Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Inhibitory Signals on the Priming of Drug Hapten–Specific T Cells That Express Distinct Vβ Receptors

Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
Pseudogymnoascus destructans transcriptome changes during white-nose syndrome infections

ABSTRACT White nose syndrome (WNS) is caused by the psychrophilic fungus Pseudogymnoascus destructans that can grow in the environment saprotrophically or parasitically by infecting hibernating bats. Infections are pathological in many species of North American bats, disrupting hibernation and causing mortality. To determine what fungal pathways are involved in infection of living tissue, we examined fungal gene expression using RNA-Seq. We compared P. destructans gene expression when grown in culture to that during infection of a North American bat species, Myotis lucifugus, that shows high WNS mortality. Cultured P. destructans was grown at 10 to 14 C and P. destructans growing in vivo was presumably exposed to temperatures ranging from 4 to 8 C during torpor and up to 37 C during periodic arousals. We found that when P. destructans is causing WNS, the most significant differentially expressed genes were involved in heat shock responses, cell wall remodeling, and micronutrient acquisition. These results indicate that this fungal pathogen responds to host-pathogen interactions by regulating gene expression in ways that may contribute to evasion of host responses. Alterations in fungal cell wall structures could allow P. destructans to avoid detection by host pattern recognition receptors and antibody responses. This study has also identified several fungal pathways upregulated during WNS infection that may be candidates for mitigating infection pathology. By identifying host-specific pathogen responses, these observations have important implications for host-pathogen evolutionary relationships in WNS and other fungal diseases.
Spanish–English speech perception in children and adults: Developmental trends

This study explored the developmental trends and phonetic category formation in bilingual children and adults. Participants included 30 fluent Spanish–English bilingual children, aged 8–11, and bilingual adults, aged 18–40. All completed gating tasks that incorporated code-mixed Spanish–English stimuli. There were significant differences in performance according to phonotactic construction of the stimuli, with fastest word recognition on words with voiceless initial consonants. Analysis of developmental trends revealed significant differences in children's performance by grade level and fastest recognition on English voiceless initial consonants than Spanish voiceless initial consonants. Differences in voice onset time between English and Spanish may have contributed to quicker recognition of English voiceless consonants than Spanish voiceless consonants. It is also possible that increased exposure to both spoken and written English may account for faster recognition of English voiceless words than Spanish voiceless words. In conclusion, multiple factors may influence perception of a second language.
TGF-β1 Promotes Migration and Invasion of Salivary Adenoid Cystic Carcinoma

Salivary adenoid cystic carcinoma (SACC) is one of the most common subtypes of salivary gland carcinomas and frequently metastasizes to distant organs. However, little is known about the molecular mechanisms that promote SACC metastasis. In this study, we report that transforming growth factor (TGF)-β1 was highly expressed in the highly metastatic SACC-LM cell line as compared with its parental low-metastatic SACC-83 cell line. Exogenous addition of TGF-β1 induced Smad2 phosphorylation and promoted the migration and invasion of SACC-83 cells. Consistently, the inhibition of endogenous TGF-β1 signaling in SACC-LM cells by an inhibitor specific to the type I TGF-β1 receptor (TβRI) suppressed cell migration and invasion. Moreover, we found that TGF-β1 expression was significantly increased in human primary SACC samples with metastasis. Taken together, our results suggest that TGF-β1 may play a crucial role in SACC metastasis.
Widespread choroidal thickening and abnormal midperipheral fundus autofluorescence characterize exudative age-related macular degeneration with choroidal vascular hyperpermeability

