julilili42/papers huggingface dataset:
Development of a musculoskeletal model of the wrist to predict frictional work dissipated due to tendon gliding resistance in the carpal tunnel
2020-12-27

Carpal tunnel syndrome is an entrapment neuropathy that has been associated with the aggravation of tendon gliding resistance due to forceful, high velocity, awkwardly angled, and repetitive wrist motions. Cadaveric and epidemiological studies have shown that combinations of these risk factors have a more than additive effect. The aim of the current study was to develop a musculoskeletal model of the wrist that could evaluate these risk factors by simulating frictional work dissipated due to the gliding resistance of the third flexor digitorum superficialis tendon. Three flexion angle zones, three extension angle zones, five levels of task repetitiveness, and five levels of task effort were derived from ergonomic standards. Of the simulations performed by systematically combining these parameters, the extreme wrist flexion zone, at peak task repetitiveness and effort, dissipated the most frictional work. This zone dissipated approximately double the amount of frictional work compared to its equivalent zone in extension. For all motions, a multiplicative effect of the combination of task repetitiveness and effort on frictional work was identified by the musculoskeletal model, corroborating previous epidemiological and experimental studies. Overall, these results suggest that the ergonomic standards for wrist flexion-extension may need to be adjusted to reflect equivalent biomechanical impact and that workplace tasks should be designed to minimise exposure to combinations of highly repetitive and highly forceful work, especially when the wrist is highly flexed.
Pushing the Limits of Acene Chemistry: The Recent Surge of Large Acenes
2020-12-28

Abstract Acenes, consisting of linearly fused benzene rings, are an important fundamental class of organic compounds with various applications. Hexacene is the largest acene that was synthesized and isolated in the 20th century. The next largest member of the acene family, heptacene, was observed in 2007 and since then significant progress in preparing acenes has been reported. Significantly larger acenes, up to undecacene, could be studied by means of low‐temperature matrix isolation spectroscopy with in situ photolytic generation, and up to dodecacene by means of on‐surface synthesis employing innovative precursors and highly defined crystalline metal surfaces under ultrahigh vacuum conditions. The review summarizes recent experimental and theoretical advances in the area of acenes that give a significantly deeper insight into the fundamental properties and nature of the electronic structure of this fascinating class of organic compounds.
Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer by Pattern of Metastatic Spread: ARCHES Post Hoc Analyses
2020-12-28

These findings indicate that treatment with enzalutamide plus androgen deprivation therapy provides improvements in men with bone and/or lymph node metastases but may be less effective in men with visceral patterns of spread.
Dapagliflozin effects on haematocrit, red blood cell count and reticulocytes in insulin-treated patients with type 2 diabetes
2020-12-28

Abstract Recent studies have shown that high-risk patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose cotransporter 2 (SGLT2) inhibitors have improved cardiovascular (CV) outcomes. In an exploratory analysis of data from the EMPA-REG study, elevations in haematocrit were shown to be strongly associated with beneficial CV effects. As insulin treatment has been shown to be antinatriuretic, with an associated increase in extracellular fluid volume, it is important to confirm whether haematocrit increase is maintained with concomitant insulin therapy. Here, we investigate the effect of the SGLT2 inhibitor dapagliflozin on haematocrit, red blood cell (RBC) counts and reticulocyte levels in high-risk patients with T2DM receiving insulin. A 24-week, double-blinded, randomised, placebo-controlled trial (ClinicalTrials.gov: NCT00673231) was reported previously with extension periods of 24 and 56 weeks (total of 104 weeks). Patients receiving insulin were randomised 1:1:1:1 to placebo or dapagliflozin at 2.5, 5 or 10 mg. Haematocrit, RBC and reticulocyte measurements were conducted during this study, and a longitudinal repeated-measures analysis was performed here to examine change from baseline during treatment. Dapagliflozin treatment in combination with insulin resulted in a dose-dependent increase in haematocrit levels and RBCs over a 104 week period. There was a short-term increase in reticulocyte levels at the start of treatment, which dropped to below baseline after 8 weeks. SGLT2 inhibition with dapagliflozin leads to a sustained increase in haematocrit in patients receiving chronic insulin treatment.
Testing general relativity with x-ray reflection spectroscopy: The Konoplya-Rezzolla-Zhidenko parametrization
2020-12-28

X-ray reflection spectroscopy is a promising technique for testing general relativity in the strong-field regime as it can be used to test the Kerr black hole hypothesis. In this context, the parametrically deformed black hole metrics proposed by Konoplya, Rezzolla, and Zhidenko [Phys. Rev. D 93, 064015 (2016)] form an important class of non-Kerr black holes. We implement this class of black hole metrics in relxill_nk, which is a framework we have developed for testing for non-Kerr black holes using x-ray reflection spectroscopy. We perform a qualitative analysis of the effect of the leading order strong-field deformation parameters on typical observables like the innermost stable circular orbits and the reflection spectra. We also present the first x-ray constraints on some of the deformation parameters of this metric, using Suzaku data from the supermassive black hole in Ark 564, and compare them with those obtained (or expected) from other observational techniques like gravitational waves and black hole imaging.
Cyclic Stretch of Either PNS or CNS Located Nerves Can Stimulate Neurite Outgrowth
2020-12-28

