gebhart/patrepeval huggingface dataset:
Characterization of AvrHah1, a novel AvrBs3‐like effector from Xanthomonas gardneri with virulence and avirulence activity (2008)

Many phytopathogenic bacteria inject virulence effector proteins into plant cells. To identify novel virulence effectors of the bacterial plant pathogen Xanthomonas, a worldwide collection of pepper (Capsicum annuum) pathogenic Xanthomonas strains was studied. Xanthomonas gardneri strains produced in pepper enhanced watersoaking, a phenotype that is typical of a compatible interaction. Transfer of X. gardneri library clones into a Xanthomonas euvesicatoria recipient strain revealed that enhanced watersoaking was attributable to avrHah1 (avirulence (avr) gene homologous to avrBs3 and hax2, No. 1), a novel avrBs3-like gene. avrHah1 is a novel member of the avrBs3 family that encodes tandemly arranged repeat units of both 34 and 35 amino acid lengths. Although AvrHah1 is only distantly related to AvrBs3, it was shown to trigger a Bs3-dependent hypersensitive response (HR). When fused to a nuclear export signal, AvrHah1 is no longer capable of triggering a Bs3 HR, indicating that nuclear targeting of AvrHah1 is crucial to its recognition. Phylogenetic analysis revealed that, although AvrBs3 and AvrHah1 are only distantly related, they share blocks of high homology within potentially solvent-exposed repeat units. Thus, these data suggest that the recognition specificity of AvrBs3-like proteins is predominantly determined by solvent-exposed residues, rather than by overall homology or repeat unit length.
Evaluation of a Capacitively-Coupled, Non-Contact (through Clothing) Electrode or ECG Monitoring and Life Signs Detection for the Objective Force Warfighter (2004)

A new device that measures ECG inter-beat intervals through clothing is described and compared to a resistive contact electrode. The capacitively coupled non-contact electrode (CCNE) underwent a 40 person human trial at the Walter Reed Army Institute of Research this past year. This sensor can detect ECG and respiratory signals thru clothing and is being considered by the US Army as a physiological monitoring detection sensor on the Objective WarFighter uniform of the future. In this study, three CCNE sensors were compared to an FDA-approved monitor (3-lead) using contact electrodes to determine if the R-R inter-beat intervals of the two methods were the same or not. Results of the at rest in supine position for determining heart rate based on inter-beat intervals of the ECG are presented. The test results indicate that, relative to the ECG contact electrode, the CCNE sensors work for determining R-R inter-beat intervals reliably. Test subject variability in the different weight categories indicates similarity between the two types of electrodes and statistics for comparison are presented. The CCNE sensor gives "unbiased" estimates (116 out of 117 difference signals gave "unbiased" estimates). The CCNE sensor gave close estimates of the inter-beat intervals in 30 out of 39 test subjects with less than 14 ms differences. The CCNE difference signals give statistically "similar" results within each test subject (37 out of 39 test subjects had statistically similar results). Females showed more variability than males for each weight class. Males and females in weight class 5 had the largest measures of variability. Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The views of the authors do not purport to reflect the position of the Department of the Army or the Department of Defense, (para 4-3), AR 360.5.
Identification and Characterization of CD39/Vascular ATP Diphosphohydrolase (1996)

Vascular ATP diphosphohydrolase (ATPDase) is a plasma membrane-bound enzyme that hydrolyses extracellular ATP and ADP to AMP. Analysis of amino acid sequences available from various mammalian and avian ATPDases revealed their close homology with CD39, a putative B-cell activation marker. We, therefore, isolated CD39 cDNA from human endothelial cells and expressed this in COS-7 cells. CD39 was found to have both immunological identity to, and functional characteristics of, the vascular ATPDase. We also demonstrated that ATPDase could inhibit platelet aggregation in response to ADP, collagen, and thrombin, and that this activity in transfected COS-7 cells was lost following exposure to oxidative stress. ATPDase mRNA was present in human placenta, lung, skeletal muscle, kidney, and heart and was not detected in brain. Multiple RNA bands were detected with the CD39 cDNA probe that most probably represent different splicing products. Finally, we identified an unique conserved motif, DLGGASTQ, that could be crucial for nucleotide binding, activity, and/or structure of ATPDase. Because ATPDase activity is lost with endothelial cell activation, overexpression of the functional enzyme, or a truncated mutant thereof, may prevent platelet activation associated with vascular inflammation.
Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells (2016)

