julilili42/papers huggingface dataset:
Multimode Vibrational Strong Coupling of Methyl Salicylate to a Fabry–Pérot Microcavity
2020-06-15

The strong coupling of an IR-active molecular transition with an optical mode of the cavity results in vibrational polaritons, which opens a new way to control chemical reactivity via confined electromagnetic fields of the cavity. In this study, we design a voltage-tunable open microcavity and we show the formation of multiple vibrational polaritons in methyl salicylate. A Rabi splitting and polariton anticrossing behaviour is observed when the cavity mode hybridizes with the C=O stretching vibration of methyl salicylate. As this vibration contributes to the reaction coordinate of the photoinduced proton transfer process in methyl salicylate, we suggest the coupling might be used to modulate the photophysical properties of the molecule. Furthermore, the proposed theoretical model based on coupled harmonic oscillator reveals that the absorption of uncoupled molecules must also be considered to model the experimental spectra properly and that simultaneous coupling of multiple molecular vibrations to the same cavity mode has a significant influence on the Rabi splitting.
Comparison of soil characteristics from geophysical and geochemical techniques along a climate and ecological gradient, Chilean Coastal Cordillera (26° to 38° S)
2020-06-15

Abstract. In this study, we combine geophysical observations from Ground Penetrating Radar (GPR) with soil physical, and geochemical properties from pedons excavated in four study areas spanning 1,300 km of the climate and ecological gradient in the Chilean Coastal Cordillera. Our aims are to: (1) relate GPR observations to depth varying soil physical and weathering-related chemical properties in adjacent pedons, and (2) evaluate the lateral extent to which these properties can be extrapolated along a hillslope using GPR observations. Physical observations considered include soil bulk density and grain size distribution whereas chemical observations are based on major and trace element analysis. Results indicate that visually-determined soil thickness and the transition from the soil B to C horizons generally correlate with maximums in the 500 and 1000 MHz GPR envelope profiles. To a lesser degree, these maximums in the GPR envelope profiles agree with maximums in weathering related indices such as the Chemical Index of Alteration (CIA) and the chemical index of mass transfer (τ) for Na. Finally, we find that up-scaling from the pedon to hillslope scale is possible with geophysical methods for certain pedon properties available. Taken together, these findings suggest that the GPR profiles along hillslopes can be used to infer lateral thickness variations in soil horizons, and to some degree the physical and chemical variations with depth.
Advanced Age Increases Immunosuppression in the Brain and Decreases Immunotherapeutic Efficacy in Subjects with Glioblastoma
2020-06-16

Abstract Purpose: Wild-type isocitrate dehydrogenase–expressing glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median age at diagnosis of ≥65 years. It accounts for approximately 90% of all GBMs and has a median overall survival (OS) of &amp;lt;15 months. Although immune checkpoint blockade (ICB) therapy has achieved remarkable survival benefits in a variety of aggressive malignancies, similar success has yet to be achieved for GBM among phase III clinical trials to date. Our study aimed to understand the relationship between subject age and immunotherapeutic efficacy as it relates to survival from glioma. Experimental Design: (i) Clinical data: GBM patient datasets from The Cancer Genome Atlas, Northwestern Medicine Enterprise Data Warehouse, and clinical studies evaluating ICB were stratified by age and compared for OS. (ii) Animal models: young, middle-aged, and older adult wild-type and indoleamine 2,3 dioxygenase (IDO)-knockout syngeneic mice were intracranially engrafted with CT-2A or GL261 glioma cell lines and treated with or without CTLA-4/PD-L1 mAbs, or radiation, anti–PD-1 mAb, and/or a pharmacologic IDO enzyme inhibitor. Results: Advanced age was associated with decreased GBM patient survival regardless of treatment with ICB. The advanced age–associated increase of brain IDO expression was linked to the suppression of immunotherapeutic efficacy and was not reversed by IDO enzyme inhibitor treatment. Conclusions: Immunosuppression increases in the brain during advanced age and inhibits antiglioma immunity in older adults. Going forward, it will be important to fully understand the factors and mechanisms in the elderly brain that contribute to the decreased survival of older patients with GBM during treatment with ICB.
Scalar leptoquark pair production at hadron colliders
2020-06-16

We revisit scalar leptoquark pair-production at hadron colliders and\\nsignificantly improve the level of precision of the cross section calculations.\\nApart from QCD contributions, we include lepton t-channel exchange diagrams\\nthat turn out to be relevant in the light of the recent B-anomalies. We\\nevaluate all contributions at next-to-leading-order accuracy in QCD and resum,\\nin the threshold regime, soft-gluon radiation at next-to-next-to-leading\\nlogarithmic accuracy. Our predictions consist hence in the most precise\\nleptoquark cross section calculations available to date, and are necessary for\\nthe best exploitation of leptoquark searches at the LHC.\\n
IMPROVEjob – Participatory intervention to improve job satisfaction of general practice teams: a model for structural and behavioural prevention in small and medium-sized enterprises – a study protocol of a cluster-randomised controlled trial
2020-06-16

