gebhart/patrepeval huggingface dataset:
In vitro effects of bisantrene on fresh clonogenic leukemia cells: a preliminary study on 15 cases. (1991)

In vitro clonogenic assays may be useful for determining the sensitivity of leukemic cells to chemotherapeutic agents. We evaluated the antileukemic effect of Bisantrene (an anthracene derivative now undergoing phase II clinical trials in relapsed/resistant acute non lymphoid leukemias-ANLL) using the ANLL cell clonogenic assay. Fifteen cases were studied (9 newly diagnosed, 5 relapsed and 1 refractory ANLL). Normal CFU-GM sensitivity was tested in a subset of 10 normal controls. A wide range of concentrations (from 0.01 to 10 micrograms/ml) at 3 durations of exposure (30 min, 120 min, continuous) was employed. Bisantrene proved effective in 12 out of 15 ANLL cases, inhibiting blast colony growth (50% at 1 micrograms/ml; nearly 100% at 10 micrograms/ml) in a dose-dependent, time-independent way. Three cases were unresponsive both in vitro and in vivo. Normal CFU-GM were inhibited at lower doses (50% at 0.5 micrograms/ml; 100% at 5 micrograms/ml). We conclude that: 1) Bisantrene is active in vitro on leukemic clonogenic cells at doses corresponding to plasmatic levels achievable in patients, with a parallel activity in vivo in 3 relapsed cases. It should be tested in vitro before therapeutic use in order to avoid, if possible, improper use in resistant patients. 2) Normal CFU-GM are more sensitive than clonogenic leukemic cells. This must be taken into account, in view of possible prolonged neutropenias after therapy. 3) The time-independent effect of the drug should be evaluated in the design of new therapeutic schedules.
Effect of insulin on kinetics of sugar transport in heart muscle. (1978)

Insulin increased the maximal rate of sugar transport in the perfused rat heart, but had essentially no effect on the Michaelis constant of sugar entry or half-maximal constant for equilibrium exchange. In control hearts, the following kinetic parameters of 3-O-methylglucose transport were measured: Michaelis constant for entry, 7-10 mM; equilibrium exchange constant, 7 mM; and activity constant (Vmax/Km) from 0.02 to 0.1 ml/g.min. In insulin-treated hearts, these values were 6 mM, 3 MM, and 2.2 ml/g.min, respectively. These changes in transport constants were consistent with a model in which 1) sequestered carrier was released by the hormone or 2) carrier movement, in all forms and directions, was accelerated. Measurements of glucose transport in control hearts indicated that the Michaelis constant for entry was 4 mM and the activity constant, 0.5 ml/g.min. In insulin-treated hearts, quantitation of transport parameters was prevented by accumulation of intracellular glucose.
Electron Affinic Sensitization (1971)

SummaryThe radiosensitizing properties of the highly electron-affinic nitroketone, para-nitroacetophenone (PNAP) have been investigated in resistant and sensitive bacteria, fern spores, mammalian cells in tissue culture and in suspensions of bacteriophage. Radiosensitization occurs in anoxic suspensions of Serratia marcescens Micrococcus radiodurans and in anoxic preparations of Chinese hamster cells line V79–379A. The sensitization of the mammalian cells (enhancement ratio 1·7 for 0·4 mM PNAP) is not inhibited in the presence of serum protein. No sensitization was observed for the spore of the fern Osmunda regalis.PNAP resembles oxygen in conferring some radioprotection on suspensions of bacteriophage T7 irradiated in broth.
Prediction of Wind Farm Power Ramp Rates: A Data-Mining Approach (2009)

In this paper, multivariate time series models were built to predict the power ramp rates of a wind farm. The power changes were predicted at 10 min intervals. Multivariate time series models were built with data-mining algorithms. Five different data-mining algorithms were tested using data collected at a wind farm. The support vector machine regression algorithm performed best out of the five algorithms studied in this research. It provided predictions of the power ramp rate for a time horizon of 10–60 min. The boosting tree algorithm selects parameters for enhancement of the prediction accuracy of the power ramp rate. The data used in this research originated at a wind farm of 100 turbines. The test results of multivariate time series models were presented in this paper. Suggestions for future research were provided.
A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment (2016)