The central nervous system (CNS) does not recover from traumatic axonal injury, but the peripheral nervous system (PNS) does. We hypothesize that this fundamental difference in regenerative capacity may be based upon the absence of stimulatory mechanical forces in the CNS due to the protective rigidity of the vertebral column and skull. We developed a bioreactor to apply low-strain cyclic axonal stretch to adult rat dorsal root ganglia (DRG) connected to either the peripheral or central nerves in an explant model for inducing axonal growth. In response, larger diameter DRG neurons, mechanoreceptors and proprioceptors showed enhanced neurite outgrowth as well as increased Activating Transcription Factor 3 (ATF3).
On the Challenges of Open World Recognition Under Shifting Visual Domains
2020-12-28

Robotic visual systems operating in the wild must act in unconstrained\\nscenarios, under different environmental conditions while facing a variety of\\nsemantic concepts, including unknown ones. To this end, recent works tried to\\nempower visual object recognition methods with the capability to i) detect\\nunseen concepts and ii) extended their knowledge over time, as images of new\\nsemantic classes arrive. This setting, called Open World Recognition (OWR), has\\nthe goal to produce systems capable of breaking the semantic limits present in\\nthe initial training set. However, this training set imposes to the system not\\nonly its own semantic limits, but also environmental ones, due to its bias\\ntoward certain acquisition conditions that do not necessarily reflect the high\\nvariability of the real-world. This discrepancy between training and test\\ndistribution is called domain-shift. This work investigates whether OWR\\nalgorithms are effective under domain-shift, presenting the first benchmark\\nsetup for assessing fairly the performances of OWR algorithms, with and without\\ndomain-shift. We then use this benchmark to conduct analyses in various\\nscenarios, showing how existing OWR algorithms indeed suffer a severe\\nperformance degradation when train and test distributions differ. Our analysis\\nshows that this degradation is only slightly mitigated by coupling OWR with\\ndomain generalization techniques, indicating that the mere plug-and-play of\\nexisting algorithms is not enough to recognize new and unknown categories in\\nunseen domains. Our results clearly point toward open issues and future\\nresearch directions, that need to be investigated for building robot visual\\nsystems able to function reliably under these challenging yet very real\\nconditions. Code available at\\nhttps://github.com/DarioFontanel/OWR-VisualDomains\\n
Non invasive in vivo monitoring of dimethyl fumarate treatment in EAE by assessing the glucose metabolism in secondary lymphoid organs
2020-12-28

[<sup>18</sup> F]FDG-PET/CT is a high sensitive functional diagnostic imaging modality to monitor tumor but also immune cell activation by determination of the glucose metabolism. Our results show that the anti-inflammatory effects of immunotherapeutics like DMF can be assessed non invasively in vivo during Th1/Th17 cell-mediated encephalomyelitis (EAE) by [<sup>18</sup> F]FDG-PET/CT imaging of the draining lymph nodes.
Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
2020-12-29

Significance Low sunlight exposure and low vitamin D (vitD) levels are risk factors for the development of multiple sclerosis. However, there is still an ongoing debate, whether sunlight and vitD also modulate disease severity and worsening. Observational studies suggested vitD-dependent effects, but prospective supplementation studies have so far been inconclusive and reverse causality cannot be excluded as a source of bias. By using the sun-exposure measures vitD and latitude, we show correlations between vitD/latitude, vitD/disease severity, and latitude/disease severity in two multicentric cohorts. Although vitD cannot be proven as the causal factor, we provide evidence for clinically relevant effects of sunlight exposure. Furthermore, this study suggests sunlight-triggered pathways other than vitD could play additional and modulatory roles, as well.
Collective Perception: A Safety Perspective
2020-12-29

Vehicle-to-everything (V2X) communication is seen as one of the main enabling technologies for automated vehicles. Collective perception is especially promising, as it allows connected traffic participants to “see through the eyes of others” by sharing sensor-detected objects via V2X communication. Its benefit is typically assessed in terms of the increased object update rate, redundancy, and awareness. To determine the safety improvement thanks to collective perception, the authors introduce new metrics, which quantify the environmental risk awareness of the traffic participants. The performance of the V2X service is then analyzed with the help of the test platform TEPLITS, using real traffic traces from German highways, amounting to over 100 h of total driving time. The results in the considered scenarios clearly show that collective perception not only contributes to the accuracy and integrity of the vehicles’ environmental perception, but also that a V2X market penetration of at least 25% is necessary to increase traffic safety from a “risk of serious traffic accidents” to a “residual hypothetical risk of collisions without minor injuries” for traffic participants equipped with non-redundant 360° sensor systems. These results support the ongoing worldwide standardization efforts of the collective perception service.
Energetics of Formation of Cyclacenes from 2,3‐Didehydroacenes and Implications for Astrochemistry
2020-12-29

