gebhart/patrepeval huggingface dataset:
Cell-sized, supported artificial membranes (pseudocytes): response of precursor cytotoxic T lymphocytes to class I MHC proteins. (1986)

Novel cell-sized, supported artificial membranes bearing class I antigens have been prepared by a simple dialysis procedure and then used to study the requirements for antigen recognition by precursor cytotoxic T lymphocytes (CTL). The membranes were made by mixing lipid, H-2 antigen, and C18 alkylated 5 microns silica beads in deoxycholate, and dialyzing to remove the detergent. The H-2 antigen-bearing, cell-sized beads, termed pseudocytes (artificial cells), were able to simulate generation of secondary CTL responses with the same specificity as alloantigen-bearing spleen cells. Comparative analyses demonstrated that the size of an antigen-bearing structure, and thus its potential for multivalent interaction, was a critical determinant of effectiveness of antigen recognition, and showed that H-2 antigen was recognized as effectively on cell-sized beads as on allogeneic spleen cells. Generation of a response to antigen on the cell-sized beads was completely dependent on addition of lymphokines to the cultures. Thus, unlike liposomes, H-2 antigen on beads was not available to accessory cells for stimulation of Ia-dependent production of lymphokines by T helper cells. These results, as well as direct observations by microscopy, strongly indicate that antigen is recognized on the surface of the beads. Despite effective stimulation of secondary CTL responses, antigen on beads was completely inactive in stimulating a primary CTL response by naive spleen cells. The results of mixing experiments by using beads and alloantigen-bearing cells or plasma membrane vesicles indicate that the lack of a primary response may result from a requirement for a soluble factor(s) that is not needed for generation of secondary responses. The unique advantages of cell-size supported membranes for studying antigen recognition by T cells are discussed. The beads can be handled and used like antigen-bearing cells in functional assays, while possessing well-defined, readily varied, and easily quantitated composition.
The role of cytokines in chlamydial infections (1996)

Chlamydiae are important human pathogens responsible for a wide range of infections and diseases. Chronic infections can be particularly devastating, as shown by diseases caused by Chlamydia trachomatis, such as trachoma and post-infectious tubal infertility, or possibly associated with Chlamydia pneumoniae, such as atherosclerosis. Cytokines are likely to be involved for the early resolution of chlamydial infections. However, recent data suggest a role played by cytokines in establishing chlamydial persistence, thus possibly contributing to chronic disease through immunopathological responses. Recent information from in-vitro cell culture systems and experimental animal models is discussed. Moreover, some new evidence about the effector functions of other immune mediators is presented.
The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015)

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding a peroxisomal ABC transporter. In this review, we compare estimates of incidence derived from different populations in order to provide an overview of the worldwide incidence of X-ALD. X-ALD presents with heterogeneous phenotypes ranging from adrenomyeloneuropathy (AMN) to inflammatory demyelinating cerebral ALD (CALD). A large number of different mutations has been described, providing a unique opportunity for analysis of functional domains within ABC transporters. Yet the molecular basis for the heterogeneity of clinical symptoms is still largely unresolved, as no correlation between genotype and phenotype exists in X-ALD. Beyond ABCD1, environmental triggers and other genetic factors have been suggested as modifiers of the disease course. Here, we summarize the findings of numerous reports that aimed at identifying modifier genes in X-ALD and discuss potential problems and future approaches to address this issue. Different options for prenatal diagnosis are summarized, and potential pitfalls when applying next-generation sequencing approaches are discussed. Recently, the measurement of very long-chain fatty acids in lysophosphatidylcholine for the identification of peroxisomal disorders was included in newborn screening programs.
Reactivity of coagulase-negative staphylococci isolated from cow and goat milk with monoclonal antibodies to Staphylococcus aureus capsular polysaccharide types 5 and 8 (1990)

