gebhart/patrepeval huggingface dataset:
Field programmable port extender (FPX) for distributed routing and queuing (2000)

Field Programmable Gate Arrays (FPGAs) are being used to provide fast Internet Protocol (IP) packet routing and advanced queuing in a highly scalable network switch. A new module, called the Field-programmable Port Extender (FPX), is being built to augment the Washington University Gigabit Switch (WUGS) with reprogrammable logic.
Effects of barium on stimulus‐induced rises of [K+]o in human epileptic non‐sclerotic and sclerotic hippocampal area CA1 (2000)

In the hippocampus of patients with therapy-refractory temporal lobe epilepsy, glial cells of area CA1 might be less able to take up potassium ions via barium-sensitive inwardly rectifying and voltage-independent potassium channels. Using ion-selective microelectrodes we investigated the effects of barium on rises in [K+]o induced by repetitive alvear stimulation in slices from surgically removed hippocampi with and without Ammon's horn sclerosis (AHS and non-AHS). In non-AHS tissue, barium augmented rises in [K+]o by 147% and prolonged the half time of recovery by 90%. The barium effect was reversible, concentration dependent, and persisted in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid [GABA(A)] receptor antagonists. In AHS tissue, barium caused a decrease in the baseline level of [K+]o. In contrast to non-AHS slices, in AHS slices with intact synaptic transmission, barium had no effect on the stimulus-induced rises of [K+]o, and the half time of recovery from the rise was less prolonged (by 57%). Under conditions of blocked synaptic transmission, barium augmented stimulus-induced rises in [K+]o, but only by 40%. In both tissues, barium significantly reduced negative slow-field potentials following repetitive stimulation but did not alter the mean population spike amplitude. The findings suggest a significant contribution of glial barium-sensitive K+-channels to K+-buffering in non-AHS tissue and an impairment of glial barium-sensitive K+-uptake in AHS tissue.
The Biological Activity of Cross-Linked β Nerve Growth Factor Protein (1974)

The β nerve growth factor protein (βNGF), isolated from the high molecular weight 7S NGF complex in the mouse submaxillary gland, is a basic protein of molecular weight 26,500 which contains two identical peptide chains held together by noncovalent forces. The two chains separate in denaturing solvents. βNGF was cross-linked with dimethylsuberimidate at pH 9.5 and the cross-linked dimer separated from higher and lower molecular species by chromatography on an agarose column in the presence of guanidine hydrochloride. The behavior of the cross-linked βNGF, compared either to native βNGF or βNGF reacted with but not cross-linked by dimethylsuberimidate, on a agarose column in the presence of guanidine hydrochloride or on electrophoresis in the presence of sodium dodecyl sulfate confirmed that its two peptide chains were covalently linked. Cross-linked βNGF also gave a molecular weight of 27,000 by measurement of sedimentation equilibrium and the same amino acid composition as native βNGF except for some loss of lysine, arginine, tyrosine and cysteine. The cross-linked dimer of βNGF was indistinguishable from native βNGF in its ability to elicit fiber outgrowth from dorsal root ganglia in the bioassay. Cross-linked βNGF also recombined with the α and γ subunits of 7S NGF to reform a 7S NGF complex.
Binding energies and electronic structures of adsorbed titanium chains on carbon nanotubes (2002)

We have studied the binding energies and electronic structures of metal (Ti, Al, Au) chains adsorbed on single-wall carbon nanotubes (SWNT) using first-principles methods. Our calculations have shown that titanium is much more favored energetically over gold and aluminum to form a continuous chain on a variety of SWNT's. The interaction between titanium and carbon nanotube significantly modifies the electronic structures around Fermi energy for both zigzag and armchair tubes. The delocalized $3d$ electrons from the titanium chain generate additional states in the band-gap regions of the semiconducting tubes, transforming them into metals.
Synthesis and structure-activity relationships of 6-substituted 2',3'-dideoxypurine nucleosides as potential anti-human immunodeficiency virus agents (1990)

