ambrosio G., Amorim D., Amstutz O., Anderlini L., Andreazza A., Andreini M., Andriatis A., Andris C., Andronic A., Angelucci M., Antinori F., Antipov S.A., Antonelli M., Antonello M., Antonioli P., Antusch S., Anulli F., Apolinario L., Apollinari G., Apollonio A., Appelo D., Appleby R.B., Apyan A., Arbey A., Arbuzov A., Arduini G., Ari V., Arias S., Armesto N., Arnaldi R., Arsenyev S.A., Arzeo M., Asai S., Aslanides E., Assmann R.W., Astapovych D., Atanasov M., Atieh S., Attie D., Auchmann B., Audurier A., Aull S., Aumon S., Aune S., Avino F., Avrillaud G., Aydin G., Azatov A., Azuelos G., Azzi P., Azzolini O., Azzurri P., Bacchetta N., Bacchiocchi E., Bachacou H., Baek Y.W., Baglin V., Bai Y., Baird S., Baker M.J., Baldwin M.J., Ball A.H., Ballarino A., Banerjee S., Barber D.P., Barducci D., Barjhoux P., Barna D., Barnafoldi G.G., Barnes M.J., Barr A., Barranco Garcia J., Barreiro Guimaraes da Costa J., Bartmann W., Baryshevsky V., Barzi E., Bass S.A., Bastianin A., Baudouy B., Bauer F., Bauer M., Baumgartner T., Bautista-Guzman I., Bayindir C., Beaudette F., Bedeschi F., Beguin M., Bellafont I., Bellagamba L., Bellegarde N., Belli E., Bellingeri E., Bellini F., Bellomo G., Belomestnykh S., Bencivenni G., Benedikt M., Bernardi G., Bernardi J., Bernet C., Bernhardt J.M., Bernini C., Berriaud C., Bertarelli A., Bertolucci S., Besana M.I., Besancon M., Beznosov O., Bhat P., Bhat C., Biagini M.E., Biarrotte J.-L., Bibet Chevalier A., Bielert E.R., Biglietti M., Bilei G.M., Bilki B., Biscari C., Bishara F., Blanco-Garcia O.R., Blanquez F.R., Blekman F., Blondel A., Blumlein J., Boccali T., Boels R., Bogacz S.A., Bogomyagkov A., Boine-Frankenheim O., Boland M.J., Bologna S., Bolukbasi O., Bomben M., Bondarenko S., Bonvini M., Boos E., Bordini B., Bordry F., Borghello G., Borgonovi L., Borowka S., Bortoletto D., Boscherini D., Boscolo M., Boselli S., Bosley R.R., Bossu F., Botta C., Bottura L., Boughezal R., Boutin D., Bovone G., Bozovic Jelisavic I., Bozbey A., Bozzi C., Bozzini D., Braccini V., Braibant-Giacomelli S., Bramante J., Braun-Munzinger P., Briffa J.A., Britzger D., Brodsky S.J., Brooke J.J., Bruce R., Bruckman De Renstrom P., Bruna E., Bruning O., Brunner O., Brunner K., Bruzzone P., Buffat X., Bulyak E., Burkart F., Burkhardt H., Burnet J.-P., Butin F., Buttazzo D., Butterworth A., Caccia M., Cai Y., Caiffi B., Cairo V., Cakir O., Calaga R., Calatroni S., Calderini G., Calderola G., Caliskan A., Calvet D., Calviani M., Camalich J.M., Camarri P., Campanelli M., Camporesi T., Canbay A.C., Canepa A., Cantergiani E., Cantore-Cavalli D., Capeans M., Cardarelli R., Cardella U., Cardini A., Carloni Calame C.M., Carra F., Carra S., Carvalho A., Casalbuoni S., Casas J., Cascella M., Castelnovo P., Castorina G., Catalano G., Cavasinni V., Cazzato E., Cennini E., Cerri A., Cerutti F., Cervantes J., Chaikovska I., Chakrabortty J., Chala M., Chamizo-Llatas M., Chanal H., Chanal D., Chance S., Chance A., Charitos P., Charles J., Charles T.K., Chattopadhyay S., Chehab R., Chekanov S.V., Chen N., Chernoded A., Chetvertkova V., Chevalier L., Chiarelli G., Chiarello G., Chiesa M., Chiggiato P., Childers J.T., Chmielinska A., Cholakian A., Chomaz P., Chorowski M., Chou W., Chrzaszcz M., Chyhyrynets E., Cibinetto G., Ciftci A.K., Ciftci R., Cimino R., Ciuchini M., Clark P.J., Coadou Y., Cobal M., Coccaro A., Cogan J., Cogneras E., Collamati F., Colldelram C., Collier P., Collot J., Contino R., Conventi F., Cook C.T.A., Cooley L., Corcella G., Cornell A.S., Corral G.H., Correia-Rodrigues H., Costanza F., Costa Pinto P., Couderc F., Coupard J., Craig N., Crespo Garrido I., Crivellin A., Croteau J.F., Crouch M., Cruz Alaniz E., Cure B., Curti J., Curtin D., Czech M., Dachauer C., D'Agnolo R.T., Daibo M., Dainese A., Dalena B., Daljevec A., Dallapiazza W., D'Aloia Schwartzentruber L., Dam M., D'Ambrosio G., Das S.P., DasBakshi S., da Silva W., da Silveira G.G., D'Auria V., D'Auria S., David A., Davidek T., Deandrea A., de Blas J., Debono C.J., De Curtis S., De Filippis N., de Florian D., Deghaye S., de Jong S.J., Del Bo C., Del Duca V., Delikaris D., Deliot F., Dell'Acqua A., Delle Rose L., Delmastro M., De Lucia E., Demarteau M., Denegri D., Deniau L., Denisov D., Denizli H., Denner A., d'Enterria D., de Rijk G., De Roeck A., Derue F., Deschamps O., Descotes-Genon S., Dev P.S.B., de Vivie de Regie J.B., Dewanjee R.K., Di Ciaccio A., Di Cicco A., Dillon B.M., Di Micco B., Di Nezza P., Di Vita S., Doblhammer A., Dominjon A., D'Onofrio M., Dordei F., Drago A., Draper P., Drasal Z., Drewes M., Duarte L., Dubovyk I., Duda P., Dudarev A., Dudko L., Duellmann D., Dunser M., du Pree T., Durante M., Duran Yildiz H., Dutta S., Duval F., Duval J.M., Dydyshka Y., Dziewit B., Eisenhardt S., Eisterer M., Ekelof T., El Khechen D., Ellis S.A., Ellis J., Ellison J.A., Elsener K., Elsing M., Enari Y., Englert C., Eriksson H., Eskola K.J., Esposito L.S., Etisken O., Etzion E., Fabbricatore P., Falkowski A., Falou A., Faltova J., Fan J., Fano L., Farilla A., Farinelli R., Farinon S., Faroughy D.A., Fartoukh S.D., Faus-Golfe A., Fawcett W.J., Felici G., Felsberger L., Ferdeghini C., Fernandez Navarro A.M., Fernandez-Tellez A., Ferradas Troitino J., Ferrara G., Ferrari R., Ferreira L., Ferreira da Silva P., Ferrera G., Ferro F., Fiascaris M., Fiorendi S., Fiorio C., Fischer O., Fischer E., Flieger W., Florio M., Fonnesu D., Fontanesi E., Foppiani N., Foraz K., Forkel-Wirth D., Forte S., Fouaidy M., Fournier D., Fowler T., Fox J., Francavilla P., Franceschini R., Franchino S., Franco E., Freitas A., Fuks B., Furukawa K., Furuseth S.V., Gabrielli E., Gaddi A., Galanti M., Gallo E., Ganjour S., Gao J., Garcia Diaz V., Garcia Perez M., Garcia Tabares L., Garion C., Garzelli M.V., Garzia I., Gascon-Shotkin S.M., Gaudio G., Gay P., Ge S.