gebhart/patrepeval huggingface dataset:
Distinct Role of TNFR1 and TNFR2 in Protective Immunity Against Orientia tsutsugamushi Infection in Mice (2022)

Infection with <i>Orientia tsutsugamushi</i>, an obligate intracellular bacterium, can cause mild or severe scrub typhus. Some patients develop acute lung injury, multi-organ failure, and fatal infection; however, little is known regarding key immune mediators that mediate infection control or disease pathogenesis. Using murine models of scrub typhus, we demonstrated in this study the requirement of TNF-TNFR signaling in protective immunity against this infection. Mice lacking both TNF receptors (TNFR1 and TNFR2) were highly susceptible to <i>O. tsutsugamushi</i> infection, displaying significantly increased tissue bacterial burdens and succumbing to infection by day 9, while most wild-type mice survived through day 20. This increased susceptibility correlated with poor activation of cellular immunity in inflamed tissues. Flow cytometry of lung- and spleen-derived cells revealed profound deficiencies in total numbers and activation status of NK cells, neutrophils, and macrophages, as well as CD4 and CD8 T cells. To define the role of individual receptors in <i>O. tsutsugamushi</i> infection, we used mice lacking either TNFR1 or TNFR2. While deficiency in either receptor alone was sufficient to increase host susceptibility to the infection, TNFR1 and TNFR2 played a distinct role in cellular responses. TNF signaling through TNFR1 promoted inflammatory responses and effector T cell expansion, while TNFR2 signaling was associated with anti-inflammatory action and tissue homeostasis. Moreover, TNFRs played an intrinsic role in CD8<sup>+</sup> T cell activation, revealing an indispensable role of TNF in protective immunity against <i>O. tsutsugamushi</i> infection.
Metal-Catalyzed Oxidation of Phenylalanine-Sensitive 3-Deoxy- <scp>d</scp> - <i>arabino</i> -Heptulosonate-7-Phosphate Synthase from <i>Escherichia coli</i> : Inactivation and Destabilization by Oxidation of Active-Site Cysteines (1999)

The in vitro instability of the phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase [DAHPS(Phe)] from Escherichia coli has been found to be due to a metal-catalyzed oxidation mechanism. DAHPS(Phe) is one of three differentially feedback-regulated isoforms of the enzyme which catalyzes the first step of aromatic biosynthesis, the formation of DAHP from phosphoenolpyruvate and D-erythrose-4-phosphate. The activity of the apoenzyme decayed exponentially, with a half-life of about 1 day at room temperature, and the heterotetramer slowly dissociated to the monomeric state. The enzyme was stabilized by the presence of phosphoenolpyruvate or EDTA, indicating that in the absence of substrate, a trace metal(s) was the inactivating agent. Cu2+ and Fe2+, but none of the other divalent metals that activate the enzyme, greatly accelerated the rate of inactivation and subunit dissociation. Both anaerobiosis and the addition of catalase significantly reduced Cu2+-catalyzed inactivation. In the spontaneously inactivated enzyme, there was a net loss of two of the seven thiols per subunit; this value increased with increasing concentrations of added Cu2+. Dithiothreitol completely restored the enzymatic activity and the two lost thiols in the spontaneously inactivated enzyme but was only partially effective in reactivation of the Cu2+-inactivated enzyme. Mutant enzymes with conservative replacements at either of the two active-site cysteines, Cys61 or Cys328, were insensitive to the metal attack. Peptide mapping of the Cu2+-inactivated enzyme revealed a disulfide linkage between these two cysteine residues. All results indicate that DAHPS(Phe) is a metal-catalyzed oxidation system wherein bound substrate protects active-site residues from oxidative attack catalyzed by bound redox metal cofactor. A mechanism of inactivation of DAHPS is proposed that features a metal redox cycle that requires the sequential oxidation of its two active-site cysteines.
Diffuse photon probes of structural and dynamical properties of turbid media: Theory and biomedical applications (1996)

