gebhart/patrepeval huggingface dataset:
Cloned Transgenic Calves Produced from Nonquiescent Fetal Fibroblasts (1998)

An efficient system for genetic modification and large-scale cloning of cattle is of importance for agriculture, biotechnology, and human medicine. Here, actively dividing fetal fibroblasts were genetically modified with a marker gene, a clonal line was selected, and the cells were fused to enucleated mature oocytes. Out of 28 embryos transferred to 11 recipient cows, three healthy, identical, transgenic calves were generated. Furthermore, the life-span of near senescent fibroblasts could be extended by nuclear transfer, as indicated by population doublings in fibroblast lines derived from a 40-day-old fetal clone. With the ability to extend the life-span of these primary cultured cells, this system would be useful for inducing complex genetic modifications in cattle.
Dichloroacetate improves immune dysfunction caused by tumor‐secreted lactic acid and increases antitumor immunoreactivity (2013)

The activation of oncogenic signaling pathways induces the reprogramming of glucose metabolism in tumor cells and increases lactic acid secretion into the tumor microenvironment. This is a well-known characteristic of tumor cells, termed the Warburg effect, and is a candidate target for antitumor therapy. Previous reports show that lactic acid secreted by tumor cells is a proinflammatory mediator that activates the IL-23/IL-17 pathway, thereby inducing inflammation, angiogenesis and tissue remodeling. Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T-cell proliferation and activation. Accordingly, we hypothesized that counteraction of the immune effects by lactic acid might suppress tumor development. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL-23/IL-17 pathway and the expression of ARG1 by lactic acid. Furthermore, lactic acid-pretreated macrophages inhibited CD8+ T-cell proliferation, but CD8+ T-cell proliferation was restored when macrophages were pretreated with lactic acid and DCA. DCA treatment decreased ARG1 expression in tumor-infiltrating immune cells and increased the number of IFN-γ-producing CD8+ T cells and NK cells in tumor-bearing mouse spleen. Although DCA treatment alone did not suppress tumor growth, it increased antitumor immunotherapeutic activity of Poly(IC) in both CD8+ T cell- and NK cell-sensitive tumor models. Therefore, DCA acts not only on tumor cells to suppress glycolysis but also on immune cells to improve the immune status modulated by lactic acid and to increase the effectiveness of antitumor immunotherapy.
Safety, Efficacy and Pharmacokinetics of Peginterferon α2a (40 kd) in Children With Chronic Hepatitis C (2006)

Chronic hepatitis C virus (HCV) infection in children is a problem affecting thousands of children worldwide. Although standard interferon (INF) has better efficacy in pediatric patients than in adults, results in children with genotype 1 are poor; response rates to combination treatment with standard INF and ribavirin are better but the treatment requires thrice-weekly injections. The improved antiviral efficacy of weekly pegylated interferons relative to standard interferons in adults with chronic HCV infection suggests that pegylated interferons may also improve antiviral efficacy in children. We therefore investigated the pharmacokinetics, efficacy and safety of peginterferon alpha2a (pegINF-alpha2a) (40 kd) in 14 children ages 2 to 8 years with chronic hepatitis C (13 genotype 1, 1 non-1 genotype). Drug dose was calculated from each patient's body surface area (BSA) according to the formula BSA (m2)/(1.73 m2) x 180 microg, and patients were administered once-weekly subcutaneous injections for 48 weeks. Viral load and pharmacokinetic parameters were determined from blood drawn throughout the study and during follow-up. At week 24, the mean trough concentration was about 20% below values obtained from adults treated with pegINF-alpha2a, and the area under the curve from 0 to 168 hours was about 20% above adult values, suggesting that drug doses calculated from BSA achieved therapeutically adequate concentrations. Six of 14 patients (43%), all infected with genotype 1, achieved a sustained virological response. Adverse events were those commonly associated with INF-based treatment, and none was deemed serious. In conclusion, our findings provide a basis for larger studies evaluating the efficacy and safety of pegINF-alpha2a as monotherapy as well as in combination with ribavirin in pediatric patients with chronic hepatitis C.
Highly Functionalized Pyranopyrans from Furans:  A Synthesis of the C27−C38 and C44−C53 Subunits of Norhalichondrin B (2007)