Purpose To investigate the clinical findings that characterize exudative age-related macular degeneration (AMD) with choroidal vascular hyperpermeability (CVH). Design Retrospective comparative study. Participants Forty-eight consecutive patients attending the outpatient clinic of Tokyo University Hospital between May 2013 and July 2013. Methods The presence or absence of CVH was determined with indocyanine green angiography performed at the latest visit. When CVH was observed, the eye was categorized as CVH(+) AMD, otherwise it was categorized as CVH(-) AMD. Using high-penetration optical coherence tomography, we measured choroidal thickness at the fovea and at four midperipheral areas (mean choroidal thickness at points on 6- and 9-papilla diameter circles superior, inferior, temporal, and nasal to the fovea). Ultrawide field retinal imaging was used to investigate abnormalities in midperipheral fundus autofluorescence (FAF). Choroidal thickness and the proportion of FAF abnormalities were compared between the CVH(+) AMD and CVH(−) AMD eyes and between eyes with polypoidal choroidal vasculopathy and typical AMD. Multiple regression analysis was used to control for treatment history and other characteristics. Results CVH was observed in 17 cases. Choroidal thickness was higher in the CVH(+) AMD eyes than in the CVH(−) AMD eyes at the fovea (325 μm versus 229 μm, respectively; P=0.0010, t-test), superior point (277 μm versus 215 μm, respectively; P=0.0021, t-test), inferior point (225 μm versus 161 μm, respectively; P=0.0002, t-test), and nasal point (202 μm versus 165 μm, respectively; P=0.042, t-test). The significance was maintained after controlling for possible confounders. The choroid was thicker at the fovea and at the inferior point in polypoidal choroidal vasculopathy than in typical AMD. The rate of midperipheral FAF abnormality was significantly higher in the CVH(+) AMD eyes than in the CVH(−) AMD eyes (82% versus 48%, respectively; P=0.031). Conclusion AMD with CVH is associated with widespread choroidal thickening and peripheral FAF abnormalities.
Draft consensus guidelines for diagnosis and treatment of Shwachman‐Diamond syndrome

Shwachman‐Diamond syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic exocrine insufficiency and bone marrow failure, often associated with neurodevelopmental and skeletal abnormalities. Mutations in the SBDS gene have been shown to cause SDS. The purpose of this document is to provide draft guidelines for diagnosis, evaluation of organ and system abnormalities, and treatment of hematologic, pancreatic, dietary, dental, skeletal, and neurodevelopmental complications. New recommendations regarding diagnosis and management are presented, reflecting advances in understanding the genetic basis and clinical manifestations of the disease based on the consensus of experienced clinicians from Canada, Europe, and the United States. Whenever possible, evidence‐based conclusions are made, but as with other rare diseases, the data on SDS are often anecdotal. The authors welcome comments from readers.
Identifying protist consumers of photosynthetic picoeukaryotes in the surface ocean using stable isotope probing

Photosynthetic picoeukaryotes contribute a significant fraction of primary production in the upper ocean. Micromonas pusilla is an ecologically relevant photosynthetic picoeukaryote, abundantly and widely distributed in marine waters. Grazing by protists may control the abundance of picoeukaryotes such as M. pusilla, but the diversity of the responsible grazers is poorly understood. To identify protists consuming photosynthetic picoeukaryotes in a productive North Pacific Ocean region, we amended seawater with living 15 N, 13 C-labelled M. pusilla cells in a 24-h replicated bottle experiment. DNA stable isotope probing, combined with high-throughput sequencing of V4 hypervariable regions from 18S rRNA gene amplicons (Tag-SIP), identified 19 operational taxonomic units (OTUs) of microbial eukaryotes that consumed M. pusilla. These OTUs were distantly related to cultured taxa within the dinoflagellates, ciliates, stramenopiles (MAST-1C and MAST-3 clades) and Telonema flagellates, thus, far known only from their environmental 18S rRNA gene sequences. Our discovery of eukaryotic prey consumption by MAST cells confirms that their trophic role in marine microbial food webs includes grazing upon picoeukaryotes. Our study provides new experimental evidence directly linking the genetic identity of diverse uncultivated microbial eukaryotes to the consumption of picoeukaryotic phytoplankton in the upper ocean.
Environmental influences on the intensity changes of tropical cyclones over the western North Pacific

Abstract. The influence of environmental conditions on the intensity changes of tropical cyclones (TCs) over the western North Pacific (WNP) is investigated through examination of 37 TCs during 2000–2011 that interacted directly with the western North Pacific subtropical high (WNPSH). Comprehensive composite analysis of the environmental conditions is performed for two stages of storms: one is categorized as intensifying events (maximum wind speed increases by 15 kn over 48 h) and the other is categorized as weakening events (maximum wind speed decreases by 15 kn over 48 h). Comparison of the composite analysis of these two cases show that environmental conditions associated with the WNPSH play important roles in the intensity changes of TCs over the WNP. When a TC moves along the southern periphery of the WNPSH, the relatively weaker easterly environmental vertical wind shear helps bring warm moist air from the south and southeast to its southeast quadrant within 500 km, which is favorable for the TC to intensify. However, when a TC moves along the western edge of the WNPSH, under the combined influences of the WNPSH and an upper-level westerly trough, a strong westerly vertical shear promotes the intrusion of dry environmental air associated with the WNPSH from the north and northwest, which may lead to the inhibition of moisture supply and convection over the western half of the TC and thus its weakening. These composite results are consistent with those with additional geographic restrictions, suggesting that the dry air intrusion and the vertical wind shear (VWS) associated with the WNPSH, indeed affect the intensity changes of TCs over the WNP beyond the difference related solely to variations in geographical locations. The average sea surface temperature (SST) of 27.6 °C for the weakening events is also lower than an average of 28.9 °C for the strengthening events, but remains above the critical value of 27 °C for TC intensification, suggesting that the SST may be regarded as a less positive factor for the weakening events.
Inverse statistical physics of protein sequences: a key issues review

