gebhart/patrepeval huggingface dataset:
Plasminogen activator inhibitor-1 (PAI-1) expression in vascular smooth muscle cells involves a SRC/MEK/USF signal cascade (2005)

Background High PAI-1 levels associate with increased cardiovascular disease risk. PAI-1 targeting may be an important approach to the therapy of vascular disorders. Methods Pathway-specific pharmacologic/molecular agents were used to define signaling events associated with PAI-1 expression. Results MEK (PD98059, U0126) or src family (PP1) kinase inhibitors attenuated growth factor-stimulated PAI-1 transcription in smooth muscle cells. PP1 blocked ERK1/2 activation suggesting that the required src kinase is upstream of ERK1/2. Transfection of a dominant-negative pp60c-src construct, moreover, reduced PAI-1 levels to that of PP1-treated controls implicating pp60c-src as the involved src kinase. An E box motif in the PAI-1 promoter was determined to be a USF-1 binding site. Mutation of this site or transfection of dominant-negative USF-1 constructs attenuated PAI-1 expression in smooth muscle cells. Nuclear USF-1 was determined to be a phosphorylation target of translocated ERK1/2 by both in situ co-localization microscopy and co-immunoprecipitation. Conclusions A major phenotypic characteristic of “activated” smooth muscle cells (i.e., transcription of fibrosis-associated target genes[e.g., PAI-1]) requires pp60c-src kinase activity and MEK signaling and involves activation of the USF transcription factor likely by ERK family MAP kinases. Pharmacologic or genetically-targeted manipulation of this pathway may have therapeutic usefulness in treatment of vascular disease. Clinical Pharmacology & Therapeutics (2005) 77, P11–P11; doi: 10.1016/j.clpt.2004.11.043
Blind wideband source separation (2002)

This paper deals with the general problem of separating two independent wideband sources when they are mixed by unknown filters. In order to solve this problem, a backward framework is proposed which is composed of two different stages. The first one consists of two linear predictors devoted to improve the source separation, whitening the input signals. Their coefficients are calculated applying the LMS algorithm, minimizing the mean squared errors between the predicted signals and the output of the separation network. The second stage is formed by decoupling filters that have to be blindly estimated imposing an independence criterion to the outputs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intrinsic instability of the essential cell division protein FtsL of Bacillus subtilis and a role for DivIB protein in FtsL turnover (2000)

Cell division in most eubacteria is driven by an assembly of about eight conserved division proteins. These proteins form a ring structure that constricts in parallel with the formation of the division septum. Here, we show that one of the division proteins, FtsL, is highly unstable. We also show that the protein is targeted to the ring structure and that targeting occurs in concert with the recruitment of several other membrane-associated division proteins. FtsL stability is further reduced in the absence of DivIB protein (probably homologous to E. coli FtsQ) at high temperature, suggesting that DivIB is involved in the control of FtsL turnover. The reduced stability of FtsL may explain the temperature dependence of divIB mutants, because their phenotype can be suppressed by overexpression of FtsL. The results provide new insights into the roles of the FtsL and DivIB proteins in bacterial cell division.
Evidence that the β-Amyloid Plaques of Alzheimer's Disease Represent the Redox-silencing and Entombment of Aβ by Zinc (2000)

Abeta binds Zn(2+), Cu(2+), and Fe(3+) in vitro, and these metals are markedly elevated in the neocortex and especially enriched in amyloid plaque deposits of individuals with Alzheimer's disease (AD). Zn(2+) precipitates Abeta in vitro, and Cu(2+) interaction with Abeta promotes its neurotoxicity, correlating with metal reduction and the cell-free generation of H(2)O(2) (Abeta1-42 > Abeta1-40 > ratAbeta1-40). Because Zn(2+) is redox-inert, we studied the possibility that it may play an inhibitory role in H(2)O(2)-mediated Abeta toxicity. In competition to the cytotoxic potentiation caused by coincubation with Cu(2+), Zn(2+) rescued primary cortical and human embryonic kidney 293 cells that were exposed to Abeta1-42, correlating with the effect of Zn(2+) in suppressing Cu(2+)-dependent H(2)O(2) formation from Abeta1-42. Since plaques contain exceptionally high concentrations of Zn(2+), we examined the relationship between oxidation (8-OH guanosine) levels in AD-affected tissue and histological amyloid burden and found a significant negative correlation. These data suggest a protective role for Zn(2+) in AD, where plaques form as the result of a more robust Zn(2+) antioxidant response to the underlying oxidative attack.
Synthesis of AZT 5′-O-Hydrogen Phospholipidsand their Derivatives (2003)

