Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of methods for phylogenetic B‐cell lineage inference using time‐resolved antibody repertoire simulations (AbSim)

Motivation: The evolution of antibody repertoires represents a hallmark feature of adaptive B‐cell immunity. Recent advancements in high‐throughput sequencing have dramatically increased the resolution to which we can measure the molecular diversity of antibody repertoires, thereby offering for the first time the possibility to capture the antigen‐driven evolution of B cells. However, there does not exist a repertoire simulation framework yet that enables the comparison of commonly utilized phylogenetic methods with regard to their accuracy in inferring antibody evolution. Results: Here, we developed AbSim, a time‐resolved antibody repertoire simulation framework, which we exploited for testing the accuracy of methods for the phylogenetic reconstruction of B‐cell lineages and antibody molecular evolution. AbSim enables the (i) simulation of intermediate stages of antibody sequence evolution and (ii) the modeling of immunologically relevant parameters such as duration of repertoire evolution, and the method and frequency of mutations. First, we validated that our repertoire simulation framework recreates replicates topological similarities observed in experimental sequencing data. Second, we leveraged Absim to show that current methods fail to a certain extent to predict the true phylogenetic tree correctly. Finally, we formulated simulation‐validated guidelines for antibody evolution, which in the future will enable the development of accurate phylogenetic methods. Availability and implementation: https://cran.r‐project.org/web/packages/AbSim/index.html Contact: sai.reddy@ethz.ch Supplementary information: Supplementary data are available at Bioinformatics online.
Effect of Combined Treatment of Modern and Herbal Supplement in the Management of Letrozole Induced Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) has a prevalence of developing obesity, Type II diabetes, and cardiovascular disorder. These metabolic disorders and PCOS pathogenesis involve Oxidative Stress (OS) and low-grade inflammation. There are many modern drugs available for the treatment of PCOS, such as Clomifene Citrate (CC) but these drugs not work with abovementioned etiologies of PCOS. Hence, treatment of PCOS required an herbal supplement to manage the OS and low-grade inflammation. Exudates of Commiphora Mukul (CM) having anti-inflammatory and antioxidant properties was used as an herbal supplement. The purpose of the study was to evaluate the protective effect of CM alone and in combination with CC in Letrozole (LTZ) induced PCOS rats. Letrozole induced PCOS rats showed a significant increase in testosterone level, High Sensitive C-Reactive Protein (HSCRP), interleukin6 (IL-6), Lipid Peroxidation (LPO), significant decrease in the level of Superoxide Dismutase (SOD) and catalase. Combined treatment of CM and CC significantly decreases testosterone, HSCRP, IL-6, LPO and increases SOD and catalase. The combined treatment also induces ovulation and decreases number of cystic follicles. This study indicates the supplement of CM with CC have higher therapeutic value as compared to modern drug CC.
Group B Streptococci Colonization in Pregnant Guatemalan Women: Prevalence, Risk Factors, and Vaginal Microbiome

Abstract Background Infection causes 1 of every 5 neonatal deaths globally. Group B Streptococcus (GBS) is the most significant pathogen, although little is known about its epidemiology and risk in low-income countries. Methods A cross-sectional study in 2015 at a public hospital in Guatemala City enrolled women ≥35 weeks’ gestation. Vaginal and rectal swabs were processed using Lim broth and GBS CHROMagar then agglutination testing. Risk factors were assessed using multivariate analysis. Vaginal microbiota were profiled by 16S ribosomal ribonucleic acid sequencing in a subset of 94 women. Results Of 896 pregnant women, 155 (17.3%; 95% confidence interval [CI], 14.9–19.9) were GBS colonized. Colonization was associated with history of previous infant with poor outcome (odds ratio [OR], 1.94; 95% CI, 1.15–3.27) and increasing maternal age (OR, 1.05; 95% CI, 1.02–1.09). Multiparity was protective (OR, .39; 95% CI, .21–.72). Four (6%) GBS-exposed infants had early-onset neonatal sepsis. Vaginal microbiome composition was associated with previous antibiotic exposure (P = .003) and previous low birth weight infant (P = .03), but not GBS colonization (P = .72). Several individual taxa differed in abundance between colonized and noncolonized women. Conclusions Group B Streptococcus is prevalent in pregnant women from Guatemala with different risk factors than previously described. Although the vaginal microbiome was not altered significantly in GBS-colonized women, use of antibiotics had an effect on its composition.
Spatial Group Sparsity Regularized Nonnegative Matrix Factorization for Hyperspectral Unmixing

