gebhart/patrepeval huggingface dataset:
Structure and chromosomal location of the human CD6 gene: detection of five human CD6 isoforms (1997)

The CD6 protein has been shown to play important roles in T cell costimulation and adhesion. Recently, variably spliced isoforms of CD6 mRNA have been identified in both human and murine T cells. Here we report on the genomic organization of the human CD6 gene, its chromosomal localization, and the characterization of novel isoforms. Human CD6 is encoded by at least 13 exons. The amino terminal signal sequence, extracellular region, and transmembrane domain are encoded by seven exons, while the cytoplasmic domain of CD6 is encoded by six exons. Each of the three extracellular scavenger receptor cysteine-rich domains is encoded by a separate exon. Fluorescence in situ hybridization studies and screening of a chromosome-specific YAC (yeast artificial chromosome) library revealed that the gene encoding CD6 is located on chromosome 11 at 11q13 in close proximity to the gene encoding the related molecule CD5 and within 600 kb of CD20. Analysis of mRNA transcripts encoding CD6 isolated from mitogen-activated PBMC and from B cells obtained from patients with chronic lymphocytic leukemia revealed the presence of at least five different CD6 transcripts. These transcripts arise via variable splicing of exons encoding the cytoplasmic domain of CD6. The existence of these isoforms suggests that signaling through CD6 could be regulated via alternative splicing of cytoplasmic encoding exons.
Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis (2005)

CD4+CD25+ regulatory T cells (T reg cells) play a key role in controlling autoimmunity and inflammation. Therefore, therapeutic agents that are capable of elevating numbers or increasing effector functions of this T cell subset are highly desirable. In a previous report we showed that a superagonistic monoclonal antibody specific for rat CD28 (JJ316) expands and activates T reg cells in vivo and upon short-term in vitro culture. Here we demonstrate that application of very low dosages of the CD28 superagonist into normal Lewis rats is sufficient to induce T reg cell expansion in vivo without the generalized lymphocytosis observed with high dosages of JJ316. Single i.v. administration of a low dose of the CD28 superagonist into Dark Agouti (DA) rats or Lewis rats that suffered from experimental autoimmune encephalomyelitis (EAE) proved to be highly and equally efficacious as high-dose treatment. Finally, we show that T reg cells that were isolated from CD28-treated animals displayed enhanced suppressive activity toward myelin basic protein-specific T cells in vitro, and, upon adoptive transfer, protected recipients from EAE. Our data indicate that this class of CD28-specific monoclonal antibodies targets CD4+CD25+ T reg cells and provides a novel means for the effective treatment of multiple sclerosis and other autoimmune diseases.
Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase (1997)

gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, is synthesized by two glutamate decarboxylase isoforms, GAD65 and GAD67. The separate role of the two isoforms is unknown, but differences in saturation with cofactor and subcellular localization suggest that GAD65 may provide reserve pools of GABA for regulation of inhibitory neurotransmission. We have disrupted the gene encoding GAD65 and backcrossed the mutation into the C57BL/6 strain of mice. In contrast to GAD67-/- animals, which are born with developmental abnormalities and die shortly after birth, GAD65-/- mice appear normal at birth. Basal GABA levels and holo-GAD activity are normal, but the pyridoxal 5' phosphate-inducible apo-enzyme reservoir is significantly decreased. GAD65-/- mice develop spontaneous seizures that result in increased mortality. Seizures can be precipitated by fear or mild stress. Seizure susceptibility is dramatically increased in GAD65-/- mice backcrossed into a second genetic background, the nonobese diabetic (NOD/LtJ) strain of mice enabling electroencephalogram analysis of the seizures. The generally higher basal brain GABA levels in this backcross are significantly decreased by the GAD65-/- mutation, suggesting that the relative contribution of GABA synthesized by GAD65 to total brain GABA levels is genetically determined. Seizure-associated c-fos-like immunoreactivity reveals the involvement of limbic regions of the brain. These data suggest that GABA synthesized by GAD65 is important in the dynamic regulation of neural network excitability, implicate at least one modifier locus in the NOD/LtJ strain, and present GAD65-/- animals as a model of epilepsy involving GABA-ergic pathways.
Effect of positive end-expiratory pressure on right and left ventricular function in patients with the adult respiratory distress syndrome. (1987)