Abstract Background Perceived high chronic stress is twice as prevalent among German general practitioners (GPs) and non-physician medical staff compared to the general population. The reasons are multi-factorial and include patient, practice, healthcare system and societal factors, such as multi-morbidity, the diversity of populations and innovations in medical care. Also, practice-related factors, like stressful patient-staff interactions, poor process management of waiting times and lack of leadership, play a role. This publicly funded study evaluates the effectiveness of the newly developed participatory, interdisciplinary, and multimodal IMPROVE job intervention on improving job satisfaction among general practice personnel. The intervention aims at structural stress prevention with regard to working conditions and behavioural stress prevention for leaders and other practice personnel. Methods In this cluster-randomised controlled trial, a total of 56 general practices will be assigned to either (1) participation in the IMPROVE job intervention or (2) the waiting-list control group. The IMPROVE job intervention consists of the following elements: three workshops, a toolbox with supplemental material and an implementation period with regular contact to so-called IMPROVE job facilitators. The first workshop, addressing leadership issues, is designed for physicians with leadership responsibilities only. The two subsequent workshops target all GP and non-physician personnel; they address issues of communication (with patients and within the team), self-care and team-care and practice organisation. During the 9-month implementation period, practices will be contacted by IMPROVE job facilitators to enhance motivation. Additionally, the practices will have access to the toolbox materials online. All participants will complete questionnaires at baseline and follow up. The primary outcome is the change in job satisfaction as measured by the respective scale of the validated German version of the Copenhagen Psychosocial Questionnaire (COPSOQ, version 2018). Secondary outcomes obtained by questionnaires and - qualitatively - by facilitators comprise psychosocial working conditions including leadership aspects, expectations and experiences of the workshops, team and individual efforts and organisational changes. Discussion It is hypothesised that participation in the IMPROVE job intervention will improve job satisfaction and thus constitute a structural and behavioural prevention strategy for the promotion of psychological wellbeing of personnel in general practices and prospectively in other small and medium sized enterprises. Trial registration German Clinical Trials Register: DRKS00012677 . Registered on 16 October 2019. Retrospectively, https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&amp;TRIAL_ID = DRKS00012677.
System Identification with Biophysical Constraints: A Circuit Model of the Inner Retina
2020-06-16

Abstract Visual processing in the retina has been studied in great detail at all levels such that a comprehensive picture of the retina’s cell types and the many neural circuits they form is emerging. However, the currently best performing models of retinal function are black-box CNN models which are agnostic to such biological knowledge. In particular, these models typically neglect the role of the many inhibitory circuits involving amacrine cells and the biophysical mechanisms underlying synaptic release. Here, we present a computational model of temporal processing in the inner retina, including inhibitory feedback circuits and realistic synaptic release mechanisms. Fit to the responses of bipolar cells, the model generalized well to new stimuli including natural movie sequences, performing on par with or better than a benchmark black-box model. In pharmacology experiments, the model replicated in silico the effect of blocking specific amacrine cell populations with high fidelity, indicating that it had learned key circuit functions. Also, more in depth comparisons showed that connectivity patterns learned by the model were well matched to connectivity patterns extracted from connectomics data. Thus, our model provides a biologically interpretable data-driven account of temporal processing in the inner retina, filling the gap between purely black-box and detailed biophysical modeling.
Fc gamma receptor expression serves as prognostic and diagnostic factor in AML
2020-06-16

Risk assessment in acute myeloid leukemia (AML) mainly relies on (cyto-)genetic and morphologic features. Nonetheless, further markers are needed to allow for accurate risk stratification. Type I Fc gamma receptors (FcγRs) such as CD16, CD32, and CD64 play an important role in mediating immunomodulatory functions in different myeloid cell types as well as NK and B cells. We here evaluated expression of the three FcγR on peripheral blood AML blasts. Using flow cytometry, we found heterogeneous expression of the FcγR throughout the patient cohort. Correlation of expression levels with disease outcome revealed significantly shorter OS in patients with CD16<sup>+</sup> blasts at first diagnosis. CD32 and CD64 expression showed no association with survival but correlated with a mature phenotype and FAB M6. Our data provide clear evidence for the value of immunophenotyping FcγR expression on leukemic cells using peripheral blood, which is rapidly available and improves risk stratification in AML.
First description of an ostrich from the late Miocene of Kerassia (Euboea, Greece): remarks on its cervical anatomy
2020-06-16

