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Polymer education relies on generally agreed terminology and nomenclature rules. The Polymer Division of the International Union of Pure and Applied Chemistry (IUPAC) generates and recommends such rules for naming processes and materials in polymer science. It is the goal of IUPAC that these recommendations be applied in polymer science curricula worldwide. For this purpose, a large amount of material has been provided by the Polymer Division of IUPAC, and in this paper these resources are described from the personal perspective of the authors. A discussion of terminology is then provided, including a detailed discussion of the term "dispersity" (M[subscript w]/M[subscript n]) and the rationale behind the recommended IUPAC names of different polymerization mechanisms. This is followed by a commentary on polymer nomenclature with examples. Finally, exemplary applications of resources provided by the Polymer Division of IUPAC for educational purposes around the world are presented.

A laboratory experiment was designed for upper-level students in a Chemical Analysis course to illustrate the theoretical and practical applications of 0.8% agarose gel electrophoresis and to reinforce an understanding of weak acids/bases using easy-to-visualize pH indicators. The careful choice of indicators included acid and base types with amphiprotic intermediates, species that become either singly or doubly deprotonated, and molecules with molecular weights that span from 269 to 670 g/mol. Students measure the rate of migration of the pH indicators relative to the rate of migration of a red dye standard. The relative rates are interpreted with respect to the indicators' fractions of deprotonation (and resulting molecule charges), molecular weights, and shapes. This procedure occurs under acidic (pH 4.0) and basic (pH 7.5) conditions with lower and higher applied voltages to understand the impact of changing protonation/deprotonation. This experiment has been successfully completed by over 200 analytical chemistry students with consistent results. Overall, this procedure teaches students to evaluate the controls on molecule movement in an electrical field critically, while gaining insight into weak acid/base equilibria.

A study conducted shows that if digital photography is combined with regular thin-layer chromatography (TLC), it could perform highly improved qualitative analysis as well as make accurate quantitative analysis possible for a much lower cost than commercial equipment. The findings suggest that digitally enhanced TLC (DE-TLC) is low-cost and easy to use and could be utilized in a similar manner as a TLC scanner in any science lab, including college and high school labs.

Despite the widespread discussion of organisational learning, there is little scholarly contribution on promoting learning through the practical application of management tools. This is especially true in a complex internal supply chain context of an organisation. This paper seeks to address this gap by exploring and analysing the capability of the benchmarking tool to promote learning in the internal supply chain context of a large organisation. A longitudinal in-depth case study of a project that benchmarked the filling and packing internal supply chain with its internal and external interfaces was conducted within the German chemical company BASF. Four key management areas were identified to facilitate learning during a benchmarking project: knowledge management, change management, project management, and leadership. This research proposes a set of propositions combining benchmarking and learning within the context of internal supply chains that are grounded in the empirical data and the extant learning theory. (Contains 4 tables and 3 figures.)

The University of Illinois at Urbana-Champaign School of Chemical Sciences undertook a comprehensive review of management practices in three phases: (1) internal business office procedural review; (2) user opinion survey; and (3) external assessment by campus business and personnel administration. The substantial year-long effort was justified by results. (MSE)

The project accounting system used by the University of Illinois Urbana-Champaign School of Chemical Sciences exchanges financial data with the campus' central accounting system and allows integration of this information with user-entered data to produce an easily read, fully obligated project accounting statement for the budget and period awarded. (MSE)

Abstract Iron(III) molybdate (Fe2(MoO4)3) is a commercial catalyst for the oxidative dehydrogenation (ODH) of methanol, but it has recently been shown to be relevant for other substrates as well. Despite its commercial use, a detailed mechanistic understanding of Fe2(MoO4)3 catalysts at the surface and in the bulk has been lacking, largely hampered by the lack of suitable spectroscopic methods, directly applicable under reaction conditions. Using propane ODH as an example, we highlight the potential of operando Raman and impedance spectroscopy combined with transient IR spectroscopy, to identify surface active sites and monitor the hydrogen transfer and oxygen dynamics. By comparison with the behavior of reference compounds (MoO3, MoOx/Fe2O3) a mechanistic model is proposed. The presence of iron greatly influences the reactivity behavior via oxygen diffusion but is moderated in its oxidative capacity by surface MoOx. Our approach directly elucidates fundamental properties of Fe2(MoO4)3 of general importance to selective oxidation catalysis.

The world population is continuously increasing. Smart farming is required to keep up with this development by producing more food in a sustainable way. In many new sensor solution developments, the results of the sensor itself is at the target, but the whole solution fails to meet the requirements of the agriculture sensing use cases: the developments suffer from singular approaches with a constricted view solely on the sensor, which might be exchangeable. In this article, we present a holistic approach that can help to overcome these challenges. This approach considers the whole use case, from sense, compute, and connect to power. The approach is discussed with the example of the PLANtAR project, where we develop a soil nitrate sensor and a new leaf wetness and microclimate sensor for application in a greenhouse. The resulting sensor is integrated into a sensor node and compared to a state-of-the-art system. The work shows what is needed to assess the best tradeoffs for agriculture use cases based on a horticulture application.

Head and neck squamous cell carcinoma (HNSCC) is associated with high morbidity and mortality. New personalized treatment strategies represent an unmet medical need to improve the overall survival and the quality of life of patients, which are often limited by the toxicity of established multimodal treatment protocols. Several studies have reported an increased expression of the estrogen receptor 1 (ESR1) in HNSCC, but its potential role in the disease outcome of these tumors remains elusive. Using an integrative analysis of multiomics and clinical data from The Cancer Genome Atlas (TCGA)-HNSC, we established a prognostic risk model based on an ESR1-related 25-gene set. The prognostic value was confirmed in an independent cohort of HNSCC and other solid tumors from TCGA. Finally, we performed in silico drug sensitivity modeling to explore potential vulnerabilities for both risk groups. This approach predicted a higher sensitivity for HNSCC, with prominent ESR1 pathway activity under treatment with specific estrogen receptor modulators. In conclusion, our data confirm the involvement of ESR1-related pathway activity in the progression of a defined subset of HNSCC, provide compelling evidence that these tumors share a specific vulnerability to endocrine therapy, and pave the way for preclinical studies and clinical trials to demonstrate the efficacy of this new therapeutic option.

