gebhart/patrepeval huggingface dataset:
Adjacent-segment degeneration after lumbar fusion: a review of clinical, biomechanical, and radiologic studies. (1999)

Lumbar fusion is commonly performed to relieve pain from degenerative conditions, including spinal stenosis and spondylolisthesis. While clinical studies have reported favorable fusion rates with limited complications, few have investigated the effect of fusion on the adjacent motion segment. A solid fusion alters the biomechanics at the adjacent level, resulting in increased mechanical demands. There have been reports of increased rates of adjacent-level pathologic lesions after fusion, but these have not accounted for the natural history of degenerative changes. Biomechanical and radiographic studies have shown increased forces, mobility, and intradiscal pressure in adjacent segments after fusion. It has been hypothesized that these changes lead to an acceleration in pathologic changes.
Lymphocyte fluorescence polarization measurements with the cellscan system: Application to the SCM cancer test (1996)

The SCM (Structuredness of Cytoplasmic Matrix) cancer test, a procedure based on detection of differences in lymphocyte activation between individuals with and without cancer, has remained controversial with inconsistent results reported by different authors. As originally described, the test includes two technically demanding steps, the first a lymphocyte separation procedure and the second a series of fluorescence polarization measurements. The Cellscan, a high-precision static cytometer system has been configured to perform the SCM test. The apparatus facilitates the polarization measurements and can analyze cells separated using simpler procedures than were originally described. Using methods and diagnostic criteria adapted for the Cellscan system, the SCM test correctly classified > 90% of patients with cancer and > 90% of individuals without cancer.
Applications of a Rat Multiple Tissue Gene Expression Data Set (2004)

With the sequencing and assembly of the rat genome comes the difficult task of assigning functions to genes. Tissue localization of gene expression gives some information about the potential role of a gene in physiology. Various examples of the utility of multiple tissue gene expression data sets are illustrated here. First, we highlight their use in finding genes that might play an important role in a particular tissue on the basis of exclusive expression in that tissue or coexpression with a gene or genes with known function. Second, we show how this data might be used to explain known phenotypic differences between strains. Third, we show how expression patterns of genes in a genomic interval might identify candidate genes in quantitative trait loci (QTL) mapping studies. Lastly, we show how multiple tissue and species data can help researchers prioritize follow up studies to microarray experiments. All of these applications of multiple tissue gene expression data sets will play a role in functionally annotating the rat genome.
On-chip mid-infrared gas detection using chalcogenide glass waveguide (2016)

We demonstrate an on-chip sensor for room-temperature detection of methane gas using a broadband spiral chalcogenide glass waveguide coupled with off-chip laser and detector. The waveguide is fabricated using UV lithography patterning and lift-off after thermal evaporation. We measure the intensity change due to the presence and concentration of methane gas in the mid-infrared (MIR) range. This work provides an approach for broadband planar MIR gas sensing.
Human Drug Metabolism and the Cytochromes P450: Application and Relevance of In Vitro Models (2001)

The cytochromes P450 (CYPs) constitute a superfamily of hemoprotein enzymes that are responsible for the biotransformation of numerous xenobiotics, including therapeutic agents. Studies of the biochemical and enzymatic properties of these enzymes and their molecular genetics and regulation of gene expression and activity have greatly enhanced our understanding of several aspects of clinical pharmacology such as pharmacokinetic variability, drug toxicity, and drug interactions. This review evaluates the major human hepatic drug-metabolizing CYP enzymes and their clinically relevant substrates, inhibitors, and inducers. Also discussed are the molecular bases and clinical implications of genetic polymorphisms that affect the CYPs. Much of the information on the specificity of substrates and inhibitors of the CYP enzymes is derived from in vitro studies using human liver microsomes and heterologously expressed CYP enzymes. These methods are discussed, and guidelines are provided for designing enzyme kinetic and reaction phenotyping studies using multiple approaches. The strengths, weaknesses, and discrepancies among the different approaches are considered using representative examples. The mathematical models used in predicting the pharmacokinetic clearance of a drug from in vitro estimates of intrinsic clearance and the principles of quantitative in vitro-in vivo scaling of metabolic drug interactions are also discussed.
Reduction of Latent Infection and Enhancement of Disease Resistance in Muskmelon by Preharvest Application of Harpin (2011)

