gebhart/patrepeval huggingface dataset:
Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death (2000)

Clusterin [CLU, a.k.a. TRPM-2, SGP-2, or ionizing radiation (IR)-induced protein-8 (XIP8)] was implicated in apoptosis, tissue injury, and aging. Its function remains elusive. We reisolated CLU/XIP8 by yeast two-hybrid analyses using as bait the DNA double-strand break repair protein Ku70. We show that a delayed (2-3 days), low-dose (0.02-10 Gy) IR-inducible nuclear CLU/XIP8 protein coimmunoprecipitated and colocalized (by confocal microscopy) in vivo with Ku70/Ku80, a DNA damage sensor and key double-strand break repair protein, in human MCF-7:WS8 breast cancer cells. Overexpression of nuclear CLU/XIP8 or its minimal Ku70 binding domain (120 aa of CLU/XIP8 C terminus) in nonirradiated MCF-7:WS8 cells dramatically reduced cell growth and colony-forming ability concomitant with increased G(1) cell cycle checkpoint arrest and increased cell death. Enhanced expression and accumulation of nuclear CLU/XIP8-Ku70/Ku80 complexes appears to be an important cell death signal after IR exposure.
A neutralizing epitope of human immunodeficiency virus type 1 has homologous amino acid sequences with the active site of inter-α-trypsin inhibitor (1989)

A neutralizing epitope (epitope beta) of the HTLV-IIIB strain of HIV-1 was mapped to 24 amino acids of an external envelope glycoprotein (gp120) using a neutralizing monoclonal antibody (0.5 beta) and hetero-antisera against synthetic peptides encoding gp120. Proteins that have homologous sequences with epitope beta were sought from a databank of protein sequences to assess biological features of epitope beta. The results showed that epitope beta was found to have homologous sequences to inter-alpha-trypsin inhibitor (ITI). The homologous region of ITI included the active site of the protein. Synthesized peptides including epitope beta were good substrates for trypsin, because these peptides inhibited trypsin activities in a competitive manner (Ki = 24.5 microM). Human urinary trypsin inhibitor (UTI), a protein indistinguishable from ITI, as well as synthetic peptides including epitope beta inhibited syncytium formation caused by the LAV-1-infected CCRF-CEM and uninfected Molt-4 cells in a dose-dependent manner (0.1-1 mM). These findings suggest that epitope beta of HIV-1 could be substrate of protease upon HIV-1 infection and also suggest that protease inhibitory activity of epitope beta may play a role in the pathophysiology of HIV-1-infected individuals.
Committing Embryonic Stem Cells to Early Endocrine Pancreas In Vitro (2004)

A panel of genetic markers was used to assess the in vitro commitment of murine embryonic stem (ES) cells toward the endoderm-derived pancreas and to distinguish insulin-expressing cells of this lineage from other lineages such as neuron, liver, and yolk sac. There are two nonallelic insulin genes in mice. Neuronal cells express only insulin II, whereas the pancreas expresses both insulin I and II. Yolk sac and fetal liver express predominately insulin II, small amounts of insulin I, and no glucagon. We found that ES-derived embryoid bodies cultured in the presence of stage-specific concentrations of monothio-glycerol and 15% fetal calf serum, followed by serum-free conditions, give rise to a population that expresses insulin I, insulin II, pdx-1 (a pancreas marker), and Sox17 (an endoderm marker). Immunohistochemical staining shows intracellular insulin particles, and its de novo production was confirmed by staining for C-peptide. Most, but not all, of the insulin+ or C-peptide+ cells coexpress glucagon, demonstrating a differentiation pathway to pancreas rather than yolk sac or fetal liver. Addition of beta-cell specification and differentiation factors activin beta B, nicotinamide, and exendin-4 to later-stage culture increased insulin-positive cells to 2.73% of the total population, compared with the control culture, which gave rise to less than 1% insulin-staining cells. These findings suggest that stepwise culture manipulations can direct ES cells to become early endocrine pancreas.
Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis (2012)

Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.
Cutting Edge: Lipopolysaccharide Induces Physical Proximity Between CD14 and Toll-Like Receptor 4 (TLR4) Prior to Nuclear Translocation of NF-κB (2000)

