gebhart/patrepeval huggingface dataset:
Release and Activity of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 by Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease (2002)

Destruction of lung elastin is critical for development of emphysema associated with chronic obstructive pulmonary disease (COPD). Lung macrophages release elastolytic enzymes, including matrix metalloproteinase (MMP)-9, along with tissue inhibitors of MMP (TIMP). We examined the production and activity of macrophage-derived MMP-9 and TIMP-1 from alveolar macrophages (AM) from smokers with COPD, healthy smokers (HS), and nonsmokers (NS). AM were stimulated with either lipopolysaccharide (LPS), interleukin (IL)-1 beta, or cigarette smoke-conditioned culture medium (CSM). AM from patients with COPD released greater amounts of MMP-9 with greater enzymatic activity than HS and NS. In contrast, AM from NS released more TIMP-1 than cells from HS and subjects with COPD. LPS and IL-1 beta caused a dose-dependent increase in MMP-9 release and activity, together with increased levels of TIMP-1. Dexamethasone prevented the increase in MMP-9 release, and increased TIMP-1 release. CSM increased MMP-9 and TIMP-1 release from AM of all groups. Dexamethasone decreased CSM-stimulated MMP-9 release, but had no effect on MMP-9 activity This study suggests that macrophages might be important in the development of COPD because these cells exhibit increased levels of elastolytic activity.
Efalizumab binding to the LFA-1 αLI domain blocks ICAM-1 binding via steric hindrance (2009)

Lymphocyte function-associated antigen 1 (LFA-1) plays important roles in immune cell adhesion, trafficking, and activation and is a therapeutic target for the treatment of multiple autoimmune diseases. Efalizumab is one of the most efficacious antibody drugs for treating psoriasis, a very common skin disease, through inhibition of the binding of LFA-1 to the ligand intercellular adhesion molecule 1 (ICAM-1). We report here the crystal structures of the Efalizumab Fab alone and in complex with the LFA-1 alpha(L) I domain, which reveal the molecular mechanism of inhibition of LFA-1 by Efalizumab. The Fab binds with an epitope on the inserted (I) domain that is distinct from the ligand-binding site. Efalizumab binding blocks the binding of LFA-1 to ICAM-1 via steric hindrance between its light chain and ICAM-1 domain 2 and thus inhibits the activities of LFA-1. These results have important implications for the development of improved antibodies and new therapeutic strategies for the treatment of autoimmune diseases.
An In Vivo Model to Study Immunotoxin-Induced Vascular Leak in Human Tissue (1999)

Phase I/II clinical trials using ricin A chain-containing immunotoxins (RTA-ITs) in > 125 patients with lymphoma have established that vascular leak syndrome (VLS) is the dose-limiting toxicity. A similar side effect has also been described for other immunotoxins (ITs) and for cytokines, growth factors, antibodies, and chemotherapeutic agents. To better reproduce the conditions underlying vascular leak syndrome in patients treated with immunotoxins, human skin grafts were transplanted onto SCID mice and modifications in the graft were studied after systemic administration of a RTA-IT. Compared with mice receiving saline, an increase in wet/dry weight ratios of these grafts was observed in mice injected with RTA-IT. An increase in the permeability of the human blood vessels was also demonstrated by the extravasation of Carbon Black and the accumulation of Evans Blue dye in the graft. Taken together, these observations suggest that the RTA-IT can induce VLS-like manifestations. This model should facilitate the testing of potential inhibitors of VLS, which might reduce the toxicity of ITs and other therapeutic agents.
Determination of the regime of rapid reacting systems in stopped- and steady-flow investigations by the velocity probe method (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of the regime of rapid reacting systems in stopped- and steady-flow investigations by the velocity probe methodRaymond E. Hansen and Mark W. TonsagerCite this: J. Phys. Chem. 1988, 92, 8, 2189–2196Publication Date (Print):April 1, 1988Publication History Published online1 May 2002Published inissue 1 April 1988https://pubs.acs.org/doi/10.1021/j100319a022https://doi.org/10.1021/j100319a022research-articleACS PublicationsRequest reuse permissionsArticle Views34Altmetric-Citations4LEARN 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 options Get e-Alerts
HLA-A2-Restricted Protection against Lethal Lymphocytic Choriomeningitis (2006)