A series of AZT 5′-O-hydrogen phospholipids 5a-e were synthesized by a tandem transesterification of diphenyl phosphite (DPP) with AZT and a long-chain alcohol. This method has the merits of easy operation and high yields. The corresponding phosphonates, phosphorothionates and phosphoroselenoates of 5d and 5e and the phosphoramidates conjugated with l-amino acid methyl ester 9a and 9b were also synthesized.
Heat shock factor 2 is activated during mouse heart development (2000)

Two members of the heat shock transcription factor family, HSF1 and HSF2, have been identified as activators of mammalian heat shock gene expression. HSF1 acts as a classical stress-responsive factor, whereas HSF2 might play a role in embryogenesis, since it is active during pre- and post-implantation periods up to 15.5 days of mouse embryonic development. In this study, we analyzed HSF1 and HSF2 expression and activation during mouse heart formation. Our results show an abundant expression of HSF1 throughout heart development. In contrast, expression of the alternatively spliced HSF2-alpha and HSF2-beta, and an additional higher molecular weight isoform is strongly upregulated in the developing mouse heart at E11.5-12.5, a stage after which tubular heart has looped and chambers formed, and the myocardial walls are maturating and the valves differentiating. At the same developmental stage, HSF2 DNA-binding activity is transiently induced, whereas the weak HSE-binding activity, which is detected throughout heart development, consists primarily of HSF1. Interestingly, heat shock gene expression shows no temporal or spatial correlation with HSF2 expression and activation. Taken together, our results indicate that HSF2 activation is associated with specific stages of heart formation but is not involved in the regulation of inducible heat shock gene expression.
Plasma CD14 decreases monocyte responses to LPS by transferring cell-bound LPS to plasma lipoproteins (2001)

CD14, a myeloid cell-surface receptor and soluble plasma protein, binds LPS and other microbial molecules and initiates the innate immune response to bacterial invasion. The blood concentration of soluble CD14 (sCD14) increases during the systemic response to infection. Although high sCD14 blood levels have correlated with increased risk of dying from severe sepsis, sCD14 can diminish cell responses to LPS. We show here that in human serum, sCD14 increases the rate at which cell-bound LPS is released from the monocyte surface and binds to plasma lipoproteins. This enhanced rate of LPS efflux is associated with a significant reduction in the ability of monocytes to produce cytokines in response to LPS. Serum from septic patients reduced the LPS-monocyte interaction by as much as tenfold, and depletion of sCD14 from the serum restored LPS-monocyte binding and release kinetics to near normal levels. In serum from septic patients, monocyte-bound LPS also moved more rapidly into lipoproteins, which completely neutralized the biologic activity of the LPS that bound to them. In human plasma, sCD14 thus diminishes monocyte responses to LPS by transferring cell-bound LPS to lipoproteins. Stress-related increases in plasma sCD14 levels may help prevent inflammatory responses within the blood.
Substitutions in the Pheromone-Responsive Gβ Protein of Saccharomyces cerevisiae Confer a Defect in Recovery from Pheromone Treatment (1998)

The pheromone-responsive Galpha protein of Saccharomyces cerevisiae, Gpa1p, stimulates an adaptive mechanism that downregulates the mating signal. In a genetic screen designed to identify signaling elements required for Gpa1p-mediated adaptation, a large collection of adaptive-defective (Adp-) mutants were recovered. Of the 49 mutants characterized thus far, approximately three-quarters exhibit a dominant defect in the negative regulation of the pheromone response. Eight of the dominant Adp- mutations showed tight linkage to the gene encoding the pheromone-responsive Gbeta, STE4. Sequence analysis of the STE4 locus in the relevant mutant strains revealed seven novel STE4 alleles, each of which was shown to disrupt proper regulation of the pheromone response. Although the STE4 mutations had only minor effects on basal mating pathway activity, the mutant forms of Gbeta dramatically affected the ability of the cell to turn off the mating response after exposure to pheromone. Moreover, the signaling activity of the aberrant Gbetagamma subunits was suppressed by G322E, a mutant form of Gpa1p that blocks the pheromone response by sequestering Gbetagamma, but not by E364K, a hyperadaptive form of Gpa1p. On the basis of these observations, we propose that Gpa1p-mediated adaptation involves the binding of an unknown negative regulator to Gbetagamma.
Neutral oligosaccharide structures linked to asparagines of porcine zona pellucida glycoproteins (1991)

