5,506 results on '"Jacobsen, A"'
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2. SPECIFIC INHIBITORS AND THE CHEMISTRY OF FIBRIN POLYMERIZATION.
- Author
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LORAND L and JACOBSEN A
- Subjects
- Humans, Amides, Amines, Blood Coagulation, Chemical Phenomena, Chemistry, Fibrin, Histamine, Polymerization, Research
- Published
- 1964
- Full Text
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3. Development of an Inventory for Alternative Conception among Students in Chemistry
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Eggen, Per-Odd, Persson, Jonas, Jacobsen, Elisabeth Egholm, and Hafskjold, Bjørn
- Abstract
A chemistry concept inventory (Chemical Concept Inventory 3.0/CCI 3.0) has been developed for assessing students learning and identifying the alternative conceptions that students may have in general chemistry. The conceptions in question are assumed to be mainly learned in school and to a less degree in student's daily life. The inventory presented here aims at functioning as a tool for adjusting teaching practices in chemistry and is mainly designed for assessing the learning outcome during university general chemistry courses. Used as a pre-test the inventory may also give information about student's starting point when entering university's first year chemistry courses.The inventory also aims at functioning as a tool for adjusting teaching practices in chemistry. It has been administered as a pre- and post-test in general chemistry courses at the Norwegian University of Science and Technology (NTNU), and evaluated using different statistical tests, focusing both on item analysis and the on the entire test. The results indicate that the concept inventory is a reliable and discriminating tool in the present context.
- Published
- 2017
4. Selective Extraction Process and Characterization of Antioxidant Phenolic Compounds from Pereskia aculeata Leaves Using UPLC-ESI-Q-TOF-MS/MS
- Author
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Simone Silva Jacobsen, Fernanda Caroline Knob, Anna Paulla Simon, and Tatiane Luiza Cadorin Oldoni
- Subjects
Chemistry ,QD1-999 - Published
- 2024
- Full Text
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5. JCE Resources for Chemistry: Health and Wellness
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Jacobsen, Erica K.
- Abstract
Many simple actions such as eating or reaching for a pain reliever, which we perform without thinking, are tied to chemistry. The American Chemical Society has capitalized on this ubiquitousness with their chosen theme for National Chemistry Week (NCW) 2004: "Health and Wellness."
- Published
- 2004
6. JCE Resources for Chemistry and Art.
- Author
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Jacobsen, Erica K.
- Abstract
Includes an annotated bibliography of articles featured in this journal on art, dyes, glass, pottery and ceramics, interdisciplinary courses in art and chemistry, light and color, metalwork, and music. (YDS)
- Published
- 2001
7. Pyridine-Based Small-Molecule Fluorescent Probes as Optical Sensors for Benzene and Gasoline Adulteration
- Author
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Thiago Jacobsen Peglow, Marcelo Marques Vieira, Nathalia Batista Padilha, Bianca T. Dalberto, Henrique de Castro Silva Júnior, Fabiano Severo Rodembusch, and Paulo Henrique Schneider
- Subjects
organylethynylpyridine ,fuel adulterants ,benzene sensing ,commercial gasoline ,optical sensor ,Chemistry ,QD1-999 - Abstract
Here we present simple fluorophores based on the pyridine core, obtained with straightforward synthetic methodologies. These compounds present in solution absorption maxima in the UV region and fluorescence emission of between 300 and 450 nm, depending on the solvent and chemical structure of the fluorophore. The nature of the solvent was shown to play a fundamental role in their excite-state deactivation, which allowed successful exploration of these compounds as optical sensors for benzene and fuel adulteration in gasoline. In ethanolic solution, upon the addition of benzene, in general the fluorophores presented fluorescence quenching, where a linear correlation between the emission intensity and the amount of benzene (quencher) was observed. In addition, the application of an optical sensor for the detection of fuel adulteration in commercial standard and premium gasoline was successfully presented and discussed. Theoretical calculations were also applied to better understand the solvent–fluorophore interactions.
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- 2023
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8. Synthesis of Enantiopure (S)-Atenolol by Utilization of Lipase-Catalyzed Kinetic Resolution of a Key Intermediate
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Mari Bergan Hansen, Anna Lifen Tennfjord, Fredrik Heen Blindheim, Lucas Hugo Yvan Bocquin, and Elisabeth Egholm Jacobsen
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enantiopure (S)-atenolol ,Candida antarctica lipase B ,base catalysis ,Chiralcel OD-H column ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% enantiomeric excess (ee) with the use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. A catalytic amount of base was used in deprotonation of the phenol building block. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination to yield the final drug. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles. The overall yield of (S)-atenolol was 9.9%, which will be further optimized.
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- 2024
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9. Highly Efficient Ru-Based Catalysts for Lactic Acid Conversion to Alanine
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Iunia Podolean, Mara Dogaru, Nicolae Cristian Guzo, Oana Adriana Petcuta, Elisabeth E. Jacobsen, Adela Nicolaev, Bogdan Cojocaru, Madalina Tudorache, Vasile I. Parvulescu, and Simona M. Coman
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ruthenium nanoparticles ,MWCNT ,beta-zeolite ,magnetic nanoparticles ,amination ,lactic acid ,Chemistry ,QD1-999 - Abstract
The primary objective of this research was to develop efficient solid catalysts that can directly convert the lactic acid (LA) obtained from lignocellulosic biomass into alanine (AL) through a reductive amination process. To achieve this, various catalysts based on ruthenium were synthesized using different carriers such as multi-walled carbon nanotubes (MWCNTs), beta-zeolite, and magnetic nanoparticles (MNPs). Among these catalysts, Ru/MNP demonstrated a remarkable yield of 74.0% for alanine at a temperature of 200 °C. This yield was found to be superior not only to the Ru/CNT (55.7%) and Ru/BEA (6.6%) catalysts but also to most of the previously reported catalysts. The characterization of the catalysts and their catalytic results revealed that metallic ruthenium nanoparticles, which were highly dispersed on the external surface of the magnetic carrier, significantly enhanced the catalyst’s ability for dehydrogenation. Additionally, the -NH2 basic sites on the catalyst further facilitated the formation of alanine by promoting the adsorption of acidic reactants. Furthermore, the catalyst could be easily separated using an external magnetic field and exhibited the potential for multiple reuses without any significant loss in its catalytic performance. These practical advantages further enhance its appeal for applications in the reductive amination of lactic acid to alanine.
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- 2024
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10. Soup or Salad? Investigating the Action of Enzymes in Fruit on Gelatin.
- Author
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Jacobsen, Erica
- Abstract
Presents an activity in which students observe gelatin samples treated with substances that may or may not have an enzymatic effect on the protein on the gelatin. (WRM)
- Published
- 1999
11. Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis
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James R. Anderson, Emily Johnson, Rosalind Jenkins, Stine Jacobsen, Daniel Green, Marie Walters, Louise Bundgaard, Bas A. C. Hausmans, Guus van den Akker, Tim J. M. Welting, Alzbeta Chabronova, Yalda A. Kharaz, Emily J. Clarke, Victoria James, and Mandy J. Peffers
- Subjects
extracellular vesicles ,osteoarthritis ,multi-omics ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Extracellular vesicles (EVs) contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Synovial fluid-derived EVs have the potential to be direct biomarkers in the causal pathway of disease but also enable understanding of their role in disease progression. Utilizing a temporal model of osteoarthritis, we defined the changes in matched synovial fluid and plasma-derived EV small non-coding RNA and protein cargo using sequencing and mass spectrometry. Data exploration included time series clustering, factor analysis and gene enrichment interrogation. Chondrocyte signalling was analysed using luciferase-based transcription factor activity assays. EV protein cargo appears to be more important during osteoarthritis progression than small non-coding RNAs. Cluster analysis revealed plasma-EVs represented a time-dependent response to osteoarthritis induction associated with supramolecular complexes. Clusters for synovial fluid-derived EVs were associated with initial osteoarthritis response and represented immune/inflammatory pathways. Factor analysis for plasma-derived EVs correlated with day post-induction and were primarily composed of proteins modulating lipid metabolism. Synovial fluid-derived EVs factors represented intermediate filament and supramolecular complexes reflecting tissue repair. There was a significant interaction between time and osteoarthritis for CRE, NFkB, SRE, SRF with a trend for osteoarthritis synovial fluid-derived EVs at later time points to have a more pronounced effect.