A synthesis of highly functionalized pyranopyrans based on an Achmatowicz oxidation followed by a remarkably diastereoselective Kishi reduction is described in the context of studies directed toward norhalichondrin B.
Pyroptotic Neuronal Cell Death Mediated by the AIM2 Inflammasome (2014)

The central nervous system (CNS) is an active participant in the innate immune response to infection and injury. In these studies, we show embryonic cortical neurons express a functional, deoxyribonucleic acid (DNA)-responsive, absent in melanoma 2 (AIM2) inflammasome that activates caspase-1. Neurons undergo pyroptosis, a proinflammatory cell death mechanism characterized by the following: (a) oligomerization of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC); (b) caspase-1 dependency; (c) formation of discrete pores in the plasma membrane; and (d) release of the inflammatory cytokine interleukin-1β (IL-1β). Probenecid and Brilliant Blue FCF, inhibitors of the pannexin1 channel, prevent AIM2 inflammasome-mediated cell death, identifying pannexin1 as a cell death effector during pyroptosis and probenecid as a novel pyroptosis inhibitor. Furthermore, we show activation of the AIM2 inflammasome in neurons by cerebrospinal fluid (CSF) from traumatic brain injury (TBI) patients and oligomerization of ASC. These findings suggest neuronal pyroptosis is an important cell death mechanism during CNS infection and injury that may be attenuated by probenecid.
The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin. (1996)

Previous studies have demonstrated that the Mycobacterium tuberculosis phagosome in human monocyte-derived macrophages acquires markers of early and late endosomes, but direct evidence of interaction of the M. tuberculosis phagosome with the endosomal compartment has been lacking. Using the cryosection immunogold technique, we have found that the M. tuberculosis phagosome acquires exogenously added transferrin in a time-dependent fashion. Near-maximal acquisition of transferrin occurs within 15 min, kinetics of acquisition consistent with interaction of the M. tuberculosis phagosome with early endosomes. Transferrin is chased out of the M. tuberculosis phagosome by incubation of the infected macrophages in culture medium lacking human transferrin. Phagosomes containing latex beads or heat-killed M. tuberculosis, on the other hand, do not acquire staining for transferrin. These and other findings demonstrate that M. tuberculosis arrests the maturation of its phagosome at a stage at which the phagosome interacts with early and late endosomes, but not with lysosomes. The transferrin endocytic pathway potentially provides a novel route for targeting antimicrobials to the M. tuberculosis phagosome.
The nucleotide sequence of the gene encoding the attachment protein H of canine distemper virus (1991)

The sequence of the H gene and flanking sequences in the F and L genes of canine distemper virus (CDV) have been determined. The H gene of CDV (1946 nucleotides) contains one large open reading frame starting at position 21 and terminating at position 1835, encoding a protein of 604 amino acid residues. This protein contains three potential glycosylation sites in the extracellular domain and, like all other paramyxoviruses, a N-terminal membrane-spanning hydrophobic anchor domain. The deduced H protein sequence shows an identity of 36% with rinderpest virus (RPV) and measles virus (MV). The identities at the nucleotide level are higher (RPV 52% and MV 53%). The amino acid sequence shows conservation of all the structural determinants with the H proteins of MV and RPV. The data also show that CDV is evolutionarily equidistant to RPV and MV with respect to the H gene.
Left ventricular failure induced by long-term hypertension in rats. (1990)