Within tumors, some areas are less oxygenated than others. Since their home ground is under chronic hypoxia, tumor cells adapt to this condition by activating aerobic glycolysis; however, this hypoxic environment is very harsh for incoming immune cells. Deprivation of oxygen limits availability of energy sources and induces accumulation of extracellular adenosine in tumors. Extracellular adenosine, upon binding with adenosine receptors on the surface of various immune cells, suppresses pro-inflammatory activities. In addition, signaling through adenosine receptors upregulates a number of anti-inflammatory molecules and immunoregulatory cells, leading to the establishment of a long-lasting immunosuppressive environment. Thus, due to hypoxia and adenosine, tumors can discourage anti-tumor immune responses no matter how the response was induced, whether it was spontaneous or artificially introduced with a therapeutic intention. Preclinical studies have shown the significance of adenosine in tumor survival strategy by demonstrating tumor regression after inactivation of adenosine receptors, inhibition of adenosine-producing enzymes or reversal of tissue hypoxia. These promising results indicate a potential use of the inhibitors of the hypoxia-adenosine pathway for cancer immunotherapy.
Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression. (1994)

Apolipoprotein E-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides and reduced high-density lipoprotein. The mice develop arterial lesions in a time-dependent manner. Lesional distribution was centered in the aortic sinus in young mice, and the lesions were widely distributed throughout the arterial tree in mice at 8 to 9 months of age. In young mice, subendothelial foam cell deposits were present in the aortic sinus adjacent to valve-attachment sites. By 5 months of age, foam cell deposits, free cholesterol, and admixed smooth muscle cells composed the developing atherosclerotic lesions. After 8 to 9 months of age, the arterial lesions showed increased complexity, and fibrous cap lesions were present. Transmission electron microscopy showed foam cells, smooth muscle cells (both contractile and synthetic varieties), cellular debris, and acicular cholesterol deposits within the plaques. By scanning electron microscopy, subendothelial collections of foam cells were present within the aortic sinus and ascending aorta. The results show that the complexity of the atherosclerotic lesions that develop in these apo E deficient-mice are similar to those described in other species and therefore represent an important model for studies of genetic and environmental influences on the atherosclerotic process.
Psoralen photochemical inactivation of Orientia tsutsugamushi in platelet concentrates (2000)

The psoralen AMT, in conjunction with UVA light exposure, effectively abolished the infectivity of PCs deliberately contaminated with the scrub typhus organism O. tsutsugamushi, as tested in a mouse infectivity assay.
Computational analysis of off-rate selection experiments to optimize affinity maturation by directed evolution (2010)

Directed evolution is a powerful approach for isolating high-affinity binders from complex libraries. In affinity maturation experiments, binders with the highest affinities in the library are typically isolated through selections for decreased off rate using a suitable selection platform (e.g. phage display or ribosome display). In such experiments, the library is initially exposed to biotinylated antigen and the binding reaction is allowed to proceed. A large excess of unbiotinylated antigen is then added as a competitor to capture the vast majority of rapidly dissociating molecules; the slowly dissociating library members can subsequently be rescued by capturing the biotin-carrying complexes. To optimize the parameters for such affinity maturation experiments, we performed both deterministic and stochastic simulations of off-rate selection experiments using different input libraries. Our results suggest that the most critical parameters for achieving the lowest off rates after selection are the ratio of competitor antigen to selectable antigen and the selection time. Furthermore, the selection time has an optimum that depends on the experimental setup and the nature of the library. Notably, if selections are carried out for times much longer than the optimum, equilibrium is reached and the selection pressure is weakened or lost. Comparison of different selection strategies revealed that sequential selection rounds with lower stringency are favored over high-stringency selection experiments due to enhanced diversity in the selected pools. Such simulations may be helpful in optimizing affinity maturation strategies and off-rate selection experiments.
Persistent dysfunction of regenerated endothelium after balloon angioplasty of rabbit iliac artery. (1990)

