gebhart/patrepeval huggingface dataset:
Photochemical inactivation of pathogenic bacteria in human platelet concentrates (1994)

Platelet concentrates (PC) may be infrequently contaminated with low levels of bacteria that can cause septicemia and death in patients receiving transfusion therapy. We evaluated the efficacy of a photochemical decontamination (PCD) technique using 8-methoxypsoralen (8-MOP) and long wavelength UV light (UVA) to inactivate bacteria in standard therapeutic PC. Twelve phylogenetically distinct pathogenic bacteria, 5 gram-positive and 7 gram-negative organisms, were seeded into PC to a final challenge dose ranging from 10(5) to 10(7) colony-forming units (CFU)/mL. Contaminated PC were treated with 8-MOP (5 micrograms/mL) and 5 J/cm2 of UVA, a PCD treatment regimen found to adequately preserve in vitro platelet function. Greater than 10(5) CFU/mL of all 5 gram-positive (Staphylococcus aureus, Streptococcus epidermidis, Streptococcus pyogenes, Listeria monocytogenes, and Corynebacterium minutissimum) and 2 of the gram-negative (Escherichia coli and Yersinia enterocolitica) organisms were inactivated. The remaining 5 gram-negative organisms were more resistant, with less than 10(1) to 10(3.7) CFU/mL inactivated under these conditions. The inactivation efficiency for this resistant group of gram-negative organisms was improved when PC were resuspended in a synthetic storage medium with reduced plasma protein concentration (15%) and an increased 8-MOP concentration (23.4 micrograms/mL). Illumination with 3 J/cm2 of UVA in this system inactivated greater than 10(5) CFU/mL of 4 resistant gram-negative organisms (Salmonella choleraesuis, Enterobacter cloacae, Serratia marcescens, and Klebsiella pneumoniae) and 10(4.1) CFU/mL of the most resistant gram-negative organism (Pseudomonas aeruginosa). This level of PCD treatment did not adversely affect in vitro platelet function. These results demonstrate that PCD using 8-MOP (5 to 23.4 micrograms/mL) effectively inactivated high levels of pathogenic bacteria in PC with adequate preservation of in vitro platelet properties.
DOE/Opt: a system for design of experiments, response surface modeling, and optimization using process and device simulation (1994)

Rapid modeling and optimization of manufacturing processes, devices, and circuits are required to support modern integrated circuit technology development and yield improvement. We have prototyped and applied an integrated system, called DOE/Opt, for performing Design of Experiments (DOE), Response Surface Modeling (RSM), and Optimization (Opt). The system to be modeled and optimized can be either physical or simulation based. Within the DOE/Opt system, coupling to external simulation or experimental tools is achieved via an embedded extension language based on Tcl. The external problem then appears to DOE/Opt as a model with user defined inputs and outputs. DOE/Opt is used to generate splits for experiments, to dynamically build and evaluate regression models from experimental runs, and to perform nonlinear constrained optimizations using either regression models or embedded executions. The intermediate regression modeling can appreciably accelerate the optimization task when simulation or physical experiments are expensive. The primary application of DOE/Opt has been to process optimization using coupled process and device simulation. DOE/Opt has also been applied to process and device simulator tuning, and to aid in device characterization. Such a DOE/Opt system is expected to augment the use of TCAD tools and to utilize data collected by CIM systems in support of process synthesis. We have demonstrated the application of the system to process parameter determination, simulator tuning, process control modeling, and statistical process optimization. We are extending the system to more fully support emerging device design and process synthesis methodologies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
DIAGNOSIS OF OCCULT SUBRETINAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION BY INFRARED SCANNING LASER VIDEOANGIOGRAPHY (1993)

180 consecutive patients with exudative age-related macular degeneration and clinical signs of subretinal neovascular membranes were examined by scanning laser fluorescein angiography. This technique demonstrated well-defined, newly formed subretinal vessels in approximately 50%, ill-defined subretinal vessels in approximately 20%, and not visible or occult subretinal vessels in the remaining 30% of the patients. Patients with ill-defined or occult neovascular membranes were also examined with scanning laser infrared angiography with cardiogreen. Newly formed subretinal vessels were well defined in approximately 40% of these patients, and ill defined in 23%. In 37% of the patients, neovascularizations were also not visible with infrared angiography. Results of scanning laser infrared angiography seem to be superior to earlier methods of infrared angiography. Conditions are discussed under which fluorescein and cardiogreen angiography can demonstrate subretinal membranes in age-related maculopathy.
Ziram Causes Dopaminergic Cell Damage by Inhibiting E1 Ligase of the Proteasome (2008)

