gebhart/patrepeval huggingface dataset:
High resolution imaged laser speckle strain gauge for vascular applications (2000)

An imaged laser speckle strain gauge that yields strain rates directly is described for vascular applications. The strain gauge does not rely upon cross correlations between a reference image and subsequent strain-modulated images as most current speckle interferometric methods do. Instead, it relies upon a two-dimensional frequency transform of "stacked speckle histories" which are time series of one-dimensional views of the speckle patterns arranged into a spatio-temporal array such that space is along the abscissa and time is along the ordinate. The tilt of the stacked speckle histories is related to the time rate of speckle pattern shift. The strain gauge is sensitive only to in-plane strains. Strain rates of 30.1 +/- 3.2 and 24.83 +/- 2.1 mu epsilon/s were evaluated in vitro on a fresh human tibial artery and rat inferior vena cava, respectively. The total strains measured were 21.6 and 19.86 mu epsilon, respectively. This is at least one order of magnitude more sensitive than other current soft-tissue strain measurement techniques.
Ectopic pancreas formation in Hes1-knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas (2006)

Ectopic pancreas is a developmental anomaly occasionally found in humans. Hes1, a main effector of Notch signaling, regulates the fate and differentiation of many cell types during development. To gain insights into the role of the Notch pathway in pancreatic fate determination, we combined the use of Hes1-knockout mice and lineage tracing employing the Cre/loxP system to specifically mark pancreatic precursor cells and their progeny in Ptf1a-cre and Rosa26 reporter mice. We show that inactivation of Hes1 induces misexpression of Ptf1a in discrete regions of the primitive stomach and duodenum and throughout the common bile duct. All ectopic Ptf1a-expressing cells were reprogrammed, or transcommitted, to multipotent pancreatic progenitor status and subsequently differentiated into mature pancreatic exocrine, endocrine, and duct cells. This process recapitulated normal pancreatogenesis in terms of morphological and genetic features. Furthermore, analysis of Hes1/Ptf1a double mutants revealed that ectopic Ptf1a-cre lineage-labeled cells adopted the fate of region-appropriate gut epithelium or endocrine cells similarly to Ptf1a-inactivated cells in the native pancreatic buds. Our data demonstrate that the Hes1-mediated Notch pathway is required for region-appropriate specification of pancreas in the developing foregut endoderm through regulation of Ptf1a expression, providing novel insight into the pathogenesis of ectopic pancreas development in a mouse model.
Modulation of dendritic cell differentiation and function by YopJ of Yersinia pestis (2007)

Yersinia pestis evades immune responses in part by injecting into host immune cells several effector proteins called Yersinia outer proteins (Yops) that impair cellular function. This has been best characterized in the innate effector cells, but much less so for cells involved in adaptive immune responses. Dendritic cells (DC) sit at the crossroads between innate and adaptive immunity, and can function to initiate or inhibit adaptive immune responses. Although Y. pestis can target and inactivate DC, the mechanism responsible for this remains unclear. We have found that injection of Y. pestis YopJ into DC progenitors disrupts key signal transduction pathways and interferes with DC differentiation and subsequent function. YopJ injection prevents up-regulation of the NF-kappaB transcription factor Rel B and inhibits MAPK/ERK activation--both having key roles in DC differentiation. Furthermore, YopJ injection prevents costimulatory ligand up-regulation, LPS-induced cytokine expression, and yields differentiated DC with diminished capability to induce T cell proliferation and IFN-gamma induction. By modulating DC function through YopJ-mediated disruption of signaling pathways during progenitor to DC differentiation, Yersinia may interfere with the adaptive responses necessary to clear the infection as well as establish a tolerant immune environment that leads to chronic infection/carrier state in the surviving host.
Identification of metabolically stable 5′-phosphate analogs that support single-stranded siRNA activity (2015)

