Miracle-dz/UniFAR-FTUs huggingface dataset:
Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer

Background T-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT+ CD8+ T-cells remain to be further explored in muscle-invasive bladder cancer (MIBC). Methods 259 patients with MIBC from two clinical centers (Zhongshan Hospital, n=141; Shanghai Cancer Center, n=118) were analyzed to evaluate the prognostic value and immune contexture association of TIGIT+ CD8+ T-cells through immunohistochemistry. Fresh tumor tissue samples from 26 patients with MIBC were examined to discover the phenotype of this CD8 subpopulation by flow cytometry. Results High infiltration of intratumoral TIGIT+ CD8+ T-cells predicted poor overall survival (OS) and recurrence-free survival (RFS) in MIBC. For patients with stage II MIBC with low infiltration of TIGIT+ CD8+ cells, adjuvant chemotherapy (ACT) could significantly prolong their OS and RFS. Intratumoral TIGIT+ CD8+ T-cell abundance was correlated with impaired CD8+ T-cell cytotoxicity and exhibited production of immunosuppressive cytokine IL-10. Further analysis of tumor-infiltrating immune cell landscape revealed TIGIT+ CD8+ T-cells were associated with suppressive immune contexture, including Th2 cells, regulatory T-cells, mast cells and neutrophils. Conclusion Intratumoral TIGIT+ CD8+ T-cell abundance could serve as an independent prognosticator for clinical outcome and a predictive biomarker for inferior ACT responsiveness. Intratumoral TIGIT+ CD8+ T-cell abundance correlated with dampened CD8+ T-cell antitumor immunity and immunosuppressive contexture abundance, highlighting a tumor-promoting role of TIGIT+ CD8+ T-cells.
Domain architecture divergence leads to functional divergence in binding and catalytic domains of bacterial and fungal cellobiohydrolases

Cellobiohydrolases directly convert crystalline cellulose into cellobiose and are of biotechnological interest to achieve efficient biomass utilization. As a result, much research in the field has focused on identifying cellobiohydrolases that are very fast. Cellobiohydrolase A from the bacterium Cellulomonas fimi (CfCel6B) and cellobiohydrolase II from the fungus Trichoderma reesei (TrCel6A) have similar catalytic domains (CDs) and show similar hydrolytic activity. However, TrCel6A and CfCel6B have different cellulose-binding domains (CBDs) and linkers: TrCel6A has a glycosylated peptide linker, whereas CfCel6B's linker consists of three fibronectin type 3 domains. We previously found that TrCel6A's linker plays an important role in increasing the binding rate constant to crystalline cellulose. However, it was not clear whether CfCel6B's linker has similar function. Here we analyze kinetic parameters of CfCel6B using single-molecule fluorescence imaging to compare CfCel6B and TrCel6A. We find that CBD is important for initial binding of CfCel6B, but the contribution of the linker to the binding rate constant or to the dissociation rate constant is minor. The crystal structure of the CfCel6B CD showed longer loops at the entrance and exit of the substrate-binding tunnel compared with TrCel6A CD, which results in higher processivity. Furthermore, CfCel6B CD showed not only fast surface diffusion but also slow processive movement, which is not observed in TrCel6A CD. Combined with the results of a phylogenetic tree analysis, we propose that bacterial cellobiohydrolases are designed to degrade crystalline cellulose using high-affinity CBD and high-processivity CD.
The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair

Abstract Nucleotide excision repair (NER) is an essential pathway to remove bulky lesions affecting one strand of DNA. Defects in components of this repair system are at the ground of genetic diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The XP complementation group G (XPG) endonuclease cleaves the damaged DNA strand on the 3′ side of the lesion coordinated with DNA re-synthesis. Here, we determined crystal structures of the XPG nuclease domain in the absence and presence of DNA. The overall fold exhibits similarities to other flap endonucleases but XPG harbors a dynamic helical arch that is uniquely oriented and defines a gateway. DNA binding through a helix-2-turn-helix motif, assisted by one flanking α-helix on each side, shows high plasticity, which is likely relevant for DNA scanning. A positively-charged canyon defined by the hydrophobic wedge and β-pin motifs provides an additional DNA-binding surface. Mutational analysis identifies helical arch residues that play critical roles in XPG function. A model for XPG participation in NER is proposed. Our structures and biochemical data represent a valuable tool to understand the atomic ground of XP and CS, and constitute a starting point for potential therapeutic applications.
Data perturbation analysis of a linear model