The etiology of Parkinson disease (PD) is unclear but may involve environmental toxins such as pesticides leading to dysfunction of the ubiquitin proteasome system (UPS). Here, we measured the relative toxicity of ziram (a UPS inhibitor) and analogs to dopaminergic neurons and examined the mechanism of cell death. UPS (26 S) activity was measured in cell lines after exposure to ziram and related compounds. Dimethyl- and diethyldithiocarbamates including ziram were potent UPS inhibitors. Primary ventral mesencephalic cultures were exposed to ziram, and cell toxicity was assessed by staining for tyrosine hydroxylase (TH) and NeuN antigen. Ziram caused a preferential damage to TH+ neurons and elevated alpha-synuclein levels but did not increase aggregate formation. Mechanistically, ziram altered UPS function through interfering with the targeting of substrates by inhibiting ubiquitin E1 ligase. Sodium dimethyldithiocarbamate administered to mice for 2 weeks resulted in persistent motor deficits and a mild reduction in striatal TH staining but no nigral cell loss. These results demonstrate that ziram causes selective dopaminergic cell damage in vitro by inhibiting an important degradative pathway implicated in the etiology of PD. Chronic exposure to widely used dithiocarbamate fungicides may contribute to the development of PD, and elucidation of its mechanism would identify a new potential therapeutic target.
Fine Specificity of the Myelin-Reactive T Cell Repertoire: Implications for TCR Antagonism in Autoimmunity (1998)

The use of altered peptide ligands (APL) to modulate T cell responses has been suggested as a means of treating T cell-mediated autoimmune disorders. We have assessed the therapeutic potential of TCR antagonist peptides in autoimmunity using murine experimental autoimmune encephalomyelitis (EAE) as a model. The Tg4 transgenic mouse expresses an MHC class II-restricted TCR specific for the immunodominant encephalitogenic epitope of myelin basic protein, Ac1-9 (acetylated N-terminal nonamer). We have used T cell lines derived from Tg4 mice to define the TCR contact residues within Ac1-9. APL with appropriate substitutions at the primary TCR contact residue were effective antagonists of Tg4 T cells. These antagonist APL, however, were found to induce EAE in susceptible, nontransgenic strains of mice. Underlying this, the Ac1-9-specific T cell repertoire of normal mice, rather than reflecting the Tg4 phenotype, showed considerable diversity in fine specificity and was able to respond to the Tg4 antagonist APL. Defining antagonist APL in vitro using T cell clones, therefore, was not a reliable approach for the identification of APL with EAE-suppressing potential in vivo. Our findings highlight the complexities of the autoreactive T cell repertoire and have major implications for the use of APL in autoimmune diseases.
Hypochlorous Acid, a Macrophage Product, Induces Endothelial Apoptosis and Tissue Factor Expression (2004)

Objective— Superficial erosion of coronary plaques due to endothelial loss causes acute coronary syndromes (ACS). Macrophages at erosive sites of human coronary atheroma present myeloperoxidase (MPO), an enzyme that produces hypochlorous acid (HOCl). Methods and Results— Activated MPO-positive macrophages or exogenous HOCl promoted detachment of endothelial cells (EC) from “Matrigel” substrata in vitro. Pathophysiologically relevant concentrations of HOCl caused EC death in a concentration-dependent manner: HOCl (20 to 50 μmol/L) induced rapid shrinkage of EC with nuclear condensation and disruption of EC monolayers, whereas concentrations >100 μmol/L immediately induced blebbing of the EC plasma membrane without shrinkage. HOCl (30 to 50 μmol/L) also induced caspase-3 activation, poly (ADP-ribose) polymerase degradation, and DNA laddering in EC. HOCl rapidly decreased endothelial Bcl-2 and induced cytochrome-C release, indicating that HOCl activates apoptotic EC death, partially via mitochondrial damage....
A Role for the RASSF1A Tumor Suppressor in the Regulation of Tubulin Polymerization and Genomic Stability (2004)