-F., Gehrmann T., Genest M.H., Gerard R., Gerigk F., Gerwig H., Giacomelli P., Giagu S., Gianfelice-Wendt E., Gianotti F., Giffoni F., Gilardoni S.S., Gil Costa M., Giovannetti M., Giovannozzi M., Giubellino P., Giudice G.F., Giunta A., Gladilin L.K., Glukhov S., Gluza J., Gobbi G., Goddard B., Goertz F., Golling T., Goncalves V.P., Goncalo R., Gonzalez Gomez L.A., Gorgi Zadeh S., Gorine G., Gorini E., Gourlay S.A., Gouskos L., Grancagnolo F., Grassellino A., Grau A., Graverini E., Gray H.M., Greco M., Grenard J.-L., Grimm O., Grojean C., Gromov V.A., Grosse-Oetringhaus J.F., Grudiev A., Grzanka K., Gu J., Guadagnoli D., Guidi V., Guiducci S., Guillermo Canton G., Gunaydin Y.O., Gupta R., Gupta R.S., Gutierrez J., Gutleber J., Guyot C., Guzey V., Gwenlan C., Haberstroh C., Hacisahinoglu B., Haerer B., Hahn K., Hahn T., Hammad A., Han C., Hance M., Hannah A., Harris P.C., Hati C., Haug S., Hauptman J., Haurylavets V., He H.-J., Hegglin A., Hegner B., Heinemann K., Heinemeyer S., Helsens C., Henriques A., Hernandez P., Hernandez-Pinto R.J., Hernandez-Sanchez J., Herzig T., Hiekkanen I., Hillert W., Hoehn T., Hofer M., Hofle W., Holdener F., Holleis S., Holzer B., Hong D.K., Honorato C.G., Hopkins S.C., Hrdinka J., Hug F., Humann B., Humer H., Hurth T., Hutton A., Iacobucci G., Ibarrola N., Iconomidou-Fayard L., Ilyina-Brunner K., Incandela J., Infantino A., Ippolito V., Ishino M., Islam R., Ita H., Ivanovs A., Iwamoto S., Iyer A., Izquierdo Bermudez S., Jadach S., Jamin D.O., Janot P., Jarry P., Jeff A., Jenny P., Jensen E., Jensen M., Jiang X., Jimenez J.M., Jones M.A., Jones O.R., Jowett J.M., Jung S., Kaabi W., Kado M., Kahle K., Kalinovskaya L., Kalinowski J., Kamenik J.F., Kannike K., Kara S.O., Karadeniz H., Karaventzas V., Karpov I., Kartal S., Karyukhin A., Kashikhin V., Katharina Behr J., Kaya U., Keintzel J., Keinz P.A., Keppel K., Kersevan R., Kershaw K., Khanpour H., Khatibi S., Khatiri Yanehsari M., Khoze V.V., Kieseler J., Kilic A., Kilpinen A., Kim Y.-K., Kim D.W., Klein U., Klein M., Kling F., Klinkenberg N., Kloppel S., Klute M., Klyukhin V.I., Knecht M., Kniehl B., Kocak F., Koeberl C., Kolano A.M., Kollegger A., Kolodziej K., Kolomiets A.A., Komppula J., Koop I., Koppenburg P., Koratzinos M., Kordiaczynska M., Korjik M., Kortner O., Kostka P., Kotlarski W., Kotnig C., Kottig T., Kotwal A.V., Kovalenko A.D., Kowalski S., Kozaczuk J., Kozlov G.A., Kozub S.S., Krainer A.M., Kramer T., Kramer M., Krammer M., Krasnov A.A., Krauss F., Kravalis K., Kretzschmar L., Kriske R.M., Kritscher H., Krkotic P., Kroha H., Kucharczyk M., Kuday S., Kuendig A., Kuhlmann G., Kulesza A., Kumar M., Kusina A., Kuttimalai S., Kuze M., Kwon T., Lackner F., Lackner M., La Francesca E., Laine M., Lamanna G., La Mendola S., Lancon E., Landsberg G., Langacker P., Lange C., Langner A., Lankford A.J., Lansberg J.P., Lari T., Laycock P.J., Lebrun P., Lechner A., Lee K., Lee S., Lee R., Lefevre T., Le Guen P., Lehtinen T., Leith S.B., Lenzi P., Leogrande E., Leonidopoulos C., Leon-Monzon I., Lerner G., Leroy O., Lesiak T., Levai P., Leveratto A., Levichev E., Li G., Li S., Li R., Liberati D., Liepe M., Lissauer D.A., Liu Z., Lobko A., Locci E., Logothetis Agaliotis E., Lombardo M.P., Long A.J., Lorin C., Losito R., Louzguiti A., Low I., Lucchesi D., Lucchini M.T., Luciani A., Lueckhof M., Lunt A.J.G., Luzum M., Lyubimtsev D.A., Maggiora M., Magnin N., Mahmoud M.A., Mahmoudi F., Maitre J., Makarenko V., Malagoli A., Malcles J., Malgeri L., Mallon P.J., Maltoni F., Malvezzi S., Malyshev O.B., Mancinelli G., Mandrik P., Manfrinetti P., Mangano M., Manil P., Mannelli M., Marchiori G., Marhauser F., Mariani V., Marinozzi V., Mariotto S., Marquard P., Marquet C., Marriott-Dodington T., Martin R., Martin O., Martin Camalich J., Martinez T., Martinez Bruzual H., Martinez-Hernandez M.I., Martins D.E., Marzani S., Marzocca D., Marzola L., Masciocchi S., Masina I., Massimiliano A., Massironi A., Masubuchi T., Matveev V.A., Mazzoni M.A., McCullough M., McIntosh P.A., Meade P., Medina L., Meier A., Meignan J., Mele B., Mendes Saraiva J.G., Menez F., Mentink M., Meoni E., Meridiani P., Merk M., Mermod P., Mertens V., Mether L., Metral E., Migliorati M., Milanese A., Milardi C., Milhano G., Militsyn B.L., Millet F., Minashvili I., Minervini J.V., Miralles L.S., Mirarchi D., Mishima S., Missiaen D.P., Mitselmakher G., Mitshuhashi T., Mnich J., Mohammadi Najafabadi M., Mohapatra R.N., Mokhov N., Molson J.G., Monge R., Montag C., Montagna G., Monteil S., Montenero G., Montesinos E., Moortgat F., Morange N., Morello G., Moreno Llacer M., Moretti M., Moretti S., Morley A.K., Moros A., Morozov I., Morretta V., Morrone M., Mostacci A., Muanza S., Muchnoi N., Muhlegger M., Mulder M., Mulders M., Muller B., Muller F., Muller A.-S., Munilla J., Murray M.J., Muttoni Y., Myers S., Mylona M., Nachtman J., Nakamoto T., Nardecchia M., Nardini G., Nason P., Nergiz Z., Nesterenko A.V., Netto J.A., Nettstrater A., Neubuser C., Neundorf J., Niccoli F., Nicrosini O., Nie Y., Niedermayer U., Niedziela J., Niemi A., Nikitin S.A., Nisati A., No J.M., Nonis M., Nosochkov Y., Novak M., Novokhatski A., O'Callaghan J.M., Ochando C., Ogur S., Ohmi K., Oide K., Okorokov V.A., Okumura Y., Oleari C., Olness F.I., Onel Y., Ortino M., Osborne J., Osland P., Otto T., Oyulmaz K.Y., Ozansoy A., Ozcan V., Ozdemir K., Pagliarone C.E., Pais da Silva H.F., Palmieri E., Palumbo L., Pampaloni A., Pan R.