The linear model features were carefully studied in the cases of data perturbation and mean shift perturbation. Some important features were also proved mathematically. The results show that the mean shift perturbation is equivalent to the data perturbation, that is, adding a parameter to an observation equation means that this set of data is deleted from the data set. The estimate of this parameter is its predicted residual in fact.
Are the Drivers and Role of Online Trust the Same for All Web Sites and Consumers?: A Large-Scale Exploratory Empirical Study

Abstract The authors develop a conceptual model that links Web site and consumer characteristics, online trust, and behavioral intent. They estimate this model on data from 6831 consumers across 25 sites from eight Web site categories, using structural equation analysis with a priori and post hoc segmentation. The results show that the influences of the determinants of online trust are different across site categories and consumers. Privacy and order fulfillment are the most influential determinants of trust for sites in which both information risk and involvement are high, such as travel sites. Navigation is strongest for information-intensive sites, such as sports, portal, and community sites. Brand strength is critical for high-involvement categories, such as automobile and financial services sites. Online trust partially mediates the relationships between Web site and consumer characteristics and behavioral intent, and this mediation is strongest (weakest) for sites oriented toward infrequently (frequ.
Integrative systematic studies on tardigrades from Antarctica identify new genera and new species within Macrobiotoidea and Echiniscoidea

Abstract. Tardigrades represent one of the most abundant groups of Antarctic metazoans in terms of abundance and diversity, thanks to their ability to withstand desiccation and freezing; however, their biodiversity is underestimated. Antarctic tardigrades from Dronning Maud Land and Victoria Land were analysed from a morphological point of view with light microscopy and scanning electron microscopy, and from a molecular point of view using two genes (18S, 28S) analysed in Bayesian inference and maximum-likelihood frameworks. In addition, indel-coding datasets were used for the first time to infer tardigrade phylogenies. We also compared Antarctic specimens with those from Italy and Greenland. A combined morphological and molecular analysis led to the identification of two new evolutionary lineages, for which we here erect the new genera Acanthechiniscus, gen. nov. (Echiniscidae, Echiniscoidea) and Mesobiotus, gen. nov. (Macrobiotidae, Macrobiotoidea). Moreover, two species new to science were discovered: Pseudechiniscus titianae, sp. nov. (Echiniscidae : Echiniscoidea) and Mesobiotus hilariae, sp. nov. (Macrobiotidae : Macrobiotoidea). This study highlights the high tardigrade diversity in Antarctica and the importance of an integrated approach in faunal and taxonomic studies. http://zoobank.org/urn:lsid:zoobank.org:pub:8AAB42BF-B781-4418-A385-DC80C18EC31D
Deciphering the in vivo role of the Drosophila RNA-binding protein Imp in cell motility