Abstract The carriers of the diffuse interstellar bands (DIBs) are still largely unknown although polycyclic aromatic hydrocarbons, carbon chains, and fullerenes are likely candidates. A recent analysis of the properties of n ‐acenes of general formula C 4 n +2 H 2 n +4 suggested that these could be potential carriers of some DIBs. Dehydrogenation reactions of n ‐acenes after absorption of an interstellar UV photon may result in dehydroacenes. Here the reaction energies and barriers for formation of n ‐cyclacenes from 2,3‐didehydroacenes ( n ‐DDA) by intramolecular Diels–Alder reaction to dihydro‐etheno‐cyclacenes ( n ‐DEC) followed by ejection of ethyne by retro‐Diels–Alder reactions are analyzed using thermally assisted occupation density functional theory (TAO‐DFT) for n =10–20. It is found that the barriers for each of the steps depend on the ring strain of the underlying n ‐cyclacene, and that the ring strain of n ‐DEC is about 75 % of that of the corresponding n ‐cyclacene. In each case, ethyne extrusion is the step with the highest energy barrier, but these barriers are smaller than CH bond dissociation energies, suggesting that formation of cyclacenes is an energetically conceivable fate of n ‐acenes after multiple absorption of UV photons.
Long-Term Consumption of Anthocyanin-Rich Fruit Juice: Impact on Gut Microbiota and Antioxidant Markers in Lymphocytes of Healthy Males
2020-12-29

Polyphenols are considered protective against diseases associated with oxidative stress. Short-term intake of an anthocyanin-rich fruit juice resulted in significantly reduced deoxyribonucleic acid (DNA) strand-breaks in peripheral blood lymphocytes (PBLs) and affected antioxidant markers in healthy volunteers. Consequently, effects of long-term consumption of fruit juice are of particular interest. In focus was the impact on nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), the Nrf2-regulated genes NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) as well as effects on the gut microbiota. In a nine-week placebo-controlled intervention trial with 57 healthy male volunteers, consumption of anthocyanin-rich juice significantly increased NQO-1 and HO-1 transcript levels in PBLs compared to a placebo beverage as measured by real-time polymerase chain reaction (PCR). Three Nrf2-promotor single nucleotide polymorphisms (SNPs), analyzed by pyrosequencing, indicated an association between individual Nrf2 transcript levels and genotype. Moreover, the Nrf2 genotype appeared to correlate with the presence of specific microbial organisms identified by 16S-PCR and classified as Spirochaetaceae. Furthermore, the microbial community was significantly affected by the duration of juice consumption and intake of juice itself. Taken together, long-term consumption of anthocyanin-rich fruit juice affected Nrf2-dependent transcription in PBLs, indicating systemic effects. Individual Nrf2 genotypes may influence the antioxidant response, thus requiring consideration in future intervention studies focusing on the Nrf2 pathway. Anthocyanin-rich fruit juice had an extensive impact on the gut microbiota.
Gravitational Higgs mechanism and resulting observational effects
2020-12-29

Recently, a toy model was introduced to demonstrate that screening mechanisms in alternative theories of gravitation can hide additional effects. In this model a scalar field is charged under a U(1) symmetry. In sufficiently compact objects the scalar field spontaneously grows, i.e., the object scalarizes, spontaneously breaking the U(1) symmetry. Exactly as in the U(1) Higgs mechanism this leads to the emergence of a mass for the gauge field. The aim of this paper is to provide an example of the physical consequences if we consider this toy model as a prototype of Weak Equivalence Principle (WEP) violations. We model neutron stars with a dipolar magnetic field to compare the magnetic field behavior of stars in Einstein-Maxwell theory on the one hand and in scalar-tensor theory with the, so-called, gravitational Higgs mechanism on the other hand.
A Dataset of neurophysiological measurements of patients with completely locked-In syndrome
2020-12-29

This is a dataset used for the psychophysiological assessment of four patients with amyotrophic lateral sclerosis (ALS) at advanced stages of the diseases with no means of communication, referred to as patients with complete locked-in syndrome (CLIS). These datasets contain electroencephalogram (EEG), electrooculography (EOG) and functional near-infrared spectroscopy (fNIRS) recordings. During a four-day visit, each patient was recorded performing the various passive and active experiments at a sensory, perceptual, and cognitive level. The dataset includes somatosensory evoked potentials (SEPs), auditory evoked potentials (AEPs), resting-state in two conditions while eyes are open and eyes closed, Brain-Computer Interface (BCI) communication attempt, and during sleep.
Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development
2020-12-30

