Miracle-dz/UniFAR-FTUs huggingface dataset:
Thermal decay rates for an asymmetric cusped barrier at strong friction

The thermal decay of a metastable state over an asymmetric cusped barrier in the regime of overdamping (strong friction) is considered. This seems to be of importance for the nanoscale experiments on pulling polymeric molecules. The decay process is simulated numerically through computer solving of the Langevin equation. The quasistationary rates RD , as well as the mean lifetimes and transient times, are extracted from the numerical time-dependent rates Rn (t). The impact of the backscattering on the value of RD is discussed. The approximate analytical decay rate is derived for the asymmetric cusped barrier. The numerical results are confronted with this formula and with another analytical formula (the integral Kramers rate) available in the literature.
CD4+ resident memory T cells dominate immunosurveillance and orchestrate local recall responses

This study examines the extent to which memory CD4+ T cells share immunosurveillance strategies with CD8+ resident memory T cells (TRM). After acute viral infection, memory CD4+ T cells predominantly used residence to survey nonlymphoid tissues, albeit not as stringently as observed for CD8+ T cells. In contrast, memory CD4+ T cells were more likely to be resident within lymphoid organs than CD8+ T cells. Migration properties of memory-phenotype CD4+ T cells in non-SPF parabionts were similar, generalizing these results to diverse infections and conditions. CD4+ and CD8+ TRM shared overlapping transcriptional signatures and location-specific features, such as granzyme B expression in the small intestine, revealing tissue-specific and migration property–specific, in addition to lineage-specific, differentiation programs. Functionally, mucosal CD4+ TRM reactivation locally triggered both chemokine expression and broad immune cell activation. Thus, residence provides a dominant mechanism for regionalizing CD4+ T cell immunity, and location enforces shared transcriptional, phenotypic, and functional properties with CD8+ T cells.
The Use of Volatile Anesthetics as Sedatives for Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) remains to pose a high morbidity and mortality without any targeted therapies. Sedation, usually given intravenously, is an important part of clinical practice in intensive care unit (ICU), and the effect of sedatives on patients’ outcomes has been studied intensively. Although volatile anesthetics are not routine sedatives in ICU, preclinical and clinical studies suggested their potential benefit in pulmonary pathophysiology. This review will summarize the current knowledge of ARDS and the role of volatile anesthetic sedation in this setting from both clinical and mechanistic standpoints. In addition, we will review the infrastructure to use volatile anesthetics.
New light for old enigmas in epithelial transport?

The maintenance of a layer of fluid at the surface of the air-ways and the gas exchange region of the lung is an essential activity of the respiratory epithelium, ensuring efficient gas exchange and mucociliary clearance-driven bacterial removal, among other functions. Regulation of the height of this airway or alveolar surface liquid layer is dependent on opposing secretory and absorptive fluid transportprocessesthat,inturn,aredrivenbyiontransport.Secretion into the alveolar surface liquid layer requires blood-to-lumen Cl − flow mediated by cystic fibrosis transmembrane conductance regulator (CFTR) channels, whose functional significance is highlighted by the fact that their impairment is associated to cystic fibrosis. Absorptive fluxes affecting the alveolar surface liquid layer are dependent on Na + movement mediated by the apical membrane epithelial Na + channel (ENaC) and basolaterally located Na + –K + pump. The relevance of the ENaC in the respiratory system can be gauged from the consequence of human mutations enhancing its activity or overexpression in trans-genic mice, both of which lead to cystic fibrosis-like pathology. The ENaC and its relationship with Na + –K + pump are therefore important in the physiology of the respiratory epithelium and in potentially life-threatening pathological states. Our knowledge of ENaC physiology and the cell biology determining its expression and localization are of great interest. Two remarkable observations are presented in a paper from Luis Galietta ' s laboratory in this issue of Experimental Physiology (Musante et al., 2019). First, immunolocalization
Cumulative acquisition of pathogenicity islands has shaped virulence potential and contributed to the emergence of LEE-negative Shiga toxin-producing Escherichia coli strains

ABSTRACT Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens causing severe gastroenteritis, which may lead to hemolytic uremic syndrome. The Locus of Enterocyte Effacement (LEE), a Pathogenicity Island (PAI), is a major determinant of intestinal epithelium attachment of a group of STEC strains; however, the virulence repertoire of STEC strains lacking LEE, has not been fully characterized. The incidence of LEE-negative STEC strains has increased in several countries, highlighting the relevance of their study. In order to gain insights into the basis for the emergence of LEE-negative STEC strains, we performed a large-scale genomic analysis of 367 strains isolated worldwide from humans, animals, food and the environment. We identified uncharacterized genomic islands, including two PAIs and one Integrative Conjugative Element. Additionally, the Locus of Adhesion and Autoaggregation (LAA) was the most prevalent PAI among LEE-negative strains and we found that it contributes to colonization of the mice intestine. Our comprehensive and rigorous comparative genomic and phylogenetic analyses suggest that the accumulative acquisition of PAIs has played an important, but currently unappreciated role, in the evolution of virulence in these strains. This study provides new knowledge on the pathogenicity of LEE-negative STEC strains and identifies molecular markers for their epidemiological surveillance.
Direct Detection of Local Electric Polarization in the Interfacial Region in Ferroelectric Polymer Nanocomposites