The consequences of human lymphocytic choriomeningitis virus (LCMV) infection can be severe, including aseptic meningitis in immunocompetent individuals, hydrocephalus or chorioretinitis in fetal infection, or a highly lethal outcome in immunosuppressed individuals. In murine models of LCMV infection, CD8(+) T cells play a primary role in providing protective immunity, and there is evidence that cellular immunity may also be important in related arenavirus infections in humans. For this reason, we sought to identify HLA-A2 supertype-restricted epitopes from the LCMV proteome and evaluate them as vaccine determinants in HLA transgenic mice. We identified four HLA-A*0201-restricted peptides-nucleoprotein NP(69-77), glycoprotein precursor GPC(10-18), GPC(447-455), and zinc-binding protein Z(49-58)-that displayed high-affinity binding (< or =275 nM) to HLA-A*0201, induced CD8(+) T-cell responses of high functional avidity in HLA-A*0201 transgenic mice, and were naturally processed from native LCMV antigens in HLA-restricted human antigen presenting cells. One of the epitopes (GPC(447-455)), after peptide immunization of HLA-A*0201 mice, induced CD8(+) T cells capable of killing peptide-pulsed HLA-A*0201-restricted target cells in vivo and protected mice against lethal intracranial challenge with LCMV.
Letter (1994)

Dear Editor I am interested in working with children with special needs in the community.
First Real Time Measurements of Downhole Vibrations, Forces, and Pressures Used To Monitor Directional Drilling Operations (1989)

ABSTRACT A drilling mechanics sub has been developed to measure the dynamic collar forces, accelerations, and fluid pressures just above the bit. These quantities can be transmitted to surface using mud pulse telemetry to provide the driller with real time information about downhole conditions. The measurements have been obtained for the first time on two directional wells in the Gulf of Mexico. On the first well the sub was run in a rotary drilling assembly in the inclined section. On the second well the sub was run behind a steerable system on the build and tangent section of the well. The bending moment measurements gave a detailed description of the well trajectory each time a course correction was made; during jetting operations for the first well, and during oriented and rotary drilling using the steerable motor for the second well. Relatively high transverse acceleration levels were found to be associated with the doglegs of the wells, while relatively low axial acceleration levels were associated with drilling the soft shale formations. The transverse vibrations were shown, for the particular assemblies used, to vary almost linearly with rotary speed for the range studied. However, the transverse vibrations, as well as the bending moment were shown to be sensitive to downhole boundary conditions, especially in open hole sections. On each well measurements were made, at various flow rates, of the differential pressure across the components below the measurement sub; the bit for the first well, and a positive displacement motor plus the bit for the second well. From this data inferences could be drawn concerning pump efficiency and calibration of the downhole weight on bit measurement. In addition, measurement of the differential pressure can be seen as a potential aid in the identification of drillstring washouts, erosion or blocking of nozzles, and bearing wear in downhole motors.
Recent Developments in the Synthesis and Utilization of Chiral Sulfoxides (2003)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRecent Developments in the Synthesis and Utilization of Chiral SulfoxidesInmaculada Fernández and Noureddine KhiarView Author Information Instituto de Investigaciones Químicas, C.S.I.C-Universidad de Sevilla, c/. Américo Vespucio, s/n., Isla de la Cartuja, 41092 Sevilla, Spain, and Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain Cite this: Chem. Rev. 2003, 103, 9, 3651–3706Publication Date (Web):August 1, 2003Publication History Received8 April 2002Published online1 August 2003Published inissue 1 September 2003https://pubs.acs.org/doi/10.1021/cr990372uhttps://doi.org/10.1021/cr990372uresearch-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views9882Altmetric-Citations1063LEARN 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 SUBJECTS:Alkyls,Ligands,Oxidation,Oxides,Sulfides Get e-Alerts
Coupling of DNA Helicase and Endonuclease Activities of Yeast Dna2 Facilitates Okazaki Fragment Processing (2002)