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- 2023
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12. Visible light-promoted synthesis of 2-aryl-(3-organoselanyl)thieno[2,3-b]pyridines
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Ricardo Hellwig Bartz, Thiago Jacobsen Peglow, Filipe Penteado, Raquel Guimarães Jacob, Eder João Lenardão, and Gelson Perin
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Organochalcogen ,thieno[2,3-b]pyridines ,green chemistry ,visible light-promoted reaction ,heterocycles ,selenocyclization ,Science ,Chemistry ,QD1-999 - Abstract
We describe a simple and environment-friendly visible light-promoted protocol to access 2-aryl-(3-organoselanyl)thieno[2,3-b]pyridines, through the selenocyclization of 3-(arylethynyl)-2-(alkylthio)pyridines in the presence of diorganyl diselenides as selenium source. The Se-based reactive species were generated in situ by the homolytic Se-Se bond cleavage using blue LED in an O2 atmosphere at room temperature. The protocol was suitable for a wide range of substrates bearing different substituents, allowing the synthesis of twenty-one thieno[2,3-b]pyridines in good to excellent yields (57–99%).
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- 2022
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13. Development and Application of Oligonucleotide Assays for Site-Directed RNA Editing
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Jacobsen, Casey Stephen
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Chemistry ,ADAR ,Proteins ,RNA ,RNA Editing ,Transcriptome - Abstract
Adenosine Deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosine to inosine in duplex RNA. The inosine product preferentially base pairs with cytidine resulting in an effective A-to-G edit in RNA. ADAR editing can result in a recoding event alongside other alterations to RNA function. A consequence of ADARs’ selective activity on duplex RNA is that guide RNAs (gRNAs) can be designed to target an adenosine of interest and promote a desired recoding event. One of ADAR’s main limitations is its preference to edit adenosines with specific 5’ and 3’ nearest neighbor nucleotides (e.g. 5’U, 3’G). Current rational design approaches are well-suited for this ideal sequence context but limited when applied to difficult-to-edit sites. Another limitation of ADAR editing is its specificity. ADARs can edit non-target sites due to the presence of good targets elsewhere. To achieve more specific editing, a gRNA may be discovered that allows for a reduction in off-target editing.In this dissertation, I describe a strategy for the in vitro evaluation of very large libraries of ADAR substrates, called En Mass Evaluation of RNA Guides (EMERGe). EMERGe allows for a comprehensive screening of ADAR substrate RNAs that complements current design approaches. I used this approach to identify sequence motifs for gRNAs that enable editing in otherwise difficult-to-edit target sites. EMERGe provides an advancement in screening that not only allows for novel gRNA design, but also furthers our understanding of ADARs’ specific RNA-protein interactions. Chapter 1 provides a general introduction to ADARs and their application for site-directed RNA editing. This chapter also describes current advancements in gRNA design and discovery. Chapter 2 outlines the studies used before the EMERGe assay. Additionally, this chapter will also describe the development of the EMERGe assay. The validation of the EMERGe assay is discussed within Chapter 3. Other discoveries made by the EMERGe assays will be tested in vitro within this chapter. Finally, Chapter 4 discusses in cellula applications of EMERGe-derived results. This includes testing EMERGe-derived gRNAs, in cellula results with a previously untested chemical modification, and the limitations of a new yeast-based assay.
- Published
- 2023
14. The Use of Soy and Egg Phosphatidylcholines Modified with Caffeic Acid Enhances the Oxidative Stability of High-Fat (70%) Fish Oil-in-Water Emulsions
- Author
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Betül Yesiltas, Pedro J. García-Moreno, Ann-Dorit M. Sørensen, Chiranjib Banerjee, Sampson Anankanbil, Zheng Guo, Peter R. Ogilby, and Charlotte Jacobsen
- Subjects
emulsifiers ,surfactants ,oxidation ,oil-water interface ,microscopy ,Chemistry ,QD1-999 - Abstract
This study investigated the effect of the combined use of sodium caseinate (CAS), commercial phosphatidylcholine (PC), and modified PCs on the physical and oxidative stability of 70% fish oil-in-water emulsions. Caffeic acid was covalently attached to both modified PCs (PCs originated from soy and eggs) in order to increase the antioxidant activity of PCs and investigate the advantage of bringing the antioxidant activity to the close proximity of the oil-water interface. Results showed that oxidative stability was improved when part of the PC was substituted with modified soy PC or egg PC. Emulsions containing a low concentration of modified PCs (10 wt.% of total PC) resulted in a prooxidative effect on the formation of hydroperoxides compared to emulsions with free caffeic acid. On the other hand, a decrease in the formation of volatile oxidation products was observed for emulsions containing higher levels of modified PCs (60 wt.% of total PC) compared to the emulsions with free caffeic acid added at its equivalent concentration. Increased concentrations of modified PCs provided better oxidative stability in high-fat emulsions, independent of the modified PC type. Moreover, when oxidation was initiated by producing singlet oxygen near a single oil droplet using a focused laser, fluorescence imaging showed that the oxidation did not propagate from one oil droplet to another oil droplet.
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- 2023
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15. The Effect of Cellulose Nanofibres on Dewatering during Wet-Forming and the Mechanical Properties of Thermoformed Specimens Made of Thermomechanical and Kraft Pulps
- Author
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Eirik Ulsaker Jacobsen, Simen Prang Følkner, Jørgen Blindheim, Dag Molteberg, Martin Steinert, and Gary Chinga-Carrasco
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wet-forming ,thermoforming ,wood pulp ,nanocellulose ,food packaging ,sustainable ,Chemistry ,QD1-999 - Abstract
Due to environmental concerns regarding single-use plastic materials, major efforts are being made to develop new material concepts based on biodegradable and renewable resources, e.g., wood pulp. In this study, we assessed two types of wood pulp fibres, i.e., thermomechanical pulp (TMP) and Kraft pulp fibres, and tested the performance of the fibres in wet-moulding and thermopressing trials. Kraft pulp fibres appeared to retain more water than TMP, increasing the dewatering time during wet-moulding and apparently increasing the compression resistance of the pulp during thermoforming. Additionally, cellulose nanofibres (CNF) were added to the pulps, which improved the mechanical properties of the final thermopressed specimens. However, the addition of CNF to the pulps (from 2 to 6%) had a further decrease in the dewatering efficiency in the wet-moulding process, and this effect was more pronounced in the Kraft pulp specimens. The mechanical performance of the thermoformed specimens was in the same range as the plastic materials that are conventionally used in food packaging, i.e., modulus 0.6–1.2 GPa, strength 49 MPa and elongation 6–9%. Finally, this study demonstrates the potential of wood pulps to form three-dimensional thermoformed products.