Cultured motile cells show a highly enriched belt of actin at the tip of their lamellipodial protrusions, termed the leading edge. It is at this leading edge that researchers have uncovered pools of highly localized mRNAs encoding actin and actin-regulatory proteins, including β-actin, Profilin, Cofilin and all seven subunits of the Arp2/3 complex, whose local translation is then required for proper cell migration. The localization and local translation of these mRNAs are regulated by RNA-binding proteins, including Imp, which localizes β-actin mRNA at the leading edge. However, published studies have so far failed to determine if Imp is required to localize β-actin mRNA and/or other mRNAs at the leading edge of migratory cells in vivo. Our examination of Drosophila embryonic macrophage migration in vivo revealed that actin is not enriched at the leading edge, compared with cultured macrophages, demonstrating that a single cell population employs different mechanisms of cytoskeletal arrangement when migrating in vivo, compared with an ex vivo migration along a 2D substrate. It is therefore not surprising that we did not observe Imp at the leading edge of macrophages in vivo. However, overexpression of Imp reduced both the velocity and directionality of macrophages and inhibited cell-to-cell contact inhibition, suggesting a defect in microtubule dynamics, although we have yet to establish a mechanism for this. We show that Imp binds the 3’UTR of β-actin, profilin, and β-integrin mRNAs and reveal three sites of primary sequence that are required for Imp binding to β-actin mRNA. Our results suggest that, in contrast to cultured migratory cells, β-actin mRNA is unlikely to be localized to, and locally translated, at the leading edge of macrophages in vivo. However, cytoplasmic mRNA regulation is likely to play some kind of role in cell migration, as revealed by overexpression of Imp, which impairs macrophage motility. This thesis highlights a crucial requirement for studies to determine the mechanisms of cytoplasmic mRNA regulation in motile cells in vivo, which appear to be distinct from those employed in some cultured cells.
Behavioural ecology of white sharks carcharodon carcharias in False Bay, South Africa: towards improved management and conservation of a threatened apex predator

The coastal waters off South Africa support a significant proportion of the global white shark population, with at least four well-established coastal aggregation sites. How critical these sites are to the southern African and hence global white shark population depends to a large extent, on their levels of residency and site fidelity, in relation to potential threats. Here, I attempt to provide such data by studying the annual and seasonal presence of white sharks in False Bay. From 1 April 2004 31 December 2007, a total of 68 (46 female, 22 male) sharks, ranging in length from 1.7 to 5 m, were tagged with acoustic transmitters and monitored on an array of 30 receivers, distributed along the Inshore region of False Bay and at Seal Island, for a maximum of 1349 days. I used generalized linear mixed effects models to investigate the effects of season, habitat type, sex, size and time of day on shark presence. Most tagged sharks were immature animals, some of which were detected in the Bay in all months and across all years. In autumn and winter, males and females aggregated around Seal Island, where they fed predominantly on young-of-the-year seals. Sharks, regardless of sex or size, over-dispersed on the South side of the Island at sunrise, where the probability of encountering predator-naïve seals was highest. Shark presence at Seal Island mirrored the spatial distribution of predation around the Island, which was highest on the South side within 400 m of the Island, and at sunrise. In spring and summer, there was marked sexual segregation in presence, with females frequenting the Inshore areas and males seldom being detected in the Bay. Within the Inshore region, female white sharks showed a preference for beach, compared to rocky, mixed and harbour habitats. The preference for beach habitat likely reflects a combination of high prey availability, in addition to an open habitat suitable for detecting and securing prey. Overall, the results confirm False Bay as a critical area for white shark conservation as both sexes, across a range of sizes, show high levels of fidelity to the
A new approach to gratitude interventions in high schools that supports student wellbeing

ABSTRACT Adolescents face unprecedented wellbeing challenges, compared to previous generations, and many schools are underprepared to meet these needs. Social emotional learning (SEL) programs help, but could better support moral development. Here we propose a modern approach to gratitude interventions (GI) in schools that addresses critical limitations and provides preliminary results of effectiveness. The GI combines a psychoeducational top-down technique with a bottom-up social-media-app modality that supports the autonomous practice of interpersonal and general gratitude. Compared to students in waitlist/control classes, students in GI classes demonstrated improved outcomes in trait gratitude, mental health, and personal/social wellbeing after 6 weeks. Students’ use of the app also demonstrated more grateful personality behaviors and personal engagement. Lastly, we examined the importance of interpersonal gratitude in general and found that expressing thanks contributed to improvements in SEL competencies among waitlist/control students 6 weeks later. Implications for improving character/SEL programs through school GIs are discussed.
Inactive endosialidase-based detection of bacterial and oncofetal polysialic acid