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques, sequence data accumulate at unprecedented pace. This provides large sets of so-called homologous, i.e. evolutionarily related protein sequences, to which methods of inverse statistical physics can be applied. Using sequence data as the basis for the inference of Boltzmann distributions from samples of microscopic configurations or observables, it is possible to extract information about evolutionary constraints and thus protein function and structure. Here we give an overview over some biologically important questions, and how statistical-mechanics inspired modeling approaches can help to answer them. Finally, we discuss some open questions, which we expect to be addressed over the next years.
Effect of Process Variables on the Quality Attributes of Briquettes from Wheat, Oat, Canola and Barley

Biomass is a renewable energy source and environmentally friendly substitute for fossil fuels such as coal and petroleum products. Major limitation of biomass for successful energy application is its low bulk density, which makes it very difficult and costly to transport and handle. To overcome this limitation, biomass has to be densified. The commonly used technologies for densification of biomass are pelletization and briquetting. Briquetting offers many advantages at it can densify larger particles sizes of biomass at higher moisture contents. Briquetting is influenced by a number of feedstock and process variables such as moisture content, particle size distribution, and some operating variables such as temperature and densification pressure. In the present study, experiments were designed and conducted based on Box-Behnken design to produce briquettes using barley, wheat, canola and barley straws. A laboratory scale hydraulic briquette press was used for the present study. The experimental process variables and their levels used in the present study were pressure levels (7.5, 10, 12.5 MPa), three levels of temperature (90, 110, 130C), at three moisture content levels (9, 12, 15% w.b.), and three levels of particle size (19.1, 25.04, 31.75 mm). The quality variables studied includes moisture content, initial density and final briquette density after two weeks of storage, size distribution index and durability. The raw biomass was initially chopped and size reduced using a hammer mill. The ground biomass was conditioned at different moisture contents and was further densified using laboratory hydraulic press. For each treatment combination, ten briquettes were manufactured at a residence time of about 30 s after compression pressure setpoint was achieved. After compression, the initial dimensions and the final dimensions after 2 weeks of storage in controlled environment of all the samples were measured. Durability, dimensional stability, and moisture content tests were conducted after two weeks of storage of the briquettes produced. Initial results indicated that moisture content played a significant role on briquettes durability, stability, and density. Low moisture content of the straws (7-12%) gave more durable briquettes. Briquette density increased with increasing pressure depending on the moisture content value. The axial expansion was more significant than the lateral expansion, which in some cases tended to be nill depending on the material and operating variables. Further data analysis is in progress in order to understand the significance of the process variables based on ANOVA. Regression models were developed to predict the changes in quality of briquettes with respect of the process variables under study.
The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States.

BACKGROUND The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. METHODS We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. RESULTS While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. CONCLUSIONS It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.
Differential cellular response to linear and strain stiffening hydrogel substrates

The mechanical properties of the substrate upon which cells are cultured have been shown to influence a variety of cell properties including cell adhesion, spreading, protein expression and differentiation. The work presented here examines how the nonlinear mechanical properties of biopolymer gels affect the cellular responses to substrate stiffness. Cell spread area decreases with decreasing substrate stiffness when cells are cultured on linearly elastic polyacrylamide gels but display no spread area sensitivity when cultured on fibrin gels of various moduli. Fibrin gels, and other semiflexible biopolymer networks, exhibit strain stiffening, whereby the elastic modulus of the gel increases with increasing applied strain. Mechanosensitive cells and strain stiffening gels engage in a mechanical feedback loop with cells increasing their applied force and the gel modulus increasing as a result until the cells reach their maximum spread area. Cell applied forces locally induce anisotropy in an initially isotropic matrix providing a mechanism for cell/cell communication over a distance of ~5 cell lengths. This results in alignment of adjacent cells and formation of ring-like multicellular patterns. Finally, due in part to its mechanical properties, fibrin is an appealing scaffold for neural tissue repair. Initial animal studies confirm that salmon derived fibrin mitigates pain and inflammation after injury to the central nervous system. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Bioengineering First Advisor Paul Janmey
Seasonal, sub-seasonal and spatial fluctuations in oxygen-depleted bottom waters in an embayment of an eastern boundary upwelling system: St Helena Bay

