gebhart/patrepeval huggingface dataset:
An archaeal antioxidant: Characterization of a Dps-like protein from Sulfolobus solfataricus (2005)

Evolution of an oxygenic atmosphere required primordial life to accommodate the toxicity associated with reactive oxygen species. We have characterized an archaeal antioxidant from the hyperthermophilic acidophile Sulfolobus solfataricus. The amino acid sequence of this approximately 22-kDa protein shares little sequence similarity with proteins with known function. However, the protein shares high sequence similarity with hypothetical proteins in other archaeal and bacterial genomes. Nine of these hypothetical proteins form a monophyletic cluster within the broad superfamily of ferritin-like diiron-carboxylate proteins. Higher order structural predictions and image reconstructions indicate that the S. solfataricus protein is structurally related to a class of DNA-binding protein from starved cells (Dps). The recombinant protein self assembles into a hollow dodecameric protein cage having tetrahedral symmetry (SsDps). The outer shell diameter is approximately 10 nm, and the interior diameter is approximately 5 nm. Dps proteins have been shown to protect nucleic acids by physically shielding DNA against oxidative damage and by consuming constituents involved in Fenton chemistry. In vitro, the assembled archaeal protein efficiently uses H2O2 to oxidize Fe(II) to Fe(III) and stores the oxide as a mineral core on the interior surface of the protein cage. The ssdps gene is up-regulated in S. solfataricus cultures grown in iron-depleted media and upon H2O2 stress, but is not induced by other stresses. SsDps-mediated reduction of hydrogen peroxide and possible DNA-binding capabilities of this archaeal Dps protein are mechanisms by which S. solfataricus mitigates oxidative damage.
Protein Interaction Networks by Proteome Peptide Scanning (2004)

A substantial proportion of protein interactions relies on small domains binding to short peptides in the partner proteins. Many of these interactions are relatively low affinity and transient, and they impact on signal transduction. However, neither the number of potential interactions mediated by each domain nor the degree of promiscuity at a whole proteome level has been investigated. We have used a combination of phage display and SPOT synthesis to discover all the peptides in the yeast proteome that have the potential to bind to eight SH3 domains. We first identified the peptides that match a relaxed consensus, as deduced from peptides selected by phage display experiments. Next, we synthesized all the matching peptides at high density on a cellulose membrane, and we probed them directly with the SH3 domains. The domains that we have studied were grouped by this approach into five classes with partially overlapping specificity. Within the classes, however, the domains display a high promiscuity and bind to a large number of common targets with comparable affinity. We estimate that the yeast proteome contains as few as six peptides that bind to the Abp1 SH3 domain with a dissociation constant lower than 100 microM, while it contains as many as 50-80 peptides with corresponding affinity for the SH3 domain of Yfr024c. All the targets of the Abp1 SH3 domain, identified by this approach, bind to the native protein in vivo, as shown by coimmunoprecipitation experiments. Finally, we demonstrate that this strategy can be extended to the analysis of the entire human proteome. We have developed an approach, named WISE (whole interactome scanning experiment), that permits rapid and reliable identification of the partners of any peptide recognition module by peptide scanning of a proteome. Since the SPOT synthesis approach is semiquantitative and provides an approximation of the dissociation constants of the several thousands of interactions that are simultaneously analyzed in an array format, the likelihood of each interaction occurring in any given physiological settings can be evaluated. WISE can be easily extended to a variety of protein interaction domains, including those binding to modified peptides, thereby offering a powerful proteomic tool to help completing a full description of the cell interactome.
T30177, an oligonucleotide stabilized by an intramolecular guanosine octet, is a potent inhibitor of laboratory strains and clinical isolates of human immunodeficiency virus type 1 (1995)