Chemical modification of small molecule hydrophobic drugs is a clinically proven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubility while maintaining high potency against cancer cells. We found that camptothecin (CPT) prodrugs created by conjugating two CPT molecules onto a hydrophilic segment can associate into filamentous nanostructures in water. Our results suggest that these SAPD exhibit much greater efficacy against primary brain cancer cells relative to that of irinotecan, a clinically used CPT prodrug. We believe these findings open a new avenue for rational design of supramolecular prodrugs for cancer treatment.
Role for Inducible Costimulator in Control ofSalmonella entericaSerovar Typhimurium Infection in Mice (2006)

Inducible costimulator (ICOS) is expressed on activated T cells and plays a key role in sustaining and enhancing the effector function of CD4 T cells. Given the function of this molecule in sustaining T-cell responses, we reasoned that ICOS might play an important role in a prolonged infection model, such as Salmonella infection of mice. To test this hypothesis, wild-type (WT) and ICOS-deficient (ICOS-/-) mice were infected systemically with a Salmonella enterica serovar Typhimurium strain expressing the chicken ovalbumin gene (Salmonella-OVA). ICOS-/- mice exhibited greater splenomegaly than WT mice and showed delayed bacterial clearance. The acquired immune response in this model was slow to develop. Maximal T-cell responses to Salmonella-OVA were detected at 3 weeks postinfection in both WT and ICOS-/- mice. CD4 T-cell-dependent gamma interferon production and a class switch to immunoglobulin G2a were severely reduced in ICOS-/- mice. ICOS-/- mice also exhibited a substantial defect in antigen-specific CD8 T-cell responses. In vitro, the effect of anti-ICOS on CD8 T-cell division was greater when CD8 T cells rather than CD4 T cells expressed ICOS, suggesting that the in vivo effects of ICOS on CD8 T cells could be direct. Taken together, these studies show that ICOS plays a critical role in control of Salmonella infection in mice, with effects on antibody, Th1, and CD8 T-cell responses.
CSK: a protein-tyrosine kinase involved in regulation of src family kinases. (1991)

The functions of src family protein-tyrosine kinases are thought to be regulated negatively by the phosphorylation of highly conserved tyrosine residues close to their carboxyl termini. Recently we have purified and cloned a protein-tyrosine kinase (designated as CSK) that can specifically phosphorylate the negative regulatory site of p60c-src. To elucidate the relationship between CSK and other types of src family kinases, we investigated the tissue distribution of CSK and examined whether CSK could phosphorylate the negative regulatory sites of src family kinases other than p60c-src. Western blot analysis indicated that CSK was enriched at the highest level in lymphoid tissues in which the expression of p60c-src is considerably lower than those of other types of src family kinases. CSK phosphorylated p56lyn and p59fyn, which are known to be expressed in lymphoid tissues at a relatively high level. The putative regulatory site, tyrosine 508, was found to be essential for phosphorylation in p56lyn, and the kinase activities of these src family kinases were repressed by phosphorylation with CSK. These findings raise the possibility that CSK might act as a universal regulator for src family kinases.
The caspase inhibitor z-VAD is more effective than CD18 adhesion blockade in reducing muscle ischemia-reperfusion injury: implication for clinical trials (2002)

Ischemia-reperfusion (I/R) leads to organ injury and organ dysfunction in a variety of clinical disorders. Preclinical investigations examining leukocyte adhesion molecules in I/R provided overwhelming evidence that blocking the function of leukocyte adhesion molecules would be highly effective in improving outcome in clinically relevant diseases. Unfortunately, all 9 of the recently completed phase 2 and 3 clinical trials examining antiadhesion therapy have failed. In this report, we show that a modest increase in ischemic time results in conversion from a CD18-dependent to a CD18-independent injury. This fundamental change in the mechanism of injury can be reduced by inhibition of caspases leading to blockade of apoptosis. Muscle injury resulting from aortic clamping was measured by release of creatine kinase. I/R injury following ischemia of 60 minutes or less and 3 hours of reperfusion was significantly reduced by pretreatment with anti-CD18 monoclonal antibody. However, 90 minutes of ischemia resulted in a marked increase in injury that was not reduced by CD18 blockade. Importantly, the injury resulting from 90 or 120 minutes of ischemia was reduced by the pancaspase inhibitor z-VAD. We propose that the length of ischemia can result in a fundamental change in the mechanism of injury and that all preclinical investigations of I/R must be evaluated with increasing ischemia if they are to model the clinical disease. The result showing CD18-independent I/R injury is not unique; likewise, protection by caspase inhibitors is not unique. However, we show for the first time that caspase inhibitors are effective when CD18 blockade is not.
Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats. (1985)

We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of GM2-gangliosidosis type II. Histologic and ultra-structural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of GM2-gangliosidosis which is similar to but different from the only other known feline model.
Characterization and biodistribution of recombinant and recombinant/chimeric constructs of monoclonal antibody B72.3. (1989)