Latent infection was analyzed when harpin at 50 mg/L was sprayed on muskmelon 4 times at four different stages: florescence, young fruit, fruit enlarging, and netting periods. Results showed that the latent infection was significantly lower in sprayed muskmelons than in the control fruit. Meanwhile, the activities of peroxidase, phenylalanine ammonia-lyase, β-1,3-glucanase, and chitinase increased significantly in the fruit treated with harpin. It also resulted in an increase of contents of total phenolic compounds, flavanoids, and lignin. In addition, the treatment of harpin increased the activity of superoxide dismutase, enhanced the content of hydrogen peroxide, and reduced catalase activity. Furthermore, harpin treatments contributed to the reinforcement of cell walls of pericarp in fruit, the reduction of postharvest decay, and the improvement of postharvest qualities. These results suggested that harpin effectively participated in inducing resistance and could be a new strategy for preventing latent infection in muskmelon.
Nerve growth factor receptors. Characterization of two distinct classes of binding sites on chick embryo sensory ganglia cells. (1979)

Steady state and kinetic studies on the binding of 125I-beta nerve growth factor (NGF) to single cells from sensory ganglia of 8-day-old chick embryos show two distinct, saturable binding sites with dissociation constants of Kd(I) = 2.3 X 10(-11) M and Kd(II) = 1.7 X 10(-9) M. The difference in the affinities is due to different rate constants of dissociation (k-1(I) = 10(-3) s-1, k-1(II) = 2 X 10(-1 s-1). The association to both sites is apparently diffusion controlled (k+1(I) = 4.8 X 10(7) M-1s-1, k+2(II) = 10(7) to 10(8) M-1s-1). The binding of betaNGF to both sites is specific, since none of a number of hormones or proteins tested compete for the binding of 125I-betaNGF to either of those two sites. The heterogeneity of the binding of 125I-betaNGF is not due to heterogeneity of the 125I-betaNGF preparation nor to a negatively cooperative binding. In experiments where the dissociation of 125I-betaNGF is induced by the addition of saturating amounts of unlabeled betaNGF, the ratio of the 125I-betaNGF released with either of the two dissociation rate constants is solely dependent on the occupancy of the two sites before dissociation is started and is independent of the total occupancy of the sites during dissociation. The rate of dissociation of 125I-betaNGF from the higher affinity binding site I is accelerated by unlabeled betaNGF under conditions where the occupancy is both increased and decreased. Although the dissociation characteristics of 125I-beta NGF change with increasing times of exposure of the cells to the ligand, and 125I-beta NGF is degraded after it binds to the cells, these secondary processes do not interfere with the analysis of the binding data. At the lowest concentration of 125I-beta NGF used for the analysis less than 10% of the 125I-beta NGF is degraded. Both kinetic and steady state binding data reveal the two NGF binding sites at 2 degrees C as well as at 37 degrees C.
Isolation, structure and expression of mammalian genes for histidyl-tRNA synthetase (1987)

A full length cDNA clone that codes for human histidyl-tRNA synthetase (HRS) and cDNA clones that span the full length transcript of hamster HRS have been isolated. The full length human HRS cDNA was expressed after transfection into Cos 1 cells and a CHO ts mutant defective in the gene for HRS. The complete nucleotide sequence of the hamster and human gene were obtained and extensive homologies were observed in three regions on comparing these sequences between themselves and with the sequence of HRS derived from yeast. These results provide unequivocal evidence that we have indeed cloned the hamster and human gene for HRS. Three overlapping phage recombinants containing the complete hamster chromosomal gene for HRS have also been isolated. The genomic HRS is divided into 13 exons. The precise locations of each of the 5' and 3' exon-intron boundaries were defined by sequencing the appropriate regions of the cloned genomic DNA and aligning them with the sequence of HRS cDNAs. These studies provide the basis for future structural and functional analysis of the gene for HRS. In particular, it will be of interest to examine if different exons of HRS correlate to different domains of the HRS polypeptide.
Implications of Tachykinins and Calcitonin Gene-Related Peptide in Inflammatory Bowel Disease (1998)