The ss-siRNA activity in vivo requires a metabolically stable 5'-phosphate analog. In this report we used crystal structure of the 5'-phosphate binding pocket of Ago-2 bound with guide strand to design and synthesize ss-siRNAs containing various 5'-phosphate analogs. Our results indicate that the electronic and spatial orientation of the 5'-phosphate analog was critical for ss-siRNA activity. Chemically modified ss-siRNA targeting human apoC III mRNA demonstrated good potency for inhibiting ApoC III mRNA and protein in transgenic mice. Moreover, ApoC III ss-siRNAs were able to reduce the triglyceride and LDL cholesterol in transgenic mice demonstrating pharmacological effect of ss-siRNA. Our study provides guidance to develop surrogate phosphate analog for ss-siRNA and demonstrates that ss-siRNA provides an alternative strategy for therapeutic gene silencing.
Testosterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen independence in prostate cancer. (2000)

Although initially reported as an androgen-repressed gene in the rat prostate, the functional role of testosterone-repressed prostate message-2 (TRPM-2) in apoptosis remains undefined. Inhibition of castration-induced apoptosis by calcium channel blocker treatment in androgen-dependent Shionogi tumors resulted in the prevention of TRPM-2 gene up-regulation, suggesting that TRPM-2 is not directly androgen-repressed, but is regulated by apoptotic stimuli. The overexpression of the TRPM-2 gene in human androgen-dependent LNCaP prostate cancer cells by stable transfection rendered them highly resistant to androgen ablation in vivo. We then tested the efficacy of antisense TRPM-2 oligodeoxynucleotide (ODN) therapy in the Shionogi tumor model and demonstrated that the systemic administration of antisense TRPM-2 ODNs in mice bearing Shionogi tumors after castration resulted in a more rapid onset of apoptosis and time to complete regression, as well as a significant delay of emergence of androgen-independent recurrent tumors compared to control ODN treatment. Collectively, these findings illustrate that TRPM-2 is an antiapoptotic rather than an androgen-repressed gene that confers resistance to androgen ablation and thereby helps accelerate the progression to androgen independence.
IFN-λ determines the intestinal epithelial antiviral host defense (2011)

Type I and type III IFNs bind to different cell-surface receptors but induce identical signal transduction pathways, leading to the expression of antiviral host effector molecules. Despite the fact that type III IFN (IFN-λ) has been shown to predominantly act on mucosal organs, in vivo infection studies have failed to attribute a specific, nonredundant function. Instead, a predominant role of type I IFN was observed, which was explained by the ubiquitous expression of the type I IFN receptor. Here we comparatively analyzed the role of functional IFN-λ and type I IFN receptor signaling in the innate immune response to intestinal rotavirus infection in vivo, and determined viral replication and antiviral gene expression on the cellular level. We observed that both suckling and adult mice lacking functional receptors for IFN-λ were impaired in the control of oral rotavirus infection, whereas animals lacking functional receptors for type I IFN were similar to wild-type mice. Using Mx1 protein accumulation as marker for IFN responsiveness of individual cells, we demonstrate that intestinal epithelial cells, which are the prime target cells of rotavirus, strongly responded to IFN-λ but only marginally to type I IFN in vivo. Systemic treatment of suckling mice with IFN-λ repressed rotavirus replication in the gut, whereas treatment with type I IFN was not effective. These results are unique in identifying a critical role of IFN-λ in the epithelial antiviral host defense.
A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation (2001)

Autophagy is a normal degradative pathway that involves the sequestration of cytoplasmic portions and intracellular organelles in a membrane vacuole called the autophagosome. These vesicles fuse with lysosomes and the sequestered material is degraded. Owing to the complexity of the autophagic pathway and to its inaccessibility to external probes, little is known about the molecular mechanisms that regulate autophagy in higher eukaryotic cells. We used the autofluorescent drug monodansylcadaverine (MDC), a specific autophagolysosome marker to analyze at the molecular level the machinery involved in the autophagic process. We have developed a morphological and biochemical assay to study authophagy in living cells based on the incorporation of MDC. With this assay we observed that the accumulation of MDC was specifically induced by amino acid deprivation and was inhibited by 3-methlyadenine, a classical inhibitor of the autophagic pathway. Additionally, wortmannin, an inhibitor of PI3-kinases that blocks autophagy at an early stage, inhibited the accumulation of MDC in autophagic vacuoles. We also found that treatment of the cells with N-ethylmaleimide (NEM), an agent known to inhibit several vesicular transport events, completely blocked the incorporation of MDC, suggesting that an NEM-sensitive protein is required for the formation of autophagic vacuoles. Conversely, vinblastine, a microtubule depolymerizing agent that induces the accumulation of autophagic vacuoles by preventing their degradation, increased the accumulation of MDC and altered the distribution and size of the autophagic vacuoles. Our results indicate that in the presence of vinblastine very large MDC-vacuoles accumulated mainly under starvation conditions, indicating that the expansion of autophagosomes is upregulated by amino acid deprivation. Furthermore, these MDC-vacuoles were labeled with LC3, one of the mammalian homologues of the yeast protein Apg8/Aut7 that plays an important role in autophagosome formation.
A cytomegalovirus DNA sequence containing tracts of tandemly repeated CA dinucleotides hybridizes to highly repetitive dispersed elements in mammalian cell genomes. (1983)

