gebhart/patrepeval huggingface dataset:
Chronic Effects of a Nonpeptide Corticotropin-Releasing Hormone Type I Receptor Antagonist on Pituitary-Adrenal Function, Body Weight, and Metabolic Regulation (1998)

CRH, the principal regulator of the hypothalamic-pituitary-adrenal axis and modulator of autonomic nervous system activity, also participates in the regulation of appetite and energy expenditure. Antalarmin, a pyrrolopyrimidine compound, antagonizes CRH type 1 receptor-mediated effects of CRH, including pituitary ACTH release, stress behaviors, and acute inflammation. We administered antalarmin chronically to evaluate its effects on hypothalamic-pituitary-adrenal axis function and metabolic status. Adult male rats were treated twice daily with 20 mg/kg of ip antalarmin or placebo over 11 days. The animals were weighed; plasma ACTH, corticosterone, leptin, and blood glucose levels were determined; and morphometric analyses were performed to determine adrenal size and structure, including sizing, histochemistry, immunohistochemistry, and electron microscopy. Leptin messenger RNA expression in peripheral fat was analyzed by Northern blot. Antalarmin decreased plasma ACTH (mean ± sd, 2.62 ± 0.063 pg/ml) and corticosterone concentrations (10.21 ± 1.80 μg/dl) compared with those in vehicle-treated rats [respectively, 5.3 ± 2.0 (P < 0.05) and 57.02 ± 8.86 (P < 0.01)]. Antalarmin had no significant effect on body weight, plasma leptin, or blood glucose concentrations or fat cell leptin messenger RNA levels. The width of the adrenal cortex of animals treated with antalarmin was reduced by 31% compared with that in controls without atrophy of the gland. On the ultrastructural level, adrenocortical cells were in a hypofunctional state characterized by reduced vascularization, increased content of lipid droplets, and tubulovesicular mitochondria with fewer inner membranes. The apoptotic rate was increased in the outer zona fasciculata of animals treated with the antagonist (26.6 ± 3.58%) compared with that in placebo-treated controls (6.8 ± 0.91%).
Rat models of autosomal dominant polycystic kidney disease (1996)

Several rat models of polycystic kidney disease (PKD) have been published. The only rat model of autosomal dominant polycystic kidney disease currently used is the so-called Hannover rat (Han:SPRD cy/+). This model is characterized by a slow progression of uraemia, proteinuria and hyperlipidaemia. Histological changes clearly resemble those seen is human PKD. The localization of Na+/K(+)-ATPase correlating with the phenotype of the cysts--basal in moderately expanded and apical in highly expanded cysts--suggests that the mislocation of the Na+/K(+)-ATPase is involved in the mechanism of cyst expansion rather than formation, and a consequence of cell dedifferentiation rather than an initial event. Of note is a considerable gender difference in disease severity. Disease anticipation or genetic imprinting does not occur. In addition to gender, a number of interventions influence the progression rate: acceleration is noted after unilateral nephrectomy, the induction of acidosis, chloride feeding or an increased protein intake; slowing down of the course occurs after the induction of alkalosis and castration, and after treatment with lovastatin and methylprednisolone. Thus the Han:SPRD cy/+ rat represents the only well-documented rat model of autosomal dominant PKD resembling a number of features of the human disease.
Towards an intelligent domain-specific traceability solution (2014)

State-of-the-art software trace retrieval techniques are unable to perform the complex reasoning that a human analyst follows in order to create accurate trace links between artifacts such as regulatory codes and requirements. As a result, current algorithms often generate imprecise links. To address this problem, we present the Domain-Contextualized Intelligent Traceability Solution (DoCIT), designed to mimic some of the higher level reasoning that a human trace analyst performs. We focus our efforts on the complex domain of communication and control in a transportation system. DoCIT includes rules for extracting ``action units'' from software artifacts, a domain-specific knowledge base for relating semantically similar concepts across action units, and a set of link-creation heuristics which utilize the action units to establish meaningful trace links across pairs of artifacts. Our approach significantly improves the quality of the generated trace links. We illustrate and evaluate DoCIT with examples and experiments from the control and communication sector of a transportation domain.
Changes in Seminal Plasma Transferrin Concentration Following Administration of Clomiphene Citrate (1993)

