Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Municipal Sewage on Soil Properties and Chemical Build-up in Vegetable Crops Grown on Haplustepts of Sub-humid Southern Plains of Rajasthan

A mini-lysimeter study was undertaken using two texturally different soils and three sewage dilutions viz. well water and sewage water as such and in their equal proportions for growing cauliflower, carrot and Indian spinach as test crops. Though application of sewage water as such or in its dilutions improved the physico-chemical properties and nutrient status of the soil but did result in a higher per cent build-up of metallic cations in soil and Zn, Pb and Ni in particular, in sandy clay loam soil and Cu and Cd in sandy loam soil. The soil where Indian spinach was raised with sewage water as such or in its dilution contributed towards an increase in organic carbon content while, in soil where cauliflower and carrot were raised, decreased the CaCO3 content. Metallic cation content in the leaves and roots of the crops recorded an increase when crops were irrigated with sewage water as such or in its dilution, though, the metallic cation content in the leaves and roots were quite below the maximum permissible limits. However, a definite metallic cation contamination of crops under study is apparent looking into the per cent build-up of metallic cations in the leaves and roots of the crops under study when irrigated with sewage water as against well water. Results show that there is a need for the establishment of a municipal sewage treatment plant before such waters are diverted for irrigation.
Planting the seed for sound change: Evidence from real-time MRI of velum kinematics in German

Abstract:Velum movement signals generated from real-time magnetic resonance imaging videos of thirty-five German speakers were used to investigate the physiological conditions that might promote sound change involving the development of contrastive vowel nasality. The results suggest that, in comparison to when a nasal consonant precedes a voiced obstruent, the velum gesture associated with a nasal consonant preceding a voiceless obstruent undergoes gestural rescaling and temporal rephasing. This further suggests that the diachronic development of contrastive vowel nasality comprises two stages: the first stage involves gestural shortening and realignment, while the second stage involves a trading relationship between source and effect.
The ACF chromatin remodeling complex is essential for Polycomb repression

Establishing and maintaining appropriate gene repression is critical for the health and development of multicellular organisms. Histone H3 lysine 27 (H3K27) methylation is a chromatin modification associated with repressed facultative heterochromatin, but the mechanism of this repression remains unclear. We used a forward genetic approach to identify genes involved in transcriptional silencing of H3K27-methylated chromatin in the filamentous fungus Neurospora crassa. We found that the N. crassa homologs of ISWI (NCU03875) and ACF (NCU00164) are required for repression of a subset of H3K27-methylated genes and that they form an ACF chromatin remodeling complex. This N. crassa ACF complex interacts with chromatin throughout the genome, yet association with facultative heterochromatin is specifically promoted by the H3K27 methyltransferase, SET-7. H3K27-methylated genes that are upregulated when iswi or acf1 are deleted show a downstream shift of the +1 nucleosome, suggesting that proper nucleosome positioning is critical for repression of facultative heterochromatin. Our findings support a direct role for the ACF complex in Polycomb repression.
Oxidative phosphorylation is required for powering motility and development of the sleeping sickness parasite Trypanosoma brucei within the tsetse fly vector

The single-celled parasite Trypanosoma brucei causes sleeping sickness in humans and nagana in livestock and is transmitted by hematophagous tsetse flies. Lifecycle progression from mammalian bloodstream form to tsetse midgut form and, subsequently, infective salivary gland form depends on complex developmental steps and migration within different fly tissues. As the parasite colonises the glucose-poor insect midgut, its ATP production is thought to depend on activation of mitochondrial amino acid catabolism via oxidative phosphorylation. This process involves respiratory chain complexes and the F1FO-ATP synthase, and it requires protein subunits of these complexes that are encoded in the parasite’s mitochondrial DNA (kinetoplast or kDNA). Here we show that a progressive loss of kDNA-encoded functions correlates with an increasingly impaired ability of T. brucei to initiate and complete its development in the tsetse. First, parasites with a mutated F1FO-ATP synthase with a reduced capacity for oxidative phosphorylation can initiate differentiation from bloodstream to insect form, but they are unable to proliferate in vitro. Unexpectedly, these cells can still colonise the tsetse midgut. However, these parasites exhibit a motility defect and are severely impaired in colonising or migrating to subsequent tsetse tissues. Second, parasites with a fully disrupted F1FO-ATP synthase complex that is completely unable to produce ATP by oxidative phosphorylation can still differentiate to the first insect stage in vitro but die within a few days and cannot establish a midgut infection in vivo. Third, mutant parasites lacking kDNA entirely can initiate differentiation but die within 24 h. Together, these three scenarios show that efficient ATP production via oxidative phosphorylation is not essential for initial colonisation of the tsetse vector, but it is required to power trypanosome migration within the fly.
Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays

Tissue microarrays (TMAs) have been used in thousands of cancer biomarker studies. To what extent batch effects, measurement error in biomarker levels between slides, affects TMA-based studies has not been assessed systematically. We evaluated 20 protein biomarkers on 14 TMAs with prospectively collected tumor tissue from 1,448 primary prostate cancers. In half of the biomarkers, more than 10% of biomarker variance was attributable to between-TMA differences (range, 1–48%). We implemented different methods to mitigate batch effects (R package batchtma), tested in plasmode simulation. Biomarker levels were more similar between mitigation approaches compared to uncorrected values. For some biomarkers, associations with clinical features changed substantially after addressing batch effects. Batch effects and resulting bias are not an error of an individual study but an inherent feature of TMA-based protein biomarker studies. They always need to be considered during study design and addressed analytically in studies using more than one TMA.
Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients

Progression to metastatic disease remains the main cause of cancer death. Yet, the underlying genomic mechanisms driving metastasis remain largely unknown. Here, we present MSK-MET, an integrated pan-cancer cohort of tumor genomic and clinical outcome data from more than 25,000 patients. We analyzed this dataset to identify associations between tumor genomic alterations and patterns of metastatic dissemination across 50 tumor types. We found that chromosomal instability is strongly correlated with metastatic burden in some tumor types, including prostate adenocarcinoma, lung adenocarcinoma and HR-positive breast ductal carcinoma, but not in others, such as colorectal adenocarcinoma, pancreatic adenocarcinoma and high-grade serous ovarian cancer. We also identified specific somatic alterations associated with increased metastatic burden and specific routes of metastatic spread. Our data offer a unique resource for the investigation of the biological basis for metastatic spread and highlight the crucial role of chromosomal instability in cancer progression.
Single Cell T Cell Receptor Repertoire Profiling for Dogs

Background Spontaneous cancers in companion dogs are increasingly recognized as robust models of human disease. This recognition has led to translational clinical trials in companion dogs with osteosarcoma, lymphoma, melanoma, squamous cell carcinoma, and soft tissue sarcoma. The ability to precisely track tumor-specific immune responses in such clinical trials would benefit from reagents to perform species-specific single cell T cell receptor sequencing (scTCRseq). This technology defines clones of T cells reacting to immune interventions and can help identify the specific epitope of response. Single cell gene expression data give insights into the activity and polarization of the T cell. To date, scTCRseq has not been demonstrated for canine samples. Methods Samples from two responding dogs in a trial of an autologous deglycosylated melanoma vaccine were selected to demonstrate applicability of scTCRseq in a cancer immunotherapy setting. A single-cell suspension of cryopreserved peripheral blood mononuclear cells (PBMC) was prepared for 10X single cell sequencing. Full length 10X cDNA was amplified using a custom-designed nested PCR of the alpha/beta V(D)J region. A library made from this enriched product (scTCRseq) and a 10X gene expression (GEX) library (scRNAseq) were sequenced on the NovaSeq 6000. Results 1,850-2,172 estimated V(D)J-expressing cells yielded 87-103.7 million reads with 73.8%-75.8% mapped to a V(D)J gene (beta/alpha chains ratio 1.5:1). 43 TRAJ, 29 TRAV, 12 TRBJ, and 22 TRBV gene segments were observed representing 72.9%, 51.8%, 100%, and 62.9% of all known V and J gene segments respectively. A large diversity of clonotypes was captured with 966-1,253 TRA/TRB clonotypes identified. Both dogs also exhibited a small number of highly abundant T cell clonotypes suggesting the presence of an anti-tumor T cell population. GEX enriched libraries successfully defined large clusters of CD8+ and CD4+ T cells that overlapped with V(D)J-expressing cells. Discussion The developed reagents successfully generated scTCRseq data, for the first time, which allowed the T cell repertoire to be surveyed in dogs responding to anti-tumor immunotherapy. These reagents will allow longitudinal tracking of anti-tumor T cell dynamics in canine cancer immunotherapy trials.
Simultaneous in vivo Pharmacokinetics and Pharmacodynamics of TDF Intravaginal Ring during High-dose Vaginal SHIV Challenge in Pigtail Macaques