Polysialic acid is a carbohydrate polymer which consist of N-acetylneuraminic acid units joined by α2,8-linkages. It is developmentally regulated and has an important role during normal neuronal development. In adults, it participates in complex neurological processes, such as memory, neural plasticity, tumor cell growth and metastasis. Polysialic acid also constitutes the capsule of some meningitis and sepsis-causing bacteria, such as Escherichia coli K1, group B meningococci, Mannheimia haemolytica A2 and Moraxella nonliquefaciens. Polysialic acid is poorly immunogenic; therefore high affinity antibodies against it are difficult to prepare, thus specific and fast detection methods are needed. Endosialidase is an enzyme derived from the E. coli K1 bacteriophage, which specifically recognizes and degrades polysialic acid. In this study, a novel detection method for polysialic acid was developed based on a fusion protein of inactive endosialidase and the green fluorescent protein. It utilizes the ability of the mutant, inactive endosialidase to bind but not cleave polysialic acid. Sequencing of the endosialidase gene revealed that amino acid substitutions near the active site of the enzyme differentiate the active and inactive forms of the enzyme. The fusion protein was applied for the detection of polysialic acid in bacteria and neuroblastoma. The results indicate that the fusion protein is a fast, sensitive and specific reagent for the detection of polysialic acid. The use of an inactive enzyme as a specific molecular tool for the detection of its substrate represents an approach which could potentially find wide applicability in the specific detection of diverse macromolecules.
Star Formation in Damped Lyman α Selected Galaxies

Abstract I present results from an ongoing survey to study galaxies associated with damped Lyman-α (DLA) systems at redshifts z>2. Integral field spectroscopy is used to search for Lyα emission line objects at the wavelengths where the emission from the quasars have been absorbed by the DLAs. The DLA galaxy candidates detected in this survey are found at distances of 10–20 kpc from the quasar line of sight, implying that galaxies are surrounded by neutral hydrogen at large distances. If we assume that the distribution of neutral gas is exponential, the scale length of the neutral gas is ~6 kpc, similar to large disk galaxies in the local Universe. The emission line luminosities imply smaller star formation rates compared to other high redshift galaxies found in luminosity selected samples.
Exploring what leaders can do to improve and sustain social alignment over time. BY ANDREW BURTON-JONES, ALICIA GILCHRIST, PETER GREEN, AND MICHAEL DRAHEIM

an Australian health service.a Given the size and consequences of transformational projects, this is a context where social alignment is likely to be critical. We found in our research that the process of achieving social misalignment involved four phases as did the process of achieving social alignment. These processes were linked, such that stakeholders moved through misalignment and alignment in a non-linear fashion. When we studied the trajectory closely and mapped it out, we noticed improvements in the trajectory
The impact of non-academic variables on the study experience of second year Hospitality Management students at selected South African Higher Education Institutions

Many variables can impact a student's experience during the transition to university from high school. Hence, the objective of this study was to determine the non-academic variables that impact on the overall study experience of second year Hospitality Management students at selected higher education institutions in South Africa. In order to identify the non-academic variables that could influence on the study experience of students, 228 participants from five selected universities completed a questionnaire. To determine the variables that impacted on the study experience, cross tabulations between categorical variables were tested for significance using Chi-square tests at the 5% level of significance. Results revealed statistically significant non-academic relationships for the social adjustment of students when starting university (<0.01) and the fear students had towards unemployment after graduation (<0.04). Higher education institutions are therefore increasingly challenged with ways to prepare students for success at university by assisting them to become part of the educated population, by providing support to improve the determination of students to successfully complete their learning programme.
CHANGING THE CONTEXT OF RESEARCHERS’ WORK IN ACADEMIA

The main purpose of this paper is to explore the changes that have occurred in the work of academic researchers. It also addresses particularities and changes affecting the professionalisation processes in the last five years. Within the framework of the sociology of professions, it complements analyses of statistical data with a qualitative study in Slovenia and from selected European countries. The paper finds that the organisation of researchers’ work and its position as a semi-profession is deteriorating dramatically. Researchers are confronted with the pressures of reduced public funding, higher unemployment, short-term research contracts, unproductive internal and external competitiveness and detachment from teaching processes.
Budding performance of Nagpur mandarin on different rootstocks under Hadoti region of Rajasthan