This study was designed to investigate the functional changes in Sertoli cells following clomiphene citrate administration to patients with idiopathic infertility. The agent was administered to 44 oligozoospermic patients. Patients with improvement in sperm concentration after treatment (improvement group) showed significantly lower pretreatment follicle-stimulating hormone (FSH) levels in serum. Serum FSH and testosterone levels significantly increased in the improvement group after treatment (both p < 0.05). Seminal transferrin concentration significantly increased in the improvement group after treatment (p < 0.05), although there was no significant difference between pretreatment seminal transferrin concentration in the improvement group and that in patients with no improvement in sperm concentration. Seminal plasma transferrin concentration in patients in whom pretreatment luteinizing hormone level in serum was below 10 mIU/mL, and in those in whom the ratio of post- to pretreatment values was 1.5 or more, tended to increase after treatment. This group also contained a few more patients with improvement in sperm concentration than the other groups. The patients showing low pretreatment FSH levels and a high ratio of post- to pretreatment values demonstrated a significant increase in seminal plasma transferrin concentration after treatment (p < 0.01), and this group contained more patients with improvement than the other groups. It would appear that Sertoli cell stimulation may induce an increase in sperm concentration after clomiphene citrate administration, and the elevated transferrin secretion seems to be associated with the increase of serum FSH level after treatment.
Measuring system XY-5i (1995)

The progress of integration in semiconductor (LSI) is remarkable. We expect that the mass-production of 256M DRAM shall start in the next few years. The design rules for this level of integration will require even more accurately in a system to measure a reticle pattern's position. To meet the measurement requirements for future IC designs, Nikon Corporation has developed to XY-5i. During development, we introduced some new technologies to improve the systems' measurement performance. In this paper, we will explain the new flexure compensation concept and the reduction of measurement error caused by temperature drift. These are the key technologies used to attain the improved performance. This performance will be demonstrated with actual measurement data from the XY-5i.
Lesch‐nyhan syndrome: A study of motor behavior and cerebrospinal fluid neurotransmitters (1988)

We studied 5 boys, 2 to 10 years old, with marked or complete deficiency of hypoxanthine-guanine phosphoribosyltransferase and Lesch-Nyhan syndrome with varying degrees of mental retardation, dysarthria, chorea, dystonia, spasticity, and ataxia. Four patients had marked reduction of homovanillic acid in the cerebrospinal fluid (CSF) and all showed low CSF 3-methoxy-4-hydroxy phenylethylene glycol, indicating reduced dopamine and norepinephrine turnover. Three patients showed high CSF 5-hydroxyindoleacetic acid, suggesting increased serotonin turnover. Some patients improved with carbidopa-levodopa, but others benefited from tetrabenazine, a monoamine-depleting agent. This study provides support for the theory of abnormal central monoamine metabolism in Lesch-Nyhan syndrome.
Clinical Significance ofTROP2Expression in Colorectal Cancer (2006)

TROP2 is one of the cancer-related genes that correlates with biological aggressiveness and poor prognosis of colorectal cancer. Thus, TROP2 is a possible candidate gene for diagnosis and molecular target therapy of colorectal cancer.
The Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder (1999)

A task force consisting of six authors reviewed the published literature on the therapy of the restless legs syndrome or periodic limb movements in sleep available in indices through April, 1998. They selected the 45 articles for detailed review which presented original investigations of therapeutic impact on the restless legs syndrome (RLS) or periodic limb movements (PLM) and which met minimal standards. These articles dealt with a range of pharmacological and other treatment modalities, although most dealt with medications and almost half of those concentrated on dopaminergic agents, especially levodopa in various formulations. Almost half of the articles reviewed used controlled methodologies, most commonly cross-over methodologies with randomized allocation of subjects. Multi-center studies with large numbers of subjects and long-term controlled studies were not found. Information was extracted from the articles and study design, clinical definition, evaluative measures, side effects, and outcomes were tabulated in 6 evidence tables and summarized in the accompanying text. This literature was evaluated for the nature of the studies performed and its coverage of potential therapies. The review concludes with comments on possible future directions for therapeutic investigation based on the current state of the literature.
Soluble Epoxide Hydrolase Inhibition Lowers Arterial Blood Pressure in Angiotensin II Hypertension (2002)