The inventory system designed for six storerooms in three buildings at the University of Illinois at Urbana-Champaign's School of Chemical Sciences replaced an issue-slip and transactions record system with barcode technology. Data collection error reductions have been significant, making it easier to determine stock levels and plan purchases. (MSE)

A simple model is described for the binding of ligands to macromolecules. The model is applied to the cooperative binding by hemoglobin and aspartate transcarbamylase. The sequential and allosteric models of cooperative binding are considered. (BB)

We present a basic principle and good practices of the rheology of polymers, particularly for teachers or lecturers at colleges or universities for educational purposes, as well as for beginner researchers who may refer to this article as their self-learning resources. Basic consideration of the experimental methods using parallel-plate oscillatory rheometer and step-by-step guidelines for the estimation of the power law dependence of storage, G′ and loss, G″ modulus as well as the estimation of the relaxation time at f cross G′−G′′ ${f}_{\,\mathrm{cross}}^{\,{G}^{\prime }-{G}^{\prime \prime }}$ at terminal zone using various approaches such as commercial graphical software, manual graphical approach and commercial rheometer software are highlighted. Good practices for data interpretation using different approaches are described and compared where the outcomes revealed the manual graphical approach or commercial graphical software yield comparable results with the commercial rheometer software. In order to have better insight, several examples and exercises which are applicable for teaching and self-learning activities are also provided.

To better understand the role of atmospheric dynamics in modulating surface concentrations of fine particulate matter (PM2.5), we relate the anticyclonic wave activity (AWA) metric and PM2.5 data from the Interagency Monitoring of Protected Visual Environment (IMPROVE) data for the period of 1988–2014 over the US. The observational results are compared with hindcast simulations over the past 2 decades using the National Center for Atmospheric Research–Community Earth System Model (NCAR CESM). We find that PM2.5 is positively correlated (up to R=0.65) with AWA changes close to the observing sites using regression analysis. The composite AWA for high-aerosol days (all daily PM2.5 above the 90th percentile) shows a similarly strong correlation between PM2.5 and AWA. The most prominent correlation occurs in the Midwestern US. Furthermore, the higher quantiles of PM2.5 levels are more sensitive to the changes in AWA. For example, we find that the averaged sensitivity of the 90th-percentile PM2.5 to changes in AWA is approximately 3 times as strong as the sensitivity of 10th-percentile PM2.5 at one site (Arendtsville, Pennsylvania; 39.92∘ N, 77.31∘ W). The higher values of the 90th percentile compared to the 50th percentile in quantile regression slopes are most prominent over the northeastern US. In addition, future changes in US PM2.5 based only on changes in climate are estimated to increase PM2.5 concentrations due to increased AWA in summer over areas where PM2.5 variations are dominated by meteorological changes, especially over the western US. Changes between current and future climates in AWA can explain up to 75 % of PM2.5 variability using a linear regression model. Our analysis indicates that higher PM2.5 concentrations occur when a positive AWA anomaly is prominent, which could be critical for understanding how pollutants respond to changing atmospheric circulation as well as for developing robust pollution projections.

While significant progress has been made in understanding global carbon (C) cycling, the mechanisms regulating belowground C fluxes and storage are still uncertain. New molecular technologies have the power to elucidate these processes, yet we have no widespread standardized implementation of molecular techniques. To address this gap, we introduce the Molecular Observation Network (MONet), a decadal vision from the Environmental Molecular Sciences Laboratory (EMSL), to develop a national network for understanding the molecular composition, physical structure, and hydraulic and biological properties of soil and water. These data are essential for advancing the next generation of multiscale Earth systems models. In this paper, we discuss the 1000 Soils Pilot for MONet, including a description of standardized sampling materials and protocols and a use case to highlight the utility of molecular-level and microstructural measurements for assessing the impacts of wildfire on soil. While the 1000 Soils Pilot generated a plethora of data, we focus on assessments of soil organic matter (SOM) chemistry via Fourier-transform ion cyclotron resonance-mass spectrometry and microstructural properties via X-ray computed tomography to highlight the effects of recent fire history in forested ecosystems on belowground C cycling. We observed decreases in soil respiration, microbial biomass, and potential enzyme activity in soils with high frequency burns. Additionally, the nominal oxidation state of carbon in SOM increased with burn frequency in surface soils. This results in a quantifiable shift in the molecular signature of SOM and shows that wildfire may result in oxidation of SOM and structural changes to soil pore networks that persist into deeper soils.

The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.