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- 2023
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16. Design of an Autonomous Cooperative Drone Swarm for Inspections of Safety Critical Infrastructure
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Rune Hylsberg Jacobsen, Lea Matlekovic, Liping Shi, Nicolaj Malle, Naeem Ayoub, Kaspar Hageman, Simon Hansen, Frederik Falk Nyboe, and Emad Ebeid
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unmanned aerial vehicle (UAV) ,drone ,autonomous ,cooperation ,swarming ,infrastructure inspection ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Inspection of critical infrastructure with drones is experiencing an increasing uptake in the industry driven by a demand for reduced cost, time, and risk for inspectors. Early deployments of drone inspection services involve manual drone operations with a pilot and do not obtain the technological benefits concerning autonomy, coordination, and cooperation. In this paper, we study the design needed to handle the complexity of an Unmanned Aerial System (UAS) to support autonomous inspection of safety-critical infrastructure. We apply a constructive research approach to link innovation needs with concepts, designs, and validations that include simulation and demonstration of key design parts. Our design approach addresses the complexity of the UAS and provides a selection of technology components for drone and ground control hardware and software including algorithms for autonomous operation and interaction with cloud services. The paper presents a drone perception system with accelerated onboard computing, communication technologies of the UAS, as well as algorithms for swarm membership, formation flying, object detection, and fault detection with artificial intelligence. We find that the design of a cooperative drone swarm and its integration into a custom-built UAS for infrastructure inspection is highly feasible given the current state of the art in electronic components, software, and communication technology.
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- 2023
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17. Chemo-Enzymatic Synthesis of Enantiopure β-Antagonist (S)-Betaxolol
- Author
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Susanne Hansen Troøyen and Elisabeth Egholm Jacobsen
- Subjects
(S)-betaxolol ,enantiopure building blocks ,Candida antarctica lipase B ,chiral chromatography ,Chemical technology ,TP1-1185 ,Chemistry ,QD1-999 - Abstract
The β-blocker (S)-betaxolol has been synthesized in 99% enantiomeric excess (ee) from the commercially available precursor 4-(2-hydroxyethyl)phenol. The racemic chlorohydrin 1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol was esterified with vinyl acetate catalyzed by lipase B from Candida antarctica, which gave the R-chlorhydrin (R)-1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol in 99% ee with 38% yield. The enantiomeric excess of the R-chlorohydrin was retained in an amination reaction with isopropylamine in methanol to yield (S)-betaxolol in 99% ee and with 9% overall yield. We are under way to improve the yield.
- Published
- 2022
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18. Investigation of Structural Alterations in Inherited Retinal Diseases: A Quantitative SD-OCT-Analysis of Retinal Layer Thicknesses in Light of Underlying Genetic Mutations
- Author
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Julia Gersch, Katerina Hufendiek, Julien Delarocque, Carsten Framme, Christina Jacobsen, Heidi Stöhr, Ulrich Kellner, and Karsten Hufendiek
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inherited retinal diseases ,SD-OCT ,biomarkers ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Inherited retinal diseases can result from various genetic defects and are one of the leading causes for blindness in the working-age population. The present study aims to provide a comprehensive description of changes in retinal structure associated with phenotypic disease entities and underlying genetic mutations. Full macular spectral domain optical coherence tomography scans were obtained and manually segmented in 16 patients with retinitis pigmentosa, 7 patients with cone–rod dystrophy, and 7 patients with Stargardt disease, as well as 23 age- and sex-matched controls without retinal disease, to assess retinal layer thicknesses. As indicated by generalized least squares models, all IRDs were associated with retinal thinning (p < 0.001), especially of the outer nuclear layer (ONL, p < 0.001). Except for the retinal nerve fiber layer, such thinning was associated with a reduced visual acuity (p < 0.001). These advances in our understanding of ultrastructural retinal changes are important for the development of gene-, cell-, and optogenetic therapy. Longitudinal studies are warranted to describe the temporal component of those changes.
- Published
- 2022
- Full Text
- View/download PDF
19. Chemoenzymatic Protocol for the Synthesis of Enantiopure β-Blocker (S)-Bisoprolol
- Author
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Lucas Bocquin and Elisabeth Egholm Jacobsen
- Subjects
(S)-bisoprolol ,enantiopure building blocks ,Candida antarctica lipase B ,chiral chromatography ,Chemical technology ,TP1-1185 ,Chemistry ,QD1-999 - Abstract
The β-blocker (S)-bisoprolol hemifumarate has been synthesised in 96% enantiomeric excess with 19% total yield in a six-step synthesis. A transesterification reaction of the racemic chlorohydrin 1-chloro-3-(4-((2-isopropoxyethoxy)methyl)phenoxy)propan-2-ol catalysed by lipase B from Candida antarctica resulted in the R-chlorohydrin in high enantiomeric purity. Reaction of this building block with isopropylamine in methanol gave (S)-bisoprolol, and further reaction with fumaric acid gave (S)-bisoprolol fumarate in 96% ee. Specific rotation value confirmed the absolute configuration of the enantiopure drug.
- Published
- 2022
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20. A Sense of Community
- Author
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Jacobsen, Erica K.
- Abstract
Members of the teaching and learning community share a spirit of camaraderie when they meet during conferences or seminars even though they may not know each other. Also there are programs like the ACS's ChemClub pilot program, which will encourage binding between the fraternities and help them to achieve the same purpose of building connections among teachers, students and chemistry.
- Published
- 2007
21. 'Only When You Know the Hazards...'
- Author
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Jacobsen, Erica K.
- Abstract
The disposal of hazardous chemicals and chemical containing products is of much concern and there is a need for a document that describes the hazards of a chemical, to consider the precautionary measures to be taken. Many classic demonstrations however cannot be performed due to safety concerns since sometimes chemicals are deemed too hazardous or cause too much difficulty with disposal.
- Published
- 2005
22. Basic Energy Sciences Network Requirements Review - Final Report
- Author
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Dart, Eli, Bell, Greg, Boehnlein, Amber, Dalesio, Robert, Dattoria, Vince, Davenport, Jim, Freericks, Jim, Griffin, Mike, Hester, Mary, Jacobsen, Christopher, Lee, Steve, Lessner, Eliane, Kettimuthu, Raj, Ndousse-Fetter, Thomas, Oefelein, Joe, Ophus, Colin, Parkinson, Dula, Pederson, Mark, Persson, Kristen, Preuss, Don, Proffen, Thomas, Rotman, Lauren, Sethian, James, Sumpter, Bobby, Tull, Craig, Vashishta, Priya, and Zurawski, Jason
- Subjects
Basic Energy Sciences ,Synchrotron ,Free Electron Laser ,Facility ,High Performance Computing ,High Performance Networking ,ESnet ,Chemistry ,Combustion ,Materials Science ,Applied Mathematics ,Neutron Source - Abstract
The Energy Sciences Network (ESnet) is the primary provider of network connectivity for the US De- partment of Energy (DOE) Office of Science (SC), the single largest supporter of basic research in the physical sciences in the United States. In support of the Office of Science programs, ESnet regularly updates and refreshes its understanding of the networking requirements of the instruments, facilities, scientists, and science programs that it serves. This focus has helped ESnet to be a highly successful enabler of scientific discovery for over 25 years.In September 2014, ESnet and the Office of Basic Energy Sciences (BES), of the DOE Office of Science, organized a review to characterize the networking requirements of the programs funded by the BES program office.Several key findings resulted from the review.
- Published
- 2015
23. Water Filtration
- Author
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Jacobsen, Erica K.
- Abstract
A water filtration column is devised by students using a two-liter plastic bottle containing gravel, sand, and activated charcoal, to test the filtration potential of the column. Results indicate that the filtration column eliminates many of the contaminating materials, but does not kill bacteria.
