gebhart/patrepeval huggingface dataset:
Cationic lipids reduce time and dose of c-myc antisense oligodeoxynucleotides required to specifically inhibit Burkitt's lymphoma cell growth. (1996)

Burkitt's lymphoma is characterized by a translocation of the c-myc gene with one of the immunoglobulin loci which activates overexpression of the c-myc oncogene. Antisense-oligodeoxynucleotides (AS-ODNs) offer the potential to block specific c-myc gene expression within lymphoma cells, but often exhibit a low efficiency of AS-ODN uptake. In this study, a polycationic lipid reagent, Lipofectamine (LFM), was utilized as a vehicle to increase efficiency of delivery, decrease the time needed to observe an inhibitory effect, and decrease the AS-ODN dose. The objective was to develop a more efficient and rapid in vitro AS-ODN strategy to inhibit proliferation of c-myc-dependent lymphoma cells and to test the specificity of Burkitt's lymphoma cell line-directed AS-ODNs for potential use as molecular purging agents in bone marrow transplantation. Proliferation assays were performed to determine the inhibitory effect of the AS-ODNs on two Burkitt's lymphoma cell lines with different chromosomal translocations, Daudi and ST486, in medium containing 8.5 microM LFM. AS-ODNs at a concentration of 0.36 microM induced a significant decrease in proliferation for both cell lines using the specific AS-ODN for each respective translocation. Within 5 h, Daudi responded to its specific AS-ODN/lipid complexes with a 35% decrease in proliferation, compared to cells which received no treatment or Daudi-specific AS-ODN without LFM (P = 0.0001). Daudi showed an insignificant decrease in proliferation when treated with an AS-ODN specific for the ST486 translocation (4%, P = 0.26). ST486 proliferation was decreased by 52% when treated with the specific antisense for ST486 compared to no treatment or ST486-specific AS-ODN without LFM (P < 0.003). Treatment with the AS-ODN specific for Daudi showed an insignificant 4% decrease (P = 0.42). Controls, including sense ODN for structure, reverse AS-ODN for structure and base composition, and AS-ODN without LFM, did not produce a significant change in cells treated with LFM alone or cells receiving no treatment. Clonogenic assays of both Daudi and ST486 treated with their specific AS-ODNs revealed a 50% inhibition of colony formation after the 5 h incubation as compared to no treatment. Confocal laser scanning microscopy verified that cellular uptake of AS-ODN was enhanced by cationic lipids. Immunoblot analysis showed a 63 +/- 5% and a 50 +/- 3% reduction in intracellular c-myc levels for Daudi and ST486, respectively, when their respective AS-ODNs were administered. Normal bone marrow progenitors were unaffected by the ODN/LFM complexes. These results suggest that the specific c-myc AS-ODN/LFM complexes inhibit c-myc-dependent tumor proliferation at an earlier time and at a lower dose compared to no lipid facilitation. This approach may form the basis for utilizing specific AS-ODN/LFM therapy either alone or in a cocktail of other agents as an ex vivo molecular purging approach to autologous stem cell transplantation in Burkitt's lymphoma.
Digital current-mode controller for DC-DC converters (2005)

This paper introduces a digital average current-mode controller architecture based on a low-resolution current A/D converter and a simple digital controller realization. The proposed approach combines advantages of practical digital realization and current-mode control for DC-DC converters operating at high switching frequencies. An experimental test circuit includes an experimental prototype current A/D converter, a controller implemented on an FPGA, and a 6 V-to-1.8 V, 10 A synchronous buck power stage operating at 200 KHz. Experimental verification results are described.
Lactate-stimulated ethanol oxidation in isolated hepatocytes (1978)