Saccharomyces cerevisiae Dna2 possesses both helicase and endonuclease activities. Its endonuclease activity is essential and well suited to remove RNA-DNA primers of Okazaki fragments. In contrast, its helicase activity, although required for optimal growth, is not essential when the rate of cell growth is reduced. These findings suggest that DNA unwinding activity of Dna2 plays an auxiliary role in Okazaki fragment processing. To address this issue, we examined whether the Dna2 helicase activity influenced its intrinsic endonuclease activity using two mutant proteins, Dna2D657A and Dna2K1080E, which contain only helicase or endonuclease activity, respectively. Experiments performed with a mixture of Dna2D657A and Dna2K1080E enzymes revealed that cleavage of a single-stranded DNA by endonuclease activity of Dna2 occurs while the enzyme translocates along the substrate. In addition, DNA unwinding activity efficiently removed the secondary structure formed in the flap structure, which was further aided by replication protein A. Our results suggest that the Dna2 unwinding activity plays a role in facilitating the removal of the flap DNA by its intrinsic endonuclease activity.
A Phase 1, Randomized Ascending Single-Dose Study of Antagonist Anti-Human CD40 ASKP1240 in Healthy Subjects (2013)

This first-in-human, phase I study evaluated the safety, tolerability, pharmacokinetic and pharmacodynamic profile of ASKP1240 in healthy subjects. Twelve sequential groups (each 6 active and 3 placebo) were randomly assigned to placebo or single ascending doses of intravenous ASKP1240 (0.00003-10 mg/kg). ASKP1240 exhibited nonlinear pharmacokinetics, with mean maximal serum concentrations and area under the serum concentration-time curves ranging from 0.7 to 251.6 μg/mL and 6.5 to 55409.6 h·μg/mL following doses 0.1 mg/kg-10 mg/kg, respectively. CD40 receptor occupancy by ASKP1240, which was dose-dependent, reached a maximum at doses above 0.01 mg/kg. ASKP1240 was well tolerated, with no evidence of cytokine release syndrome or thromboembolic events. Treatment emergent antibodies to ASKP1240 were detected in 5/70 (7.1%) ASKP1240 recipients. In conclusion, antagonism of the CD40/CD154 interaction with ASKP1240 was safe and well tolerated at the doses tested.
A novel fiber‐optic pH sensor incorporating carboxy SNAFL‐2 and fluorescent wavelength‐ratiometric detection (1998)

A fiber-optic pH sensor was prepared using the self-referencing fluorescent pH probe carboxy seminaphthofluorescein (SNAFL-2). The ratio of the emission from the base form of this dye and the emission near the isoemissive point is insensitive to variations in the excitation intensity and photobleaching. The carboxy SNAFL-2 and a photoaffinity crosslinker, 4-azido-2,3,5,6-tetrafluorobenzoic acid, succinimidyl ester, were attached onto poly(acrylamide-co-vinylamine) to form a hydrophilic functional membrane for the fiber-optic sensor. Photo crosslinking was used to create a crosslinked pH-sensing membrane and covalently bind the membrane onto the surface of the PMMA optical fiber. The fluorescent properties of the membrane-fiber conjugate have been determined. The membrane is stable, and the pH sensor shows a fast response time and excellent resolution in a wide pH range of 3 to 11. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 9–15, 1998.
Characterization of Large Peptide Fragments Derived from the N-Terminal Domain of the Ribosomal Protein L9:  Definition of the Minimum Folding Motif and Characterization of Local Electrostatic Interactions (2002)

