gebhart/patrepeval huggingface dataset:
Roles of protein kinases and phosphatases in signal transduction. (1990)

Most, if not all, signal transduction at cell surface receptors in animal cells appears to occur by one of four basic mechanisms, 1) cyclic nucleotide systems; 2) phosphoinositidase systems; 3) ion channel systems; 4) tyrosine kinase systems. The end effects of all four signal transduction systems are largely mediated by protein (serine/threonine) kinases and/or phosphatases. Thus, the only known high affinity intracellular receptors for cyclic nucleotides and diacylglycerol are cyclic nucleotide-dependent protein kinases and protein kinase C respectively, while activation of tyrosine kinase systems causes concomitant activation of several different protein (serine/threonine) kinases. Many, although not all, effects of elevated Ca2+ are also mediated by calmodulin-dependent protein kinases. Initial tests of the involvement of any of these kinases in control of a physiological system can be made using cell-permeable kinase activators or inhibitors, e.g. cyclic nucleotide analogues, phorbol esters or Ca2+ ionophores. A family of four protein (serine/threonine) phosphatases account for dephosphorylation of all known cytosolic or nuclear substrates phosphorylated by these protein kinases. Two of these (PP1 and PP2A) have a broad substrate specificity and appear to be highly conserved during evolution, being present in both animal and plant kingdoms. PP1 is potently inhibited by protein inhibitors-1 and -2, while the marine toxin and tumour promoter, okadaic acid, inhibits PP2A with extreme potency and PP1 less potently. Okadaic acid provides a novel cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological process. Recent examples of its use are discussed. These approaches can provide initial evidence that a particular protein is regulated in response to an extracellular signal by protein phosphorylation. Confirmation of this hypothesis may be obtained by showing that the precise residue(s) phosphorylated by the protein kinase in a cell-free system are also phosphorylated in intact cells in response to the extracellular signal. Sensitive methods are now available for the analysis of phosphorylation sites by gas phase sequencing and Fast Atom Bombardment (FAB) mass spectrometry. Sequencing of phosphorylation sites also allows the development of synthetic peptide assays for the various kinases involved. These methods will be illustrated using the author's own studies on phosphorylation of enzymes of lipid metabolism.
LINEBACKER: LINE-Speed Bio-Inspired Analysis and Characterization for Event Recognition (2016)

The cyber world is a complex domain, with digital systems mediating a wide spectrum of human and machine behaviors. While this is enabling a revolution in the way humans interact with each other and data, it also is exposing previously unreachable infrastructure to a worldwide set of actors. Existing solutions for intrusion detection and prevention that are signature-focused typically seek to detect anomalous and/or malicious activity for the sake of preventing or mitigating negative impacts. But a growing interest in behavior-based detection is driving new forms of analysis that move the emphasis from static indicators (e.g. rule-based alarms or tripwires) to behavioral indicators that accommodate a wider contextual perspective. Similar to cyber systems, biosystems have always existed in resource-constrained hostile environments where behaviors are tuned by context. So we look to biosystems as an inspiration for addressing behavior-based cyber challenges. In this paper, we introduce LINEBACKER, a behavior-model based approach to recognizing anomalous events in network traffic and present the design of this approach of bio-inspired and statistical models working in tandem to produce individualized alerting for a collection of systems. Preliminary results of these models operating on historic data are presented along with a plugin to support real-world cyber operations.
A Potential Role for Insulin-Like Growth Factor Binding Protein-4 Proteolysis in the Establishment of Ovarian Follicular Dominance in Cattle1 (2001)