Epoxyeicosatrienoic acids (EETs) have antihypertensive properties and play a part in the maintenance of renal microvascular function. A novel approach to increase EET levels is to inhibit epoxide hydrolase enzymes that are responsible for conversion of biologically active EETs to dihydroxyeicosatrienoic acids (DHETs) that are void of effects on the preglomerular vasculature. We hypothesized that inhibition of soluble epoxide hydrolase (sEH) would lower blood pressure in angiotensin II (Ang II) hypertension. Rat renal cortical tissue was harvested and urine collected 2 weeks following implantation of an osmotic minipump containing Ang II (60 ng/min). Renal cortical sEH protein expression was significantly higher in Ang II hypertension compared with normotensive animals. Likewise, urinary 14,15-DHET levels were significantly increased in hypertensive compared with normotensive animals and averaged 8.1 +/- 1.3 and 2.7 +/- 1.1 ng/d; respectively. In additional experiments, the sEH inhibitor N-cyclohexyl-N-dodecyl urea (NCND; 3 mg/d) or vehicle (corn oil, 0.5 mL) was administered daily by intraperitoneal injection starting on day 10. Administration of NCND for 4 days lowered systolic blood pressure by 30 mm Hg in Ang II hypertensive animals, whereas the corn oil vehicle had no effect on blood pressure in normotensive or Ang II hypertensive animals. Measurement of blood pressure by indwelling arterial catheters in conscious animals with free movement in their cages confirmed that NCND had antihypertensive properties. Arterial blood pressure averaged 119 +/- 5 mm Hg in normotensive, 170 +/- 3 mm Hg in hypertensive and 149 +/- 10 mm Hg in NCND-treated, Ang II-infused animals. Administration of the potential metabolite of NCND, N-cyclohexylformamide to Ang II hypertensive rats did not lower the systolic blood pressure. These studies demonstrate that increased sEH expression in the Ang II hypertensive kidney leads to increased EET hydration. Moreover, sEH plays a role in the regulation of blood pressure, and inhibition of sEH during Ang II hypertension is antihypertensive.
Metabolic, enzymatic, and transporter responses in human muscle during three consecutive days of exercise and recovery (2008)

This study investigated the responses in substrate- and energy-based properties to repetitive days of prolonged submaximal exercise and recovery. Twelve untrained volunteers (Vo(2)(peak) = 44.8 +/- 2.0 ml.kg(-1).min(-1), mean +/- SE) cycled ( approximately 60 Vo(2)(peak)) on three consecutive days followed by 3 days of recovery. Tissue samples were extracted from the vastus lateralis both pre- and postexercise on day 1 (E1), day 3 (E3), and during recovery (R1, R2, R3) and were analyzed for changes in metabolism, substrate, and enzymatic and transporter responses. For the metabolic properties (mmol/kg(-1) dry wt), exercise on E1 resulted in reductions (P < 0.05) in phosphocreatine (PCr; 80 +/- 1.9 vs. 41.2 +/- 3.0) and increases (P < 0.05) in inosine monophosphate (IMP; 0.13 +/- 0.01 vs. 0.61 +/- 0.2) and lactate (3.1 +/- 0.4 vs. 19.2 +/- 4.3). At E3, both IMP and lactate were lower (P < 0.05) during exercise. For the transporters, the experimental protocol resulted in a decrease (P < 0.05) in glucose transporter-1 (GLUT1; 29% by R1), an increase in GLUT4 (29% by E3), and increases (P < 0.05) for both monocarboxylate transporters (MCT) (for MCT1, 23% by R2 and for MCT4, 18% by R1). Of the mitochondrial and cytosolic enzyme activities examined, cytochrome c oxidase (COX), and hexokinase were both reduced (P < 0.05) by exercise at E1 and in the case of hexokinase and phosphorylase by exercise on E3. With the exception at COX, which was lower (P < 0.05) at R1, no differences in enzyme activities existed at rest between E, E3, and recovery days. Results suggest that the glucose and lactate transporters are among the earliest adaptive responses of substrate and metabolic properties studied to the sudden onset of regular low-intensity exercise.
Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety (2008)

