gebhart/patrepeval huggingface dataset:
Ultrastructural localization of blood-retinal barrier breakdown in diabetic and galactosemic rats. (1990)

Breakdown of the blood-retinal barrier (BRB) is an early event in diabetic and galactosemic rats, but the location and nature of the specific defect(s) are controversial. Using an electron microscopic immunocytochemical technique, the retinas of normal, diabetic, and galactosemic rats were immunostained for endogenous albumin. Normal rats showed little evidence of BRB breakdown at either the inner barrier (retinal vasculature) or the outer barrier (retinal pigment epithelium) (RPE). In diabetic and galactosemic rats, as was true in human diabetics, BRB breakdown occurred predominantly at the inner BRB, but in some cases at the outer barrier as well. Treatment with the aldose reductase inhibitor sorbinil largely prevented BRB failure in galactosemic rats. In the inner retina of diabetic and galactosemic rats, albumin was frequently demonstrated on the abluminal side of the retinal capillary endothelium (RCE) in intercellular spaces, basal laminae, pericytes, ganglion cells, astrocytes, and the perinuclear cytoplasm of cells in the inner nuclear layer. Albumin did not appear to cross RCE cell junctions; however, it was occasionally seen in RCE cytoplasm of galactosemic rats. In the outer retina, albumin was frequently detected in the subretinal space, in the intercellular space between photoreceptors, and in the perinuclear cytoplasm of photoreceptor cells, but was only infrequently found in the RPE cells constituting the barrier. Albumin derived from the choroidal vasculature did not appear to cross the tight junctions of the RPE. These findings suggest that specific sites of BRB compromise are infrequent but that once albumin has crossed the RCE or RPE it freely permeates the retinal tissue by filling intercellular spaces and permeating the membranes of cells not implicated in BRB formation. The diffuse cytoplasmic staining of some RCE and RPE cells suggests that the predominant means of BRB breakdown in diabetes and galactosemia involves increased focal permeability of the surface membranes of the RCE and RPE cells rather than defective tight junctions or vesicular transport.
Amylin evokes phosphorylation of P20 in rat skeletal muscle (1999)

To investigate the signal transduction events underlying amylin's actions, the amylin-evoked protein phosphorylation cascade was analysed using two-dimensional gel electrophoresis. We found that phosphorylation of three isoelectric variants of P20 (termed ARPP1, ARPP2 and ARPP3) was associated with amylin's actions in rat skeletal muscle. Amylin decreased phosphorylation of ARPP1 and increased phosphorylation of ARPP2 and ARPP3 in a dose-dependent manner. Insulin inhibited amylin-evoked phosphorylation of ARPP2 and ARPP3. The amylin-selective antagonist rat amylin-(8-37) completely reversed amylin's action on ARPP3 and partially decreased phosphorylation of ARPP2. By contrast, the CGRP-selective antagonist, human CGRP-(8-37) blocked phosphorylation of ARPP2 but had little effect on ARPP3. These results suggest that amylin modifies phosphorylation of P20 via two independent mechanisms, and that P20 might be a molecule mediating amylin's biological functions.
Porous Multilayer-Coated PDMS Stamps for Protein Printing (2009)

A polyelectrolyte multilayer was assembled on top of a patterned PDMS stamp employing the layer-by-layer (LbL) assembly technique. By post-treatment with a base and further cross-linking, a porous multilayer-coated PDMS composite stamp was obtained. With the pore structures acting as an ink reservoir, the multiple printing of proteins was successfully achieved without the need to re-ink the stamp.
Hospital-Based Use of Therapeutic Hypothermia after Cardiac Arrest in Adults (2009)

Improving survival and brain function after initial resuscitation from cardiac arrest remains a critical challenge with few therapeutic options. The publication of several randomized controlled trials supporting the use of therapeutic hypothermia in cardiac arrest survivors has provided a remarkable opportunity to reduce mortality and neurologic disability from this leading cause of death. On the strength of these trials, therapeutic hypothermia has now been incorporated in the American Heart Association guidelines for post-resuscitation care. This review will focus on the hospital-based application of therapeutic hypothermia in adult cardiac arrest survivors, with special attention to practical aspects of cooling, protocol development, and evaluation of recent data from "real world" experiences using hypothermia as a treatment option. Finally, remaining research questions and directions for future improvements in therapy will be discussed.
Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types. (1989)

