gebhart/patrepeval huggingface dataset:
Ab initio protein structure prediction of CASP III targets using ROSETTA (1999)

To generate structures consistent with both the local and nonlocal interactions responsible for protein stability, 3 and 9 residue fragments of known structures with local sequences similar to the target sequence were assembled into complete tertiary structures using a Monte Carlo simulated annealing procedure (Simons et al., J Mol Biol 1997; 268:209-225). The scoring function used in the simulated annealing procedure consists of sequence-dependent terms representing hydrophobic burial and specific pair interactions such as electrostatics and disulfide bonding and sequence-independent terms representing hard sphere packing, alpha-helix and beta-strand packing, and the collection of beta-strands in beta-sheets (Simons et al., Proteins 1999;34:82-95). For each of 21 small, ab initio targets, 1,200 final structures were constructed, each the result of 100,000 attempted fragment substitutions. The five structures submitted for the CASP III experiment were chosen from the approximately 25 structures with the lowest scores in the broadest minima (assessed through the number of structural neighbors; Shortle et al., Proc Natl Acad Sci USA 1998;95:1158-1162). The results were encouraging: highlights of the predictions include a 99-residue segment for MarA with an rmsd of 6.4 A to the native structure, a 95-residue (full length) prediction for the EH2 domain of EPS15 with an rmsd of 6.0 A, a 75-residue segment of DNAB helicase with an rmsd of 4.7 A, and a 67-residue segment of ribosomal protein L30 with an rmsd of 3.8 A. These results suggest that ab initio methods may soon become useful for low-resolution structure prediction for proteins that lack a close homologue of known structure.
Affinity chromatography of yeast α-glucosidase using ligand-mediated chromatography on immobilized phenylboronic acids (1981)

The synthesis of 3-nitro-4-(6-aminohexylamido)phenylboronic acid is described. The properties of two novel forms of immobilized phenylboronate agarose adsorbents [m-aminophenylboronic acid-Matrex Gel and 3-nitro-4-(6-aminohexylamido)phenylboronic acid-Sepharose CL-6B] were investigated. Both gels bind and selectively retard the glycoprotein alpha-glucosidase from yeast. The retardation is affected by following parameters: (i) pH, (ii) presence of sugar, (iii) concentration of sugar and (iv) buffer species (especially triethanolamine). Five sugars were studied, namely sorbitol, fructose, ribose, glucose and maltose. The concentration of sugar required to produce significant retardation increased in the above order, whereas the ability of sugar to form a complex with boron decreases in the same order. These effects were observed with crude as well as pure enzyme. Since alpha-glucosidase is a glycoprotein, it is proposed that this protein is mainly bound to these immobilized phenylboronates via sugar (glyco) residues. Displacement of the enzyme from the column is effected by the sugar in the buffer (or in a preincubation mixture). However, the marked pH-dependence (this retardation effect could only be observed at pH 7.4) suggests that these results are not due solely to hydrophobic or ionic mechanisms and are more complex than simple sugar-phenylboronic acid interactions.
Cloning of an arylalkylamine N-acetyltransferase (aaNAT1) from Drosophila melanogaster expressed in the nervous system and the gut. (1996)

In insects, neurotransmitter catabolism, melatonin precursor formation, and sclerotization involve arylalkylamine N-acetyltransferase (aaNAT, EC 2.3.1.87) activity. It is not known if one or multiple aaNAT enzymes are responsible for these activities. We recently have purified an aaNAT from Drosophila melanogaster. Here, we report the cloning of the corresponding aaNAT cDNA (aaNAT1) that upon COS cell expression acetylates dopamine, tryptamine, and the immediate melatonin precursor serotonin. aaNAT1 represents a novel gene family unrelated to known acetyl-transferases, except in two weakly conserved amino acid motifs. In situ hybridization studies of aaNAT1 mRNA in embryos reveal hybridization signals in the brain, the ventral cord, the gut, and probably in oenocytes, indicating a broad tissue distribution of aaNAT1 transcripts. Moreover, in day/ night studies we demonstrate a diurnal rhythm of melatonin concentration without a clear-cut change in aaNAT1 mRNA levels. The data suggest that tissue-specific regulation of aaNAT1 may be associated with different enzymatic functions and do not exclude the possibility of additional aaNAT genes.
Regulation of inflammatory responses by oncostatin M. (1999)