T30177, an oligonucleotide composed of only deoxyguanosine and thymidine, is 17 nucleotides in length and contains single phosphorothioate internucleoside linkages at its 5' and 3' ends for stability. This oligonucleotide does not share significant primary sequence homology with or possess any complementary (antisense) sequence motifs to the human immunodeficiency virus type 1 (HIV-1) genome. T30177 inhibited replication of multiple laboratory strains of HIV-1 in human T-cell lines, peripheral blood lymphocytes, and macrophages. T30177 was also found to be capable of inhibiting multiple clinical isolates of HIV-1 and preventing the cytopathic effect of HIV-1 in primary CD4+ T lymphocytes. In assays with human peripheral blood lymphocytes there was no observable toxicity associated with T30177 at the highest concentration tested (100 microM), while the median inhibitory concentration was determined to be in the range of 0.1 to 1.0 microM for the clinical isolates tested, resulting in a high therapeutic index for this drug. In temporal studies, the kinetics of addition of T30177 to infected cell cultures indicated that, like the known viral adsorption blocking agents dextran sulfate and Chicago sky blue, T30177 needed to be added to cells during or very soon after viral infection. However, analysis of nucleic acids extracted at 12 h postinfection from cells treated with T30177 at the time of virus infection established the presence of unintegrated viral cDNA, including circular proviral DNA, in the treated cells. In vitro analysis of viral enzymes revealed that T30177 was a potent inhibitor of HIV-1 integrase, reducing enzymatic activity by 50% at concentrations in the range of 0.050 to 0.09 microM. T30177 was also able to inhibit viral reverse transcriptase activity; however, the 50% inhibitory value obtained was in the range of 1 to 10 microM, depending on the template used in the enzymatic assay. No observable inhibition of viral protease was detected at the highest concentration of T30177 used (10 microM). In experiments in which T30177 was removed from infected cell cultures at 4 days post-HIV-1 infection, total suppression of virus production was observed for more than 27 days. PCR analysis of DNA extracted from cells treated in this fashion was unable to detect the presence of viral DNA 11 days after removal of the drug from the infected cell cultures. The ability of T30177 to inhibit both laboratory and clinical isolates of HIV-1 and the experimental data which suggest that T30177 represents a novel class of integrase inhibitors indicate that this compound is a viable candidate for evaluation as a therapeutic agent against HIV-1 in humans.
II. The Protective Effect of Intraluminal Glucose as Energy Substrate (1970)

The intestinal mucosal lesion caused by low-flow states may lead to grave consequences. In a series of canine experiments, the superior mesenteric arteries were clamped for 60 minutes. Significant protection of the intestinal mucosa was obtained with glucose introduced into the lumen of the bowel as soon as possible after the onset of ischemia. Morphological damage was minimized, and the mucosal adenosine triphosphate content increased. Mannitol is not normally absorbed from the intestine. Intraluminal mannitol, with a concentration equivalent osmotically to that of glucose, failed to protect intestinal mucosa from ischemia. Furthermore, the tissue lactate in the mucosa of sacs containing glucose was elevated. It appears, therefore, that glucose acted by virtue of its role as an energy substrate rather than by an osmotic effect.
Identification of suspected tuberculosis patients based on natural language processing of chest radiograph reports. (1996)

Identification of eligible patients from electronically available patient data is a key difficulty in computerizing clinical practice guidelines because a large amount of the relevant data is stored as free text. We have been using MedLEE (Medical Language Extraction and Encoding System), a natural language processing system, to encode the clinical information in all chest radiograph and mammogram reports. This paper describes a retrospective study to determine if MedLEE can identify patients at risk for having tuberculosis (TB) based on their admission chest radiographs. Reports of 171 adult inpatients with culture-positive TB during 1992 and 1993 were manually coded (by a TB specialist) using seven terms suggestive of TB, and were also encoded by MedLEE. Using manual coding as the gold standard, MedLEE agreed on the classification of 152/171 (88.9%) reports--129/142 (90.8%) suspicious for TB and 23/29 (79.3%) not suspicious for TB; and 1072/1197 (89.6%) terms indicative of TB. Analysis showed that most of the discrepancies were caused by MedLEE not finding the location of the infiltrate. By ignoring the location of the infiltrate, the agreement became 157/171 (91.8%) reports and 946/1026 (92.2%) terms. Thus, natural language processing offers a practical alternative for using free-text reports to determine patient eligibility for computerized clinical practice guidelines.
A high-performance silicon micropump for an implantable drug delivery system (1999)