Preterm birth is the leading cause of neonatal mortality and morbidity and long-term disability of non-anomalous infants. Previous studies have identified a prior early spontaneous preterm birth as the risk factor with the highest predictive value for recurrence. Two recent double blind randomized placebo controlled trials reported lower preterm birth rate with the use of either intramuscular 17 alpha-hydroxyprogesterone caproate (IM 17OHP-C) or intravaginal micronized progesterone suppositories in women at risk for preterm delivery. However, it is still unclear which high-risk women would truly benefit from this treatment in a general clinical setting and whether socio-cultural, racial and genetic differences play a role in patient's response to supplemental progesterone. In addition the patient's acceptance of such recommendation is also in question. More research is still required on identification of at risk group, the optimal gestational age at initiation, mode of administration, dose of progesterone and long-term safety.
Binning for IC quality: experimental studies on the SEMATECH data (2002)

In semiconductor manufacturing, the observed clustering of defects on a wafer has often led to the practice of discarding die from wafers, or parts of the wafer, that display a high incidence of failures. In recent work we have formalized and refined this process with the goal of minimizing test escapes during production testing. In the new approach, in evaluating the quality of test results for a particular die, test results for the die's neighbors are also considered. Among other results, it has been shown that by exploiting defect clustering information it is possible to bin dice following testing so as to separate out a high quality bin with defect levels up to an order of magnitude better than the average for the lot. In this paper we present the first experimental results on the effectiveness of die screening for a modern submicron CMOS process. The data comes from the SEMATECH test methods experiment conducted at IBM on 18,466 from a production ASIC in a 0.5 /spl mu/m process.
On-Chip Proteolytic Digestion and Analysis Using “Wrong-Way-Round” Electrospray Time-of-Flight Mass Spectrometry (2001)

Rapid protein digestion and analysis using a hybrid microchip nanoelectrospray device and time-of-flight mass spectrometry detection are reported. The device consists of a planar glass chip with microfabricated channels coupled to a disposable nanospray emitter. Reactions between substrate and enzyme (trypsin), mixed off-chip and then immediately loaded into a sample reservoir on the device, are monitored in real time following the onset of electrospray. Protein cleavage products are determined at the optimum pH for generating tryptic fragments, directly from the digestion buffer using "wrong-way-round" electrospray, i.e., monitoring (MH)+ ions from basic solutions. Intense tryptic peptide ions are observed within a few minutes following sample loading on the microchip. Proteins were identified from low femtomole or even attomole quantities of analyte/spectrum using peptide mass fingerprinting, loading 0.1-2 pmol/microL of sample on the chip. The sequence coverage for analyzed proteins ranged from 70 to 95%. The rapid analysis of human hemoglobin is demonstrated using the technique.
Practical Considerations for Using Pooled Lentiviral CRISPR Libraries (2016)

CRISPR/Cas9 technology is ideally suited for genome-wide screening applications due to the ease of generating guide RNAs (gRNAs) and the versatility of Cas9 or Cas9 derivatives to knockout, repress, or activate expression of target genes. Several pooled lentiviral CRISPR libraries have been developed and are now publicly available, but while using CRISPR/Cas9 for genetic experiments has become widely adopted, genome-wide screening experiments remain technically challenging. This review covers the basics of CRISPR/Cas9, describes several publicly available CRISPR libraries, and provides a general protocol for conducting genome-wide screening experiments using CRISPR/Cas9. © 2016 by John Wiley & Sons, Inc.
Physical characterization of controlled release of paclitaxel from the TAXUS™ Express2™ drug‐eluting stent (2004)

The polymer carrier technology in the TAXUS drug-eluting stent consists of a thermoplastic elastomer poly(styrene-b-isobutylene-b-styrene) (SIBS) with microphase-separated morphology resulting in optimal properties for a drug-delivery stent coating. Comprehensive physical characterization of the stent coatings and cast film formulations showed that paclitaxel (PTx) exists primarily as discrete nanoparticles embedded in the SIBS matrix. Thermal and chemical analysis did not show any evidence of solubility of PTx in SIBS or of any molecular miscibility between PTx and SIBS. Atomic force microscope data images revealed for the first time three-dimensional stent coating surfaces at high spatial resolutions in air and in situ under phosphate-buffered saline as drug was released. PTx release involves the initial dissolution of drug particles from the PTx/SIBS coating surface. Morphological examination of the stent coatings in vitro supported an early burst release in most formulations because of surface PTx followed by a sustained slower release of PTx from the bulk coating. The in vitro PTx release kinetics were dependent on the formulation and correlated to the drug-to-polymer ratio. Atomic force microscopy analysis confirmed this correlation and further supported the concept of a matrix-based drug-release coating.
Immunogenicity of native or pegylated E. coli and Erwinia asparaginases assessed by ELISA and surface plasmon resonance (SPR-biacore) assays of IgG antibodies (Ab) in sera from patients with acute lymphoblastic leukemia (ALL). (2009)

