gebhart/patrepeval huggingface dataset:
Parasite strain specificity of bovine cytotoxic T cell responses to Theileria parva is determined primarily by immunodominance (1995)

The parasite strain specificity of CTL responses to Theileria parva varies among cattle immunized with the same parasite stock. We have investigated the influence of class I MHC on the strain specificity of CTL responses to T. parva in 19 cattle of defined class I phenotype immunized with either of two T. parva populations, in which protection to subsequent reciprocal challenge correlated with CTL strain specificity. In the majority of animals the response was restricted by the products of one MHC haplotype and there was a consistent bias to some haplotypes in preference to others. In 10 of 13 cattle expressing the molecularly defined MHC specificities A10 and KN104 on one haplotype, the CTL response was restricted entirely by this haplotype, thus allowing a precise analysis of the MHC restriction specificities. The MHC restriction specificity and the parasite population used for immunization both influenced the strain specificity of the response. By examining responses in identical twins immunized with different parasites or in animals before and after challenge with heterologous parasites, animals that mounted a strain-specific response to primary infection were shown to be capable of responding to Ags shared by the two parasite populations. These findings indicate that the strain specificity of CTL responses to T. parva is not determined primarily by immune response genes that define the inherent capacity to respond, but rather is a consequence of the response in individual animals being biased toward a limited number of immunodominant peptide-MHC determinants.
An intervention trial on efficacy of atropine and multi‐focal glasses in controlling myopic progression (2001)

The 0.5% atropine with multi-focal lenses can slow down the progression rate of myopia. However, multi-focal lenses alone showed no difference in effect compared to control.
Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome (1992)

The androgen insensitivity syndrome (AIS) is a disorder of male sexual development resulting in a wide range of clinical phenotypes. AIS is classified into two phenotypic forms: complete (CAIS) and partial (PAIS). To determine the molecular basis of the phenotypic diversity in AIS, we have studied 27 subjects (13 CAIS, 14 PAIS), spanning the full range of AIS phenotypes. We report the results of a mutation screen of the androgen receptor gene. The coding regions of the gene were amplified by the polymerase chain reaction and screened for single strand conformation polymorphisms to identify mutations. This was followed by DNA sequencing of putative mutant segments. Androgen receptor gene mutations were identified in nine CAIS and five PAIS subjects. Two of the CAIS mutations in exon A resulted in frameshifts. A third CAIS mutation resulted in the deletion of a single amino acid from the ligand binding domain of the receptor. All other mutations caused single amino acid substitutions in the ligand binding domain. These results suggest that mutations affecting the ligand binding domain of the androgen receptor are the most frequent cause of AIS, although some cases of PAIS may be the result of other, as yet undefined, genetic lesions.
The RNA structures engaged in replication and transcription of the A59 strain of mouse hepatitis virus (2001)

In addition to the RI (replicative intermediate RNA) and native RF (replicative form RNA), mouse hepatitis virus-infected cells contained six species of RNA intermediates active in transcribing subgenomic mRNA. We have named these transcriptive intermediates (TIs) and native transcriptive forms (TFs) because they are not replicating genome-sized RNA. Based on solubility in high salt solutions, approximately 70% of the replicating and transcribing structures that accumulated in infected cells by 5-6 h post-infection were multi-stranded intermediates, the RI/TIs. The other 30% were in double-stranded structures, the native RF/TFs. These replicating and transcribing structures were separated by velocity sedimentation on sucrose gradients or by gel filtration chromatography on Sepharose 2B and Sephacryl S-1000, and migrated on agarose gels during electrophoresis, according to their size. Digestion with RNase T1 at 1-10 units/microgram RNA resolved RI/TIs into RF/TF cores and left native RF/TFs intact, whereas RNase A at concentrations of 0.02 microgram/microgram RNA or higher degraded both native RF/TFs and RI/TIs. Viral RI/TIs and native RF/TFs bound to magnetic beads containing oligo(dT)(25), suggesting that the poly(A) sequence on the 3' end of the positive strands was longer than any poly(U) on the negative strands. Kinetics of incorporation of [(3)H]uridine showed that both the RI and TIs were transcriptionally active and the labelling of RI/TIs was not the dead-end product of aberrant negative-strand synthesis. Failure originally to find TIs and TF cores was probably due to overdigestion with RNase A.
Sequential targeted therapy for relapsed acute promyelocytic leukemia with all-trans retinoic acid and anti-CD33 monoclonal antibody M195. (1995)