A single 880-base-pair region within the genome of simian cytomegalovirus strain Colburn contains sequences that hybridize intensely with both human and mouse total genome DNA probes. This sequence was also found in a second simian cytomegalovirus isolate and was retained in both plaque-purified virus subclones and in plasmid DNA clones containing the SalI P fragment. Cleaved genomic DNAs from several mammalian species all exhibited strong dispersed hybridization with the SalI-P probes, and over 70% of the lambda clones in a mouse genomic library plus several selected clones containing globin, 45S rDNA, or 5S rDNA genes all formed hybrids with SalI-P. The appropriate region of cytomegalovirus SalI-P contains relatively A + T-rich unique sequences interrupted by three stretches of the simple alternating dinucleotides, (CA)15, (CA)22, and (CA)21, which we show to be responsible for most of the cell-virus homology. We conclude that discrete, tandemly repeated (CA) dinucleotide tracts capable of forming left-handed Z-DNA helices punctuate mammalian genomes at greater than 10(5) copies per cell and that three adjacent copies of what appear to be a family of interspersed repetitive elements containing these (CA)n stretches are carried in the genomes of simian cytomegaloviruses.
Complement activation by human monoclonal antibodies to human immunodeficiency virus (1993)

It has been shown that the incubation of human immunodeficiency virus (HIV) with polyclonal antibodies from HIV-infected persons and complement results in complement-mediated neutralization due, at least in part, to virolysis. The current study was performed to determine whether any of a panel of 16 human monoclonal antibodies to HIV could activate complement and, if so, which determinants of the HIV envelope could serve as targets for antibody-dependent complement-mediated effects. Human monoclonal antibodies directed to the third variable region (V3 region) of HIVMN gp120 induced C3 deposition on infected cells and virolysis of free virus. Antibodies to two other sites on HIVMN gp120 and two sites on gp41 induced few or no complement-mediated effects. Similarly, only anti-V3 antibodies efficiently caused complement-mediated effects on the HIVIIIB isolate. In general, the level of C3 deposition on infected cells paralleled the relative level of bound monoclonal antibodies. As expected, pooled polyclonal antibodies from infected persons were much more efficient than monoclonal antibodies inducing C3 deposition per unit of bound immunoglobulin. Treatment of virus or infected cells with soluble CD4 resulted in increases in anti-gp41 antibody-mediated virolysis and C3 deposition but decreases in anti-V3 antibody-mediated virolysis and C3 deposition. In general, virolysis of HIV was more sensitive as an indicator of complement-mediated effects than infected-cell surface C3 deposition, suggesting the absence of or reduced expression of functional complement control proteins on the surface of free virus. Thus, this study shows that human monoclonal antibodies to the V3 region of gp120 are most efficient in causing virolysis of free virus and C3 deposition on infected cells. Elution of gp120 with soluble CD4 exposes epitopes on gp41 that can also bind antibody, resulting in virolysis and C3 deposition. These findings establish a serologically defined model system for the further study of the interaction of complement and HIV.
Monoclonal antibodies: physical development and therapeutic perspectives (2006)