Oncostatin M (OM) is a pleiotropic cytokine produced late in the activation cycle of T cells and macrophages. In vitro it shares properties with related proteins of the IL-6 family of cytokines; however, its in vivo properties and physiological function are as yet ill defined. We show that administration of OM inhibited bacterial LPS-induced production of TNF-alpha and lethality in a dose-dependent manner. Consistent with these findings, OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and Ab production were not impaired by OM treatment. Taken together these data indicate the activities of this cytokine in vivo are antiinflammatory without concordant immunosuppression.
Structure and function of P-glycoprotein in the normal liver and intestine. (1990)

Multidrug resistance (MDR) genes encode a family of membrane glycoproteins of approximately 170 kD (P-glycoproteins). In man and mouse, the MDR 1 (mdr 1) genes confer resistance to relatively hydrophobic cationic anti-cancer drugs (i.e., vinblastin, adriamycin). Anti-cancer drug sensitivity is restored by addition of other drugs (i.e., verapamil, reserpine) which are also P-glycoprotein substrates. Transfection of MDR 1 genes produces the resistance phenotype and overexpression of P-glycoprotein. Parenchymal cells in several normal tissues express P-glycoprotein in the secretory domain of the plasma membrane (i.e., bile canaliculus of hepatocytes, brush border of proximal tubular, and small intestinal cells). Studies using plasma membrane vesicles of different sidedness derived from the bile canaliculus and small intestinal brush border permit characterization of P-glycoprotein as a unidirectional, temperature dependent, saturable, ATP-dependent transporter which is competitively inhibited by various anti-cancer drugs and other compounds. Transport studies using single cell fluorescence microscopy with image analysis confirm observations in vesicles. No natural substrate has been identified. Structural studies indicate that the requirements for substrates are molecular weight of 350 to 100, hydrophobicity, two planar rings, and a weak cationic charge. Alternative mechanisms of transport function are considered. The identity of P-glycoproteins in normal rat and human tissues has not been established. Antibody reactions suggest that they may belong to the MDR 2 or 3 class. Studies using everted gut sacs suggest that inhibition of P-glycoprotein may facilitate accumulation of anti-cancer drugs in the tissue.
Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells (2000)

The serum-borne lysophospholipid mediators sphingosine 1-phosphate (Sph-1-P) and lysophosphatidic acid (LPA) have been shown to be released from activated platelets and to act on endothelial cells. In this study, we employed the repeated lipid extraction (under alkaline and acidic conditions), capable of detecting Sph-1-P, LPA, and possibly structurally similar lysophospholipids, whereby a marked formation of [32P]Sph-1-P, but not [32P]LPA, was observed in [32P]orthophosphate-labeled platelets. Platelet Sph-1-P release, possibly mediated by protein kinase C, was greatly enhanced in the presence of albumin, which formed a complex with Sph-1-P. This finding suggests that platelet Sph-1-P may become accessible to depletion by albumin when its transbilayer movement (flipping) across the plasma membrane is enhanced by protein kinase C. Although human umbilical vein endothelial cells expressed receptors for both Sph-1-P and LPA, Sph-1-P acted much more potently than LPA on the cells in terms of intracellular Ca++ mobilization, cytoskeletal reorganization, and migration. The results suggest that Sph-1-P, rather than LPA, is a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells, under the conditions in which critical platelet-endothelial interactions (including thrombosis, angiogenesis, and atherosclerosis) occur. Furthermore, albumin-bound Sph-1-P may account for at least some of the serum biological activities on endothelial cells, which have been ascribed to the effects of albumin-bound LPA, based on the similarities between LPA and serum effects.
Predictive proteomic signatures for response of pancreatic cancer patients receiving chemotherapy (2019)