In recent years, blind source separation (BSS) has received much attention in the hyperspectral unmixing field due to the fact that it allows the simultaneous estimation of both endmembers and fractional abundances. Although great performances can be obtained by the BSS-based unmixing methods, the decomposition results are still unstable and sensitive to noise. Motivated by the first law of geography, some recent studies have revealed that spatial information can lead to an improvement in the decomposition stability. In this paper, the group-structured prior information of hyperspectral images is incorporated into the nonnegative matrix factorization optimization, where the data are organized into spatial groups. Pixels within a local spatial group are expected to share the same sparse structure in the low-rank matrix (abundance). To fully exploit the group structure, image segmentation is introduced to generate the spatial groups. Instead of a predefined group with a regular shape (e.g., a cross or a square window), the spatial groups are adaptively represented by superpixels. Moreover, the spatial group structure and sparsity of the abundance are integrated as a modified mixed-norm regularization to exploit the shared sparse pattern, and to avoid the loss of spatial details within a spatial group. The experimental results obtained with both simulated and real hyperspectral data confirm the high efficiency and precision of the proposed algorithm.
Privacy-preserving crowd incident detection: a holistic experimental approach

Detecting dangerous situations is crucial for emergency management. Surveillance systems detect dangerous situations by analyzing crowd dynamics. This paper presents a holistic video-based approach for privacy-preserving crowd density estimation. Our experimental approach leverages distributed, on-board pre-processing, allowing privacy as well as the use of low-power, low-throughput wireless communications to interconnect cameras. We developed a multicamera grid-based people counting algorithm which provides the density per cell for an overall view on the monitored area. This view comes from a merger of infrared and Kinect camera data. We describe our approach using a layered model for data aggregation and abstraction together with a workflow model for the involved software components, focusing on their functionality. The power of our approach is illustrated through the real-world experiment that we carried out at the Schönefeld airport in the city of Berlin.
Exploring the Amino Acid Residue Requirements of the RNA Polymerase (RNAP) α Subunit C-Terminal Domain for Productive Interaction between Spx and RNAP of Bacillus subtilis

ABSTRACT Bacillus subtilis Spx is a global transcriptional regulator that is conserved among Gram-positive bacteria, in which Spx is required for preventing oxidatively induced proteotoxicity. Upon stress induction, Spx engages RNA polymerase (RNAP) through interaction with the C-terminal domain of the rpoA-encoded RNAP α subunit (αCTD). Previous mutational analysis of rpoA revealed that substitutions of Y263 in αCTD severely impaired Spx-activated transcription. Attempts to substitute alanine for αCTD R261, R268, R289, E255, E298, and K294 were unsuccessful, suggesting that these residues are essential. To determine whether these RpoA residues were required for productive Spx-RNAP interaction, we ectopically expressed the putatively lethal rpoA mutant alleles in the rpoAY263C mutant, where “Y263C” indicates the amino acid change that results from mutation of the allele. By complementation analysis, we show that Spx-bound αCTD amino acid residues are not essential for Spx-activated transcription in vivo but that R261A, E298A, and E255A mutants confer a partial defect in NaCl-stress induction of Spx-controlled genes. In addition, strains expressing rpoAE255A are defective in disulfide stress resistance and produce RNAP having a reduced affinity for Spx. The E255 residue corresponds to Escherichia coli αD259, which has been implicated in αCTD-σ70 interaction (σ70 R603, corresponding to R362 of B. subtilis σA). However, the combined rpoAE255A and sigAR362A mutations have an additive negative effect on Spx-dependent expression, suggesting the residues' differing roles in Spx-activated transcription. Our findings suggest that, while αCTD is essential for Spx-activated transcription, Spx is the primary DNA-binding determinant of the Spx-αCTD complex. IMPORTANCE Though extensively studied in Escherichia coli, the role of αCTD in activator-stimulated transcription is largely uncharacterized in Bacillus subtilis. Here, we conduct phenotypic analyses of putatively lethal αCTD alanine codon substitution mutants to determine whether these residues function in specific DNA binding at the Spx-αCTD-DNA interface. Our findings suggest that multisubunit RNAP contact to Spx is optimal for activation while Spx fulfills the most stringent requirement of upstream promoter binding. Furthermore, several αCTD residues targeted for mutagenesis in this study are conserved among many bacterial species and thus insights on their function in other regulatory systems may be suggested herein.
Prognostic impact of bone marrow fibrosis and dyserythropoiesis in autoimmune hemolytic anemia