CD14, a GPI-linked protein, plays a pivotal role in LPS-mediated signaling by potentiating leukocyte adherence, activation, and cytokine production. Recent studies have identified the Toll-like receptor 4 (TLR4) as a membrane cofactor in LPS-mediated transmembrane signaling in cytokine induction, although the mechanism responsible for this cooperation is unknown. Using fluorescence resonance energy transfer (RET) techniques, we demonstrate that LPS triggers a physical association between CD14 and TLR4. Because LPS stimulation upregulates CD14 and TLR4 expression, it was necessary to control for the possibility that these newly expressed molecules were associated with one another independent of LPS stimulation. Although the calcium ionophore A23187 increased the expression of CD14 and TLR4, they did not exhibit energy transfer. However, following A23187 treatment, LPS promoted physical proximity between CD14 and TLR4. Therefore, we suggest that a close interaction between CD14 and TLR4 participates in LPS signaling, leading to nuclear translocation of NF-kappaB.
The Chicken Hypersensitivity Site 4 Core Insulator Blocks Promoter Interference in Lentiviral Vectors (2013)

Lentiviral vectors, including double internal promoters, can be used to express two transgenes in a single vector construct; however, transcriptional activities from double internal promoters are often inhibited by promoter interference. To determine whether the chicken hypersensitivity site 4 insulator (cHS4) could block promoter interference, lentiviral vectors including an MSCV-U3 promoter (Mp) and an EF1α promoter (Ep) were generated, and transgene expression was evaluated among transduced cells. In the Ep-Mp configuration, transcriptional activity from Mp was much lower, while Mp-Ep had similar transcription levels from both promoters. The cHS4 core insulator increased expression levels from Mp in HeLa cells, hematopoietic cell lines, and mouse peripheral blood cells following hematopoietic stem cell transplantation transduced with the Mp-Ep configured vector. This blocking function was mainly mediated by barrier activity regions in the insulator but not by CCCTC-binding factor (CTCF) binding sites. Cytosine-phosphate-guanine (CpG) methylation did not contribute to this barrier activity. In summary, combining the cHS4 insulator in double promoter vectors can improve transgene expression levels in various cell lines and mouse hematopoietic repopulating cells. These findings are useful for developing hematopoietic stem cell gene therapy.
Expression of leptin and leptin receptor isoforms in the human stomach (2000)

Leptin and leptin receptors are expressed in human gastric mucosa. These findings suggest a paracrine and/or autocrine effect of leptin on gastric epithelial cell function.
Phenotypic correction of ornithine transcarbamylase deficiency using low dose helper‐dependent adenoviral vectors (2008)

Vectors containing the expression cassette used in the present study, combined with other strategies for improving HDAd therapeutic index, will likely permit application of these vectors for the treatment of OTC deficiency as well as other urea cycle disorders.
Immunotherapy Targeting the CD40/CD154 Costimulatory Pathway for Treatment of Autoimmune Disease (2004)

The CD154-CD40 ligand pair interaction plays a central role in both induction of the immune response and in immune effector functions. Indeed, many animal disease models and human autoimmune diseases have demonstrated a central role for CD154 expression. The expression of CD154 is very tightly regulated by the immune system through a number of non-redundant overlapping mechanisms that ensure its limited initial induction, along with its temporal maintenance and rapid elimination from the cell surface, and its functional neutralization by the release of soluble CD40. In this review, we discuss the current state of understanding of CD154 regulation during the activation of the immune system and describe numerous strategic mechanisms by which modulation of CD154-CD40 interactions may be applied to treat autoimmune disease.
Integrated optical switches and gas sensors (1984)

We have demonstrated new switching and gas-sensing effects in integrated optics using input and output grating couplers and Bragg reflector gratings with 1200 lines/mm on planar SiO(2)-TiO(2) waveguides. Switching is actuated by adsorption or desorption of water or other adsorbates on the waveguide surface through a change in the effective index of the guided modes under the grating. We derived theoretically the ultimate sensitivity limits of the grating devices employed either as switches or as gas sensors. Switching requires the adsorption and desorption, respectively, of less than one H(2)O monolayer. Sensors can detect variations in surface coverage of 1/100 of an H(2)O monolayer.
Knit: component composition for systems software (2000)

Knit is a new component definition and linking language for systems code. Knit helps make C code more understandable and reusable by third parties, helps eliminate much of the performance overhead of componentization, detects subtle errors in component composition that cannot be caught with normal component type systems, and provides a foundation for developing future analyses over C-based components, such as cross-component optimization. The language is especially designed for use with component kits, where standard linking tools provide inadequate support for component configuration. In particular, we developed Knit for use with the OSKit, a large collection of components for building low-level systems. However, Knit is not OSKit-specific, and we have implemented parts of the Click modular router in terms of Knit components to illustrate the expressiveness and flexibility of our language. This paper provides an overview of the Knit language and its applications.
Molecular cloning and sequence analysis of the phosphoprotein, nucleocapsid protein, matrix protein and 22K (M2) protein of the ovine respiratory syncytial virus (1994)

