PepPre: Promote Peptide Identification Using Accurate and Comprehensive Precursors.

Accurate and comprehensive peptide precursor ions are crucial to tandem mass-spectrometry-based peptide identification. An identification engine can derive great advantages from the search space reduction enabled by credible and detailed precursors. Furthermore, by considering multiple precursors per spectrum, both the number of identifications and the spectrum explainability can be substantially improved.

Comparative Analysis of Chemical Cross-Linking Mass Spectrometry Data Indicates That Protein STY Residues Rarely React with -Hydroxysuccinimide Ester Cross-Linkers.

When it comes to mass spectrometry data analysis for identification of peptide pairs linked by -hydroxysuccinimide (NHS) ester cross-linkers, search engines bifurcate in their setting of cross-linkable sites. Some restrict NHS ester cross-linkable sites to lysine (K) and protein N-terminus, referred to as K only for short, whereas others additionally include serine (S), threonine (T), and tyrosine (Y) by default. Here, by setting amino acids with chemically inert side chains such as glycine (G), valine (V), and leucine (L) as cross-linkable sites, which serves as a negative control, we show that software-identified STY-cross-links are only as reliable as GVL-cross-links.

pDeep3: Toward More Accurate Spectrum Prediction with Fast Few-Shot Learning.

Spectrum prediction using deep learning has attracted a lot of attention in recent years. Although existing deep learning methods have dramatically increased the prediction accuracy, there is still considerable space for improvement, which is presently limited by the difference of fragmentation types or instrument settings. In this work, we use the few-shot learning method to fit the data online to make up for the shortcoming.

The NINDS Parkinson's disease biomarkers program.

Background: Neuroprotection for Parkinson's disease (PD) remains elusive. Biomarkers hold the promise of removing roadblocks to therapy development. The National Institute of Neurological Disorders and Stroke has therefore established the Parkinson's Disease Biomarkers Program to promote discovery of PD biomarkers for use in phase II and III clinical trials.

Detection of treatment-induced changes in signaling pathways in gastrointestinal stromal tumors using transcriptomic data.

Cell signaling plays a central role in the etiology of cancer. Numerous therapeutics in use or under development target signaling proteins; however, off-target effects often limit assignment of positive clinical response to the intended target. As direct measurements of signaling protein activity are not generally feasible during treatment, there is a need for more powerful methods to determine if therapeutics inhibit their targets and when off-target effects occur.

High density DNA array analysis reveals distinct genomic profiles in a subset of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) generally harbor activating mutations in KIT or platelet-derived growth facter receptor (PDGFRA). Mutations in these receptor tyrosine kinases lead to dysregulation of downstream signaling pathways that contribute to GIST pathogenesis. GISTs with KIT or PDGFRA mutations also undergo secondary cytogenetic alterations that may indicate the involvement of additional genes important in tumor progression.

Real-time polarization mode dispersion monitoring system for a multiple-erbium-doped fiber amplifier, dense wavelength division multiplexing optical fiber transmission by amplified spontaneous emission modulation and acousto-optic tunable fiber scanning techniques.

Without interruption or affecting the transmission of ordinary payload channels, we propose a real time polarization mode dispersion (PMD) monitoring system for long-haul, multiple erbium-doped fiber amplifier (EDFA), dense wavelength division multiplexing (DWDM) optical fiber transmission using modulated amplified spontaneous emission (ASE) of one of the EDFAs as the supervisory (SV) signal source. An acousto-optic tunable filter (AOTF) at the receiver side is adopted to scan the spectrum of the transmitted ASE SV signal. Using the fixed-analyzer method, PMDs of different wavelength bands that range from 1545 to 1580 nm of a DWDM fiber-optic communication system can be found by adaptively changing the radio frequency of the AOTF.

Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors.

A subset of gastrointestinal stromal tumors (GISTs) lack gain-of-function mutations in c-KIT and PDGFRalpha. These so-called wild-type (WT) GISTs tend to be less responsive to imatinib-based therapies and have a poor prognosis. We identified amplification of IGF1R in a SNP analysis of GIST and thus studied its potential as a therapeutic target in WT and mutant GIST.

Polarization changing and beam profile deformation of light during the isotropic Raman-nath acousto-optic interaction.