Based on the cohort investigated, our data suggested that systemic proteome alterations involved in pathways associated with inflammation, immunoresponse, coagulation and complement cascades may be reporters of chemo-treatment outcome in PDAC patients. For the majority of the patients involved, the panel consisting of PZ, SHBG, VWF and CA 19-9 was able to segregate Good-responders from Limited-responders effectively. Our data also showed that dramatic fluctuations of biomarker concentration in the circulating system of a PDAC patient, which might result from biological heterogeneity or confounding complications, could diminish the performance of a biomarker. Categorization of PDAC patients in terms of their tumor stages and histological types could potentially facilitate patient stratification for treatment.
The receptor-binding domain of human apolipoprotein E. Binding of apolipoprotein E fragments. (1983)

To identify the domain of apolipoprotein E (apo-E) involved in binding to low density lipoprotein (LDL) receptors on cultured human fibroblasts, apo-E was cleaved and the fragments were tested for receptor binding activity. Two large thrombolytic peptides (residues 1-191 and 216-299) of normal apo-E3 were combined with the phospholipid dimyristoylphosphatidylcholine (DMPC) and tested for their ability to compete with 125I-LDL for binding to the LDL (apo-B,E) receptors on human fibroblasts. The NH2-terminal two-thirds (residues 1-191) of apo-E3 was as active as intact apo-E3 . DMPC, while the smaller peptide (residues 216-299) was devoid of receptor-binding activity. When apo-E3 was digested with cyanogen bromide (CNBr) and the four largest CNBr fragments were combined with DMPC and tested, only one fragment competed with 125I-LDL for binding to cultured human fibroblasts (CNBr II, residues 126-218). This fragment possessed binding activity similar to that of human LDL. The 125I-labeled CNBr II . DMPC complex also demonstrated high affinity, calcium-dependent saturable binding to solubilized bovine adrenal membranes. The binding of CNBr II . DMPC was inhibited by 1,2-cyclohexanedione modification of arginyl residues or diketene modification of lysyl residues. In addition, the CNBr II had to be combined with DMPC before it demonstrated any receptor-binding activity. Pronase treatment of the membranes abolished the ability of this fragment to bind to the apo-B,E receptors. This same basic region in the center of the molecule has been implicated as the apo-B,E receptor-binding domain not only by this study but also by other studies showing that 1) natural mutants of apo-E that display defective binding have single amino acid substitutions at residues 145, 146, or 158; and 2) the apo-E epitope of the monoclonal antibody 1D7, which inhibits apo-E binding, is centered around residues 139-146.
24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease (2010)

Aspirin-induced cyclooxygenase (COX)-1 acetylation is irreversible and it is assumed that the platelet thromboxane-A2 aggregation pathway is inhibited for at least 24 hours (h) after aspirin ingestion. However, time course of biological efficacy of daily low-dose aspirin has rarely been assessed in patients with coronary artery disease (CAD). We aimed to assess the 24-h biological efficacy of daily low-dose aspirin in CAD patients. The peak and trough (2 h-24 h) effect of a chronic treatment with once daily dose aspirin were studied in 150 consecutive stable CAD patients. The main outcome measure was light transmission aggregometry (LTA) triggered with 0.5 mg/ml arachidonic acid (AA). In the last 47 consecutive patients, additional tests were conducted at 6, 12, 16, 20 h after last aspirin administration. 4.7% of the patients had significant aggregation (>20% maximal intensity LTA-AA) 2 h after aspirin ingestion and 24.7% at 24 h (p<0.0001). The more precise assessments in the last 47 patients showed that significant platelet aggregation progressively reappeared with time after aspirin intake (2 h--4% of patients, 6 h-- 4%, 12 h--11%, 16 h--16%, 20 h--19% and 24 h--28%). Concordant results were observed using production of thromboxane-B2 and other techniques evaluating AA-induced platelet aggregation/activation. No significant differences were found between lower (75-100 mg/day) and higher (>100 mg/day) dose aspirin. Such aspirin «resistance» at 24 h after ingestion was related to biological inflammatory markers, current smoking and diabetes. In conclusion, once daily aspirin does not provide stable 24-h antiplatelet protection in a significant proportion of CAD patients. Any biological assessment of aspirin efficacy should take time since last aspirin intake into consideration.
Treatment of Herpes simplex virus infections with topical antiviral agents. (1998)