Diffusing photons can be used to detect, localize, and characterize optical and dynamical spatial inhomogeneities embedded in turbid media. Measurements of the intensity of diffuse photons reveal information about the optical properties of a system. Speckle fluctuations carry information about the dynamical and optical properties. This dissertation shows that simple diffusion theories accurately model the intensity and speckle correlation signals that diffuse through turbid media with spatially varying properties and discusses possible biomedical applications. We first look at the intensity of diffuse photons provided by a light source that is intensity modulated. This generates diffuse photon density waves (DPDW's) which exhibit classical wave behavior. We demonstrate experimentally and theoretically the refraction, diffraction, and scattering of DPDW's. Using accurate signal and noise models, we then present a detailed analysis which shows that DPDW's can be used to detect and locate objects larger than 3 mm and to characterize objects larger than 1 cm which are embedded inside turbid media with biologically relevant parameters. This diffuse photon probe should find applications in medicine as a bed-side brain hematoma monitor, or for screening breast cancer, or other functional imaging applications. We then consider the coherence properties of the diffuse photons as revealed by speckle intensity fluctuations and show that the temporal autocorrelation function of these fluctuations is accurately modeled by a correlation diffusion equation. Because the correlation diffusion equation is analogous to the photon diffusion equation, all concepts and ideas developed for DPDW's can be directly applied to the diffusion of correlation. We show experimentally and with Monte Carlo simulations that the diffusion of correlation can be viewed as a correlation wave that propagates spherically outwards from the source and scatters from macroscopic spatial variations in dynamical and/or optical properties. We also demonstrate the utility of inverse scattering algorithms for reconstructing images of the spatially varying dynamical properties of turbid media. The biomedical applicability of this diffuse probe is illustrated with examples of monitoring blood flow and probing the depth of burned tissue.
HLA-DR2 and Dw2 in Narcolepsy and in Other Disorders of Excessive Somnolence Without Cataplexy (1986)

Studies on HLA antigens were conducted in several patient populations with the following findings: (a) All 135 Japanese narcoleptic patients, eight of whom were considered to have "symptomatic" narcolepsy, were found to be HLA-DR2 and HLA-DQw1 positive. All 17 members of a subgroup of the original population were also found to be HLA-Dw2-positive. It was concluded that HLA-DR2 is a prerequisite for the development of narcolepsy and that the diagnosis of narcolepsy can be excluded if HLA-DR2 or HLA-Dw2 is negative. The distinction between idiopathic and symptomatic narcolepsy needs to be reconsidered. (b) Haplotype studies in three families with narcoleptic members enabled detection of children at high risk for narcolepsy. (c) Of the 54 patients with disorders of excessive daytime sleepiness other than narcolepsy, those with essential hypersomnia (EHS) had a higher frequency of HLA-DR2; the others had a lower frequency. The DR2-positive EHS group could include members with an incomplete form of narcolepsy; the DR2-negative EHS group had disorders essentially different from narcolepsy, although both positive and negative groups manifested hypnagogic hallucinations, sleep paralysis, and sleep onset REMs. Two further studies were conducted in subgroups of the original narcoleptic population studied. In a subgroup of 30 patients who underwent lymphocyte subset studies, no T-cell abnormalities were detected; it is unlikely that an autoimmune mechanism is involved in the development of narcolepsy. In a subgroup of 33 narcoleptic patients, Southern's blot analysis of DNA using a DQ beta probe revealed three specific restriction fragments. Further studies are necessary to locate the DNA locus that carries the susceptibility gene for narcolepsy.
Improved Coronary Artery Definition With T2-Weighted, Free-Breathing, Three-Dimensional Coronary MRA (1999)

Free-breathing, T2prep, 3D coronary MRA with a shorter acquisition window resulted in improved CNR and better coronary artery definition, allowing the assessment of coronary disease. This approach offers the potential for free-breathing, noninvasive assessment of the major coronary arteries.
Efficient center-line extraction for quantification of vessels in confocal microscopy images (2003)

In this paper we present a novel method for the three-dimensional (3-D) centerline extraction of elongated objects such as vessels. This method combines the basic ideas in distance transform-based, thinning, and path planning methods to extract thin and connected centerlines. This efficient approach needs no user interaction or any prior knowledge of the object shape. We used the path planning approach, which has exclusively been used in the virtual endoscopy or robotics, to obtain the medial curve of the objects. To make our approach fully automated, a distance transform mapping is used to identify the end points of the object branches. The initial paths are also constructed on the surface of the object, traversing the same distance map. Then a thinning algorithm centralizes the paths. The proposed approach is especially efficient for centerline extraction of the complex branching structures. The method has been applied on the confocal microscopy images of rat brains and the results confirm its efficiency in extracting the medial curve of vessels, essential for the computation of quantitative parameters.
Velocity Profiles in Shear-Banding Wormlike Micelles (2003)

Using dynamic light scattering in heterodyne mode, we measure velocity profiles in a much studied system of wormlike micelles (CPCl/NaSal) known to exhibit both shear-banding and stress plateau behavior. Our data provide evidence for the simplest shear-banding scenario, according to which the effective viscosity drop in the system is due to the nucleation and growth of a highly sheared band in the gap, whose thickness linearly increases with the imposed shear rate. We discuss various details of the velocity profiles in all the regions of the flow curve and emphasize the complex, non-Newtonian nature of the flow in the highly sheared band.
A Usual G‐Protein‐Coupled Receptor in Unusual Membranes (2015)