Acute promyelocytic leukemia (APL) provides a model to examine the sequential use of selective oncogene product-targeted and lineage-targeted agents. All-trans retinoic acid (RA) has been shown to produce brief remissions by a novel differentiating mechanism in most patients with APL. M195, a mouse monoclonal antibody (moAb) reactive with the cell-surface antigen CD33, can target myeloid leukemia cells in patients and reduce large leukemic burdens when labeled with 131I. We studied whether 131I-M195 could safely reduce minimal residual disease and prolong remission and survival durations in patients with relapsed APL after they had attained remission with all-trans RA. Seven patients with relapsed APL in second remission were treated with either 70 (n = 2) or 50 (n = 5) mCi/m2 of 131I-M195. As a measure of minimal residual disease, we serially monitored PML/RAR-alpha mRNA by a reverse transcription polymerase chain reaction (RT-PCR) assay. There was no immediate toxicity. Late toxicity was limited to myelosuppression, but no episodes of febrile neutropenia were seen. Six patients had detectable PML/RAR-alpha mRNA after all-trans RA therapy; two had single negative RT-PCR determinations following 131I-M195. Median disease-free survival of the seven patients was 8 months (range 3-14.5). Four patients with median follow-up of 24 months remain alive, and median overall survival exceeds 21+ months (range 5.5-33+). This regimen based on targeted therapy compares favorably to other approaches for the treatment of relapsed APL, including that used in the immediately preceding trial in which patients were induced into remission and maintained with all-trans RA, as well as other chemotherapy-based regimens. These data support further study of moAb-based therapy for minimal residual disease in acute leukemia.
Inhibitors of LRRK2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson's disease models (2011)

Mutations in leucine-rich repeat kinase 2 (LRRK2) have been identified as a genetic cause of familial Parkinson's disease (PD) and have also been found in the more common sporadic form of PD, thus positioning LRRK2 as important in the pathogenesis of PD. Biochemical studies of the disease-causing mutants of LRRK2 implicates an enhancement of kinase activity as the basis of neuronal toxicity and thus possibly the pathogenesis of PD due to LRRK2 mutations. Previously, a chemical library screen identified inhibitors of LRRK2 kinase activity. Here, two of these inhibitors, GW5074 and sorafenib, are shown to protect against G2019S LRRK2-induced neurodegeneration in vivo in Caenorhabditis elegans and in Drosophila. These findings indicate that increased kinase activity of LRRK2 is neurotoxic and that inhibition of LRRK2 activity can have a disease-modifying effect. This suggests that inhibition of LRRK2 holds promise as a treatment for PD.
MANGO ? Modal Analysis for Grid Operation: A Method for Damping Improvement through Operating Point Adjustment (2010)

Small signal stability problems are one of the major threats to grid stability and reliability in the U.S. power grid. An undamped mode can cause large-amplitude oscillations and may result in system breakups and large-scale blackouts. There have been several incidents of system-wide oscillations. Of those incidents, the most notable is the August 10, 1996 western system breakup, a result of undamped system-wide oscillations. Significant efforts have been devoted to monitoring system oscillatory behaviors from measurements in the past 20 years. The deployment of phasor measurement units (PMU) provides high-precision, time-synchronized data needed for detecting oscillation modes. Measurement-based modal analysis, also known as ModeMeter, uses real-time phasor measurements to identify system oscillation modes and their damping. Low damping indicates potential system stability issues. Modal analysis has been demonstrated with phasor measurements to have the capability of estimating system modes from both oscillation signals and ambient data. With more and more phasor measurements available and ModeMeter techniques maturing, there is yet a need for methods to bring modal analysis from monitoring to actions. The methods should be able to associate low damping with grid operating conditions, so operators or automated operation schemes can respond when low damping is observed. The work presented in this report aims to develop such a method and establish a Modal Analysis for Grid Operation (MANGO) procedure to aid grid operation decision making to increase inter-area modal damping. The procedure can provide operation suggestions (such as increasing generation or decreasing load) for mitigating inter-area oscillations.
Blasticidin S Deaminase Gene(BSD):a New Selection Marker Gene for Transformation ofArabidopsis thalianaandNicotiana tabacum (1995)