The predominant mechanism of the cardiac output reduction associated with positive end-expiratory pressure (PEEP) is unclear. Reported possibilities include decreased systemic venous return, increased pulmonary vascular resistance, or change in ventricular contractility. We investigated this question by studying 9 patients with the adult respiratory distress syndrome (ARDS) during PEEP application. We used an equilibrium radionuclide angiography method modified for improved right ventricular imaging to evaluate changes in left and right ventricular volume and contractility. Thermodilution cardiac output and stroke volume progressively declined (27 and 33% mean decrease, respectively) with increasing increments of PEEP. Right and left ventricular end diastolic counts, reflecting volume, also progressively diminished as PEEP increased (38 and 27% mean decrease in RV and LV counts, respectively; p less than 0.001 for both ventricles). A slight upward trend in ejection fraction was found for both ventricles. These findings support the concept that during PEEP application the reduction in cardiac output is due to biventricular reduction in blood volume. This biventricular volume reduction is compatible with either preload reduction to both ventricles because of impeded venous return or to change in ventricular configuration caused by external compression of both ventricles.
Real-time PCR for single-cell genotyping in sickle cell and thalassemia syndromes as a rapid, accurate, reliable, and widely applicable protocol for preimplantation genetic diagnosis (2004)

Sickle-cell and beta-thalassemia syndromes are priority genetic diseases for prevention programs involving population screening with the option of prenatal diagnosis for carrier couples. Preimplantation genetic diagnosis (PGD) represents a specialized alternative to prenatal diagnosis and is most appropriately used for couples with an unsuccessful reproductive history and/or undergoing assisted reproduction. However, clinical application of PGD has been hindered by difficulties in reliably transferring molecular diagnostic protocols to the single-cell level. We standardized and validated a protocol involving first-round multiplex PCR, amplifying the region of the beta-globin gene containing most of the common disease mutations world-wide and two unlinked microsatellite markers (GABRB3 and D13S314), followed by: 1) analysis of beta-globin genotypes with real-time PCR and 2) microsatellite sizing to exclude chance contamination. The protocol was standardized on 100 single lymphocytes from a beta-thalassemia heterozygote, including 15 artificially contaminated samples, the latter demonstrated through microsatellite analysis. PCR failure and allele drop-out (ADO) were observed in one (uncontaminated) sample each (1.2%). A pilot study in six clinical PGD cycles with five different beta-globin genotype interactions achieved results (in 5-6 hr) in 46 out of 50 single blastomeres (92%), all concordant with results from an established PGD method applied simultaneously; microsatellite analysis detected only parental alleles, excluding contamination. Beta-globin genotypes were also confirmed in two blastomeres through prenatal diagnosis (twin pregnancy), and in 11 out of 12 spare embryos, revealing one incident of ADO. Overall, the protocol proved to be sensitive, accurate, reliable, rapid, and applicable for many genotype interactions, with internal monitoring of contamination, thus fulfilling all requirements for clinical PGD application.
Reduction of Beam-Hardening Artifacts in X-Ray CT (2005)

Our goal is to decrease the importance of beam- hardening artifacts in X-ray computed tomography by address- ing the polyenergetic nature of the X-ray source. We use the same physical model as De Man and al [1]. We next adopt an estimation framework for the reconstruction: the attenuation coefficients are determined by a likelihood-based estimator. This approach leads to minimization of an objective function which exhibits a complex structure. Nonetheless, we develop a numerical procedure with satisfactory numerical efficiency : we use a nonlinear conjugate gradient method. The three major contributions of this communication are : the positivity of the solution ensured by a change of variables, the convergence properties of the algorithm, and a satisfying computation time.
System Isolation and Network Fast Fail Capability in Solaris (1995)