To characterize the host range of different strains of HIV-1, we have used four types of cells, primary monocyte-derived macrophages (MDM), primary PBL, a promonocyte cell line (U937), and a CD4+ T cell line (SUP-T1). These cells were infected with three prototype strains of HIV-1, a putative lymphocyte-tropic strain (IIIB), and two putative monocyte-tropic strains (SF162 and DV). Infections were monitored by assays for infectious virus, for cell-free and cell-associated viral antigen (p24), and for the proportion of cells infected by immunohistochemical staining. It was concluded that: (a) the use of four different cell types provides a useful biological matrix for distinguishing the tropism of different strains of HIV-1; this matrix yields more information than the infection of any single cell type. (b) A monocyte-tropic strain of HIV-1, such as strain SF162, shows a reciprocal host range when compared with a lymphocyte-tropic strain such as IIIB; strain SF162 replicates well in primary MDM but not in U937 or SUP-T1 cells, while strain IIIB replicates well in both U937 and SUP-T1 cells but not in MDM. (c) Both lymphocyte-tropic and monocyte-tropic strains of HIV-1 replicate well in PBL. (d) The promonocyte cell line, U937, and the T cell line, SUP-T1, differ markedly from primary cells, such as MDM and PBL, in their ability to support the replication of different strains of HIV-1; these cell lines cannot be used as surrogates for primary cells in host range studies of HIV-1 strains.
Toxicity of disodium sebacate (1990)

Investigations of the acute toxicity of disodium sebacate after oral, i.p. and i.v. administration were carried out on 220 Wistar rats (110 males and 110 females) and 204 New Zealand rabbits (102 males and 102 females). No oral acute toxicity was found. On the contrary LD50 +/- s.e. of 5500 +/- 830 mg/kg b.w. and 6000 +/- 850 mg/kg b.w. were found respectively for rats and rabbits after i.p. sebacate administration. When sebacate was given i.v., the median lethal dose +/- s.e. was 560 +/- 86.5 mg/kg b.w. for rats and 1400 +/- 267.2 mg/kg b.w. for rabbits. Similar results were obtained in corresponding groups of animals (in total 220 rats and 204 rabbits) given oral, i.p. and i.v. saline solutions with added glucose in order to obtain the same value of osmolarity and sodium ion concentration. The above results appear indicative of low toxicity of disodium sebacate, and suggest that the toxic effects found could be due to the sodium content of the compound administered. Similarly, subacute and chronic toxicity was investigated in forty rats and forty rabbits (twenty males and twenty females) fed disodium sebacate incorporated into pellets. When compared to the control animals, no significant differences in biological parameters (clinical, chemical and haematological values, growth curves and histological findings for the different organs) were observed in the test groups during the treatment period. In addition, fetal toxicity, teratogenicity and neonatal toxicity were investigated in twenty female rats and twenty female rabbits. Sebacic acid did not show any teratogenic effect and the development of the fetuses was regular.
Large Scale Preparation of Crystalline Glucose from Raw Starch in Corn Flour (1998)

Starch in considerable amount is lost during its purification from raw materials. Further, purification costs energy and time. To avoid these, starch in corn flour was hydrolyzed by the synergistic action of α-amylase and glucoamylase while avoiding high temperature gelatinization and liquefaction processes. When 1600 g (16%, W/W suspension) and 4000 g (40%, WW suspension) corn flour was hydrolyzed and purified, 76.0% and 50.2% glucose yields were obtained. The residues obtained were rich in protein and minerals.
Colchicine binding to antibodies. (1980)

Antibodies to colchicine have been prepared by injecting rabbits with an antigen prepared by coupling deacetylcolchicine to bovine serum albumin with a water-soluble carbodiimide. Sera of high titer were obtained with apparent dissociation constants for colchicine ranging from 5 to 17 nM. Binding was rapid and occurred at low temperatures. The chemical specificity of the binding site(s) resembled that in tubulin for the A and B rings of colchicine. Unlike tubulin, the antibody binding site tolerated numerous changes in the tropolone moiety (C ring). In contrast to tubulin, binding of colchicine to the antibody site did not promote fluorescence. The colchicine binding capacity of the antibody was high enough to prevent colchicine fluorescence in the presence of tubulin and to restore polymerization in colchicine-inhibited tubulin preparations.
multithreaded context for robust conversational interfaces (2004)