- Published
- 2004
24. Use of Photocatalytically Active Supramolecular Organic–Inorganic Magnetic Composites as Efficient Route to Remove β-Lactam Antibiotics from Water
- Author
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Sabina G. Ion, Octavian D. Pavel, Nicolae Guzo, Madalina Tudorache, Simona M. Coman, Vasile I. Parvulescu, Bogdan Cojocaru, and Elisabeth E. Jacobsen
- Subjects
layered double hydroxides ,magnetic nanoparticles ,phthalocyanines ,antibiotics removal ,Chemical technology ,TP1-1185 ,Chemistry ,QD1-999 - Abstract
Considerable efforts have been made in recent years to identify an optimal treatment method for the removal of antibiotics from wastewaters. A series of supramolecular organic-inorganic magnetic composites containing Zn-modified MgAl LDHs and Cu-phthalocyanine as photosensitizers were prepared with the aim of removing β-lactam antibiotics from aqueous solutions. The characterization of these materials confirmed the anchorage of Cu-phthalocyanine onto the edges of the LDH lamellae, with a negligible part inserted in the interlayer space. The removal of the β-lactam antibiotics occurred via concerted adsorption and photocatalytic degradation. The efficiency of the composites depended on (i) the LDH: magnetic nanoparticle (MP) ratio, which was strongly correlated with the textural properties of the catalysts, and (ii) the phthalocyanine loading in the final composite. The maximum efficiency was achieved with a removal of ~93% of the antibiotics after 2 h of reaction.
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- 2022
- Full Text
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25. Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β-Blockers (S)-Esmolol and (S)-Penbutolol
- Author
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Susanne Hansen Troøyen, Lucas Bocquin, Anna Lifen Tennfjord, Kristoffer Klungseth, and Elisabeth Egholm Jacobsen
- Subjects
(S)-esmolol ,(S)-penbutolol ,enantiopure building blocks ,characterisation of a dimeric by-product ,Candida antarctica lipase B ,chiral chromatography ,Chemical technology ,TP1-1185 ,Chemistry ,QD1-999 - Abstract
The β-blocker (S)-esmolol, has been synthesized in 97% enantiomeric excess and 26% total yield in a four-step synthesis, with a transesterification step of the racemic chlorohydrin methyl 3-(4-(3-chloro-2-hydroxypropoxy)phenyl)propanoate, catalysed by lipase B from Candida antarctica from Syncozymes, Shanghai, China. The β-blocker (S)-penbutolol, has been synthesized in 99% enantiomeric excess and in 22% total yield. The transesterification step of the racemic chlorohydrin 1-chloro-3-(2-cyclopentylphenoxy)propan-2-ol was catalyzed by the same lipase as used for the esmolol building block. We have used different bases for the deprotonation step of the starting phenols, and vinyl butanoate as the acyl donor in the transesterification reactions. The reaction times for the kinetic resolution steps catalysed by the lipase varied from 23 to 48 h, and were run at 30–38 °C. Specific rotation values confirmed the absolute configuration of the enantiopure drugs, however, an earlier report of the specific rotation value of (S)-esmolol is not consistent with our measured specific rotation values, and we here claim that our data are correct. Compared to the previously reported syntheses of these two enantiopure drugs, we have replaced toluene or dichloromethane with acetonitrile, and replaced the flammable acetyl chloride with lithium chloride. We have also reduced the amount of epichlorohydrin and bases, and identified dimeric byproducts in order to obtain higher yields.
- Published
- 2022
- Full Text
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26. Peptidylarginine Deiminase 2 Gene Polymorphisms in Subjects with Periodontitis Predispose to Rheumatoid Arthritis
- Author
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Laura Massarenti, Christian Enevold, Dres Damgaard, Peter Riis Hansen, Morten Frisch, Niels Ødum, Søren Jacobsen, and Claus Henrik Nielsen
- Subjects
rheumatoid arthritis ,peptidylarginine deiminases ,anti-citrullinated protein antibodies (ACPAs) ,single nucleotide polymorphism ,periodontitis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Epidemiologic studies have shown associations between periodontitis and rheumatoid arthritis (RA), but a causal relationship has not been established. Citrullination of gingival proteins by human peptidylarginine deiminases (PADs) or PAD from Porphyromonas gingivalis has been proposed to generate autoantigens in anti-CCP-positive RA. This study investigated whether the association between periodontitis and RA is influenced by single nucleotide polymorphisms (SNPs) in the genes encoding PAD2 and PAD4 that catalyze aberrant citrullination in RA and often are overexpressed in inflamed gingival connective tissue in subjects with periodontitis. The study included 137 RA patients and 161 controls with self-reported periodontitis. Periodontitis onset preceded RA onset by 13 years on average and was not associated with any of the SNPs investigated. In subjects with periodontitis, carriage of the minor alleles of rs2057094 and rs2235912 in PADI2 significantly increased the risk of RA (odds ratios 1.42 [p = 0.03] and 1.48 [p = 0.02], respectively), and this effect was driven by the anti-CCP-negative RA patients. The minor alleles of these SNPs only increased risk of anti-CCP-positive RA in individuals with periodontitis and a history of smoking. These data suggest that individuals with periodontitis carrying the minor alleles of SNPs rs2057094, rs2076616 and rs2235912 in PADI2 may be at increased risk of RA.
- Published
- 2022
- Full Text
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27. An Advanced Approach for MgZnAl-LDH Catalysts Synthesis Used in Claisen-Schmidt Condensation
- Author
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Rodica Zăvoianu, Silvana-Denisa Mihăilă, Bogdan Cojocaru, Mădălina Tudorache, Vasile I. Pârvulescu, Octavian Dumitru Pavel, Solon Oikonomopoulos, and Elisabeth Egholm Jacobsen
- Subjects
layered double hydroxides (LDH) ,mechano-chemical/co-precipitation synthesis ,organic alkalis (tetramethylammonium hydroxide) ,memory effect ,Claisen-Schmidt condensation ,self-cyclohexanone condensation ,Chemical technology ,TP1-1185 ,Chemistry ,QD1-999 - Abstract
Using organic-base tetramethylammonium hydroxide (TMAH) is a viable, cheap, and fast option for the synthesis of MgZnAl-LDH-type materials by both co-precipitation and mechano-chemical methods. TMAH presents several advantages, such as the smaller quantity of water required in the washing step compared to the use of inorganic alkalis, the prevention of LDH contamination with alkali cations, and its action as a template molecule in texture tailoring. It also has disadvantages, such as its presence in small quantities in the resulting layered materials. Regardless of the use of organic/inorganic bases and co-precipitation/mechano-chemical methods, zincite stable phase was found in all the synthesized solids. The basicity of catalysts followed the trend: mixed oxides > reconstructed > parent LDH. The memory effect of LDH was supported only by the presence of Mg and Al cations, while Zn remained as a zincite stable phase. The catalytic activities for Claisen-Schmidt condensation of benzaldehyde with cyclohexanone provided values higher than 90% after 2 h, with a total selectivity toward 2,6-dibenzylidenecyclohexanone, while self-condensation of cyclohexanone yielded no more than 7.29% after 5 h. These behaviors depended on catalyst basicity as well as on the planar rigidity of the compound.
- Published
- 2022
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28. Characterization of Glycosaminoglycans in Gaping and Intact Connective Tissues of Farmed Atlantic Salmon (Salmo salar) Fillets by Mass Spectrometry
- Author
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Ása Jacobsen, Xiaofeng Shi, Chun Shao, Jonhard Eysturskarδ, Svein-Ole Mikalsen, and Joseph Zaia
- Subjects
Chemistry ,QD1-999 - Published
- 2019
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29. Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer
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Frederik J. Hansen, Zhiyuan Wu, Paul David, Anke Mittelstädt, Anne Jacobsen, Malgorzata J. Podolska, Kenia Ubieta, Maximilian Brunner, Dina Kouhestani, Izabela Swierzy, Lotta Roßdeutsch, Bettina Klösch, Isabella Kutschick, Susanne Merkel, Axel Denz, Klaus Weber, Carol Geppert, Robert Grützmann, Alan Bénard, and Georg F. Weber
- Subjects
CD20 ,B-cells ,CD73 ,colorectal cancer ,neoadjuvant treatment ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73+ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73+ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73+ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73+ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.