A critical transition in ovarian follicular development is the selection of a dominant follicle, capable of ovulating, from a cohort of synchronously growing antral follicles. However, little is known about mechanisms and factors that regulate the selection and growth of dominant ovarian follicles. We have investigated whether a component of the insulin-like growth factor (IGF) system, namely IGFBP-4 protease, is associated with the establishment of follicular dominance in cattle. IGFBP proteases degrade IGFBPs, freeing IGFs to interact with their receptors. In experiment 1, follicular fluid from preovulatory follicles (n = 4) degraded about 80% of the added recombinant human (rh) IGFBP-4 within 18 h of incubation. The IGFBP-4 protease exhibited optimal activity at neutral/basic pH and its sensitivity to various protease inhibitors suggested a metalloprotease. The decline in the intensity of the band corresponding to intact rhIGFBP-4 was accompanied by the appearance of immunoreactive fragments of molecular weights approximately 18 and 14 kDa, which were not detectable by ligand blot analysis. In experiment 2, follicular fluid samples were collected from dominant and subordinate follicles on Day 2 or 3 of the first follicular wave, after ovariectomy (experiment 2a, n = 3/day) or by ultrasound-guided follicular aspiration (experiment 2b, n = 4-5/day). Estradiol concentrations in follicular fluid from dominant vs. subordinate follicles confirmed their identities and indicated that the dominant follicle had been selected by Day 2 of the follicular wave. In both experiments 2a and 2b, IGFBP-4 proteolytic activity was 2- to 3.5-fold (P < 0.05) and 5-fold (P < 0.01) higher in follicular fluid from dominant than subordinate follicles on Days 2 and 3 of the follicular wave, respectively. The finding that IGFBP-4 proteolytic activity is higher in dominant, estrogen-active follicles than in subordinate follicles of the same cohort, as early as Day 2 of the follicular wave, strongly suggests a role for IGFBP-4 protease in the establishment of ovarian follicular dominance.
Antipsychotic medications and seizures. (1991)

This chapter will review the in vitro laboratory as well as animal and clinical studies of the comparative effect of antipsychotic medications on the seizure threshold. It will critically examine current theories relating antipsychotic medications and seizure induction. Finally, it will provide guidelines for the clinical applications of this literature to treatment of both epileptic and non-epileptic populations.
Fidelity and Mutational Spectrum of Pfu DNA Polymerase on a Human Mitochondrial DNA Sequence (1997)

The study of rare genetic changes in human tissues requires specialized techniques. Point mutations at fractions at or below 10(-6) must be observed to discover even the most prominent features of the point mutational spectrum. PCR permits the increase in number of mutant copies but does so at the expense of creating many additional mutations or "PCR noise". Thus, each DNA sequence studied must be characterized with regard to the DNA polymerase and conditions used to avoid interpreting a PCR-generated mutation as one arising in human tissue. The thermostable DNA polymerase derived from Pyrococcus furiosus designated Pfu has the highest fidelity of any DNA thermostable polymerase studied to date, and this property recommends it for analyses of tissue mutational spectra. Here, we apply constant denaturant capillary electrophoresis (CDCE) to separate and isolate the products of DNA amplification. This new strategy permitted direct enumeration and identification of point mutations created by Pfu DNA polymerase in a 96-bp low melting domain of a human mitochondrial sequence despite the very low mutant fractions generated in the PCR process. This sequence, containing part of the tRNA glycine and NADH dehydrogenase subunit 3 genes, is the target of our studies of mitochondrial mutagenesis in human cells and tissues. Incorrectly synthesized sequences were separated from the wild type as mutant/wild-type heteroduplexes by sequential enrichment on CDCE. An artificially constructed mutant was used as an internal standard to permit calculation of the mutant fraction. Our study found that the average error rate (mutations per base pair duplication) of Pfu was 6.5 x 10(-7), and five of its more frequent mutations (hot spots) consisted of three transversions (GC-->TA, AT-->TA, and AT-->CG), one transition (AT-->GC), and one 1-bp deletion (in an AAAAAA sequence). To achieve an even higher sensitivity, the amount of Pfu-induced mutants must be reduced.
Preparation and Characterization of Human HIV Type 1 Neutralizing Reference Sera (1995)