The present study describes an almost complete cervical region of the fossil ostrich Struthio karatheodoris from the Turolian locality of Kerassia (Euboea, Greece). The material comes from two distinct fossiliferous horizons and consists of twelve cervical vertebrae, ten of which belong to the same individual. These specimens are the first remains of a large flightless bird from Kerassia and represent some of the very few findings of the genus Struthio in the sub-Paratethyan (Balkan-Iranian) bioprovince from the late Miocene. The morphology of the cervical vertebrae implies that the neck of S. karatheodoris had similar biomechanical properties to that of extant ostriches, pointing to similar ecological adaptations, relating to food procurement. However, it probably had a more flexible and stronger neck, which might indicate a somewhat different ecology. Furthermore, considerable intraspecific size and morphological variation of the cervical vertebrae of S. karatheodoris is observed. This signifies that S. karatheodoris was not necessarily larger than S. camelus as previously suspected, but their size ranges in fact overlap significantly.
Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk
2020-06-16

Abstract In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non- BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859–1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482–1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Rapid adaptive evolution to drought in a subset of plant traits in a large-scale climate change experiment
2020-06-16

Rapid evolution of traits and of plasticity may enable adaptation to climate change, yet solid experimental evidence under natural conditions is scarce. Here, we imposed rainfall manipulations (+30%, control, -30%) for ten years on entire natural plant communities in two Eastern Mediterranean sites. Additional sites along a natural rainfall gradient and selection analyses in a greenhouse assessed whether potential responses were adaptive. In both sites, our annual target species Biscutella didyma consistently evolved earlier phenology and higher reproductive allocation under drought. Multiple arguments suggest that this response was adaptive: it aligned with theory, corresponding trait shifts along the natural rainfall gradient, and selection analyses under differential watering in the greenhouse. However, another seven candidate traits did not evolve, and there was little support for evolution of plasticity. Our results provide compelling evidence for rapid adaptive evolution under climate change. Yet, several non-evolving traits may indicate potential constraints to full adaptation.
The roles of online and offline replay in planning
2020-06-17

Animals and humans replay neural patterns encoding trajectories through their environment, both whilst they solve decision-making tasks and during rest. Both on-task and off-task replay are believed to contribute to flexible decision making, though how their relative contributions differ remains unclear. We investigated this question by using magnetoencephalography (MEG) to study human subjects while they performed a decision-making task that was designed to reveal the decision algorithms employed. We characterised subjects in terms of how flexibly each adjusted their choices to changes in temporal, spatial and reward structure. The more flexible a subject, the more they replayed trajectories during task performance, and this replay was coupled with re-planning of the encoded trajectories. The less flexible a subject, the more they replayed previously preferred trajectories during rest periods between task epochs. The data suggest that online and offline replay both participate in planning but support distinct decision strategies.
Near‐IR to Near‐IR Upconversion Luminescence in Molecular Chromium Ytterbium Salts
2020-06-17

Abstract Upconversion photoluminescence in hetero‐oligonuclear metal complex architectures featuring organic ligands is an interesting but still rarely observed phenomenon, despite its great potential from a basic research and application perspective. In this context, a new photonic material consisting of molecular chromium(III) and ytterbium(III) complex ions was developed that exhibits excitation‐power density‐dependent cooperative sensitization of the chromium‐centered 2 E/ 2 T 1 phosphorescence at approximately 775 nm after excitation of the ytterbium band 2 F 7/2 → 2 F 5/2 at approximately 980 nm in the solid state at ambient temperature. The upconversion process is insensitive to atmospheric oxygen and can be observed in the presence of water molecules in the crystal lattice.
The Arabidopsis Nα‐acetyltransferase NAA60 locates to the plasma membrane and is vital for the high salt stress response
2020-06-17

