Miracle-dz/UniFAR-FTUs huggingface dataset:
A Pilot Trial of Thymalfasin (Tα1) to Treat Hospitalized Patients with Hypoxemia and Lymphocytopenia due to COVID-19 Infection

Abstract Background Thymosin-α-1 (Tα1) may be a treatment option for COVID-19, but efficacy and safety data remain limited. Methods Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of Tα1), compared with standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. Results 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low flow oxygen (subdistribution hazard ratio [SHR]: 1.48; 95% CI: 0.68–3.25) or baseline high flow oxygen (SHR: 1.28; 95% CI: 0.35–4.63), although neither were significant. Among patients with baseline low flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4+ T cells on Day 5 than on Day 1 (p = 0.0113). Nine serious adverse events among treated patients were deemed not related to Tα1. Conclusion Tα1 increases CD4+ T cell count among patients with baseline low flow oxygen support faster than standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19.
Seasonal changes in day length induce multisynaptic neurotransmitter switching to regulate hypothalamic network activity and behavior

Seasonal changes in day length (photoperiod) affect numerous physiological functions. The suprachiasmatic nucleus (SCN)–paraventricular nucleus (PVN) axis plays a key role in processing photoperiod-related information. Seasonal variations in SCN and PVN neurotransmitter expression have been observed in humans and animal models. However, the molecular mechanisms by which the SCN-PVN network responds to altered photoperiod is unknown. Here, we show in mice that neuromedin S (NMS) and vasoactive intestinal polypeptide (VIP) neurons in the SCN display photoperiod-induced neurotransmitter plasticity. In vivo recording of calcium dynamics revealed that NMS neurons alter PVN network activity in response to winter-like photoperiod. Chronic manipulation of NMS neurons is sufficient to induce neurotransmitter switching in PVN neurons and affects locomotor activity. Our findings reveal previously unidentified molecular adaptations of the SCN-PVN network in response to seasonality and the role for NMS neurons in adjusting hypothalamic function to day length via a coordinated multisynaptic neurotransmitter switching affecting behavior.
Continued exposure to D‐galactose in postnatal period may inhibit excessive primordial follicle reduction in rats exposed prenatally to D‐galactose

We aimed to compare the ovarian reserve of rats exposed to oral D‐galactose during prenatal and early life with rats exposed to D‐galactose only during the prenatal period. Fifteen female pregnant Wistar rats were randomly divided into three groups. The first and second groups were fed a D‐galactose enriched diet (35%) from the third day of pregnancy to parturition (PP) and the third day to the end of lactation (PL), respectively. The control group (C group) was fed a standard diet. The study population was the female offspring of three groups (PP′, PL′, and C′), in which some reproductive factors were examined between 45 and 50 days of age. When compared with the PP′ group, the number of primordial follicles was significantly higher in the PL′ group at PND 45–50 (40 vs. 30; p = .01); however, the antimullerian hormone level was significantly reduced in the PL′ group versus control group (−2.2, 95% confidence interval [CI]: −2.83, −1.53 ng/ml p = .000), and follicle‐stimulating hormone level significantly increased in PP′ group versus control (4.5 mIU/ml, 95% CI: 1.40–7.62, p = .005). There was no significant difference in leukocyte infiltration or antiovarian antibody among the groups. Continued exposure to D‐galactose during the lactation period inhibits the primordial follicle loss in rats in terms of producing fewer atretic follicles.
Native and activated antithrombin inhibits TMPRSS2 activity and SARS‐CoV‐2 infection

Host cell proteases such as TMPRSS2 are critical determinants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad‐spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS‐CoV, MERS‐CoV, hCoV‐229E, SARS‐CoV‐2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS‐CoV‐2. Thus, AT is an endogenous inhibitor of SARS‐CoV‐2 that may be involved in COVID‐19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti‐TMPRSS2 and anti‐SARS‐CoV‐2 activity of AT, suggesting that repurposing of native and activated AT for COVID‐19 treatment should be explored.
A red nucleus–VTA glutamate pathway underlies exercise reward and the therapeutic effect of exercise on cocaine use