The high frequency with which the novel tumor suppressor RASSF1A is inactivated by promoter methylation suggests that it plays a key role in the development of many primary human tumors. Yet the mechanism of RASSF1A action remains unknown. We now show that RASSF1A associates with microtubules and that this association is essential for RASSF1A to mediate its growth inhibitory effects. Overexpression of RASSF1A promotes the formation of stable microtubules, whereas a dominant-negative fragment of RASSF1A destabilizes microtubule networks. The RASSF1 protein is expressed as two main isoforms, 1A and 1C. The smaller 1C isoform also associates with microtubules but is less effective at stabilizing them. Because RASSF1A and RASSF1C localize to the mitotic spindle, we examined their effects upon genomic instability. RASSF1A and RASSF1C block activated Ras-induced genomic instability. However, a point mutant of RASSF1C, identified in human tumors, was severely defective for stabilizing tubulin and was unable to block the genomic destabilizing effects of Ras. Thus, we identify a role for RASSF1A/C in the control of microtubule polymerization and potentially in the maintenance of genomic stability.
High-Power Generator for Radiofrequency Ablation: Larger Electrodes and Pulsing Algorithms in Bovine ex Vivo and Porcine in Vivo Settings (2007)

Markedly larger coagulation zones can be achieved with optimized high-power RF ablation. This may require longer pulsing intervals compared with those previously used.
Molecular Determinants of the Mechanism Underlying Acceleration of the Interaction between Antithrombin and Factor Xa by Heparin Pentasaccharide (2002)

The control of coagulation enzymes by antithrombin is vital for maintenance of normal hemostasis. Antithrombin requires the co-factor, heparin, to efficiently inhibit target proteinases. A specific pentasaccharide sequence (H5) in high affinity heparin induces a conformational change in antithrombin that is particularly important for factor Xa (fXa) inhibition. Thus, synthetic H5 accelerates the interaction between antithrombin and fXa 100-fold as compared with only 2-fold versus thrombin. We built molecular models and identified residues unique to the active site of fXa that we predicted were important for interacting with the reactive center loop of H5-activated antithrombin. To test our predictions, we generated the mutants E37A, E37Q, E39A, E39Q, Q61A, S173A, and F174A in human fXa and examined the rate of association of these mutants with antithrombin in the presence and absence of H5. fXa(Q61A) interacts with antithrombin alone with a nearly normal k(ass); however, we observe only a 4-fold increase in k(ass) in the presence of H5. The x-ray crystal structure of fXa reveals that Gln(61) forms part of the S1' and S3' pocket, suggesting that the P' region of the reactive center loop of antithrombin is crucial for mediating the acceleration in the rate of inhibition of fXa by H5-activated antithrombin.
Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. (1985)

R24 is an IgG3 mouse monoclonal antibody that identifies GD3, a prominent ganglioside on the surface of melanoma cells and other cells of neuroectodermal origin. Twelve patients with metastatic melanoma were treated with R24 at three dose levels, 8, 80, or 240 mg/m2, over a period of 2 weeks. Peak antibody levels in the serum were dose related and ranged from less than 0.1 to 62 micrograms/ml. Inflammatory reactions (urticaria, pruritus, erythema, subcutaneous ecchymoses) were observed around tumor sites in patients treated at doses greater than or equal to 80 mg/m2. Tumor biopsies during and after treatment showed lymphocyte and mast cell infiltration, mast cell degranulation, and complement deposition. Side effects were mild and were readily controlled by antihistamines. Major tumor regression has been observed in three patients.
Caspase-8 Serves Both Apoptotic and Nonapoptotic Roles (2004)

Knockout of caspase-8, a cysteine protease that participates in the signaling for cell death by receptors of the TNF/nerve growth factor family, is lethal to mice in utero. To explore tissue-specific roles of this enzyme, we established its conditional knockout using the Cre/loxP recombination system. Consistent with its role in cell death induction, deletion of caspase-8 in hepatocytes protected them from Fas-induced caspase activation and death. However, application of the conditional knockout approach to investigate the cause of death of caspase-8 knockout embryos revealed that this enzyme also serves cellular functions that are nonapoptotic. Its deletion in endothelial cells resulted in degeneration of the yolk sac vasculature and embryonal death due to circulatory failure. Caspase-8 deletion in bone-marrow cells resulted in arrest of hemopoietic progenitor functioning, and in cells of the myelomonocytic lineage, its deletion led to arrest of differentiation into macrophages and to cell death. Thus, besides participating in cell death induction by receptors of the TNF/nerve growth factor family, caspase-8, apparently independently of these receptors, also mediates nonapoptotic and perhaps even antiapoptotic activities.
Foldamers as Dynamic Receptors: Probing the Mechanism of Molecular Association between Helical Oligomers and Rodlike Ligands (2002)