-Q., Panareo M., Panella O., Panico G., Panizzo G., Pankov A.A., Pantsyrny V., Papadopoulos C.G., Papaefstathiou A., Papaphilippou Y., Parker M.A., Parma V., Pasquali M., Patra S.K., Patterson R., Paukkunen H., Pauss F., Peggs S., Penttinen J.-P., Peon G., Perepelkin E.E., Perez E., Perez J.C., Perez G., Perez F., Perez Codina E., Perez Morales J., Perfilov M., Pernegger H., Peruzzi M., Pes C., Peters K., Petracca S., Petriello F., Pezzotti L., Pfeiffer S., Piccinini F., Pieloni T., Pierini M., Pikhartova H., Pikurs G., Pilicer E., Piminov P., Pira C., Pittau R., Placzek W., Plagge M., Plehn T., Pleier M.-A., Ploskon M., Podeur M., Podlech H., Podzorny T., Poggioli L., Poiron A., Polesello G., Poli Lener M., Polini A., Polinski J., Polozov S.M., Ponce L., Pont M., Pontecorvo L., Portaluri T., Potamianos K., Prasse C., Prausa M., Preinerstorfer A., Premat E., Price T., Primavera M., Prino F., Prioli M., Proudfoot J., Provino A., Pugnat T., Pukhaeva N., Pulawski S., Pulikowski D., Punzi G., Putti M., Pyarelal A., Quack H., Quispe M., Racioppi A., Rafique H., Raginel V., Raidal M., Ramirez-Uribe N.S., Ramsey-Musolf M.J., Rata R., Ratoff P., Ravotti F., Rebello Teles P., Reboud M., Redaelli S., Renner E., Renteria-Olivo A.E., Rescigno M., Reuter J., Ribon A., Ricci A.M., Riegler W., Riemann S., Riemann B., Riemann T., Rifflet J.M., Rimmer R.A., Rinaldesi R., Rinolfi L., Rios Rubiras O., Risselada T., Rivetti A., Rivkin L., Rizzo T., Robens T., Robert F., Robson A.J., Rochepault E., Roda C., Rodrigo G., Rodriguez-Cahuantzi M., Rogan C., Roig M., Rojas-Torres S., Rojo J., Rolandi G., Rolando G., Roloff P., Romanenko A., Romanov A., Roncarolo F., Rosado Sanchez A., Rosaz G., Rossi L., Rossi A., Rossmanith R., Rousset B., Royon C., Ruan X., Ruehl I., Ruhlmann-Kleider V., Ruiz R., Rumyantsev L., Ruprecht R., Ryazanov A.I., Saba A., Sadykov R., Saez de Jauregui D., Sahin M., Sailer B., Saito M., Sala F., Salam G.P., Salfeld-Nebgen J., Salgado C.A., Salini S., Sallese J.M., Salmi T., Salzburger A., Sampayo O.A., Sanfilippo S., Santiago J., Santopinto E., Santoro R., Sanz Ull A., Sarasola X., Sarpun I.H., Sauvain M., Savelyeva S., Sawada R., Sborlini G.F.R., Schaffer A., Schaumann M., Schenk M., Scheuerlein C., Schienbein I., Schlenga K., Schmickler H., Schmidt R., Schoerling D., Schoning A., Schorner-Sadenius T., Schott M., Schulte D., Schwaller P., Schwanenberger C., Schwemling P., Schwerg N., Scibile L., Sciuto A., Scomparin E., Sebastiani C., Seeber B., Segreti M., Selva P., Selvaggi M., Senatore C., Senol A., Serin L., Serluca M., Serra N., Seryi A., Sestini L., Sfyrla A., Shaposhnikov M., Shaposhnikova E., Sharkov B.Y., Shatilov D., Shelton J., Shiltsev V., Shipsey I.P., Shirkov G.D., Shivaji A., Shwartz D., Sian T., Sidorov S., Siemko A., Silvestrini L., Simand N., Simon F., Singh B.K., Siodmok A., Sirois Y., Sirtori E., Sirvinskaite R., Sitar B., Sjostrand T., Skands P., Skordis E., Skovpen K., Skrzypek M., Slade E., Slavich P., Slovak R., Smaluk V., Smirnov V., Snoeys W., Soffi L., Sollander P., Solovyanov O., Soltveit H.K., Song H., Sopicki P., Sorbi M., Spallino L., Spannowsky M., Spataro B., Sphicas P., Spiesberger H., Spiller P., Spira M., Srivastava T., Stachel J., Stakia A., Stanyard J.L., Starchenko E., Starikov A.Y., Stasto A.M., Statera M., Steerenberg R., Steggemann J., Stenvall A., Stivanello F., Stockinger D., Stoel L.S., Stoger-Pollach M., Strauss B., Stuart M., Stupakov G., Su S., Sublet A., Sugita K., Sulak L., Sullivan M.K., Sultansoy S., Sumida T., Suzuki K., Sylva G., Syphers M.J., Sznajder A., Taborelli M., Tahir N.A., Takeuchi M., Tal Hod E., Tambasco C., Tanaka J., Tang K., Tapan I., Taroni S., Tartarelli G.F., Tassielli G., Tavian L., Taylor T.M., Taylor G.N., Teixeira A.M., Tejeda-Munoz G., Telnov V.I., Tenchini R., ten Kate H.H.J., Terashi K., Tesi A., Testa M., Tetrel C., Teytelman D., Thaler J., Thamm A., Thomas S., Tiirakari M.T., Tikhomirov V., Tikhonov D., Timko H., Tisserand V., Tkachenko L.M., Tkaczuk J., Tock J.P., Todd B., Todesco E., Tomas Garcia R., Tommasini D., Tonelli G., Toral F., Torims T., Torre R., Townsend Z., Trant R., Treille D., Trentadue L., Tricoli A., Tricomi A., Trischuk W., Tropin I.S., Tuchming B., Tudora A.A., Turbiarz B., Turk Cakir I., Turri M., Tydecks T., Usovitsch J., Uythoven J., Vaglio R., Valassi A., Valchkova F., Valdivia Garcia M.A., Valente P., Valente R.U., Valente-Feliciano A.-M., Valentino G., Vale Silva L., Valet J.M., Valizadeh R., Valle J.W.F., Vallecorsa S., Vallone G., van Leeuwen M., van Rienen U.H., van Riesen-Haupt L., Varasteh M., Vecchi L., Vedrine P., Velev G., Veness R., Ventura A., Venturini Delsolaro W., Verducci M., Verhaaren C.B., Vernieri C., Verweij A.P., Verwilligen O., Viazlo O., Vicini A., Viehhauser G., Vignaroli N., Vignolo M., Vitrano A., Vivarelli I., Vlachos S., Vogel M., Vogt D.M., Volkl V., Volkov P., Volpini G., von Ahnen J., Vorotnikov G., Voutsinas G.G., Vysotsky V., Wagner U., Wallny R., Wang L.-T., Wang R., Wang K., Ward B.F.L., Watson T.P., Watson N.K., Ws Z., Weiland C., Weinzierl S., Welsch C.P., Wenninger J., Widorski M., Wiedemann U.A., Wienands H.-U., Wilkinson G., Williams P.H., Winter A., Wohlfahrt A., Wojton T., Wollmann D., Womersley J., Woog D., Wu X., Wulzer A., Yanehsari M.K., Yang G., Yang H.J., Yao W.-M., Yazgan E., Yermolchik V., Yilmaz A., Yoo H.-D., Yost S.A., You T., Young C., Yu T.-T., Yu F., Zaborowska A., Zadeh S.G., Zahnd M., Zanetti M., Zanotto L., Zawiejski L., Zeiler P., Zerlauth M., Zernov S.M., Zevi Dell Porta G., Zhang Z., Zhang Y., Zhang C., Zhang H., Zhao Z., Zhong Y.-M., Zhou J., Zhou D., Zhuang P., Zick G., Zimmermann F., Zinn-Justin J., Zivkovic L., Zlobin A.V., Zobov M., Zupan J., Zurita J., BAİBÜ, Fen Edebiyat Fakültesi, Fizik Bölümü, Denizli, Haluk, TOBB ETU, Faculty of Engineering, Department of Electrical & Electronics Engineering, TOBB ETU, Faculty of Engineering, Department of Material Science & Nanotechnology Engineering, TOBB ETÜ, Mühendislik Fakültesi, Elektrik ve Elektronik Mühendisliği Bölümü, TOBB ETÜ, Mühendislik Fakültesi, Malzeme Bilimi ve Nanoteknoloji Mühendisliği Bölümü, Bozbey, Ali, Sultansoy, Saleh, Özdemir, Kadri, Giresun Üniversitesi, UCL - SST/IRMP - Institut de recherche en mathématique et physique, and Ege Üniversitesi