Physical exercise is rewarding and protective against drug abuse and addiction. However, the neural mechanisms underlying these actions remain unclear. Here, we report that long-term wheel-running produced a more robust increase in c-fos expression in the red nucleus (RN) than in other brain regions. Anatomic and functional assays demonstrated that most RN magnocellular portion (RNm) neurons are glutamatergic. Wheel-running activates a subset of RNm glutamate neurons that project to ventral tegmental area (VTA) dopamine neurons. Optogenetic stimulation of this pathway was rewarding, as assessed by intracranial self-stimulation and conditioned place preference, whereas optical inhibition blocked wheel-running behavior. Running wheel access decreased cocaine self-administration and cocaine seeking during extinction. Last, optogenetic stimulation of the RNm-to-VTA glutamate pathway inhibited responding to cocaine. Together, these findings indicate that physical exercise activates a specific RNm-to-VTA glutamatergic pathway, producing exercise reward and reducing cocaine intake.
Identification of novel neutralizing determinants for protection against HCV

Background and Aims: HCV evasion of neutralizing antibodies (nAb) results in viral persistence and poses challenges to the development of an urgently needed vaccine. N‐linked glycosylation of viral envelope proteins is a key mechanism for such evasion. To facilitate rational vaccine design, we aimed to identify determinants of protection of conserved neutralizing epitopes. Approach and Results: Using a reverse evolutionary approach, we passaged genotype 1a, 1b, 2a, 3a, and 4a HCV with envelope proteins (E1 and E2) derived from chronically infected patients without selective pressure by nAb in cell culture. Compared with the original viruses, HCV recombinants, engineered to harbor substitutions identified in polyclonal cell culture–passaged viruses, showed highly increased fitness and exposure of conserved neutralizing epitopes in antigenic regions 3 and 4, associated with protection from chronic infection. Further reverse genetic studies of acquired E1/E2 substitutions identified positions 418 and 532 in the N1 and N6 glycosylation motifs, localizing to adjacent E2 areas, as key regulators of changes of the E1/E2 conformational state, which governed viral sensitivity to nAb. These effects were independent of predicted glycan occupancy. Conclusions: We show how N‐linked glycosylation motifs can trigger dramatic changes in HCV sensitivity to nAb, independent of glycan occupancy. These findings aid in the understanding of HCV nAb evasion and rational vaccine design, as they can be exploited to stabilize the structurally flexible envelope proteins in an open conformation, exposing important neutralizing epitopes. Finally, this work resulted in a panel of highly fit cell culture infectious HCV recombinants.
Effects of nutrient heterogeneity on root foraging and plant growth at the individual and community level.

Plants enhance nutrient uptake in heterogeneous nutrient environments through selective root placement. Many studies have documented that plants grow better under heterogeneous than under homogeneous nutrient distribution, but comprehensive syntheses are relatively few. We examined the effects of patch scale and contrast on plant responses through synthesizing the effects of nutrient heterogeneity on root foraging and plant growth in 131 comparative studies. Plant responses to nutrient heterogeneity were phylogenetically conserved, and the response in shoot biomass was significantly correlated with the response in root biomass but not with root foraging precision. Root precision depended on the competition regime, and plants had lower precision in interspecific than in conspecific competition. Community-level growth was significantly promoted by nutrient heterogeneity and less variable than individual-level responses. Along with increasing patch scale, overall shoot and root responses of individuals increased but root foraging precision declined. In addition, moderate patch contrast induced highest root responses. Our results indicate that plants optimize nutrient acquisition from heterogeneous patches mainly through increasing root growth, and plant communities exploit heterogeneous nutrients more effectively than individuals. Understanding the roles of patch attributes in nutrient-heterogeneity effects may help design fertilization practices to promote productivity and conserve biodiversity.
Diversity in new flagellum tip attachment in bloodstream form African trypanosomes