To determine whether the duration of hypertension is an essential component in the evolution of myocardial dysfunction, renal artery constriction was performed in male Fischer 344 rats at 4 months of age, and in vivo global cardiac performance of sham-operated and experimental animals was evaluated 8 months later. Systemic arterial blood pressure increased to 173 +/- 5 mm Hg 2 weeks after the arteries were clipped and remained elevated for the following 5 months. Blood pressure decreased over the remaining 3 months to a value not significantly different from control rats that were killed, 132 +/- 4 mm Hg. After 8 months of renovascular hypertension, we observed that the elevated level of systolic arterial pressure was accompanied by a distinct absence of left ventricular hypertrophy when measured at the ventricular weight level. Moreover, left ventricular end-diastolic pressure increased in hypertensive animals from 6.0 to 24.0 mm Hg while peak left ventricular pressure was identical to controls. In addition, peak +dP/dt and -dP/dt were depressed in hypertensive animals. Although stroke volume was unaltered, cardiac output in renal artery clipped animals was depressed by 34% while total peripheral resistance was elevated by 50%. Ventricular chamber remodeling in the hearts of hypertensive animals was evidenced as a 19% increase in the transverse and a 16% increase in the longitudinal axes of the left ventricle with a 27% diminution of wall thickness. Myocardial damage, in the form of myocyte loss and replacement fibrosis, increased in the hearts of hypertensive animals resulting in a ninefold augmentation in the volume fraction of collagen within the ventricular wall. These alterations in the architectural properties of chamber geometry coupled with the abnormalities in contractile performance resulted in a severe reduction in ejection fraction from 82% to 47% and a marked elevation in transmural diastolic and systolic stress in hypertensive animals. The gradient in stress across the ventricular wall, from epicardium to endocardium, revealed a direct correlation with the regional distribution of myocardial damage. In conclusion, the loading state of the myocardium, tissue injury, and myocardial fibrosis all appear to be critical determinants in the genesis of left ventricular failure in long-term pressure overload.
<title>MOSAD IR focal plane per pixel A/D development</title> (1996)

An on focal plane digital readout development suggested by the Army Night Vision &amp; Electronics Sensors Directorate is proceeding under a combined program with the development of two color HCT detector arrays. The on focal plane A/D process is based on the Amain patented multiplexed oversample A/D, MOSAD, technology. In the first year of the program, prototype on focal plane analog to digital converters for both staring arrays and scanning arrays were built and demonstrated. The prototypes included a 2 loop double ended switched MOSAD and a 1 loop single ended MOSAD. Results from the original experimental prototypes showed conclusively that better than 14 bits could be achieved and that well capacity could be increased to support high background HCT needs approaching 10<SUP>9</SUP> electrons. In the second year, a 64 X 64 staring array for HCT LWIR detectors, 50 micron centers, was built based on these original prototype designs. The layout of the per pixel MOSAD A/D staring array used Orbit 1.2 micron CMOS process and achieved a pixel size of 40 microns with a well capacity of 1.9 X 10<SUP>8</SUP> electrons. Integration capacitors were built using Orbit's normal double poly capacitors with a standard buffered direct inject TIA detector interface configuration. Preliminary testing has been completed indicating complete functionality. Fermionics LWIR HCT detectors with cutoff at 9 microns have been built for attachment to the readout but indium bumping was not completed in time to report system level testing results. However, some noise tests have been performed using on array current mirrors. These tests indicate that better than 12 bits has been achieved, but lower noise current sources will be required for a more accurate measurement.
Occurrence of Biomarkers in Green River Shale Oil (1983)

Biological markers, compounds derived essentially unchanged from living organisms, are found in oil-bearing rocks, petroleum and most ancient sediments. We are investigating the variation in ratios of certain biomarkers in shale oils and their use as tracers for relating oil to source rock during in-situ retorting. We have produced oil samples at heating rates of about 10°C/min from 1- and 2-foot shale composites from three Green River formation cores and have measured the occurrence of several isoprenoid and polycycloalkane compounds in the oils using capillary gas chromatography. To eliminate the effect of heating rate on alkene/alkane ratios, we used the sum of ene and ane forms where applicable to calculate ratios. Variations in biomarker content with depth, grade, odd/even ratios, normal alkene/alkane ratios and atomic nitrogen/organic carbon ratios were studied and cross correlations were determined. Correlations were particularly high between pairs of isoprenoid compounds. There is sufficient variation to use biomarkers as retort diagnostics and to demonstrate a variation in source material.
The Pancreatitis-associated Protein I Promoter Allows Targeting to the Pancreas of a Foreign Gene, Whose Expression Is Up-regulated during Pancreatic Inflammation (1997)