Subjects: Beam losses, IMPACT, Physics::Instrumentation and Detectors, Physics beyond the Standard Model, EVENT BUILDER, hadron collider, General Physics and Astronomy, Mathematics and natural science: 400::Physics: 430::Nuclear and elementary particle physics: 431 [VDP], 01 natural sciences, 7. Clean energy, law.invention, Subatomär fysik, chemistry.chemical_compound, Conceptual design, Colliding beam accelerators, law, HE-LHC, Subatomic Physics, General Materials Science, Hadron colliders, Física::Física de partícules::Hadrons [Àrees temàtiques de la UPC], Large Hadron Collider, Acceleradors de partícules, Physics, Settore FIS/01 - Fisica Sperimentale, Beams (radiation), Settore FIS/02 - Fisica Teorica, Modelli e Metodi Matematici, Upgrade, Impact, collimators, partikkelfysikk, Future Circular Collider, High-Energy, Systems engineering, HE-LHC: The High-Energy Large Hadron Collider, Col·lisionadors d'hadrons, Applied physics, Collimators, Socio-culturale, Fizik, Hadrons, Accelerator Physics and Instrumentation, HE-LHC physics, Condensed Matter::Materials Science, 0103 physical sciences, Physics::Atomic and Molecular Clusters, beam losses, ddc:530, High Energy Physics, partikkelakselerator, Physical and Theoretical Chemistry, Niobium-tin, 010306 general physics, Collider, Particle Physics, Beams (radiation) | Collimators | Beam losses, Energies::Energia nuclear [Àrees temàtiques de la UPC], Large Hadron Collider HE-LHC, 010308 nuclear & particles physics, High Energy Physics::Phenomenology, Colliders (Nuclear physics), Acceleratorfysik och instrumentering, Event builder, Accelerators and Storage Rings, Particle accelerators, chemistry, Experimental High Energy Physics, Physics::Accelerator Physics, High Energy Physics::Experiment, Future Colliders
Abstract: Authors: A. AbadaM. AbbresciaS. S. AbdusSalamI. AbdyukhanovJ. Abelleira FernandezA. AbramovM. AburaiaA. O. AcarP. R. AdzicP. AgrawalJ. A. Aguilar-SaavedraJ. J. Aguilera-VerdugoM. AibaI. AichingerG. AielliA. AkayA. AkhundovH. AksakalJ. L. AlbaceteS. AlbergoA. AlekouM. AleksaR. AleksanR. M. Alemany FernandezY. AlexahinR. G. AlíaS. AlioliN. Alipour TehraniB. C. AllanachP. P. AllportM. AltınlıW. AltmannshoferG. AmbrosioD. AmorimO. AmstutzL. AnderliniA. AndreazzaM. AndreiniA. AndriatisC. AndrisA. AndronicM. AngelucciF. AntinoriS. A. AntipovM. AntonelliM. AntonelloP. AntonioliS. AntuschF. AnulliL. ApolinárioG. ApollinariA. ApollonioD. AppelöR. B. ApplebyA. ApyanA. ApyanA. ArbeyA. ArbuzovG. ArduiniV. ArıS. AriasN. ArmestoR. ArnaldiS. A. ArsenyevM. ArzeoS. AsaiE. AslanidesR. W. AßmannD. AstapovychM. AtanasovS. AtiehD. AttiéB. AuchmannA. AudurierS. AullS. AumonS. AuneF. AvinoG. AvrillaudG. AydınA. AzatovG. AzuelosP. AzziO. AzzoliniP. AzzurriN. BacchettaE. BacchiocchiH. BachacouY. W. BaekV. BaglinY. BaiS. BairdM. J. BakerM. J. BaldwinA. H. BallA. BallarinoS. BanerjeeD. P. BarberD. BarducciP. BarjhouxD. BarnaG. G. BarnaföldiM. J. BarnesA. BarrJ. Barranco GarcíaJ. Barreiro Guimarães da CostaW. BartmannV. BaryshevskyE. BarziS. A. BassA. BastianinB. BaudouyF. BauerM. BauerT. BaumgartnerI. Bautista-GuzmánC. BayındırF. BeaudetteF. BedeschiM. BéguinI. BellafontL. BellagambaN. BellegardeE. BelliE. BellingeriF. BelliniG. BellomoS. BelomestnykhG. BencivenniM. BenediktG. BernardiJ. BernardiC. BernetJ. M. BernhardtC. BerniniC. BerriaudA. BertarelliS. BertolucciM. I. BesanaM. BesançonO. BeznosovP. BhatC. BhatM. E. BiaginiJ. -L. BiarrotteA. Bibet ChevalierE. R. BielertM. BigliettiG. M. BileiB. BilkiC. BiscariF. BisharaO. R. Blanco-GarcíaF. R. BlánquezF. BlekmanA. BlondelJ. BlümleinT. BoccaliR. BoelsS. A. BogaczA. BogomyagkovO. Boine-FrankenheimM. J. BolandS. BolognaO. BolukbasiM. BombenS. BondarenkoM. BonviniE. BoosB. BordiniF. BordryG. BorghelloL. BorgonoviS. BorowkaD. 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ChattopadhyayR. ChehabS. V. ChekanovN. ChenA. ChernodedV. ChetvertkovaL. ChevalierG. ChiarelliG. ChiarelloM. ChiesaP. ChiggiatoJ. T. ChildersA. ChmielińskaA. CholakianP. ChomazM. ChorowskiW. ChouM. ChrzaszczE. ChyhyrynetsG. CibinettoA. K. CiftciR. CiftciR. CiminoM. CiuchiniP. J. ClarkY. CoadouM. CobalA. CoccaroJ. CoganE. CognerasF. CollamatiC. ColldelramP. CollierJ. CollotR. ContinoF. ConventiC. T. A. CookL. CooleyG. CorcellaA. S. CornellG. H. CorralH. Correia-RodriguesF. CostanzaP. Costa PintoF. CoudercJ. CoupardN. CraigI. Crespo GarridoA. CrivellinJ. F. CroteauM. CrouchE. Cruz AlanizB. CuréJ. CurtiD. CurtinM. CzechC. DachauerR. T. D’AgnoloM. DaiboA. DaineseB. DalenaA. DaljevecW. DallapiazzaL. D’Aloia SchwartzentruberM. DamG. D’AmbrosioS. P. DasS. DasBakshiW. da SilvaG. G. da SilveiraV. D’AuriaS. D’AuriaA. DavidT. DavidekA. DeandreaJ. de BlasC. J. DebonoS. De CurtisN. De FilippisD. de FlorianS. DeghayeS. J. de JongC. Del BoV. Del DucaD. DelikarisF. DeliotA. Dell’AcquaL. Delle RoseM. DelmastroE. De LuciaM. DemarteauD. DenegriL. DeniauD. DenisovH. DenizliA. DennerD. d’EnterriaG. de RijkA. De RoeckF. DerueO. DeschampsS. Descotes-GenonP. S. B. DevJ. B. de Vivie de RégieR. K. DewanjeeA. Di CiaccioA. Di CiccoB. M. DillonB. Di MiccoP. Di NezzaS. Di VitaA. DoblhammerA. DominjonM. D’OnofrioF. DordeiA. DragoP. DraperZ. DrasalM. DrewesL. DuarteI. DubovykP. DudaA. DudarevL. DudkoD. DuellmannM. DünserT. du