This study investigated the vasodilator function of endothelium that regenerated after balloon angioplasty and the relation of this function to the extent of vascular injury and to subsequent intimal proliferation. Balloon angioplasty was performed in the left iliac artery of 47 New Zealand White rabbits. Vascular responses were examined in vitro 2 and 4 weeks after a "severe" injury (3.0-mm balloon) or a "moderate" injury (2.5-mm balloon). Both degrees of balloon injury caused complete endothelial denudation. Endothelial regrowth 2 weeks after either injury was confirmed histologically. Although the regenerated cells had irregular sizes and polygonal shapes and lacked the typical alignment in the direction of blood flow, immunocytochemical staining for factor VIII-related antigen identified these cells as endothelium. To study the vasodilator function of regenerated endothelium, rings of balloon-injured and control (contralateral) iliac arteries were suspended in organ chambers for recording of isometric force. Endothelium-dependent relaxation of balloon-injured vessels to acetylcholine and to the calcium ionophore A23187 were reduced at 2 and at 4 weeks after severe injury. After moderate injury, endothelium-dependent relaxations to these agents were reduced at 2 weeks but had normalized by 4 weeks. Endothelium-independent relaxation to sodium nitroprusside, however, was preserved in all study groups. Morphometric analysis revealed an inverse correlation between the degree of intimal thickening and maximal relaxation to acetylcholine (r = 0.45, p less than 0.01). Thus, there is a persistent attenuation of receptor- and nonreceptor-mediated endothelium-dependent relaxations after arterial injury. The regenerated cells have an altered morphological appearance, but staining for factor VIII-related antigen confirms their endothelial origin. The degree and duration of endothelial dysfunction depends on the severity of the initial injury and is related to the extent of intimal thickness.
Sequence analysis of amphotropic and 10A1 murine leukemia viruses: close relationship to mink cell focus-inducing viruses (1990)

Viral interference studies have demonstrated the existence of four distinct murine leukemia virus (MuLV) receptors on NIH 3T3 mouse cells. The four viral interference groups are ecotropic MuLV; mink cell focus inducing virus (MCF); amphotropic MuLV; and 10A1, a recombinant derivative of amphotropic MuLV that uses a unique receptor but also retains affinity for the amphotropic MuLV receptor. We report here that 10A1 infects rat and hamster cells, unlike its amphotropic parent. We isolated an infectious molecular clone of 10A1 and present here the sequences of the env genes and enhancer regions of amphotropic MuLV and 10A1. The deduced amino acid sequences of amphotropic MuLV and 10A1 gp70su are remarkably similar to those of MCF and xenotropic MuLV (for which mouse cells lack receptors), with 64% amino acids identical in the four groups. We generated a consensus from these comparisons. Further, the differences are largely localized to a few discrete regions: (i) amphotropic MuLV has two short insertions relative to MCF, at residues 87 to 92 and 163 to 169, and (ii) amphotropic MuLV and MCF are totally different in a hypervariable region, which is greater than 30% proline, at residues approximately 253 to 304. 10A1 closely resembles amphotropic MuLV in its N terminus but contains an MCF-type hypervariable region. These results suggest the possibility that receptor specificity is localized in these short variable regions and further that the unique receptor specificity of 10A1 is due to the novel combination of amphotropic MuLV and MCF sequences rather than to the presence of any novel sequences. The Env proteins of ecotropic MuLV are far more distantly related to those of the other four groups than the latter are to each other. We also found that the enhancer regions of amphotropic MuLV and 10A1 are nearly identical, although 10A1 is far more leukemogenic than amphotropic MuLV.
Cloning and expression of murine IL-12 (1992)