- Published
- 2022
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30. Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin
- Author
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Mai Bay Stie, Johan Ring Gätke, Ioannis S. Chronakis, Jette Jacobsen, and Hanne Mørck Nielsen
- Subjects
sublingual delivery ,biopharmaceuticals ,peptide drug delivery ,electrospinning ,mucoadhesion ,ex vivo flow retention model ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber–film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.
- Published
- 2022
- Full Text
- View/download PDF
31. Evolution of Xylem Lignification and Hydrogel Transport Regulation
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Boyce, C. Kevin, Zwieniecki, Maciej A., Cody, George D., Jacobsen, Chris, Wirick, Sue, Knoll, Andrew H., and Holbrook, N. Michele
- Published
- 2004
32. Evaluation of New, Sputtered Carbon SPME Fibers with a Multi-Functional Group Test Mixture
- Author
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Dhananjay I. Patel, Tuhin Roychowdhury, Collin Jacobsen, Colton Myers, Jason S. Herrington, and Matthew R. Linford
- Subjects
SPME ,test mix ,carbon ,sputtering ,gas chromatography ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
We report the first fabrication of sputtered carbon, solid-phase microextraction (SPME) fibers. These fibers have competitive extraction capabilities compared with the commercial carbon wide range (CWR) SPME fiber. This report also includes a demonstration of a newly developed SPME test mix that includes 15 different compounds with a wide range of functional groups and chemical properties. The fiber fabrication process involves sputtering carbon onto fused silica fibers, and the effects of throw distance on the morphology of the carbon coatings were studied. Four different carbon coating thicknesses were evaluated, with PDMS added as a stationary phase. These fibers were characterized with multiple analytical techniques, including scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), water contact angle (WCA) goniometry, as well as headspace (HS) and direct immersion (DI)–SPME–GC–MS. The best (11.5 µm) sputtered carbon SPME fibers, with and without PDMS, were evaluated using the new evaluation mix and compared with the commercial CWR fiber and a previously sputtered/developed silicon fiber. The new probe mix helped elucidate differences among the fibers, which would have been missed by current commercial test mixes. The sputtered carbon SPME fibers showed similar functional group selectivity as commercial CWR fibers. However, the sputtered carbon fibers showed higher responses per volume compared with the commercial CWR fiber, indicating the porous morphology of the sputtered carbon has the ability to overcome large phase thickness/volume discrepancies and increase the relative recovery for various compounds.
- Published
- 2021
- Full Text
- View/download PDF
33. Asymmetric Catalysis in Complex Target Synthesis
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Taylor, Mark S., Jacobsen, Eric N., and Halpern, Jack
- Published
- 2004
34. 100 Gbaud On–Off Keying/Pulse Amplitude Modulation Links in C-Band for Short-Reach Optical Interconnects
- Author
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Oskars Ozolins, Xiaodan Pang, Aleksejs Udalcovs, Richard Schatz, Sandis Spolitis, Vjaceslavs Bobrovs, Gunnar Jacobsen, and Sergei Popov
- Subjects
optical interconnects ,on–off keying ,pulse amplitude modulation ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
We experimentally evaluate the high-speed on–off keying (OOK) and four-level pulse amplitude modulation (PAM4) transmitter’s performance in C-band for short-reach optical interconnects. We demonstrate up to 100 Gbaud OOK and PAM4 transmission over a 400 m standard single-mode fiber with a monolithically integrated externally modulated laser (EML) having 100 GHz 3 dB bandwidth with 2 dB ripple. We evaluate its capabilities to enable 800 GbE client-side links based on eight, and even four, optical lanes for optical interconnect applications. We study the equalizer’s complexity when increasing the baud rate of PAM4 signals. Furthermore, we extend our work with numerical simulations showing the required received optical power (ROP) for a certain bit error rate (BER) for the different combinations of the effective number of bits (ENOB) and extinction ratio (ER) at the transmitter. We also show a possibility to achieve around 1 km dispersion uncompensated transmission with a simple decision feedback equalizer (DFE) for a 100 Gbaud OOK, PAM4, and eight-level PAM (PAM8) link having the received power penalty of around 1 dB.
- Published
- 2021
- Full Text
- View/download PDF
35. Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol
- Author
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Morten Andre Gundersen, Guro Buaas Austli, Sigrid Sløgedal Løvland, Mari Bergan Hansen, Mari Rødseth, and Elisabeth Egholm Jacobsen
- Subjects
(S)-practolol ,paracetamol ,(S)-pindolol ,(S)-carteolol ,Candida antarctica Lipase B ,chiral chromatography ,Chemical technology ,TP1-1185 ,Chemistry ,QD1-999 - Abstract
Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker (S)-practolol ((S)-N-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. (S)-Carteolol was produced in 96% ee with low yield, which easily can be improved.
- Published
- 2021
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36. Discovery of FeBi2
- Author
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James P. S. Walsh, Samantha M. Clarke, Yue Meng, Steven D. Jacobsen, and Danna E. Freedman
- Subjects
Chemistry ,QD1-999 - Published
- 2016
- Full Text
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37. Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy
- Author
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Steffan Noe Christiansen, Stine Bøttcher Jacobsen, Jeppe Dyrberg Andersen, Marie-Louise Kampmann, Linea Christine Trudsø, Kristine Boisen Olsen, Jacob Tfelt-Hansen, Jytte Banner, and Niels Morling
- Subjects
epigenetics ,genetics ,DNA methylation ,RNA ,molecular autopsy ,sudden cardiac death ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Sudden cardiac death (SCD) is a diagnostic challenge in forensic medicine. In a relatively large proportion of the SCDs, the deaths remain unexplained after autopsy. This challenge is likely caused by unknown disease mechanisms. Changes in DNA methylation have been associated with several heart diseases, but the role of DNA methylation in SCD is unknown. In this study, we investigated DNA methylation in two SCD subtypes, sudden unexplained death (SUD) and sudden unexpected death in epilepsy (SUDEP). We assessed DNA methylation of more than 850,000 positions in cardiac tissue from nine SUD and 14 SUDEP cases using the Illumina Infinium MethylationEPIC BeadChip. In total, six differently methylated regions (DMRs) between the SUD and SUDEP cases were identified. The DMRs were located in proximity to or overlapping genes encoding proteins that are a part of the glutathione S-transferase (GST) superfamily. Whole genome sequencing (WGS) showed that the DNA methylation alterations were not caused by genetic changes, while whole transcriptome sequencing (WTS) showed that DNA methylation was associated with expression levels of the GSTT1 gene. In conclusion, our results indicate that cardiac DNA methylation is similar in SUD and SUDEP, but with regional differential methylation in proximity to GST genes.
- Published
- 2021
- Full Text
- View/download PDF
38. Synergistic Ion-Binding Catalysis Demonstrated via an Enantioselective, Catalytic [2,3]-Wittig Rearrangement
- Author
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C. Rose Kennedy, Jennifer A. Guidera, and Eric N. Jacobsen
- Subjects
Chemistry ,QD1-999 - Published
- 2016
- Full Text
- View/download PDF
39. Engineering ergothioneine production in Yarrowia lipolytica
- Author
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Irene Hjorth Jacobsen, Douglas B. Kell, José L. Martínez, Steven Axel van der Hoek, Irina Borodina, and Matej Rusnák
- Subjects
Yarrowia lipolytica ,0106 biological sciences ,Antioxidant ,Phosphate-limitation ,medicine.medical_treatment ,Biophysics ,Yarrowia ,01 natural sciences ,Biochemistry ,Phosphates ,Neurospora crassa ,Metabolic engineering ,03 medical and health sciences ,chemistry.chemical_compound ,Bioreactors ,SDG 3 - Good Health and Well-being ,Structural Biology ,010608 biotechnology ,Genetics ,medicine ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,biology ,Ergothioneine ,Cell Biology ,biology.organism_classification ,Claviceps purpurea ,Yeast ,Metabolic Engineering ,chemistry ,Fermentation ,Nutraceutical - Abstract
Ergothioneine is a naturally occurring antioxidant that has shown potential in ameliorating neurodegenerative and cardiovascular diseases. In this study, we investigated the potential of the Crabtree-negative, oleaginous yeast Yarrowia lipolytica as an alternative host for ergothioneine production. We expressed the biosynthetic enzymes EGT1 from Neurospora crassa and EGT2 from Claviceps purpurea to obtain 158 mg/L of ergothioneine in small-scale cultivation, with an additional copy of each gene improving the titer to 205 mg/L. The effect of phosphate limitation on ergothioneine production was studied, and finally, a phosphate-limited fed-batch fermentation in 1 L bioreactors yielded 1.63 ± 0.04 g/L ergothioneine in 220 hours, corresponding to an overall volumetric productivity of 7.41 mg L-1 h-1 , showing that Yarrowia lipolytica is a promising host for ergothioneine production.