1. Hepatocytes isolated from starved rats and incubated without other substrates oxidized ethanol at a rate of 0.8–0.9μmol/min per g wet wt. of cells. Addition of 10mm-lactate increased this rate 2-fold. 2. Quinolinate (5mm) or tryptophan (1mm) decreased the rate of gluconeogenesis with 10mm-lactate and 8mm-ethanol from 0.39 to 0.04–0.08μmol/min per g wet wt. of cells, but rates of ethanol oxidation were not decreased. From these results it appears that acceleration of ethanol oxidation by lactate is not dependent upon the stimulation of gluconeogenesis and the consequent increased demand for ATP. 3. As another test of the relationship between ethanol oxidation and gluconeogenesis, the initial lactate concentration was varied from 0.5mm to 10mm and pyruvate was added to give an initial [lactate]/[pyruvate] ratio of 10. This substrate combination gave a large stimulation of ethanol oxidation (from 0.8 to 2.6μmol/min per g wet wt. of cells) at low lactate concentrations (0.5–2.0mm), but rates remained nearly constant (2.6–3.0μmol/min per g wet wt. of cells) at higher lactate concentrations (2.0–10mm). 4. In contrast, owing to the presence of ethanol, the rate of glucose synthesis was only slightly increased (from 0.08 to 0.12μmol/min per g wet wt. of cells) between 0.5mm- and 2.0mm-lactate and continued to increase (from 0.12 to 0.65μmol/min per g wet wt. of cells) with lactate concentrations between 2 and 10mm. 5. In the presence of ethanol, O2 uptake increased with increasing substrate concentration over the entire range. 6. Changes in concentrations of glutamate and 2-oxoglutarate closely paralleled changes in the rate of ethanol oxidation. 7. In isolated hepatocytes, rates of ethanol oxidation are lower than those in vivo apparently because of depletion of malate–aspartate shuttle intermediates during cell preparation. Rates are returned to those observed in vivo by substrates that increase the intracellular concentration of shuttle metabolites.
Endogenous Ghrelin in Pancreatic Islets Restricts Insulin Release by Attenuating Ca2+ Signaling in β-Cells (2004)

Ghrelin, isolated from the human and rat stomach, is the endogenous ligand for the growth hormone (GH) secretagogue receptor, which is expressed in a variety of tissues, including the pancreatic islets. It has been shown that low plasma ghrelin levels correlates with elevated fasting insulin levels and type 2 diabetes. Here we show a physiological role of endogenous ghrelin in the regulation of insulin release and blood glucose in rodents. Acylated ghrelin, the active form of the peptide, was detected in the pancreatic islets. Counteraction of endogenous ghrelin by intraperitoneal injection of specific GH secretagogue receptor antagonists markedly lowered fasting glucose concentrations, attenuated plasma glucose elevation, and enhanced insulin responses during the glucose tolerance test (GTT). Conversely, intraperitoneal exogenous ghrelin GH-independently elevated fasting glucose concentrations, enhanced plasma glucose elevation, and attenuated insulin responses during GTT. Neither GH secretagogue receptor antagonist nor ghrelin affected the profiles of the insulin tolerance test. In isolated islets, GH secretagogue receptor blockade and antiserum against acylated ghrelin markedly enhanced glucose-induced increases in insulin release and intracellular Ca2+ concentration ([Ca2+]i), whereas ghrelin at a relatively high concentration (10 nmol/l) suppressed insulin release. In single beta-cells, ghrelin attenuated glucose-induced first-phase and oscillatory [Ca2+]i increases via the GH secretagogue receptor and in a pertussis toxin-sensitive manner. Ghrelin also increased tetraethylammonium-sensitive delayed outward K+ currents in single beta-cells. These findings reveal that endogenous ghrelin in islets acts on beta-cells to restrict glucose-induced insulin release at least partly via attenuation of Ca2+ signaling, and that this insulinostatic action may be implicated in the upward control of blood glucose. This function of ghrelin, together with inducing GH release and feeding, suggests that ghrelin underlies the integrative regulation of energy homeostasis.
The global epidemic of human immunodeficiency virus infection (1995)

The impact of the global epidemic of human immunodeficiency virus (HIV) infection in developed countries has been far reaching, but its impact in developing countries is much more devastating. The common underlying theme that helps explain HIV and acquired immunodeficiency syndrome (AIDS) is inequality. The resources available to nurses in all these countries vary markedly. Although there are many instances of nurses responding in an altruistic manner, the evidence indicates that many nurses are reluctant to provide care for individuals with HIV infection. HIV and AIDS have enabled an examination of broader, fundamental questions about the nature of nursing in health care and in society.
In Vitro Characterization of Transforming Growth Factor-ß1-Loaded Composites of Biodegradable Polymer and Mesenchymal Cells (1995)