Human IL-12 (NK cell stimulatory factor, cytotoxic lymphocyte maturation factor) is a heterodimeric cytokine that can act as a growth factor for activated human T and NK cells, enhance the lytic activity of human NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting human PBMC. Because in our hands, human IL-12 did not elicit similar responses in murine lymphocytes, we have cloned and expressed the murine IL-12 subunit cDNA in order to obtain recombinant protein for murine studies. Comparison of the predicted amino acid sequences of the murine subunits with their human counterparts revealed that the p40 subunits are more highly conserved than the p35 subunits (70% vs 60% identity, respectively). The sizes of the p35 and p40 subunit mRNA were estimated to be 1.5 kb and 2.6 kb, respectively. RNA blot analysis showed that p35 mRNA was expressed in lymphoid tissues (spleen, thymus) and nonlymphoid tissues (lung, brain), whereas p40 mRNA expression was only detected in lymphoid cells. Incubation of splenocytes with pokeweed mitogen did not significantly affect p35 mRNA levels, however, it resulted in a decrease of p40 mRNA. Coexpression of the murine p35 and p40 cDNA clones in COS cells resulted in the secretion of IL-12, which was active in human and mouse T cell proliferation, murine NK cell activation, and murine IFN-gamma induction assays. Transfection of each subunit cDNA alone did not result in measurable secreted IL-12 activity. A hybrid heterodimer consisting of murine p35 and human p40 subunits retained bioactivity on murine cells; however, the combination of human p35 and murine p40 was completely inactive on murine cells. These results indicate that the observed inability of human IL-12 to act on murine cells is largely determined by the p35 subunit.
The T-cell Lymphokine Interleukin-26 Targets Epithelial Cells through the Interleukin-20 Receptor 1 and Interleukin-10 Receptor 2 Chains (2004)

The cellular members of the interleukin-10 (IL-10) cytokine family share sequence homology with IL-10, whereas their sites of expression and their functions are divergent. One of these factors, AK155 or IL-26, was discovered because of its overexpression in human T lymphocytes after growth transformation by the simian rhadinovirus herpesvirus saimiri. In addition, the gene is transcribed in various types of primary and immortalized T-cells. Here we describe epithelial cells, namely colon carcinoma cells and keratinocytes, as targets of this T-cellular lymphokine. Purified recombinant IL-26 induced the rapid phosphorylation of the signal transducer and activator of transcription factors 1 and 3. As a result, secretion of IL-10 and IL-8, as well as cell surface expression of CD54 were enhanced. Moreover, we show that the IL-26 protein binds to heparin, is released from the cell surface, and can be functionally inhibited by heparin. The sensitivity to recombinant IL-26 of various cell lines strictly correlated with the expression of the long chain of the IL-20 receptor. Because blocking antibodies against either the short chain of the IL-10 receptor or the long chain of the IL-20 receptor inhibited IL-26-dependent signal transduction, and transient expression of these receptor chains induced IL-26 responsivity in non-sensitive cells, we propose that the IL-20 receptor 1 and IL-10 receptor 2 chains participate in forming the IL-26 receptor. Targeting epithelial cells, the T-cell lymphokine IL-26 is likely to play a role in local mechanisms of mucosal and cutaneous immunity.
Functional Defects and the Influence of Age on the Frequency of CD4+CD25+ T-Cells in Type 1 Diabetes (2005)

CD4+ CD25+ T-cells appear to play a crucial role in regulating the immune response. Therefore, we evaluated the peripheral blood frequency and function of CD4+ CD25+ T-cells in 70 type 1 diabetic patients and 37 healthy individuals. Interestingly, a positive correlation was observed between increasing age and CD4+ CD25+ T-cell frequency in both subject groups. In contrast to previous studies of nonobese diabetic mice and type 1 diabetic patients, similar frequencies of CD4+ CD25+ and CD4+ CD25(+Bright) T-cells were observed in healthy control subjects and type 1 diabetic patients of similar age. There was no difference between type 1 diabetic subjects of recent-onset versus those with established disease in terms of their CD4+ CD25+ or CD4+ CD25(+Bright) T-cell frequency. However, type 1 diabetic patients were markedly defective in their ability to suppress the proliferation of autologous effector T-cells in vitro. This type 1 diabetes-associated defect in suppression was associated with reduced production of interleukin (IL)-2, gamma-interferon, and transforming growth factor-beta, whereas other cytokines including those of adaptive and innate immunity (IL-10, IL-1beta, IL-6, IL-8, IL-12p70, and tumor necrosis factor-alpha) were similar in control subjects and type 1 diabetic patients. These data suggest that age strongly influences the frequency of CD4+ CD25+ T-cells and that function, rather than frequency, may represent the means by which these cells associate with type 1 diabetes in humans.
Effect of local delivery of heparin and methotrexate on neointimal proliferation in stented porcine coronary arteries (1992)

