gebhart/patrepeval huggingface dataset:
Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia (1999)

Pathological evidence suggests that alterations of the blood-brain barrier (BBB) may occur in association with human immunodeficiency virus (HIV) dementia (HIVD). Increased BBB permeability could contribute to the development of dementia by facilitating the entry of activated and infected monocytes, as well as potentially toxic serum proteins, into the central nervous system. One mechanism by which BBB permeability may be altered is through increased activity of select matrix metalloproteinases (MMPs). In the present study, we examined the possibility that MMPs that target critical BBB proteins, including laminin, entactin, and collagen type IV, are elevated in the cerebrospinal fluid (CSF) of patients with HIVD. We also examined the possibility that such MMPs could be produced by brain-derived cells, and that MMP production by these cells might be increased by tumor necrosis factor-alpha, an inflammatory cytokine that is produced by HIV-infected monocytes/microglia and is elevated in HIVD. By using western blot and enzyme-linked immunosorbent assay, we observed that CSF levels of pro-MMP-2 and pro-MMP-7 were increased in association with HIVD. In addition, through the use of gelatin substrate zymography, a sensitive functional assay for MMP-2 and MMP-9, we observed that MMP-2 or pro-MMP-9 activity was more frequently detectable in the CSF of individuals with HIV dementia (9/16) than in the CSF from either nondemented seropositive (2/11) or seronegative (0/11) controls. Although the presence of MMPs in the serum could contribute to elevated levels in the CSF, we also show that brain-derived cells release MMP-2, 7, and 9, and that such release is increased after their stimulation with tumor necrosis factor-alpha. Together, these results suggest that elevated CSF levels of select MMPs may reflect immune activation within the central nervous system. They also suggest that further studies may be warranted to determine whether these proteins may play a role in the development of symptomatic neurological disease.
Autonomic nervous system evaluation in allergic rhinitis (2007)

ANS dysfunction, specifically sympathetic hypofunction, was identified in all of the allergic rhinitis patients studied. Further characterization of the type of ANS abnormality may allow the development of novel pharmacologic therapies for these disorders.
Non-thermal plasmas in and in contact with liquids (2009)

During the last two decades atmospheric ( or high) pressure non-thermal plasmas in and in contact with liquids have received a lot of attention in view of their considerable environmental and medical applications. The simultaneous generation of intense UV radiation, shock waves and active radicals makes these discharges particularly suitable for decontamination, sterilization and purification purposes. This paper reviews the current status of research on atmospheric pressure non-thermal discharges in and in contact with liquids. The emphasis is on their generation mechanisms and their physical characteristics.
A fluorescent reporter assay of differential gene expression response to insulin in hepatocytes (2019)

Insulin regulates multiple hepatic metabolic pathways in a seemingly heterogeneous manner. To understand this heterogeneity, we hypothesized that different subpopulations of hepatocytes have different sensitivity to insulin. To test this hypothesis, we developed a fluorescent reporter in which the insulin-responsive fatty acid synthase (FAS) promoter drove expression of a time-dependent fluorescent protein ("timer") and characterized timer expression in flow-sorted cell populations. In Hepa1c1c7 and AML12 hepatocytes, we found that different cell populations express distinct timer fluorescence following insulin treatment, consistent with cellular heterogeneity in the response to insulin. RNA measurements indicated an enrichment of forkhead box O transcription factors in cells with a greater response to insulin. Moreover, we found evidence of increased Akt activation. These data are consistent with a heterogeneous cellular response to insulin and raise the possibility that these different subpopulations underlie the peculiar pathophysiology of hepatic insulin resistance.
Multiple Novel Inhibitors of the NorA Multidrug Transporter of Staphylococcus aureus (1999)