A set of peptides derived from the N-terminal domain of the ribosomal protein L9 (NTL9) have been characterized in an effort to define the minimum unit of this domain required to fold and to provide model peptides for the analysis of electrostatic interactions in the unfolded state. NTL9 is a 56-residue alpha-beta protein with a beta1-loop-beta2-alpha1-beta3-alpha2 topology. The beta-sheet together with the first helix comprise a simple example of a common supersecondary motif called the split beta-alpha-beta fold. Peptides corresponding to the beta1-loop-beta2 unit are unstructured even when constrained by an introduced disulfide. The pK(a)s of Asp-8 and Glu-17 in these peptides are slightly lower than the values found for shorter peptides but are considerably higher than the values in NTL9. A 34-residue peptide, which represents the beta1-loop-beta2-alpha1 portion of NTL9, is also unstructured. In contrast, a 39-residue peptide corresponding to the entire split beta-alpha-beta motif is folded and monomeric as judged by near- and far-UV CD, two-dimensional NMR, ANS binding experiments, pK(a) measurements, and analytical ultracentrifugation. The fold is very similar to the structure of this region in the intact protein. Thermal and urea unfolding experiments show that it is cooperatively folded with a DeltaG degrees of unfolding of 1.8-2.0 kcal/mol and a T(m) of 58 degrees C. This peptide represents the first demonstration of the independent folding of an isolated split beta-alpha-beta motif, and is one of only four naturally occurring sequences of fewer than 40 residues that has been shown to fold cooperatively in the absence of disulfides or ligand binding.
The cellodextrinase from Pseudomonas fluorescens subsp. cellulosa consists of multiple functional domains (1991)

A genomic library of Pseudomonas fluorescens subsp. cellulosa DNA was constructed in pUC18 and Escherichia coli recombinants expressing 4-methylumbelliferyl beta-D-cellobioside-hydrolysing activity (MUCase) were isolated. Enzyme produced by MUCase-positive clones did not hydrolyse either cellobiose or cellotriose but converted cellotetraose into cellobiose and cleaved cellopentaose and cellohexaose, producing a mixture of cellobiose and cellotriose. There was no activity against CM-cellulose, insoluble cellulose or xylan. On this basis, the enzyme is identified as an endo-acting cellodextrinase and is designated cellodextrinase C (CELC). Nucleotide sequencing of the gene (celC) which directs the synthesis of CELC revealed an open reading frame of 2153 bp, encoding a protein of Mr 80,189. The deduced primary sequence of CELC was confirmed by the Mr of purified CELC (77,000) and by the experimentally determined N-terminus of the enzyme which was identical with residues 38-47 of the translated sequence. The N-terminal region of CELC showed strong homology with endoglucanase, xylanases and an arabinofuranosidase of Ps. fluorescens subsp. cellulosa; homologous sequences included highly conserved serine-rich regions. Full-length CELC bound tightly to crystalline cellulose. Truncated forms of celC from which the DNA sequence encoding the conserved domain had been deleted, directed the synthesis of a functional cellodextrinase that did not bind to crystalline cellulose. This is consistent with the N-terminal region of CELC comprising a non-catalytic cellulose-binding domain which is distinct from the catalytic domain. The role of the cellulose-binding region is discussed.
Prevention of clindamycin-induced mortality in hamsters by Saccharomyces boulardii (1984)