A spatial Fourier transform approach is used to study the phenomena of polarization changing and beam profile deformation of light during the Raman-Nath, acousto-optic interaction in isotropic media. Starting from the vector version of the well-known Raman-Nath interaction equation and using a spatial Fourier transform allows analytic solutions that encompass the effects of polarization changing and beam-profile deformation for the multiple scattered light to be found in the spatial-frequency domain. Two kinds of sound wave, longitudinal and shear, are assumed to be interacted with the light, whose transverse spatial profile and state of polarization are arbitrary.

Polarization-mode dispersion effect of an acousto-optic tunable filter.

The effect of the polarization-mode dispersion (PMD) of an acousto-optic tunable filter (AOTF) is studied both theoretically and experimentally. A coupled-mode method derived from Maxwell's equations is proposed to study the evolution of the polarization of light and hence the deterministic dynamics of the PMD inside an AOTF. It is found that the PMD value of a typical AOTF is around several picoseconds and is adjustable by tuning the strength of the applied sound signal.

The molecular pathogenesis of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are clinically diagnosed by positive immunohistochemical staining of KIT, a type III receptor tyrosine kinase. Most GISTs contain gain-of-function, ie, oncogenic mutations in c-KIT or in platelet-derived growth factor receptor-alpha (PDGFR-alpha), which appears to be the major initiating event that drives the pathogenesis for GIST. Furthermore, mutations in either of these genes appear to be required for tumor growth and progression.

Therapeutic effect of imatinib in gastrointestinal stromal tumors: AKT signaling dependent and independent mechanisms.

Most gastrointestinal stromal tumors (GISTs) possess a gain-of-function mutation in c-KIT. Imatinib mesylate, a small-molecule inhibitor against several receptor tyrosine kinases, including KIT, platelet-derived growth factor receptor-alpha, and BCR-ABL, has therapeutic benefit for GISTs both via KIT and via unknown mechanisms. Clinical evidence suggests that a potential therapeutic benefit of imatinib might result from decreased glucose uptake as measured by positron emission tomography using 18-fluoro-2-deoxy-d-glucose.

Molecular research directions in the management of gastrointestinal stromal tumors.

Imatinib mesylate (STI571) is an oral 2-phenylaminopyrimidine derivative that acts as a selective inhibitor against several receptor tyrosine kinases and has been viewed as one of the therapeutic success stories of the 21st century. Imatinib was first shown to inhibit the causative molecular translocation in chronic myelogenous leukemia, BCR-ABL. Because imatinib could also inhibit the activity of KIT, a 145-kD transmembrane glycoprotein, and because gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are characterized by expression of a gain-of-function mutation in KIT, imatinib was used in therapeutic trials of GISTs beginning in 1999.

Theoretical and experimental studies of polarization mode dispersion of an electro-optic Mach-Zehnder modulator.

A theoretical model is developed to study the polarization mode dispersion effect in an electro-optic Mach-Zehnder interferometric (MZI) modulator. The Stokes parameters and differential group delay (DGD) of the output light of a MZI modulator can be analytically derived with the proposed model, which is based on a three-dimensional Maxwell's wave equation approach. The theoretical model is validated to the extent possible by comparing the theoretical results of the Stokes parameters and DGD with experimental measurements that are based on the wavelength-scanning method and the Jones matrix eigenanalysis method.

Development of a novel system to study hepatitis delta virus genome replication.

Hepatitis delta virus (HDV) genome replication requires the virus-encoded small delta protein (deltaAg). During replication, nucleotide sequence changes accumulate on the HDV RNA, leading to the translation of deltaAg species that are nonfunctional or even inhibitory. A replication system was devised where all deltaAg was conditionally provided from a separate and unchanging source.

Analysis of KIT mutations in sporadic and familial gastrointestinal stromal tumors: therapeutic implications through protein modeling.

Purpose: Gastrointestinal stromal tumors (GIST) are characterized by expressing a gain-of-function mutation in KIT, and to a lesser extent, PDGFR. Imatinib mesylate, a tyrosine kinase inhibitor, has activity against GISTs that contain oncogenic mutations of KIT. In this study, KIT and PDGFRalpha mutation status was analyzed and protein modeling approaches were used to assess the potential effect of KIT mutations in response to imatinib therapy.

Hepatitis B virus X protein activates the p38 mitogen-activated protein kinase pathway in dedifferentiated hepatocytes.

Hepatitis B virus X protein (pX) is implicated in hepatocarcinogenesis by an unknown mechanism. Employing a cellular model linked to pX-mediated transformation, we investigated the role of the previously reported Stat3 activation by pX in hepatocyte transformation. Our model is composed of a differentiated hepatocyte (AML12) 3pX-1 cell line that undergoes pX-dependent transformation and a dedifferentiated hepatocyte (AML12) 4pX-1 cell line that does not exhibit transformation by pX.