- Published
- 2021
40. Chiral Ureas, Thioureas, and Squaramides in Anion‐Binding Catalysis with Co‐catalytic <scp>B</scp> rønsted/ <scp>L</scp> ewis Acids
- Author
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Eric N. Jacobsen and Adam H. Trotta
- Subjects
Chemistry ,Anion binding ,Combinatorial chemistry ,Catalysis - Published
- 2021
41. Mechanism of siRNA production by a plant Dicer-RNA complex in dicing-competent conformation
- Author
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Laixing Zhang, Steven E. Jacobsen, Jiamu Du, Zhe Wu, C. Jake Harris, Sisi Li, Zhenhui Zhong, Qian Wang, Maojun Yang, Changshi Wang, Zhenlin Yang, Suhua Feng, Jixian Zhai, Yan Xue, and Lifan Xiao
- Subjects
Models, Molecular ,Ribonuclease III ,Protein Conformation ,Arabidopsis ,Article ,Protein Domains ,Phosphorylation ,RNA, Small Interfering ,Multidisciplinary ,biology ,Arabidopsis Proteins ,Chemistry ,Mechanism (biology) ,Cryoelectron Microscopy ,RNA ,Cell biology ,enzymes and coenzymes (carbohydrates) ,Mutagenesis ,RNA, Plant ,Transfer RNA ,biology.protein ,Nucleic Acid Conformation ,Wafer dicing ,Biogenesis ,Protein Binding ,Dicer - Abstract
In eukaryotes, small RNAs (sRNAs) play critical roles in multiple biological processes. Dicer endonucleases are a central part of sRNA biogenesis. In plants, DICER-LIKE PROTEIN 3 (DCL3) produces 24-nucleotide (nt) small interfering RNAs (siRNAs) that determine the specificity of the RNA-directed DNA methylation pathway. Here, we determined the structure of a DCL3–pre-siRNA complex in an active dicing-competent state. The 5′-phosphorylated A1 of the guide strand and the 1-nt 3′ overhang of the complementary strand are specifically recognized by a positively charged pocket and an aromatic cap, respectively. The 24-nt siRNA length dependence relies on the separation between the 5′-phosphorylated end of the guide RNA and dual cleavage sites formed by the paired ribonuclease III domains. These structural studies, complemented by functional data, provide insight into the dicing principle for Dicers in general.
- Published
- 2021
42. Pharmacological inhibition of Carbonic Anhydrase IX and XII to enhance targeting of acute myeloid leukaemia cells under hypoxic conditions
- Author
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Austyn Colter, James Ropa, Melissa L. Fishel, Brian Parkin, Maegan L. Capitano, Heiko Konig, George E. Sandusky, Claudiu T. Supuran, Callista Maguire, Fangli Chen, Daniela N. Petrusca, Max Jacobsen, Xue Wu, H. Scott Boswell, Emilia Licarete, Fabrizio Carta, and Magdalena Czader
- Subjects
Adult ,Male ,Programmed cell death ,IDH1 ,Cell Survival ,medicine.medical_treatment ,Intracellular pH ,CD33 ,Gene Expression ,Antineoplastic Agents ,acute myeloid leukemia ,Young Adult ,Antigens, Neoplasm ,Cell Line, Tumor ,Gene Duplication ,hemic and lymphatic diseases ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Carbonic Anhydrase IX ,Carbonic Anhydrase Inhibitors ,Carbonic Anhydrases ,Aged ,Chemotherapy ,drug resistance ,hypoxia ,Chemistry ,Drug Synergism ,Original Articles ,Cell Biology ,Hydrogen-Ion Concentration ,Middle Aged ,Hypoxia (medical) ,Immunohistochemistry ,Xenograft Model Antitumor Assays ,Transmembrane protein ,Disease Models, Animal ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,fms-Like Tyrosine Kinase 3 ,pH regulation ,Cancer research ,Tumor Hypoxia ,Molecular Medicine ,Original Article ,Female ,Bone marrow ,medicine.symptom - Abstract
Acute myeloid leukaemia (AML) is an aggressive form of blood cancer that carries a dismal prognosis. Several studies suggest that the poor outcome is due to a small fraction of leukaemic cells that elude treatment and survive in specialised, oxygen (O2)‐deprived niches of the bone marrow. Although several AML drug targets such as FLT3, IDH1/2 and CD33 have been established in recent years, survival rates remain unsatisfactory, which indicates that other, yet unrecognized, mechanisms influence the ability of AML cells to escape cell death and to proliferate in hypoxic environments. Our data illustrates that Carbonic Anhydrases IX and XII (CA IX/XII) are critical for leukaemic cell survival in the O2‐deprived milieu. CA IX and XII function as transmembrane proteins that mediate intracellular pH under low O2 conditions. Because maintaining a neutral pH represents a key survival mechanism for tumour cells in O2‐deprived settings, we sought to elucidate the role of dual CA IX/XII inhibition as a novel strategy to eliminate AML cells under hypoxic conditions. Our findings demonstrate that the dual CA IX/XII inhibitor FC531 may prove to be of value as an adjunct to chemotherapy for the treatment of AML.
