gebhart/patrepeval huggingface dataset:
Comparison of the Antibodies in Lymphocyte Supernatant and Antibody-Secreting Cell Assays for Measuring Intestinal Mucosal Immune Response to a Novel Oral Typhoid Vaccine (M01ZH09) (2005)

Antibody-secreting cell (ASC) and antibodies in lymphocyte supernatant (ALS) assays are used to assess intestinal mucosal responses to enteric infections and vaccines. The ALS assay, performed on cell supernatants, may represent a convenient alternative to the more established ASC assay. The two methods, measuring immunoglobulin A to Salmonella enterica serovar Typhi lipopolysaccharide, were compared in volunteers vaccinated with a live-attenuated typhoid vaccine M01ZH09. The specificity of the ALS assay compared to the ASC assay was excellent (100%), as was sensitivity (82%). The ALS assay was less sensitive than the ASC assay at <or=42 spots/10(6) peripheral blood lymphocytes.
Suicidal age and childhood onychophagia among neurotic veterans (1978)

Investigated the relationship between childhood onychophagia (fingernail biting) and the suicidal and non-suicidal mean age among 60 hospitalized neurotic veterans. The results show no significant mean age difference between suicidal and non-suicidal veterans; neither does the childhood onychophagia variable "focal suicide" significantly lower either the mean age of suicidal veterans or the mean age of non-suicidal veterans.
Isolation, characterization and synthesis of peptides from human fibrinogen that block the staphylococcal clumping reaction and construction of a synthetic clumping particle (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation, characterization and synthesis of peptides from human fibrinogen that block the staphylococcal clumping reaction and construction of a synthetic clumping particleDonna D. Strong, Andrew P. Laudano, Jacek Hawiger, and Russell F. DoolittleCite this: Biochemistry 1982, 21, 6, 1414–1420Publication Date (Print):March 16, 1982Publication History Published online1 May 2002Published inissue 16 March 1982https://pubs.acs.org/doi/10.1021/bi00535a048https://doi.org/10.1021/bi00535a048research-articleACS PublicationsRequest reuse permissionsArticle Views80Altmetric-Citations51LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity (1987)

We have shown in a murine model system for acute, lethal cytomegalovirus (CMV) disease in the immunocompromised natural host that control of virus multiplication in tissues, protection from virus-caused tissue destruction, and survival are mediated by virus-specific CD8+ CD4-T lymphocytes. Protection from a lethal course of disease did not result in a rapid establishment of virus latency, but led to a long-lasting, persistent state of infection. The CD8- CD4+ subset of T lymphocytes was not effective by itself in controlling murine CMV (MCMV) multiplication in tissue or essential for the protective function of the CD8+ CD4- effector cells. The antiviral efficacy of the purified CD8+ CD4- subset was not impaired by preincubation with fibroblasts that presented viral structural antigens, but was significantly reduced after depletion of effector cells specific for the nonstructural immediate-early antigens of MCMV, which are specified by the first among a multitude of viral genes expressed during MCMV replication in permissive cells. Thus, MCMV disease provides the first example of a role for nonstructural herpesvirus immediate-early antigens in protective immunity.
A Muscle-specific Promoter Directs Pitx3 Gene Expression in Skeletal Muscle Cells (2007)

The Pitx homeobox transcription factor genes have been implicated in different developmental processes, including determination of hind limb identity for Pitx1, left-right asymmetry for Pitx2, and eye development and survival of midbrain dopaminergic neurons for Pitx3. Pitx1 and Pitx2 have partly redundant activities in craniofacial development, including in pituitary organogenesis, as indicated by their names. These genes also exhibit redundant activities in the control of hind limb bud growth. Recent studies have shown expression of the three Pitx genes in muscle, with Pitx3 being the most widely expressed in all skeletal muscles. We now report the identification of a muscle-specific promoter within the Pitx3 gene that is situated between the first exon for eye and brain expression and exon 2 that contains the initiator ATG codon. Sequences proximal to this muscle-specific exon 1 are essential and sufficient to confer muscle-specific expression in transgenic mice, they are responsive to myogenic basic helix-loop-helix regulatory factors, and they recruit these factors in vivo. In agreement with exclusive use of the muscle-specific promoter in aphakia mice that are deleted of the brain promoter, the trimethyl-lysine 4 histone H3 promoter signature shifts to this promoter in embryonic day 13 ak limb bud muscle cells. Myogenic basic helix-loop-helix regulatory factor activation of Pitx3 transcription may be part of a positive feedback loop contributing to establishment of the myogenic program.
Wetting in Color: Colorimetric Differentiation of Organic Liquids with High Selectivity (2011)