Ein dynamischer Bindungsmechanismus ermöglicht die Assoziatbildung des hantelförmigen Liganden 2 mit helicalen gefalteten Oligo(m-phenylenethinylenen) 1 (siehe Schema). Die Assoziationskonstanten hängen von der Länge des Oligomers ab, wobei man die höchsten Werte für das Icosamer und das Docosamer findet. Die Oligomere nehmen helicale Konformationen ein, die formkomplementär zu 1 sind; kürzere und längere Oligomere weisen um etwa eine Größenordnung kleinere Assoziationskonstanten auf.
(+)-Catechin−Aldehyde Condensations:  Competition between Acetaldehyde and Glyoxylic Acid (2005)

(+)-Catechin reaction with two aldehydes (acetaldehyde and glyoxylic acid) was studied in winelike model solution. The two aldehydes were reacted either individually or together with (+)-catechin and in molar excess. The reactions were followed by HLPC-UV and HPLC-ESI/MS to monitor (+)-catechin disappearance as well as dimer and polymer appearance. In all reactions a reaction order of close to 1 for (+)-catechin disappearance was observed. (+)-Catechin disappearance was slower in the presence of acetaldehyde (t(1/2) = 6.7 +/- 0.2 h) compared to glyoxylic acid (t(1/2) = 2.3 +/- 0.2 h). When the two aldehydes were reacted together, (+)-catechin disappearance was faster (t(1/2) = 2.2 +/- 0.5 h). When aldehydes were reacted separately, the dimer appearance was independent of the type of aldehyde used but the ethyl-bridged dimer disappearance was slower with acetaldehyde. When aldehydes were reacted together, the dimer appearance changed. Ethyl-bridged dimers appeared before carboxymethine-bridged dimers, and their disappearance occurred earlier. Copolymers containing both ethyl and carboxymethine bridges were also observed.
Characterization of a glutathione-dependent formaldehyde dehydrogenase from Rhodobacter sphaeroides (1996)

Glutathione-dependent formaldehyde dehydrogenases (GSH-FDH) represent a ubiquitous class of enzymes, found in both prokaryotes and eukaryotes. During the course of studying energy-generating pathways in the photosynthetic bacterium Rhodobacter sphaeroides, a gene (adhI) encoding a GSH-FDH homolog has been identified as part of an operon (adhI-cycI) that also encodes an isoform of the cytochrome c2 family of electron transport proteins (isocytochrome c2). Enzyme assays with crude Escherichia coli extracts expressing AdhI show that this protein has the characteristic substrate preference of a GSH-FDH. Ferguson plot analysis with zymograms suggests that the functional form of AdhI is a homodimer of approximately40-kDa subunits, analogous to other GSH-FDH enzymes. These properties of AdhI were used to show that mutations which increase or decrease adhI expression change the specific activity of GSH-FDH in R. sphaeroides extracts. In addition, expression of the presumed adhI-cycI operon appears to be transcriptionally regulated, since the abundance of the major adhI-specific primer extension product is increased by the trans-acting spd-7 mutation, which increases the level of both isocytochrome c2 and AdhI activity. While transcriptional linkage of adhI and cycI could suggest a function in a common metabolic pathway, isocytochrome c2 (periplasm) and AdhI (cytoplasm) are localized in separate compartments of R. sphaeroides. Potential roles for AdhI in carbon and energy generation and the possible relationship of GSH-FDH activity to isocytochrome c2 will be discussed based on the commonly accepted physiological functions of GSH-FDH enzymes in prokaryotes and eukaryotes.
Identification of the high affinity binding site of transforming growth factor-alpha (TGF-alpha) for the chicken epidermal growth factor (EGF) receptor using EGF/TGF-alpha chimeras. (1994)

Human epidermal growth factor (hEGF) and human transforming growth factor-alpha (hTGF-alpha) are structurally related growth factors that share relatively little sequence homology. They both exert their biological action by binding to the cell-surface EGF receptor. hEGF and hTGF-alpha bind with similar affinity to the hEGF receptor, but hEGF binds with an approximately 100-fold lower affinity to the chicken EGF receptor compared with hTGF-alpha. To map the region in hTGF-alpha that confers its ability to bind with high affinity to the chicken EGF receptor, 10 hybrids of hEGF and hTGF-alpha were constructed by exchanging domains bordered by the third, fourth, and sixth conserved cysteine residues. The activity of the expressed chimeric proteins was determined by their ability to compete with 125I-labeled mouse EGF for binding to NIH-3T3 cells transfected with the hEGF receptor. Subsequent binding competition studies of NIH-3T3 cells transfected with the chicken EGF receptor showed that chimeras carrying TGF-alpha sequences COOH-terminal of the sixth cysteine have a high affinity for this receptor, similar to hTGF-alpha. In contrast, chimeras with EGF sequences in this COOH-terminal domain have only low binding affinity, similar to hEGF. We conclude that the COOH-terminal linear region of hTGF-alpha is important for its high affinity interaction with the chicken EGF receptor.
Microencapsulating Properties of Whey Proteins. 1. Microencapsulation of Anhydrous Milk Fat (1993)

Anhydrous milk fat was microencapsulated in whey protein concentrates and a whey protein isolate by spray drying. The effects of microencapsulating agent type and concentration (10 to 30% wtlwt) and of fat load (25 to 75% wt/wt) on the microencapsulation yield and efficiency were determined. Encapsulation yields of more than 90% were obtained for all evaluated systems. Microencapsulation efficiency was enhanced by increased solids concentration of wall solutions only in systems with low fat load. Microencapsulation efficiency was adversely affected by anhydrous milk fat load. Protein to lactose ratio affected the microencapsulation efficiency. Partial (50%) replacement of whey proteins by lactose resulted in the highest (95%) microencapsulation efficiency even at 75% fat load. Spherical microcapsules in which the milk fat was well isolated from the environment were obtained in all cases. The results indicate that microencapsulation of anhydrous milk fat by whey proteins is feasible and may have new applications for milk fat in food and dairy products. (Key words: anhydrous milk fat
Calcium mobilization by angiotensin II and neurotransmitter receptors expressed in Xenopus laevis oocytes (1988)

Specific receptors for angiotensin II (AII) were expressed in albino Xenopus laevis oocytes co-injected with poly(A)+ mRNA isolated from rat adrenal cortex and the calcium-specific photoprotein, aequorin. In such oocytes, AII elicited rapid, dose-dependent rises in cytosolic free calcium with light emission responses up to 100-fold above basal levels. Ligand-induced light emission was also observed in oocytes injected with rat brain mRNA and stimulated with acetylcholine and glutamate. These findings demonstrate that mammalian AII receptors expressed in Xenopus oocytes are functionally linked to intracellular Ca2+ mobilization, and indicate the potential value of aequorin-injected oocytes for rapid and specific screening of mRNAs transcribed from expression libraries containing cloned receptor cDNAs.
Evaluation of biocompatibility of the surface of polyethylene films modified with various water soluble polymers using Ar plasma-post polymerization technique (2000)

Surface modified polyethylene (g-PE), PMPC-g-PE, PGEMA-g-PE, PNIPAAm-g-PE and PHPMA-g-PE films with the water soluble polymers such as poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC), poly[2-(glucosyloxy)ethyl methacrylate] (PGEMA), poly(N-isopropylacrylamide) (PNIPAAm) and poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) were prepared by graft copolymerization using an Ar plasma-post polymerization technique. The surface of the g-PE films was characterized by means of X-ray photoelectron spectroscopy and the grafting percentage of PMPC, PNIPAAm and PHPMA was found to be 5.31, 2.83, and 3.40% for the corresponding g-PE film. Biocompatibility of the g-PE films was evaluated by the adsorption of serum proteins and the Michaelis constant (Km) for the enzymatic reaction of thrombin with synthetic substrate S-2238 in the presence of g-PE film. The biocompatibility of water soluble polymers such as PMPC, polyoxyethylene (POE), PGEMA, PNIPAAm and PHPMA was also evaluated by the same enzymatic reaction of thrombin with S-2238 in their polymer solutions. The Km values in the presence of water soluble polymers was found to decrease in the order PMPC > POE > PGEMA > PNIPAAm > PHPMA. As a conclusion, PMPC-g-PE film exhibited the most biocompatibility among g-PE films because its surface adsorbed less protein than those of the untreated PE and other g-PE films and it showed the largest Km for the enzymatic reaction.