Ammonia (NH3) plays a central role in the chemistry of inorganic secondary aerosols in the atmosphere. The largest emission sector for NH3 is agriculture, where NH3 is volatilized from livestock wastes and fertilized soils. Although the NH3 volatilization from soils is driven by the soil temperature and moisture, many atmospheric chemistry models prescribe the emission using yearly emission inventories and climatological seasonal variations. Here we evaluate an alternative approach where the NH3 emissions from agriculture are simulated interactively using the process model FANv2 (Flow of Agricultural Nitrogen, version 2) coupled to the Community Atmospheric Model with Chemistry (CAM-chem). We run a set of 6-year global simulations using the NH3 emission from FANv2 and three global emission inventories (EDGAR, CEDS and HTAP) and evaluate the model performance using a global set of multi-component (atmospheric NH3 and NH4+, and NH4+ wet deposition) in situ observations. Over East Asia, Europe and North America, the simulations with different emissions perform similarly when compared with the observed geographical patterns. The seasonal distributions of NH3 emissions differ between the inventories, and the comparison to observations suggests that both FANv2 and the inventories would benefit from more realistic timing of fertilizer applications. The largest differences between the simulations occur over data-scarce regions. In Africa, the emissions simulated by FANv2 are 200 %–300 % higher than in the inventories, and the available in situ observations from western and central Africa, as well as NH3 retrievals from the Infrared Atmospheric Sounding Interferometer (IASI) instrument, are consistent with the higher NH3 emissions as simulated by FANv2. Overall, in simulating ammonia and ammonium concentrations over regions with detailed regional emission inventories, the inventories based on these details (HTAP, CEDS) capture the atmospheric concentrations and their seasonal variability the best. However these inventories cannot capture the impact of meteorological variability on the emissions, nor can these inventories couple the emissions to the biogeochemical cycles and their changes with climate drivers. Finally, we show with sensitivity experiments that the simulated time-averaged nitrate concentration in air is sensitive to the temporal resolution of the NH3 emissions. Over the CASTNET monitoring network covering the US, resolving the NH3 emissions hourly instead monthly reduced the positive model bias from approximately 80 % to 60 % of the observed yearly mean nitrate concentration. This suggests that some of the commonly reported overestimation of aerosol nitrate over the US may be related to unresolved temporal variability in the NH3 emissions.

The silver nanoparticles (AgNPs) green synthesis has been investigated by selecting naturally occurred reduction and stabilizing/capping agents. In this work, Ilex paraguariensis aqueous extract in the one-step biosynthesis of AgNPs is reported. The synthesis was carried out at room temperature under different pH (5.0, 6.8 and 8.5) and extract concentrations (2.5, 5.0 and 7.5% v v−1) resulting in average diameters ranging from 34 to 144 nm and polydispersity index (PDI) up to 0.51. The morphological characterization was performed by Transmission Electron Microscopy, associated with the UV–Vis Spectroscopy, showing that at higher pH the shape of AgNPs was more spherical rather than ellipsoidal. X-ray diffraction (XRD) pattern of AgNPs exhibited 2θ values corresponding to silver nanocrystals. Colloidal AgNPs solution synthesized with pH 8.5 and extract concentration of 2.5% v v−1 remained stable for 10 months of storage at ambient temperature. Fourier Transform Infrared Spectroscopy suggested that the polyphenols were responsible for the AgNPs formation. AgNPs presented bacteriostatic and bactericidal activity. AgNPs presented in vitro rat brain acetylcholinesterase (AChE) activity, with higher inhibition potential at 200 µL. So, it is concluded that AgNPs were synthesized with success, the pH and extract concentration influences in AgNPs size and morphology, consequently in its antimicrobial and AChE activity.

Converting linear to rotary motion is a typical and enabling task for macroscale machinery, but the process is not yet established at the nano- and microscale. Linear motion is generated by the motor proteins kinesin and dynein as they move along microtubules, and a microtubule immobilized on the circumference of a microsphere could create rotary motion as it is propelled by surface-adhered motors, enabling microscale machines such as “active ball bearings”. This paper describes the attachment of microtubules to microspheres and the resulting types of motion as the microtubule-microsphere assemblies interact with a surface covered with kinesin-1 motor proteins. Dragging, pushing, spinning and rotating motions are observed and analyzed, demonstrating a pathway to microscale rotations driven by linear biomolecular motors.

The atmospheric issue of acid rains is subjected to a five-part laboratory experiment by concentrating on the chemistry of the infiltration process of acid rainwater through soils. This procedure of quantitative scrutiny helps students realize the efficacy of soil minerals in the consumption of surplus acidity in rainwater.

In this study we report an affordable synthesis and preparation of an electrochemically exfoliated few-layer 2-dimensional (2D) SnS2 anode material of high cycling durability and demonstrate its performance on the example of alkali metal batteries. The metalation mechanism consists of highly unusual and previously only speculated Sn (III)-state grasped by operando Raman spectroelectrochemistry aided by symmetry analysis. The prepared 2D material flakes were characterized by high resolution transmission electron microscopy, X-ray photoelectron and Raman spectroscopies. The operando Raman spectroelectrochemistry was chosen as a dedicated tool for the investigation of alkali-metal-ion intercalation (Li, Na, K), whereby the distortion of the A1g Raman active mode (out-of-plane S-Sn-S vibration) during battery charging exhibited a substantial dependence on the electrochemically applied potential. As a result of the structural dynamics a considerable Raman red-shift of 17.6 cm−1 was observed during metalation. Linewidth changes were used to evaluate the expansion caused by metalation, which in case of sodium and potassium were found to be minimal compared to lithium. Based on the spectroscopic and electrochemical results, a mechanism for the de-/intercalation of lithium, sodium and potassium is proposed which includes alloying in few-layer 2D SnS2 materials and the generation of point-defects.

Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of perineural invasion by pathologic examination is limited due to the availability of tumor samples from surgical resection, which can arise in cases of definitive nonsurgical treatment. To address this medical need, we established a random forest prediction model for the risk assessment of perineural invasion, including occult perineural invasion, and characterized distinct cellular and molecular features based on our new and extended classification. RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas were used as a training cohort to identify differentially expressed genes that are associated with perineural invasion. A random forest classification model was established based on these differentially expressed genes and was validated by inspection of H&E-stained whole image slides. Differences in epigenetic regulation and the mutational landscape were detected by an integrative analysis of multiomics data and single-cell RNA-sequencing data were analyzed. We identified a 44-gene expression signature related to perineural invasion and enriched for genes mainly expressed in cancer cells according to single-cell RNA-sequencing data. A machine learning model was trained based on the expression pattern of the 44-gene set with the unique feature to predict occult perineural invasion. This extended classification model enabled a more accurate analysis of alterations in the mutational landscape and epigenetic regulation by DNA methylation as well as quantitative and qualitative differences in the cellular composition in the tumor microenvironment between head and neck squamous cell carcinoma with or without perineural invasion. In conclusion, the newly established model could not only complement histopathologic examination as an additional diagnostic tool but also guide the identification of new drug targets for therapeutic intervention in future clinical trials with head and neck squamous cell carcinoma patients at a higher risk for treatment failure due to perineural invasion.