The demonstration of complete protection of macaques in a repeated low dose virus challenge by a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR) and the success of the dapivirine IVR in clinical trials highlighted the potential of IVRs as pre- exposure prophylaxis against HIV. Efficacy of TDF ring was not investigated in sexually active women. Our understanding of the mechanisms of protection is limited. To address this knowledge gap, we performed simultaneous pharmacokinetic and pharmacodynamic analysis of a TDF-IVR at the site of SIV challenge in pigtail macaques at the anatomical and cellular level. Specifically, we challenged TDF-IVR administered pigtail macaques with a single high dose of a non-replicative SIV-based vector containing a dual reporter system that helped us to identify the earliest targets of SIV infection within the mucosa. Two and three days after challenge, the macaques were euthanized and tenofovir (TFV) concentrations were measured in the female reproductive tract (FRT) by HPLC-MS/MS to correlate drug concentrations and SIV-vector transduction efficiency. TFV formed a gradient through the mucosal tissue, with the highest concentrations near the ring, in the upper vagina and endocervix. Despite this, several transduction events were identified with the most common sites being in the ovaries. Moreover, proviral DNA was detected in the cervix and vagina. Thus, our studies demonstrate an uneven distribution of TFV in the FRT of macaques after release from a TDF-IVR that leads to incomplete FRT protection from high viral dose challenge.
Optogenetic stimulation of medial amygdala GABA neurons with kinetically different channelrhodopsin variants yield opposite behavioral outcomes

Optogenetic manipulation of genetically-specified neuron populations has become a key tool in circuit neuroscience. The medial amygdala (MeA) receives pheromone information about conspecifics and has crucial functions in social behaviors; interestingly, this amygdalar structure contains a majority of GABAergic projection neurons. A previous study showed that optogenetic activation of MeA GABA neurons with channelrhodopsin-2H134R (ChR2) strongly enhanced inter-male aggression (Hong et al. 2014, Cell). When we attempted to reproduce these findings, accidentally using a faster channelrhodopsin variant (channelrhodopsin-2H134R,E123T or ChETA), we found the opposite results. We therefore systematically compared the behavioral outcome of optogenetic stimulation of MeApd GABA neurons with ChETA versus ChR2, employing two widely used AAV serotypes. This revealed that optogenetic stimulation with ChETA suppressed aggression, whereas optogenetic stimulation with ChR2 increased aggression. Recordings of membrane potential changes following optogenetic stimulation with ChETA versus ChR2 revealed larger plateau depolarizations, smaller action potential amplitudes, and larger local inhibition of neighboring inhibitory neurons with ChR2 as compared to ChETA. Our study shows that channelrhodopsin variants have to be chosen with care for in-vivo optogenetic experiments. Furthermore, the role of MeApd GABA neurons in aggression control should be re- evaluated.
Epigenetic regulation of nuclear lamina-associated heterochromatin by HAT1 and the acetylation of newly synthesized histones