The multidrug transporter NorA contributes to the resistance of Staphylococcus aureus to fluoroquinolone antibiotics by promoting their active extrusion from the cell. Previous studies with the alkaloid reserpine, the first identified inhibitor of NorA, indicate that the combination of a chemical NorA inhibitor with a fluoroquinolone could improve the efficacy of this class of antibiotics. Since reserpine is toxic to humans at the concentrations required to inhibit NorA, we sought to identify new inhibitors of NorA that may be used in a clinical setting. Screening of a chemical library yielded a number of structurally diverse inhibitors of NorA that were more potent than reserpine. The new inhibitors act in a synergistic manner with the most widely used fluoroquinolone, ciprofloxacin, by substantially increasing its activity against both NorA-overexpressing and wild-type S. aureus isolates. Furthermore, the inhibitors dramatically suppress the emergence of ciprofloxacin-resistant S. aureus upon in vitro selection with this drug. Some of these new inhibitors, or their derivatives, may prove useful for augmentation of the antibacterial activities of fluoroquinolones in the clinical setting.
Ultrathin Self-Assembled Layers at the ITO Interface to Control Charge Injection and Electroluminescence Efficiency in Polymer Light-Emitting Diodes (1998)

Modification of polymer LED operating characteristics has been achieved by interposing a conducting, semiconducting, or insulating polymer layer at the interface between the indium tin oxide (ITO) electrode and the emissive polymer. The Figure shows schematically a conducting polymer interlayer (sulfonated polyaniline and hexadimethrine polymer) fabricated by the polyelectrolyte self-assembly technique.
gadd45 Is Not Required for Activation of c-Jun N-terminal Kinase or p38 during Acute Stress (1999)

Cells respond to environmental stress with activation of c-Jun N-terminal kinase (JNK) and p38. Recent studies have implicated Gadd45 and two related proteins, MyD118/Gadd45beta and CR6/Gadd45gamma, as initiators of JNK/p38 signaling via their interaction with an upstream kinase MTK1. It was proposed that stress-induced expression of the Gadd45-related proteins leads to MTK1 activation and subsequent JNK/p38 activation. Using embryo fibroblasts from gadd45-null mice, we have addressed the requirement for Gadd45 in mediating JNK/p38 activation during acute stress. Comparison of JNK/p38 activities in response to methyl methanesulfonate, hydrogen peroxide, UVC irradiation, sorbitol, and anisomycin treatment of gadd45(+/+) and gadd45(-/-) fibroblasts revealed no deficiency in JNK/p38 activation in gadd45(-/-) fibroblasts. In addition, in wild type cells, JNK and p38 activation significantly preceded gadd45 induction with all stresses. Examination of myd118/gadd45beta and cr6/gadd45gamma expression in gadd45(+/+) and gadd45(-/-) fibroblasts revealed similar induction patterns in the two cell types, which, like gadd45 expression, was delayed relative to JNK/p38 activation. We conclude that gadd45 expression is not required for activation of JNK/p38 by environmental stresses, nor are stress-induced increases in myd118/gadd45beta and cr6/gadd45gamma expression necessary for kinase activation in response to such insults.
Official Tradition and Intellectual Narations—“Folklore Movement” in the Era of the “Republic of China” (1912-1949) (2002)

(2002). Official Tradition and Intellectual Narations—“Folklore Movement” in the Era of the “Republic of China” (1912-1949) Comparative Literature: East & West: Vol. 4, No. 1, pp. 213-215.
Liquid Drops Impacting Superamphiphobic Coatings (2013)

The dynamics of liquid drops impacting superamphiphobic coatings is studied by high-speed video microscopy. Superamphiphobic coatings repel water and oils. The coating consists of a fractal-like hydrophobized silica network. Mixtures of ethanol-water and glycerin-water are chosen to investigate the influence of interfacial tension and viscosity on spreading and retraction dynamics. Drop spreading is dominated by inertia. At low impact velocity, the drops completely rebound. However, the contact time increases with impact velocity, whereas the restitution coefficient decreases. We suggest that the drop temporarily impales the superamphiphobic coating, although the drop completely rebounds. From an estimate of the pressure, it can be concluded that impalement is dominated by depinning rather than sagging. With increasing velocity, the drops partially pin, and an increasing amount of liquid remains on the coating. A time-resolved study of the retraction dynamics reveals two well-separated phases: a fast inertia-dominated phase followed by a slow decrease of the contact diameter of the drop. The crossover occurs when the diameter of the retracting drop matches the diameter of the drop before impact. We suggest that the depth of impalement increases with impact velocity, where impalement is confined to the initial impact zone of the drop. If the drop partially pins on the coating, the depth of impalement exceeds a depth, preventing the whole drop from being removed during the retraction phase.
Management techniques of aquaculture and harvesting in context of carrying capacity of fresh water ponds. (2010)