This paper describes the design and the measurement results of a new silicon piezoelectric micropump developed to be the heart of an implantable drug infusion system. The device is based on silicon bulk micromachining, silicon pyrex anodic bonding and piezoelectric actuation. This pumping mechanism has been designed for maximum safety and reliability together with high open-loop accuracy (/spl plusmn/10%) in a low flow rate range (0-100 /spl mu/1/h). It ensures constant stroke volume (150 nl) over a wide range of working conditions through the implementation of a double limiter, controlling the range of the pumping membrane. Consequently, the flow rate is linear with actuation frequency and virtually insensitive to inlet and outlet pressure, actuation voltage, temperature, viscosity and aging. The pump is self-priming with a stroke over dead volume ratio /spl Delta/V/V/sub 0/=1.15. It also features an on-chip barrier filter for particle protection and a functional detector. More than 100 pumps of the last generation have been fabricated and fully tested.
Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatment after resection of nodal metastases. (1997)

Postsurgical adjuvant therapy with autologous DNP-modified vaccine appears to produce survival rates that are markedly higher than have been reported with surgery alone. Moreover, this approach has some intriguing immunobiologic features that might provide insights into the human tumor-host relationship.
Miniature snapshot multispectral imager (2011)

We present a miniature snapshot multispectral imager based on using a monolithic filter array that operates in the short wavelength infrared spectral region and has a number of defense and commercial applications. The system is low-weight, portable with a miniature platform, and requires low power. The imager uses a 4×4 Fabry-Pérot filter array operating from 1487 to 1769 nm with a spectral bandpass ∼10 nm. The design of the filters is based on using a shadow mask technique to fabricate an array of Fabry-Pérot etalons with two multilayer dielectric mirrors. The filter array is installed in a commercial handheld InGaAs camera, replacing the imaging lens with a custom designed 4×4 microlens assembly with telecentric imaging performance in each of the 16 subimaging channels. We imaged several indoor and outdoor scenes. The microlens assembly and filter design is quite flexible and can be tailored for any wavelength region from the ultraviolet to the longwave infrared, and the spectral bandpass can also be customized to meet sensing requirements. In this paper we discuss the design and characterization of the filter array, the microlens optical assembly, and imager and present imaging results.
Self-Assembly Molecular Squares with Metal Complexes as Bridging Ligands (2000)

A series of heterometallic square complexes with general molecular formula [Br(CO)3Re(μ-(pyterpy)2M)]4(PF6)8, where M = Fe, Ru, or Os and where pyterpy is 4‘-(4‘ ‘‘-pyridyl)-2,2‘:6‘,2‘ ‘-terpyridine, were prepared by self-assembly between BrRe(CO)5 and (pyterpy)2M(PF6)2. The luminescence properties and host−guest chemistry of the complexes are explored.
Comparative clinical study of port-closure techniques following laparoscopic surgery. (1996)

The Carter-Thomason device is our preferred method for the closure of port sites after laparoscopic surgery.
Genetic variability in forced and voluntary endurance exercise performance in seven inbred mouse strains (2002)

The goal of this study was to characterize the genetic contribution to both forced and voluntary exercise performance and to determine whether performance in these two paradigms is controlled by similar genetic influences. There were marked strain differences in treadmill exercise performance, with Swiss Webster (SW) and FVB/NJ mice showing elevated performance and C57BL/6J animals showing decreased performance compared with all other strains. There was no apparent relationship between treadmill performance and voluntary wheel performance, with the exception of SW mice, which demonstrated high performances on both the treadmill and the voluntary wheel. Numerous properties were measured to attempt to understand the basis for these differences in exercise performance. DBA/1J and SW mice exhibited significantly greater cardiac contractility than all other analyzed strains. Conversely, BALB/cByJ mice exhibited significantly reduced cardiac contractility compared with all other strains. Expression of molecular indicators of hypertrophy (atrial natriuretic factor and beta-myosin heavy chain) was significantly elevated in DBA/2J myocardium compared with all other analyzed strains.
Unstitching the Tapestry: Levi-Strauss' Structuralism in Theory and Practice (2000)