UNIX hosts configured for network operation typically hang, or freeze, when temporarily disconnected from the network. This failure is unacceptable to the user of a mobile host who purposely disconnects the host from the network in order to move it to another location not serviced by a network connection. This paper describes an approach that automatically enables a system to continue to function, in a diminished capacity, when disconnected from the network. 1.0 Introduction - Why is there a problem? Modern computing environments typically consist of a core cluster of servers and many desktop workstations. Together they implement a client-server model of decentralized distributed processing that depends on a robust functional network for successful operation. This type of distributed processing avoids reliance on a particular host and, instead, places the emphasis on the network. In other words, &amp;quot;the network is the computer.&amp;quot; The problem is, if a network operation fails, the system ...
Histopathology of nonalcoholic fatty liver disease (2010)

Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease (NAFLD) are measured. Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD, i.e. nonalcoholic steatohepatitis (NASH) and fibrosis. Included in the lesions of NAFLD are steatosis, lobular and portal inflammation, hepatocyte injury in the forms of ballooning and apoptosis, and fibrosis. However, patterns of these lesions are as distinguishing as the lesions themselves. Liver injury in adults and children due to NAFLD may have different histological patterns. In this review, the rationale for liver biopsy, as well as the histopathological lesions, the microscopically observable patterns of injury, and the differential diagnoses of NAFLD and NASH are discussed.
Finding and understanding bugs in C compilers (2011)

Compilers should be correct. To improve the quality of C compilers, we created Csmith, a randomized test-case generation tool, and spent three years using it to find compiler bugs. During this period we reported more than 325 previously unknown bugs to compiler developers. Every compiler we tested was found to crash and also to silently generate wrong code when presented with valid input. In this paper we present our compiler-testing tool and the results of our bug-hunting study. Our first contribution is to advance the state of the art in compiler testing. Unlike previous tools, Csmith generates programs that cover a large subset of C while avoiding the undefined and unspecified behaviors that would destroy its ability to automatically find wrong-code bugs. Our second contribution is a collection of qualitative and quantitative results about the bugs we have found in open-source C compilers.
Continuously tuned external cavity semiconductor laser (1993)

Continuous tuning (no mode hops) of a grating-tuned external-cavity semiconductor laser by rotation of the grating about a carefully selected point is analyzed and demonstrated using a laser containing a prism beam expander. The analysis predicts the continuous tuning range as a function of pivot-point position and is used to select the point for maximum continuous tuning range. Because dispersive optical elements in the cavity were found to limit the continuous tuning range, the model was modified to include dispersion to first order. The dispersion correction improved the maximum observed tuning range of the 1300-nm-wavelength laser from 600 GHz to nearly 3000 GHz. Details of the cavity and mechanical design as well as pivot-point tolerances are also included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of air pollution on blood pressure and heart rate variability: a panel study of vehicular traffic controllers in the city of São Paulo, Brazil (2004)

This study supplies biological plausibility for observational studies on air pollution-related cardiovascular morbidity and mortality.
Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function (2007)

Retinoid X receptors (RXRalpha, -beta, and -gamma) occupy a central position in the nuclear receptor superfamily, because they form heterodimers with many other family members and hence are involved in the control of a variety of (patho)physiologic processes. Selective RXR ligands, referred to as rexinoids, are already used or are being developed for cancer therapy and have promise for the treatment of metabolic diseases. However, important side effects remain associated with existing rexinoids. Here we describe the rational design and functional characterization of a spectrum of RXR modulators ranging from partial to pure antagonists and demonstrate their utility as tools to probe the implication of RXRs in cell biological phenomena. One of these ligands renders RXR activity particularly sensitive to coactivator levels and has the potential to act as a cell-specific RXR modulator. A combination of crystallographic and fluorescence anisotropy studies reveals the molecular details accounting for the agonist-to-antagonist transition and provides direct experimental evidence for a correlation between the pharmacological activity of a ligand and its impact on the structural dynamics of the activation helix H12. Using RXR and its cognate ligands as a model system, our correlative analysis of 3D structures and dynamic data provides an original view on ligand actions and enables the establishment of mechanistic concepts, which will aid in the development of selective nuclear receptor modulators.
Nickel Allergy in Mice: Enhanced Sensitization Capacity of Nickel at Higher Oxidation States (1999)