Colorimetric litmus tests such as pH paper have enjoyed wide commercial success due to their inexpensive production and exceptional ease of use. Expansion of colorimetry to new sensing paradigms is challenging because macroscopic color changes are seldom coupled to arbitrary differences in the physical/chemical properties of a system. Here we present in detail the design of a "Wetting In Color Kit" (WICK), an inexpensive and highly selective colorimetric indicator for organic liquids that exploits chemically encoded inverse-opal photonic crystals to project minute differences in liquids' wettability to macroscopically distinct, easy-to-visualize structural color patterns. We show experimentally and corroborate with theoretical modeling using percolation theory that the highly symmetric structure of our large-area, defect-free SiO(2) inverse-opal films leads to sharply defined threshold wettability for liquid infiltration, occurring at intrinsic contact angles near 20° with an estimated resolution smaller than 5°. The regular structure also produces a bright iridescent color, which disappears when infiltrated with liquid, naturally coupling the optical and fluidic responses. To deterministically design a WICK that differentiates a broad range of liquids, we introduced a nondestructive quality control procedure to regulate the pore structure and developed two new surface modification protocols, both requiring only silanization and selective oxidation. The resulting tunable, built-in horizontal and vertical chemistry gradients let us tailor the wettability threshold to specific liquids across a continuous range. With patterned oxidation as a final step, we control the shape of the liquid-specific patterns displayed, making WICK easier to read. Using these techniques, we demonstrate the applicability of WICKs in several exemplary systems that colorimetrically distinguish (i) ethanol-water mixtures varying by only 2.5% in concentration; (ii) methanol, ethanol, and isopropyl alcohol; (iii) hexane, heptane, octane, nonane, and decane; and (iv) samples of gasoline (regular unleaded) and diesel. As wetting is a generic fluidic phenomenon, we envision that WICK could be suitable for applications in authentication or identification of unknown liquids across a broad range of industries.
Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer (2007)

Mycobacterium ulcerans is found in aquatic ecosystems and causes Buruli ulcer in humans, a neglected but devastating necrotic disease of subcutaneous tissue that is rampant throughout West and Central Africa. Here, we report the complete 5.8-Mb genome sequence of M. ulcerans and show that it comprises two circular replicons, a chromosome of 5632 kb and a virulence plasmid of 174 kb. The plasmid is required for production of the polyketide toxin mycolactone, which provokes necrosis. Comparisons with the recently completed 6.6-Mb genome of Mycobacterium marinum revealed >98% nucleotide sequence identity and genome-wide synteny. However, as well as the plasmid, M. ulcerans has accumulated 213 copies of the insertion sequence IS2404, 91 copies of IS2606, 771 pseudogenes, two bacteriophages, and multiple DNA deletions and rearrangements. These data indicate that M. ulcerans has recently evolved via lateral gene transfer and reductive evolution from the generalist, more rapid-growing environmental species M. marinum to become a niche-adapted specialist. Predictions based on genome inspection for the production of modified mycobacterial virulence factors, such as the highly abundant phthiodiolone lipids, were confirmed by structural analyses. Similarly, 11 protein-coding sequences identified as M. ulcerans-specific by comparative genomics were verified as such by PCR screening a diverse collection of 33 strains of M. ulcerans and M. marinum. This work offers significant insight into the biology and evolution of mycobacterial pathogens and is an important component of international efforts to counter Buruli ulcer.
Equine herpesvirus type 1 (2012)

Equine herpesvirus type 1 (EHV-1) remains a severe threat to horse industry despite widespread vaccination. The control of EHV-1 infection is mainly dependent on cellular immunity that is mediated by CD8+ cytotoxic T lymphocytes (CTLs). EHV-1, as its relatives in the large Herpesviridae family, has evolved strategies to evade CTL immunity by interfering with the major histocompatibility complex class I (MHC-I) antigen presentation pathway. In the first part of this thesis, we identified a novel immunomodulatory protein involved in the downregulation of MHC-I from the cell surface. The responsible viral protein, pUL56, which is encoded by EHV-1 open reading frame 1 (ORF1), is a phosphorylated early protein, which is expressed as different forms and predominantly localizes to Golgi-derived membranes. In addition, the transmembrane (TM) domain of pUL56 was shown to be indispensable for correct subcellular localization and proper function. The function of pUL56 was independent of that mediated by pUL49.5, a viral protein known to inhibit the transporter associated with antigen processing (TAP) and encoded by EHV-1 and related viruses. Surprisingly, pUL56 by itself was not capable of downregulating MHC-I and likely needs (an)other unidentified viral protein(s) to perform this action. EHV-1 has recently been demonstrated to be a promising viral vehicle for delivery of foreign antigens. In the second part of the thesis, we utilized ORF1 as the locus for the insertion of foreign genes, more specifically the VP2 and/or VP5 genes of bluetongue virus serotype 8 (BTV-8). BTV-8 can infect most domestic and wild ruminants species and was responsible for an epizootic in northern Europe in 2006. The EHV-1 recombinant viruses generated stably expressed the transgenes and grew with kinetics that were identical to those of parental virus in vitro. After immunization of mice, a BTV-8-specific neutralizing antibody response was elicited. In a challenge experiment using a lethal dose of BTV-8, 100% of interferonreceptor- deficient (IFNAR-/-) mice vaccinated with the recombinant EHV-1 carrying both VP2 and VP5, but not VP2 alone, survived. VP7 was not included in the vectored vaccines and was successfully used as a marker for differentiating infected from vaccinated animals (DIVA). In conclusion, EHV-1 ORF1-encoded pUL56 is a novel immune evasion protein involved in the interference of MHC-I surface expression, but is unable to perform its function outside of the context of viral infection. An EHV-I recombinant carrying VP2 and VP5 of BTV-8 in the ORF1 locus is capable of eliciting protective immunity in a murine infection model and as such may be an alternative for BTV vaccination strategies.
How strict is the correlation between STIM1 and Orai1 expression, puncta formation, andICRACactivation? (2008)