G-protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and constitute about 50% of all known drug targets. They offer great potential for membrane protein nanotechnologies. We report here a charge-interaction-directed reconstitution mechanism that induces spontaneous insertion of bovine rhodopsin, the eukaryotic GPCR, into both lipid- and polymer-based artificial membranes. We reveal a new allosteric mode of rhodopsin activation incurred by the non-biological membranes: the cationic membrane drives a transition from the inactive MI to the activated MII state in the absence of high [H(+)] or negative spontaneous curvature. We attribute this activation to the attractive charge interaction between the membrane surface and the deprotonated Glu134 residue of the rhodopsin-conserved ERY sequence motif that helps break the cytoplasmic "ionic lock". This study unveils a novel design concept of non-biological membranes to reconstitute and harness GPCR functions in synthetic systems.
Isoelectric focusing and non‐isoelectric precipitation of ferritin in immobilized pH gradients: An improved protocol overcoming protein‐matrix interactions (1987)

Abstract It has been impossible, up to now, to focus ferritin (a large, ca. 450 000 Da, ironstorage protein ubiquitous in mammalian systems) in immobilized pH gradients (IPG). This was not a sieving problem, as ferritin focuses readily in a 4%T polyacrylamide (or polytrisacryl) gel in conventional carrier ampholyte isoelectric focusing. A strong interaction with the IPG matrix was suspected, but an auto‐buffered (pH 6.0) soluble IPG polymer failed to precipitate ferritin from solution, although it altered its visible spectrum, suggesting the formation of soluble complexes. By a Takeo plot, the dissociation constant ( K d )of the ferritin‐IPG matrix complex was estimated to be 0.1 mM. However, even a 100‐fold dilution of Immobilines into the IPG matrix with a concomitant addition of competing ions (up to 3 % carrier ampholytes) failed to produce good focusing patterns. An unsuspected, hitherto un‐reported, precipitating power of free Immobilines in solution on the ferritin macroion was found to be the key to the riddle. The precipitating ions are (in order of aggregation power): p K 9.3 > p K 7.0 > p K 6.2. None of the acidic Immobilines (p K s 3.6, 4.4 and 4.6) and, among the basic, only the p K 8.5, exhibit any precipitation power on ferritin and other complex protein mixtures. In a new IPG pH 4–5 interval, containing only the p K 4.6 as buffering and the p K 8.5 Immobilines as titrant ions, excellent focusing patterns of ferritin were obtained. It is hypothesized that the precipitating Immobilines act as cationic detergents, and are able to cross‐link macroions with a mixed‐type, hydrophobic‐ionic interaction at the two extremities of the molecule. Guidelines are given for handling this major problem on a short‐term basis, the longterm goal being the replacement of the ‘unfavorable’ Immobilines (p K s 9.3, 7.0 and 6.2) by new chemical structures of the desirable type (the non‐precipitating p K 8.5 species).
Phosphido Pincer Complexes of Palladium as New Efficient Catalysts for Allylation of Aldehydes (2008)

Palladium complexes supported by tridentate phosphido diphosphine ligands (P(o-C6H4PR2)2: 1, R = iPr; 2, R = Ph) have been synthesized, characterized, and tested as catalysts for the electrophilic allylation of aldehydes. The palladium complex 2 resulted in an interesting catalyst for electrophilic allylation in the presence of allyltributyltin, giving good yields under very mild reaction conditions and even in the absence of the solvent.
Aptamers for Targeted Drug Delivery (2010)

Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.
Composition of Peritoneal Dialysis Solutions: Potential Hazards (1989)

The ideal components of peritoneal dialysate and their ideal concentrations have yet to be defined. This article reviews the hazards inherent in present solutions and emphasises the dual needs for uniformity of approach to composition and for agreement on minimal international standards for solution quality control.
Gender difference in antidiuretic response to desmopressin (2011)

Increased age and female gender are well-known risk factors for the development of desmopressin-induced hyponatremia. However, little focus has been on exploring gender differences in the antidiuretic response to desmopressin. Based on an exploratory analysis from three clinical trials, we report a significant gender difference in the effects of desmopressin on nocturnal urine volume that could not be explained by pharmacokinetic differences. Mean desmopressin concentration profiles were tested for covariates, and age and gender were not statistically significant and only weight was significant for log(C(max)) (P = 0.0183) and borderline significant for log(AUC) (P = 0.0571). The decrease in nocturnal urine volume in nocturia patients treated with desmopressin over 28 days was significantly larger for women at the lower desmopressin melt doses of 10 and 25 μg than for men. The ED(50) for men was modeled to be 43.2 μg and 16.1 μg for women, with the ED(50) men/women estimated to be 2.7 (1.3-8.1 95% CI), corresponding to significantly higher sensitivity to desmopressin in women. An increasing incidence of hyponatremia with increasing dose was found, and at the highest dose level of 100 μg decreases in serum sodium were approximately twofold greater in women over 50 yr of age than in men. A new dose recommendation stratified by gender is suggested in the treatment of nocturia: for men, 50- to 100-μg melt is an efficacious and safe dose, while for women a dose of 25 μg melt is recommended as efficacious with no observed incidences of hyponatremia. Areas for further research are proposed to uncover pathophysiological mechanism(s) behind these gender differences.
Angiotensin I-Converting-Enzyme-Inhibitory and Antibacterial Peptides from <i>Lactobacillus helveticus</i> PR4 Proteinase-Hydrolyzed Caseins of Milk from Six Species (2003)