International audience
Systems Pharmacology Modeling Predicts Delayed Presentation and Species Differences in Bile Acid–Mediated Troglitazone Hepatotoxicity (2014)

Troglitazone (TGZ) causes delayed, life-threatening drug-induced liver injury in some patients but was not hepatotoxic in rats. This study investigated altered bile acid homeostasis as a mechanism of TGZ hepatotoxicity using a systems pharmacology model incorporating drug/metabolite disposition, bile acid physiology/pathophysiology, hepatocyte life cycle, and liver injury biomarkers. In the simulated human population, TGZ (200-600 mg/day × 6 months) resulted in delayed increases in serum alanine transaminase >3× the upper limit of normal in 0.3-5.1%, with concomitant bilirubin elevations >2× the upper limit of normal in 0.3-3.6%, of the population. By contrast, pioglitazone (15-45 mg/day × 6 months) did not elicit hepatotoxicity, consistent with clinical data. TGZ was not hepatotoxic in the simulated rat population. In summary, mechanistic modeling based only on bile acid effects accurately predicted the incidence, delayed presentation, and species differences in TGZ hepatotoxicity, in addition to predicting the relative liver safety of pioglitazone. Systems pharmacology models integrating physiology and experimental data can evaluate drug-induced liver injury mechanisms and may be useful to predict the hepatotoxic potential of drug candidates.
The Lactobacillus and Bifidobacterium microflora of the human intestine: composition and succession. (2001)

Lactobacillus and bifidobacterial cultures are increasingly used as probiotics in pharmaceuticals and in foods. The selection of strains is performed often for technological rather than for microecological reasons. Detailed reports about species and strains composition of these microorganisms in the intestinal microflora of man are rare. Our investigations were performed with samples originating from infants and adults, taken from faeces and from upper sections of the intestinal tract including mouth and stomach, and from caecum and colon. Post mortem cases as well as test subjects under physiological conditions were analyzed using an automatic capsule system sampling at defined times in different parts of the intestinal tract. The fate of selected strains after oral intake was studied, too. Furthermore, influences of the microflora originating from food were considered. The identification of autochthonous (indigenous) and allochthonous (transient) species could be achieved with descriptions of new species in the genera Lactobacillus and Bifidobacterium. L. gasseri and L. reuteri proved to be predominant autochthonous Lactobacillus species in infants as well as in adults. Both species were occasionally present even in the stomach. This was also the case with an anaerobic lactic acid bacterium, previously named Catenabacterium catenaforme, later classified as L. ruminis, a non-motile variant of this species. The bifidobacterial microflora differed in composition between infants and adults and in different stages of the host's life. Up to 5 species or special strains of bifidobacteria could be present in different, individually fixed, combinations. Species typical for infants were B. bifidum, B. infantis, B. breve, and B. parvulorum. Typical for adults were 4 different variants of B. adolescentis. B. bifidum and B. longum could often be found in both groups, but in lower numbers. B. longum showed some oxygen tolerance whereas B. bifidum and B. adolescentis required strict anaerobic and fastidious conditions for cultivation. The autochthonous Lactobacillus and Bifidobacterium microflora in man will remain stable life-long. With lactobacilli, however, some successions may be caused by transient species derived from food or from the oral cavity, thus giving the impression of an altered microflora. Nevertheless L. gasseri, L. reuteri, L. ruminis, and to some degree, L. salivarius, may be present as autochthonous species all of the time. With bifidobacteria, a decreasing tendency in counts and in multiple composition in elderly people exists. Furthermore, this microflora is also influenced by consumption habits, which are probably caused by geographical circumstances.
Hypoxia-dependent Protein Expression: Erythropoietin (2001)

Normal cell homeostasis relies on the ordered flow of nutrients and substrates through metabolic pathways. Any perturbation of this flow eventually leads to dysfunction, impairment of defense mechanisms, loss of viability and death. High altitude and pathological hypoxia represent a serious and frequent cause for the loss of cell viability. Although organisms customarily respond by triggering adaptive or maladaptive mechanisms, all forms of life eventually succumb to hypoxia if it is severe enough, irrespectively of the primary cause. This paper reviews one of the mechanisms by which organisms respond to hypoxia: erythropoiesis. Although such response is not always beneficial, the discovery of the biochemical mechanisms underlying erythropoiesis has triggered an active field of research that is actually applying lessons learned in the mountains to a more clinical environment.
Direct Susceptibility Testing of Positive Blood Cultures by Using Sensititre Broth Microdilution Plates (2003)