Monoclonal antibodies to Staphylococcus aureus capsular polysaccharide types 5 and 8 were used in an enzyme-linked immunosorbent assay to serotype 74 and 42 coagulase-negative isolates from cow and goat milk, respectively. Eighteen (15.5%) isolates were typable: 13 Staphylococcus haemolyticus, 1 S. hyicus, 1 S. simulans, and 1 S. warneri from bovine origin and 2 S. lentus from caprine origin. Type 5 was predominant, accounting for about 89% of typable isolates. Reactivity with monoclonal antibodies varied considerably according to isolates. The significance and the potential importance of these findings are discussed.
The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord (2016)

Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells.
Multiplexing fiber bragg grating sensors (1991)

Abstract Bragg reflection gratings and out-coupling taps for sensors can be written holographically within the core of many commercial fibers available today. The gratings appear to be permanent and have been tested to temperatures in excess of 500°C. Quasi-distributed temperature, strain, pressure, chemical, and interferometric sensors can be made with the wavelength selective, reflection gratings, and taps. The fiber gratings, and the different types of sensors they can make, conveniently lend themselves to (wavelength-division multiplexing) WDM, (time-division multiplexing) TDM, and (frequency-division multiplexing) FDM types of multiplexing schemes. Instrumentation to detect the multiple sensors and measure their spectral shift for localized and quasi-distributed sensing is currently under development.
Principles and pitfalls in designing site‐directed peptide ligands (1993)

An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallographically refined structures of 14 peptide-protein complexes at 2.7 A resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change in conformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program an end-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligands were diffused into preexisting crystals. In such a large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints.
A specific endpoint assay for ubiquitin. (1987)

Simple endpoint assays for free ubiquitin (Ub) and for the Ub-activating enzyme are described. The method for measuring Ub makes use of the reaction of iodoacetamide-treated Ub-activating enzyme (E): [3H]ATP + Ub + E----E X [3H]AMP-Ub + PPi and PPi----2Pi (in the presence of pyrophosphatase). The Ub is then measured by determining the acid-insoluble radioactivity. The reaction is accompanied by a slow enzyme-catalyzed hydrolysis of the complex to AMP plus Ub. The presence of ubiquitin-activating enzyme in excess of Ub by approximately equal to 0.1 microM assures that the steady state will be close to the endpoint for total Ub. A preparation of the activating enzyme from human erythrocytes that does not depend on affinity chromatography is described. Several applications of the assay are presented.
Testosterone dose-response relationships in healthy young men (2001)

Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.
The Role of Multi-detector CT as Preoperative Assessment of Hypervascular Hepatocellular Carcinoma Compared with Digital Subtraction Angiography (2006)

The purpose of this study was to determine whether triphasic multi-detector row computed tomography (MDCT) can substitute digital subtraction angiography (DSA) for the preoperative detection of hypervascular hepatocellular carcinoma (HCC). Forty-three patients with nodular HCC underwent first triphasic MDCT examination: pre-contrast, hepatic arterial, portovenous, and delayed phase. Within 4 weeks, they underwent digital hepatic angiography with an intra-arterial chemoembolization with iodized oil and Pharmorubicin. Lipiodol computed tomography (CT) was performed in 4 weeks after infusion. A follow-up MDCT examination was performed between 3 to 6 months after lipiodol CT. Serial CT scans were reviewed and compared with DSA images to detect hepatic nodules. MDCT and DSA had the same sensitivity in detecting nodules ＞20mm in diameter. For the nodules 10-20 mm, MDCT detected 56 (sensitivity=94.6%), DSA detected 49 (sensitivity=89.5%, p=0.003). For the nodules ＜10mm, MDCT identified 72 (sensitivity=94.7%), DSA detected 60, sensitivity was 78.9% (p=0.001). Because of superior lesion detectability of MDCT as compared with DSA, MDCT may substitute DSA in the preoperative examination for hypervascular HCC.
A retrospective ESI‐MS/MS analysis of newborn blood spots from 18 symptomatic patients with organic acid and fatty acid oxidation disorders diagnosed either in infancy or in childhood (2007)

To assess the usefulness of newborn mass screening by ESI-MS/MS in Japan, an acylcarnitine analysis of blood spots on filter paper from collected from newborn infants at the age of 5 days was retrospectively conducted on 18 cases of inherited metabolic diseases that had already been diagnosed. The patients had organic acid disorders in 8 cases, fatty acid oxidation disorders in 7 cases, and amino acid disorders in 3 cases. The time of onset was from 0 days to 1 year 8 months of age. In 16 out of the 18 cases studied, it was confirmed that the analysis of the blood spots on filter paper collected during the newborn period could detect disorders. One case each of CPT-2 deficiency and citrin deficiency could not be detected in the newborn period. Regarding CPT-2 deficiency, the establishment of sufficient nutrition might have interfered with the detection of the disorder because the blood was collected at 5 days of age. The disorders occurred within 1 week after birth in 4 out of 18 cases, 2 of which died at an early stage. Among 13 cases in which the disorders occurred after 1 month, 10 cases were caused by defective metabolism due to infections. The prognoses of inherited metabolic diseases that occur in the early newborn period are limited. However, this study suggests that prognoses of metabolic disorders that occur after the newborn period can expect to be improved by early detection.
Nanocavitation in Self-Assembled Amphiphilic Block Copolymer-Modified Epoxy (2008)

An amphiphilic block copolymer toughener was incorporated into a liquid epoxy resin formulation and self-assembled into well-dispersed nanometer scale spherical micelles with a size of about 15 nm. The nanosized block copolymer at 5 wt % loading can significantly improve the fracture toughness of cured epoxy thermosets without reduction in modulus at room temperature and with only a slight drop in glass transition temperature. The toughening mechanisms were investigated, and it was found that the 15 nm size block copolymer micelles could cavitate to induce matrix shear banding, which mainly accounted for the observed remarkable toughening effect. Other mechanisms, such as crack tip blunting, may also play a role in the toughening. A discussion of the possible reasons responsible for the observed attractive mechanical property improvements due to the block copolymer modification is given. Implications of the present finding for designing toughened polymers are also discussed.
Comparison of pressor responses to angiotensin I, II, and III in pulmonary vascular bed of cats (1994)

Pulmonary vascular responses to angiotensin (ANG) peptides were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. Intralobar injections of ANG I, II, and III caused dose-related increases in lobar arterial pressure, whereas ANG (1-7) and ANG (3-8) (ANG IV) had modest pressor activity. ANG I, II, and III had similar activity and were more potent than norepinephrine and ANG (1-7) and ANG IV but less potent than the thromboxane A2 mimic, U-46619, in increasing lobar arterial pressure. The time course of responses to ANG I, II, and III was similar, and after administration of ANG receptor antagonists, DuP 532 and L-158,809, responses to ANG I, II, and III was reduced, whereas responses to norepinephrine, serotonin, and U-46619 were not altered. After administration of the ANG-converting-enzyme inhibitor, captopril, responses to ANG I were reduced. The converting-enzyme inhibitor enhanced pressor responses to ANG II and III but did not alter responses to norepinephrine, U-46619, or serotonin. Moreover, under elevated-tone conditions, pulmonary vasodilator responses to bradykinin were increased following administration of captopril, whereas vasodilator responses to acetylcholine and nitrovasodilators were not altered. These results demonstrate that ANG I, II, and III have similar pulmonary pressor activity and that responses are mediated by ANG II type 1 receptors. Pressor responses to ANG I are reduced, whereas vasodilator responses to bradykinin are enhanced by captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
Isolation and Characterization of an Arabidopsis Mutant Deficient in the Thylakoid Lipid Digalactosyl Diacylglycerol (1995)

, Susanne Hoffmann-Benning, Ilse Balbo, Christoph Benning, Isolation and Characterization of an Arabidopsis Mutant Deficient in the Thylakoid Lipid Digalactosyl Diacylglycerol, The Plant Cell, Vol. 7, No. 11 (Nov., 1995), pp. 1801-1810
A Prime-Boost Approach to HIV Preventive Vaccine Using a Recombinant Canarypox Virus Expressing Glycoprotein 160 (MN) followed by a Recombinant Glycoprotein 160 (MN/LAI) (1995)

The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immunodeficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgp160), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 20) received vCP125 (10(6) TCID50) at 0 and 1 month, followed randomly by rgp160 formulated in alum or in Freund's incomplete adjuvant (FIA) at 3 and 6 months. Local and systemic reactions were mild or moderate and resolved within the first 72 hr after immunization. No significant biological changes in routine tests were observed in any volunteer. Two injections of vCP125 did not elicit antibodies. Neutralizing antibodies (NA) against the HIV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively. Six months after the last boost, only 55% were still positive. Seven of 14 sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp 160 was detected in 25% of the subjects after vCP125 and in all subjects after the first booster injection and 12 months after the first injection. An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3+, CD8+, MHC class I restricted. The adjuvant formulation did not influence significantly the immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Thymidylate synthase inhibitors. (1999)

Thymidylate synthase (TS) is a critical enzyme for DNA replication and cell growth because it is the only de novo source of thymine nucleotide precursors for DNA synthesis. TS is the primary target of 5-fluorouracil (5-FU), which has been used for cancer treatment for more than 40 years. However, dissatisfaction with the overall activity of 5-FU against the major cancers, and the recognition that TS still remains an attractive target for anticancer drugs because of its central position in the pathway of DNA synthesis, led to a search for new inhibitors of TS structurally analogous to 5,10-methylenetetrahydrofolate, the second substrate of TS. TS inhibitory antifolates developed to date that are in various stages of clinical evaluation are ZD 1694 and ZD9331 (Astra-Zeneca, London, UK), (Eli Lilly, Indianapolis, IN), LY231514 (BW1843U89 (Glaxo-Wellcome, Research Triangle Park, NC), and AG337 and AG331 (Agouron, La Jolla, CA). Although each of these compounds has TS as its major intracellular site of action, they differ in propensity for polyglutamylation and for transport by the reduced folate carrier. LY231514 also has secondary target enzymes. As a result, each compound is likely to have a different spectrum of antitumor activity and toxicity. This review will summarize the development and properties of this new class of TS inhibitors.
Inhibition of influenza viral polymerases by minimal viral RNA decoys. (1997)

All gene segments of influenza virus share a common feature at their respective termini. Both the 5'- and 3'-terminal sequences are highly conserved and possess partial inverted complementarity. This allows for the formation of a double-stranded duplex, which plays a major role in transcription, replication and packaging of the viral genome. In vitro studies have shown that the viral polymerase binds to short RNA molecules containing these termini. In this study, attempts were made to test whether mini-RNA decoys containing either or both termini can inhibit the activity of the viral polymerase in vivo. RNA molecules containing either the 5' or the 3' noncoding sequences were unable to inhibit NS-CAT RNA replication, while mini-RNA decoys consisting of both the 5' and 3' noncoding sequences of vRNA or cRNA were able to efficiently inhibit the activity of the viral polymerases expressed from vaccinia virus vectors.
Parsing Videos of Actions with Segmental Grammars (2014)

Real-world videos of human activities exhibit temporal structure at various scales, long videos are typically composed out of multiple action instances, where each instance is itself composed of sub-actions with variable durations and orderings. Temporal grammars can presumably model such hierarchical structure, but are computationally difficult to apply for long video streams. We describe simple grammars that capture hierarchical temporal structure while admitting inference with a finite-state-machine. This makes parsing linear time, constant storage, and naturally online. We train grammar parameters using a latent structural SVM, where latent subactions are learned automatically. We illustrate the effectiveness of our approach over common baselines on a new half-million frame dataset of continuous YouTube videos.