The vast majority (81/84 = 96.4%) of the IgG Ab(+) were neutralizing. The SPR Ab determination technique is reliable, accurate and more sensitive than the ELISA method.
Calcium/Calmodulin-dependent Protein Kinase II (CaMKII) Inhibition Induces Neurotoxicity via Dysregulation of Glutamate/Calcium Signaling and Hyperexcitability (2012)

Aberrant glutamate and calcium signalings are neurotoxic to specific neuronal populations. Calcium/calmodulin-dependent kinase II (CaMKII), a multifunctional serine/threonine protein kinase in neurons, is believed to regulate neurotransmission and synaptic plasticity in response to calcium signaling produced by neuronal activity. Importantly, several CaMKII substrates control neuronal structure, excitability, and plasticity. Here, we demonstrate that CaMKII inhibition for >4 h using small molecule and peptide inhibitors induces apoptosis in cultured cortical neurons. The neuronal death produced by prolonged CaMKII inhibition is associated with an increase in TUNEL staining and caspase-3 cleavage and is blocked with the translation inhibitor cycloheximide. Thus, this neurotoxicity is consistent with apoptotic mechanisms, a conclusion that is further supported by dysregulated calcium signaling with CaMKII inhibition. CaMKII inhibitory peptides also enhance the number of action potentials generated by a ramp depolarization, suggesting increased neuronal excitability with a loss of CaMKII activity. Extracellular glutamate concentrations are augmented with prolonged inhibition of CaMKII. Enzymatic buffering of extracellular glutamate and antagonism of the NMDA subtype of glutamate receptors prevent the calcium dysregulation and neurotoxicity associated with prolonged CaMKII inhibition. However, in the absence of CaMKII inhibition, elevated glutamate levels do not induce neurotoxicity, suggesting that a combination of CaMKII inhibition and elevated extracellular glutamate levels results in neuronal death. In sum, the loss of CaMKII observed with multiple pathological states in the central nervous system, including epilepsy, brain trauma, and ischemia, likely exacerbates programmed cell death by sensitizing vulnerable neuronal populations to excitotoxic glutamate signaling and inducing an excitotoxic insult itself.
Regulation of theMycobacterium tuberculosishypoxic response gene encoding α-crystallin (2001)

Unlike many pathogens that are overtly toxic to their hosts, the primary virulence determinant of Mycobacterium tuberculosis appears to be its ability to persist for years or decades within humans in a clinically latent state. Since early in the 20th century latency has been linked to hypoxic conditions within the host, but the response of M. tuberculosis to a hypoxic signal remains poorly characterized. The M. tuberculosis alpha-crystallin (acr) gene is powerfully and rapidly induced at reduced oxygen tensions, providing us with a means to identify regulators of the hypoxic response. Using a whole genome microarray, we identified >100 genes whose expression is rapidly altered by defined hypoxic conditions. Numerous genes involved in biosynthesis and aerobic metabolism are repressed, whereas a high proportion of the induced genes have no known function. Among the induced genes is an apparent operon that includes the putative two-component response regulator pair Rv3133c/Rv3132c. When we interrupted expression of this operon by targeted disruption of the upstream gene Rv3134c, the hypoxic regulation of acr was eliminated. These results suggest a possible role for Rv3132c/3133c/3134c in mycobacterial latency.
Detection of Enzyme Activity through Catalytic Signal Amplification with Functionalized Gold Nanoparticles (2011)

A cascade of two catalytic events was used to detect enzyme activity: When a peptide substrate acting as an inhibitor for a catalytic gold nanoparticle was hydrolyzed by an enzyme, the catalytic activity of the nanoparticle was restored, and a large amount of a yellow reporter molecule was produced (see picture; S=substrate, P=product). The assay can be made selective for a particular enzyme by changing the inhibitory peptide.