Genotype List String: a grammar for describing HLA and KIR genotyping results in a text string

Knowledge of an individual's human leukocyte antigen (HLA) genotype is essential for modern medical genetics, and is crucial for hematopoietic stem cell and solid-organ transplantation. However, the high levels of polymorphism known for the HLA genes make it difficult to generate an HLA genotype that unambiguously identifies the alleles that are present at a given HLA locus in an individual. For the last 20 years, the histocompatibility and immunogenetics community has recorded this HLA genotyping ambiguity using allele codes developed by the National Marrow Donor Program (NMDP). While these allele codes may have been effective for recording an HLA genotyping result when initially developed, their use today results in increased ambiguity in an HLA genotype, and they are no longer suitable in the era of rapid allele discovery and ultra-high allele polymorphism. Here, we present a text string format capable of fully representing HLA genotyping results. This Genotype List (GL) String format is an extension of a proposed standard for reporting killer-cell immunoglobulin-like receptor (KIR) genotype data that can be applied to any genetic data that use a standard nomenclature for identifying variants. The GL String format uses a hierarchical set of operators to describe the relationships between alleles, lists of possible alleles, phased alleles, genotypes, lists of possible genotypes, and multilocus unphased genotypes, without losing typing information or increasing typing ambiguity. When used in concert with appropriate tools to create, exchange, and parse these strings, we anticipate that GL Strings will replace NMDP allele codes for reporting HLA genotypes

Truncated tau interferes with the autophagy and endolysosomal pathway and results in lipid accumulation

This is the final version. Available from Springer via the DOI in this record. Availability of data and material. The data that support the findings of this study are available from the corresponding author upon reasonable request.The autophagy-lysosomal pathway plays a critical role in the clearance of tau protein aggregates that deposit in the brain in tauopathies, and defects in this system are associated with disease pathogenesis. Here, we report that expression of Tau35, a tauopathy-associated carboxy-terminal fragment of tau, leads to lipid accumulation in cell lines and primary cortical neurons. Our findings suggest that this is likely due to a deleterious block of autophagic clearance and lysosomal degradative capacity by Tau35. Notably, upon induction of autophagy by Torin 1, Tau35 inhibited nuclear translocation of transcription factor EB (TFEB), a key regulator of lysosomal biogenesis. Both cell lines and primary cortical neurons expressing Tau35 also exhibited changes in endosomal protein expression. These findings implicate autophagic and endolysosomal dysfunction as key pathological mechanisms through which disease-associated tau fragments could lead to the development and progression of tauopathy

Microdevices for extensional rheometry of low viscosity elastic liquids : a review

Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations

Remote Manipulation of Droplets on a Flexible Magnetically Responsive Film

The manipulation of droplets is used in a wide range of applications, from lab-on-a-chip devices to bioinspired functional surfaces. Although a variety of droplet manipulation techniques have been proposed, active, fast and reversible manipulation of pure discrete droplets remains elusive due to the technical limitations of previous techniques. Here, we describe a novel technique that enables active, fast, precise and reversible control over the position and motion of a pure discrete droplet with only a permanent magnet by utilizing a magnetically responsive flexible film possessing actuating hierarchical pillars on the surface. This magnetically responsive surface shows reliable actuating capabilities with immediate field responses and maximum tilting angles of ???90??. Furthermore, the magnetic responsive film exhibits superhydrophobicity regardless of tilting angles of the actuating pillars. Using this magnetically responsive film, we demonstrate active and reversible manipulation of droplets with a remote magnetic force.open0

Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report

<p>Abstract</p> <p>Introduction</p> <p>We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity.</p> <p>Case presentation</p> <p>As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region.</p> <p>Conclusion</p> <p>Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever.</p

Multifrequency Strategies for the Identification of Gamma-Ray Sources

More than half the sources in the Third EGRET (3EG) catalog have no firmly established counterparts at other wavelengths and are unidentified. Some of these unidentified sources have remained a mystery since the first surveys of the gamma-ray sky with the COS-B satellite. The unidentified sources generally have large error circles, and finding counterparts has often been a challenging job. A multiwavelength approach, using X-ray, optical, and radio data, is often needed to understand the nature of these sources. This chapter reviews the technique of identification of EGRET sources using multiwavelength studies of the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer Academic Press, 2004. For complete article and higher resolution figures, go to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd

Current diagnosis and treatment algorithms for anal incontinence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75666/1/j.1464-410X.2006.06307.x.pd

A novel SNP analysis method to detect copy number alterations with an unbiased reference signal directly from tumor samples

<p>Abstract</p> <p>Background</p> <p>Genomic instability in cancer leads to abnormal genome copy number alterations (CNA) as a mechanism underlying tumorigenesis. Using microarrays and other technologies, tumor CNA are detected by comparing tumor sample CN to normal reference sample CN. While advances in microarray technology have improved detection of copy number alterations, the increase in the number of measured signals, noise from array probes, variations in signal-to-noise ratio across batches and disparity across laboratories leads to significant limitations for the accurate identification of CNA regions when comparing tumor and normal samples.</p> <p>Methods</p> <p>To address these limitations, we designed a novel "Virtual Normal" algorithm (VN), which allowed for construction of an unbiased reference signal directly from test samples within an experiment using any publicly available normal reference set as a baseline thus eliminating the need for an in-lab normal reference set.</p> <p>Results</p> <p>The algorithm was tested using an optimal, paired tumor/normal data set as well as previously uncharacterized pediatric malignant gliomas for which a normal reference set was not available. Using Affymetrix 250K Sty microarrays, we demonstrated improved signal-to-noise ratio and detected significant copy number alterations using the VN algorithm that were validated by independent PCR analysis of the target CNA regions.</p> <p>Conclusions</p> <p>We developed and validated an algorithm to provide a virtual normal reference signal directly from tumor samples and minimize noise in the derivation of the raw CN signal. The algorithm reduces the variability of assays performed across different reagent and array batches, methods of sample preservation, multiple personnel, and among different laboratories. This approach may be valuable when matched normal samples are unavailable or the paired normal specimens have been subjected to variations in methods of preservation.</p

Does bright light have an anxiolytic effect? - an open trial

<p>Abstract</p> <p>Background</p> <p>The aim of this open trial was to examine the influence of acute bright light exposure on anxiety in older and young adults.</p> <p>Methods</p> <p>This study was ancillary to a complex 5-day laboratory experiment testing phase-responses to light at all times of the day. On 3 consecutive days, participants were exposed to bright light (3,000 lux) for 3 hours. The Spielberger State-Trait Anxiety Inventory (Form Y1) was administered 5 minutes before and 20 minutes after each treatment. Mean state anxiety before and after treatment were analyzed by age, sex, and time ANOVA. To avoid floor effects, only participants with baseline STAI levels of ≥ 25 were included.</p> <p>Results</p> <p>A significant anxiolytic effect of bright light was found for the mean data, as well as for each of the three days. No significant main effect of age, sex, or interaction of these factors with STAI change were found.</p> <p>Conclusion</p> <p>The results show consistent and significant (albeit modest) anxiolytic effects following acute bright light exposure in low anxiety adults. Further randomized, controlled trials in clinically anxious individuals are needed.</p