Attempts to induce contact hypersensitivity to nickel in mice using, e.g., Ni(II)Cl2 often failed. Here, we report that sensitization was achieved by injecting Ni(II)Cl2 in combination with either CFA or an irritant, such as SDS and PMA, or IL-12, or by administering nickel at higher oxidation states, i.e., Ni(III) and Ni(IV). Although Ni(II), given alone, was ineffective in T cell priming, it sufficed for eliciting recall responses in vivo and in vitro, suggesting that Ni(II) is able to provide an effective signal 1 for T cell activation, but is unable to provide an adequate signal 2 for priming. Immunization of mice with nickel-binding proteins pretreated with Ni(IV), but not with Ni(II), allowed them to generate nickel-specific CD4+ T cell hybridomas. Ni(II) sufficed for restimulation of T cell hybridomas; in this and other aspects as well, the hybridomas resembled the nickel-specific human T cell clones reported in the literature. Interestingly, restimulation of hybridomas did not require the original Ni(IV)-protein complex used for priming, suggesting either that the nickel ions underwent ligand exchange toward unknown self proteins or peptides or that nickel recognition by the TCR is carrier-independent. In conclusion, we found that Ni(III) and Ni(IV), but not Ni(II) alone, were able to sensitize naive T cells. Since both Ni(III) and Ni(IV) can be generated from Ni(II) by reactive oxygen species, released during inflammation, our findings might explain why in humans nickel contact dermatitis develops much more readily in irritated than in normal skin.
Synthesis and Characteristics of Succinic Anhydride- and Disodium Succinate-Terminated Low Molecular Weight Polyethylenes (2009)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTSynthesis and Characteristics of Succinic Anhydride- and Disodium Succinate-Terminated Low Molecular Weight PolyethylenesAnnadanam V. Sesha Sainath, Motoaki Isokawa, Makoto Suzuki, Seiichi Ishii, Sadahiko Matsuura, Naoshi Nagai, and Terunori Fujita*View Author Information Research Center, Mitsui Chemicals, Inc., 580-32 Nagaura, Sodegaura, Chiba 299-0265, Japan*Corresponding author. E-mail: [email protected]Cite this: Macromolecules 2009, 42, 13, 4356–4358Publication Date (Web):June 10, 2009Publication History Received20 April 2009Revised31 May 2009Published online10 June 2009Published inissue 14 July 2009https://pubs.acs.org/doi/10.1021/ma900858ehttps://doi.org/10.1021/ma900858erapid-communicationACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views1598Altmetric-Citations26LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Catalysts,Fibers,Materials,Nanoparticles,Selectivity Get e-Alerts
Lysine 2,3-Aminomutase:  Rapid Mix−Freeze−Quench Electron Paramagnetic Resonance Studies Establishing the Kinetic Competence of a Substrate-Based Radical Intermediate (1996)

Lysine 2,3-aminomutase from Clostridia catalyzes the interconversion of L-lysine and L-beta-lysine. The enzyme contains iron-sulfur clusters and is activated by pyridoxal 5'-phosphate and S-adenosylmethionine, all of which participate in catalysis. Current spectroscopic evidence implicates two substrate-based organic radicals as intermediates in the mechanism. One of these species, the radical N3-(5'-phosphopyridoxylidene)-beta-lysin-2-yl (3), appears in the steady state of the reaction of lysine and has been definitively characterized by EPR and ESEEM spectroscopy. The 2-deuterio form of this radical, 3-2-d, which is generated in the reaction of L-[2-2H]lysine, can be distinguished by line shape analysis from 3. The rate at which the signal for 3-2-d is transformed into that for 3 has been measured by rapid mix-freeze quench kinetic analysis. The rate constant for this process is 24 +/- 8 s-1 at 21 degrees C. This is the rate constant for the turnover of radical 3 and is indistinguishable from the turnover number of lysine 2,3-aminomutase. Therefore, radical 3 is kinetically competent as an intermediate in the reaction of lysine 2,3-aminomutase.
Pre-steady-state transition-state analysis of the hydrolytic reaction catalyzed by purine nucleoside phosphorylase (1995)