We focus on the issue of robustness of conversational interfaces that are flexible enough to allow natural "multithreaded" conversational flow. Our main advance is to use context-sensitive speech recognition in a general way, with a representation of dialogue context that is rich and flexible enough to support conversation about multiple interleaved topics, as well as the interpretation of corrective fragments. We explain, by use of worked examples, the use of our "Conversational Intelligence Architecture" (CIA) to represent conversational threads, and how each thread can be associated with a language model (LM) for more robust speech recognition. The CIA uses fine-grained dynamic representations of dialogue context, which supersede those used in finite-state or form-based dialogue managers. In an evaluation of a dialogue system built using this architecture we found that 87.9% of recognized utterances were recognized using a context-specific language model, resulting in an 11.5% reduction in the overall utterance recognition error rate, and a 13.4% reduction in concept error rate. Thus we show that by using context-sensitive recognition based on the predicted type of the user's next dialogue move, a more flexible dialogue system can also exhibit an improvement in speech recognition performance.
The impact of silicon nano-wire technology on the design of single-work-function CMOS transistors and circuits (2006)

This three-dimensional exploratory study on vertical silicon wire MOS transistors with metal gates and undoped bodies demonstrates that these transistors dissipate less power and occupy less layout area while producing comparable transient response with respect to the state-of-the-art bulk and SOI technologies. The study selects a single metal gate work function for both NMOS and PMOS transistors to alleviate fabrication difficulties and then determines a common device geometry to produce an OFF current smaller than 1 pA for each transistor. Once an optimum wire radius and effective channel length is determined, DC characteristics including threshold voltage roll-off, drain-induced barrier lowering and sub-threshold slope of each transistor are measured. Simple CMOS gates such as an inverter, two- and three-input NAND, NOR and XOR gates and a full adder, composed of the optimum NMOS and PMOS transistors, are built to measure transient performance, power dissipation and layout area. Simulation results indicate that worst-case transient time and worst-case delay are 1.63 and 1.46 ps, respectively, for a two-input NAND gate and 7.51 and 7.43 ps, respectively, for a full adder for a fan-out of six transistor gates (24 aF). Worst-case power dissipation is 62.1 nW for a two-input NAND gate and 118.1 nW for a full adder at 1 GHz for the same output capacitance. The layout areas are 0.0066 µm2 for the two-input NAND gate and 0.049 µm2 for the full adder circuits.
Composition of Fatty Acids in Winged Bean [Psophocarpus tetragonolobus (L.) DC] Seed Oil (1995)

Abstract The oil content and fatty acid composition of 19 genetically improved cultivars of winged bean [ Psophocarpus teragonolobus (L.) DC] seeds were determined. The oil content ranged from 14.5% to 22.7%. Oleic acid (41.4% ± 1.5) and linoleic acid (29.7% ± 1.1) were main constitutents and contributed above 70%, however, the total unsaturated fatty acid ranged from 66.8% to 78.9% (73.9% ± 0.9). Varieties BRWS‐103. BRWS‐114 and BRWS‐118 have higher linoleic acid while BRWS‐101, BRWS‐102 and BRWS‐105 have many fold higher oleic acid. Palmitic (10.9% ± 0.6), behenic 6.7% ± 0.4) and stearic (3.5 % ± 0.3) acids were the major saturated fatty acids. Parinanc acid, a toxic fatty acid was absent in seed oil of all the varieties. The oil can be stored for longer period being low in hnolenic acid (0.9% ± 0.1). Fettsäure‐Zusammensetzung des Samenöls von Psophocarpus tetragonolobus (L.) DC Der Ölgehalt und die Fettsäure‐Zusammcnsetzung von 19 genctisch veränderten Sorten von Psophocarpus tetragonolobus (L.) DC wurden untersucht. Dcr Ölgehalt schwankte zwischen 14.5% und 22.7 %. Ölsäure (41.4% ± 1.5) und Linolsäure (29.7% ± 1.1) waren die Hauptbestandteile (mehr als 70%); dcr Gehalt an ungesäitigten Fettsäuren lag zwischen 66.8% und 78.9% (73.9% ± 0.9). Die Sortcn BRWS‐103. BRWS‐114 und BRWS‐118 hatten einen hohen Linolsäuregehalt, während die Sortcn BRWS‐101, BRWS‐102 und BRWS‐105 einen vielfach höhercn Ölsäuregchalt aufwiesen. Palmitin‐(10.9% ± 0.6), Bchen‐(6.7% + 0.4) und Stcarinsäure (3.5% + 0.3) waren die wichtigstcn gesättigten Fettsäuren. Die toxische Parinarsäure war in alien Sortcn nicht vorhanden. Das Öl enthält wenig Linolensäure (0.9%n ± 0.1) und kann langcre Zeit gelagert werden.
Mechanism of ganciclovir uptake by rabbit retina and human retinal pigmented epithelium cell line ARPE-19 (2004)