Resumen Los anticuerpos monoclonales son glucoproteinas especializadas que hacen parte del sistema inmune, producidas por las celulas B, con la capacidad de reconocer moleculas especificas (antigenos). Los anticuerpos monoclonales son herramientas esenciales en el ambito clinico y biotecnologico, y han probado ser utiles en el diagnostico y tratamiento de enfermedades infecciosas, inmunologicas y neopla-sicas, asi como tambien en el estudio de las interacciones patogeno-hospedero y la marcacion, deteccion y cuantificacion de diversas moleculas. Actualmente, la incorporacion de las tecnicas de biologia molecular e ingenieria genetica y proteica han permitido ampliar el horizonte de la generacion de anticuerpos monoclonales y sus usos, y se han encontrado tecnicas como la hibridacion, la quimerizacion, la humanizacion y la produccion de anticuerpos monoclonales totalmente humanos. Es una de las areas de mayor crecimiento en la industria biotecnologica y farmaceutica; en el mercado se encuentran cerca de 29 anticuerpos monoclonales aprobados por la Food and Drug Administration (FDA) de los Estados Unidos para uso en humanos. Palabras clave: anticuerpos monoclonales, inmunoglobulinas, inmunoterapia. Anticuerpos monoclonales: desarrollo fisico y perspectivas terapeuticas
The Risk of Transfusion-Transmitted Infection (1992)

Four key measures help keep the use of blood safe. First, all who prescribe blood should try to limit the frequency of homologous transfusion by responding only to patients' physiologic needs and by using alternatives such as autologous transfusion and intraoperative blood salvage. Second, the selection of safe donors provides the greatest safety. For example, the current detection rate for human immunodeficiency virus (HIV) infection among active blood donors in the United States is between 5 and 10 confirmed positive results per 100,000 — that is, 1/40 to 1/80 of the rate anticipated in a random sample of the population, . . .
Rosuvastatin reduces the pro-inflammatory effects of adriamycin on the expression of HMGB1 and RAGE in rats (2018)

Rosuvastatin has cardiac protective effects through its anti‑inflammatory effects. The nuclear protein high‑mobility group box 1 (HMGB1) can activate inflammatory pathways when released from dying cells. The present study aimed to investigate the effects of rosuvastatin in adriamycin (ADR)‑treated rats. Adult male rats were randomized to three groups: i) Control group, ii) ADR group, and iii) ADR+rosuvastatin group. Serum biochemical indices were measured using an enzyme‑linked immunosorbent assay. Cardiac function was assessed by echocardiography. The expression of HMGB1 and receptors for advanced glycation end products (RAGE) were assessed by reverse transcription‑quantitative polymerase chain reaction analysis, western blot analysis, and immunohistochemistry. Cytokines were measured using flow cytometry. Rosuvastatin improved the biochemical indices and cardiac morphology and alleviated the pathological lesions. In the ADR+rosuvastatin group, the mRNA and protein levels of HMGB1 and RAGE in the myocardium were significantly lower compared with those in the ADR group (both P<0.05). The results showed that rosuvastatin significantly reduced the levels of HMGB1 and RAGE in the myocardium of the ADR‑treated rats. These results suggest that the protective effects of rosuvastatin may be associated with attenuation of the HMGB1/RAGE‑mediated inflammatory response in ADR‑treated rats. Despite this protective effect of rosuvastatin in the present study, it did not improve cardiac function in terms of the diastolic left ventricular internal dimension, systolic left ventricular internal dimension, left ventricular ejection fraction and left ventricular fractional shortening; this may be due the observation duration being insufficient.
Bit-flipping BIST (1996)

A scan-based BIST scheme is presented which guarantees complete fault coverage with very low hardware overhead. A probabilistic analysis shows that the output of an LFSR which feeds a scan path has to be modified only at a few bits in order to transform the random patterns into a complete test set. These modifications may be implemented by a bit-flipping function which has the LFSR-state as an input, and flips the value shifted into the scan path at certain times. A procedure is described for synthesizing the additional bit-flipping circuitry, and the experimental results indicate that this mixed-mode BIST scheme requires less hardware for complete fault coverage than all the other scan-based BIST approaches published so far.
Diabetic Nephropathy: The Proteinuria Hypothesis (2005)

While diabetic nephropathy is a disease model for the potential use of proteinuria as a surrogate marker for renal progression, this shift in perspective will require prospective data from additional clinical trials, particularly of non-renin-angiotensin blocking drugs, to be complete.
Effects of subminimal inhibitory concentrations of antibiotics on the adherence of Pseudomonas aeruginosa to tracheobronchial mucin (1987)