Calcitonin gene-related peptide (CGRP) and the preprotachykinin A gene-derived peptides substance P (SP) and neurokinin A (NKA) are expressed in extrinsic primary afferent nerve fibres and intrinsic enteric neurons of the gut. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors, while the gastro-intestinal actions of CGRP are brought about by CGRP1 and possibly other CGRP receptors. These neuropeptide transmitters are expressed by enteric neurons, intestinal muscle, epithelium and vascular system in a cell-specific manner and enable SP, NKA and CGRP to influence motility, electrolyte and fluid secretion, vascular and immune functions in a peptide- and region-specific fashion. Inflammatory disorders of various aetiology involve changes in the peptidergic innervation of the gut, and inflammatory bowel disease is associated with NK1 receptor upregulation in intestinal blood vessels and lymphoid structures. Some of these alterations are reproduced in experimental models of gastro-intestinal disease, and there is mounting evidence that an imbalanced function of peptidergic neurons contributes to motor, secretory, vascular and immunological disturbances in intestinal anaphylaxis, infection and inflammation. In a therapeutic perspective it seems conceivable that tachykinin and CGRP receptors antagonists can be employed as spasmolytic, antidiarrhoeal, anti-inflammatory and antinociceptive drugs.
TIP-1 Translocation onto the Cell Plasma Membrane Is a Molecular Biomarker of Tumor Response to Ionizing Radiation (2010)

This study by use of tumor-bearing mice and cultured cancer cells suggested that imaging of the radiation-inducible TIP-1 translocation onto the cancer cell surface may predict the tumor responsiveness to radiation in a time-efficient manner and thus tailor radiotherapy of cancer.
Fluorescence Polarization Assays in Signal Transduction Discovery (2003)

Fluorescence polarization (FP) has become widely employed for high throughput screening used in pharmaceutical drug discovery. Assays of important signal transduction targets are now adapted to FP. In this review we examine assays for cyclic adenosine monophosphate, phosphodiesterases, and protein kinases and phosphatases using FP competitive immunoassays and a direct enzymatic method called IMAP.
HER2-Targeted Therapy Reduces Incidence and Progression of Midlife Mammary Tumors in Female Murine Mammary Tumor Virus huHER2-Transgenic Mice (2004)

Early intervention with mu4D5 was of benefit in our transgenic mice at high risk for developing huHER2-overexpressing breast cancer. This study suggests a potential benefit of early treatment with Herceptin in HER2-positive primary breast cancer.
Low-Fat/Calorie Foods: Current State and Perspectives (2000)

Low-fat/calorie products were originally developed for diabetics and people with specific health problems and they were considerably expensive. Nowadays, consumers' demand for low-fat/calorie products has significantly raised in an attempt to limit health problems, to lose or stabilize their weight, and to work within the frame of a healthier diet. The food industry has been confronted with a new challenge in order to satisfy consumers; development of low-fat/calories products with acceptable sensory characteristics and competitive price, by preferably employing the conventional processing equipment and in agreement with current strict legislation. The role of fat replacers and sugar substitutes in the successful manufacture of these products is crucial.
Mechanism of Inhibition of Poly(ADP-ribose) Glycohydrolase by Adenosine Diphosphate (Hydroxymethyl)pyrrolidinediol (1995)

Adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD), a nitrogen-in-the-ring analog of ADP-ribose, was recently shown to be a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase. Analysis of the inhibition kinetics of the hydrolase by ADP-HPD using the method of Lineweaver and Burk yields a noncompetitive double-reciprocal plot. Both the intercept (1/V) versus [inhibitor] replot and the slope (Km/V) versus [inhibitor] replot are hyperbolic, indicating partial noncompetitive inhibition. Inhibitor dissociation constants Kii = 52 nM and Kis = 80 nM were determined for ADP-HPD by analysis of the intercept versus [inhibitor] and slope versus [inhibitor] replots. These results show that although ADP-HPD is extremely potent in inhibiting poly(ADP-ribose) glycohydrolase, its effectiveness is limited by its partial inhibition. ADP-HPD was significantly less potent as an inhibitor of the NAD glycohydrolase from Bungarus fasciatus venom. Analysis of the inhibition kinetics using the Lineweaver and Burk method indicated that ADP-HPD was a linear-competitive inhibitor of the NAD glycohydrolase with a Ki of 94 microM. The results indicate that at low concentration ADP-HPD will be a selective inhibitor of poly(ADP-ribose) glycohydrolase; however, complete inactivation of the activity will be difficult to obtain.
System-level fault-tolerance in large-scale parallel machines with buffered coscheduling (2004)