Our results indicate that although the rabbit retina and the ARPE-19 cell line express nucleoside and nucleobase transporters, translocation of ganciclovir does not involve any carrier-mediated transport process. Rather, ganciclovir uptake by the rabbit retina and ARPE-19 cells is governed primarily by passive diffusion.
Characterization of three loci for homologous gene targeting and transgene expression (2013)

Integrative gene transfer is widely used for bioproduction, drug screening, and therapeutic applications but usual viral methods lead to random and multicopy insertions, contribute to unstable transgene expression and can disturb endogenous gene expression. Homologous targeting of an expression cassette using rare-cutting endonucleases is a potential solution; however the number of studied loci remains limited. Furthermore, the behavior and performance of various types of gene cassettes following gene targeting is poorly defined. Here we have evaluated three loci for gene targeting, including one locus compatible with the proposed Safe Harbor criteria for human translational applications. Using optimized conditions for homologous gene targeting, reporter genes under the control of different promoters were efficiently inserted at each locus in both sense and antisense orientations. Sustainable expression was achieved at all three loci without detectable disturbance of flanking gene expression. However, the promoter, the integration locus and the cassette orientation have a strong impact on transgene expression. Finally, single targeted integrations exhibited greatly improved transgene expression stability versus multicopy or random integration. Taken together, our data suggest a potential set of loci for site-specific transgene integration, suitable for a variety of biotechnological applications.
IL-12 directly stimulates expression of IL-10 by CD5+ B cells and IL-6 by both CD5+ and CD5- B cells: possible involvement in age-associated cytokine dysregulation (1997)

Constitutive expression of p35 and p40 IL-12 mRNA was detected in splenic macrophages isolated from aged mice. Macrophages were also implicated as the cell type responsible for the dysregulated IL-6 and tumor necrosis factor (TNF)-alpha commonly observed to be constitutively produced by lymphoid cells from aged donors. A role for IL-12 in the aging process was suggested when it was found that recombinant IL-12 (rIL-12) directly stimulated splenic CD5+ B cells to secrete IL-10, and both CD5+ and CD5- B cells could be directly induced to produce IL-6 in response to rIL-12. Furthermore, splenocytes from aged animals cultured in the presence of anti-IL-12 antibodies demonstrated a significant reduction in spontaneous IL-6, IL-10 and IFN-gamma production. Based on these observations it was concluded that IL-12 might be responsible for the dysregulated production of IL-10 and IFN-gamma known to occur in aged animals. Treatment of aged animals with low doses of dehydroepiandrosterone sulfate, previously established to be immunocorrective in immunosenescent animals, reduced the age-associated alterations in IL-12 mRNA and protein expression. The mechanisms responsible for the abnormal constitutive expression of inflammatory cytokines by the macrophages of aged animals may play an important afferent role in establishing the immunosenescent phenotype.
Optical properties of manganese-doped nanocrystals of ZnS (1994)