Clinical studies of topical therapy against Herpes simplex virus (HSV) infections have been reviewed. Idoxuridine (IDU) 15% in dimethyl sulfoxide (DMSO), interferons, and penciclovir result in significant clinical benefit against this virus. IDU reduced pain duration and decreased time to loss of crust in a study of 301 patients. Alpha-interferon has shown synergism with other anti-HSV drugs such as caffeine, trifluorothymidine (TFT), DMSO, and nonoxynol-9. Finally, in a study of over 2,000 patients, application of penciclovir cream, both early and late in the course of HSV infection, decreased the duration of lesions, pain, and viral shedding. Acyclovir (ACV)-resistant strains of HSV are susceptible to (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and ascorbic acid shows promising effects against HSV. Using a vehicle that enhances skin penetration of a drug or possibly further exploring combination therapy may result in efficacious treatment of HSV. The possibility of topical vaccination or topical gene therapy may also prove beneficial in the future.
Chain of Custody Requirements in Admissibility of Evidence (1976)

Chain Of Custody Requirements In Admissibility Of Evidence
Electrical fields, nerve growth and nerve regeneration (1991)

The presence of voltage gradients within developing and damaged tissues led to the notion that the resultant electrical fields provide instructional cues to cells. Field effects on avian and amphibian neurones in vitro include increased differentiation, turning of neurites towards the cathode, increased rate of growth towards the cathode, resorption of anodefacing neurites, increased branching and increased filopodial activity. Electric fields enhance regeneration of damaged PNS and CNS neurones in animals as diverse as lampreys, frogs, rats and guinea-pigs, but the mechanisms by which fields produce their effects are not understood. Further examination of the interaction of fields with intracellular elements, such as the cytoskeleton and second messenger systems, may offer some insight.
GEMNET: a generalized, shuffle-exchange-based, regular, scalable, modular, multihop, WDM lightwave network (1995)

GEMNET is a generalization of shuffle-exchange networks and it can represent a family of network structures (including ShuffleNet and de Bruijn graph) for an arbitrary number of nodes. GEMNET employs a regular interconnection graph with highly desirable properties such as small nodal degree, simple routing, small diameter, and growth capability (viz. scalability). GEMNET can serve as a logical (virtual), packet-switched, multihop topology which can be employed for constructing the next generation of lightwave networks using wavelength-division multiplexing (WDM). Various properties of GEMNET are studied.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Complexities in the Treatment of Autoimmune Disease (1996)

Excitement has been high in the immunological community, as animal and human studies have suggested that autoimmune diseases can be prevented or inhibited by treatment with the offending endogenous antigen. But two cautionary reports in Science ( p. 2054 and p. 1707 ) indicate that under some circumstances oral or parental treatment with antigen can exacerbate the autoimmune attack. In his Perspective, McFarland summarizes these new results and explains the great complexity of the immune system that they imply.
A Monoclonal Antibody Enhances Ligand Binding of Fibronectin MSCRAMM (Adhesin) from Streptococcus dysgalactiae (1996)

A monoclonal antibody 3A10, generated from a mouse immunized with the Streptococcus dysgalactiae fibronectin (Fn) binding protein FnbA, was isolated, and its effect on ligand binding by the antigen was examined. The epitope for 3A10 was localized to a previously unidentified Fn binding motif (designated An) just N-terminal of the repeat domain which represents the primary ligand binding site on FnbA. Fn binding to Au was enhanced by 3A10 rather than inhibited. This effect was demonstrated in two different assays. First, in the presence of 3A10 the Au-containing proteins and synthetic peptide more effectively competed with bacterial cells for binding to Fn. Second, 3A10 dramatically increased the binding of biotin-labeled forms of the Au-containing proteins to Fn immobilized on a blotting membrane. Pure 3A10 IgG did not recognize the antigen by itself, and Fn was required for the immunological interaction between the antibody and the epitope. This induction effect of Fn was shown in both Western blot and enzyme-linked immunosorbent assay in which immobilized Au-containing molecules were probed with 3A10 in the presence of varying concentrations of Fn. Specificity analyses of 3A10 revealed that the monoclonal also recognized a ligand binding motif in a Streptococcus pyogenes Fn binding MSCRAMM but not the corresponding motifs in two related adhesins from Staphylococcus aureus and S. dysgalactiae. Furthermore, 3A10 stimulated Fn binding by S. pyogenes cells. These results together with subsequent biophysical studies presented in the accompanying paper (House-Pomepeo, K., Xu, Y., Joh, D., Speziale, P., and Höök, M. (1996) J. Biol. Chem. 271, 1379-1384) indicate that the ligand binding sites of Fn binding MSCRAMMs have little or no secondary structure. However, on binding to Fn, they appear to undergo a structural rearrangement resulting in a defined structure rich in beta sheet and expressing a ligand-induced binding site for antibodies such as 3A10.
Expanding the Reaction Scope of DNA-Templated Synthesis (2002)