Stromal interaction molecule 1 (STIM1) and Orai1 have been identified as crucial elements of the store-operated Ca(2+) entry (SOCE) pathway, but the mechanism of their functional interaction remains controversial. It is now well established that, upon depletion of the stores, both molecules can accumulate and colocalize in specific areas (puncta) where the endoplasmic reticulum comes in close proximity to the plasma membrane. Some models propose a direct interaction between STIM1 and Orai1 as the most straightforward mechanism for signal transduction from the stores to the plasma membrane. To test some of the predictions of a conformational coupling model, we assessed how tight the relationships are between STIM1 and Orai1 expression, puncta formation, and SOCE activation. Here we present evidence that STIM1 accumulates in puncta equally well in the presence or absence of Orai1 expression, that STIM1 accumulation is not sufficient for Orai1 accumulation in the same areas, and that normal Ca(2+) release-activated Ca(2+) current (I(CRAC)) can be activated in STIM1-deficient cells. These data challenge the idea of direct conformational coupling between STIM1 and Orai1 as a viable mechanism of puncta formation and SOCE activation and uncover greater complexity in their relationship, which may require additional intermediate elements.
Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing # (2008)

This work is a comprehensive analysis of 80% of ABCB11 missense mutations and single-nucleotide polymorphisms at pre-mRNA splicing and protein processing/functional levels. We show that aberrant pre-mRNA splicing occurs in a considerable number of cases, leading to reduced levels of normal mRNA. Thus, primary defects at either the protein or the mRNA level (or both) contribute significantly to BSEP deficiency. These results will help to develop mutation-specific therapies for children and adults suffering from intrahepatic cholestasis due to BSEP deficiency.
Histologic Fate and Endothelial Changes of Distended and Nondistended Vein Grafts (1976)

Sixty-two autogenous cephalic vein segments were grafted into the femoral arteries of 31 mongrel dog: the left side receiving non-distended (control) grafts and the right side distended (experimental) grafts. Distending media were heparinized blood and saline. Veins were distended at 600 mm Hg for 2 minutes. Specimens were taken at intervals from 15 minutes to 3 months, and were studied by gross inspection, surface observations (light scanning stereoscope to X 70 scanning electron microscope to x 6,000) and routine histologic techniques (light microscope to X 1000). In general, grafting of veins in the arterial system was followed by progressive degenerative changes in all layers of the vein, including endothelial cell involution, desquamation and re-endothelialization. Often a variable degree of subendothelial fibrous and/or myoepithelial proliferation occurred which might compromise even a lumen lined by healthy endothelium. Distention caused these changes to occur earlier (2–4 weeks) and to be more pronounced. Distention with saline caused more damage to the endothelium than did distention with blood. We conclude that preimplant distention of vein grafts (to overcome spasm) should be employed sparingly, as it adversely affects the endothelial covering of the flow surface, accelerates the development of degenerative changes, and may predispose the graft to early thrombotic complications.
Coexpression and assembly of myosin heavy chain and myosin light chain in Escherichia coli. (1988)

A fragment of the Dictyostelium discoideum myosin heavy chain gene representing heavy meromyosin was coexpressed in Escherichia coli with the entire essential myosin light chain from the scallop. The expressed myosin heavy chain and essential myosin light chain copurify through ammonium sulfate fractionation, anion exchange, and gel filtration chromatography. The purified complex consists of about 1 mol of light chain per mol of heavy chain. This stoichiometry, which is that of native myosin, suggests that no special eukaryotic machinery is required for coassembly of these two proteins. By coexpressing different myosin heavy chain and myosin light chain combinations, it should be possible to study various isoforms of these two proteins, which are both products of multigene families in mammals. E. coli is thus an ideal system in which to study expression and multimeric assembly of individual components of the eukaryotic contractile apparatus.
Krylov-Secant Methods for Accelerating the Solution of Fully Implicit Formulations (2005)

