A reference haplotype panel for genome-wide imputation of short tandem repeats.

Short tandem repeats (STRs) are involved in dozens of Mendelian disorders and have been implicated in complex traits. However, genotyping arrays used in genome-wide association studies focus on single nucleotide polymorphisms (SNPs) and do not readily allow identification of STR associations. We leverage next-generation sequencing (NGS) from 479 families to create a SNP + STR reference haplotype panel. Our panel enables imputing STR genotypes into SNP array data when NGS is not available for directly genotyping STRs. Imputed genotypes achieve mean concordance of 97% with observed genotypes in an external dataset compared to 71% expected under a naive model. Performance varies widely across STRs, with near perfect concordance at bi-allelic STRs vs. 70% at highly polymorphic repeats. Imputation increases power over individual SNPs to detect STR associations with gene expression. Imputing STRs into existing SNP datasets will enable the first large-scale STR association studies across a range of complex traits

Depth from Defocus Technique: A Simple Calibration-Free Approach for Dispersion Size Measurement

Dispersed particle size measurement is crucial in a variety of applications, be it in the sizing of spray droplets, tracking of particulate matter in multiphase flows, or the detection of target markers in machine vision systems. Further to sizing, such systems are characterised by extracting quantitative information like spatial position and associated velocity of the dispersed phase particles. In the present study we propose an imaging based volumetric measurement approach for estimating the size and position of spherically dispersed particles. The approach builds on the 'Depth from Defocus' (DFD) technique using a single camera approach. The simple optical configuration, consisting of a shadowgraph setup and a straightforward calibration procedure, makes this method readily deployable and accessible for broader applications

A review on pregabalin for the treatment of painful diabetic peripheral neuropathy

Pregabalin is an anti-epileptic drug which has been used for the treatment of diabetic peripheral neuropathy. Earlier, it was more prescribed as an adjuvant therapy for treating the partial seizures with or without secondary generalization in adults. It is an antagonist of voltage sensitive calcium ion channel on the presynaptic neuron. Pregabalin has a very good pharmacokinetic profile, possesses linear pharmacokinetics with low inter-variability of subjects. It does not show protein binding and does not interfere with the metabolism of other drugs because pregabalin undergoes very less metabolism. This factor has confirmedly shown that its benefits outweigh the risk. Different clinical trials and case reports have confirmed the fact that is reduces the pain involved in peripheral neuropathy. Though, more drugs have come like tricyclic antidepressant to manage the pain but due to their adverse effects, they are less used. This reappraisal is all about the pregabalin, its role, and where it stands among other drugs for management of pain aassociaed with diabetic peripheral neuropathy

The impact of short tandem repeat variation on gene expression.

Short tandem repeats (STRs) have been implicated in a variety of complex traits in humans. However, genome-wide studies of the effects of STRs on gene expression thus far have had limited power to detect associations and provide insights into putative mechanisms. Here, we leverage whole-genome sequencing and expression data for 17 tissues from the Genotype-Tissue Expression Project to identify more than 28,000 STRs for which repeat number is associated with expression of nearby genes (eSTRs). We use fine-mapping to quantify the probability that each eSTR is causal and characterize the top 1,400 fine-mapped eSTRs. We identify hundreds of eSTRs linked with published genome-wide association study signals and implicate specific eSTRs in complex traits, including height, schizophrenia, inflammatory bowel disease and intelligence. Overall, our results support the hypothesis that eSTRs contribute to a range of human phenotypes, and our data should serve as a valuable resource for future studies of complex traits

Outage-Watch: Early Prediction of Outages using Extreme Event Regularizer

Cloud services are omnipresent and critical cloud service failure is a fact of life. In order to retain customers and prevent revenue loss, it is important to provide high reliability guarantees for these services. One way to do this is by predicting outages in advance, which can help in reducing the severity as well as time to recovery. It is difficult to forecast critical failures due to the rarity of these events. Moreover, critical failures are ill-defined in terms of observable data. Our proposed method, Outage-Watch, defines critical service outages as deteriorations in the Quality of Service (QoS) captured by a set of metrics. Outage-Watch detects such outages in advance by using current system state to predict whether the QoS metrics will cross a threshold and initiate an extreme event. A mixture of Gaussian is used to model the distribution of the QoS metrics for flexibility and an extreme event regularizer helps in improving learning in tail of the distribution. An outage is predicted if the probability of any one of the QoS metrics crossing threshold changes significantly. Our evaluation on a real-world SaaS company dataset shows that Outage-Watch significantly outperforms traditional methods with an average AUC of 0.98. Additionally, Outage-Watch detects all the outages exhibiting a change in service metrics and reduces the Mean Time To Detection (MTTD) of outages by up to 88% when deployed in an enterprise cloud-service system, demonstrating efficacy of our proposed method.Comment: Accepted to ESEC/FSE 202