REFERENCES [1] Natale R, Charu V, Sch€ utte W, et al. 9248 Safety of romiplostim for treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with advanced non-small cell lung cancer (NSCLC). Eur J Cancer Suppl. 2009;7:574. [2] Parameswaran R, Lunning M, Mantha S, et al. Romiplostim for management of chemotherapy-induced thrombocytopenia. Support Care Cancer. 2014;22:1217–1222. [3] Vadhan-Raj S, Hagemeister F, Fayad LE, et al. Randomized, doubleblind, placebo-controlled, dose and schedule-finding study of AMG 531 in chemotherapy-induced thrombocytopenia (CIT): results of a phase I/II study. Blood. 2010;116:1544–1544. [4] Al-Samkari H, Kuter D, Goodarzi K, et al. Romiplostim for treatment and prevention of chemotherapy-associated thrombocytopenia. Blood. 2016;128(22):3748. [5] Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther. 2004;76(6):628–638. [6] Prandoni P. How I treat venous thromboembolism in patients with cancer. Blood. 2005;106(13):4027–4033.
A predictive coding account of bistable perception - a model-based fMRI study

In bistable vision, subjective perception wavers between two interpretations of a constant ambiguous stimulus. This dissociation between conscious perception and sensory stimulation has motivated various empirical studies on the neural correlates of bistable perception, but the neurocomputational mechanism behind endogenous perceptual transitions has remained elusive. Here, we recurred to a generic Bayesian framework of predictive coding and devised a model that casts endogenous perceptual transitions as a consequence of prediction errors emerging from residual evidence for the suppressed percept. Data simulations revealed close similarities between the model’s predictions and key temporal characteristics of perceptual bistability, indicating that the model was able to reproduce bistable perception. Fitting the predictive coding model to behavioural data from an fMRI-experiment on bistable perception, we found a correlation across participants between the model parameter encoding perceptual stabilization and the behaviourally measured frequency of perceptual transitions, corroborating that the model successfully accounted for participants’ perception. Formal model comparison with established models of bistable perception based on mutual inhibition and adaptation, noise or a combination of adaptation and noise was used for the validation of the predictive coding model against the established models. Most importantly, model-based analyses of the fMRI data revealed that prediction error time-courses derived from the predictive coding model correlated with neural signal time-courses in bilateral inferior frontal gyri and anterior insulae. Voxel-wise model selection indicated a superiority of the predictive coding model over conventional analysis approaches in explaining neural activity in these frontal areas, suggesting that frontal cortex encodes prediction errors that mediate endogenous perceptual transitions in bistable perception. Taken together, our current work provides a theoretical framework that allows for the analysis of behavioural and neural data using a predictive coding perspective on bistable perception. In this, our approach posits a crucial role of prediction error signalling for the resolution of perceptual ambiguities.
The Distribution of the Value of the Firm and Stochastic Interest Rates

The time evolution of the value of a firm is commonly modeled by a linear, scalar stochastic differential equation (SDE) of the type where the coefficient in the drift term denotes the (exogenous) stochastic short term interest rate and is the given volatility of the value process. In turn, the dynamics of the short term interest rate are modeled by a scalar SDE. It is shown that exhibits a lognormal distribution when is a normal/Gaussian process defined by a common variety of narrow sense linear SDEs. The results can be applied to different financial situations where modeling value of the firm is critical. For example, with the context of the structural models, using this result one can readily compute the probability of default of a firm.
Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

BACKGROUND Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). MATERIALS AND METHODS Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count <50,000 cells per µL within 7 days of AMI. RESULTS Of 118 patients with hematologic malignancies who had AMI, 58 (49%) had sTP. Twenty-five patients (43%) with sTP received aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p = .0001) and thienopyridine treatment (27% vs. 3%; p = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. CONCLUSION Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count < 50,000 cells/µL), guideline-recommended medical therapy is often withheld because of the fear of major bleeding. In this study, aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort.
An energy optimization method for vector processing mechanisms

In order to achieve a low energy execution for any multimedia applications (MMAs) on a vector processing mechanism (VPM), the number of parallel arithmetic pipelines and the number of cache ports of VPM must be properly configured for each MMAs. Therefore, this paper proposes an energy optimization method for VPMs (EOM-VP), which finds the lowest energy configuration by using the greedy searching method and an analytical model. As the evaluation results suggest, EOM-VP could find the lowest or the second lowest energy configuration for all the benchmark programs in the evaluation.
Deciphering Multifactorial Resistance Phenotypes in Acinetobacter baumannii by Genomics and Targeted Label-free Proteomics*