Reference neutralizing antibody (NA) reagents are needed for laboratories to be able to compare results of neutralization assays that will be used to monitor HIV-1 vaccine recipients. In an effort to establish such reference reagents two asymptomatic, seropositive patients were identified with medium to high amounts of cross-reactive NA activity against a number of HIV-1 strains. Sera obtained from each individual at three or four sequential phlebotomies were pooled, and the two pools were each distributed in > 3000 aliquots into glass ampoules and lyophilized, and the ampoules were flame sealed. An HIV-1 antibody-negative reference serum was prepared in a similar fashion after pooling serum from four individuals. Ampoules were tested for uniformity of fill, sterility, moisture content, residual oxygen, stability, infectivity, and presence of antibody. An international collaborative study was conducted to determine the potency of the samples in six laboratories, each using their own neutralization assays and reagents. The results indicated reasonable consistency between laboratories and that both sera have sufficient titers against a variety of strains for use as reference reagents. These reference sera have been included in the World Health Organization (WHO) AIDS Reagent Project and are available through the three AIDS reagent repositories.
Non-Invasive Detection of Respiration and Heart Rate with a Vehicle Seat Sensor (2018)

This study demonstrates the feasibility of using a seat sensor designed for occupant classification from a production passenger vehicle to measure an occupant&rsquo;s respiration rate (RR) and heart rate (HR) in a laboratory setting. Relaying occupant vital signs after a crash could improve emergency response by adding a direct measure of the occupant state to an Advanced Automatic Collision Notification (AACN) system. Data was collected from eleven participants with body weights ranging from 42 to 91 kg using a Ford Mustang passenger seat and seat sensor. Using a ballistocardiography (BCG) approach, the data was processed by time domain filtering and frequency domain analysis using the fast Fourier transform to yield RR and HR in a 1-min sliding window. Resting rates over the 30-min data collection and continuous RR and HR signals were compared to laboratory physiological instruments using the Bland-Altman approach. Differences between the seat sensor and reference sensor were within 5 breaths per minute for resting RR and within 15 beats per minute for resting HR. The time series comparisons for RR and HR were promising with the frequency analysis technique outperforming the peak detection technique. However, future work is necessary for more accurate and reliable real-time monitoring of RR and HR outside the laboratory setting.
The Activation of Glycogen Synthase by Insulin Switches from Kinase Inhibition to Phosphatase Activation during Adipogenesis in 3T3-L1 Cells (1998)

The effects of insulin and platelet-derived growth factor (PDGF) on glycogen synthase activation were compared in 3T3-L1 fibroblasts and adipocytes. In the fibroblasts, PDGF elicited a stronger phosphorylation of mitogen-activated protein kinase (MAPK) and AKT than did insulin. Both agents caused a comparable stimulation of receptor autophosphorylation, MAPK, and phosphatidylinositol 3-kinase (PI3-K) activation in the adipocytes. However, adipogenesis resulted in the uncoupling of PI3-K activation by PDGF from subsequent AKT phosphorylation. The relative contributions of glycogen synthase kinase-3 (GSK-3) inactivation and protein phosphatase-1 (PP1) activation in the regulation of glycogen synthase in both cell types were evaluated. Insulin and PDGF caused a small increase in glycogen synthase a activity in the fibroblasts. Additionally, both agents caused a similar inhibition of GSK-3, while having no effect on PP1 activity. Following differentiation, insulin treatment resulted in a 5-fold stimulation of glycogen synthase, whereas PDGF was without effect. Both agents caused a comparable inhibition of GSK-3 activity in the adipocytes, whereas only insulin activated PP1. Finally, wortmannin completely blocked the stimulation of PP1 by insulin in 3T3-L1 adipocytes, indicating that PI3-K inhibition can impinge on PP1 activation. Cumulatively these results suggest that the weak activation of glycogen synthase in 3T3-L1 fibroblasts is mediated by GSK-3 inactivation, whereas in the more metabolically active adipocytes, the insulin-specific activation of glycogen synthase is mediated by PP1 activation.
Gibberellins Promote Flowering of Arabidopsis by Activating the LEAFY Promoter (1998)