N-Linked sugar chains were liberated by hydrazinolysis from porcine zona pellucida glycoproteins obtained from ovarian follicular oocytes. Neutral sugar chains were separated from acidic ones by paper electrophoresis and fractionated with a serial lectin column chromatography and Bio-Gel P-4 column chromatography. Their structural analysis by sequential glycosidase digestion in combination with methylation analysis revealed that the neutral sugar chains are of bi-, tri-, and tetraantennary complex type with a fucosylated trimannosyl core. Twenty-six percent of the sugar chains contain N-acetyllactosamine repeating structures in their outer chain moieties. Only linear N-acetyllactosamine repeats, the maximum size of which is hexasaccharide, are detected. A characteristic feature is that 39% of the sugar chains contain N-acetylglucosamine residues at their nonreducing termini in spite of the absence of bisected sugar chains. This study provided, for the first time, the substantial information about the sugar chain structures of mammalian zona pellucida glycoproteins.
Serospecific antigens of Legionella pneumophila (1986)

Serospecific antigens isolated by EDTA extraction from four serogroups of Legionella pneumophila were analyzed for their chemical composition, molecular heterogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunological properties. The antigens were shown to be lipopolysaccharides and to differ from the lipopolysaccharides of other gram-negative bacteria. The serospecific antigens contained rhamnose, mannose, glucosamine, and two unidentified sugars together with 2-keto-3-deoxyoctonate, phosphate, and fatty acids. The fatty acid composition was predominantly branched-chain acids with smaller amounts of 3-hydroxymyristic acid. The antigens contain periodate-sensitive groups; mannosyl residues were completely cleaved by periodate oxidation. Hydrolysis of the total lipopolysaccharide by acetic acid resulted in the separation of a lipid A-like material that cross-reacted with the antiserum to lipid A from Salmonella minnesota but did not comigrate with it on sodium dodecyl sulfate gels. None of the four antigens contained heptose. All of the antigen preparations showed endotoxicity when tested by the Limulus amebocyte lysate assay. The results of this study indicate that the serogroup-specific antigens of L. pneumophila are lipopolysaccharides containing an unusual lipid A and core structure and different from those of other gram-negative bacteria.
Virtualization Without Direct Execution or Jitting: Designing a Portable Virtual Machine Infrastructure (2008)

A recent trend in x86 virtualization products from Microsoft, VMware, and XenSource has been the reliance on hardware virtualization features found in current 64-bit microprocessors. Hardware virtualization allows for direct execution of guest code and potentially simplifies the implementation of a Virtual Machine Monitor (or hypervisor) 1 . Until recently, hypervisors on the PC platform have relied on a variety of techniques ranging from the slow but simple approach of pure interpretation, the memory intensive approach of dynamic recompilation of guest code into translated code cache, to a hardware assisted technique known as ring compression which relies on the host MMU for hardware memory protection. These techniques traditionally either deliver poor performance 2
DNA Hybridization Test: Rapid Diagnostic Tool for Excluding Bacterial Vaginosis in Pregnant Women with Symptoms Suggestive of Infection (2002)

This prospective comparative study evaluated a DNA hybridization test (Affirm VPIII) as an alternative to Gram stain for the diagnosis of bacterial vaginosis. We examined vaginal smears from 1,725 pregnant women between the 12th and 36th weeks of gestation with clinical signs of vaginal infection. The DNA hybridization test compared well with Gram stain and can be used as a rapid diagnostic tool to exclude bacterial vaginosis.
Rescue of Aβ1–42‐induced memory impairment in day‐old chick by facilitation of astrocytic oxidative metabolism: implications for Alzheimer’s disease (2009)