Ferroelectric polymer nanocomposites are widely used in capacitive energy storage, electrocaloric refrigeration, and mechanical energy harvesting due to their exceptional electric polarization property and ease of fabrication. It is generally considered that the abnormal performance of ferroelectric nanocomposites stems from the interfacial region between the polymer matrix and embedded nanoparticles. However, direct evidence of the distinct local electric polarization property at the interfacial region is not yet accessible. Herein, a modified Kelvin probe force microscopy (KPFM) method with nanoscale spatial resolution is reported for direct detection of local polarization property at the matrix/particle interface in ferroelectric nanocomposites. Typical ferroelectric nanocomposites are studied using the present method. It is quantitatively probed that the electric polarization at matrix/particle interfacial region is higher than the polymer matrix under applied electric fields. Taking into account the enhanced local electric polarization gauged by the modified KPFM, the dielectric property of ferroelectric polymer nanocomposites matches with bulk experimental characterizations, indicating that the established method is reliable. It is anticipated that the present method, opening up new possibilities in understanding the matrix/particle interfacial region, may help with judicious design and engineering of high‐performance ferroelectric polymer nanocomposites.
Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity

The demise of amphibians? Rapid spread of disease is a hazard in our interconnected world. The chytrid fungus Batrachochytrium dendrobatidis was identified in amphibian populations about 20 years ago and has caused death and species extinction at a global scale. Scheele et al. found that the fungus has caused declines in amphibian populations everywhere except at its origin in Asia (see the Perspective by Greenberg and Palen). A majority of species and populations are still experiencing decline, but there is evidence of limited recovery in some species. The analysis also suggests some conditions that predict resilience. Science, this issue p. 1459; see also p. 1386 A quantitative assessment reveals the effects of chytridiomycosis on amphibian communities worldwide. Anthropogenic trade and development have broken down dispersal barriers, facilitating the spread of diseases that threaten Earth’s biodiversity. We present a global, quantitative assessment of the amphibian chytridiomycosis panzootic, one of the most impactful examples of disease spread, and demonstrate its role in the decline of at least 501 amphibian species over the past half-century, including 90 presumed extinctions. The effects of chytridiomycosis have been greatest in large-bodied, range-restricted anurans in wet climates in the Americas and Australia. Declines peaked in the 1980s, and only 12% of declined species show signs of recovery, whereas 39% are experiencing ongoing decline. There is risk of further chytridiomycosis outbreaks in new areas. The chytridiomycosis panzootic represents the greatest recorded loss of biodiversity attributable to a disease.
Is NPP proportional to GPP? Waring's hypothesis twenty years on.

Gross primary production (GPP) is partitioned to autotrophic respiration (Ra) and net primary production (NPP), the latter being used to build plant tissues and synthesize non-structural and secondary compounds. Waring et al. (1998) suggested that a NPP:GPP ratio of 0.47 ± 0.04 (s.d.) is universal across biomes, tree species and stand ages. Representing NPP in models as a fixed fraction of GPP, they argued, would be both simpler and more accurate than trying to simulate Ra mechanistically. This paper reviews progress in understanding the NPP:GPP ratio in forests during the 20 years since Waring et al. Research has confirmed the existence of pervasive acclimation mechanisms that tend to stabilize the NPP:GPP ratio, and indicates that Ra should not be modelled independently of GPP. Nonetheless, studies indicate that the value of this ratio is influenced by environmental factors, stand age and management. The average NPP:GPP ratio in over 200 studies, representing different biomes, species and forest stand ages, was found to be 0.46, consistent with the central value that Waring et al. proposed but with a much larger standard deviation (± 0.12) and a total range (0.22 to 0.79) that is too large to be disregarded.
Susceptibility of Corn Earworm (Lepidoptera: Noctuidae) to Cry1A.105 and Cry2Ab2 in North and South Carolina