During S phase, eukaryotic cells must faithfully duplicate both the sequence of the genome and the regulatory information found in the epigenome. A central component of the epigenome is the pattern of histone post-translational modifications that play a critical role in the formation of specific chromatin states. During DNA replication, parental nucleosomes are disrupted and re-deposited on the nascent DNA near their original location to preserve the spatial memory of the epigenetic modifications. Newly synthesized histones must also be incorporated into the nascent chromatin to maintain nucleosome density. Transfer of modification patterns from parental histones to new histones is a fundamental step in epigenetic inheritance. Whether new histones play an active or passive role in epigenetic inheritance is unknown. Here we report that HAT1, which acetylates lysines 5 and 12 of newly synthesized histone H4 during replication-coupled chromatin assembly, regulates the epigenetic inheritance of chromatin states. HAT1 regulates the accessibility of large domains of heterochromatin termed HAT1-dependent Accessibility Domains (HADs). HADs are mega base-scale domains that comprise ~10% of the mouse genome. HAT1 functions as a global negative regulator of H3 K9me2/3 and HADs correspond to the regions of the genome that display HAT1-dependent increases in H3 K9me3 peak density. HADs display a high degree of overlap with a subset of Lamin-Associated Domains (LADs). HAT1 is required to maintain nuclear structure and integrity. These results indicate that HAT1 and the acetylation of newly synthesized histones are critical regulators of the epigenetic inheritance of heterochromatin and suggest a new mechanism for the epigenetic regulation of nuclear lamina-heterochromatin interactions.
Children are full of optimism, but those rose-tinted glasses are fading – reduced learning from negative outcomes drives hyperoptimism in children

Believing that good things will happen in life is essential to maintain motivation and achieve highly ambitious goals. This optimism bias, the overestimation of positive outcomes, may be particularly important during childhood when motivation must be maintained in the face of negative outcomes. In a learning task, we have thus studied the mechanisms underlying the development of optimism bias. Investigating children (8-9 year-olds), early (12-13 year-olds) and late adolescents (16-17 year-olds), we find a consistent optimism bias across age groups. However, children were particularly hyperoptimistic, with the optimism bias decreasing with age. Using computational modelling, we show that this was driven by a reduced learning from worse-than-expected outcomes, and this reduced learning explains why children are hyperoptimistic. Our findings thus show that insensitivity to bad outcomes in childhood helps to prevent taking on an overly realistic perspective and maintain motivation.
Host Cellular RNA Helicases Regulate SARS-CoV-2 Infection

SARS-CoV-2 has a large RNA genome, of approximately 30 kb. To regulate and maintain such a large viral RNA genome, host RNA helicases may be involved in SARS-CoV-2 replication. ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the largest RNA genome, approximately 30 kb, among RNA viruses. The DDX DEAD box RNA helicase is a multifunctional protein involved in all aspects of RNA metabolism. Therefore, host RNA helicases may regulate and maintain such a large viral RNA genome. In this study, I investigated the potential role of several host cellular RNA helicases in SARS-CoV-2 infection. Notably, DDX21 knockdown markedly accumulated intracellular viral RNA and viral production, as well as viral infectivity of SARS-CoV-2, indicating that DDX21 strongly restricts the SARS-CoV-2 infection. In addition, MOV10 RNA helicase also suppressed the SARS-CoV-2 infection. In contrast, DDX1, DDX5, and DDX6 RNA helicases were required for SARS-CoV-2 replication. Indeed, SARS-CoV-2 infection dispersed the P-body formation of DDX6 and MOV10 RNA helicases as well as XRN1 exonuclease, while the viral infection did not induce stress granule formation. Accordingly, the SARS-CoV-2 nucleocapsid (N) protein interacted with DDX1, DDX3, DDX5, DDX6, DDX21, and MOV10 and disrupted the P-body formation, suggesting that SARS-CoV-2 N hijacks DDX6 to carry out viral replication. Conversely, DDX21 and MOV10 restricted SARS-CoV-2 infection through an interaction of SARS-CoV-2 N with host cellular RNA helicases. Altogether, host cellular RNA helicases seem to regulate the SARS-CoV-2 infection. IMPORTANCE SARS-CoV-2 has a large RNA genome, of approximately 30 kb. To regulate and maintain such a large viral RNA genome, host RNA helicases may be involved in SARS-CoV-2 replication. In this study, I have demonstrated that DDX21 and MOV10 RNA helicases limit viral infection and replication. In contrast, DDX1, DDX5, and DDX6 are required for SARS-CoV-2 infection. Interestingly, SARS-CoV-2 infection disrupted P-body formation and attenuated or suppressed stress granule formation. Thus, SARS-CoV-2 seems to hijack host cellular RNA helicases to play a proviral role by facilitating viral infection and replication and by suppressing the host innate immune system.
Relationships between community composition, productivity and invasion resistance in semi-natural bacterial microcosms