- Published
- 2021
43. Biomarkers of DNA Damage Response Enable Flow Cytometry-Based Diagnostic to Identify Inborn DNA Repair Defects in Primary Immunodeficiencies
- Author
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Martin Wetzke, Bernd Auber, Ulrich Baumann, Kerstin Felgentreff, Klaus-Michael Debatin, Sandra von Hardenberg, Manfred Hoenig, Catharina Schuetz, Christian Klemann, Ansgar Schulz, Ulrich Pannicke, Dorothee Viemann, Klaus Schwarz, and Eva-Maria Jacobsen
- Subjects
DNA Repair ,DNA damage ,DNA repair ,Immunology ,Cell ,DNA damage response ,Radiation Tolerance ,Radiosensitivity ,chemistry.chemical_compound ,DDC 570 / Life sciences ,Immundefekt ,medicine ,Immunodeficiency ,Humans ,Immunology and Allergy ,DNS-Reparatur ,business.industry ,T-cell receptor excision circles ,Reproducibility of Results ,Strahlensensibilität ,Flow Cytometry ,medicine.disease ,medicine.anatomical_structure ,chemistry ,Cancer Susceptibility ,Apoptosis ,Ataxia-telangiectasia ,Cancer research ,business ,DDC 610 / Medicine & health ,Biomarkers ,DNA ,DNA Damage - Abstract
DNA damage is a constant event in every cell caused by exogenous factors such as ultraviolet and ionizing radiation (UVR/IR) and intercalating drugs, or endogenous metabolic and replicative stress. Proteins of the DNA damage response (DDR) network sense DNA lesions and induce cell cycle arrest, DNA repair, and apoptosis. Genetic defects of DDR or DNA repair proteins can be associated with immunodeficiency, bone marrow failure syndromes, and cancer susceptibility. Although various diagnostic tools are available to evaluate DNA damage, their quality to identify DNA repair deficiencies differs enormously and depends on affected pathways. In this study, we investigated the DDR biomarkers γH2AX (Ser139), p-ATM (Ser1981), and p-CHK2 (Thr68) using flow cytometry on peripheral blood cells obtained from patients with combined immunodeficiencies due to non-homologous end-joining (NHEJ) defects and ataxia telangiectasia (AT) in response to low-dose IR. Significantly reduced induction of all three markers was observed in AT patients compared to controls. However, delayed downregulation of γH2AX was found in patients with NHEJ defects. In contrast to previous reports of DDR in cellular models, these biomarkers were not sensitive enough to identify ARTEMIS deficiency with sufficient reliability. In summary, DDR biomarkers are suitable for diagnosing NHEJ defects and AT, which can be useful in neonates with abnormal TREC levels (T cell receptor excision circles) identified by newborn screening. We conclude that DDR biomarkers have benefits and some limitations depending on the underlying DNA repair deficiency., publishedVersion
- Published
- 2021
44. Ecology and climate sensitivity of a groundwater-fed lake on subtropical North Stradbroke Island (Minjerribah), Queensland, Australia over the last 7500 years
- Author
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John Tibby, Melanie J. Leng, Barry H. Lomax, Haidee Cadd, Glenn B. McGregor, Cameron Barr, Geraldine Jacobsen, Cameron Schulz, Jonathan J. Tyler, Charles Maxson, and Jonathan C. Marshall
- Subjects
chemistry.chemical_classification ,geography ,geography.geographical_feature_category ,Environmental change ,Ecology ,Drainage basin ,Climate change ,Subtropics ,Vegetation ,Aquatic Science ,chemistry ,Environmental science ,Climate sensitivity ,Organic matter ,Holocene ,Earth-Surface Processes - Abstract
Lake sediments are important archives of past climate variability and lake responses to climate. In order to accurately infer past climates, it is necessary to understand, and account for, the ecological processes that affect the record of indicators preserved in lake sediment. This is particularly the case with respect to the concentration of carbon and nitrogen (TOC, TN, and calculated C:N), and the stable isotope composition of organic matter preserved in lake sediments. These are common, yet ambiguous, tracers of environmental change. Ideally, palaeoenvironmental reconstructions using the concentration and isotope composition of organic matter should be grounded in a detailed understanding of the sources of the organic material. This study documents the history and evolution of Blue Lake, an environmentally and culturally important oligotrophic, groundwater window lake on North Stradbroke Island, Queensland, Australia. We utilise organic matter δ13C, TOC, TN, and C:N from a 2.4 m sediment core with a basal age of 7.5 cal kyr BP, to investigate changing organic matter sources as a measure of the climate sensitivity of Blue Lake. This interpretation is supported by data from contemporary algae, aquatic and terrestrial plants, and catchment soils. We show that lake nutrient dynamics drove an increase in algal biomass at 4.2 cal kyr BP. This change coincides with a widely documented intensification of the El Nino-Southern Oscillation, which we infer to have influenced lake nutrient concentrations by reducing groundwater throughflow. Climatic changes resulted in marked changes in lake primary productivity, despite relatively little turnover of the lake diatom flora and catchment vegetation. This suggests that south-east Queensland dune lakes are sensitive to climate changes and helps to refine past and future palaeoclimate research using sediments from these lakes. It also indicates that increased nutrient concentrations in Blue Lake may result from projected changes in 21st Century climate.
- Published
- 2021
45. Carboxypeptidase A1 (CPA1) Immunohistochemistry Is Highly Sensitive and Specific for Acinar Cell Carcinoma (ACC) of the Pancreas
- Author
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Andreas M. Luebke, Frank Jacobsen, Daniel Perez, Franziska Büscheck, Hendrina Contreras, Sören Weidemann, Christoph Fraune, Claudia Hube-Magg, David Dum, Ronald Simon, Andrea Hinsch, Jörg Schrader, Till Krech, Andreas Marx, Waldemar Wilczak, Doris Höflmayer, Martina Kluth, Anne Menz, Guido Sauter, Till S. Clauditz, Sarah Minner, Ria Uhlig, Christian Bernreuther, Natalia Gorbokon, Stefan Steurer, Rainer Krech, Eike Burandt, Jakob R. Izbicki, Patrick Lebok, and Katharina Möller
- Subjects
Carboxypeptidases A ,Carcinoma, Acinar Cell ,Chemistry ,Reproducibility of Results ,Acinar cell carcinoma ,Immunohistochemistry ,Molecular biology ,Pathology and Forensic Medicine ,Highly sensitive ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Predictive Value of Tests ,Tissue Array Analysis ,Germany ,Biomarkers, Tumor ,medicine ,Humans ,Surgery ,Anatomy ,Pancreas ,Carboxypeptidase A1 - Abstract
Carboxypeptidase A1 (CPA1) is a zinc metalloprotease that is produced in pancreatic acinar cells and plays a role in cleaving C-terminal branched-chain and aromatic amino acids from dietary proteins. This study assessed the utility of immunohistochemical CPA1 staining for diagnosing pancreatic acinar cell carcinoma (ACC). A total of 12,274 tumor samples from 132 different tumor types and subtypes as well as 8 samples each of 76 different normal tissue types were interpretable by immunohistochemistry in a tissue microarray format. CPA1 was strongly expressed in acinar cells of all normal pancreas samples but not in any other normal tissues. CPA1 immunostaining was detected in 100% of 11 pancreatic ACCs and 1 mixed acinar endocrine carcinoma, but absent in 449 pancreatic ductal adenocarcinomas, 75 adenocarcinomas of the ampulla Vateri, and 11,739 other evaluable cancers from 128 different tumor entities. A weak to moderate diffuse staining of epithelial and stromal cells of cancer tissues immediately adjacent to non-neoplastic pancreatic acinar cells often occurred and was considered to be caused by the diffusion of the highly abundant CPA1 from normal acinar cells that may have suffered some autolytic cell damage. In conclusion, our data show that CPA1 is a highly sensitive and largely specific marker for normal and neoplastic pancreatic acinar cells. CPA1 immunohistochemistry greatly facilitates the otherwise often difficult diagnosis of pancreatic ACC.