A porous, biodegradable polymer composite was fabricated from poly(L-lactic acid) (PLLA) using a solvent- casting particulate-leaching technique, and loaded with recombinant human transforming growth factor ß-1 (TGF-ß1). Tissue culture polystyrene (TCPS) and PLLA disks loaded with bovine serum albumin (BSA) served as controls. Polymer specimens were seeded at high cell density with C3H10T1/2 cells, a mouse embryonic cell line capable of differentiating into various connective tissue cell types. The polymer matrices degraded slowly in physiological saline over four weeks, with a sustained yet sporadic release of active TGF-ß1; a more controlled release of TGF-ß1 was observed in serum-containing culture medium and with cell seeding. Compared to controls, cells seeded on TGF-ß1-Ioaded PLLA disks showed significantly enhanced DNA and proteoglycan synthesis, while collagen biosynthesis was greater in all PLLA cultures compared to those on TCPS. Scanning electron microscopy revealed extensive cell proliferation, with a chondrocyte-like phenotype, throughout the porous matrix, while histology showed intact cell bodies and minimal cellular necrosis. These results suggest that the TGF-ß1-loaded cell-polymer composite supports cell proliferation/differentiation, and is a candidate template for connective tissue engineering.
Consequences of Mast Cell Signaling in Peripheral Nerve (2006)

Expression of the human epidermal growth factor receptor (EGFR) in murine Schwann cells provides a simplified model of early peripheral nerve pathologies that manifest in neurofibromatosis type 1 (NF1).EGFR + mice develop Schwann cell hyperplasia, mast cell infiltration, nerve hypertophy, collagen deposition, and loss of axon-glial interactions.Historically, mast cells have been viewed as effector cells in allergy and inflammation, but a growing body of literature suggests that they play vital roles in tissue homeostasis and the development of numerous pathologies.The major objective of this work was to explore the contribution of mast cells to the nerve pathology of EGFR + mice.The first set of studies demonstrates that mast cell degranulation is necessary for the development of NF1-related nerve pathology in EGFR + mice by genetic mast cell ablation, mast cell reconstitution via bone marrow engraftment, and pharmacologic mast cell stabilization.We show that EGFR + mutant nerve upregulates the expression of several mast cell chemoattractants, which may serve to recruit or activate mast cells, and together, these cells drive peripheral nerve disruption.In the second set of studies, we attempt to define which mast cell mediators, released upon degranulation, drive nerve pathology.We outline a possible pathologic role for NGF and histamine, and conclude that several other mediators may also contribute to nerve pathology.In all, this work defines a pathologic role for mast cells in the development of EGFR + nerve pathology, supports continued investigation of mast cells in Nf1 model systems, and suggests a possible role for global mast cell stabilizers in the treatment of NF1 patients.
Studies on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil co-administered orally to tumor-bearing rats. (1980)

The metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) plus uracil (1:4, UFT) was compared with that of FT alone and that of uracil alone in tumor-bearing rats by using 3H-tracer. After oral administration of UFT, both FT and uracil were rapidly absorbed and no interaction of their absorptions was observed. The levels of 5-fluorouracil (5-FU) in the blood and tissues and the excretion of 5-FU in the urine of rats given UFT were temporarily higher, and the levels of alpha-fluoro-beta-ureidopropionic acid (a catabolic metabolite of 5-FU) in almost all tissues were lower than in rats given FT. The levels of 5-FU, 5-fluorouridine, and fluoronucleotides increased more in the tumors than in normal tissues of rats given UFT, but not in those given FT. The metabolism of uracil administered exogenously as UFT was not influenced by 5-FU or its metabolites derived from FT.
[Dynamic changes and the meanings of blood cytokines in severe acute respiratory syndrome]. (2003)

Proinflammatory cytokines and TGF-beta1 were elevated during the early phase of SARS, a phenomenon which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during the whole disease course. It suggested that the immune state of SARS was obviously abnormal. Observing the dynamic changes in blood cytokine levels can provide us with a scientific basis to assess pathogenesis and efficacy of clinical treatment of SARS.
27.6% Conversion efficiency, a new record for single-junction solar cells under 1 sun illumination (2011)