Summary form only given. As the number of processors for multiteraflop systems grows to tens of thousands, with proposed petaflops systems likely to contain hundreds of thousands of processors, the assumption of fully reliable hardware has been abandoned. Although the mean time between failures for the individual components can be very high, the large total component count will inevitably lead to frequent failures. It is therefore of paramount importance to develop new software solutions to deal with the unavoidable reality of hardware faults. We will first describe the nature of the failures of current large-scale machines, and extrapolate these results to future machines. Based on this preliminary analysis we will present a new technology that we are currently developing, buffered coscheduling, which seeks to implement fault tolerance at the operating system level. Major design goals include dynamic reallocation of resources to allow continuing execution in the presence of hardware failures, very high scalability, high efficiency (low overhead), and transparency - requiring no changes to user applications. Preliminary results show that this is attainable with current hardware.
Negative human papillomavirus testing in normal smears selects a population at low risk for developing high-grade cervical lesions (2004)

High-risk human papillomaviruses (HR-HPV) are the necessary cause of cervical carcinomas and there is an increasing interest in using HR-HPV DNA detection in adjunction to cytological examination for primary cervical screening. To determine whether women with a normal smear negative for HR-HPV DNA detection with the Hybrid Capture II assay might represent a low-risk population for developing a high-grade squamous intraepithelial lesion (HSIL), 4401 women have been followed in a period of 12-72 months (median=34 months). During this follow-up, four HSIL and one microinvasive carcinoma have been detected in this cohort (three in the cohort of 3526 women >29 years). The global negative predictive value (NPV) of double-negative tests is thus of 99.9% (ninety-five percent confidence interval (95% CI): 99.8-100%), whereas cytology alone gives an NPV of 99.2% (95% CI: 98.9-99.5%). If we obtain a second negative HR-HPV test 1-2 years after the initial test, the NPV is 100%. The NPV is also of 100% in the cohort of women >49 years. We conclude that all these women could be safely screened at longer intervals between 3 and 5 years. This policy will offset the increased costs induced by an additional HR-HPV testing in primary screening.
What is an anxiety disorder? (2009)

Initiated as part of the ongoing deliberation about the nosological structure of DSM, this review aims to evaluate whether the anxiety disorders share features of responding that define them and make them distinct from depressive disorders, and/or that differentiate fear disorders from anxious-misery disorders. The review covers symptom self-report as well as on-line indices of behavioral, physiological, cognitive, and neural responding in the presence of aversive stimuli. The data indicate that the anxiety disorders share self-reported symptoms of anxiety and fear; heightened anxiety and fear responding to cues that signal threat, cues that signal no threat, cues that formerly signaled threat, and contexts associated with threat; elevated stress reactivity to aversive stimuli; attentional biases to threat-relevant stimuli and threat-based appraisals of ambiguous stimuli; and elevated amygdala responses to threat-relevant stimuli. Some differences exist among anxiety disorders, and between anxiety disorders and depressive disorders. However, the differences are not fully consistent with proposed subdivisions of fear disorders vs. anxious misery disorders, and comparative data in large part are lacking. Given the high rates of co-morbidity, advances in our understanding of the features of responding that are shared across vs. unique to anxiety and depressive disorders will require dimensional approaches. In summary, the extant data help to define the features of responding that are shared across anxiety disorders, but are insufficient to justify revisions to the DSM nosology at this time.
Erythropoietin Production by Human Renal Carcinoma Cells in Culture (1976)