Traditional susceptibility testing of blood cultures requires overnight incubation in order to obtain isolated colonies. Susceptibility results can be reported up to 24 h sooner by using a bacterial pellet from the blood culture broth. This study evaluated the accuracy of direct susceptibility testing from positive ESP blood culture broths by using Sensititre broth microdilution plates compared to testing with isolated colonies. Practical inclusion criteria were applied to gram-positive organisms to avoid reporting susceptibilities for probable contaminants. All gram-negative organisms were tested directly. An aliquot of the blood culture was centrifuged, and the resulting pellet was used to make a 0.5 McFarland suspension. Microdilution plates were inoculated and interpreted according to the manufacturer's instructions. Colony counts were performed to ensure proper colony density was achieved. A total of 199 patient and seeded blood cultures were evaluated for both essential (within +/-1 twofold dilution) and categorical (sensitive, intermediate, or resistant) agreement. Testing of 93 gram-positive isolates (1,214 antimicrobial agent-organism combinations) yielded 98% essential agreement and categorical error rates of 0.3% minor, no major (false resistance), and 1.7% very major (false susceptibility) errors. For 106 gram-negative isolates (1,828 antimicrobial agent-organism combinations), the essential agreement was 99%. Categorical error rates were 0.5, 0, and 2.0% for minor, major, and very major errors, respectively. Performance was comparable for both gram-positive and gram-negative isolates, as well as for both aerobic and anaerobic media. Using this direct testing methodology, reliable susceptibility results can be reported to physicians 24 h sooner, allowing earlier appropriate modification of antimicrobial therapy.
Understanding Static Pressure (2002)

WHAT IS STATIC PRESSURE? Static pressure is defined as “the pressure exerted by a still liquid or gas, especially water or air.” For turkey growers, this simply relates to the occurrence of a slight decrease in pressure within a turkey building relative to outside air pressure when one or more exhaust fans are turned on. It is important that we understand this concept because the use of exhaust fans, or negative pressure ventilation, is the most common form of power ventilating turkey buildings in Utah. Negative pressure ventilation is also the easiest and most efficient method to control air exchange.
The HSP70 Molecular Chaperone Is Not Beneficial in a Mouse Model of α-synucleinopathy (2010)

Overexpressing HSP70 in a mouse model of alpha-synucleinopathy did not lower the toxic load of alpha-synuclein species and had no beneficial effect on alpha-synuclein-related motor deficits.
Inhibition of pseudocholinesterase activity protects from cocaine-induced cardiorespiratory toxicity in rats. (1992)

We studied the effect of inhibition of pseudocholinesterase by a specific pseudocholinesterase inhibitor, tetraisopropyl pyrophosphoramide (ISO-OMPA) on the cardiorespiratory toxicity of intravenously injected cocaine in rats. Group 1 rats received ISO-OMPA subcutaneously, whereas group 2 rats received saline placebo subcutaneously. Thirty minutes later, rats were anesthetized with 40 mg/kg of sodium pentobarbital intraperitoneally and were then given 10 mg/kg (least toxic dose) cocaine intravenously. Thirty minutes after the first injection of cocaine, about half of the rats that survived from each group were given 12 mg/kg cocaine (low toxic dose) intravenously, and the other half was given 13.5 mg/kg cocaine (high toxic dose) intravenously. Five minutes after each injection, rats were classified as either survivors or fatalities. In group 1 (ISO-OMPA treated), five of 29 (17%) rats that received 10 mg/kg cocaine, two of 11 (19%) that received 12 mg/kg cocaine, and three of 13 (24%) that received 13.5 mg/kg cocaine died of cardiorespiratory toxicity. In group 2 (saline treated), two of 29 (7%) that received 10 mg/kg cocaine, six of 12 (50%) that received 12 mg/kg cocaine, and 10 of 15 (67%) that received 13.5 mg/kg cocaine died of cardiorespiratory toxicity (p less than 0.03). Pseudocholinesterase activity (mean +/- SEM) of groups 1 and 2 were 0.6 +/- 0.2 and 7.3 +/- 0.7 units, respectively (p less than 0.01). Our results show that rats with lower pseudocholinesterase activity had lower fatality rates than rats with higher pseudocholinesterase activity.
Natriuretic Peptide Receptor-B (Guanylyl Cyclase-B) Mediates C-type Natriuretic Peptide Relaxation of Precontracted Rat Aorta (1995)