The cross-linking of structural proteins is critical for establishing the mechanical stability of the epithelial compartments of the skin and skin appendages. The introduction of isopeptide bonds between glutamine and lysine residues depends on catalysis by transglutaminases and represents the main protein cross-linking mechanism besides the formation of disulfide bonds. Here, we used a fluorescent labeling protocol to localize the activity of transglutaminases on thin sections of the integument and its appendages in mammals and birds. In human tissues, transglutaminase activity was detected in the granular layer of the epidermis, suprabasal layers of the gingival epithelium, the duct of sweat glands, hair follicles and the nail matrix. In the skin appendages of chickens, transglutaminase activity was present in the claw matrix, the feather follicle sheath, the feather sheath and in differentiating keratinocytes of feather barb ridges. During chicken embryogenesis, active transglutaminase was found in the cornifying epidermis, the periderm and the subperiderm. Transglutaminase activity was also detected in the filiform papillae on the tongue of mice and in conical papillae on the tongue of chickens. In summary, our study reveals that transglutaminase activities are widely distributed in integumentary structures and suggests that transglutamination contributes to the cornification of hard skin appendages such as nails and feathers.

Osteoporotic fractures are often linked to persisting chronic pain and poor healing outcomes. Substance P (SP), α-calcitonin gene-related peptide (α-CGRP) and sympathetic neurotransmitters are involved in bone remodeling after trauma and nociceptive processes, e.g., fracture-induced hyperalgesia. We aimed to link sensory and sympathetic signaling to fracture healing and fracture-induced hyperalgesia under osteoporotic conditions. Externally stabilized femoral fractures were set 28 days after OVX in wild type (WT), α-CGRP- deficient (α-CGRP −/−), SP-deficient (Tac1−/−) and sympathectomized (SYX) mice. Functional MRI (fMRI) was performed two days before and five and 21 days post fracture, followed by µCT and biomechanical tests. Sympathectomy affected structural bone properties in the fracture callus whereas loss of sensory neurotransmitters affected trabecular structures in contralateral, non-fractured bones. Biomechanical properties were mostly similar in all groups. Both nociceptive and resting-state (RS) fMRI revealed significant baseline differences in functional connectivity (FC) between WT and neurotransmitter-deficient mice. The fracture-induced hyperalgesia modulated central nociception and had robust impact on RS FC in all groups. The changes demonstrated in RS FC in fMRI might potentially be used as a bone traumata-induced biomarker regarding fracture healing under pathophysiological musculoskeletal conditions. The findings are of clinical importance and relevance as they advance our understanding of pain during osteoporotic fracture healing and provide a potential imaging biomarker for fracture-related hyperalgesia and its temporal development. Overall, this may help to reduce the development of chronic pain after fracture thereby improving the treatment of osteoporotic fractures.

Exogenous corticosterone administration reduces GABAergic transmission and impairs its 5-HT7 receptor-dependent modulation in the rat dorsal raphe nucleus (DRN), but it is largely unknown how neuronal functions of the DRN are affected by repeated physical and psychological stress. This study compared the effects of repeated restraint stress and corticosterone injections on DRN neuronal excitability, spontaneous synaptic transmission, and its 5-HT7 receptor-dependent modulation. Male Wistar rats received corticosterone injections for 7 or 14 days or were restrained for 10 min twice daily for 3 days. Repeated restraint stress and repeated corticosterone administration evoked similar changes in performance in the forced swim test. They increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from DRN neurons. In contrast to the treatment with corticosterone, restraint stress-induced changes in sEPSC kinetics and decreased intrinsic excitability of DRN neurons did not modify inhibitory transmission. Repeated injections of the 5-HT7 receptor antagonist SB 269970 ameliorated the effects of restraint on excitability and sEPSC frequency but did not restore the altered kinetics of sEPSCs. Thus, repeated restraint stress and repeated corticosterone administration differ in consequences for the intrinsic excitability of DRN projection neurons and their excitatory and inhibitory synaptic inputs. Effects of repeated restraint stress on DRN neurons can be partially abrogated by blocking the 5-HT7 receptor.

Local finite-amplitude wave activity (LWA) measures the waviness of the local flow. In this work we relate the anticyclonic part of LWA, AWA (anticyclonic wave activity), to surface ozone in summertime over the US on interannual to decadal timescales. Interannual covariance between AWA diagnosed from the European Centre for Medium-Range Weather Forecast Era-Interim reanalysis and ozone measured at EPA Clean Air Status and Trends Network (CASTNET) stations is analyzed using maximum covariance analysis (MCA). The first two modes in the MCA analysis explain 84 % of the covariance between the AWA and MDA8 (maximum daily 8 h average ozone), explaining 29 % and 14 % of the MDA8 ozone variance, respectively. Over most of the US we find a significant relationship between ozone at most locations and AWA over the analysis domain (24–53∘ N and 130–65∘ W) using a linear regression model. This relationship is diagnosed (i) using reanalysis meteorology and measured ozone from CASTNET, or (ii) using meteorology and ozone simulated by the Community Atmospheric Model version 4 with chemistry (CAM4-chem) within the Community Earth System Model (CESM1). Using the linear regression model we find that meteorological biases in AWA in CAM4-chem, as compared to the reanalysis meteorology, induce ozone changes between −4 and +8 ppb in CAM4-chem. Future changes (ca. 2100) in AWA are diagnosed in different climate change simulations in CAM4-chem, simulations which differ in their initial conditions and in one case differ in their reactive species emissions. All future simulations have enhanced AWA over the US, with the maximum enhancement in the southwest. As diagnosed using the linear regression model, the future change in AWA is predicted to cause a corresponding change in ozone ranging between −6 and 6 ppb. The location of this change depends on subtle features of the change in AWA. In a number of locations this change is consistent with the magnitude and the sign of the overall simulated future ozone change.