The paper judged to be the best student essay submitted to Scholia by 30 June for the preceding year is published annually as the B. X. de Wet Essay. The competition, which is sponsored by the Classical Association of South Africa, is open to undergraduate students every year and to Honours students in even-numbered years. There is a prize of R250. This essay is named in honour of South African classicist B. X. de Wet.
State-of-the-Art Review: Anticoagulation: The Present and Future (2001)

Thrombin is a central bioregulator of coagulation and is therefore a key target in the therapeutic prevention and treatment of thromboembolic disorders, including deep vein thrombosis and pulmonary embolism. The current mainstays of anticoagulation treatment are heparins, which are indirect thrombin inhibitors, and coumarins, such as warfarin, which modulate the synthesis of vitamin K-dependent proteins. Although efficacious and widely used, heparins and coumarins have limitations because their pharmacokinetics and anticoagulant effects are unpredictable, with the risk of bleeding and other complications resulting in the need for close monitoring with their use. Low-molecular-weight heparins (LMWHs) provide a more predictable anticoagulant response, but their use is limited by the need for subcutaneous administration. In addition, discontinuation of heparin treatment can result in a thrombotic rebound due to the inability of these compounds to inhibit clot-bound thrombin. Direct thrombin inhibitors (DTI) are able to target both free and clot-bound thrombin. The first to be used was hirudin, but DTIs with lower molecular weights, such as DuP 714, PPACK, and efegatran, have subsequently been developed, and these agents are better able to inhibit clot-bound thrombin and the thrombotic processes that take place at sites of arterial damage. Such compounds inhibit thrombin by covalently binding to it, but this can result in toxicity and nonspecific binding. The development of reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.
Structural insight into distinct mechanisms of protease inhibition by antibodies (2007)

To better understand how the relatively flat antigen-combining sites of antibodies interact with the concave shaped substrate-binding clefts of proteases, we determined the structures of two antibodies in complex with the trypsin-like hepatocyte growth-factor activator (HGFA). The two inhibitory antibodies, Ab58 and Ab75, were generated from a human Fab phage display library with synthetic diversity in the three complementarity determining regions (H1, H2, and H3) of the heavy chain, mimicking the natural diversity of the human Ig repertoire. Biochemical studies and the structures of the Fab58:HGFA (3.5-A resolution) and the Fab75:HGFA (2.2-A resolution) complexes revealed that Ab58 obstructed substrate access to the active site, whereas Ab75 allosterically inhibited substrate hydrolysis. In both cases, the antibodies interacted with the same protruding element (99-loop), which forms part of the substrate-binding cleft. Ab58 inserted its H1 and H2 loops in the cleft to occupy important substrate interaction sites (S3 and S2). In contrast, Ab75 bound at the backside of the cleft to a region corresponding to thrombin exosite II, which is known to interact with allosteric effector molecules. In agreement with the structural analysis, binding assays with active site inhibitors and enzymatic assays showed that Ab58 is a competitive inhibitor, and Ab75 is a partial competitive inhibitor. These results provide structural insight into antibody-mediated protease inhibition. They suggest that unlike canonical inhibitors, antibodies may preferentially target protruding loops at the rim of the substrate-binding cleft to interfere with the catalytic machinery of proteases without requiring long insertion loops.
Cooperative interaction of nuclear factor-kappa B- and cis-regulatory enhancer binding protein-like factor binding elements in activating the interleukin-8 gene by pro-inflammatory cytokines. (1990)