The most potent known agonist for the natriuretic peptide receptor-B (NPR-B)/guanylyl cyclase-B is C-type natriuretic peptide (CNP). A homologous ligand-receptor system consists of atrial natriuretic peptide (ANP) and NPR-A/guanylyl cyclase-A. A third member of this family is NPR-C, a non-guanylyl cyclase receptor. Monoclonal antibodies were raised against NPR-B by immunizing mice with a purified receptor-IgG fusion protein consisting of the extracellular domain of NPR-B and the Fc portion of human IgG-gamma 1. One monoclonal antibody, 3G12, did not recognize NPR-A or NPR-C and bound to human and rat NPR-B. CNP binding to NPR-B and stimulation of cGMP synthesis were inhibited by 3G12. With cells isolated from either the media or adventitia layers of rat thoracic aorta, 3G12 did not interfere with ANP-stimulated cGMP synthesis, but it inhibited CNP-stimulated cGMP levels in cells from both layers. CNP (IC50 = 10 nM) and ANP (IC50 = 1 nM) caused relaxation of phenylephrine-contracted rat aortic rings. 3G12 caused a marked increase in the IC50 for CNP, from 10 nM to 140 nM, but failed to affect ANP-mediated relaxation. Therefore, our results for the first time demonstrate that CNP relaxes vascular smooth muscle by virtue of its binding to NPR-B.
c-Jun N-terminal kinase inhibitor favors transforming growth factor-β to antagonize hepatitis B virus X protein-induced cell growth promotion in hepatocellular carcinoma (2015)

Transforming growth factor (TGF)-β induces cell growth arrest in well-differentiated hepatocellular carcinoma (HCC) while hepatitis B virus X protein (HBx) minimizes the tumor suppression of TGF-β signaling in early chronic hepatitis B. However, how to reverse the oncogenic effect of HBx and sustain the tumor-suppressive action of TGF-β has yet to be investigated. The present study examined the effect of TGF-β and a c-Jun N-terminal kinase (JNK) inhibitor on cell growth in HCC cells with forced expression of HBx. It was found that HBx promoted cell growth via activation of the JNK/pSMAD3L pathway and inhibition of the transforming growth factor-beta type I receptor (TβRI)/pSMAD3C pathway. pSMAD3L/SMAD4 and pSMAD3C/SMAD4 complexes antagonized each other to regulate c-Myc expression. In the absence of HBx, TGF-β induced cell growth arrest through activation of the TβRI/pSMAD3C pathway in well-differentiated HCC cells. In the presence of HBx, TGF-β had no effect on cell growth. JNK inhibitor SP600125 significantly reversed the oncogenic action of HBx and favored TGF-β to regain the ability to inhibit the cell growth in HBx-expressing well-differentiated HCC cells. In conclusion, targeting JNK signaling favors TGF-β to block HBx-induced cell growth promotion in well-differentiated HCC cells. As an adjunct to anti-viral therapy, the combination of TGF-β and inhibition of JNK signaling is a potential therapy for HBV-infected HCC.
A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia (2016)

Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates. We validate selected genes using genetic and pharmacological inhibition, and chose KAT2A as a candidate for downstream study. KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells. Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies.
Dosimetric properties of a novel brachytherapy balloon applicator for the treatment of malignant brain-tumor resection-cavity margins (1998)

This device, when filled with 125I solution, is suitable for classical LDR treatments and may be preferable to 125I interstitial-seed implants in several respects. Manipulation of the dosimetric properties of the device can improve its characteristics for brain tumor treatment and may make it suitable for boosting the lumpectomy margins in conservative breast cancer treatment.