Experiments with artificial communities have suggested that invasion resistance in microbial communities is often a side-effect of community members’ contribution towards overall community productivity (broadly defined as cumulative cell density and/or growth rate). However, few experiments have investigated this in natural microbial communities. We conducted experimental invasions of two bacterial species (Pseudomonas fluorescens and Pseudomonas putida) into laboratory microcosms inoculated with 680 different mixtures of bacteria derived from naturally-occurring microbial communities collected in the field. Using 16S amplicon sequencing to characterise microcosm starting composition, and high-throughput assays of community phenotypes including productivity and invader survival, we determined that productivity is a key predictor of invasion resistance in natural microbial communities, substantially mediating the effect of composition on invasion resistance. The results suggest that similar general principles govern invasion in artificial and natural communities, and that factors affecting resident community productivity should be a focal point for future microbial invasion experiments.
QSPR Study on the permeability of drugs across Caco-2 monolayer.

Caco-2 monolayer was used to simulate or predict the human intestinal absorption,and the effect was better than the isolated intestinal membrane.Quantitative structure-property relationship(QSPR) between the permeable coefficients of drugs across Caco-2 monolayer and VolSurf parameters was studied with partial least square analysis technique.Good result was obtained(r2 =0.95 and q2=0.75). The prediction results demonstrate that the model has some predictivity for peptide drugs and homologues.But the predictivity of the model decreases when more flexible bonds in the molecule result in intramolecular hydrogen bonds.The analysis of descriptors showed that the suitable hydrogen bond donors and acceptors are favorable to the permeability and the large local energy minima are beneficial to the permeability of drugs.To some extent,large volume and high globularity are favorable factors.
ArsoNISQ: Analyzing Quantum Algorithms on Near-Term Architectures

While scalable, fully error corrected quantum computing is years or even decades away, there is considerable interest in noisy intermediate-scale quantum computing (NISQ). In this paper, we introduce the ArsoNISQ framework that determines the tolerable error rate of a given quantum algorithm computation, i.e. quantum circuits, and the success probability of the computation given a success criterion and a NISQ computer. ArsoNISQ is based on simulations of quantum circuits subject to errors according to the Pauli error model.ArsoNISQ was evaluated on a set of quantum algorithms that can incur a quantum speedup or are otherwise relevant to NISQ computing. Despite optimistic expectations in recent literature, we did not observe quantum algorithms with intrinsic robustness, i.e. algorithms that tolerate one error on average, in this evaluation. The evaluation demonstrated, however, that the quantum circuit size sets an upper bound for its tolerable error rate and quantified the difference in tolerate error rates for quantum circuits of similar sizes. Thus, the framework can assist quantum algorithm developers in improving their implementation and selecting a suitable NISQ computing platform. Extrapolating the results into the quantum advantage regime suggests that the error rate of larger quantum computers must decrease substantially or active quantum error correction will need to be deployed for most of the evaluated algorithms.
The Diversity-Innovation Paradox in Open-Source Software

Prior studies have shown that, in open-source software (OSS), diversity is a positive indicator of productivity. Yet, code submissions from underrepresented groups are less successful. This mirrors the diversity-innovation paradox found in science—diverse groups produce more innovations, but historically underrepresented people have less successful careers in these groups. In this preliminary research, we want to investigate whether the effect of the diversity-innovation paradox is present in OSS. We define software innovation as a novel co-usage of two packages in the same project. Using World of Code, we identified JavaScript projects’ innovations from late 2008 to early 2014. We intend to calculate diversity measures for the authors who produced the innovations and build models to test the presence of the diversity-innovation paradox in OSS.