A novel cytokine, interleukin-8 (IL-8), may play major roles in the inflammatory process by recruiting neutrophils and T cells into inflammatory sites. The production of this cytokine is not constitutive and is induced in a variety of cell types by stimulation with mitogens and cytokines. Among cytokines, only IL-1 and tumor necrosis factor (TNF) can induce IL-8 gene expression at the transcriptional level. Transfection of a human fibrosarcoma cell line with chloramphenicol acetyltransferase expression plasmids linked to a 5'-flanking deletion mutants of the IL-8 gene demonstrated that the nucleotides between -94 and -71 base pairs from the start of the first exon are essential and sufficient for the IL-8 induction by either IL-1, TNF, or phorbol 12-myristate 13-acetate. This sequence is composed of two cis-elements; one is the potential binding site for a nuclear factor-kappa B-like factor and the other for a cis-regulatory enhancer binding protein-like factor. Mutations in either elements abolished IL-1, TNF, and phorbol 12-myristate 13-acetate responsiveness. This report provides the first evidence that cooperation between two distinct cis-elements may be required for induction of gene expression by either IL-1 or TNF.
Complete Antitumor Protection by Perioperative Immunization with GM3/VSSP Vaccine in a Preclinical Mouse Melanoma Model (2006)

Preclinical evidence suggests that GM3/VSSP vaccine might have therapeutic potential to induce antitumor immunity in patients with minimal residual disease after surgery, thereby preventing or prolonging the time to recurrence.
Identification of the Binding Site for a Novel Class of CCR2b Chemokine Receptor Antagonists (2000)

Monocyte chemoattracant-1 (MCP-1) stimulates leukocyte chemotaxis to inflammatory sites, such as rheumatoid arthritis, atherosclerosis, and asthma, by use of the MCP-1 receptor, CCR2, a member of the G-protein-coupled seven-transmembrane receptor superfamily. These studies identified a family of antagonists, spiropiperidines. One of the more potent compounds blocks MCP-1 binding to CCR2 with a K(d) of 60 nm, but it is unable to block binding to CXCR1, CCR1, or CCR3. These compounds were effective inhibitors of chemotaxis toward MCP-1 but were very poor inhibitors of CCR1-mediated chemotaxis. The compounds are effective blockers of MCP-1-driven inhibition of adenylate cyclase and MCP-1- and MCP-3-driven cytosolic calcium influx; the compounds are not agonists for these pathways. We showed that glutamate 291 (Glu(291)) of CCR2 is a critical residue for high affinity binding and that this residue contributes little to MCP-1 binding to CCR2. The basic nitrogen present in the spiropiperidine compounds may be the interaction partner for Glu(291), because the basicity of this nitrogen was essential for affinity; furthermore, a different class of antagonists, a class that does not have a basic nitrogen (2-carboxypyrroles), were not affected by mutations of Glu(291). In addition to the CCR2 receptor, spiropiperidine compounds have affinity for several biogenic amine receptors. Receptor models indicate that the acidic residue, Glu(291), from transmembrane-7 of CCR2 is in a position similar to the acidic residue contributed from transmembrane-3 of biogenic amine receptors, which may account for the shared affinity of spiropiperidines for these two receptor classes. The models suggest that the acid-base pair, Glu(291) to piperidine nitrogen, anchors the spiropiperidine compound within the transmembrane ovoid bundle. This binding site may overlap with the space required by MCP-1 during binding and signaling; thus the small molecule ligands act as antagonists. An acidic residue in transmembrane region 7 is found in most chemokine receptors and is rare in other serpentine receptors. The model of the binding site may suggest ways to make new small molecule chemokine receptor antagonists, and it may rationalize the design of more potent and selective antagonists.
The phase transfer catalysed synthesis of isoflavone-O-glucosides (1998)

Daidzin 1, genistin 2, ononin 3 and sissotrin 4 are the major products of the phase transfer catalysed reaction between the isoflavone aglycones daidzein, genistein, formononetin and biochanin A, respectively, and 1-bromo-2,3,4,6-tetra-O-acetyl-α-glucopyranose. Complete proton and carbon NMR assignments are presented for compounds 1–4.