Bacterial adherence to mucins may be important in tracheobronchial infections in cystic fibrosis. Sublethal concentrations of antibiotics reduce bacterial adherence to epithelial cells and mucins. This reduction in adherence may be a component of antimicrobial effects in infections at anatomical sites where bactericidal concentrations of antibiotics are difficult to achieve. We therefore tested the effects of sublethal concentrations of an aminoglycoside, tobramycin, and a beta-lactam antibiotic, ceftazidime, on the adherence of Pseudomonas aeruginosa to tracheobronchial mucin, since mucus secretions are often colonized by P. aeruginosa in cystic fibrosis. Adherence of the mucoid strains tested was inhibited by ceftazidime, but not by tobramycin. This effect of ceftazidime may partially explain its efficacy in patients with cystic fibrosis despite variables achieved in sputum.
Development and Characterization of a Series of Soluble Tetrameric and Monomeric Streptavidin Muteins with Differential Biotin Binding Affinities (2001)

The strong biotin-streptavidin interaction limits the application of streptavidin as a reversible affinity matrix for purification of biotinylated biomolecules. To address this concern, a series of single, double, and triple streptavidin muteins with different affinities to biotin were designed. The strategy involves mutating one to three strategically positioned residues (Ser-45, Thr-90, and Asp-128) that interact with biotin and other framework structure-maintaining residues of streptavidin. The muteins were produced in soluble forms via secretion from Bacillus subtilis. The impact of individual residues on the overall structure of streptavidin is reflected by the formation of monomeric streptavidin to different extents. Of the three targeted residues, Asp-128 has the most dramatic effect (Asp-128 > Thr-90 > Ser-45). Conversion of all three targeted residues to alanine results in a soluble biotin binding mutein that exists 100% in the monomeric state. Both wild-type and mutated (monomeric and tetrameric) streptavidin proteins were purified, and their kinetic parameters (on- and off-rates) were determined using a BIAcore biosensor with biotin-conjugated bovine serum albumin immobilized to the sensor chip. This series of muteins shows a wide spectrum of affinity toward biotin (K(d) from 10(-6) to 10(-11) m). Some of them have the potential to serve as reversible biotin binding agents.
Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor (2004)

The Ig new antigen receptors (IgNARs) are single-domain antibodies found in the serum of sharks. Here, we report 2.2- and 2.8-A structures of the type 2 IgNAR variable domains 12Y-1 and 12Y-2. Structural features include, first, an Ig superfamily topology transitional between cell adhesion molecules, antibodies, and T cell receptors; and, second, a vestigial complementarity-determining region 2 at the "bottom" of the molecule, apparently discontinuous from the antigen-binding paratope and similar to that observed in cell adhesion molecules. Thus, we suggest that IgNARs originated as cell-surface adhesion molecules coopted to the immune repertoire and represent an evolutionary lineage independent of variable heavy chain/variable light chain type antibodies. Additionally, both 12Y-1 and 12Y-2 form unique crystallographic dimers, predominantly mediated by main-chain framework interactions, which represent a possible model for primordial cell-based interactions. Unusually, the 12Y-2 complementarity-determining region 3 also adopts an extended beta-hairpin structure, suggesting a distinct selective advantage in accessing cryptic antigenic epitopes.
A Comparison of Three Methods for Selecting Values of Input Variables in the Analysis of Output From a Computer Code (2000)

Two types of sampling plans are examined as alternatives to simple random sampling in Monte Carlo studies. These plans are shown to be improvements over simple random sampling with respect to variance for a class of estimators which includes the sample mean and the empirical distribution function.
Transcriptional Regulation inSaccharomyces cerevisiae: Transcription Factor Regulation and Function, Mechanisms of Initiation, and Roles of Activators and Coactivators (2011)

Here we review recent advances in understanding the regulation of mRNA synthesis in Saccharomyces cerevisiae. Many fundamental gene regulatory mechanisms have been conserved in all eukaryotes, and budding yeast has been at the forefront in the discovery and dissection of these conserved mechanisms. Topics covered include upstream activation sequence and promoter structure, transcription factor classification, and examples of regulated transcription factor activity. We also examine advances in understanding the RNA polymerase II transcription machinery, conserved coactivator complexes, transcription activation domains, and the cooperation of these factors in gene regulatory mechanisms.