Abstract. The considerable impact of oxygen deficient waters on marine resources in St Helena Bay has generated interest in exploring the vulnerability of South Africa's largest and most productive bay to further deoxygenation in response to climate change. Seasonal, sub-seasonal and spatial fluctuations in bottom dissolved oxygen (DO) are examined in St Helena Bay to facilitate better interpretation of historical data. DO measurements in relation to physical, chemical and biological variables were made between November 2013 and November 2014. Alongshore bay characteristics were assessed through comparison of variables along the 50 m depth contour. A mean coefficient of variation of 0.35 provided a measure of the relative variability of near-bottom DO concentrations along this contour. Across-shelf transects captured the seasonal development of hypoxia in relation to the distribution of phytoplankton biomass. DO was lowest in autumn in the south of the bay prior to winter ventilation of the bottom waters. Exceptional dinoflagellate blooms forming extensive subsurface thin layers preceded the autumn DO minima. The development of hypoxia at inner and central stations prior to expansion beyond the boundaries of the bay provided evidence of local drawdown. Coincident with the seasonal decline of DO within the bay was an increase in macronutrient concentrations which tended to mirror DO concentrations. Indication of denitrification in the suboxic waters in the south of the bay was provided through evidence of a nitrate deficit in autumn supported by elevated nitrite concentrations. Superimposed on the seasonal decline of DO concentrations in the bottom waters were sub-seasonal events of hypoxia and anoxia linked to episodic deposition of organic matter as indicated by increases in bottom Chl a concentrations.
Measured and Estimated Water Vapor Advection in the Atmospheric Surface Layer

The flux of water vapor due to advection is measured using high-resolution Raman lidar that was orientated horizontally across a land‐lake transition.At the same time, a fullsurface energy balance is performed toassess the impact of scalar advection on energy budget closure. The flux of water vapor due to advection is then estimated with analytical solutions to the humidity transport equation that show excellent agreement with the field measurements. Although the magnitude of the advection was not sufficient to account for the total energy deficit for this field site, the analytical approach is used to explore situations where advection would be the dominanttransportmechanism.Theauthorsfindthatadvectionisatmaximumwhenthemeasurementheightis 0.036 times the distance to a land surfacetransition. The framework proposed in this paper can beused to predict the potential impact of advection on surface flux measurements prior to field deployment and can be used as a data analysis algorithm to calculate the flux of water vapor due to advection from field measurements.
Barrier and mechanical properties of methylcellulose–whey protein films

Water vapour permeability (WVP) and mechanical properties were assessed in edible films prepared from methylcellulose (MC) and MC–whey protein isolate (WPI) or MC–whey protein concentrate (WPC). Glycerol (Gly) was used as the plasticizer. Two MC–WP films were formulated. For Group I films, the mass ratio of WP : Gly was constant, whereas for Group II films the mass ratio of polymer (MC + WP) : Gly was constant. The WVP of MC–Gly film decreased with increasing MC concentration, while the tensile strength (TS) and percent elongation (E) increased. The WVP of Group I and Group II films decreased erratically and TS increased when the MC concentration was increased. Group I films had higher TS values than Group II films at the same MC : WP ratios. E of both groups increased with increasing MC concentration (p < 0.05), excluding the films with the highest MC : WP ratio tested (0.8) in Group I films. Group I films had lower E values than Group II films at the same MC : WP ratios. MC effectively governed WVP, TS and E of the WP films. Generally, MC–WP films of this work showed lower WVP than that of MC‐ and WP‐based edible films in the literature. This can potentially make MC–WP films a suitable film material for moisture‐sensitive food products. Copyright © 2005 John Wiley & Sons, Ltd.
Lower Pill Burden and Once-Daily Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials

Once-daily compared with twice-daily antiretroviral therapy regimens increased adherence; however, the difference was modest and not associated with a difference in virological suppression. In addition, higher pill burden was associated with lower rates of virological suppression, whether once- or twice-daily regimens.