In order to study the structure-activity relationships of 2',3'-dideoxypurine nucleosides as potential anti-HIV agents, various 6-substituted purine analogues have been synthesized and examined in virus-infected and uninfected human peripheral blood mononuclear cells. N6-methyl-2',3'-dideoxyadenosine (D2MeA, 7a) was initially synthesized from adenosine via 2',3'-O-bisxanthate 3. As extension of this reaction to other N6-substituted compounds failed, a total synthetic method utilizing 2',3'-dideoxyribose derivative 9 was used for the synthesis of other purine nucleosides. An acid-stable derivative of N6-methyl-2',3'-dideoxyadenosine, 2'-fluoroarabinofuranosyl analogue 32 (D2MeFA), has been synthesized from the appropriate carbohydrate 24 by condensation with N6-methyladenine 23. Among these compounds, N6-methyl derivative (D2MeA) 7a proved to be one of the most potent antiviral agents. The order of potency for the 6-substituted compounds was NHMe greater than NH2 greater than Cl approximately N(Me)2 greater than SMe greater than OH approximately NHEt greater than SH greater than NHBn approximately H. The results suggest that a bulk tolerance effect at the 6-position of the 2',3'-dideoxypurine nucleoside may dictate the antiviral activity of these compounds. Acid-stable analogue 32 (D2MeFA) was found to be 20-fold less potent than the parent compound. Both D2MeA and D2MeFA were resistant to calf intestine adenosine deaminase. The presence of a fluorine atom in the carbohydrate moiety greatly increased stability to acid, making D2MeFA a potential orally active antiviral agent that could be useful for the treatment of retroviral infections in humans.
Adeno-associated virus capsid antigen presentation is dependent on endosomal escape (2013)

Adeno-associated virus (AAV) vectors are attractive for gene delivery-based therapeutics, but data from recent clinical trials have indicated that AAV capsids induce a cytotoxic T lymphocyte (CTL) response that eliminates transduced cells. In this study, we used traditional pharmacological agents and AAV mutants to elucidate the pathway of capsid cross-presentation in AAV-permissive cells. Endosomal acidification inhibitors blocked AAV2 antigen presentation by over 90%, while proteasome inhibitors completely abrogated antigen presentation. Using mutant viruses that are defective for nuclear entry, we observed a 90% decrease in capsid antigen presentation. Different antigen presentation efficiencies were achieved by selectively mutating virion nuclear localization signals. Low antigen presentation was demonstrated with basic region 1 (BR1) mutants, despite relatively high transduction efficiency, whereas there was no difference in antigen presentation between BR2 and BR3 mutants defective for transduction, as compared with wild-type AAV2. These results suggest that effective AAV2 capsid antigen presentation is dependent on AAV virion escape from the endosome/lysosome for antigen degradation by proteasomes, but is independent of nuclear uncoating. These results should facilitate the design of effective strategies to evade capsid-specific CTL-mediated elimination of AAV-transduced target cells in future clinical trials.
An improved long distance treatment for mutual inductance (2005)

This paper examines the controversy between two approaches to inductance extraction: loop versus partial treatments for integrated circuit applications. We advocate the first one, and explicitly show that the alternative demands monopole-like magnetic configurations as well as dense inductance matrices. We argue that the uncertainties in the loop inductance treatment associated with possibly unknown return paths are in fact negligible for frequencies where inductance effects are important. Within the loop formulation, we develop an efficient way of computing mutual inductances between loops in terms of the field generated by a magnetic dipole. We derive easily computable analytical formulas. On numerical simulations, this dipole approximation (DA) shows good accuracy when compared to FastHenry, down to distances smaller than 30 /spl mu/m for 90-nm lithography. The DA leads naturally to selection rules for discarding the coupling for certain geometrical configurations, an experimentally verifiable prediction.
Estimation of Blood-Brain Barrier Crossing of Drugs Using Molecular Size and Shape, and H-Bonding Descriptors (1998)

The influence of physicochemical properties, including lipophilicity, H-bonding capacity and molecular size and shape descriptors on brain uptake has been investigated using a selection of marketed CNS and CNS-inactive drugs. It is demonstrated that the polar surface area of a drug can be used as a suitable descriptor for the drugs' H-bonding potential. A combination of a H-bonding and a molecular size descriptor, i.e., the major components of lipophilicity and permeability, avoiding knowledge of distribution coefficients, is proposed to estimate brain penetration potential of new drug candidates. Previously reported experimental surface activity data appear to be strongly correlated to molecular size of the drug compounds. Present analysis offers a modern basis for property-based design and targeting of CNS drugs.
Enhanced Expression of ANGPTL2 in the Microvascular Lesions of Diabetic Glomerulopathy (2007)