Arabidopsis thaliana and Nicotiana tabacum were transformed to blasticidin S (BS) resistance with BSD (the BS deaminase gene from Aspergillus terreus) using the Agrobacterium-mediated transformation method. Expression of BSD allowed direct selection of transformants by the fungicide, and both kinds of transgenic plants showed high level of resistance phenotype at 100 ppm of BS sprayed on the leaves. Using Botrytis cinerea, the causal fungus of gray mold disease, it was exemplified that application of BS could control the disease in transgenic tobacco with negligible phytotoxicity.
Automated analysis of digital relay data based on expert system (2005)

Modern digital protective relays generate various flies and reports which contain abundant data regarding fault disturbances and protection system operation. This paper presents an expert system based application for automated analysis of digital relay data. In this application, forward chaining reasoning is used to predict expected protection operation while backward chaining reasoning is employed to validate and diagnosis of actual protection operation. An EMTP/C++ based digital relay model with capability of insertion of user-defined errors and generation of files and reports is developed. The analysis capability of this application is tested using the relay model.
CHOLESTASIS IN THE RAT BY MEANS OF INTRAVENOUS ADMINISTRATION OF CYCLOSPORINE VEHICLE, CREMOPHOR EL (1989)

The effect of cyclosporine vehicle, Cremophor EL, on bile flow and biliary bile acids and bilirubin output was studied in anesthetized male Wistar rats. Intravenous administration of Cremophor EL or castor oil as a single bolus reduced bile flow and the biliary output of bile acids and bilirubin. The Cremophor EL-induced cholestasis was an immediate and reversible phenomenon, since at 30-35 min after drug injection all parameters evaluated had returned to control values. A slight increase in serum bilirubin concentrations was observed. Our data indicate that the observed cholestasis is related to a reduction in both bile acid-dependent and bile acid-independent bile flow, probably due to a transitory hepatotoxic effect of Cremophor EL. We conclude that the clinically used vehicle for i.v. administration of cyclosporine, Cremophor EL, has adverse effects on hepatobiliary physiology in the rat and suggest that an alternative vehicle should be used.
Evaluating Operation Strategies via Integrated Asset Modeling (2002)

Abstract An integrated asset modeling approach was used to evaluate gas compression and operating strategies for six gas fields in offshore Trinidad. Material balance and well models were linked to a pipeline network model. These IAM models were successfully used to evaluate the benefits of compression and looping of a pipeline segment. The modeling allowed the impact of interference of fields, different sand units within a field, wells, and facility constraints to be quantified. Compression could increase the gas recovery from six Trinidad fields by between 8.8% and 11.7 % of the original gas in place.
Messenger RNA electroporation: an efficient tool in immunotherapy and stem cell research. (2005)

Over the last decades medicine has developed tremendously, but still many diseases are incurable. The last years, cellular (gene) therapy has become a hot topic in biomedical research for the potential treatment of cancer, AIDS and diseases involving cell loss or degeneration. Here, we will focus on two major areas within cellular therapy, cellular immunotherapy and stem cell therapy, that could benefit from the introduction of neo-expressed genes through mRNA electroporation for basic research as well as for clinical applications. For cellular immunotherapy, we will provide a state-of-the-art on loading antigen-presenting cells with antigens in the mRNA format for manipulation of T cell immunity. In the area of stem cell research, we will highlight current gene transfer methods into adult and embryonic stem cells and discuss the use of mRNA electroporation for controlling guided differentiation of stem cells into specialized cell lineages.
Randomized, controlled trial of telcagepant for the acute treatment of migraine (2009)