Sodium caseinates prepared from bovine, sheep, goat, pig, buffalo or human milk were hydrolyzed by a partially purified proteinase of Lactobacillus helveticus PR4. Peptides in each hydrolysate were fractionated by reversed-phase fast-protein liquid chromatography. The fractions which showed the highest angiotensin I-converting-enzyme (ACE)-inhibitory or antibacterial activity were sequenced by mass spectrum and Edman degradation analyses. Various ACE-inhibitory peptides were found in the hydrolysates: the bovine alpha(S1)-casein (alpha(S1)-CN) 24-47 fragment (f24-47), f169-193, and beta-CN f58-76; ovine alpha(S1)-CN f1-6 and alpha(S2)-CN f182-185 and f186-188; caprine beta-CN f58-65 and alpha(S2)-CN f182-187; buffalo beta-CN f58-66; and a mixture of three tripeptides originating from human beta-CN. A mixture of peptides with a C-terminal sequence, Pro-Gly-Pro, was found in the most active fraction of the pig sodium caseinate hydrolysate. The highest ACE-inhibitory activity of some peptides corresponded to the concentration of the ACE inhibitor (S)-N-(1-[ethoxycarbonyl]-3-phenylpropyl)-ala-pro maleate (enalapril) of 49.253 micro g/ml (100 micro mol/liter). Several of the above sequences had features in common with other ACE-inhibitory peptides reported in the literature. The 50% inhibitory concentration (IC(50)) of some of the crude peptide fractions was very low (16 to 100 micro g/ml). Some identified peptides were chemically synthesized, and the ACE-inhibitory activity and IC(50)s were confirmed. An antibacterial peptide corresponding to beta-CN f184-210 was identified in human sodium caseinate hydrolysate. It showed a very large spectrum of inhibition against gram-positive and -negative bacteria, including species of potential clinical interest, such as Enterococcus faecium, Bacillus megaterium, Escherichia coli, Listeria innocua, Salmonella spp., Yersinia enterocolitica, and Staphylococcus aureus. The MIC for E. coli F19 was ca. 50 micro g/ml. Once generated, the bioactive peptides were resistant to further degradation by proteinase of L. helveticus PR4 or by trypsin and chymotrypsin.
7-Substituted 2,3-diazabicyclo[2.2.1]heptane derivatives. Synthesis of a stable ketone hydrate (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT7-Substituted 2,3-diazabicyclo[2.2.1]heptane derivatives. Synthesis of a stable ketone hydrateN. P. Marullo and J. A. AlfordCite this: J. Org. Chem. 1968, 33, 6, 2368–2370Publication Date (Print):June 1, 1968Publication History Published online1 May 2002Published inissue 1 June 1968https://pubs.acs.org/doi/10.1021/jo01270a041https://doi.org/10.1021/jo01270a041research-articleACS PublicationsRequest reuse permissionsArticle Views123Altmetric-Citations17LEARN 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
Joining dataflow with predicates (2005)

Dataflow analyses sacrifice path-sensitivity for efficiency and lead to false positives when used for verification. Predicate refinement based model checking methods are path-sensitive but must perform many expensive iterations to find all the relevant facts about a program, not all of which are naturally expressed and analyzed using predicates. We show how to join these complementary techniques to obtain efficient and precise versions of any lattice-based dataflow analysis using predicated lattices. A predicated lattice partitions the program state according to a set of predicates and tracks a lattice element for each partition. The resulting dataflow analysis is more precise than the eager dataflow analysis without the predicates.In addition, we automatically infer predicates to rule out imprecisions. The result is a dataflow analysis that can adaptively refine its precision. We then instantiate this generic framework using a symbolic execution lattice, which tracks pointer and value information precisely. We give experimental evidence that our combined analysis is both more precise than the eager analysis in that it is sensitive enough to prove various properties, as well as much faster than the lazy analysis, as many relevant facts are eagerly computed, thus reducing the number of iterations.This results in an order of magnitude improvement in the running times from a purely lazy analysis.
Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor Specific Antibody Positive Kidney Transplant Recipients (2018)

The combined use of dd-cfDNA and DSA testing may improve the noninvasive diagnosis of active ABMR in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ results have a high probability of active ABMR.