Respiratory syncytial viruses (RSVs) cause serious respiratory tract disease in infants and children worldwide and similar disease in calves. Strains have been isolated from other ruminant animals such as sheep and goats, but these viruses have not been characterized at the molecular level. In this study, we report the cloning and sequencing of four structural genes coding for the phosphoprotein, nucleocapsid (N) protein, matrix (M) protein and 22K protein of an ovine RSV strain. Comparisons of these sequences with those of bovine and human RSV show that the M and N proteins are the most conserved between ruminant RSV strains and the N protein is the most conserved protein between human and ruminant RSV strains. The attachment G glycoprotein and the small hydrophobic protein are the most divergent proteins among human and ruminant RSV subgroups.
Iron Overload in Human Disease (2012)

Iron is both essential and toxic. The authors review how the body absorbs, uses, and loses iron and explore both common and unusual causes of iron overload and treatment of the resulting disorders.
Cytochrome P450 Profile of Colorectal Cancer: Identification of Markers of Prognosis (2005)

The expression of individual P450s has been established in colorectal cancer. Several P450s show increased expression in colorectal cancer. High expression of CYP51 or CYP2S1 were associated with poor prognosis and CYP51 is an independent marker of prognosis.
Abstract B48: A first-in-human Phase I study of the novel cancer stem cell (CSC) targeting antibody OMP-52M51 (anti-Notch1) administered intravenously to patients with certain advanced solid tumors. (2013)

Abstract Background: The Notch pathway plays a central role in embryonic development, the regulation of stem and progenitor cells, and is implicated centrally in many forms of human cancer. Notch1 is known to be frequently activated in certain solid tumor types. OMP-52M51 is a humanized IgG2 antibody that inhibits the signaling function of the Notch1 receptor. Mouse xenograft studies using minimally-passaged, patient-derived xenografts have shown that OMP-52M51 impedes tumor growth and selectively eliminates CSCs in a range of tumor types particularly in tumors with activated Notch1 signaling. In these models, anti-Notch1 antibody also has anti-angiogenic effects leading to tumor growth inhibition. As such, OMP-52M51 is a novel anti-cancer agent that inhibits tumor growth through direct actions on tumor cells, including CSCs, and effects on tumor angiogenesis. Methods: A phase I dose escalation and expansion study was initiated in patients with certain advanced solid tumor indications (cholangiocarcinoma, breast, colorectal, esophageal, gastric, and small cell lung cancers) that have frequencies of Notch1 activation of 12-29% (AACR 2013; #3728). OMP-52M51 was administered intravenously to study safety, pharmacokinetics (PK), pharmacodynamics (PD), preliminary efficacy, and to determine the maximum tolerated dose (MTD). The trial has a Notch1 IHC biomarker selected expansion cohort to test for single-agent response rate. Results: Ten patients have been enrolled in 4 dose-escalation cohorts at doses of 0.25, 0.5, 1, and 2.5mg/kg administered every 4 weeks (Q4W). The most frequently reported drug-related adverse events were: mild to moderate diarrhea (56%), rash (22%), and nausea (22%). One patient developed grade 3 diarrhea for 24 hours controlled with Imodium. No dose-limiting toxicities (DLTs) have occurred and dose escalation continues. The PK of OMP-52M51 in patients is characterized by dose-dependent clearance. One patient with colorectal cancer has prolonged stable disease for &amp;gt;100 days with a decline in CEA tumor marker. Biomarker analyses for Notch pathway modulation and activation are ongoing. Conclusions: OMP-52M51 is generally well tolerated. Dose escalation continues and updated results will be presented. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B48. Citation Format: S. Lindsey Davis, Patricia LoRusso, Lu Xu, Ann M. Kapoun, Jakob Dupont, Pamela Munster, S. Gail Eckhardt, Amita Patnaik. A first-in-human Phase I study of the novel cancer stem cell (CSC) targeting antibody OMP-52M51 (anti-Notch1) administered intravenously to patients with certain advanced solid tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B48.
On the Emerging Role of Chemistry in the Fashioning of Biologics: Synthesis of a Bidomainal Fucosyl GM1-Based Vaccine for the Treatment of Small Cell Lung Cancer (2009)

The synthesis of the novel small cell lung cancer (SCLC) fucosyl GM1-based vaccine construct, featuring insertion of the HLA-DR binding 15 amino acid sequence derived from Plasmodium falciparum, is described. The resultant glycopeptide has been synthesized in an efficient manner. Finally, successful conjugation of the glycopeptide to the keyhole limpet hemocyanin (KLH) carrier protein completed the preparation of the vaccine.
Detection and Summarization of Novel Network Attacks Using Data Mining (2003)