The gibberellin class of plant hormones has been implicated in the control of flowering in several species. In Arabidopsis, severe reduction of endogenous gibberellins delays flowering in long days and prevents flowering in short days. We have investigated how the differential effects of gibberellins on flowering correlate with expression of LEAFY, a floral meristem identity gene. We have found that the failure of gibberellin-deficient ga1-3 mutants to flower in short days was paralleled by the absence of LEAFY promoter induction. A causal connection between these two events was confirmed by the ability of a constitutively expressed LEAFY transgene to restore flowering to ga1-3 mutants in short days. In contrast to short days, impairment of gibberellin biosynthesis caused merely a reduction of LEAFY expression when plants were grown in long days or with sucrose in the dark. As a first step toward identifying other small molecules that might regulate flowering, we have developed a rapid in vitro assay for LEAFY promoter activity.
Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma. (1996)

Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation to NGF values in asthma patients. NGF was significantly increased in the 42 allergic (skin-test- or radioallergosorbent-test-positive) subjects (49.7 +/- 28.8 pg/ml) versus the 18 matched controls (3.8 +/- 1.7 pg/ml; P < 0.001). NGF levels in allergic patients with asthma, rhinoconjunctivitis, and urticaria-angioedema were 132.1 +/- 90.8, 17.6 +/- 6.1, and 7.6 +/- 1.8 pg/ml (P < 0.001, P < 0.002, and P < 0.05 versus controls), respectively. Patients with more than one allergic disease had higher NGF serum values than those with a single disease. When asthma patients were considered as a group, NGF serum values (87.6 +/- 59.8 pg/ml) were still significantly higher than those of control groups (P < 0.001), but allergic asthma patients had elevated NGF serum levels compared with nonallergic asthma patients (132.1 +/- 90.8 versus 4.9 +/- 2.9 pg/ml; P < 0.001). NGF serum levels correlate to total IgE serum values (rho = 0.43; P < 0.02). The highest NGF values were found in patients with severe allergic asthma, a high degree of bronchial hyperreactivity, and high total IgE and eosinophil cationic protein serum levels. This study represents the first observation (that we know of) that NGF is increased in human allergic inflammatory diseases and asthma.
Human thioredoxin attenuates hypoxia‐reoxygenation injury of murine endothelial cells in a thiol‐free condition (2000)

The adult T cell leukemia-derived factor (ADF), or human thioredoxin (hTRX), has a radical scavenging effect similar to that of N-acetyl cysteine (NAC). We have recently shown that ADF/hTRX protects the lung and the heart from ischemia-reperfusion induced injury. To elucidate mechanisms of the protective effect, a hypoxia-reoxygenation (H-R) injury model was developed using a murine endothelial cell line, cultured in a thiol-free medium. In this condition, cells became much more vulnerable to H-R injury. The viability of cells decreased significantly after 1 h of hypoxic incubation followed by 1 h of reoxygenation. The injury was reduced by ADF/hTRX (100 μM) or NAC (10 mM). These two agents also demonstrated an additive protective effect. When cells were cultured in thiol-free medium for 2 h in a normoxic condition, intracellular hydrogen peroxide production was increased, which was associated with a decrease in glutathione level. NAC (10 mM) attenuated these changes whereas ADF/hTRX (100 μM) did not. These results suggest that although both ADF/hTRX and NAC protected cells from H-R injury, the underlying mechanisms are different. Because the cytoprotective effect of ADF/hTRX occurs in the thiol-free condition, it must be mediated via a novel mechanism other than enhancing thiol uptake. The additive cytoprotective effect between ADF/hTRX and NAC suggests that we should combine these two agents clinically. J. Cell. Physiol. 182:33–40, 2000. © 2000 Wiley-Liss, Inc.
Complementary Logic Gate Arrays Based on Carbon Nanotube Network Transistors (2012)

An efficient technique of fabricating high performance n- and p- type single-walled carbon nanotube (SWNT) network field-effect transistors (NET-FETs) is successfully demonstrated. Complementary inverters, NOR, NAND, OR, AND logic gates have been achieved from integrating these p- and n-type SWNT-NET-FETs. The processing technique described here is fully compatible with conventional silicon microelectronic technologies and it is readily suitable for scalable integration.
Real-Time Image Distortion Correction using FPGA-based System (2006)