The pancreatitis-associated protein I (PAP I) is a pancreatic secretory protein expressed in pancreas during acute pancreatitis but not in the healthy pancreas. The promoter of the PAP I gene thus represents a potential candidate to drive expression of therapeutic molecules to the diseased pancreas. In this work, we have constructed recombinant adenoviruses harboring the chloramphenicol acetyltransferase (CAT) gene driven by several fragments of the PAP I promoter and have characterized their properties in vitro and in vivo. In vitro studies showed that the transduction of the pancreatic cell line AR-42J with these adenoviruses led to low levels of CAT activity in basal conditions. After stimulation with a combination of interleukin-6 and dexamethasone or after induction of oxidative stress, CAT activity was strongly induced, a characteristic of the endogenous PAP I gene. Stimulation was maximal when constructs comprised 1253 base pairs of the PAP I promoter, upstream from initiation of transcription, and decreased with shorter fragments of 317, 180, 118 or 61 base pairs. The recombinant adenovirus containing the CAT gene under the control of the PAP I promoter fragment (-1253/+10) was also tested in vivo. Following administration by intravenous injection into mice, CAT activity was measured in several tissues 96 h later. In healthy animals, low but significant CAT activity was detected in pancreas, compared with near background values observed in the other tissues. When experimental acute pancreatitis was induced, CAT expression was strongly enhanced only in pancreas. In control experiments with adenoviruses in which the CAT gene was driven by the cytomegalovirus promoter, higher levels of expression were observed in all tissues. Expression was not modified after induction of acute pancreatitis. In conclusion, this study shows that (i) a recombinant adenovirus containing a fragment of the PAP I promoter allows specific targeting of a reporter gene to the mouse pancreas and (ii) expression of the reporter gene in pancreas is induced during acute pancreatitis. Adenovirus-mediated gene therapy of acute pancreatitis is therefore conceivable.
Offline handwritten English character recognition based on convolutional neural network (2012)

This paper applies Convolutional Neural Networks (CNNs) for offline handwritten English character recognition. We use a modified LeNet-5 CNN model, with special settings of the number of neurons in each layer and the connecting way between some layers. Outputs of the CNN are set with error-correcting codes, thus the CNN has the ability to reject recognition results. For training of the CNN, an error-samples-based reinforcement learning strategy is developed. Experiments are evaluated on UNIPEN lowercase and uppercase datasets, with recognition rates of 93.7% for uppercase and 90.2% for lowercase, respectively.
Inhibition of hepatic microsomal cytochrome P450 by cannabidiol in adult male rats. (1990)

The mechanism of inhibitory effect of cannabidiol (CBD) on the hepatic drug-metabolizing enzyme system was studied in adult male rats in vivo. Time course studies revealed that microsomal d-benzphetamine N-demethylation and testosterone 2 alpha-, 16 alpha- and 17-oxidation were markedly suppressed 6 to 48 h after the single administration of CBD (10 mg/kg, intraperitoneally). Decreases in activities of aniline hydroxylation and p-nitroanisole O-demethylation and in content of total cytochrome P450 were intermittent and moderate. On the other hand, no change was observed in reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase activity or cytochrome b5 content in the hepatic microsomes of the CBD-treated rats. Western blotting analysis showed a marked decrease in the male-specific cytochrome P450 UT-2 in the hepatic microsomes, especially 24 to 48 h after pretreatment with CBD. It is possible that CBD given 6 to 12 h before the sacrifice might interact with cytochrome P450 as a substrate, resulting in inhibition of the drug-metabolizing enzyme activities in the earlier stages. In the later stages from 24 to 48 h after CBD treatment, the reduction in content of the male-specific cytochrome P450 UT-2 may play a major role in the inhibitory effect of CBD on the hepatic drug-metabolizing enzyme system in the adult male rat in vivo.
Solid-Phase SN2 Macrocyclization Reactions To Form β-Turn Mimics (1999)