This study confirmed previous findings that telcagepant 300 mg was effective at relieving pain and other migraine symptoms at 2 hours and providing sustained pain freedom up to 24 hours. In this study, telcagepant 150 mg was also effective. Telcagepant was generally well tolerated.
Purification and characterization of GlcNAc-6-P 2-epimerase from Escherichia coli K92. (2007)

N-Acetylmannosamine (ManNAc) is the first committed intermediate in sialic acid metabolism. Thus, the mechanisms that control intracellular ManNAc levels are important regulators of sialic acid production. In prokaryotic organisms, UDP-N-acetylglucosamine (GlcNAc) 2-epimerase and GlcNAc-6-P 2-epimerase are two enzymes capable of generating ManNAc from UDP-GlcNAc and GlcNAc-6-P, respectively. We have purified for the first time native GlcNAc-6-P 2-epimerase from bacterial source to apparent homogeneity (1 200 fold) using Butyl-agarose, DEAE-FPLC and Mannose-6-P-agarose chromatography. By SDS/PAGE the pure enzyme showed a molecular mass of 38.4 +/- 0.2 kDa. The maximum activity was achieved at pH 7.8 and 37 degrees C. Under these conditions, the K(m) calculated for GlcNAc-6-P was 1.5 mM. The 2-epimerase activity was activated by Na(+) and inhibited by mannose-6-P but not mannose-1-P. Genetic analysis revealed high homology with bacterial isomerases. GlcNAc-6-P 2-epimerase from E. coli K92 is a ManNAc-inducible protein and is detected from the early logarithmic phase of growth. Our results indicate that, unlike UDP-GlcNAc 2-epimerase, which promotes the biosynthesis of sialic acid, GlcNAc-6-P 2-epimerase plays a catabolic role. When E. coli grows using ManNAc as a carbon source, this enzyme converts the intracellular ManNAc-6-P generated into GlcNAc-6-P, diverting the metabolic flux of ManNAc to GlcNAc.
Perivascular Drug Delivery Systems for the Inhibition of Intimal Hyperplasia (2005)

The long-term clinical success of autologous vein and synthetic vascular grafts is limited due to the development of anastomotic intimal hyperplasia (IH).Previously published data suggests that cyclosporine (CyA) (an immunosuppressive drug) may reduce the development of IH in a canine model [1].However, systemic administration of CyA could create serious adverse effects.Therefore, it is our long-term goal to test the hypothesis that the controlled local release of cyclosporine from a polymeric vascular wrap will prevent the development of IH.In order to test this hypothesis, we developed three controlled release polymeric devices that could be placed around vascular graft anastomotic sites to deliver therapeutic drugs locally.The first device is a poly(ethylene glycol) (PEG) hydrogel sheet.The second device is a composite device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres dispersed in the PEG hydrogel sheet.The third device is in the form of a ring (referred to as PolyRing from here on) that can be slipped around the anastomotic sites.PolyRing is a composite polymeric device consisting of PLGA microspheres embedded in a PEG hydrogel.In-vitro studies were conducted on the three devices to evaluate the effects of different sterilization procedures on the properties of the device.It was
Clinical comparison of technetium-99m-EC, technetium-99m-MAG3 and iodine-131-OIH in renal disorders. (1995)

This limited study demonstrates the pharmacokinetic and renal clearance properties of 99mTc-EC. This agent has good potential for renal function evaluation.
Cache profiling and the SPEC benchmarks: a case study (1994)

A vital tool-box component, the CProf cache profiling system lets programmers identify hot spots by providing cache performance information at the source-line and data-structure level. Our purpose is to introduce a broad audience to cache performance profiling and tuning techniques. Although used sporadically in the supercomputer and multiprocessor communities, these techniques also have broad applicability to programs running on fast uniprocessor workstations. We show that cache profiling, using our CProf cache profiling system, improves program performance by focusing a programmer's attention on problematic code sections and providing insight into appropriate program transformations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Chronic Vagus Nerve Stimulation Improves Autonomic Control and Attenuates Systemic Inflammation and Heart Failure Progression in a Canine High-Rate Pacing Model (2009)