The upregulation of ANGPTL2 in diabetic glomerulopathy shows a close relationship to abnormal microvasculature and endothelial inflammation. ANGPTL2 may play an important role in the pathogenesis of diabetic glomerulopathy.
Total Knee Arthroplasty Without Patellar Resurfacing (1986)

Twenty-seven knees treated between 1974 and 1980 had a total condylar type knee arthroplasty without patellar resurfacing; the average follow-up period was 5.2 years. Compared with a previously reported group of 100 consecutive total condylar arthroplasties, the overall results in this series were very similar. However, there was a significant difference in stair-climbing ability, and one-third of the patients could not use the operated knee for this activity. In most knees the patella could be resurfaced. A working hypothesis assumes that the patellar button can be omitted in patients with relatively normal patellar cartilage, or relatively young, active, or obese patients who are considered a high risk for patellar bone fractures.
An open trial of OKT3 in patients with multiple sclerosis (1991)

We report our experience with treatment with Muromonab-CD3 (Orthoclone OKT3) of 16 patients with multiple sclerosis (MS) who were in a progressive phase of their disease (n = 13) or in an acute severe attack lasting longer than 1 month without recovery (n = 3). We induced acute severe T-cytopenia with OKT3. Fifteen patients completed treatment for 10 days. Side effects were common and severe and included hypotension, nausea and vomiting, diarrhea, fever, and myalgia. In two of two patients tested, there was a transient though major rise in the levels of interferon gamma and tumor necrosis factor in the first 12 hours of treatment. Nonetheless, we did not detect new clinical or MRI activity of MS during the period of treatment, although many patients deteriorated transiently in disability scores. At the conclusion of follow-up, only four patients had deteriorated by 1.0 or more points on the Expanded Disability Status Scale of Kurtzke (EDSS) (73% stabilization rate). Of those patients who deteriorated, two died of complications of MS (EDSS 10). Only two patients had clinical improvement at 1 year follow-up. The attendant toxicity of OKT3 makes it unlikely that it will play a major role in the treatment of MS.
Utilisation of CO2 as a chemical feedstock: opportunities and challenges (2007)

The need to reduce the accumulation of CO(2) into the atmosphere requires new technologies able to reduce the CO(2) emission. The utilization of CO(2) as a building block may represent an interesting approach to synthetic methodologies less intensive in carbon and energy. In this paper the general properties of carbon dioxide and its interaction with metal centres is first considered. The potential of carbon dioxide as a raw material in the synthesis of chemicals such as carboxylates, carbonates, carbamates is then discussed. The utilization of CO(2) as source of carbon for the synthesis of fuels or other C(1) molecules such as formic acid and methanol is also described and the conditions for its implementation are outlined. A comparison of chemical and biotechnological conversion routes of CO(2) is made and the barriers to their exploitation are highlighted.
Complexes between nucleic acid bases and bivalent metal ions. III. Syntheses and spectral analyses of cytosine-calcium chloride complexes. (1980)

New 2 : 1 cytosine-CaCl2 and 1 : 1 cytosine-CaCl2 complexes were obtained from 70% ethanol and water solutions, respectively. The infrared and proton magnetic resonance spectra of the complexes were characterized in comparison with those of many cytosinemetal complexes. On the basis of these data, it is suggested that calcium coordinates with the N (3) and C (2)=O sites of cytosine in the cytosine-CaCl2 complexes.
Evidence that Leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism. (1986)