We report for the first time that doped nanocrystals of semiconductor can yield both high luminescent efficiencies and lifetime shortening at the same time. Nanocrystals of Mn-doped ZnS with sizes varying from 3.5 to 7.5 nm were prepared by a room temperature chemical process. These nanosized particles have an external photoluminescent quantum efficiency as high as 18% at room temperature and a luminescent decay at least 5 orders of magnitude faster than the corresponding ${\mathrm{Mn}}^{2+}$ radiative transition in the bulk crystals. Luminescent measurements show that the efficiency increases with decreasing size of the particles, as expected within the framework of an electron-hole localization theory. These results suggest that doped nanocrystals are indeed a new class of materials heretofore unknown.
Combined mannitol and deferoxamine therapy for myohemoglobinuric renal injury and oxidant tubular stress. Mechanistic and therapeutic implications. (1992)

Mannitol (M) and deferoxamine (DFO) can each protect against myohemoglobinuric acute renal failure (MH-ARF). This study assessed M-DFO interactions during MH-ARF to help discern mechanisms of renal injury, and to define whether M + DFO exerts additive or synergistic antioxidant/cytoprotective effects. Rats subjected to the glycerol model of MH-ARF were treated with (a) M; (b) DFO; (c) M + DFO; or (d) no protective agents. Relative degrees of protection (24-h plasma urea/creatinine concentrations) were M + DFO greater than M greater than DFO greater than or equal to no therapy. To assess whether catalytic Fe is generated during MH-ARF, the bleomycin assay was applied to plasma/urine samples obtained 0-2 h post-glycerol injection. Although striking plasma and urinary increments were noted, excess renal hydroxyl radical (.OH) production was not apparent (gauged by the salicylate trap method). M increased catalytic Fe excretion (four times), whereas DFO eliminated its urinary (but not plasma) activity. To determine direct M/DFO effects on proximal tubular cell oxidant injury, isolated rat proximal tubular segments (PTS) were incubated with toxic dosages of FeSO4 or H2O2. Despite inducing cell injury (lactic dehydrogenase release), Fe caused no .OH production. DFO conferred dose-dependent cytoprotection, correlating with increased, not decreased, .OH generation. Although M scavenged this .OH excess, it had no additive or independent, protective effect. H2O2 cytotoxicity correlated with increased catalytic Fe (but not .OH) generation. The fact that DFO (but not .OH scavengers [M and dimethylthiourea]) blocked H2O2 toxicity implied Fe-dependent, .OH-independent cell killing. In conclusion, (a) striking catalytic Fe generation occurs during MH-ARF, but augmented intrarenal .OH production may not develop; (b) DFO can block Fe toxicity despite a prooxidant effect; (c) H2O2 PTS toxicity is Fe, but possibly not .OH, dependent; and (d) M does not mitigate oxidant PTS injury, either in the presence or absence of DFO, suggesting that its additive benefit with DFO in vivo occurs via a diuretic, not antioxidant effect.
Phase I-II trials of poly IC stabilized with poly-L-lysine. (1978)

Poly IC, stabilized with poly-L-lysine and carboxymethyl cellulose (poly ICLC), resists hydrolysis by primate serum (unlike the parent compound), induces high levels of serum interferon, and is effective in acute viral infections of subhuman primates. In a phase I-II clinical trial, poly ICLC was given iv in 15 daily doses of 0.5-27.0 mg/m2 to 19 patients with various solid tumors and to six patients with acute leukemia (1-65 years of age). At least three complete trials were conducted at each of six dose levels. Toxic reactions included fever (in 100% of trials), nausea (44%) hypotension (28%), thrombocytopenia and leukopenia (68%), erythema (12%), and polyarthralgia plus myalgia (16%). Hypotension and arthralgia-myalgia were related to dose level and/or magnitude of interferon induction, but other toxic manifestations were not. Poly ICLC induced significant serum interferon levels in 76% of trials, and the correlation between dose and peak interferon titer was linear. The maximum tolerated dose for all patients at a given drug dose was 12 mg/m2; at this dose, the mean peak interferon titer was 1940 reference units/ml. At a dose of 18 mg/m2, the mean peak interferon titer was 4473 reference units/ml, but severe myalgia and arthralgia were intolerable in at least half of the patients, and most had significant hypotension. At a dose of 27 mg/m2, one patient had acute renal failure. At high doses, iv poly ICLC also induced interferon in the cerebrospinal fluid.