B72.3 is a murine monoclonal antibody (IgG1) that recognizes a tumor-associated glycoprotein, termed TAG-72. B72.3 has been shown, using a variety of methodologies, to have a high degree of selective reactivity for colorectal, ovarian, lung, and breast carcinomas. Radiolabeled B72.3 has been administered both i.v. and i.p. in patients with colorectal and ovarian cancer as well as other carcinomas and has been shown to selectively bind to approximately 70-80% of metastatic lesions. Greater than 50% of the patients that have been treated with B72.3 have developed an immunological response to murine IgG after a single injection. In an attempt to minimize the immune response of these patients to the administered murine monoclonal antibody, we developed a recombinant form of the murine B72.3 as well as a recombinant/chimeric antibody, using the variable regions of the murine B72.3 and human heavy chain (gamma 4) and light chain (kappa) constant regions. We report here that both the recombinant B72.3 [rB72.3] and the recombinant/chimeric B72.3 [cB72.3(gamma 4)] IgGs maintain the tissue binding and idiotypic specificity of the native murine IgG. The native B72.3, rB72.3, and cB72.3(gamma 4) IgGs were radiolabeled and the biodistribution of these IgGs was studied in athymic mice bearing human colon carcinoma xenografts (LS-174T). Differences were observed between the cB72.3(gamma 4) and the native B72.3 in the percentage of injected dose/g that localized in the tumor. The somewhat lower absolute amounts of the cB72.3(gamma 4) in the tumor are mostly likely due to the observed more rapid clearance from the blood and body of the mouse as compared to the native B72.3 and rB72.3. All three forms [native B72.3, rB72.3, and cB72.3(gamma 4)] of the IgG, however, were able to localize the colon tumor with similar radiolocalization indices [percentage of injected dose/g in tumor divided by the percentage of injected dose/g in normal tissue].
Highly reliable nickel-tin transient liquid phase bonding technology for high temperature operational power electronics in electrified vehicles (2012)

This paper presents an approach to nickel-tin transient liquid phase (TLP) bonding that provides high reliability for high temperature operational power electronics in electrified vehicles. The need for automotive power electronics to operate at high temperature presents significant challenges in terms of the packaging and bonding technology used. Transient liquid phase (TLP) bonding is one attachment approach that addresses these challenges. The Ni/Sn TLP bonding process exhibits a number of desirable characteristics, including a good CTE match with silicon and silicon carbide, popularity in conventional power electronics, low cost, and uniform alloy formation. The work herein presents a Ni/Sn TLP bonding technology (ready for high temperature operation up to 200°C) as applied to large size silicon power devices (12 mm × 9 mm). Analysis indicates that the resulting bondline is uniformly composed of Ni <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> Sn <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> alloy throughout. This bonding approach has exhibited excellent reliability for bonded devices after 1000 thermal cycles from -40 to 200°C.
Intraoperative Optical Spectroscopy Identifies Infiltrating Glioma Margins with High Sensitivity (2005)

We have developed a handheld, optical spectroscopic device that may be used rapidly and in near real time with high sensitivity and reproducibility as an optical tissue discrimination tool in glioma surgery.
Specific molecular activities of recombinant and hybrid leukocyte interferons. (1982)

Hybrid interferon DNA recombinants were constructed from the IFLrA and IFLrD leukocyte interferon-coding sequences. Each of the hybrid interferons was purified with the use of a monoclonal antibody to human leukocyte interferon. Three amino acid residues were identified, one or all of which function to potentiate antiviral activity on feline cells and reduce activity on human cells. Because at sufficiently high concentrations human interferons can interact with mouse and rat receptors, it is apparent that the species barrier is only relative and that interferons can be forced into heterologous receptors by mass action. In addition, the specific molecular antiviral and antiproliferative activities (molecules of interferon/cell required for a specific effect) for each of these interferons were determined. The specific molecular activities permit an accurate comparison of the efficacy of different interferons for a specific effect. Because the ratios of antiproliferative/antiviral activity of these interferons vary over a 12-fold range, it appears that the antiviral and antiproliferative activities are promulgated through different mechanisms. To account for these results, it is proposed that there are at least two distinct interferon receptors on cells.
Control method and snubber selection for a 5 MW wind turbine single active bridge DC/DC converter (2007)

In this paper the design and control aspects of the single active bridge DC/DC converter are investigated for the application to be used in a 5 MW wind turbine. The control of the converter is discussed as well as different design considerations as turn-off snubber circuits and leakage inductance of the transformer. It is found that the variable frequency control with a turn-off snubber capacitor gives the lowest losses for the application in a wind turbine. The losses for the single active bridge converter using variable frequency control is 3.2 - 3.8 % of the input power, depending on the position in the wind farm, compared to 3.8 - 4.1 % for the converter with constant frequency control.
Enrichment of Human CD4+ Vα24/Vβ11 Invariant NKT Cells in Intrahepatic Malignant Tumors (2009)