The correction of images with geometric distortion, in cameras with short-focal length lenses, can be achieved by integrating the solution into the camera's electronic hardware. By analyzing the distortion problem, the calibration parameters for a given camera are obtained to correct the image distortion. Every pixel from the original image is weighted and used to modify several pixels of influence in the output image. The weights are computed by bilinear interpolation. The final design is generic and configurable to different values of zoom and focus. It has been oriented to an FPGA, being possible the correction of the image distortion in real-time, and providing an undistorted digital video stream
Vaccinia Virus Vectors with an Inactivated Gamma Interferon Receptor Homolog Gene (B8R) Are Attenuated In Vivo without a Concomitant Reduction in Immunogenicity (2001)

The vaccinia virus (VV) B8R gene encodes a secreted protein with homology to the gamma interferon (IFN-gamma) receptor. In vitro, the B8R protein binds to and neutralizes the antiviral activity of several species of IFN-gamma, including human and rat IFN-gamma; it does not, however, bind significantly to murine IFN-gamma. Here we report on the construction and characterization of recombinant VVs (rVVs) lacking the B8R gene. While the deletion of this gene had no effect on virus replication in vitro, rVVs lacking the B8R gene were attenuated for mice. There was a significant decrease in weight loss and mortality in normal mice, and nude mice survived significantly longer than did controls inoculated with parental virus. This is a surprising result considering the minimal binding of the B8R protein to murine IFN-gamma and its failure to block the antiviral activity of this cytokine in vitro. Such reduction in virulence could not be determined in rats, since they are considerably more resistant to VV infection than are mice. Finally, deletion of the B8R gene had no detectable effects on humoral immune responses. Mice and rats vaccinated with the rVVs showed identical humoral responses to both homologous and heterologous genes expressed by VV. This study demonstrates that the deletion of the VV B8R gene leads to enhanced safety without a concomitant reduction in immunogenicity.
Parametric estimation of pulse arrival time: a robust approach to pulse wave velocity (2009)

Pulse wave velocity (PWV) is a surrogate of arterial stiffness and represents a non-invasive marker of cardiovascular risk. The non-invasive measurement of PWV requires tracking the arrival time of pressure pulses recorded in vivo, commonly referred to as pulse arrival time (PAT). In the state of the art, PAT is estimated by identifying a characteristic point of the pressure pulse waveform. This paper demonstrates that for ambulatory scenarios, where signal-to-noise ratios are below 10 dB, the performance in terms of repeatability of PAT measurements through characteristic points identification degrades drastically. Hence, we introduce a novel family of PAT estimators based on the parametric modeling of the anacrotic phase of a pressure pulse. In particular, we propose a parametric PAT estimator (TANH) that depicts high correlation with the Complior(R) characteristic point D1 (CC = 0.99), increases noise robustness and reduces by a five-fold factor the number of heartbeats required to obtain reliable PAT measurements.
The regulated expression of an intrabody produces a mutant phenotype in Drosophila (1998)

Intrabodies show great promise for controlling gene expression. As an initial attempt to evaluate the intrabody technology in Drosophila, the gene poxn was used as target. Transgenic flies harboring different anti-Poxn scFv genes integrated into various chromosomes were obtained. In one transformant, a phenocopy resembling the hypomorphic poxn-phenotype was produced in embryos and larvae following induction of expression of alpha-Poxn2 intrabody. The antisense approach was used as control. Parameters that can affect the success of intrabody technology are described.
Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing (2013)

Our results suggest that more caution should be exercised in genomic medicine settings when analyzing individual genomes, including interpreting positive and negative findings with scrutiny, especially for indels. We advocate for renewed collection and sequencing of multi-generational families to increase the overall accuracy of whole genomes.
THE MATERNAL TRANSMISSION OF VACCINIAL IMMUNITY IN SWINE (1932)

The introduction of vaccinia virus into the skin of swine calls forth a typical vesicular reaction which may be followed by a solid immunity. This acquired state of resistance was utilized in determining the route of immunity transmission from sow to young. The suckling young of immune sows, vaccinated on the 7th day or earlier, showed no reaction to the virus. Their hand-fed litter mates, however, were susceptible and reacted with the formation of vesicles. These observations indicate that the porcine placenta is largely impermeable to protective substances and establish the fact that colostrum functions as the vehicle for their transmission as it does for antibodies.