The pathogenic protozoan Leishmania donovani must gain entrance into mononuclear phagocytes to successfully parasitize man. The parasite's extra-cellular promastigote stage is ingested by human peripheral blood monocytes or monocyte-derived macrophages in the absence of serum, in a manner characteristic of receptor-mediated endocytosis. We have found remarkable similarities between the macrophage receptor(s) for promastigotes and a previously characterized eucaryotic receptor system, the mannose/fucose receptor (MFR), that mediates the binding of zymosan particles and mannose- or fucose-terminal glycoconjugates to macrophages. Ingestion of promastigotes by monocyte-derived macrophages was inhibited by several MFR ligands. Mannan (2.5 mg/ml) decreased ingestion by 63.7% (p less than 0.001), and the neoglycoproteins mannose-BSA and fucose-BSA (20 micrograms/ml) inhibited parasite ingestion by 46.5% and 39.6%, respectively (p less than 0.04). In contrast, promastigote ingestion by monocytes was unaffected by MFR ligands. These results are consistent with reports that MFR activity is present in monocyte-derived macrophages but not in monocytes. Furthermore, attachment of promastigotes to macrophages, assessed by using cytochalasin D to prevent phagocytosis, was reduced 49.8% by mannan. Reorientation of the MFR to the ventral surface of the cell was achieved by plating macrophages onto mannan-coated coverslips, reducing MFR activity on the exposed cell surface by 94% as assessed by binding of 125I-mannose-BSA. Under these conditions, ingestion of promastigotes was inhibited by 71.4% (p less than 0.006). Internalization of the MFR by exposure of macrophages to zymosan before infection with promastigotes resulted in a 62.3% decrease in parasite ingestion (p less than 0.006). Additionally NH4Cl, a weak lysosomotropic base that impairs MFR recycling, decreased macrophage ingestion of promastigotes by 38.2% (p less than 0.03, 30 mM NH4Cl). Subinhibitory concentrations of NH4Cl (10 mM) and of mannan (0.25 mg/ml) together inhibited parasite ingestion by 76.4% (p less than 0.002). These studies suggest that L. donovani promastigotes may utilize a receptor system on human monocyte-derived macrophages, the MFR, to efficiently parasitize the human host.
Quantification of Zinc Finger Nuclease-Associated Toxicity (2010)

The recent development of artificial zinc finger nucleases (ZFNs) for targeted genome editing has opened a broad range of possibilities in biotechnology and gene therapy. The ZFN technology allows a researcher to deliberately choose a target site in a complex genome and create appropriate nucleases to insert a DNA double-strand break (DSB) at that site. Gene editing frequencies of up to 50% in non-selected human cells attest to the power of this technology. Potential side effects of applying ZFNs include toxicity due to cleavage at off-target sites. This can be brought about by insufficient specificity of DNA binding, hence allowing ZFN activity at similar target sequences within the genome, or by activation of the ZFN nuclease domains before the nuclease is properly bound to the DNA. Here, we describe two different methods to quantify ZFN-associated toxicity: the genotoxicity assay is based on quantification of DSB repair foci induced by ZFNs whereas the cytotoxicity is based on assessing cell survival after application of ZFNs.
Regulation of Experimental Autoimmune Encephalomyelitis by Interleukin‐12 (1996)

We have evaluated the effects of rmIL-12 on the course of adoptively transferred EAE. When mice were injected with LNC that had been stimulated in vitro with PLP in the presence of rmIL-12, the subsequent course of disease was more severe and prolonged than controls. In vitro stimulation with PLP in the presence of IL-12 was associated with an increase in IFN-gamma and decrease in IL-4-producing cells, indicating a preferential expansion of Th1 effector cells. At peak disease, no notable differences in either the cellular composition or cytokine expression within CNS lesions was seen between groups. However, the frequency of macrophages that stained positively for inducible nitric oxide synthase (iNOS) was increased in animals challenged with rmIL-12 treated LNC. These data suggest that in addition to promoting the preferential expansion of IFN-gamma-producing cells by rmIL-12 treatment in vitro, in vivo effects leading to macrophage activation and iNOS expression may contribute to the severe, protracted course of CNS inflammation in this model. In contrast, treatment of mice with an antibody to murine IL-12 following cell transfer completely prevented paralysis with only 40% of the mice developing mild disease. These data suggest that endogenous IL-12 plays a pivotal role in the pathogenesis of this model of autoimmune disease.
Rapid purification of a cloned gene product by genetic fusion and site-specific proteolysis. (1984)

We have developed a rapid and general technique for purification of a protein encoded by a cistron contained in a recombinant DNA clone. The technique consists of fusing the target cistron DNA in the correct reading frame to a marker cistron via a piece of DNA that codes for a linker peptide. The target cistron in the example presented here is the replication initiator cistron of the plasmid R6K. The linker is a DNA fragment encoding 60 amino acids from the triple helical region of chicken pro alpha-2 collagen, and the marker cistron encodes the beta-galactosidase protein of Escherichia coli. The tripartite hybrid protein was rapidly purified by selective binding to and elution from a beta-galactosidase specific-affinity column. The hybrid protein was then digested with a purified microbial collagenase to cleave the linker, and high-pressure liquid chromatography allowed the rapid isolation of the target protein from the marker protein. Using this technique, we have purified the highly labile R6K replication initiator to homogeneity, and we have resolved the protein into NH2-terminal and COOH-terminal segments. We have further shown, by in vitro binding, that the COOH-terminal segment has at least one DNA-binding domain. The domain binds to the same restriction fragments of the R6K chromosome as the intact or beta-galactosidase-tagged initiator protein.
Recommendations for Advancing Development of Acute Stroke Therapies (2003)