Saccharomyces boulardii, a yeast used in a number of countries for general and antibiotic-associated gastrointestinal illnesses, was examined for possible application in the prevention of clindamycin-induced mortality in the hamster colitis model. Hamsters were given free access to an aqueous 5% suspension of lyophilized yeast for 3 days before and 10 days after administration of a single oral clindamycin dose of from 0.2 to 0.8 mg/kg. Mortality was recorded in groups of 7 to 20 animals every 24 h for 10 to 30 days. Mean cecal concentrations of S. boulardii were greater than 10(6) CFU/ml throughout the yeast administration period. Yeast treatment significantly decreased cumulative percent mortality by an average of 29%. Death onset was not affected by yeast treatment. Cecitis was present in 86% of moribund animals (N = 95) and was absent in all surviving animals examined (N = 27). Toxigenic Clostridium difficile was isolated from 13 of 14 moribund hamsters examined. No adverse effects of the yeast treatment were observed in animals receiving S. boulardii without clindamycin. The results suggest that S. boulardii warrants further evaluation for the prevention of antibiotic-associated colitis.
Improvement of uremic neuropathy and hypogeusia by dialysate zinc supplementation: a double-blind study. (1983)

A reduction in the plasma zinc concentration is a well-recognized complication of hemodialysis. A positive clinical response to zinc therapy under controlled conditions is the most reliable criterion of zinc deficiency. Zinc therapy using a nonproprietary zinc dialysate was evaluated in 12 dialysis patients with proven hypogeusia and polyneuropathy, in a randomized double-blind crossover comparison (preliminary phase, 4 weeks; placebo phase, 12 weeks; initial phase, 12 weeks; final phase, 6 weeks; post phase, 4 weeks). The dosage was related to the zinc plasma and erythrocyte levels, measured weekly. Nerve conduction velocity (NCV) and taste-testing were used to evaluate the effect of treatment at the end of the placebo and therapy phases. There was significant reduction in the recognition and determination threshold level for each of the four qualities of taste. The NCV improved significantly. The plasma zinc level could be elevated in all patients to the desired concentration, using individualized supplementation of dialysate with zinc. The erythrocyte zinc level remained constant, at double the normal value. The plasma zinc concentration fell back to the initial level 6 weeks after conclusion of therapy. We conclude that (1) zinc substitution may provide a specific therapy for uremic polyneuropathy, (2) the observed hypogeusia results from zinc deficiency, (3) long-term therapy is necessary to obtain a constant normal plasma zinc concentration, (4) zinc substitution by dialysate is a suitable and nonstressful method of administration.
On internal organization in compressed random-access memories (2001)

The design of a compressed random-access memory (C-RAM) is considered. Using a C-RAM at the lowest level of a system's main-memory hierarchy, cache lines are stored in a compressed format and dynamically decompressed to handle cache misses at the next higher level of memory. The requirement that compression/decompression, address translation, and memory management be performed by hardware has implications for the directory structure and storage allocation designs used within the C-RAM. Various new approaches, summarized here, are necessary in these areas in order to have methods that are amenable to hardware implementation. Furthermore, there are numerous design issues for the directory and storage management architectures. We consider a number of these issues, and present the results of evaluations of various approaches using analytic methods and simulations. This research was done as part of a project to explore the feasibility of compressed-memory systems; it forms the basis for the memory organization of IBM Memory Expansion Technology (MXT).
The complex network of musical tastes (2007)

We present an empirical study of the evolution of a social network constructed under the influence of musical tastes. The network is obtained thanks to the selfless effort of a broad community of users who share playlists of their favourite songs with other users. When two songs co-occur in a playlist a link is created between them, leading to a complex network where songs are the fundamental nodes. In this representation, songs in the same playlist could belong to different musical genres, but they are prone to be linked by a certain musical taste (e.g. if songs A and B co-occur in several playlists, an user who likes A will probably like also B). Indeed, playlist collections such as the one under study are the basic material that feeds some commercial music recommendation engines. Since playlists have an input date, we are able to evaluate the topology of this particular complex network from scratch, observing how its characteristic parameters evolve in time. We compare our results with those obtained from an artificial network defined by means of a null model. This comparison yields some insight on the evolution and structure of such a network, which could be used as ground data for the development of proper models. Finally, we gather information that can be useful for the development of music recommendation engines and give some hints about how top-hits appear.