The closely related parasites Trypanosoma brucei, T. congolense, and T. vivax cause neglected tropical diseases collectively known as African Trypanosomiasis. A characteristic feature of bloodstream form T. brucei is the flagellum that is laterally attached to the side of the cell body. During the cell cycle, the new flagellum is formed alongside the old flagellum, with the new flagellum tip embedded within a mobile transmembrane junction called the groove. The molecular composition of the groove is currently unknown, which limits the analysis of this junction and assessment of its conservation in related trypanosomatids. Here, we identified 13 proteins that localize to the flagellar groove through a small‐scale tagging screen. Functional analysis of a subset of these proteins by RNAi and gene deletion revealed three proteins, FCP4/TbKin15, FCP7, and FAZ45, that are involved in new flagellum tip attachment to the groove. Despite possessing orthologues of all 13 groove proteins, T. congolense and T. vivax did not assemble a canonical groove around the new flagellum tip according to 3D electron microscopy. This diversity in new flagellum tip attachment points to the rapid evolution of membrane‐cytoskeleton structures that can occur without large changes in gene complement and likely reflects the niche specialization of each species.
Clinical and Molecular Determinants of Clonal Evolution in Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria

PURPOSE Secondary myeloid neoplasms (sMNs) remain the most serious long-term complications in patients with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). However, sMNs lack specific predictors, dedicated surveillance measures, and early therapeutic interventions. PATIENTS AND METHODS We studied a multicenter, retrospective cohort of 1,008 patients (median follow-up 8.6 years) with AA and PNH to assess clinical and molecular determinants of clonal evolution. RESULTS Although none of the patients transplanted upfront (n = 117) developed clonal complications (either sMN or secondary PNH), the 10-year cumulative incidence of sMN in nontransplanted cases was 11.6%. In severe AA, older age at presentation and lack of response to immunosuppressive therapy were independently associated with increased risk of sMN, whereas untreated patients had the highest risk among nonsevere cases. The elapsed time from AA to sMN was 4.5 years. sMN developed in 94 patients. The 5-year overall survival reached 40% and was independently associated with bone marrow blasts at sMN onset. Myelodysplastic syndrome with high-risk phenotypes, del7/7q, and ASXL1, SETBP1, RUNX1, and RAS pathway gene mutations were the most frequent characteristics. Cross-sectional studies of clonal dynamics from baseline to evolution revealed that PIGA/human leukocyte antigen lesions decreased over time, being replaced by clones with myeloid hits. PIGA and BCOR/L1 mutation carriers had a lower risk of sMN progression, whereas myeloid driver lesions marked the group with a higher risk. CONCLUSION The risk of sMN in AA is associated with disease severity, lack of response to treatment, and patients' age. sMNs display high-risk morphological, karyotypic, and molecular features. The landscape of acquired somatic mutations is complex and incompletely understood and should be considered with caution in medical management.
Modal Subordination, Focus and Complement Anaphora

Modal Subordination (MS, Roberts 1989) is a phenomenon in natural language semantics which has two deening characteristics. A modal or other non-factual operator such as might introduces a hypothetical proposition which may be assumed as a background by subsequent modal sentences but not by sentences in`factual' mood. In addition, discourse referents introduced in a modal sentence may be picked up by anaphors in subsequent modal contexts, overcoming barriers to accessibility assumed by theories of discourse semantics such as DRT (Kamp and Reyle 1993) and DPL (Groenendijk and Stokhof 1991). 1. If John bought a book, he'll be home reading it by now. It'll be/#It's a murder mystery. 2. A thief might break in. She would/#will take the silver. In each case the interpretation and acceptability of the second sentence depends on a context set up by the rst sentence, and also a structural constraint (the presence of a modal operator). Corblin (1994a) discusses examples which are structurally similar to the classic MS examples but require the negation of thèantecedent' sentence to be assumed by subsequent discourse: 3. Mary didn't give the name of the witness. They would have killed him (ie, if she had) 4. Mary gave the name of the witness. They would have killed her (if she had not)
Sur la théorie des représentations et les algèbres d'opérateurs des produits en couronnes libres