Powerful reactions such as Wittig olefinations, nitro-aldol additions, dipolar cycloadditions, and Heck coupling reactions can be mediated by DNA templates. The yields of several DNA-templated reaction products are independent of the number of bases (n=0 or 10) separating the annealed reactive groups (as an example, the denaturing polyacrylamide gel electrophoresis of a DNA-templated Wittig reaction is shown).
Th Type 1-Stimulating Activity of Lung Macrophages Inhibits Th2-Mediated Allergic Airway Inflammation by an IFN-γ-Dependent Mechanism (2001)

In the mucosal immune system, resident dendritic cells are specialized for priming Th2-polarized immunity, whereas the Ag-presenting activity of macrophages has been linked with the development of Th1 phenotype. As an immune switch toward Th1 can protect against Th2-mediated allergic response, this study investigated the capacity of lung macrophages to stimulate Th1 responses during the secondary exposure to inhaled allergen, thereby suppressing Th2-mediated allergic airway inflammation in a murine model of allergic asthma. Following airway macrophage depletion in OVA-sensitized mice, lung T cells defaulted to a phenotype that produced less Th1 (IFN-gamma) and more Th2 (IL-4 and IL-5) cytokines, leading to more severe airway hyperreactivity and inflammation after intranasal Ag challenge. After OVA pulsing and adoptive transfer, lung macrophages selectively promoted a Th1 response in Ag-sensitized recipients and did not induce pulmonary eosinophilia. By contrast, OVA pulsing and adoptive transfer of a lung cell preparation, consisting of dendritic cells, B cells, and macrophages, promoted a Th2 response with an associated inflammatory response that was suppressed when macrophages were present and pretreated with IFN-gamma, but exacerbated when macrophages were depleted before IFN-gamma treatment. In addition, Th1-promoting activity of lung macrophages was not related to the autocrine production of IL-12p40. These results suggest that the Th1-promoting APC activity may be an inherent property of the lung macrophage population, and may play an important role, upon stimulation by IFN-gamma, in antagonizing an ongoing Th2 immunity and Th2-dependent allergic responses.
EFFECTS OF PRAVASTATIN ON CHRONIC REJECTION OF RAT CARDIAC ALLOGRAFTS1,2 (1998)

Progressive chronic vascular rejection, a leading cause of allograft failure, can be inhibited by pravastatin in a well-defined rat cardiac transplant model. Pravastatin appears to inhibit the synthesis and subsequent degradation of extracellular matrix proteins and block the infiltration of macrophages to the graft, which emphasizes that this inflammatory cell plays a major role in the pathogenesis of transplant chronic rejection.
Functional endoscopic sinus surgery in the management of chronic rhinosinusitis. An objective assessment (1991)

Considerable clinical success has been claimed for functional endoscopic sinus surgery but objective assessment of prospective series is lacking in the literature. Twenty-four patients with chronic rhino-sinusitis underwent assessment of symptoms by visual analogue scoring, nasomucociliary function by ciliary beat frequency, olfaction by qualitative olfactometry and nasal airway resistance by anterior rhinomanometry pre- and post-operatively. This demonstrated a significant improvement in all symptoms examined and in ciliary beat frequency. Quantitative olfaction and anterior rhinomanometry were not improved despite diminished symptoms. These results offer quantitative evidence of clinical improvement following functional endoscopic sinus surgery which supports the pathophysiological concepts on which the technique is based.