Summary In humans and plants, N‐terminal acetylation plays a central role in protein homeostasis, affects 80% of proteins in the cytoplasm and is catalyzed by five ribosome‐associated N‐acetyltransferases (NatA–E). Humans also possess a Golgi‐associated NatF ( Hs NAA60) that is essential for Golgi integrity. Remarkably, NAA60 is absent in fungi and has not been identified in plants. Here we identify and characterize the first plasma membrane‐anchored post‐translationally acting N‐acetyltransferase At NAA60 in the reference plant Arabidopsis thaliana by the combined application of reverse genetics, global proteomics, live‐cell imaging, microscale thermophoresis, circular dichroism spectroscopy, nano‐differential scanning fluorometry, intrinsic tryptophan fluorescence and X‐ray crystallography. We demonstrate that At NAA60, like Hs NAA60, is membrane‐localized in vivo by an α‐helical membrane anchor at its C‐terminus, but in contrast to Hs NAA60, At NAA60 localizes to the plasma membrane. The At NAA60 crystal structure provides insights into substrate‐binding, the broad substrate specificity and the catalytic mechanism probed by structure‐based mutagenesis. Characterization of the NAA60 loss‐of‐function mutants ( naa60‐1 and naa60‐2 ) uncovers a plasma membrane‐localized substrate of At NAA60 and the importance of NAA60 during high salt stress. Our findings provide evidence for the plant‐specific evolution of a plasma membrane‐anchored N‐acetyltransferase that is vital for adaptation to stress.
SARS-CoV-2 T-cell epitopes define heterologous and COVID-19-induced T-cell recognition
2020-06-17

<title>Abstract</title> The SARS-CoV-2 pandemic calls for the rapid development of diagnostic, preventive, and therapeutic approaches. CD4<sup>+</sup> and CD8<sup>+</sup> T cell-mediated immunity is central for control of and protection from viral infections<sup>[1-3]</sup>. A prerequisite to characterize T-cell immunity, but also for the development of vaccines and immunotherapies, is the identification of the exact viral T-cell epitopes presented on human leukocyte antigens (HLA)<sup>[2-8]</sup>. This is the first work identifying and characterizing SARS-CoV-2-specific and cross-reactive HLA class I and HLA-DR T-cell epitopes in SARS-CoV-2 convalescents (n = 180) as well as unexposed individuals (n = 185) and confirming their relevance for immunity and COVID-19 disease course. SARS-CoV-2-specific T-cell epitopes enabled detection of post-infectious T-cell immunity, even in seronegative convalescents. Cross-reactive SARS-CoV-2 T-cell epitopes revealed preexisting T-cell responses in 81% of unexposed individuals, and validation of similarity to common cold human coronaviruses provided a functional basis for postulated heterologous immunity<sup>[9]</sup> in SARS-CoV-2 infection<sup>[10,11]</sup>. Intensity of T-cell responses and recognition rate of T-cell epitopes was significantly higher in the convalescent donors compared to unexposed individuals, suggesting that not only expansion, but also diversity spread of SARS-CoV-2 T-cell responses occur upon active infection. Whereas anti-SARS-CoV-2 antibody levels were associated with severity of symptoms in our SARS-CoV-2 donors, intensity of T-cell responses did not negatively affect COVID-19 severity. Rather, diversity of SARS-CoV-2 T-cell responses was increased in case of mild symptoms of COVID-19, providing evidence that development of immunity requires recognition of multiple SARS-CoV-2 epitopes. Together, the specific and cross-reactive SARS-CoV-2 T-cell epitopes identified in this work enable the identification of heterologous and post-infectious T-cell immunity and facilitate the development of diagnostic, preventive, and therapeutic measures for COVID-19.
Resolving acceleration to very high energies along the jet of Centaurus A
2020-06-17

The nearby radio galaxy Centaurus A belongs to a class of active galaxies that are luminous at radio wavelengths. Most show collimated relativistic outflows known as jets, which extend over hundreds of thousands of parsecs for the most powerful sources. Accretion of matter onto the central supermassive black hole is believed to fuel these jets and power their emission1. Synchrotron radiation from relativistic electrons causes the radio emission, and it has been suggested that the X-ray emission from Centaurus A also originates in electron synchrotron processes2,3,4. Another possible explanation is inverse Compton scattering with cosmic microwave background (CMB) soft photons5,6,7. Synchrotron radiation needs ultrarelativistic electrons (about 50 teraelectronvolts) and, given their short cooling times, requires some continuous re-acceleration mechanism8. Inverse Compton scattering, on the other hand, does not require very energetic electrons, but the jets must stay highly relativistic on large scales (exceeding 1 megaparsec). Some recent evidence disfavours inverse Compton-CMB models9,10,11,12, although other work seems to be compatible with them13,14. In principle, the detection of extended γ-ray emission, which directly probes the presence of ultrarelativistic electrons, could distinguish between these options. At gigaelectronvolt energies there is also an unusual spectral hardening15,16 in Centaurus A that has not yet been explained. Here we report observations of Centaurus A at teraelectronvolt energies that resolve its large-scale jet. We interpret the data as evidence for the acceleration of ultrarelativistic electrons in the jet, and favour the synchrotron explanation for the X-rays. Given that this jet is not exceptional in terms of power, length or speed, it is possible that ultrarelativistic electrons are commonplace in the large-scale jets of radio-loud active galaxies.
Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer
2020-06-17

Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer.