gebhart/patrepeval huggingface dataset:
A Novel Chimeric Lysin Shows Superiority to Mupirocin for Skin Decolonization of Methicillin-Resistant and -Sensitive Staphylococcus aureus Strains (2010)

Staphylococcus aureus is a major human pathogen responsible for a number of serious and sometimes fatal infections. One of its reservoirs on the human body is the skin, which is known to be a source of invasive infection. The potential for an engineered staphylococcus-specific phage lysin (ClyS) to be used for topical decolonization is presented. We formulated ClyS into an ointment and applied it to a mouse model of skin colonization/infection with S. aureus. Unlike the standard topical antibacterial agent mupirocin, ClyS eradicated a significantly greater number of methicillin-susceptible S. aureus (MSSA) and -resistant S. aureus (MRSA) bacteria: a 3-log reduction with ClyS as opposed to a 2-log reduction with mupirocin in our model. The use of ClyS also demonstrated a decreased potential for the development of resistance by MRSA and MSSA organisms compared to that from the use of mupirocin in vitro. Because antibodies may affect enzyme function, we tested antibodies developed after repeated ClyS exposure for their effect on ClyS killing ability. Our results showed no inhibition of ClyS activity at various antibody titers. These data demonstrate the potential of developing ClyS as a novel class of topical antimicrobial agents specific to staphylococcus.
Impact of Microvascular Dysfunction on Left Ventricular Remodeling and Long-Term Clinical Outcome After Primary Coronary Angioplasty for Acute Myocardial Infarction (2004)

In reperfused acute myocardial infarction, MD within the risk area is an important predictor of both LV remodeling and unfavorable long-term outcome.
Reconstitution of a Disulfide Isomerization System (2002)

Isomerization of disulfide bonds is vital for the proper folding of proteins that possess multiple disulfides. In prokaryotes, the catalytic pathway responsible for disulfide isomerization involves thioredoxin, thioredoxin reductase, and the DsbC, DsbG, and DsbD proteins. To be active as isomerases, DsbC and DsbG must be kept reduced. This task is performed by the cytoplasmic membrane protein DsbD. DsbD in turn is reduced by the cytoplasmic thioredoxin and is composed of three domains. The beta domain is membrane-embedded, whereas the alpha and gamma domains are localized to the periplasm. It had been proposed that electrons are transferred within DsbD by a succession of disulfide exchange reactions between the three domains. To test this model using biochemical methods, we purified to homogeneity different polypeptides corresponding to the alpha, beta, gamma, and betagamma domains. Using these domains, we could reconstitute a DsbD activity and, for the first time, reconstitute in vitro the electron transport pathway from NADPH and thioredoxin to DsbC and DsbG. We showed that electrons are transferred from thioredoxin to the beta domain then successively to the gamma domain, the alpha domain, and finally on to DsbC or DsbG. We also determined the redox potential of the gamma domain to be -241 mV, and that of the alpha domain was found to be -229 mV. This shows that the direction of electron flow within DsbD is thermodynamically driven.
Dissecting Human Disease in the Postgenomic Era (2001)

The genomics era has provided great opportunities for deciphering the genes that are mutated in human diseases. In their Future Directions9 article,
 Peltonen and McKusick
 discuss how the human genome sequence and the completed genome sequences of other organisms will expand our understanding of human diseases, both those caused by mutations in a single gene and those where many genes and multiple factors are involved. From SNP maps to individual drug response profiling, the human genome sequence will lead to improved diagnostic testing for disease susceptibility genes and individually tailored treatment regimens for those who have already developed disease symptoms.
Depletion of Dendritic Cells Delays Ovarian Cancer Progression by Boosting Antitumor Immunity (2008)

Dendritic cells (DC) and cytokines that expand myeloid progenitors are widely used to treat cancer. Here, we show that CD11c(+)DEC205(+) DCs coexpressing alpha-smooth muscle actin and VE-cadherin home to perivascular areas in the ovarian cancer microenvironment and are required for the maintenance of tumor vasculature. Consequently, depletion of DCs in mice bearing established ovarian cancer by targeting different specific markers significantly delays tumor growth and enhances the effect of standard chemotherapies. Tumor growth restriction was associated with vascular apoptosis after DC ablation followed by necrosis, which triggered an antitumor immunogenic boost. Our findings provide a mechanistic rationale for selectively eliminating tumor-associated leukocytes to promote antitumor immunity while impeding tumor vascularization and to develop more effective DC vaccines based on a better understanding of the tumor microenvironment.
Inhibition of murine plaque-forming cell responses in vivo by ribavirin. (1981)

Abstract The effects of ribavirin, a potent inhibitor of RNA and DNA virus replication, on the generation of primary plaque-forming cell (PFC) responses in vivo has been investigated. Intraperitoneal administration of ribavirin 1 day after immunization of C3H/HeJ mice with sheep erythrocytes (SRBC) suppressed splenic IgM and IgG PFC responses by 60 to 90%. Primary IgM PFC responses of C3HeB/FeJ mice to bacterial lipopolysaccharides (LPS), a T-independent antigen, were also inhibited to a similar extent. Inhibition of splenic PFC responses, without significant reduction in nucleated cell recoveries, was dose dependent between 0.5 and 4 mg ribavirin. Varying the time of treatment determined that optimal inhibitory activity occurred when ribavirin was administered simultaneously or 1 day after antigen. Kinetic analysis of PFC responses in ribavirin-treated mice revealed that suppression did not result from a delay in development since reduced numbers of PFC were found at all times after immunization. Ribavirin-treatment after primary sensitization in vivo also impaired the capacity of spleen cells to develop secondary PFC responses in vitro, indicating that ribavirin also inhibited memory cell generation.
Relationship of 5‐HTTLPR genotypes and depression risk in the presence of trauma in a female twin sample (2007)

Several studies have implicated an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (SLC6A4; 5-HTT) in the development of mood disorders. In the present study of a sample of 247 young adult female twins from Missouri, we examine whether this polymorphism interacts with the effect of adverse life events to increase risk for developing depression. We found a significant interaction between the number of high-activity L(A) alleles and exposure to trauma (OR = 1.70, P < 0.0001). This differs from previous reports, in that the higher activity genotypes (L(A)/L(A), L(A)/S, L(A)/L(G)), rather than the low activity genotypes (S/S, S/L(G), L(G)/L(G)), are associated with an increased incidence of major depressive disease (MDD) in the presence of environmental trauma.
‘2A-like’ and ‘shifty heptamer’ motifs in penaeid shrimp infectious myonecrosis virus, a monosegmented double-stranded RNA virus (2007)

Penaeid shrimp infectious myonecrosis virus (IMNV) is a monosegmented double-stranded RNA virus that forms icosahedral virions and is tentatively assigned to the family Totiviridae. New examinations of the IMNV genome sequence revealed features not noted in the original report. These features include (i) two encoded '2A-like' motifs, which are likely involved in open reading frame (ORF) 1 polyprotein 'cleavage'; (ii) a 199 nt overlap between the end of ORF1 in frame 1 and the start of ORF2 in frame 3; and (iii) a 'shifty heptamer' motif and predicted RNA pseudoknot in the region of ORF1-ORF2 overlap, which probably allow ORF2 to be translated as a fusion with ORF1 by -1 ribosomal frameshifting. Features (ii) and (iii) bring the predicted ORF2 coding strategy of IMNV more in line with that of its closest phylogenetic relative, Giardia lamblia virus, as well as with that of several other members of the family Totiviridae including Saccharomyces cerevisiae virus L-A.
A comparison of robust control techniques for uncertain structural systems (1994)

of this paper is to compare control techprovide robustness for parametric uncertainty in structural systems. Sensitivity Weighted LQG, Maximum Entropy, Multiple Model, 'Hm and psynthesis were selected from amongst the available techniques, and are compared herein. The techniques are evaluated on: 1) computational requirements; 2) the degree to which performance is sacrificed in order to achieve robustness and 3) the maximum performance experimentally achieved on the Middeck Active Control Experiment test article. These criteria determine which techniques are suitable for the design of robust compensators for large order structural systems with parametric
Graphite surface-assisted laser desorption/ionization time-of-flight mass spectrometry of peptides and proteins from liquid solutions (1995)

Laser desorption time-of-flight mass spectra of peptides and proteins, as well as of lower molecular weight analytes, have been obtained by using a pulsed nitrogen UV laser (337 nm) to irradiate mixtures of 2-150 microns graphite particles and solutions of the analytes in glycerol. Protonated analytes as well as abundant alkali cation adducts were observed. Carbon cluster ions, Cn+, typically had a low abundance but dominated the mass spectrum at elevated laser powers. In spectra of a cytochrome c tryptic digest, all but one of the tryptic peptides were easily observed. Spectra of low molecular weight analytes dissolved in glycerol are very similar to FAB spectra of the same glycerol solution with added alkali salts. However, in many peptide and protein spectra, glycerol ion abundances are very low, and the alkali ions dominate the spectra at low mass. These spectra may correspond to wet and dry surface desorption conditions, respectively. The best spectra of the larger molecules were observed under dry conditions. In these initial experiments, we have obtained a sensitivity in the pico- to nanomole range and a mass resolution of about 300. The signal intensity is as good as that in conventional MALDI, and under optimal conditions, few background peaks appear, even at low mass.
Parental sex effect in spina bifida: A role for genomic imprinting? (1992)

Fifty families (491 individuals in 137 sibships) with more than one living case of isolated, nonsyndromic spina bifida (SB) were analyzed genetically. There were twice as many gene-carrier females (56) as gene-carrier males (28) (P < 0.005). This was not an artifact of ascertainment bias because the sex ratio of gene-carriers was the same whether the pedigree was obtained through the proband's father or mother. Also, this effect was not observed in other disorders analyzed by the same method. Neither was the effect due to differential fertility because the number and sex of affected and unaffected children per gene-carrier parent were not different for male or female gene-carrier parents. There was no evidence that the missing male gene-carriers were lost by selective spontaneous abortion. There was no deficit of male-to-male or male-to-female transmission, excluding simple X-linked or simple mitochondrial inheritance. If genomic imprinting plays a role in the unequal female and male carrier frequencies in SB, penetrance should differ with parental sex. Penetrance was higher for offspring of female parents than of male parents, but the difference was not statistically significant. In addition, both male and female gene-carriers were frequently found in the same pedigree. Thus, the present data suggest a possible role for imprinting in SB.
RETRACTED: Recombinant human migration inhibitory factor has adjuvant activity. (1992)

Recombinant human migration inhibitory factor (MIF), isolated through functional expression cloning in COS-1 cells, up-regulates expression of genes encoding HLA-DR and interleukin 1 beta (IL-1 beta) and elaboration of IL-1 beta by human monocyte-derived macrophages. Administration of soluble bovine serum albumin or human immunodeficiency virus 120-kDa glycoprotein (HIV gp120) to mice in the presence of recombinant MIF together with incomplete Freund's adjuvant induced a strong T-cell proliferative response comparable to that of complete Freund's adjuvant. Recombinant MIF also increased antibody production, especially of IgG1 and IgM, in mice. Taken together, these results indicate that recombinant MIF may be useful as an adjuvant in the development of vaccines.
Transient Techniques in NMR of Solids: An Introduction to Theory and Practice (1985)

This volume is an introduction to the theory and uses of solid-state nuclear magnetic resonance (NMR) spectroscopy. All the major areas are covered, including an introduction to concepts of time-dependent quantum mechanics as they apply to NMR spectroscopy of the solid state.
Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals (2012)

Neuronal control with high temporal precision is possible with optogenetics, yet currently available methods do not enable to control independently multiple locations in the brains of freely moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes and implanted into the brains of animals that are expressing light-responsive opsins. Each diode can be controlled separately, allowing localized light stimulation of neuronal activators and silencers in any temporal configuration and concurrent recording of the stimulated neurons. Because the only connections to the animals are via a highly flexible wire cable, unimpeded behavior is allowed for circuit monitoring and multisite perturbations in the intact brain. The capacity of the system to generate unique neural activity patterns facilitates multisite manipulation of neural circuits in a closed-loop manner and opens the door to addressing novel questions.
Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in&nbsp;synovial cells and a chronic arthritis model (2015)

The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.
The contributions of individual gamma-carboxyglutamic acid residues in the calcium-dependent binding of recombinant human protein C to acidic phospholipid vesicles (1993)

The dependence on the integrity of the human protein C (PC) gamma-carboxyglutamic acid (Gla) domain on its Ca(2+)-dependent binding properties to acidic phospholipid (PL) vesicles has been examined by analysis of these interactions with recombinant (r)-PC Gla domain muteins. The concentration of Ca2+ that results in 50% saturation (C50-Ca) of PL with wild-type (wt) r-PC was not altered by more than 2-fold for the following r-variants of PC, viz. [Gla6-->Asp]r-PC, [Gla14-->Asp]r-PC, [Gla19-->Asp]r-PC, [Gla25-->Asp]r-PC, [Gla29-->Asp]r-PC, and [Gln32-->Gla]r-PC. The C50-Ca was substantially higher than that of wtr-PC for [Gla7-->Asp]r-PC (8.2 mM), [Arg15-->Leu]r-PC (4.5 mM), [Gla16-->Asp]r-PC (> 10 mM), [Gla20-->Asp]r-PC (> 10 mM), and [Gla26-->Asp]r-PC (> 10 mM), indicating that the Ca(2+)-induced conformations of these latter variants interacted poorly with these acidic PL vesicles. Titration of the PL vesicles with wtr-PC at a constant concentration of 20 mM Ca2+ leads to calculation of a concentration of PC that results in 50% saturation of the PL (C50-PC) of 0.38 microM. Essentially this same value was determined for the r-mutants, [Gla7-->Asp]r-PC and [Gln32-->Gla]r-PC. An approximate 2-fold lower C50-PC was obtained for [Gla14-->Asp]r-PC (0.14 microM), [Gla25-->Asp]r-PC (0.16 microM), and [Gla29-->Asp]r-PC (0.15 microM). Somewhat higher C50-PC values were found for [Gla6-->Asp]r-PC (1.2 microM), [Arg15-->Leu]r-PC (1.2 microM), [Gla16-->Asp]r-PC (1.2 microM), [Gla19-->Asp]r-PC (1.8 microM), [Gla20-->Asp]r-PC (1.1 microM), and [Gla26-->Asp]r-PC (1.6 microM). The results of this investigation, in conjunction with other structural and functional studies with these mutants, and the x-ray crystallographic structure of the prothrombin Gla domain-Ca2+ complex, show that Gla16 and Gla26 are the most indispensable Gla residues for maintenance of the functional Ca(2+)-dependent structure of the Gla domain of PC, whereas Gla14 is the least critical Gla residue in this regard. Of the non-Gla residues investigated, Arg15 is of great importance for maintenance of a functional Ca(2+)-dependent structure of PC, and insertion of a Gla residue at position 32, a situation that exists in the cases of some other proteins of this type, does not significantly alter these characteristics of r-PC.
Expression of biotinylated proteins in mycobacterial gene libraries (1987)

A gene library of Mycobacterium bovis DNA in lambda gt11 was screened for the expression of M. bovis proteins using monoclonal antibodies and the streptavidin-biotinylated peroxidase detection system. Analysis of several phage that gave positive signals revealed that identical results could be obtained in the absence of specific antibody. These recombinants appear to encode biotinylated M. bovis proteins. A similar result was obtained with independently constructed libraries of M. bovis BCG and M. leprae.
Outcome following intracerebral hemorrhage and subarachnoid hemorrhage (2002)

Intracerebral hemorrhage and subarachnoid hemorrhage account for almost 20% of all stroke cases. Both forms of stroke are associated with a high morbidity and mortality rate. The incidence of intracerebral hemorrhage increases with the age and certain ethnical groups are more affected. Subarachnoid hemorrhage tends to occur in a much younger population than other types of strokes. Outcome predictors for intracerebral and subarachnoid hemorrhage have been extensively discussed in the literature. Based on the current literature, we review the morbidity and mortality rates and predictors of outcome for these two life-threatening diseases. Initial Glasgow Coma Scale (GCS) score, hematoma volume, and presence of ventricular blood are the most prominent predictors of outcome following intracerebral hemorrhage. Age and initial severity of neurologic deficits on presentation, measured by GCS, Hunt and Hess Scale or the World Federation of Neurological Surgeons Scale, are the most important predictors of outcome following subarachnoid hemorrhage.
Recent results and latest views on microcavities LED (2004)

Note: invited communication Reference LOEQ-CONF-2004-002 Record created on 2007-08-31, modified on 2017-05-12
Notas sobre la ampliación del Museo Nacional del Prado (2007)

En este articulo se describe el proyecto de ampliacion del Museo Nacional del Prado, realizado por Rafael Moneo, su concepcion espacial en torno al Claustro de los Jeronimos y las areas funcionales del Museo.
Cytotoxic T Lymphocytes (CTL) Specific for Adenovirus and CMV Can Be Generated From Umbilical Cord Blood for Adoptive Immunotherapy (2009)

The naive phenotype of cord blood (CB) cells contributes to the lower incidence and reduced severity of GvHD after umbilical cord blood transplant (CBT). However, the relatively low cell numbers and naivety of T-cell populations in CB grafts has lead to delayed immune reconstitution and higher mortality due to infection. CMV and adenovirus (Adv) are particularly problematic infections in patients after CBT. Previous studies have shown that adoptive immunotherapy with peripheral blood-derived CTL directed against CMV and Adv can effectively prevent the clinical manifestations of these viruses after HSCT suggesting that a similar approach could be developed after CBT. We hypothesized that CTL could be generated from CB for clinical use to restore anti-viral immunity and reduce viral infection post CBT. 40 × 106 CB mononuclear cells (available in the 20% fraction of frozen CB units) were thawed and used for generation of bi-virus specific CTL. A clinical-grade recombinant Adv type 5 vector pseudotyped with a type35 fiber carrying a transgene for CMVpp65 as a source of Adv and CMV antigens. CB-derived dendritic cells were transduced with the Ad5f35pp65 vector to stimulate virus-specific CTL followed by stimulation with autologous CB-derived lymphoblastoid cells (LCL) transduced with the same vector. After 3 weeks expansion, 9 CTL lines contained a mean of 83% (range 64–94%) CD8+ and 27% (range 12–40%) CD4+ T-cells. Flow cytometric analysis of memory markers revealed a predominance of CD45RA- CD62L- T-cells (69±18%; range 25–93) with a smaller population of CD45RA- CD62L+ T-cells (10±5%; range 1–23). Evaluable CB CTL lines showed specific cytolytic activity in 51Cr release assays against CMV and Adv targets. IFNγ ELISPOT assays on CTL lines demonstrated a mean of 209 (range 45–694) and 74 (range 0–188) spot-forming cells/1 × 105 T-cells following incubation with CMV-pp65 and Adv-hexon/penton peptides respectively. No significant response to irrelevant peptides was demonstrated. The expanded CB CTL had a broad Vβ repertoire and were specific for multiple viral epitopes. In addition, the virus-specific T cells were shown to be expanded only from T-cells with a naive phenotype (CD45RA+/CCR7+). These results demonstrate that, despite the generally naive nature of CB lymphocytes, bi-virus-specific responses can be expanded in vitro and could potentially be used clinically in CBT patients who develop infectious complications prior to immune reconstitution.
Lysis of cells infected with HIV-1 by human lymphocytes targeted with monoclonal antibody heteroconjugates. (1988)

The present study was undertaken to determine whether human PBL can be specifically focused to lyse cells infected with HIV-1 by mAb heteroconjugates that can bridge target and effector cells. A mAb directed against the central portion of HIV-1 glycoprotein gp110 was chemically cross-linked to a mAb directed against the CD3/TCR complex or to a mAb directed against the CD16 Fc gamma-R expressed on large granular lymphocytes (LGL). HIV-1-infected cells, but not uninfected cells, were found to be lysed to a greater extent by PBL in the presence of the gp110 X CD3 or the gp110 X CD16 antibody heteroconjugate than in the presence of the single antibodies or a mixture of the mAb comprising the heteroconjugates. Pretreatment of PBL with anti-CD3 or IL-2 augments their ability to lyse HIV-1-infected cells in the presence of the heteroconjugates. Lysis by anti-CD3-activated PBL in the presence of the gp110 X CD3 heteroconjugate was found to be mediated by CD8+-enriched T cells, whereas lysis by IL-2-treated PBL in the presence of the gp110 X CD16 heteroconjugate is mediated by PBL enriched for CD16+ cells, which are primarily LGL. Furthermore, PBL from asymptomatic, HIV-1-infected seropositive donors were found to be functional in lysing HIV-1-infected cells in the presence of the antibody heteroconjugates. Such antibody heteroconjugates, which can target T cells or LGL to lyse HIV-1-infected cells, may be of prophylactic or therapeutic value in HIV-1-infected individuals.