Alta Devices, Inc. has fabricated a thin-film GaAs device on a flexible substrate with an independently-confirmed solar energy conversion efficiency of 27.6%, under AM1.5G solar illumination at 1 sun intensity. This represents a new record for single-junction devices under non-concentrated sunlight. This surpasses the previous record, for conversion efficiency of a single-junction device under non-concentrated light, by more than 1%. This is due largely to the high open-circuit voltage (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">oc</sub> ) of this device. The high V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">oc</sub> results from precise control of the dark current. The fact that this record result has been achieved with a thin-film shows that, for GaAs material systems, the majority of the growth substrate is not needed for device performance. This allows one to consider amortizing the potentially high cost of a GaAs growth substrate by growing a thin-film, lifting it off, and reusing the same substrate multiple times. This technology therefore has the potential to be a novel high-performance, thin-film option for terrestrial photovoltaics.
Keratocyte networks visualised in the living cornea using vital dyes (1993)

Fluorescent viability probes have been used to visualise and investigate the viability, morphology and organisation of the keratocyte within the stroma of the intact living cornea. The live cell probe, calcien-AM, in combination with a dead cell probe, ethidium homodimer (Live/Dead Assay, Molecular Probes, U.S.A.) proved superior to earlier generation vital dyes such as fluorescein diacetate or 5,6-carboxyfluorescein diacetate, initially used in combination with ethidium bromide. The ubiquitous distribution of esterase enzymes that cleave calcien-AM within the keratocyte cytoplasm produced a high concentration of fluorescently active calcein throughout the cell, including fine cell processes. Epi-illuminated fluorescence microscopy on transparent corneal dissections subsequently revealed details of keratocyte microanatomy and three-dimensional network organisation in situ. Three morphologically discrete subpopulations of keratocytes were identified: two formed relatively small bands of cells, immediately subjacent to either Bowman's or Descemet's membranes, the third subpopulation constituting the majority of keratocytes typically located within the corneal stroma. The results indicate that calcein-AM is able to penetrate intact living cornea revealing cell viability, and it also has the capacity to 'trace' cellular elements and reveal fine structure within a dense connective tissue matrix.
Introduction of optical fiber transmission technology into existing cable television networks and its impact on the consumer electronics interface (1989)

The authors outline what they consider a highly likely scenario for the evolution of fiber optic technology into existing cable television networks. The use of fiber in cable television systems is summarized, the nature of present cable television network architecture is reviewed, factors which limit performance and capacity are identified, and the significance of these developments for the interface between cable television and consumer electronics is explored. A plan is proposed to target the use of optical fiber transmission against current limitations. The resulting 'fiber backbone' yields a hybrid fiber/coaxial network with significantly better reliability and transmission quality than the present systems. The potential to cost-effectivity upgrade the coaxial portion to substantially greater bandwidth than is currently practical is achieved. The optical links necessary to implement the proposed system are characterized and the development of the optical devices necessary to make these links practical are considered.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Elevated C-Reactive Protein (2001)

Recent studies have suggested that elevated plasma C-reactive protein (CRP) levels are associated with the features of insulin resistance syndrome. In the present study, we have examined the contribution of body composition measured by hydrostatic weighing and of abdominal adipose tissue (AT) accumulation assessed by computed tomography to the variation in plasma CRP levels associated with atherogenic dyslipidemia of the insulin resistance syndrome in a sample of 159 men, aged 22 to 63 years, covering a wide range of adiposity (body mass index values from 21 to 41 kg/m(2)). Plasma CRP levels showed positive and significant correlations with body fat mass (r=0.41, P<0.0001), waist girth (r=0.37, P<0.0001), and visceral AT accumulation measured by computed tomography at L4 to L5 (r=0.28, P<0.0003). Although CRP levels were associated with plasma insulin levels measured in the fasting state and after a 75-g oral glucose load, no significant correlations were found with plasma lipoprotein levels. Finally, comparison of body fatness, of abdominal fat accumulation, and of the features of the insulin resistance syndrome across quintiles of CRP revealed major differences in body fatness and in indices of abdominal AT accumulation between the lowest and the highest CRP quintiles, whereas no significant differences were found for variables of the plasma lipoprotein-lipid profile. These results suggest that obesity and abdominal AT accumulation are the critical correlates of elevated plasma CRP levels found in men with atherogenic dyslipidemia of the insulin resistance syndrome.
Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis (2013)