Invariant NKT cells (iNKT cells) recognize glycolipid Ags via an invariant TCR alpha-chain and play a central role in various immune responses. Although human CD4(+) and CD4(-) iNKT cell subsets both produce Th1 cytokines, the CD4(+) subset displays an enhanced ability to secrete Th2 cytokines and shows regulatory activity. We performed an ex vivo analysis of blood, liver, and tumor iNKT cells from patients with hepatocellular carcinoma and metastases from uveal melanoma or colon carcinoma. Frequencies of Valpha24/Vbeta11 iNKT cells were increased in tumors, especially in patients with hepatocellular carcinoma. The proportions of CD4(+), double negative, and CD8alpha(+) iNKT cell subsets in the blood of patients were similar to those of healthy donors. However, we consistently found that the proportion of CD4(+) iNKT cells increased gradually from blood to liver to tumor. Furthermore, CD4(+) iNKT cell clones generated from healthy donors were functionally distinct from their CD4(-) counterparts, exhibiting higher Th2 cytokine production and lower cytolytic activity. Thus, in the tumor microenvironment the iNKT cell repertoire is modified by the enrichment of CD4(+) iNKT cells, a subset able to generate Th2 cytokines that can inhibit the expansion of tumor Ag-specific CD8(+) T cells. Because CD4(+) iNKT cells appear inefficient in tumor defense and may even favor tumor growth and recurrence, novel iNKT-targeted therapies should restore CD4(-) iNKT cells at the tumor site and specifically induce Th1 cytokine production from all iNKT cell subsets.
Cloning and primary structure of neurocan, a developmentally regulated, aggregating chondroitin sulfate proteoglycan of brain. (1992)

We have obtained the complete coding sequence of neurocan, a chondroitin sulfate proteoglycan of rat brain which is developmentally regulated with respect to its molecular size, concentration, carbohydrate composition, sulfation, and immunocytochemical localization. Two degenerate oligonucleotides, based on amino acid sequence data from the proteoglycan isolated from adult brain by immunoaffinity chromatography with the 1D1 monoclonal antibody, were used as sense and antisense primers in the polymerase chain reaction with a brain cDNA library as template to generate an unambiguous cDNA probe. A second probe for the N-terminal portion of the early postnatal form of the proteoglycan was obtained by reverse transcription/polymerase chain reaction. The composite sequence of overlapping cDNA clones is 5.2-kilobases (kb) long, including 1.3 kb of 3'-untranslated sequence and 76 base pairs of 5'-untranslated sequence. An open reading frame of 1257 amino acids encodes a protein with a molecular mass of 136 kDa containing 10 peptide sequences present in the adult and/or early postnatal brain proteoglycans. The deduced amino acid sequence revealed a 22-amino acid signal peptide followed by an immunoglobulin domain, tandem repeats characteristic of the hyaluronic acid-binding region of aggregating proteoglycans, and an RGDS sequence. The C-terminal portion (amino acids 951-1215) has approximately 60% identity to regions in the C termini of the fibroblast and cartilage proteoglycans, versican and aggrecan, including two epidermal growth factor-like domains, a lectin-like domain, and a complement regulatory protein-like sequence. The central 595-amino acid portion of neurocan has no homology with other reported protein sequences. The proteoglycan contains six potential N-glycosylation sites and 25 potential threonine O-glycosylation sites. In the adult form of the proteoglycan (which represents the C-terminal half of neurocan) a single 32-kDa chondroitin 4-sulfate chain is linked at serin-944, whereas three additional potential chondroitin sulfate attachment sites (only two of which are utilized) are present in the larger proteoglycan species. A probe corresponding to a region of neurocan having no homology with versican or aggrecan hybridized with a single band at approximately 7.5 kb on Northern blots of mRNA from both 4-day and adult rat brain (but not with muscle, kidney, liver, or lung mRNA), indicating that the 1D1 proteoglycan of adult brain, containing a 68-kDa core protein, is generated by a developmentally regulated in vivo proteolytic processing of the 136-kDa species which is predominant in early postnatal brain.(ABSTRACT TRUNCATED AT 400 WORDS)
Process and design considerations for surface micromachined beams for a tuneable interferometer array in silicon (2002)

A special surface micromachining process, using oxidized polysilicon sacrificial layer and poly-nitride/poly membranes, has been developed for realizing the monolithic integration of light modulators with silicon devices. The design and processing considerations for developing a compact micromachined silicon Fabry-Perot interferometer are presented. Initial tests have shown that these micromachined membranes represent a compact and effective light modulating method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>