Resistance to β-lactams in Acinetobacter baumannii involves various mechanisms. To decipher them, whole genome sequencing (WGS) and real-time quantitative polymerase chain reaction (RT-qPCR) were complemented by mass spectrometry (MS) in selected reaction monitoring mode (SRM) in 39 clinical isolates. The targeted label-free proteomic approach enabled, in one hour and using a single method, the quantitative detection of 16 proteins associated with antibiotic resistance: eight acquired β-lactamases (i.e. GES, NDM-1, OXA-23, OXA-24, OXA-58, PER, TEM-1, and VEB), two resident β-lactamases (i.e. ADC and OXA-51-like) and six components of the two major efflux systems (i.e. AdeABC and AdeIJK). Results were normalized using “bacterial quantotypic peptides,” i.e. peptide markers of the bacterial quantity, to obtain precise protein quantitation (on average 8.93% coefficient of variation for three biological replicates). This allowed to correlate the levels of resistance to β-lactam with those of the production of acquired as well as resident β-lactamases or of efflux systems. SRM detected enhanced ADC or OXA-51-like production and absence or increased efflux pump production. Precise protein quantitation was particularly valuable to detect resistance mechanisms mediated by regulated genes or by overexpression of chromosomal genes. Combination of WGS and MS, two orthogonal and complementary techniques, allows thereby interpretation of the resistance phenotypes at the molecular level.
Phenopolis: an open platform for harmonization and analysis of genetic and phenotypic data

Summary Phenopolis is an open-source web server providing an intuitive interface to genetic and phenotypic databases. It integrates analysis tools such as variant filtering and gene prioritization based on phenotype. The Phenopolis platform will accelerate clinical diagnosis, gene discovery and encourage wider adoption of the Human Phenotype Ontology in the study of rare genetic diseases. Availability and Implementation A demo of the website is available at https://phenopolis.github. io . If you wish to install a local copy, source code and installation instruction are available at https://github.com/phenopolis . The software is implemented using Python, MongoDB, HTML/Javascript and various bash shell scripts. Contact n.pontikos@ucl.ac. uk. Supplementary information Supplementary data are available at Bioinformatics online.
The Chinese Impact on GDP Growth and Inflation in the Industrial Countries

The integration of China into the global economy is one of the most spectacular events in economic history. This paper investigates to what extent this process affects output growth and inflation in the advanced countries. A GVAR model is specified to explore interdependencies between business cycles in China and industrial countries, including the US, the euro area and Japan. For robustness, the results are compared to those obtained from leading structural models, such as NiGEM and OEF. Evidence is based on the responses to a Chinese demand shock arising from the recent fiscal stimulus program. The results show that the impact on output growth in the advanced economies can be quite substantial, especially for the Asian region. The expansionary effects in the US and the euro area responses are lower, as trade linkages are less intensive. The multipliers are also reduced by a sizeable effect on inflation, as Chinese firms participate in international production chains.
Comparative Analysis of the Antioxidant Capacities and Phenolic Compounds of Oat and Buckwheat Vinegars During Production Processes.

This study aimed to explore the dynamic changes in the antioxidant activities and phenolic acid profiles of oat and buckwheat vinegars during different production stages. The results showed that both oat and buckwheat vinegar products comparably attenuated D-galactose-induced oxidative damage in mice serum and liver, indicating no obvious dose dependence within the tested concentrations. However, oat vinegar product revealed more favorable in vitro antioxidant activities than those in buckwheat vinegar product as evaluated by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities. Moreover, the alcoholic fermentation, acetic acid fermentation and fumigating induced successive increase in DPPH radical scavenging abilities and phenolic acid contents of the fermentation substrates of oat and buckwheat vinegars. Importantly, the different fermentation processes of oat and buckwheat vinegars were accompanied by the dynamic migration and transformation of specific phenolic acids across bound, esterified and free fractions. Thus, the antioxidant activities of oat and buckwheat vinegars could be improved through targeted modulation of the generation of specific phenolic acid fractions during production processes. PRACTICAL APPLICATION We had evaluated the in vitro and in vivo antioxidant activities and phenolic acid contents of oat and buckwheat vinegars, and further explored the dynamic changes of bound, esterified and free phenolic acid fractions during successive fermentation processes of oat and buckwheat vinegars. This study provided the theoretical guidance for obtaining minor grain vinegar with the optimal antioxidant activities through targeted modulation of fermentation processes.