Abstract The present work is devoted to accelerate the nonlinear convergence of Newton-Krylov methods for solving fully implicit formulation in multiphase flow. The basic approach is to perform secant (Broyden) updates restricted to the Krylov subspace generated by the GMRES iterative solver. This approach is introduced as Krylov-secant methods. One of the most attractive features of these methods is to perform a sequence of rank-one updates without explicitly recalling the computation or action of the Jacobian matrix. Implications of these updates in line-search globalization strategies, computation of dynamic tolerances (forcing terms) and in the use of preconditioning strategies are presented. Numerical results show significant improvements over traditional implementations especially in those cases where nonlinearities increase due to stringent pressure and saturation changes.
Development of Inhibitors of the Aspartyl Protease Renin for the Treatment of Hypertension (2006)

Renin is the rate-limiting enzyme in the renin-angiotensin-aldosterone system (RAS) which controls blood pressure and volume. The biological function of renin is to cleave the N-terminus of angiotensinogen releasing the decapeptide, angiotensin I (ANGI). Subsequently, angiotensin I is further processed by the angiotensin converting enzyme (ACE) to produce angiotensin II (ANGII). The RAS cascade is a major target for the clinical management of hypertension. Current clinical treatments include angiotensin converting enzyme inhibitors (ACEi) and ANGII receptor blockers (ARBs). As the rate-limiting enzyme in ANGII production, renin inhibitors have been pursued as an additional class of anti-hypertensives. Clinical studies conducted with renin inhibitors have shown them to be as effective as ACE inhibitors in lowering blood pressure. Most importantly, inhibitors of renin may have a number of potential advantages over ACEi and ARBs. Renin is specific for angiotensinogen and will not carry the ancillary pharmacology associated with ACEi or ARBs. To date, no renin inhibitors have made it to market. The development of these inhibitors has been hindered by poor bioavailability and complex synthesis. However, despite the pharmacokinetic challenges of designing renin inhibitors, the enzyme remains a promising target for the development of novel treatments for hypertension. This review will consist of an overview of renin biology, the pharmacology of renin and RAS and focus in on renin as a target for blood pressure regulation. We also cover the evaluation of renin inhibitors in animal models and clinical studies. Presently a number of new generation inhibitors of renin are in development with at least one in the clinic and these will be discussed. Finally we will discuss what might distinguish renin inhibitors from current therapeutic options and discuss other therapeutic indications renin inhibitors might have.
Bezielle Selectively Targets Mitochondria of Cancer Cells to Inhibit Glycolysis and OXPHOS (2012)

Bezielle (BZL101) is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. Bezielle is an aqueous extract from the herb Scutellaria barbata. We have reported previously that Bezielle was selectively cytotoxic to cancer cells while sparing non-transformed cells. In tumor, but not in non-transformed cells, Bezielle induced generation of ROS and severe DNA damage followed by hyperactivation of PARP, depletion of the cellular ATP and NAD, and inhibition of glycolysis. We show here that tumor cells' mitochondria are the primary source of reactive oxygen species induced by Bezielle. Treatment with Bezielle induces progressively higher levels of mitochondrial superoxide as well as peroxide-type ROS. Inhibition of mitochondrial respiration prevents generation of both types of ROS and protects cells from Bezielle-induced death. In addition to glycolysis, Bezielle inhibits oxidative phosphorylation in tumor cells and depletes mitochondrial reserve capacity depriving cells of the ability to produce ATP. Tumor cells lacking functional mitochondria maintain glycolytic activity in presence of Bezielle thus supporting the hypothesis that mitochondria are the primary target of Bezielle. The metabolic effects of Bezielle towards normal cells are not significant, in agreement with the low levels of oxidative damage that Bezielle inflicts on them. Bezielle is therefore a drug that selectively targets cancer cell mitochondria, and is distinguished from other such drugs by its ability to induce not only inhibition of OXPHOS but also of glycolysis. This study provides a better understanding of the mechanism of Bezielle's cytotoxicity, and the basis of its selectivity towards cancer cells.
Crucial role of interleukin‐10/interleukin‐12 balance in the regulation of the type 2 T helper cytokine response in reactive arthritis (1997)

These data indicate that a Th2 cytokine pattern predominates in the joints of patients with ReA. Since Th1 cytokines are necessary for the elimination of ReA-associated bacteria, Th2 cytokines might contribute to bacterial persistence in the joint. Therefore, the IL-10/IL-12 balance appears to be crucial for regulation of the cytokine pattern in the joints of patients with ReA.