This paper introduces the Minnesota Intrusion Detection System (MINDS), which uses a suite of data mining techniques to automatically detect attacks against computer networks and systems. While the long-term objective of MINDS is to address all aspects of intrusion detection, in this paper we present two specific contributions. First, we present MINDS anomaly detection module that assigns a score to each connection that reflects how anomalous the connection is compared to the normal network traffic. Experimental results on live network traffic at the University of Minnesota show that our anomaly detection techniques have been successful in automatically detecting several novel intrusions that could not be identified using state-of-the-art signature-based tools such as SNORT. Many of these have been reported on the CERT/CC list of recent advisories and incident notes. We also present the results of comparing the MINDS anomaly detection module to SPADE (Statistical Packet Anomaly Detection Engine), which is designed to detect stealthy scans. Second, we present MINDS association pattern analysis module that summarizes those network connections that are ranked highly anomalous by the anomaly detection module. Given the very high volume of connections observed per unit time, such characterization of novel attacks is essential in enabling a security analyst to understand emerging threats. Experimental evaluation shows that the MINDS approach is very useful in creating accurate summaries of novel attacks.
CREW: Compression with Reversible Embedded Wavelets (2002)

Compression with Reversible Embedded Wavelets (CREW) is a unified lossless and lossy continuous tone still image compression system. It is wavelet based using a "reversible" approximation of one of the best wavelet filters. Reversible wavelets are linear filters with non linear rounding which implement exact reconstruction systems with minimal precision integer arithmetic. Wavelet coefficients are encoded in a bit significance embedded order, allowing lossy compression by simply truncating the compressed data. For coding of coefficients, CREW uses a method similar to J. Shapiro's (1993) zero tree, and a completely novel method called Horizon. Horizon coding is a context based coding that takes advantage of the spatial and spectral information available in the wavelet domain. CREW provides state of the art lossless compression of medical images (greater than 8 bits deep), and lossy and lossless compression of 8 bit deep images with a single system. CREW has reasonable software and hardware implementations.
Hot-electron electroluminescence in AlGaAs/GaAs heterojunction bipolar transistors (1993)

When biased in the active region at high collector voltages, AlGaAs/GaAs single heterojunction bipolar transistors have been observed to emit light in the 1.1–2.5 eV energy range. The spectral distribution of the emitted radiation results from the superimposition of (i) two peaks at about 1.4 and 2.1 eV, due to band-to-band recombination of cold electrons and holes, and (ii) a nearly exponential tail due to hot-electron-induced electroluminescence, whose intensity depends on reverse collector-base voltage. Moreover, a linear correlation has been found between the intensity of the hot-electron-induced electroluminescence and the current generated by impact ionization.
A Randomized Trial of the Duration of Therapy with Metronidazole plus or minus Azithromycin for Treatment of Symptomatic Bacterial Vaginosis (2006)

Cure rates for BV were significantly improved by 14 days of metronidazole treatment (compared with 7 days of treatment), but the effects were not sustained, suggesting that relapse or reinfection occurred. Combination therapy with the addition of azithromycin had no benefit. Lower baseline Nugent scores--presumably reflecting less complex vaginal flora--were significantly associated with cure, as was refraining from unprotected sex and from douching.
The heparin-binding domain of amphiregulin necessitates the precursor pro-region for growth factor secretion. (1994)

The five members of the human epidermal growth factor (EGF) family (EGF, transforming growth factor alpha [TGF-alpha], heparin-binding EGF-like growth factor [HB-EGF], betacellulin, and amphiregulin [AR]) are synthesized as transmembrane proteins whose extracellular domains are proteolytically processed to release the biologically active mature growth factors. These factors all activate the EGF receptor, but in contrast to EGF and TGF-alpha, the mature forms of HB-EGF and AR are also glycosylated, heparin-binding proteins. We have constructed a series of mutants to examine the influence of the distinct precursor domains in the biosynthesis of AR. The transmembrane and cytoplasmic domains of the precursor are not required for secretion of bioactive AR from either COS or mammary epithelium-derived cells, although proteolytic removal of the N-terminal pro-region is less efficient in the absence of the membrane anchor. Deletion of the N-terminal pro-region, however, results in rapid intracellular degradation of the molecule with no detectable secretion of active growth factor. AR secretion is preserved by replacing the native pro-region with the corresponding domain of the HB-EGF precursor but not with that of the TGF-alpha precursor. In the absence of any N-terminal pro-region, secretion of the molecule is restored by deleting the N-terminal heparin-binding domain of mature AR. Both EGF and TGF-alpha, in contrast, can be secreted without their pro-regions. However, if the protein is fused with the AR heparin-binding domain, TGF-alpha secretion is inhibited unless the AR pro-region is also present. We propose that the heparin-binding domain of mature AR necessitates the presence of a specific structural motif in an N-terminal pro-region to permit proper folding, and thus secretion, of a bioactive molecule.