PreeM. DuranteH. Duran YildizS. DuttaF. DuvalJ. M. DuvalY. DydyshkaB. DziewitS. EisenhardtM. EistererT. EkelofD. El KhechenS. A. EllisJ. EllisJ. A. EllisonK. ElsenerM. ElsingY. EnariC. EnglertH. ErikssonK. J. EskolaL. S. EspositoO. EtiskenE. EtzionP. FabbricatoreA. FalkowskiA. FalouJ. FaltovaJ. FanL. FanòA. FarillaR. FarinelliS. FarinonD. A. FaroughyS. D. FartoukhA. Faus-GolfeW. J. FawcettG. FeliciL. FelsbergerC. FerdeghiniA. M. Fernandez NavarroA. Fernández-TéllezJ. Ferradas TroitinoG. FerraraR. FerrariL. FerreiraP. Ferreira da SilvaG. FerreraF. FerroM. FiascarisS. FiorendiC. FiorioO. FischerE. FischerW. FliegerM. FlorioD. FonnesuE. FontanesiN. FoppianiK. ForazD. Forkel-WirthS. ForteM. FouaidyD. FournierT. FowlerJ. FoxP. FrancavillaR. FranceschiniS. FranchinoE. FrancoA. FreitasB. FuksK. FurukawaS. V. FurusethE. GabrielliA. GaddiM. GalantiE. GalloS. GanjourJ. GaoJ. GaoV. Garcia DiazM. García PérezL. García TabarésC. GarionM. V. GarzelliI. GarziaS. M. Gascon-ShotkinG. GaudioP. GayS. -F. GeT. GehrmannM. H. GenestR. GerardF. GerigkH. GerwigP. GiacomelliS. GiaguE. Gianfelice-WendtF. GianottiF. GiffoniS. S. GilardoniM. Gil CostaM. GiovannettiM. GiovannozziP. GiubellinoG. F. GiudiceA. GiuntaL. K. GladilinS. GlukhovJ. GluzaG. GobbiB. GoddardF. GoertzT. GollingV. P. GoncalvesR. GonçaloL. A. Gonzalez GomezS. Gorgi ZadehG. GorineE. GoriniS. A. GourlayL. GouskosF. GrancagnoloA. GrassellinoA. GrauE. GraveriniH. M. GrayMa. GrecoMi. GrecoJ. -L. GrenardO. GrimmC. GrojeanV. A. GromovJ. F. Grosse-OetringhausA. GrudievK. GrzankaJ. GuD. GuadagnoliV. GuidiS. GuiducciG. Guillermo CantonY. O. GünaydinR. GuptaR. S. GuptaJ. GutierrezJ. GutleberC. GuyotV. GuzeyC. GwenlanC. HaberstrohB. HacışahinoğluB. HaererK. HahnT. HahnA. HammadC. HanM. HanceA. HannahP. C. HarrisC. HatiS. HaugJ. HauptmanV. HaurylavetsH. -J. HeA. HegglinB. HegnerK. HeinemannS. HeinemeyerC. HelsensA. HenriquesA. HenriquesP. HernandezR. J. Hernández-PintoJ. Hernandez-SanchezT. HerzigI. HiekkanenW. HillertT. HoehnM. HoferW. HöfleF. HoldenerS. HolleisB. HolzerD. K. HongC. G. HonoratoS. C. HopkinsJ. HrdinkaF. HugB. HumannH. HumerT. HurthA. HuttonG. IacobucciN. IbarrolaL. Iconomidou-FayardK. Ilyina-BrunnerJ. IncandelaA. InfantinoV. IppolitoM. IshinoR. IslamH. ItaA. IvanovsS. IwamotoA. IyerS. Izquierdo BermudezS. JadachD. O. JaminP. JanotP. JarryA. JeffP. JennyE. JensenM. JensenX. JiangJ. M. JiménezM. A. JonesO. R. JonesJ. M. JowettS. JungW. KaabiM. KadoK. KahleL. KalinovskayaJ. KalinowskiJ. F. KamenikK. KannikeS. O. KaraH. KaradenizV. KaraventzasI. KarpovS. KartalA. KaryukhinV. KashikhinJ. Katharina BehrU. KayaJ. KeintzelP. A. KeinzK. KeppelR. KersevanK. KershawH. KhanpourS. KhatibiM. Khatiri YanehsariV. V. KhozeJ. KieselerA. KilicA. KilpinenY. -K. KimD. W. KimU. KleinM. KleinF. KlingN. KlinkenbergS. KlöppelM. KluteV. I. KlyukhinM. KnechtB. KniehlF. KocakC. KoeberlA. M. KolanoA. KolleggerK. KołodziejA. A. KolomietsJ. KomppulaI. KoopP. KoppenburgM. KoratzinosM. KordiaczyńskaM. KorjikO. KortnerP. KostkaW. KotlarskiC. KotnigT. KöttigA. V. KotwalA. D. KovalenkoS. KowalskiJ. KozaczukG. A. KozlovS. S. KozubA. M. KrainerT. KramerM. KrämerM. KrammerA. A. KrasnovF. KraussK. KravalisL. KretzschmarR. M. KriskeH. KritscherP. KrkoticH. KrohaM. KucharczykS. KudayA. KuendigG. KuhlmannA. KuleszaM. KumarM. KumarA. KusinaS. KuttimalaiM. KuzeT. KwonF. LacknerM. LacknerE. La FrancescaM. LaineG. LamannaS. La MendolaE. LançonG. LandsbergP. LangackerC. LangeA. LangnerA. J. LankfordJ. P. LansbergT. LariP. J. LaycockP. LebrunA. LechnerK. LeeS. LeeR. LeeT. LefevreP. Le GuenT. LehtinenS. B. LeithP. LenziE. LeograndeC. LeonidopoulosI. Leon-MonzonG. LernerO. LeroyT. LesiakP. LévaiA. LeverattoE. LevichevG. LiS. LiR. LiD. LiberatiM. LiepeD. A. LissauerZ. LiuA. LobkoE. LocciE. Logothetis AgaliotisM. P. LombardoA. J. LongC. LorinR. LositoA. LouzguitiI. LowD. LucchesiM. T. LucchiniA. LucianiM. LueckhofA. J. G. LuntM. LuzumD. A. LyubimtsevM. MaggioraN. MagninM. A. MahmoudF. MahmoudiJ. MaitreV. MakarenkoA. MalagoliJ. MalclésL. MalgeriP. J. MallonF. MaltoniS. MalvezziO. B. MalyshevG. MancinelliP. MandrikP. ManfrinettiM. ManganoP. ManilM. MannelliG. MarchioriF. MarhauserV. MarianiV. MarinozziS. MariottoP. MarquardC. MarquetT. Marriott-DodingtonR. MartinO. MartinJ. Martin CamalichT. MartinezH. Martinez BruzualM. I. Martínez-HernándezD. E. MartinsS. MarzaniD. MarzoccaL. MarzolaS. MasciocchiI. MasinaA. MassimilianoA. MassironiT. MasubuchiV. A. MatveevM. A. MazzoniM. McCulloughP. A. McIntoshP. MeadeL. MedinaA. MeierJ. MeignanB. MeleJ. G. Mendes SaraivaF. MenezM. MentinkE. MeoniP. MeridianiM. MerkP. MermodV. MertensL. MetherE. MétralM. MiglioratiA. MilaneseC. MilardiG. MilhanoB. L. MilitsynF. MilletI. MinashviliJ. V. MinerviniL. S. MirallesD. MirarchiS. MishimaD. P. MissiaenG. MitselmakherT. MitshuhashiJ. MnichM. Mohammadi NajafabadiR. N. MohapatraN. MokhovJ. G. MolsonR. MongeC. MontagG. MontagnaS. MonteilG. MonteneroE. MontesinosF. MoortgatN. MorangeG. MorelloM. Moreno LlácerM. MorettiS. MorettiA. K. MorleyA. MorosI. MorozovV. MorrettaM. MorroneA. MostacciS. MuanzaN. MuchnoiM. MühleggerM. MulderM. MuldersB. MüllerF. MüllerA. -S. MüllerJ. MunillaM. J. MurrayY. MuttoniS. MyersM. MylonaJ. NachtmanT. NakamotoM. NardecchiaG. NardiniP. NasonZ. NergizA. V. NesterenkoJ. A. NettoA. NettsträterC. NeubüserJ. NeundorfF. NiccoliO. NicrosiniY. NieU. NiedermayerJ. NiedzielaA. NiemiS. A. NikitinA. NisatiJ. M. NoM. NonisY. NosochkovM. NovákA. NovokhatskiJ. M. O’CallaghanC. OchandoS. OgurK. OhmiK. OideV. A. OkorokovY. OkumuraC. OleariF. I. OlnessY. OnelM. OrtinoJ. OsborneP. OslandT. OttoK. Y. OyulmazA. OzansoyV. ÖzcanK. ÖzdemirC. E. PagliaroneH. F. Pais