The hybrids of female channel catfish (Ictalurus punctatus) and male blue catfish (I. furcatus) account for >50% of US catfish production due to superior growth, feed conversion, and disease resistance compared to both parental species. However, these hybrids can rarely be naturally spawned. Sperm collection is a lethal procedure, and sperm samples are now cryopreserved for fertilization needs. Previous studies showed that variation in sperm quality causes variable embryo hatch rates, which is the limiting factor in hybrid catfish breeding. Biomarkers as indicators for sperm quality and reproductive success are currently lacking. To address this, we investigated expression changes caused by cryopreservation using transcriptome profiles of fresh and cryopreserved sperm. Sperm quality measurements revealed that cryopreservation significantly increased oxidative stress levels and DNA fragmentation, and reduced sperm kinematic parameters. The present RNA-seq study identified 849 upregulated genes after cryopreservation, including members of all five complexes in the mitochondrial electron transport chain, suggesting a boost in oxidative phosphorylation activities, which often lead to excessive production of reactive oxygen species (ROS) associated with cell death. Interestingly, functional enrichment analyses revealed compensatory changes in gene expression after cryopreservation to offset detrimental effects of ultra-cold storage: MnSOD was induced to control ROS production; chaperones and ubiquitin ligases were upregulated to correct misfolded proteins or direct them to degradation; negative regulators of apoptosis, amide biosynthesis, and cilium-related functions were also enriched. Our study provides insight into underlying molecular mechanisms of sperm cryoinjury and lays a foundation to further explore molecular biomarkers on cryo-survival and gamete quality.

Radiotherapy of head-and-neck squamous cell carcinoma (HNSCC) can cause considerable normal tissue injuries, and mesenchymal stromal cells (MSCs) have been shown to aid regeneration of irradiation-damaged normal tissues. However, utilization of MSC-based treatments for HNSCC patients undergoing radiotherapy is hampered by concerns regarding potential radioprotective effects. We therefore investigated the influence of MSCs on the radiosensitivity of HNSCCs. Several human papillomavirus (HPV)-negative and HPV-positive HNSCCs were co-cultured with human bone marrow-derived MSCs using two-dimensional and three-dimensional assays. Clonogenic survival, proliferation, and viability of HNSCCs after radiotherapy were assessed depending on MSC co-culture. Flow cytometry analyses were conducted to examine the influence of MSCs on irradiation-induced cell cycle distribution and apoptosis induction in HNSCCs. Immunofluorescence stainings of γH2AX were conducted to determine the levels of residual irradiation-induced DNA double-strand breaks. Levels of connective tissue growth factor (CTGF), a multifunctional pro-tumorigenic cytokine, were analyzed using enzyme-linked immunosorbent assays. Neither direct MSC co-culture nor MSC-conditioned medium exerted radioprotective effects on HNSCCs as determined by clonogenic survival, proliferation, and viability assays. Consistently, three-dimensional microwell arrays revealed no radioprotective effects of MSCs. Irradiation resulted in a G2/M arrest of HNSCCs at 96 h independently of MSC co-culture. HNSCCs’ apoptosis rates were increased by irradiation irrespective of MSCs. Numbers of residual γH2AX foci after irradiation with 2 or 8 Gy were comparable between mono- and co-cultures. MSC mono-cultures and HNSCC-MSC co-cultures exhibited comparable CTGF levels. We did not detect radioprotective effects of human MSCs on HNSCCs. Our results suggest that the usage of MSC-based therapies for radiotherapy-related toxicities in HNSCC patients may be safe in the context of absent radioprotection.

Avoidance of therapy-induced apoptosis is a hallmark of acquired resistance towards radiotherapy. Thus, breaking resistance still challenges modern cancer therapy. The Bcl-2 protein family is known for its regulatory role in apoptosis signaling, making Bcl-2, Mcl-1 and Bcl-xL promising targets. This study evaluates the effects of highly specific inhibitors for Bcl-xL (WEHI-539), Bcl-2 (ABT-199) and Mcl-1 (S63845) as radiosensitizers. Covering a broad spectrum of solid tumors, Non-Small-Cell Lung Cancer (NSCLC), Head and Neck Squamous Cell Carcinoma (HNSCC) and synovial sarcoma cell lines were exposed to fractionated radiation as standard therapy with or without Bcl-2 protein inhibition. Protein expression was detected by Western blot and cell death was assessed by flow cytometry measuring apoptosis. In contrast to NSCLC, a high level of Bcl-xL and its upregulation during radiotherapy indicated radioresistance in HNSCC and synovial sarcoma. Radioresistant cell lines across all entities benefited synergistically from combined therapy with Bcl-xL inhibition and fractionated radiation. In NSCLC cell lines, Mcl-1 inhibition significantly augmented radiotherapy independent of the expression level. Our data suggest that among antiapoptotic Bcl-2 proteins, targeting Bcl-xL may break resistance to radiation in HNSCC, synovial sarcoma and NSCLC in vitro. In NSCLC, Mcl-1 might be a promising target that needs further investigation.