Background Multiple systemic agents have not prevented restenosis after percutaneous transluminal coronary angioplasty. Attention has focused more recently on developing local drug delivery systems that achieve significant focal concentrations of agents potentially effective against restenosis. Recent advances in polymer design allow specific drugs to be eluted within a defined period after polymer binding onto intracoronary stents. Preliminary results suggested heparin and methotrexate may inhibit the neointimal smooth muscle cell proliferation involved in restenosis. We investigated whether a local drug delivery system involving polymer binding of methotrexate, heparin, or both agents onto an intracoronary stent would inhibit neointimal smooth muscle cell proliferation in a model involving oversized stenting of porcine coronary arteries. Methods Forty animals were randomly divided into four treatment groups. Ten pigs each received a flexible, balloon-expandable tantalum stent coated with a cellulose ester polymer that bound methotrexate, heparin, or a combination of both drugs; 10 animals received an uncoated tantalum control stent. All animals were fed a nonatherogenic diet and were killed 28 days after stenting. Morphometric analysis of stented arteries was performed; mean neointimal area and percent lumen area stenosis were compared between treatment groups. Results No statistically significant differences were found between treatment groups by 2 × 2 factorial analysis with respect to either mean neointimal area or percent lumen area stenosis. Conclusions This preliminary attempt to inhibit neointimal smooth muscle cell proliferation after vascular injury by local delivery of methotrexate and heparin with polymer-coated intracoronary stents was unsuccessful. Further efforts to refine polymer-based local drug delivery systems may involve more effective antiproliferative agents and more extensive surface areas for drug delivery.
Catalytic Asymmetric Oxidative Couplings of 2-Naphthols by Tridentate N-Ketopinidene-Based Vanadyl Dicarboxylates (2002)

[reaction: see text] A series of oxovanadium(IV) complexes derived from tridentate N-ketopinidene-alpha-amino acids were synthesized. They serve as efficient catalysts for the enantioselective oxidative couplings of various 3-, 6-, or 7-substituted 2-naphthols. The best scenario involves the use of a vanadyl complex arising from L-tert-leucine in CCl4. The asymmetric couplings of 2-naphthols can be conducted smoothly at 40-45 degrees C under a stream of gaseous oxygen, leading to 2,2'-dihydroxy-1,1'-binaphthyls in good yields (61-99%) and with enantioselectivities of up to 87%.
Multidrug-resistant Organisms in Military Wounds from Iraq and Afghanistan (2008)

Mortality from battlefield wounds has historically declined, thanks to better surgical management, faster transport of casualties, and improved antibiotics. Today, one of the major challenges facing U.S. military caregivers is the presence of multidrug-resistant organisms in orthopaedic extremity wounds. The most frequently identified resistant strains of bacteria are Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter calcoaceticus-baumannii complex. Overuse of broad-spectrum antibiotics may be an important factor in building resistant strains. Acinetobacter infections appear to hospital-acquired and not from an initial colonization of the injury. More research is required to give military physicians the tools they require to reduce the infection rate and defeat multidrug-resistant organisms.
Digital microfluidic biochip design for protein crystallization (2007)

Proteins crystallization is a commonly used technique for protein analysis. It predicts the three-dimensional (3D) arrangement of the constituent amino acids, which indicates the specific biological function of a protein. Protein crystallization experiments are typically carried out in well-plates; as a result, these experiments are slow, expensive, and errors are likely due to the need for repeated human intervention. Recently, droplet-based “digital” microfluidics has been used for executing protein assays on a chip. Protein samples are enclosed in droplets, which are manipulated using the principle of electrowetting-on--dielectric. Digital microfluidics offers a high degree of automation, and it significantly reduces the volumes of proteins required for crystallization. We present the design of a multi-well plate microfluidic biochip for protein crystallization, which can transfer protein samples, prepare candidate solutions, and carry out crystallization automatically. To reduce the manufacturing cost of such devices, we present an efficient algorithm to generate a pin-assignment plan for the proposed design. The resulting biochip enables control of a large number of on-chip electrodes using only a small number of pins.