da SilvaE. PalmieriL. PalumboA. PampaloniR. -Q. PanM. PanareoO. PanellaG. PanicoG. PanizzoA. A. PankovV. PantsyrnyC. G. PapadopoulosA. PapaefstathiouY. PapaphilippouM. A. ParkerV. ParmaM. PasqualiS. K. PatraR. PattersonH. PaukkunenF. PaussS. PeggsJ. -P. PenttinenG. PeónE. E. PerepelkinE. PerezJ. C. PerezG. PerezF. PérezE. Perez CodinaJ. Perez MoralesM. PerfilovH. PerneggerM. PeruzziC. PesK. PetersS. PetraccaF. PetrielloL. PezzottiS. PfeifferF. PiccininiT. PieloniM. PieriniH. PikhartovaG. PikursE. PilicerP. PiminovC. PiraR. PittauW. PłaczekM. PlaggeT. PlehnM. -A. PleierM. PłoskońM. PodeurH. PodlechT. PodzornyL. PoggioliA. PoironG. PoleselloM. Poli LenerA. PoliniJ. PolinskiS. M. PolozovL. PonceM. PontL. PontecorvoT. PortaluriK. PotamianosC. PrasseM. PrausaA. PreinerstorferE. PrematT. PriceM. PrimaveraF. PrinoM. PrioliJ. ProudfootA. ProvinoT. PugnatN. PukhaevaS. PuławskiD. PulikowskiG. PunziM. PuttiA. PyarelalH. QuackM. QuispeA. RacioppiH. RafiqueV. RaginelM. RaidalN. S. Ramírez-UribeM. J. Ramsey-MusolfR. RataP. RatoffF. RavottiP. Rebello TelesM. ReboudS. RedaelliE. RennerA. E. Rentería-OlivoM. RescignoJ. ReuterA. RibonA. M. RicciW. RieglerS. RiemannB. RiemannT. RiemannJ. M. RiffletR. A. RimmerR. RinaldesiL. RinolfiO. Rios RubirasT. RisseladaA. RivettiL. RivkinT. RizzoT. RobensF. RobertA. J. RobsonE. RochepaultC. RodaG. RodrigoM. Rodríguez-CahuantziC. RoganM. RoigS. Rojas-TorresJ. RojoG. RolandiG. RolandoP. RoloffA. RomanenkoA. RomanovF. RoncaroloA. Rosado SanchezG. RosazL. RossiA. RossiR. RossmanithB. RoussetC. RoyonX. RuanI. RuehlV. Ruhlmann-KleiderR. RuizL. RumyantsevR. RuprechtA. I. RyazanovA. SabaR. SadykovD. Saez de JaureguiM. SahinB. SailerM. SaitoF. SalaG. P. SalamJ. Salfeld-NebgenC. A. SalgadoS. SaliniJ. M. SalleseT. SalmiA. SalzburgerO. A. SampayoS. SanfilippoJ. SantiagoE. SantopintoR. SantoroA. Sanz UllX. SarasolaI. H. SarpünM. SauvainS. SavelyevaR. SawadaG. F. R. SborliniA. SchafferM. SchaumannM. SchenkC. ScheuerleinI. SchienbeinK. SchlengaH. SchmicklerR. SchmidtD. SchoerlingA. SchoningT. Schörner-SadeniusM. SchottD. SchulteP. SchwallerC. SchwanenbergerP. SchwemlingN. SchwergL. ScibileA. SciutoE. ScomparinC. SebastianiB. SeeberM. SegretiP. SelvaM. SelvaggiC. SenatoreA. SenolL. SerinM. SerlucaN. SerraA. SeryiL. SestiniA. SfyrlaM. ShaposhnikovE. ShaposhnikovaB. Y. SharkovD. ShatilovJ. SheltonV. ShiltsevI. P. ShipseyG. D. ShirkovA. ShivajiD. ShwartzT. SianS. SidorovA. SiemkoL. SilvestriniN. SimandF. SimonB. K. SinghA. SiódmokY. SiroisE. SirtoriR. SirvinskaiteB. SitarT. SjöstrandP. SkandsE. SkordisK. SkovpenM. SkrzypekE. SladeP. SlavichR. SlovakV. SmalukV. SmirnovW. SnoeysL. SoffiP. SollanderO. SolovyanovH. K. SoltveitH. SongP. SopickiM. SorbiL. SpallinoM. SpannowskyB. SpataroP. SphicasH. SpiesbergerP. SpillerM. SpiraT. SrivastavaJ. StachelA. StakiaJ. L. StanyardE. StarchenkoA. Y. StarikovA. M. StaśtoM. StateraR. SteerenbergJ. SteggemannA. StenvallF. StivanelloD. StöckingerL. S. StoelM. Stöger-PollachB. StraussM. StuartG. StupakovS. SuA. SubletK. SugitaL. SulakM. K. SullivanS. SultansoyT. SumidaK. SuzukiG. SylvaM. J. SyphersA. SznajderM. TaborelliN. A. TahirM. TakeuchiE. Tal HodC. TambascoJ. TanakaK. TangI. TapanS. TaroniG. F. TartarelliG. TassielliL. TavianT. M. TaylorG. N. TaylorA. M. TeixeiraG. Tejeda-MuñozV. I. TelnovR. TenchiniH. H. J. ten KateK. TerashiA. TesiM. TestaC. TetrelD. TeytelmanJ. ThalerA. ThammS. ThomasM. T. TiirakariV. TikhomirovD. TikhonovH. TimkoV. TisserandL. M. TkachenkoJ. TkaczukJ. P. TockB. ToddE. TodescoR. Tomás GarciaD. TommasiniG. TonelliF. ToralT. TorimsR. TorreZ. TownsendR. TrantD. TreilleL. TrentadueA. TricoliA. TricomiW. TrischukI. S. TropinB. TuchmingA. A. TudoraB. TurbiarzI. Turk CakirM. TurriT. TydecksJ. UsovitschJ. UythovenR. VaglioA. ValassiF. ValchkovaM. A. Valdivia GarciaP. ValenteR. U. ValenteA. -M. Valente-FelicianoG. ValentinoL. Vale SilvaJ. M. ValetR. ValizadehJ. W. F. ValleS. VallecorsaG. ValloneM. van LeeuwenU. H. van RienenL. van Riesen-HauptM. VarastehL. VecchiP. VedrineG. VelevR. VenessA. VenturaW. Venturini DelsolaroM. VerducciC. B. VerhaarenC. VernieriA. P. VerweijO. VerwilligenO. ViazloA. ViciniG. ViehhauserN. VignaroliM. VignoloA. VitranoI. VivarelliS. VlachosM. VogelD. M. VogtV. VölklP. VolkovG. VolpiniJ. von AhnenG. VorotnikovG. G. VoutsinasV. VysotskyU. WagnerR. WallnyL. -T. WangR. WangK. WangB. F. L. WardT. P. WatsonN. K. WatsonZ. WsC. WeilandS. WeinzierlC. P. WelschJ. WenningerM. WidorskiU. A. WiedemannH. -U. WienandsG. WilkinsonP. H. WilliamsA. WinterA. WohlfahrtT. WojtońD. WollmannJ. WomersleyD. WoogX. WuA. WulzerM. K. YanehsariG. YangH. J. YangW. -M. YaoE. YazganV. YermolchikA. YilmazA. YilmazH. -D. YooS. A. YostT. YouC. YoungT. -T. YuF. YuA. ZaborowskaS. G. ZadehM. ZahndM. ZanettiL. ZanottoL. ZawiejskiP. ZeilerM. ZerlauthS. M. ZernovG. Zevi Dell PortaZ. ZhangY. ZhangC. ZhangH. ZhangZ. ZhaoY. -M. ZhongJ. ZhouD. ZhouP. ZhuangG. ZickF. ZimmermannEmail authorJ. Zinn-JustinL. ZivkovicA. V. ZlobinM. ZobovJ. ZupanJ. Zuritathe FCC Collaboration, In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the fourth volume of the FCC Conceptual Design Report, devoted to the High-Energy Large Hadron Collider HE-LHC. It summarizes the HE-LHC physics discovery opportunities, presents the HE-LHC accelerator design, performance reach, and operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the HE-LHC design aims at a hadron collider with about twice the centre-of-mass collision energy that the LHC can reach. Its performance aims at exploring physics beyond the Standard Model, signi cantly extending the LHC's direct and indirect sensitivity to new physics and discoveries.
Published: 2020