Chronic VNS improves cardiac autonomic control and significantly attenuates HF development in the canine high-rate ventricular pacing model. The therapeutic benefit of VNS is associated with pronounced anti-inflammatory effects. VNS is a novel and potentially useful therapy for treating HF.
Lysosomal Delivery of a Lipophilic Gemcitabine Prodrug Using Novel Acid-Sensitive Micelles Improved Its Antitumor Activity (2012)

Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly(ethylene glycol) (PEG) with a hydrophobic stearic acid derivative (C18) using an acid-sensitive hydrazone bond (PHC). An acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the acid-sensitive PHC micelles was more cytotoxic than in the acid-insensitive PAC micelles, which may be attributed to the acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16-F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activity than GemC18 or gemcitabine solution, likely because of the prolonged circulation time and increased tumor accumulation of the GemC18 by the micelles. Importantly, the in vivo antitumor activity of GemC18-loaded PHC micelles was significantly stronger than that of the PAC micelles, demonstrating the potential of the novel acid-sensitive micelles as an anticancer drug delivery system.
Catecholamine Glucuronidation: An Important Metabolic Pathway for Dopamine in the Rat (1983)

In the present study, we found that large quantities of dopamine (DA) glucuronide were present in rat cerebrospinal fluid (CSF), plasma, and urine, whereas the glucuronides of norepinephrine (NE) and epinephrine (E) were almost undetectable. The high urinary excretion of DA glucuronide was in a range comparable to that of homovanillic acid (HVA). Sulfates of DA, NE, and E were measurable in all three body fluids, but only in small quantities. The measured DA glucuronide was predominantly of endogenous origin, as the feeding of sucrose instead of routine diet did not reduce the urinary output of DA glucuronide. Adrenalectomy but not peripheral sympathectomy induced by chronic guanethidine injection substantially decreased plasma DA glucuronide concentrations, indicating that the adrenals serve as an important source of endogenous DA glucuronide. The data suggest that glucuronidation constitutes an important metabolic pathway for endogenous DA of central and peripheral origin in rats; this route, however, is exclusive to DA and appears to play a negligible role for NE and E.
High-speed performance of Silicon Bridge die-to-die interconnects (2011)

Silicon Bridge is a dense multichip packaging architecture that enables high die-to-die interconnect density and corresponding applications. We describe the basic ideas of the concept, discuss density in the die-to-die interconnect context, and report results of electrical high-speed performance simulations, based on both two-dimensional and three-dimensional electromagnetic modeling.
Discovery and Development of Natural Product-Derived Chemotherapeutic Agents Based on a Medicinal Chemistry Approach (2010)

Medicinal plants have long been an excellent source of pharmaceutical agents. Accordingly, the long-term objectives of the author's research program are to discover and design new chemotherapeutic agents based on plant-derived compound leads by using a medicinal chemistry approach, which is a combination of chemistry and biology. Different examples of promising bioactive natural products and their synthetic analogues, including sesquiterpene lactones, quassinoids, naphthoquinones, phenylquinolones, dithiophenediones, neo-tanshinlactone, tylophorine, suksdorfin, DCK, and DCP, will be presented with respect to their discovery and preclinical development as potential clinical trial candidates. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational drug design-based modification and analogue synthesis, and structure-activity relationship and mechanism of action studies. Current clinical trial agents discovered by the Natural Products Research Laboratories, University of North Carolina, include bevirimat (dimethyl succinyl betulinic acid), which is now in phase IIb trials for treating AIDS. Bevirimat is also the first in a new class of HIV drug candidates called "maturation inhibitors". In addition, an etoposide analogue, GL-331, progressed to anticancer phase II clinical trials, and the curcumin analogue JC-9 is in phase II clinical trials for treating acne and in development for trials against prostate cancer. The discovery and development of these clinical trial candidates will also be discussed.
Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention (2007)

Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.