We confirm the MUC5B variant association with IPF. We did not observe an association with lung fibrosis in the context of SSc or sarcoidosis, potentially highlighting fundamental differences in genetic susceptibility, although the limited subgroup numbers do not allow a definitive exclusion of an association.
Enhanced Susceptibility to Sepsis After Simple Hemorrhage (1990)

To determine whether phagocytosis mediated by Fc receptors and/or receptors for the third component of complement (C3b) are altered after hemorrhage, C3H/HeN mice were subjected to nonlethal hemorrhage and then adequately resuscitated. Twelve hours after the hemorrhagic episode, a significant decrease in both Fc (-55.2%) and C3b (-46.6%) receptor-positive peritoneal macrophages was observed compared with controls. At 24 hours the extent of the depression, while still marked, was only -22.5% and -17.4% for Fc and C3b receptors, respectively. By day 3 after hemorrhage, no differences could be observed for either of these receptors. The capacity of macrophages from mice after hemorrhage to elaborate interleukin 1 or tumor necrosis factor-alpha showed no increase over that of the sham controls, and serum levels of endotoxin were not elevated 2 or 24 hours after hemorrhage. Moreover, endotoxin-tolerant C3H/HeJ mice also exhibited depression of both receptors after hemorrhage. Thus, the inability of the host macrophages to clear opsonized infectious agents after hemorrhage may be due in part to the loss of Fc and C3b receptors on macrophages.
Jumping NLP Curves: A Review of Natural Language Processing Research [Review Article] (2014)

Natural language processing (NLP) is a theory-motivated range of computational techniques for the automatic analysis and representation of human language. NLP research has evolved from the era of punch cards and batch processing (in which the analysis of a sentence could take up to 7 minutes) to the era of Google and the likes of it (in which millions of webpages can be processed in less than a second). This review paper draws on recent developments in NLP research to look at the past, present, and future of NLP technology in a new light. Borrowing the paradigm of `jumping curves' from the field of business management and marketing prediction, this survey article reinterprets the evolution of NLP research as the intersection of three overlapping curves-namely Syntactics, Semantics, and Pragmatics Curveswhich will eventually lead NLP research to evolve into natural language understanding.
Activity of the Novel Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235 against T-Cell Acute Lymphoblastic Leukemia (2010)

Recent findings have highlighted that constitutively active phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), where it upregulates cell proliferation, survival, and drug resistance. These observations lend compelling weight to the application of PI3K/Akt/mTOR inhibitors in the therapy of T-ALL. Here, we have analyzed the therapeutic potential of the novel dual PI3K/mTOR inhibitor NVP-BEZ235, an orally bioavailable imidazoquinoline derivative, which has entered clinical trials for solid tumors, on both T-ALL cell lines and patient samples. NVP-BEZ235 was cytotoxic to a panel of T-ALL cell lines as determined by MTT assays. NVP-BEZ235 treatment resulted in cell cycle arrest and apoptosis. Western blots showed a dose- and time-dependent dephosphorylation of Akt and mTORC1 downstream targets in response to NVP-BEZ235. Remarkably, NVP-BEZ235 targeted the side population of both T-ALL cell lines and patient lymphoblasts, which might correspond to leukemia-initiating cells, and synergized with chemotherapeutic agents (cyclophosphamide, cytarabine, dexamethasone) currently used for treating T-ALL patients. NVP-BEZ235 reduced chemoresistance to vincristine induced in Jurkat cells by coculturing with MS-5 stromal cells, which mimic the bone marrow microenvironment. NVP-BEZ235 was cytotoxic to T-ALL patient lymphoblasts displaying pathway activation, where the drug dephosphorylated eukaryotic initiation factor 4E-binding protein 1, at variance with rapamycin. Taken together, our findings indicate that longitudinal inhibition at two nodes of the PI3K/Akt/mTOR network with NVP-BEZ235, either alone or in combination with chemotherapeutic drugs, may be an efficient treatment of those T-ALLs that have aberrant upregulation of this signaling pathway for their proliferation and survival.