Much of plant development depends on cell-to-cell redistribution of the plant hormone auxin, which is facilitated by the plasma membrane (PM) localized PIN FORMED (PIN) proteins. Auxin export activity, developmental roles, subcellular trafficking, and polarity of PINs have been well studied, but their structure remains elusive besides a rough outline that they contain two groups of 5 alpha-helices connected by a large hydrophilic loop (HL). Here, we focus on the PIN1 HL as we could produce it in sufficient quantities for biochemical investigations to provide insights into its secondary structure. Circular dichroism (CD) studies revealed its nature as an intrinsically disordered protein (IDP), manifested by the increase of structure content upon thermal melting. Consistent with IDPs serving as interaction platforms, PIN1 loops homodimerize. PIN1 HL cytoplasmic overexpression in Arabidopsis disrupts early endocytic trafficking of PIN1 and PIN2 and causes defects in the cotyledon vasculature formation. In summary, we demonstrate that PIN1 HL has an intrinsically disordered nature, which must be considered to gain further structural insights. Some secondary structures may form transiently during pairing with known and yet-to-be-discovered interactors.

Carbon surface oxides have been demonstrated to be crucial for high performing carbon materials in various applications. Diffuse reflectance infrared Fourier transform spectroscopy represents a powerful time-resolved method to study the surfaces of functional materials under process conditions. Due to the severe overlap of the contributions of individual surface groups in combination with compared to organic molecules shifted absorption maxima meaningful analysis remains challenging. Especially due to the unknown maxima, deconvolution of the superimposed bands is strongly hindered. In this study, we developed a procedure based on hydrolysis, thermal annealing or a combination thereof, which allows to disentangle carbonyl absorption maxima of carboxylic acids, anhydrides and lactones on carbon surfaces. In order to verify the proposed transformations, thorough characterization by temperature programmed desorption, X-ray photoelectron spectroscopy, potentiometric titration and Boehm titration was carried out. Applying this procedure for a polymer derived reference material, the carbonyl absorption maximum could be deduced, which are positioned for lactones at 1771 cm−1, for carboxylic acids between 1753 cm−1 and 1760 cm−1, and for carboxylic anhydrides at 1792 cm-1 and 1852 cm-1. This allowed deconvolution of the carbonyl band, paving the way for in situ time-resolved analyses.

Painkillers are commonly used medications. Native peptide painkillers suffer from various pharmacological disadvantages, while small molecule painkillers like morphine are highly addictive. We present a general approach aimed to use backbone-cyclization to develop a peptidomimetic painkiller. Backbone-cyclization was applied to transform the linear peptide Tyr-Arg-Phe-Sar (TAPS) into an active backbone-cyclic peptide with improved drug properties. We designed and synthesized a focused backbone-cyclic TAPS library with conformational diversity, in which the members of the library have the generic name TAPS c(n-m) where n and m represent the lengths of the alkyl chains on the nitrogens of Gly and Arg, respectively. We used a combined screening approach to evaluate the pharmacological properties and the potency of the TAPS c(n-m) library. We focused on an in vivo active compound, TAPS c(2-6), which is metabolically stable and has the potential to become a peripheral painkiller being a full μ opioid receptor functional agonist. To prepare a large quantity of TAPS c(2-6), we optimized the conditions of the on-resin reductive alkylation step to increase the efficiency of its SPPS. NMR was used to determine the solution conformation of the peptide lead TAPS c(2-6).

The interferon (IFN)-stimulated gene product 15 (ISG15) represents an ubiquitin-like protein (Ubl), which in a process termed ISGylation can be covalently linked to target substrates via a cascade of E1, E2, and E3 enzymes. Furthermore, ISG15 exerts functions in its free form both, as an intracellular and as a secreted protein. In agreement with its role as a type I IFN effector, most functions of ISG15 and ISGylation are linked to the anti-pathogenic response. However, also key roles in other cellular processes such as protein translation, cytoskeleton dynamics, exosome secretion, autophagy or genome stability and cancer were described. Ubiquitin-specific protease 18 (USP18) constitutes the major ISG15 specific protease which counteracts ISG15 conjugation. Remarkably, USP18 also functions as a critical negative regulator of the IFN response irrespective of its enzymatic activity. Concordantly, lack of USP18 function causes fatal interferonopathies in humans and mice. The negative regulatory function of USP18 in IFN signaling is regulated by various protein–protein interactions and its stability is controlled via proteasomal degradation. The broad repertoire of physiological functions and regulation of ISG15 and USP18 offers a variety of potential intervention strategies which might be of therapeutic use. Due to the high mutation rates of pathogens which are often species specific and constantly give rise to a variety of immune evasion mechanisms, immune effector systems are under constant evolutionarily pressure. Therefore, it is not surprising that considerable differences in ISG15 with respect to function and sequence exist even among closely related species. Hence, it is essential to thoroughly evaluate the translational potential of results obtained in model organisms especially for therapeutic strategies. This review covers existing and conceptual assay systems to target and identify modulators of ISG15, ISGylation, USP18 function, and protein–protein interactions within this context. Strategies comprise mouse models for translational perspectives, cell-based and biochemical assays as well as chemical probes.

Abundance-based model evaluations with observations provide critical tests for the simulated mean state in models of intercontinental pollution transport, and under certain conditions may also offer constraints on model responses to emission changes. We compile multiyear measurements of peroxy acetyl nitrate (PAN) available from five mountaintop sites and apply them in a proof-of-concept approach that exploits an ensemble of global chemical transport models (HTAP1) to identify an observational emergent constraint. In April, when the signal from anthropogenic emissions on PAN is strongest, simulated PAN at northern midlatitude mountaintops correlates strongly with PAN source–receptor relationships (the response to 20 % reductions in precursor emissions within northern midlatitude continents; hereafter, SRRs). This finding implies that PAN measurements can provide constraints on PAN SRRs by limiting the SRR range to that spanned by the subset of models simulating PAN within the observed range. In some cases, regional anthropogenic volatile organic compound (AVOC) emissions, tracers of transport from different source regions, and SRRs for ozone also correlate with PAN SRRs. Given the large observed interannual variability in the limited available datasets, establishing strong constraints will require matching meteorology in the models to the PAN measurements. Application of this evaluation approach to the chemistry–climate models used to project changes in atmospheric composition will require routine, long-term mountaintop PAN measurements to discern both the climatological SRR signal and its interannual variability.