42. Quantitative Analysis of Allantoin in Dioscorea japonica Peel Using an Amino Bonded-Phase HPLC Column

Author: Ja Min Kim, Hunseong Kim, Mijeong Lee, and Dongyup Hahn
Subjects: chemistry.chemical_compound, Allantoin, Chromatography, Dioscorea japonica, biology, chemistry, Phase (matter), biology.organism_classification, Column (botany), High-performance liquid chromatography, Quantitative analysis (chemistry)
Published: 2021

43. Metabolic Syndrome Mediates ROS-miR-193b-NFYA–Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction

Author: Scott A. Hahn, Ying Tang, Mark T. Gladwin, Taijyu Satoh, Charles F. McTiernan, Kentaro Noda, Cynthia St. Hilaire, Bing Wang, Adam C. Straub, Samuel K. Wyman, Cristina Espinosa-Diez, Georgios Triantafyllou, Jeffrey J. Baust, Sruti Shiva, Matthew R Dent, Longfei Wang, Yijen L. Wu, Elena A. Goncharova, Dmitry A. Goncharov, Mike Reynolds, Yen Chun Lai, Andrea R. Levine, Elizabeth R. Rochon, Delphine Gomez, and Stephen Y. Chan
Subjects: Ventricular Dysfunction, Right, MIRN193 microRNA, Cardiorespiratory Medicine and Haematology, 030204 cardiovascular system & hematology, Cardiovascular, Mitochondria, Heart, Animals, Genetically Modified, chemistry.chemical_compound, Soluble Guanylyl Cyclase, 0302 clinical medicine, Smooth Muscle, pulmonary hypertension, Ventricular Dysfunction, 2.1 Biological and endogenous factors, nuclear factor Y, Aetiology, Metabolic Syndrome, 0303 health sciences, Diabetes, Heart, Pulmonary, Mitochondria, Right, Heart Disease, Phenotype, 5.1 Pharmaceuticals, Hypertension, Public Health and Health Services, Disease Susceptibility, Development of treatments and therapeutic interventions, Cardiology and Cardiovascular Medicine, Signal Transduction, Guanylate cyclase, medicine.medical_specialty, Physiological, Hypertension, Pulmonary, Clinical Sciences, Myocytes, Smooth Muscle, Genetically Modified, Stress, Article, Nitric oxide, 03 medical and health sciences, Downregulation and upregulation, nitric oxide, Stress, Physiological, Physiology (medical), Internal medicine, medicine, Animals, Humans, human, Obesity, Exercise, Nutrition, 030304 developmental biology, Heart Failure, Myocytes, Mir 193b, Animal, business.industry, Stroke Volume, medicine.disease, Pulmonary hypertension, Rats, Disease Models, Animal, MicroRNAs, Endocrinology, Cardiovascular System & Hematology, CCAAT-Binding Factor, Gene Expression Regulation, chemistry, Disease Models, Metabolic syndrome, Reactive Oxygen Species, Heart failure with preserved ejection fraction, business, Biomarkers
Abstract: Background: Many patients with heart failure with preserved ejection fraction have metabolic syndrome and develop exercise-induced pulmonary hypertension (EIPH). Increases in pulmonary vascular resistance in patients with heart failure with preserved ejection fraction portend a poor prognosis; this phenotype is referred to as combined precapillary and postcapillary pulmonary hypertension (CpcPH). Therapeutic trials for EIPH and CpcPH have been disappointing, suggesting the need for strategies that target upstream mechanisms of disease. This work reports novel rat EIPH models and mechanisms of pulmonary vascular dysfunction centered around the transcriptional repression of the soluble guanylate cyclase (sGC) enzyme in pulmonary artery (PA) smooth muscle cells. Methods: We used obese ZSF-1 leptin-receptor knockout rats (heart failure with preserved ejection fraction model), obese ZSF-1 rats treated with SU5416 to stimulate resting pulmonary hypertension (obese+sugen, CpcPH model), and lean ZSF-1 rats (controls). Right and left ventricular hemodynamics were evaluated using implanted catheters during treadmill exercise. PA function was evaluated with magnetic resonance imaging and myography. Overexpression of nuclear factor Y α subunit (NFYA), a transcriptional enhancer of sGC β1 subunit (sGCβ1), was performed by PA delivery of adeno-associated virus 6. Treatment groups received the SGLT2 inhibitor empagliflozin in drinking water. PA smooth muscle cells from rats and humans were cultured with palmitic acid, glucose, and insulin to induce metabolic stress. Results: Obese rats showed normal resting right ventricular systolic pressures, which significantly increased during exercise, modeling EIPH. Obese+sugen rats showed anatomic PA remodeling and developed elevated right ventricular systolic pressure at rest, which was exacerbated with exercise, modeling CpcPH. Myography and magnetic resonance imaging during dobutamine challenge revealed PA functional impairment of both obese groups. PAs of obese rats produced reactive oxygen species and decreased sGCβ1 expression. Mechanistically, cultured PA smooth muscle cells from obese rats and humans with diabetes or treated with palmitic acid, glucose, and insulin showed increased mitochondrial reactive oxygen species, which enhanced miR-193b–dependent RNA degradation of nuclear factor Y α subunit (NFYA), resulting in decreased sGCβ1-cGMP signaling. Forced NYFA expression by adeno-associated virus 6 delivery increased sGCβ1 levels and improved exercise pulmonary hypertension in obese+sugen rats. Treatment of obese+sugen rats with empagliflozin improved metabolic syndrome, reduced mitochondrial reactive oxygen species and miR-193b levels, restored NFYA/sGC activity, and prevented EIPH. Conclusions: In heart failure with preserved ejection fraction and CpcPH models, metabolic syndrome contributes to pulmonary vascular dysfunction and EIPH through enhanced reactive oxygen species and miR-193b expression, which downregulates NFYA-dependent sGCβ1 expression. Adeno-associated virus–mediated NFYA overexpression and SGLT2 inhibition restore NFYA-sGCβ1-cGMP signaling and ameliorate EIPH.
Published: 2021

44. Guiding the Catalytic Properties of Copper for Electrochemical CO2 Reduction by Metal Atom Decoration

Author: Christopher Hahn, Thomas F. Jaramillo, Carlos G. Morales-Guio, Hong-Jie Peng, Michal Bajdich, Stephanie A. Nitopi, Yusaku F. Nishimura, Lei Wang, and Frank Abild-Pedersen
Subjects: Materials science, Electrochemistry, Catalysis, Metal, chemistry.chemical_compound, chemistry, Chemical engineering, visual_art, Physical vapor deposition, visual_art.visual_art_medium, General Materials Science, Formate, Selectivity, Bimetallic strip, Oxygenate
Abstract: Tuning bimetallic effects is a promising strategy to guide catalytic properties. However, the nature of these effects can be difficult to assess and compare due to the convolution with other factors such as the catalyst surface structure and morphology and differences in testing environments. Here, we investigate the impact of atomic-scale bimetallic effects on the electrochemical CO2 reduction performance of Cu-based catalysts by leveraging a systematic approach that unifies protocols for materials synthesis and testing and enables accurate comparisons of intrinsic catalytic activity and selectivity. We used the same physical vapor deposition method to epitaxially grow Cu(100) films decorated with a small amount of noble or base metal atoms and a combination of experimental characterization and first-principles calculations to evaluate their physicochemical and catalytic properties. The results indicate that the metal atoms segregate to under-coordinated Cu sites during physical vapor deposition, suppressing CO reduction to oxygenates and hydrocarbons and promoting competing pathways to CO, formate, and hydrogen. Leveraging these insights, we rationalize bimetallic design principles to improve catalytic selectivity for CO2 reduction to CO, formate, oxygenates, or hydrocarbons. Our study provides one of the most extensive studies on Cu bimetallics for CO2 reduction, establishing a systematic approach that is broadly applicable to research in catalyst discovery.
Published: 2021

45. Photoinduced E to Z isomerization of tetraphenylethylene derivatives within organometallic supramolecular assemblies

Author: F. Ekkehardt Hahn, Xiao-Xu Liu, Ying-Feng Han, Yang Li, and Xin Li
Subjects: Ion exchange, Ligand, Supramolecular chemistry, General Chemistry, Tetraphenylethylene, Medicinal chemistry, Coupling reaction, Metal, chemistry.chemical_compound, chemistry, visual_art, visual_art.visual_art_medium, Imidazole, Isomerization
Abstract: Isolation of E-1,2-bis(4-bromophenyl)-1,2-diphenyl-ethylene from the E/Z isomer mixture obtained by a McMurry coupling reaction and reaction of this isomer with imidazole followed by N-alkylation with nBuBr and anion exchange yielded the bisimidazolium tetraphenylethylene (TPE) derivative H2-E-1(PF6)2. The reaction of H2-E-1(PF6)2 with Ag2O yielded the di-nuclear metallarectangle [Ag2(E-1)2](PF6)2 where the two bis-NHC donors E-1 bridge two silver atoms. Irradiation of [Ag2(E-1)2](PF6)2 leads to E/Z isomerization of the di-NHC ligand and formation of Z-1 in the mononuclear complex [Ag(Z-1)]PF6. Demetallation of the di-NHC ligand with NH4Cl/NH4PF6 yielded bisimidazolium salt H2-Z-1(PF6)2. The unique isomerization of the E-TPE derivative into its Z-isomer via metal complex formation/irradiation/demetallation cannot be achieved by irradiation of the individual imidazolium salt. The emissive properties of the TPE complexes [Ag2(E-1)2](PF6)2 and [Ag(Z-1)]PF6 have been investigated.
Published: 2021

46. Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia

Author: Kyu Ri Hahn, Hyun Jung Kwon, In Koo Hwang, Dae Won Kim, Hyo Young Jung, Soo Young Choi, Woosuk Kim, Yeo Sung Yoon, and Seung Myung Moon
Subjects: Programmed cell death, Microglia, Chemistry, Inflammation, General Medicine, Spinal cord, medicine.disease, medicine.disease_cause, Biochemistry, Neuroprotection, Cell biology, Cellular and Molecular Neuroscience, medicine.anatomical_structure, medicine, Tumor necrosis factor alpha, medicine.symptom, Cell damage, Oxidative stress
Abstract: p27Kip1 (p27) regulates the cell cycle by inhibiting G1 progression in cells. Several studies have shown conflicting results on the effects of p27 against cell death in various insults. In the present study, we examined the neuroprotective effects of p27 against H2O2-induced oxidative stress in NSC34 cells and against spinal cord ischemia-induced neuronal damage in rabbits. To promote delivery into NSC34 cells and motor neurons in the spinal cord, Tat-p27 fusion protein and its control protein (Control-p27) were synthesized with or without Tat peptide, respectively. Tat-p27, but not Control-27, was efficiently introduced into NSC34 cells in a concentration- and time-dependent manner, and the protein was detected in the cytoplasm. Tat-p27 showed neuroprotective effects against oxidative stress induced by H2O2 treatment and reduced the formation of reactive oxygen species, DNA fragmentation, and lipid peroxidation in NSC34 cells. Tat-p27, but not Control-p27, ameliorated ischemia-induced neurological deficits and cell damage in the rabbit spinal cord. In addition, Tat-p27 treatment reduced the expression of α-synuclein, activation of microglia, and release of pro-inflammatory cytokines such as interleukin-1β and tumor necrosis factor-α in the spinal cord. Taken together, these results suggest that Tat-p27 inhibits neuronal damage by decreasing oxidative stress, α-synuclein expression, and inflammatory responses after ischemia.
Published: 2021

47. Electrolyte-Guided Design of Electroreductive CO Coupling on Copper Surfaces

Author: Sarah Lamaison, Thomas F. Jaramillo, Sarah E. Baker, Christopher Hahn, Stephen E. Weitzner, Sneha A. Akhade, Hannah V. Eshelman, Julie Hamilton, Jeremy T. Feaster, David W. Wakerley, Joel B. Varley, Buddhinie S. Jayathilake, Lei Wang, Dong Un Lee, and Eric B. Duoss
Subjects: Coupling (electronics), Materials science, chemistry, Chemical physics, Materials Chemistry, Electrochemistry, Energy Engineering and Power Technology, Chemical Engineering (miscellaneous), chemistry.chemical_element, Electrolyte, Electrical and Electronic Engineering, Copper
Published: 2021

48. Microchip for continuous DNA analysis based on gel electrophoresis coupled with co-injection of size markers and in-channel staining

Author: Nokyoung Park, Jong Hoon Hahn, Hanok Kim, and Byoung Joo Kwak
Subjects: Gel electrophoresis, endocrine system, Capillary Tubing, Materials science, Chromatography, Sample (material), DNA, Equipment Design, Polymerase Chain Reaction, Biochemistry, Analytical Chemistry, Staining, Electrophoresis, Microchip, Electrophoresis, Electrokinetic phenomena, chemistry.chemical_compound, chemistry, Limit of Detection, Sample preparation
Abstract: A continuous-flow microchip enabling high-accuracy DNA analysis was developed. Serial consecutive analysis for multiple amplified DNA samples was demonstrated. The sample segments were continuously introduced to the microchip from the PCR device which was interfaced to the microchip through capillary tubing. Electrokinetic co-injection of the DNA samples with size marker enabled reproducible and reliable injection of the DNAs into the gel-filled separation channel providing accurate size determination of the DNA samples. Cross-contamination between serially introduced DNA samples was minimized by plugging a washing solution segment following the previous sample segment between two sample plugs. Using this microchip, continuous separation of multiple samples was performed without any inconvenient and labor-intensive sample preparation steps such as sample mixing, staining, and gel loading which are necessary for conventional gel electrophoresis. It has taken about 4 min to separate single DNA sample and taken 37 min for three serially injected samples which implies that this microchip can be a platform device for fast as well as highly accurate DNA analysis.
Published: 2021

49. Bioinspired urease-powered micromotor as an active oral drug delivery carrier in stomach

Author: Sang Hoon Jeong, Sei Kwang Hahn, Tae Yeon Kim, Hyun-Sik Choi, and Jeeyoon Yi
Subjects: Polydopamine, Urease, QH301-705.5, Biomedical Engineering, Redox, Article, Biomaterials, chemistry.chemical_compound, Dynamic light scattering, medicine, Micro- and nanomotors, Biology (General), Materials of engineering and construction. Mechanics of materials, biology, Chemistry, Stomach, Mucin, Penetration (firestop), Helicobacter pylori, biology.organism_classification, medicine.anatomical_structure, Oral delivery, TA401-492, Urea, biology.protein, Biophysics, Stomach diseases, Biotechnology
Abstract: Self-propelling micro- and nano-motors (MNMs) have been extensively investigated as an emerging oral drug delivery carrier for gastrointestinal (GI) tract diseases. However, the propulsion of current MNMs reported so far is mostly based on the redox reaction of metals (such as Zn and Mg) with severe propulsion gas generation, remaining non-degradable residue in the GI tract. Here, we develop a bioinspired enzyme-powered biopolymer micromotor mimicking the mucin penetrating behavior of Helicobacter pylori in the stomach. It converts urea to ammonia and the subsequent increase of pH induces local gel-sol transition of the mucin layer facilitating the penetration into the stomach tissue layer. The successful fabrication of micromotors is confirmed by high-resolution transmission electron microscopy, electron energy loss spectroscopy, dynamic light scattering analysis, zeta-potential analysis. In acidic condition, the immobilized urease can efficiently converted urea to ammonia, comparable with that of neutral condition because of the increase of surrounding pH during propulsion. After administration into the stomach, the micromotors show enhanced penetration and prolonged retention in the stomach for 24 h. Furthermore, histological analysis shows that the micromotors are cleared within 3 days without causing any toxicity in the GI tract. The enhanced penetration and retention of the micromotors as an active oral delivery carrier in the stomach would be successfully harnessed for the treatment of various GI tract diseases., Graphical abstract Image 1, Highlights • Polydopamine (PDA) hollow microcapsules are biocompatible, biodegradable, and muco-adhesive. • Urease-powered PDA micromotors are propelled by the decomposition of urea to ammonia and carbon dioxide. • Micromotors increase the local pH to induce the gel-sol transition of the mucus layer. • Micromotors result in enhanced penetration and prolonged retention in the stomach. • Micromotors can be effectively used for oral drug delivery with complete clearance from the GI tract.
Published: 2021

50. Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior

Author: Behnam Javidfar, Wei-Dong Yao, Fatemeh Haghighi, M. Foo, C. P. Watkins, C. G. Hahn, Søren Heissel, H. L. Phillips, Schahram Akbarian, Sohit Miglani, Jennifer Blaze, Henrik Molina, B. Rostandy, Zachary T. Pennington, Albertas Navickas, Tao Pan, Hani Goodarzi, Denise J. Cai, Hanan Alwaseem, A. Plaza-Jennings, Sergio Espeso-Gil, Christopher D. Katanski, and Hosseinali Asgharian
Subjects: Proteomics, Proteome, General Physics and Astronomy, Inbred C57BL, Synaptic Transmission, Transgenic, Epigenesis, Genetic, Mice, RNA, Transfer, Epigenetics and behaviour, Prefrontal cortex, skin and connective tissue diseases, Glycine receptor, Mice, Knockout, Neurons, Multidisciplinary, Chemistry, Depression, Epigenetics and plasticity, Cell biology, Mental Health, Transfer RNA, DNA methylation, Neurological, Synaptic signaling, Signal Transduction, Knockout, Science, Prefrontal Cortex, Mice, Transgenic, Neurotransmission, Molecular neuroscience, Basic Behavioral and Social Science, General Biochemistry, Genetics and Molecular Biology, Article, Glutamatergic, Genetic, Behavioral and Social Science, Animals, Author Correction, Depressive Disorder, Gene Expression Profiling, Neurosciences, General Chemistry, Methyltransferases, Brain Disorders, Mice, Inbred C57BL, Transfer, Synaptic plasticity, RNA, sense organs, Epigenesis
Abstract: Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m5C levels, resulting in deficits in expression of 70% of tRNAGly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids., The link between tRNA modifications, protein translation, and behavior is unclear. Here, the authors show that neuronal Nsun2 deficiency results in codon-specific epitranscriptomic changes of Gly-tRNAs and proteomic changes affecting synaptic signaling and behavior in mice.
Published: 2021

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