Abstract The corn earworm, Helicoverpa zea (Boddie), is managed in corn and cotton in the United States primarily using transgenic cultivars that produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt). However, increasing reports of resistance to one or more Bt proteins threaten the continued efficacy of Bt traits. To better understand the development of resistance of H. zea to Bt corn and cotton in the southeastern United States, we monitored for resistance to Cry1A.105 and Cry2Ab2 among 22 field populations of H. zea collected in non-Bt and Bt corn expressing Cry1A.105 + Cry2Ab2 during 2017 and 2018. Colonies were established in the laboratory and progeny were screened in diet-overlay bioassays to purified Cry1A.105 and Cry2Ab2 proteins. Compared with two susceptible laboratory colonies, all 14 field colonies tested with Cry1A.105 were highly resistant, with resistance ratios (RRs) ranging from 13.5 to >4,000. For Cry2Ab2, 19 colonies were tested and RRs ranged from 0.26 to 33.7. Field populations were significantly more susceptible to Cry2Ab2 than Cry1A.105. We documented variability in F0 and F1 pupal weight and developmental rates of natural populations of H. zea, but observed no significant correlation with susceptibility to either Cry1A.105 or Cry2Ab2. Our results expand on the recent reports of H. zea resistance to Cry1A and Cry2A proteins and will aid in the design and deployment of future pyramided crops in the United States.
Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma.

BACKGROUND PD-1 blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established. PATIENTS AND METHODS This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N = 167) or nivolumab (N = 18) in the absence of disease progression (PD) or treatment-limiting toxicity (TLT) at 14 medical centres across Europe and Australia. RESULTS Median time on treatment was 12 months (range 0.7-43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients, and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18 months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12 months (range 2-23). PD was less frequent in patients with CR (14%) compared to patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new anti-tumour response. CONCLUSIONS In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared to clinical trials. In patients obtaining a CR, and being treated for more than 6 months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed anti-tumour activity in some patients.Clinical trial registration: NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970? cond=melanoma&cntry=BE&city=Jette&rank=3).
Digital logic for soft devices

Significance Soft devices offer many useful characteristics, including safe operation in close proximity to humans, the ability to adapt to their surroundings, ease of sterilization, simplicity, low cost, and light weight. Current soft devices, however, are still actuated by hard valves and electronic controls, and reliance on these components limits the use of soft devices in applications where hard structures or electronics are not compatible. This work demonstrates completely soft digital logic gates that can be integrated into soft devices and that allow computation and control within these devices, without hard valves or electronics. We demonstrate data storage, signal processing, digital-to-analog conversion, environmental sensing, and collaborative interaction between humans and soft devices. Although soft devices (grippers, actuators, and elementary robots) are rapidly becoming an integral part of the broad field of robotics, autonomy for completely soft devices has only begun to be developed. Adaptation of conventional systems of control to soft devices requires hard valves and electronic controls. This paper describes completely soft pneumatic digital logic gates having a physical scale appropriate for use with current (macroscopic) soft actuators. Each digital logic gate utilizes a single bistable valve—the pneumatic equivalent of a Schmitt trigger—which relies on the snap-through instability of a hemispherical membrane to kink internal tubes and operates with binary high/low input and output pressures. Soft, pneumatic NOT, AND, and OR digital logic gates—which generate known pneumatic outputs as a function of one, or multiple, pneumatic inputs—allow fabrication of digital logic circuits for a set–reset latch, two-bit shift register, leading-edge detector, digital-to-analog converter (DAC), and toggle switch. The DAC and toggle switch, in turn, can control and power a soft actuator (demonstrated using a pneu-net gripper). These macroscale soft digital logic gates are scalable to high volumes of airflow, do not consume power at steady state, and can be reconfigured to achieve multiple functionalities from a single design (including configurations that receive inputs from the environment and from human users). This work represents a step toward a strategy to develop autonomous control—one not involving an electronic interface or hard components—for soft devices.
Toll‐like receptors, long non‐coding RNA NEAT1, and RIG‐I expression are associated with HBeAg‐positive chronic hepatitis B patients in the active phase

Innate immunity plays a crucial role in host‐virus interactions and greatly influences viral replication including HBV infection. However, few studies have investigated the possible antiviral immune roles played by TLRs, RIG‐I, and long no‐coding RNA NEAT1 in chronic HBV infection (CHB) patients in clinical samples and their relationships among immune responses. In this study, we sought to investigate the mRNA expression levels of TLR1‐10, RIG‐I, and NEAT1 expression in HBeAg‐positive CHB treatment‐naïve patients with the active phase.
Evaluation of Oxygen Saturation Index Compared With Oxygenation Index in Neonates With Hypoxemic Respiratory Failure

Key Points Question Is oxygen saturation index (OSI) a reliable surrogate marker of oxygenation index (OI) in neonates with hypoxemic respiratory failure? Findings In this cohort study including 1442 paired OI and OSI measurements from 220 neonates, OSI was noted to correlate strongly with OI. Derived OI from OSI was in good agreement and strongly predictive of clinically relevant OI cutoffs from 5 to 25. Meaning Derived OI from noninvasive measurements may be useful to reliably assess severity of respiratory illness and response to therapy on a continuous basis.
Shear stress makes its mark on the endothelial genome.