Molecular dynamics (MD) simulations have become increasingly useful in the modern drug development process. In this review, we give a broad overview of the current application possibilities of MD in drug discovery and pharmaceutical development. Starting from the target validation step of the drug development process, we give several examples of how MD studies can give important insights into the dynamics and function of identified drug targets such as sirtuins, RAS proteins, or intrinsically disordered proteins. The role of MD in antibody design is also reviewed. In the lead discovery and lead optimization phases, MD facilitates the evaluation of the binding energetics and kinetics of the ligand-receptor interactions, therefore guiding the choice of the best candidate molecules for further development. The importance of considering the biological lipid bilayer environment in the MD simulations of membrane proteins is also discussed, using G-protein coupled receptors and ion channels as well as the drug-metabolizing cytochrome P450 enzymes as relevant examples. Lastly, we discuss the emerging role of MD simulations in facilitating the pharmaceutical formulation development of drugs and candidate drugs. Specifically, we look at how MD can be used in studying the crystalline and amorphous solids, the stability of amorphous drug or drug-polymer formulations, and drug solubility. Moreover, since nanoparticle drug formulations are of great interest in the field of drug delivery research, different applications of nano-particle simulations are also briefly summarized using multiple recent studies as examples. In the future, the role of MD simulations in facilitating the drug development process is likely to grow substantially with the increasing computer power and advancements in the development of force fields and enhanced MD methodologies.
Inducible expression of (pp)pGpp synthetases in Staphylococcus aureus is associated with activation of stress response genes
2020-12-30

The stringent response is characterized by the synthesis of the messenger molecules pppGpp, ppGpp or pGpp (here collectively designated (pp)pGpp). The phenotypic consequences resulting from (pp)pGpp accumulation vary among species and can be mediated by different underlying mechanisms. Most genome-wide analyses have been performed under stress conditions, which often mask the immediate effects of (pp)pGpp-mediated regulatory circuits. In Staphylococcus aureus , (pp)pGpp can be synthesized via the RelA-SpoT-homolog, Rel Sau upon amino acid limitation or via one of the two small (pp)pGpp synthetases RelP or RelQ upon cell wall stress. We used RNA-Seq to compare the global effects in response to induction of the synthetase of rel-Syn (coding for the enzymatic region of Rel Sau ) or relQ without the need to apply additional stress conditions. Induction of rel-Syn resulted in changes in the nucleotide pool similar to induction of the stringent response via the tRNA synthetase inhibitor mupirocin: a reduction in the GTP pool, an increase in the ATP pool and synthesis of pppGpp, ppGpp and pGpp. Induction of all three enzymes resulted in similar changes in the transcriptome. However, RelQ was less active than Rel-Syn and RelP, indicating strong restriction of its (pp)pGpp-synthesis activity in vivo . (pp)pGpp induction resulted in the downregulation of many genes involved in protein and RNA/DNA metabolism. Many of the (pp)pGpp upregulated genes are part of the GTP sensitive CodY regulon and thus likely regulated through lowering of the GTP pool. New CodY independent transcriptional changes were detected including genes involved in the SOS response, iron storage (e.g. ftnA , dps ), oxidative stress response (e.g., perR , katA , sodA ) and the psmα1–4 and psmß1-2 operons coding for cytotoxic, phenol soluble modulins (PSMs). Analyses of the ftnA , dps and psm genes in different regulatory mutants revealed that their (pp)pGpp-dependent regulation can occur independent of the regulators PerR, Fur, SarA or CodY. Moreover, psm expression is uncoupled from expression of the quorum sensing system Agr, the main known psm activator. The expression of central genes of the oxidative stress response protects the bacteria from anticipated ROS stress derived from PSMs or exogenous sources. Thus, we identified a new link between the stringent response and oxidative stress in S . aureus that is likely crucial for survival upon phagocytosis.
Peasant Agency and the Supernatural
2020-12-30

Engaging with supernatural forces was a necessity for Carolingian peasants – Christian authorities expected this and the belief in the inevitability of these acts seems to have been widely shared by contemporaries who lived in a world far beyond their control. Miracle collections show that peasants (and others) made conscious decisions about the way in which they wanted to interact with supernatural forces. In doing this, they also took into account the networks of individuals and institutions who controlled the saints’ resting places, which could provide invaluable support for those seeking help. Others chose practices beyond what contemporary elites regarded as legitimate, such as hiring weather-makers to prevent bad weather. In some cases, peasants actively sought to enter into a saint’s dependency, either by giving themselves to the saint or by convincing their lords to hand them over to a saint and his or her shrine.