It is hoped that these suggestions will enhance future stroke trials and the development of effective, new acute stroke treatments that are maximally effective and utilized.
Nephrotic Plasma Alters Slit Diaphragm–Dependent Signaling and Translocates Nephrin, Podocin, and CD2 Associated Protein in Cultured Human Podocytes (2005)

Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the slit diaphragm (SD) proteins nephrin, podocin, and CD2-associated protein (CD2AP) to function optimally. The effects of normal human plasma and nephrotic plasma on podocytes were tested, focusing particularly on the SD complex. With the use of a conditionally immortalized human podocyte cell line, it first was shown that exposure to normal and non-nephrotic human plasma leads to a concentration of nephrin, podocin, CD2AP, and actin at the cell surface. Next, the effects of plasma from patients with nephrotic conditions to non-nephrotic conditions were compared. When exposed to all nephrotic plasma samples (and a non-human serum control), nephrin podocin and CD2AP assumed a cytoplasmic distribution; nephrin and synaptopodin were selectively downregulated, and the relocation of nephrin induced by nephrotic plasma could be rescued back to the plasma membrane by co-incubation with non-nephrotic plasma. Furthermore, intracellular calcium signaling was altered by nephrotic plasma, which was mediated by tyrosine kinase phosphorylation. With the use of nephrin mutant human cell lines, it was shown that this signaling and translocation response to normal plasma is nephrin dependent. This work demonstrates that nephrotic plasma seems to be deficient in factors that act via the podocyte SD complex, which are essential in maintaining its physiologic function.
Totally percutaneous aortic aneurysm repair: methods and outcomes using the fully integrated IntuiTrak endovascular system. (2010)

PEVAR using the IntuiTrak System with 19Fr introducer sheath with vessel closure facilitated by the Prostar XL device is feasible, even in patients with challenging access anatomy. Further evaluation in a prospective, multicenter, randomized trial is warranted.
Enhanced Inhibition of Neointimal Hyperplasia by Genetically Engineered Endothelial Progenitor Cells (2004)

Background— Circulating endothelial progenitor cells (EPCs) have been reported previously. In this study, we examined the hypothesis that overexpression of vasculoprotective gene endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1) in EPCs enhances their ability to inhibit neointimal hyperplasia. Methods and Results— EPCs were isolated from rabbit peripheral blood, expanded in culture, and transduced with pseudotyped retroviral vectors expressing human eNOS (eNOS-EPCs), HO-1 (HO-1-EPCs), or green fluorescent protein (GFP-EPCs). Transduction efficiency of EPCs ex vivo was &gt;90%. Four groups of rabbits (n=5 to 6 per group) were subjected to balloon angioplasty of the common carotid artery. Immediately after injury, ≈5×10 6 autologous eNOS-EPCs or HO-1-EPCs were transplanted into the injured vessel. Control animals received an equivalent number of GFP-EPCs or Ringer’s saline. Two weeks after transplantation, eNOS and HO-1 transgene transcripts and proteins were detected in the transduced rabbit vessels. Endothelialization was enhanced in the EPC-transplanted vessels independently of gene transfer. Neointimal thickening was significantly reduced in the GFP-EPC-treated vessels relative to the saline control. Neointima size was further reduced in vessels treated with eNOS-EPCs. Surprisingly, no additional reduction was seen in vessels treated with HO-1-EPCs relative to GFP-EPCs. Thrombosis occurred in ≈50% of the saline-treated vessels but was virtually absent in all EPC-transplanted vessels. Conclusions— We conclude that transplantation of autologous EPCs overexpressing eNOS in injured vessels enhances the vasculoprotective properties of the reconstituted endothelium, leading to inhibition of neointimal hyperplasia. This cell-based gene therapy strategy may be useful in treatment of vascular disease.