Administration of small oligomeric beta-amyloid (Abeta)(1-42) 45 min before one-trial bead discrimination learning in day-old chicks abolishes consolidation of learning 30 min post-training (Gibbs et al. Neurobiol. Aging, in press). Administration of the beta3-adrenergic agonist CL316243, which specifically stimulates astrocytic but not neuronal glucose uptake, rescues Abeta impaired memory. Weakly reinforced training can be consolidated by various metabolic substrates and we have demonstrated neuronal dependence on oxidative metabolism of glucose soon after training versus astrocytic glucose dependence 20 min later. Based on these findings we examined whether different metabolic substrates were able to counteract memory inhibition by Abeta(1-42). Although lactate, the medium-chain fatty acid octanoate, and the ketone body beta-hydroxybutyrate consolidated weakly reinforced training when injected close to learning, none of them were able to salvage Abeta-impaired memory; at this early time. All three metabolites and the astrocytic-specific acetate consolidated weak learning and rescued Abeta-impaired memory when injected 10-20 min post-training. However, neither glucose nor insulin rescued memory when injected at 20 min. Rescue of memory by providing astrocytes with alternative substrates for oxidative metabolism suggests that Abeta(1-42) exerts its amnestic effects specifically by impairing astrocytic glycolysis.
Automated Chemical Synthesis of a Protein Growth Factor for Hemopoietic Cells, Interleukin-3 (1986)

Interleukin-3 (IL-3), a protein of 140 amino acids, was chemically synthesized by means of an automated peptide synthesizer and was shown to have the biological activities attributed to native IL-3. Assays of synthetic analogues established that an amino terminal fragment has detectable IL-3 activity, but that the stable tertiary structure of the complete molecule was required for full activity. The results demonstrate that automated peptide synthesis can be applied to the study of the structure and function of proteins.
Quantitative Estimates of Vascularity in Solid Tumors by Non-Invasive Near-Infrared Spectroscopy (2001)

We examined the relationship between non-invasive estimates of the tumor hemoglobin concentration by near-infrared spectroscopy (NIRS) and histological scores of tumor vascularity by Chalkley counts in seven tumor lines in nude mice [malignant gliomas: U87, U118, U373; small cell lung cancers (SCLC): 54A, 54B, DMS79; prostate cancer: MatLyLu (MLL)]. We also evaluated the effect of continuous anti-angiogenic treatment with TNP-470 on tumor hemoglobin concentration and tumor vascularity in U87 and MLL tumors. Non-invasive NIRS recordings were performed with a custom-built flash near-infrared spectrometer using light guide-coupled reflectance measurements at 800+/-10 nm. Chalkley counts were obtained from CD31-immunostained cryosections. The NIRS recordings in arbitrary absorbance units increased with tumor size in the individual tumors until a plateau was reached at approximately 150 mm(3). This plateau was relatively tumor line-specific. NIRS recordings at the plateau phase were strongly correlated (P<.001, n=71) to the histological vessel score (Chalkley count) of the same individual tumors excised immediately after the NIRS was performed. Non-invasive NIRS recordings of the highly vascularized gliomas (U87, U118, and U373) plus the MatLyLu tumor line were significantly higher than the three less vascularized SCLC tumor lines (P<.001). Continuous treatment with the anti-angiogenic compound TNP-470, an endothelial cell inhibitor, significantly retarded tumor growth in both U87 and MLL tumors, but all tumors eventually grew. When comparing treated and untreated tumors of similar size, both NIRS recordings and Chalkley counts were significantly lower in TNP-470-treated tumors (P<.05). In conclusion, the NIRS technique provides a non-invasive measure of the degree of vascularization in untreated tumors and the NIRS technique can measure modifications in tumor vascularization by anti-angiogenic therapy.
Global divergence of the human follicle mite Demodex folliculorum : Persistent associations between host ancestry and mite lineages (2015)