The slow hydrolytic reaction catalyzed by calf spleen purine nucleoside phosphorylase [Kline, P. C., & Schramm, V. L. (1992) Biochemistry 31, 5964-5973] has been investigated using pre-steady-state kinetic isotope effects and solvolysis studies. The stoichiometric reaction between enzyme and inosine forms 1 mol of free ribose per trimer of purine nucleoside phosphorylase and a tightly bound complex of enzyme and hypoxanthine. The experimental kinetic isotope effects from [1'-3H]-, [2'-3H]-, [4'-3H]-, [5'-3H]-, [1'-14C]-, and [9-15N]inosine are 1.151 +/- 0.004, 1.145 +/- 0.003, 1.006 +/- 0.004, 1.028 +/- 0.005, 1.045 +/- 0.005, and 1.000 +/- 0.005, respectively, for the pre-steady-state conditions. Substrate trapping experiments demonstrated that there is no detectable forward commitment to catalysis for inosine hydrolysis. In contrast, bound inosine is 2.1 times more likely to form product than to dissociate when the enzyme-inosine complex is exposed to saturating PO4. The lack of an observed 9-15N isotope effect is consistent with an internal equilibrium between enzyme-inosine and the enzyme-hypoxanthine-ribose complex in which N9 of hypoxanthine is protonated. The equilibrium occurs as a consequence of slow product release and tightly bound hypoxanthine (Kd = 1.3 x 10(-12) M). This internal equilibrium has a minimal effect on the intrinsic kinetic isotope effects from ribose since equilibrium isotope effects for conversion of inosine to ribose are near unity. When the single-turnover hydrolytic reaction was accomplished in 20% methanol, approximately 85% of the product sugar was 1-methylribose. Under these conditions, the anion-binding pocket fills with solvent which competes for the oxocarbenium ion of inosine formed at the transition state. In the presence of arsenate, no methanolysis of inosine occurs [Kline, P. C., & Schramm, V. L. (1993) Biochemistry 32, 13212-13219]. The results define a transition state with oxocarbenium ion character and weak participation of the attacking solvent nucleophile. Electrostatic potential surfaces of the transition states indicate that arsenate anion is more effective in neutralizing the oxocarbenium ion than is H2O.
Evaluation of Two Tetravalent (ACYW135) Meningococcal Vaccines in Infants and Small Children: A Clinical Study Comparing Immunogenicity of O-Acetyl-Negative and O-Acetyl-Positive Group C Polysaccharides (1985)

Two different tetravalent polysaccharide vaccines against group A, C, Y, and W135 meningococci were given to 118 infants aged 6 to 23 months; the same vaccines were administered in a second dose 12 months later to those infants aged 6 to 11 months at first vaccination. Forty of the infants received vaccine containing the nonacetylated group C polysaccharide C(OAc-) and 78 the acetylated group C polysaccharide C(OAc+) together with group A, Y, and W135 polysaccharides. All polysaccharides, at a dose of 30 micrograms, induced antibody responses after administration of both vaccines in all age groups although the responses were better in the older infants. Acetylation of the sialic acid of the group C polysaccharide did not significantly influence the response. Rapid decreases in the antibody titers after the first vaccination stressed the need for one or more revaccinations. Vaccination elicited mild local and systemic reactions. Elevated temperatures were more common in the youngest infants but only four developed fever exceeding 38.5 degrees C (101.3 degrees F). We conclude that tetravalent (ACYW135) meningococcal vaccine is safe and immunologically effective in children younger than age 2 years. However, revaccinations may be required to maintain immunity.