Hepatitis B virus X protein differentially regulates cell cycle progression in X-transforming versus nontransforming hepatocyte (AML12) cell lines.

Hepatitis B virus (HBV) X protein (pX) is implicated in hepatocarcinogenesis of chronically infected HBV patients. To understand mechanism(s) of pX-mediated cellular transformation, we employed two tetracycline-regulated, pX-expressing cell lines, constructed in AML12 immortalized hepatocytes: one a differentiated (3pX-1) and the other a de-differentiated (4pX-1) hepatocyte cell line. Only 3pX-1 cells undergo pX-mediated transformation, via sustained Ras-Raf-mitogen-activated protein kinase pathway activation.

Hepatitis B virus X protein differentially activates RAS-RAF-MAPK and JNK pathways in X-transforming versus non-transforming AML12 hepatocytes.

The hepatitis B virus (HBV) X protein (pX) is implicated in hepatocarcinogenesis of chronic HBV patients by an unknown mechanism. Activities of pX likely relevant to hepatocyte transformation include activation of the mitogenic RAS-RAF-MAPK and JNK pathways. To assess the importance of mitogenic pathway activation by pX in transformation, we employed a cellular model system composed of two tetracycline-regulated, pX-expressing cell lines, constructed in AML12-immortalized hepatocytes.

Effects of fescue and clover forage on serum lactate dehydrogenase and glucose 6-phosphate dehydrogenase isoenzymic profiles in steers.

We determined the effects of forage type on isoenzymes of lactate dehydrogenase (LDH) and glucose 6-phosphate dehydrogenase (G6PDH). Forty-eight crossbred steers were randomly allotted to replicated pastures consisting of fungus-infected (Neotyphodium coenophialum) fescue or fungus-free fescue each with or without ladino clover overseeding. At the end of the 180-d grazing period, serum was harvested from the steers.

Differential immediate early gene expression in conditional hepatitis B virus pX-transforming versus nontransforming hepatocyte cell lines.

We report construction and characterization of tetracycline-controlled hepatitis B virus pX-expressing hepatocyte (AML12) cell lines. These cell lines were constructed in AML12 clonal isolates (clones 3 and 4), which express constitutively the tetracycline-controlled transactivator. Since pX is implicated in HCC, this immortalized hepatocyte model system was used to investigate the mechanism of pX in transformation.

Effects of 6-N-propyl-2-thiouracil on growth, hormonal profiles, carcass and reproductive traits of boars.

Neonatal 6-N-propyl-2-thiouracil (PTU)-induced hypothyroidism reduces body weight but increases testicular size in adult male rodents. The objective of this study was to determine the effect of prepubertal PTU treatment on boars. For Experiment I, boars (n = 28) were randomly allotted to eight pens.

The effect of 5,8,11,14-eicosatetraynoic acid on endothelial cell gene expression.

The endothelium plays a key role in inflammation, hemostasis and organ rejection. We report here that a synthetic polyunsaturated fatty acid, 5,8,11,14-eicosatetraynoic acid (ETYA), selectively inhibits the up-regulation of several genes on endothelial cells. ETYA suppresses endothelial cell activation by inhibiting the up-regulation of adhesion molecules like E-selectin.

Selective suppression of endothelial cell activation by arachidonic acid.

Endothelial cell (EC) activation plays a key role in inflammation, thrombosis and organ rejection. Normally, EC are in a quiescent state in which their function is to prevent coagulation and thrombosis, and to participate in the regulation of leukocyte migration from the bloodstream into the tissue. Upon activation with cytokines or other stimuli, EC up-regulate a number of genes, including E-selectin (ELAM-1), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, interleukin (IL)-1, IL-8, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), MCP-1 (monocyte chemoattractant protein-1) and endothelial cell inducible gene (ECI-6).

Synchronous bilateral carcinoma of the ureter in association with unilateral incomplete duplication of the ureter.

A case of bilateral synchronous ureteral tumors, in association with a unilateral incomplete duplication of ureter, is presented. This patient underwent right nephroureterectomy with removal of a cuff of bladder, partial resection of left ureter, and ileal loop interposition between renal pelvis and bladder. Followup showed no recurrence in the residual urinary tract 2-years postoperatively.