The co-occurrence of heat waves and pollution events and the resulting high mortality rates emphasize the importance of the co-occurrence of pollution and temperature extremes. Through the use of extreme value theory and other statistical methods, tropospheric surface ozone and temperature extremes and their joint occurrence are analyzed over the United States during the summer months (JJA) using measurements and simulations of the present and future climate and chemistry. Five simulations from the Chemistry-Climate Model Initiative (CCMI) reference experiment using specified dynamics (REFC1SD) were analyzed: the CESM1 CAM4-chem, CHASER, CMAM, MOCAGE and MRI-ESM1r1 simulations. In addition, a 25-year present-day simulation branched off the CCMI REFC2 simulation in the year 2000 and a 25-year future simulation branched off the CCMI REFC2 simulation in 2100 were analyzed using CESM1 CAM4-chem. The last two simulations differed in their concentration of carbon dioxide (representative of the years 2000 and 2100) but were otherwise identical. In general, regions with relatively high ozone extremes over the US do not occur in regions of relatively high temperature extremes. A new metric, the spectral density, is developed to measure the joint extremal dependence of ozone and temperature by evaluating the spectral dependence of their extremes. While in many areas of the country ozone and temperature are highly correlated overall, the correlation is significantly reduced when examined on the higher end of the distributions. Measures of spectral density are less than about 0.35 everywhere, suggesting that at most only about a third of the time do extreme temperatures coincide with extreme ozone. Two regions of the US have the strongest measured extreme dependence of ozone and temperature: the northeast and the southeast. The simulated future increase in temperature and ozone is primarily due to a shift in their distributions, not to an increase in their extremes. The locations where the right-hand side of the temperature distribution does increase (by up to 30 %) are consistent with locations where soil–moisture feedback may be expected. Future changes in the right-hand side of the ozone distribution range regionally between +20 % and −10 %. The location of future increases in the high-end tail of the ozone distribution are weakly related to those of temperature with a correlation of 0.3. However, the regions where the temperature extremes increase are not located where the extremes in ozone are large, suggesting a muted ozone response.

Many free-living flatworms have evolved a temporary adhesion system, which allows them to quickly attach to and release from diverse substrates. In the marine Macrostomum lignano, the morphology of the adhesive system and the adhesion-related proteins have been characterised. However, little is known about how temporary adhesion is performed in other aquatic environments. Here, we performed a 3D reconstruction of the M. lignano adhesive organ and compared it to the morphology of five selected Macrostomum, representing two marine, one brackish, and two freshwater species. We compared the protein domains of the two adhesive proteins, as well as an anchor cell-specific intermediate filament. We analysed the gene expression of these proteins by in situ hybridisation and performed functional knockdowns with RNA interference. Remarkably, there are almost no differences in terms of morphology, protein regions, and gene expression based on marine, brackish, and freshwater habitats. This implies that glue components produced by macrostomids are conserved among species, and this set of two-component glue functions from low to high salinity. These findings could contribute to the development of novel reversible biomimetic glues that work in all wet environments and could have applications in drug delivery systems, tissue adhesives, or wound dressings.

Due to its high relevance for designing ball joints in mechanical engineering and (artificial) hip joints in biomechanics, the almost conformal elastic contact between a sphere and a spherical cup represents an important contact problem of current research. As no closed-form analytical solution to the problem has been found to date, full computational methods such as the finite element method are needed for analysis. However, they often require incredibly long, unacceptable calculation times, making parameter studies hardly practicable. For this reason, approximate analytical and semi-analytical models are applied, capable of predicting quantities of interest with sufficient accuracy. In the present work, a very simple model based on a radially directed Winkler foundation is presented, which provides (approximate) closed-form analytical solutions for both the pressure distribution and the dependencies between macroscopic contact quantities such as normal force and indentation depth. To ensure an optimal mapping of a specific contact problem, only the foundation modulus must be defined in a suitable way. As an example, the proposed model has been successfully adapted to adequately simulate the frictionless normal contact for hard-on-soft hip implants. For this purpose, the foundation modulus was approximated with the aid of a finite element analysis instead of adopting it from already well-established models, as the latter produce clearly erroneous results for large liner thicknesses and large Poisson’s ratios. By a comparison with extensive parameter studies of finite element simulations, it is demonstrated that the proposed model provides acceptable results for all commonly used hard-on-soft hip implants. On this basis, the influence of geometrical changes of the femoral head and the acetabular cup on the maximum pressure as well as the half-contact angle is discussed, and consequences on the wear behavior are deduced.

Audio carriers are subject to a fast and irreversible decay. In order to save valuable historical recordings, the audio signal and other relevant information can be extracted from the source audio document and stored on another medium, normally a redundant digital storage system. This procedure is called ’content transfer’. It is a costly and time-consuming procedure. There are several solutions with which the cost can be reduced. One consists of picking up all tracks from a two-sided tape in one pass. This means that some tracks will be digitized forward and some backwards, to be subsequently corrected in the digital workstation. This article is concerned with the question of whether reading tracks backwards introduces unwanted effects into the signal. In particular, it investigates whether a difference can be observed between audio signals read forward or backwards and, if so, whether the difference is measurable. The results show that a difference can be observed, yet this is not enough to conclude that this “backwards” approach should not be used. The complexity of the situation is presented in the discussion. Future work includes reproducing this experiment with different audio equipment, as well as a perception test with human subjects.