- Published
- 2021
46. High-Temperature Inter-Mineral Potassium Isotope Fractionation: Implications for K–Ca–Ar Chronology
- Author
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Kun Wang, Yaray Ku, Stein B. Jacobsen, Yonghui Li, Zhongqing Wu, W. Wilson Kuhnel, Michail I. Petaev, and Shichun Huang
- Subjects
Atmospheric Science ,Mineral ,Isotopes of potassium ,Space and Planetary Science ,Geochemistry and Petrology ,Chemistry ,Environmental chemistry ,Fractionation ,Article ,Chronology - Abstract
Recent advances in high-precision potassium (K) isotopic analysis have found considerable isotopic variation in rock samples of the Earth’s continental and oceanic crusts; however, it is still uncertain whether there is any resolvable inter-mineral and mineral-melt K isotopic fractionation during igneous and metamorphic processes. Here, we report K isotope compositions of mineral separates from three extremely well preserved igneous rocks (intrusive/extrusive and mafic/intermediate/felsic) in order to investigate possible inter-mineral and mineral-melt K isotopic fractionation at magmatic temperatures. For the first time, we found large inter-mineral fractionation of K isotopes in natural samples (up to 1.072‰), where plagioclase displays a significant enrichment of heavier K isotopes compared to potassium feldspar and biotite in a granite. In addition, we also observed smaller but measurable K isotope fractionation (0.280‰±0.030‰) between ternary feldspar phenocrysts and matrix in a trachyandesite, as well as a comparable isotope fractionation (0.331‰±0.010‰) between plagioclase and the bulk in a gabbroic intrusive rock. We also evaluated such results by comparing the theoretically calculated equilibrium K isotope fractionation factors between relevant igneous minerals in literature and this study. In general, the measured inter-mineral fractionations are consistent with the theoretical calculations (i.e., plagioclase is enriched in heavier isotopes compared to potassium feldspar). Specifically, the measured K isotope fractionation between phenocryst rim and matrix in the trachyandesite agrees well with the calculated equilibrium isotope fractionation. However, the measured K isotope fractionations between phenocryst core and matrix as well as between plagioclase and K-feldspar are significantly larger (by a factor of ~2-3) than the calculated isotope fractionations, which suggest isotopic disequilibrium due to kinetic processes. Using a range of plagioclase-melt isotope fractionation factors inferred from the theoretical calculations in this study, we modeled the K isotopic fractionation during the formation of lunar anorthositic crust, and the result shows a negligible effect on the K isotopic compositions in both lunar crust and mantle. The K isotopic difference between Earth and Moon, therefore, cannot be the result of Lunar Magma Ocean differentiation. Finally, we evaluate the effect of observed inter-mineral fractionations on K-Ar and (40)Ar-(39)Ar dating. This study indicates the variation of (40)K/K ratio would contribute a maximum 0.08% error to the K-Ar and (40)Ar-(39)Ar age uncertainties. We propose a refined (40)K/total K ratio as 0.00011664±0.00000011 (116.64±0.11ppm) instead of the conventional value, 0.0001167(2) for the present Earth. Because some minerals fractionate K isotopes, ultrahigh precision age dating with the K-Ca-Ar dating systems must measure the K isotope fractionation in the same mineral fractions used for age dating.
- Published
- 2021
47. Anthropometric measures are satisfactory substitutes for the DXA‐derived visceral adipose tissue in the association with cardiometabolic risk—The Tromsø Study 2015–2016
- Author
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Jonas Johansson, Bjarne K. Jacobsen, Marie Wasmuth Lundblad, Laila Arnesdatter Hopstock, Sameline Grimsgaard, and Lene Frost Andersen
- Subjects
medicine.medical_specialty ,obesity ,Waist ,Endocrinology, Diabetes and Metabolism ,Overweight ,chemistry.chemical_compound ,Internal medicine ,Diabetes mellitus ,medicine ,overweight ,visceral adipose tissue ,Dual-energy X-ray absorptiometry ,Nutrition and Dietetics ,medicine.diagnostic_test ,VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801 ,business.industry ,dual energy x‐ray absorptiometry ,nutritional and metabolic diseases ,population studies ,Original Articles ,medicine.disease ,Obesity ,RC31-1245 ,chemistry ,Original Article ,Glycated hemoglobin ,medicine.symptom ,Metabolic syndrome ,VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801 ,business ,Body mass index ,cardiometabolic health - Abstract
Background - Body mass index (BMI) increases while cardiometabolic risk factors decrease in individuals in high-income countries. This paradoxical observation raises the question of whether current measures of overweight and obesity properly identify cardiometabolic risk. Methods - A total of 3675 participants (59% women) aged 40–84 years with whole-body dual-energy x-ray absorptiometry scans from the seventh survey of the Tromsø Study were included to examine the association between visceral adipose tissue (VAT) in grams and BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Further, their association with single cardiometabolic risk factors (blood pressure, triglycerides, total cholesterol, high-density lipoprotein [HDL] cholesterol, glycated hemoglobin, high-sensitivity C-reactive protein), modified single components from the ATP Ⅲ criteria for metabolic syndrome (hypertension, diabetes, high triglycerides, and low HDL cholesterol), and metabolic syndrome were examined. Results - VAT mass was strongly correlated with BMI (r ≥ 0.77), WC (r ≥ 0.80), WHR (r ≥ 0.58), and WHtR (r ≥ 0.78). WC was the strongest predictor for VAT (area under the curve: 0.90). Compared to anthropometric measures, the associations between VAT and metabolic syndrome as well as single components of metabolic syndrome were statistically significantly stronger, but the clinical differences were likely minor. Conclusion - Although VAT mass showed statistically stronger associations with cardiometabolic risk compared to traditional anthropometrics, the clinical importance was likely small. Simple, clinically available tools seem to satisfactory substitute for VAT to identify cardiometabolic risk.
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- 2021
48. Ketones Elicit Distinct Alterations in Adipose Mitochondrial Bioenergetics
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Chase M. Walton, Samuel M. Jacobsen, Blake W. Dallon, Erin R. Saito, Shantelle L. H. Bennett, Lance E. Davidson, David M. Thomson, Robert D. Hyldahl, and Benjamin T. Bikman
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mitochondria ,uncoupling ,ketones ,adipocyte ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Objective: The rampant growth of obesity worldwide has stimulated explosive research into human metabolism. Energy expenditure has been shown to be altered by diets differing in macronutrient composition, with low-carbohydrate, ketogenic diets eliciting a significant increase over other interventions. The central aim of this study was to explore the effects of the ketone β-hydroxybutyrate (βHB) on mitochondrial bioenergetics in adipose tissue. Methods: We employed three distinct systems—namely, cell, rodent, and human models. Following exposure to elevated βHB, we obtained adipose tissue to quantify mitochondrial function. Results: In every model, βHB robustly increased mitochondrial respiration, including an increase of roughly 91% in cultured adipocytes, 113% in rodent subcutaneous adipose tissue (SAT), and 128% in human SAT. However, this occurred without a commensurate increase in adipose ATP production. Furthermore, in cultured adipocytes and rodent adipose, we quantified and observed an increase in the gene expression involved in mitochondrial biogenesis and uncoupling status following βHB exposure. Conclusions: In conclusion, βHB increases mitochondrial respiration, but not ATP production, in mammalian adipocytes, indicating altered mitochondrial coupling. These findings may partly explain the increased metabolic rate evident in states of elevated ketones, and may facilitate the development of novel anti-obesity interventions.
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- 2020
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49. Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma
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Maximilian Brunner, Katharina Maier, Petra Rümmele, Anne Jacobsen, Susanne Merkel, Alan Benard, Christian Krautz, Stephan Kersting, Robert Grützmann, and Georg F. Weber
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cd20 ,b-cells ,b-cell aggregates ,pancreatic ductal adenocarcinoma ,survival ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3- and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61−177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7−32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6−51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic options.
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- 2020
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50. Unrepeatered 240-km 64-QAM Transmission Using Distributed Raman Amplification over SMF Fiber
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P. Rosa, G. Rizzelli, X. Pang, O. Ozolins, A. Udalcovs, M. Tan, M. Jaworski, M. Marciniak, S. Sergeyev, R. Schatz, G. Jacobsen, S. Popov, and J. D. Ania-Castañón
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distributed raman amplification ,digital backpropagation ,unrepeatered 64-qam transmission ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
We present a theoretical and experimental investigation of unrepeatered transmission over standard single-mode fiber (SMF-28) using several schemes of distributed Raman amplification, including first, second, and dual order. In order to further extend the transmission distance, we utilize advanced bidirectional higher-order ultra-long Raman fiber laser-based amplification, where we use fiber Bragg gratings (FBGs) to reflect Stokes-shifted light from the secondary pumps. Our work demonstrates the possibility of transmission up to 240-km span length with a total span loss of 52.7 dB. Here, we use a 28-Gbaud signal using a 64-quadrature amplitude modulation (QAM) modulation format. Our results highlight the contribution of nonlinear compensation using digital back propagation in a digital signal processor (DSP) code at the receiver.
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- 2020
- Full Text
- View/download PDF
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