Microscopic mites of the genus Demodex live within the hair follicles of mammals and are ubiquitous symbionts of humans, but little molecular work has been done to understand their genetic diversity or transmission. Here we sampled mite DNA from 70 human hosts of diverse geographic ancestries and analyzed 241 sequences from the mitochondrial genome of the species Demodex folliculorum. Phylogenetic analyses recovered multiple deep lineages including a globally distributed lineage common among hosts of European ancestry and three lineages that primarily include hosts of Asian, African, and Latin American ancestry. To a great extent, the ancestral geography of hosts predicted the lineages of mites found on them; 27% of the total molecular variance segregated according to the regional ancestries of hosts. We found that D. folliculorum populations are stable on an individual over the course of years and that some Asian and African American hosts maintain specific mite lineages over the course of years or generations outside their geographic region of birth or ancestry. D. folliculorum haplotypes were much more likely to be shared within families and between spouses than between unrelated individuals, indicating that transmission requires close contact. Dating analyses indicated that D. folliculorum origins may predate modern humans. Overall, D. folliculorum evolution reflects ancient human population divergences, is consistent with an out-of-Africa dispersal hypothesis, and presents an excellent model system for further understanding the history of human movement.
Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopaminein vitro (1993)

1. The centrally acting analgesic, tramadol, has low affinity for opioid receptors and therefore presumably other mechanisms of analgesic action. Neurotransmitter release and uptake experiments were used to characterize the effects of tramadol on the central noradrenergic and dopaminergic systems. 2. Tramadol inhibited the uptake of [3H]-noradrenaline into purified rat hypothalamic synaptosomes with an IC50 of 2.8 microM; the (-)-enantiomer was about ten times more potent than the (+)-enantiomer. Results with the principal metabolite O-desmethyltramadol were very similar. Inhibition of dopamine uptake into purified rabbit caudate nucleus synaptosomes was very weak with 62% inhibition of 100 microM. 3. Rat occipital cortex slices were preincubated with [3H]-noradrenaline and rabbit caudate nucleus slices with [3H]-dopamine, then superfused and stimulated electrically. Tramadol, 1 and 10 microM, enhanced the stimulation-evoked [3H]-noradrenaline overflow by 25 and 69%, respectively; the (-)-enantiomer was more potent than the racemate or the (+)-enantiomer. Tramadol, 10 microM, had no effect on dopamine release. 4. The effects of tramadol on the stimulation-evoked [3H]-noradrenaline release were abolished when uptake sites were already blocked by a high concentration of cocaine. 5. The metabolite O-desmethyltramadol showed a slight facilitation of the stimulation-evoked noradrenaline release; the effect was more pronounced in the presence of a high concentration of naloxone. In the presence of cocaine, inhibition of the release was observed similar to the effect of morphine but less potent. 6. The results show that tramadol blocks noradrenaline uptake with selectivity as compared to dopamine uptake. The interaction with the noradrenaline transporter is stereoselective. The principal metabolite O-desmethyltramadol shows in addition to noradrenaline uptake inhibition, opioid inhibition of noradrenaline release.
Practical automated detection of stealthy portscans (2002)

Portscan detectors in network intrusion detection products are easy to evade. They classify a portscan as more than N distinct probes within M seconds from a single source. This paper begins with an analysis of the scan detection problem, and then presents Spice (Stealthy Probing and Intrusion Corr elation Engine), a portscan detector that is effective against stealthy scans yet operationally practical. Our design maintains records of event likelihood, from which we approximate the anomalousness of a given packet. We use simulated annealing to cluster anomalous packets together into portscans using heuristics developed from real scans. Packets are kept around longer if they are more anomalous. This should enable us to detect all the scans detected by current techniques, plus many stealthy scans, with manageable false positives. We also discuss detection of other activity such as stealthy worms, and DDOS control networks.
Synthesis and mycobacterial growth inhibition activities of bivalent and monovalent arabinofuranoside containing alkyl glycosides (2008)

Arabinofuranosides constitute one of the important components of cell wall structures of mycobacteria. With this importance of arabinofuranosides in mind, alkyl glycosides bearing arabinofuranoside trisaccharides were prepared, wherein the sugars were presented either in the monovalent or bivalent forms. Following the synthesis, the monovalent and bivalent alkyl glycosides were tested for their activities in a mycobacterial growth assay. The growth of the mycobacterial strain M. smegmatis was assessed in the presence of the alkyl glycosides and it was realized that the alkyl glycosides acted as inhibitors of the mycobacterial growth. The inhibition of the growth, caused by the above alkyl glycosides, was not observed for the arabinofuranose trisaccharide alone, without the alkyl groups, and for an alkyl glycoside bearing maltose as the sugar component.