Etched ion-track polycarbonate membranes with conical nanochannels of aspect ratios of ~3000 are coated with Al2O3, TiO2, and SiO2 thin films of thicknesses between 10 and 20 nm by atomic layer deposition (ALD). By combining ion-track technology and ALD, the fabrication of two kinds of functional structures with customized surfaces is presented: (i) arrays of free-standing conical nanotubes with controlled geometry and wall thickness, interesting for, e.g., drug delivery and surface wettability regulation, and (ii) single nanochannel membranes with inorganic surfaces and adjustable isoelectric points for nanofluidic applications.

Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective altered secretory profile, the senescence-associated secretory phenotype (SASP), was suggested as a central process for the initiation and progression of pneumonitis and pulmonary fibrosis. We previously reported that abrogation of certain aspects of the secretome of senescent lung cells, in particular, signaling inhibition of the SASP-factor Ccl2/Mcp1 mediated radioprotection especially by limiting endothelial dysfunction. Here, we investigated the therapeutic potential of a combined metformin treatment to protect normal lung tissue from RT-induced senescence and associated lung injury using a preclinical mouse model of radiation-induced pneumopathy. Metformin treatment efficiently limited RT-induced senescence and SASP expression levels, thereby limiting vascular dysfunctions, namely increased vascular permeability associated with increased extravasation of circulating immune and tumor cells early after irradiation (acute effects). Complementary in vitro studies using normal lung epithelial cell lines confirmed the senescence-limiting effect of metformin following RT finally resulting in radioprotection, while fostering RT-induced cellular stress of cultured malignant epithelial cells accounting for radiosensitization. The radioprotective action of metformin for normal lung tissue without simultaneous protection or preferable radiosensitization of tumor tissue might increase tumor control probabilities and survival because higher radiation doses could be used.

Basal cell carcinoma (BCC) originate from Hedgehog/Patched signaling-activated epidermal stem cells. However, the chemically induced tumorigenesis of mice with a CD4Cre-mediated biallelic loss of the Hedgehog signaling repressor Patched also induces BCC formation. Here, we identified the cellular origin of CD4Cre-targeted BCC progenitors as rare Keratin 5+ epidermal cells and show that wildtype Patched offspring of these cells spread over the hair follicle/skin complex with increasing mouse age. Intriguingly, Patched mutant counterparts are undetectable in age-matched untreated skin but are getting traceable upon applying the chemical tumorigenesis protocol. Together, our data show that biallelic Patched depletion in rare Keratin 5+ epidermal cells is not sufficient to drive BCC development, because the spread of these cells is physiologically suppressed. However, bypassing the repression of Patched mutant cells, e.g., by exogenous stimuli, leads to an accumulation of BCC precursor cells and, finally, to tumor development.

Molecular chaperones, particularly the 70-kDa heat shock proteins (Hsp70s), are key orchestrators of the cellular stress response. To perform their critical functions, Hsp70s require the presence of specific co-chaperones, which include nucleotide exchange factors containing the BCL2-associated athanogene (BAG) domain. BAG-1 is one of these proteins that function in a wide range of cellular processes, including apoptosis, protein refolding, and degradation, as well as tumorigenesis. However, the origin of BAG-1 proteins and their evolution between and within species are mostly uncharacterized. This report investigated the macro- and micro-evolution of BAG-1 using orthologous sequences and single nucleotide polymorphisms (SNPs) to elucidate the evolution and understand how natural variation affects the cellular stress response. We first collected and analyzed several BAG-1 sequences across animals, plants, and fungi; mapped intron positions and phases; reconstructed phylogeny; and analyzed protein characteristics. These data indicated that BAG-1 originated before the animals, plants, and fungi split, yet most extant fungal species have lost BAG-1. Furthermore, although BAG-1’s structure has remained relatively conserved, kingdom-specific conserved differences exist at sites of known function, suggesting functional specialization within each kingdom. We then analyzed SNPs from the 1000 genomes database to determine the evolutionary patterns within humans. These analyses revealed that the SNP density is unequally distributed within the BAG1 gene, and the ratio of non-synonymous/synonymous SNPs is significantly higher than 1 in the BAG domain region, which is an indication of positive selection. To further explore this notion, we performed several biochemical assays and found that only one out of five mutations tested altered the major co-chaperone properties of BAG-1. These data collectively suggest that although the co-chaperone functions of BAG-1 are highly conserved and can probably tolerate several radical mutations, BAG-1 might have acquired specialized and potentially unexplored functions during the evolutionary process.

MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and functional annotation of target gene sets. We here present a novel method “miRlastic”, which infers miRNA-target interactions using transcriptomic data as well as prior knowledge and performs functional annotation of target genes by exploiting the local structure of the inferred network. For the network inference, we applied linear regression modeling with elastic net regularization on matched microRNA and messenger RNA expression profiling data to perform feature selection on prior knowledge from sequence-based target prediction resources. The novelty of miRlastic inference originates in predicting data-driven intra-transcriptome regulatory relationships through feature selection. With synthetic data, we showed that miRlastic outperformed commonly used methods and was suitable even for low sample sizes. To gain insight into the functional role of miRNAs and to determine joint functional properties of miRNA clusters, we introduced a local enrichment analysis procedure. The principle of this procedure lies in identifying regions of high functional similarity by evaluating the shortest paths between genes in the network. We can finally assign functional roles to the miRNAs by taking their regulatory relationships into account. We thoroughly evaluated miRlastic on a cohort of head and neck cancer (HNSCC) patients provided by The Cancer Genome Atlas. We inferred an mi-/mRNA regulatory network for human papilloma virus (HPV)-associated miRNAs in HNSCC. The resulting network best enriched for experimentally validated miRNA-target interaction, when compared to common methods. Finally, the local enrichment step identified two functional clusters of miRNAs that were predicted to mediate HPV-associated dysregulation in HNSCC. Our novel approach was able to characterize distinct pathway regulations from matched miRNA and mRNA data. An R package of miRlastic was made available through: http://icb.helmholtz-muenchen.de/mirlastic.