Dans cette these, on etudie les proprietes combinatoires, algebriques et analytiques de certains groupes quantiques compacts libres. on prouve au chapitre 2 que les duaux des groupes quantiques de reflexions complexes possedent, dans la plus part des cas, la propriete d'approximation de Haagerup. au chapitre 3, on decrit les regles de fusion du produit en, couronne libre d'un groupe discret par le groupe quantique des permutations. Pour cela on determine les espaces d'entrelaceurs entre certaines corepresentation "basiques" de ces produits en couronnes libres en termes de partitions non croisees decorees par les elements du groupe. On peut alors identifier les corepresentations irreductibles et decrire les regles de fusion. On propose ensuite plusieurs applications de ce resultat. On demontre premierement que les C*-algebres reduites de ces produits en couronnes libres sont sans la plupart des cas simples et a trace unique. Puis on prouve que les algebres se von Neumann associees sont des facteurs de type II et que ces facteurs sont pleins. On etend finalement le resultat du chapitre 2, aux produits en couronnes libres des groupes finis par le groupe quantique de permutations.
CMAR_A_242856 5677..5687

Xiaoqian Liu Jianfeng Ju Qun Liu Zongmin Zhu Chunxia Liu 1Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People’s Republic of China; 2Department of Pharmacy, Caoxian People’s Hospital of Heze City, Heze 274400, Shandong, People’s Republic of China Purpose: In recent years, traditional Chinese medicine has achieved good results in treating gliomas. This research aimed to reveal the effect of Shezhi Huangling decoction (SD) on glioma cell process. Methods: U87 and U251 cells were treated with different concentrations (10, 30 and 50 μg/mL) of SD or transfected with miR-1298-5p mimic, inhibitor and siRNA targeting TGIF1. Cell proliferation, migration, invasion and apoptosis were detected. The expression of miR-1298-5p was measured by qRT-PCR, while TGIF1 expression was examined by immunohistochemical analysis and Western blot. Results: SD treatment inhibited the proliferation, migration and invasion of glioma cells and induced the apoptosis. In addition, SD treatment induced the expression of miR-1298-5p in glioma cells. The low expression of miR-1298-5p was examined in glioma tissues and was significantly related to the high histological grade of glioma patients and predicted a poor prognosis. MiR-1298-5p directly targeted the 3ʹ-UTR of transforming growth factor β induced factor 1 (TGIF1) and reduced TGIF1 protein expression. MiR-1298-5p restricted the proliferation, migration and invasion of glioma cells and induced cell apoptosis by targeting TGIF1. Conclusion: Our data reveal that SD acts as a cancer-inhibiting agent in glioma via miR1298-5p/TGIF1 axis, suggesting a potential therapeutic application of SD in glioma.
Periodic Bounce Orbits in Magnetic Billiard Systems

This is an invitation to play magnetic billiards. We consider a billiard table that is an n-dimensional compact Riemannian manifold with smooth boundary. This is a generalization of the classical billiard game. In particular, we study periodic orbits on a prescribed energy level in the magnetic setup. We show that for sufficiently high energy values above the Mañé critical value, there exists a periodic magnetic bounce orbit with bounded period.
ALG-1 influences accurate mRNA splicing patterns in the C . elegans intestine and body muscle tissues by modulating splicing factor activities

Molecular and Cellular Biology Graduate Program, School of Life Sciences 427 East Tyler Mall Tempe, AZ 85287 4501 Virginia G. Piper Center for Personalized Diagnostics, The Biodesign Institute at Arizona State University, 1001 S McAllister Ave, Tempe, AZ, USA Barrett, The Honors College, Arizona State University, 751 E Lemon Mall, Tempe, AZ 85281 Genetics: Early Online, published on May 9, 2019 as 10.1534/genetics.119. 302223
d x 2 - y 2 superconductivity and the Hubbard model