Cells from human renal tumors were grown in monolayer cultures, and the media obtained at each medium change were assayed for erythropoietin activity. The medium from carcinoma I (a granular cell tumor) contained a high level of activity initially. The concentration of erythropoietin activity decreased with time in culture, but was significantly higher than that in controls after four months in vitro. There was , in addition, evidence of an inhibitory material present in the culture media. The activity formed by the tumor cells could be neutralized by an antibody to human urinary erythropoietin. The difference between activity measured in marrow cell cultures and that found by in vitro assay, and the chromatographic properties of the active preparation, suggest that the tumor-derived activity may be largely asialoerthropoietin. Two other renal carcinomas, of a different cellular type, produced significant erythropoietic activity.
FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse (2001)

The FKBP-12-rapamycin associated protein (FRAP, also known as mTOR and RAFT-1) is a member of the phosphoinositide kinase related kinase family. FRAP has serine/threonine kinase activity and mediates the cellular response to mitogens through signaling to p70s6 kinase (p70(s6k)) and 4E-BP1, resulting in an increase in translation of subsets of cellular mRNAs. Translational up-regulation is blocked by inactivation of FRAP signaling by rapamycin, resulting in G(1) cell cycle arrest. Rapamycin is used as an immunosuppressant for kidney transplants and is currently under investigation as an antiproliferative agent in tumors because of its ability to block FRAP activity. Although the role of FRAP has been extensively studied in vitro, characterization of mammalian FRAP function in vivo has been limited to the immune system and tumor models. Here we report the identification of a loss-of-function mutation in the mouse FRAP gene, which illustrates a requirement for FRAP activity in embryonic development. Our studies also determined that rapamycin treatment of the early embryo results in a phenotype indistinguishable from the FRAP mutant, demonstrating that rapamycin has teratogenic activity.
Brain ischemia and reperfusion activates the eukaryotic initiation factor 2α kinase, PERK (2001)

Reperfusion after global brain ischemia results initially in a widespread suppression of protein synthesis in neurons, which persists in vulnerable neurons, that is caused by the inhibition of translation initiation as a result of the phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha). To identify kinases responsible for eIF2alpha phosphorylation [eIF2alpha(P)] during brain reperfusion, we induced ischemia by bilateral carotid artery occlusion followed by post-ischemic assessment of brain eIF2alpha(P) in mice with homozygous functional knockouts in the genes encoding the heme-regulated eIF2alpha kinase (HRI), or the amino acid-regulated eIF2alpha kinase (GCN2). A 10-fold increase in eIF2alpha(P) was observed in reperfused wild-type mice and in the HRI-/- or GCN2-/- mice. However, in all reperfused groups, the RNA-dependent protein kinase (PKR)-like endoplasmic reticulum eIF2alpha kinase (PERK) exhibited an isoform mobility shift on SDS-PAGE, consistent with the activation of the kinase. These data indicate that neither HRI nor GCN2 are required for the large increase in post-ischemic brain eIF2alpha(P), and in conjunction with our previous report that eIF2alpha(P) is produced in the brain of reperfused PKR-/- mice, provides evidence that PERK is the kinase responsible for eIF2alpha phosphorylation in the early post-ischemic brain.
Pseudomonas aeruginosa: new insights into pathogenesis and host defenses (2013)

Pseudomonas aeruginosa is a metabolically versatile bacterium that can cause a wide range of severe opportunistic infections in patients with serious underlying medical conditions. These infections are characterized by an intense neutrophilic response resulting in significant damage to host tissues and often exhibit resistance to antibiotics leading to mortality. Treatment of persistent infections is additionally hampered by adaptive resistance, due to the growth state of the bacterium in the patient including the microorganism's ability to grow as a biofilm. An array of P. aeruginosa virulence factors counteract host defences and can cause direct damage to host tissues or increase the bacterium's competitiveness. New prevention and treatment methods are urgently required to improve the outcome of patients with P. aeruginosa infections. This review describes the two main types of P. aeruginosa lung infections and provides an overview of the host response and how the genomic capacity of P. aeruginosa contributes to the pathogenesis and persistence of these infections.