Blood flow induces a frictional force (wall shear stress; WSS) on the lumen of vessels that has profound effects on vascular biology. It is a key determinant of the anatomical location of atherosclerotic plaques; regions of arteries exposed to high unidirectional WSS (e.g. thoracic aorta) are protected from atherosclerosis, whereas regions exposed to low magnitude forces that oscillate in direction (e.g. aortic arch) are susceptible to disease 1 . Clinical studies and animal models revealed that WSS also regulates the progression of atherosclerosis and plaque rupture 2, 3 leading to myocardial infarction or stroke. Endothelial cells (EC) play a vital role in this system because they can sense both the magnitude and direction of WSS and convert this ‘ mechanical code ’ into appropriate biological responses, including altered transcription of multiple genes. EC populations exposed to high atheroprotective WSS are aligned in the direction of flow and adopt a homogenous quiescent phenotype with minimal turnover. This differs from EC exposed to low oscillatory WSS which induces considerable phenotypic heterogeneity including cells undergoing apoptosis, proliferation, senescence, inflammation and endothelial-to-mesenchymal transition (EndMT) which is a form of cell plasticity 1, 4-6 . genomic H3K27ac methylation, be at a single cell level specific patterns of genomic modifications to be coupled to specific EC phenotypes. these studies have the potential to identify new medicines that can slow the progression of atherosclerosis by targeting mechanosensitive epigenetic mechanisms.
Embryogenesis of the peristaltic reflex

Neurogenic gut movements start after longitudinal smooth muscle differentiation in three species (mouse, zebrafish, chicken), and at E16 in the chicken embryo. The first activity of the chicken enteric nervous system is dominated by inhibitory neurons. The embryonic enteric nervous system electromechanically couples circular and longitudinal spontaneous myogenic contractions, thereby producing a new, rostro‐caudally directed bolus transport pattern: the migrating motor complex. The response of the embryonic gut to mechanical stimulation evolves from a symmetric, myogenic response at E12, to a neurally mediated, polarized, descending inhibitory, ‘law of the intestine’‐like response at E16. High resolution, whole‐mount 3D reconstructions are presented of the enteric nervous system of the chicken embryo at the neural‐control stage E16 with the iDISCO+ tissue clarification technique.
Routine screening for HIV, hepatitis B virus and hepatitis C virus in individuals undergoing oral and maxillofacial surgery

Given the effectiveness of treatment of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, there are considerable benefits associated with determining HIV/HBV/HCV status. We evaluated the feasibility and acceptability of systematic screening and subsequent care in an oral and maxillofacial surgery department.
Spatial Analysis of Heavy Metal Emissions in Residential, Commercial and Industrial Areas Adjacent to a Scrap Metal Shredder in Winnipeg, Canada

A spatial analysis of air pollution in the South St. Boniface (SSB) and Mission Industrial Areas (MIA) of Winnipeg, in Manitoba, Canada, was conducted by mapping the results for 23 composite snow samples. Heavy metals were analyzed in the snow samples by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Higher concentrations closer to the shredder were significant for every metal, but, not for arsenic, in regression modeling R squared (0.585 for Cd, 0.462 for Pb, 0.423 for Zn, 0.343 for Cr, 0.343 for Ni, 0.244 for Mn, and 0.069 for As). Heavy metal concentrations were significantly higher in the industrial zone, with the next highest being the roadside zone, then the commercial zone and finally the residential/parkland zone, at p-value < 0.01 statistical significance levels according to the non-parametric Kruskal-Wallis H- test. The metals concentrations mapped on Arc-GIS with ArcMap 10.6 using kriging interpolation, display that all toxic metal concentrations, but particularly Pb, Ni, Zn, Cr, and Hg, are highest proximate to the scrap metal shredder. Furthermore, pollution indices, specifically contamination factor (CF), degree of contamination (DOC), and pollution load index (PLI), were undertaken registering high contamination. The CF registered high for lead, zinc, and nickel in all areas compared to the background levels, but the highest levels were nearby to the scrap metal shredder. The DOC values showed that the industrial contamination is nearly five times greater than that for the road or commercial areas and almost 20 times more contaminated compared to the residential/parkland. With PLI levels above 1 considered contaminated, the shredder (4.1), roadside (2.2), and commercial areas (1.9) were polluted. These findings point to the shredder as the cause of present-day contamination for all areas, including residential/parkland, traffic, and commercial areas. High levels of toxic metal air pollution emissions warrant further study of human exposure and health risk posed by multiple sources from the air, water, and land. Enforcement and enclosure of the outdoor shredder should be considered to reduce heavy metal exposure to the public.