The numerical studies of d x 2 - y 2 -wave pairing in the two-dimensional (2D) and the 2-leg Hubbard models are reviewed. For this purpose, the results obtained from the determinantal Quantum Monte Carlo and the Density-Matrix Renormalization-Group calculations are presented. These are calculations which were motivated by the discovery of the high- T c cuprates. In this review, the emphasis is placed on the microscopic many-body processes which are responsible for the d x 2 - y 2 -wave pairing correlations observed in the 2D and the 2-leg Hubbard models. In order to gain insight into these processes, the results on the effective pairing interaction as well as the magnetic, density and the single-particle excitations will be reviewed. In addition, comparisons will be made with the other numerical approaches to the Hubbard model and the numerical results on the t - J model. The results reviewed here indicate that an effective pairing interaction which is repulsive at ( ~ , ~ ) momentum transfer, and enhanced single-particle spectral weight near the ( ~ ,0) and (0, ~ ) points of the Brillouin zone, create optimum conditions for d x 2 - y 2 -wave pairing. These are two effects which act to enhance the d x 2 - y 2 -wave pairing correlations in the Hubbard model. Finding additional ways is an active research problem.
The Photometric Redshift Distribution and Evolutionary Properties of Galaxies up to z ∼ 4.5 in the Field of the Quasar BR 1202−0725

We present a deep BVrIK multicolor catalog of galaxies in the field of the high-redshift (z = 4.7) quasar BR 1202-0725. Reliable colors have been measured for galaxies selected down to R = 25. Taking advantage of the wide spectral coverage of the galaxies in the field, we compare the observed colors with those predicted by spectral synthesis models including UV absorption by the intergalactic medium and dust reddening. The choice of the optical filters has been optimized to define a robust multicolor selection of galaxies at 3.8 ≤ z ≤ 4.5. Within this interval the surface density of galaxy candidates with z ∼ 4 in this field is 1 arcmin-2. Photometric redshifts have been derived for the galaxies in the field with the maximum likelihood analysis using the GISSEL library of ∼106 synthetic spectra. The accuracy of the method used has been discussed and tested using galaxies in the Hubble Deep Field with known spectroscopic redshifts and accurate photometry. A peak in the redshift distribution is present at z ≃ 0.6 with relatively few galaxies at z > 1.5. At variance with brighter surveys (I < 22.5) is a tail in the distribution toward high redshifts up to z ∼ 4. The luminosity function at z ∼ 0.6 shows a steepening for MB > -19. This increase is reminiscent of that found in the most recent estimates of the local luminosity function, where a similar volume density is reached about 2 mag fainter. The observed cosmological UV luminosity density is computed in the overall redshift interval z = 0.3–4.5, reaching a value ∼2 × 1019 W Hz-1 Mpc-3 at z ∼ 0.8. Including recent local estimates, it appears that the UV luminosity density changes by a factor of ∼2.5 in the overall redshift interval z = 0.1–4, not including correction for fainter undetected galaxies. Thus we find that the evidence of a marked maximum in the luminosity density at z ∼ 1–1.5 for galaxies with R ≤ 25 is weak. Using the GISSEL libraries we have derived in a homogeneous way the physical parameters connected with the fitted spectral energy distributions. Thanks to this new approach, the problem of the star formation history of the universe is dealt with in a consistent way, taking into account the dust and metallicity distributions derived from the spectrophotometric properties of each galaxy in the sample. The bulk of the blue intermediate-redshift population with z = 0.4–1 mostly consists of very young star-forming galaxies with a median starburst age of the order of a few times 108 yr and typical mass in luminous stars ∼2 × 108 M☉. The presence of this young population is in contrast with the pure luminosity evolutionary model based on a single high-formation redshift. The cosmological mass in formed stars per unit comoving volume at z ∼ 3 is already ∼20% of that formed at z = 0.5 in our magnitude-limited sample. Predictions based on the standard hierarchical clustering models are smaller, although not far from that derived from the observations.
Shot noise of single-electron tunneling in one-dimensional arrays

We have used numerical modeling and a semi-analytical calculation method to find the low frequency value S_{I}(0) of the spectral density of fluctuations of current through 1D arrays of small tunnel junctions, using the ``orthodox theory'' of single-electron tunneling. In all three array types studied, at low temperature (kT is quite large, typically between 0.5 and 0.7 of , while the dependence of on N or \lambda is so weak that it is hidden within the random fluctuations of the crossover current.