ESRO: Experience Assisted Service Reliability against Outages

Modern cloud services are prone to failures due to their complex architecture, making diagnosis a critical process. Site Reliability Engineers (SREs) spend hours leveraging multiple sources of data, including the alerts, error logs, and domain expertise through past experiences to locate the root cause(s). These experiences are documented as natural language text in outage reports for previous outages. However, utilizing the raw yet rich semi-structured information in the reports systematically is time-consuming. Structured information, on the other hand, such as alerts that are often used during fault diagnosis, is voluminous and requires expert knowledge to discern. Several strategies have been proposed to use each source of data separately for root cause analysis. In this work, we build a diagnostic service called ESRO that recommends root causes and remediation for failures by utilizing structured as well as semi-structured sources of data systematically. ESRO constructs a causal graph using alerts and a knowledge graph using outage reports, and merges them in a novel way to form a unified graph during training. A retrieval-based mechanism is then used to search the unified graph and rank the likely root causes and remediation techniques based on the alerts fired during an outage at inference time. Not only the individual alerts, but their respective importance in predicting an outage group is taken into account during recommendation. We evaluated our model on several cloud service outages of a large SaaS enterprise over the course of ~2 years, and obtained an average improvement of 27% in rouge scores after comparing the likely root causes against the ground truth over state-of-the-art baselines. We further establish the effectiveness of ESRO through qualitative analysis on multiple real outage examples.Comment: Accepted to 38th IEEE/ACM International Conference on Automated Software Engineering (ASE 2023

In vitro Antimicrobial Properties of Pluronic F-127 Injectable Thermoresponsive Hydrogel

Pluronic F-127 (PF-127) hydrogel is a versatile biomaterial with promising applications in drug delivery, tissue engineering, and regenerative medicine. PF-127 has antiadhesive activity that prevents bacterial adhesion by creating a hydrated layer on the bacterial surface. This property makes PF-127 suitable for preventing implant-associated infections. In this study, we aimed to evaluate the antibacterial properties of PF-127 using field isolates of Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria) and compare them with different antibiotic standards. The antimicrobial potential was assessed using disk diffusion assays with four standard concentrations (20%, 25%, 30%, and 40%). The test microorganisms were inoculated on agar plates, and sterile filter paper disks infused with PF-127 hydrogels were placed alongside standard antibiotic disks. After incubation, the inhibition zones were measured to determine antimicrobial activity. Our results showed that PF-127 lacked intrinsic antimicrobial activity against S. aureus and E. coli at the tested concentrations. In conclusion, PF-127 hydrogel is a promising neutral carrier hydrogel system for loading antibiotics and antimicrobial compounds. Its unique properties, such as biocompatibility and thermo-responsive behaviour, combined with its antiadhesive activity, make it an ideal candidate for various biomedical applications

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Measurement of the Splitting Function in &ITpp &ITand Pb-Pb Collisions at root&ITsNN&IT=5.02 TeV

Data from heavy ion collisions suggest that the evolution of a parton shower is modified by interactions with the color charges in the dense partonic medium created in these collisions, but it is not known where in the shower evolution the modifications occur. The momentum ratio of the two leading partons, resolved as subjets, provides information about the parton shower evolution. This substructure observable, known as the splitting function, reflects the process of a parton splitting into two other partons and has been measured for jets with transverse momentum between 140 and 500 GeV, in pp and PbPb collisions at a center-of-mass energy of 5.02 TeV per nucleon pair. In central PbPb collisions, the splitting function indicates a more unbalanced momentum ratio, compared to peripheral PbPb and pp collisions.. The measurements are compared to various predictions from event generators and analytical calculations.Peer reviewe