[formula: see text] Efficient solid-phase SN2 macrocyclization reactions were sought to facilitate preparations of focused libraries of beta-turn mimetics. A very efficient, but undesired, cyclization reaction to give five-membered ring lactams 4 was identified in attempts to use O-nucleophiles. Subsequent studies focused exclusively on S-nucleophiles. These reactions gave the desired macrocyclization products 1 in high purities and good overall yields. Conformational analyses of illustrative macrocyclization products 1 via NMR, CD, and molecular simulations showed that they seem to sample both type I and type II beta-turn conformations in solution. CD studies indicate a curious relationship between the preferred conformation and the amino acids encapsulated in the macrocycles.
<title>Registration of visible and infrared images</title> (1993)

This paper presents an approach for registering images obtained from sensors tuned to significantly different regions of the electromagnetic spectrum. Standard correlation techniques for registration are not appropriate because of the inherent differences between the images. We present an approach which uses surface boundaries (obtained at multiple scales via an edge extraction process) to determine the affine transformation required to bring the images into registration. The affine parameters for registration are found by a hierarchical estimation process. A least squares gradient based technique is used to directly estimate the affine parameters from the blurred edges. Results of applying the algorithm to real image data are included.
CD of proline‐rich polypeptides: Application to the study of the repetitive domain of maize glutelin‐2 (1993)

An overview of CD of proline-rich peptides is reported. First, structural characteristics, theoretical CD studies, and the biological relevance of polyproline II structure in such peptides are discussed. Second, a CD study of peptides belonging to the repetitive domain of maize glutelin-2, H-(Val-His-Leu-Pro-Pro-Pro)n-OH (n = 3, 5, 8), is described. This series of peptides displayed the CD features of polyproline II structure in water (5 degrees C, pH 5). Moreover, it was shown that the addition of increasing amounts of the polyanionic molecule heparin forced a displacement of the conformational equilibrium of those peptides toward higher proportions of the polyproline II structure. In contrast, when the temperature is raised such a structure gradually disappears, leading to more disordered conformations.
Very Large Swelling in Hybrid Frameworks:  A Combined Computational and Powder Diffraction Study (2005)

Using a combination of simulations and powder diffraction, we report here the study of the very large swelling of a three-dimensional nanoporous iron(III) carboxylate (MIL-88) which exhibits almost a reversible doubling (approximately 85%) of its cell volume while fully retaining its open-framework topology. The crystal structure of the open form of MIL-88 has been successfully refined and indicates that atomic displacements larger than 4 angstroms are observed when water or various alcohols are adsorbed in the porous structure, revealing an unusually flexible crystallized framework. X-ray thermodiffractometry shows that only a displacive transition occurs during the swelling phenomenon, ruling out any bond breaking.
Immunoglobulin G3 Antibodies Specific for the 19-Kilodalton Carboxyl-Terminal Fragment ofPlasmodium yoeliiMerozoite Surface Protein 1 Transfer Protection to Mice Deficient in Fc-γRI Receptors (2000)

ABSTRACT Merozoite surface protein 1 (MSP-1 19 ) is a leading malaria vaccine candidate. Specific antibodies contribute to immunity; binding to macrophages is believed to represent the main action of malaria antibodies. We show that an MSP-1 19 -specific immunoglobulin G3 (IgG3) monoclonal antibody can passively transfer protection to mice deficient in the α chain of Fc-γRI whose macrophages cannot bind IgG3.
An evaluation of data-parallel compiler support for line-sweep applications (2003)

Data parallel compilers have long aimed to equal the performance of carefully hand-optimized parallel codes. For tightly coupled applications based on line sweeps, this goal has been particularly elusive. In the Rice dHPF compiler, we have developed a wide spectrum of optimizations that enable us to closely approach hand-coded performance for tightly-coupled line sweep applications including the NAS SP and BT benchmark codes. From lightly modified copies of standard serial versions of these benchmarks, dHPF generates MPI-based parallel code that is within 4% of the performance of the hand-crafted MPI implementations of these codes for a 102/sup 3/ problem size (Class B) on 64 processors. We describe and quantitatively evaluate the impact of partitioning, communication and memory hierarchy optimizations implemented by dHPF that enable us to approach hand-coded performance with compiler-generated parallel code.