A study was undertaken on growth performance of Nagpur mandarin scion on different rootstocks. Maximum budding success (68.31%), maximum length of scion (17.97 cm), maximum plant height (34.584 cm), maximum leaf area (19.958 cm2), relative water content in leaves (51.744%) and chlorophyll content (0.194 mg/g) were observed in scion budded on rough lemon rootstock. The maximum (37.268 mm) girth of rootstock, length (20.218 cm) of longest primary root, length (7.648 cm) of longest secondary root and number of secondary roots (29.540) were recorded on Rangpur lime rootstock. Rough lemon rootstock showed vigorous effect on Nagpur mandarin as compared to Rangpur lime, sour orange and Carrizo citrange rootstocks.
Molecular detection and antimicrobial resistance of Aeromonas from houseflies (Musca domestica) in Iran

Objective. This study aimed to report the molecular detection and antimicrobial resistance of Aeromonas among houseflies (Musca domestica) in Shahrekord and Isfahan provinces of Iran. Materials and methods. Flies were caught from household kitchens, cattle farms, animal hospitals, human hospitals, slaughter house and poultry farms and put in collection separate sterile tubes. Isolation was accomplished by culture of flies in alkaline peptone water followed by identification with Aeromonas-specific Polymerase Chain Reaction (PCR). Results. Out of 600 houseflies 73 (12.2%) were infected with Aeromonas spp. Significantly higher frequencies of Aeromonas were isolated in Shahrekord province (13.0%; 39/300) than in Isfahan province (11.3%; 34/300). The recovery frequencies of the organisms were significantly lower in kitchens as compared to those in cattle farms and hospital wards which were similar. Higher proportions of infected flies were obtained during summer whereas low proportions were obtained during winter. Conclusions. It is concluded that houseflies do harbor diarrheagenic pathogens, including Aeromonas especially during summer. The carried organisms are resistant to a number of antimicrobials at different levels. Thus, future plans aimed at stemming infections caused by these organisms should take flies into account. Control efforts of infections caused by this particular bacterium should therefore take into account Musca domestica.
Long Memory in Stock Markets: Empirical Study on Spot and Future Markets in Turkey

In this study, we examine the existence of long memory for return and volatility both in spot and future markets in Turkey. For this purpose, we apply modified GPH test of Smith (2005) to ISE-30 index and ISE-30 index futures for the period between 2005-2011. As a result, although we do not observe long memory for return series, we observe long memory for volatility both in spot market and future markets in Turkey. As volatility has long memory and is predictible, these two markets are not weak form efficient in Turkey.
Long Term Effects of Low Income Housing Vouchers on Geographic Mobility, Earnings, and Welfare Utilization

Using a propensity score matching approach coupled with difference-in-differences regression analysis, we estimate the effect of receiving a low-income housing voucher on the employment and earnings, mobility, neighborhood quality, household/family composition and childcare utilization of a large longitudinal sample of low-income families in the U.S. We observe these effects over six years following voucher receipt. Our results indicate that voucher receipt has little effect on employment, but a negative effect on earnings. The negative earnings effect is largest in the years immediately following initial receipt, and fades out over time. Full-sample results show voucher receipt to have little effect on neighborhood quality in the short-term, but some positive long-term effects. We also find that voucher receipt is tied to a higher probability of change in household/family composition in the year of voucher receipt, but greater stability in subsequent years. The results of our propensity score matching procedure show voucher receipt to be tied to a greater take-up of public child care subsidies. Several robustness tests are run to support the reliability of our findings. We discuss the implications of our findings for research and policy. Long-Term Effects of Public Low-Income Housing Vouchers on Work, Neighborhood, Family Composition and Childcare Usage