gebhart/patrepeval huggingface dataset:
[Multicomponent antithrombotic effect of the neuroprotective prolyl dipeptide GVS-111 and its major metabolite cyclo-L-prolylglycine]. (2002)

The experiments in vivo showed that the new nootropic prolyl-containing GVS-111 produces an antithrombotic effect, influencing various stages of the blood coagulation process. GVS-111 exhibits anticoagulant and fibrinolytic properties and enhances fibrin destabilization by reducing the XIIIa factor activity. These effects are manifested upon both intraperitoneal (1 mg/kg) and peroral (10 mg/kg) administration of GVS-111 (in both cases, a single daily treatment over a period of 10 days). The same effects (anticoagulant, fibrinolytic, antifibrin-stabilizing) were observed in in vitro experiments with both GVS-111 (10(-3)-10(-6) M) and its main metabolite cyclo-L-prolylglycine (up to 10(-10) M). In addition, the latter metabolite exhibited an antiaggregant effect. The antithrombotic activity of GVS-111, together with previously established neuroprotector properties, low toxicity, and the absence of complications, makes this compound a promising antistroke drug.
A meta‐analysis of the association between Caesarean section and childhood asthma (2007)

In this meta-analysis, we found a 20% increase in the subsequent risk of asthma in children who had been delivered by Caesarean section.
NITRATION: Methods and Mechanisms (2003)

A study of synthetic methods of nitration and the mechanisms involved, covering aromatic nitration and aliphatic nitration, as well as its use in the preparation of dyes, pharmaceuticals, plastics, chemical intermediates, high energy materials and the mechanistic aspects of organic chemistry.
Role of Acid pH and Deficient Efflux of Pyrazinoic Acid in Unique Susceptibility of Mycobacterium tuberculosis to Pyrazinamide (1999)

Pyrazinamide (PZA) is an important antituberculosis drug. Unlike most antibacterial agents, PZA, despite its remarkable in vivo activity, has no activity against Mycobacterium tuberculosis in vitro except at an acidic pH. M. tuberculosis is uniquely susceptible to PZA, but other mycobacteria as well as nonmycobacteria are intrinsically resistant. The role of acidic pH in PZA action and the basis for the unique PZA susceptibility of M. tuberculosis are unknown. We found that in M. tuberculosis, acidic pH enhanced the intracellular accumulation of pyrazinoic acid (POA), the active derivative of PZA, after conversion of PZA by pyrazinamidase. In contrast, at neutral or alkaline pH, POA was mainly found outside M. tuberculosis cells. PZA-resistant M. tuberculosis complex organisms did not convert PZA into POA. Unlike M. tuberculosis, intrinsically PZA-resistant M. smegmatis converted PZA into POA, but it did not accumulate POA even at an acidic pH, due to a very active POA efflux mechanism. We propose that a deficient POA efflux mechanism underlies the unique susceptibility of M. tuberculosis to PZA and that the natural PZA resistance of M. smegmatis is due to a highly active efflux pump. These findings may have implications with regard to the design of new antimycobacterial drugs.
Expression and the role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma (2010)

Sulfation represents an essential modification for various molecules and regulates many biological processes. The sulfation of glycans requires a specific transporter for 3′-phosphoadenosine 5′-phosphosulfate (PAPS) on the Golgi apparatus. This study investigated the expression of PAPS transporter genes in colorectal carcinomas and the significance of Golgi-specific sulfation in the proliferation of colorectal carcinoma cells. The relative amount of PAPST1 transcripts was found to be higher than those of PAPST2 in colorectal cancerous tissues. Immunohistochemically, the enhanced expression of PAPST1 was observed in fibroblasts in the vicinity of invasive cancer cells, whereas the expression of PAPST2 was decreased in the epithelial cells. RNA interference of either of the two PAPS transporter genes reduced the extent of sulfation of cellular proteins and cellular proliferation of DLD-1 human colorectal carcinoma cells. Silencing the PAPS transporter genes reduced fibroblast growth factor signaling in DLD-1 cells. These findings indicate that PAPS transporters play a role in the proliferation of colorectal carcinoma cells themselves and take part in a desmoplastic reaction to support cancer growth by controlling their sulfation status.
Structure−Activity and Protraction Relationship of Long-Acting Glucagon-like Peptide-1 Derivatives:  Importance of Fatty Acid Length, Polarity, and Bulkiness (2007)

We here report a series of derivatives describing the structure-activity relationship around liraglutide, a once-daily human glucagon-like peptide-1 fatty acid derivative, with respect to potency as well as protraction in vivo. The spacer region between the fatty acid and the peptide is mostly important for potency, whereas the fatty acid or fatty acid mimetic is important for both potency and protraction. The length of the fatty acid is the most important parameter for protraction.
Cationic oligonucleotides can mediate specific inhibition of gene expression in Xenopus oocytes (1998)

Base-specific hydrogen bonding between an oligonucleotide and the purines in the major groove of a DNA duplex provide an approach to selective inhibition of gene expression. Oligonucleotide-mediated triplex formation in vivo may be enhanced by a number of different chemical modifications. We have previously described an in vitro analysis of triplex formation using oligonucleotides containing internucleoside phosphate linkages modified with the cation N , N -diethyl-ethylenediamine (DEED). When compared with unmodified oligonucleotides of identical base composition, DEED-modified oligonucleotides were better able to form DNA triplexes under conditions that approximate the pH, magnesium and potassium levels found in vivo . Here we report the ability of DEED-modified oligonucleotides to inhibit the expression of plasmid DNA injected into Xenopus oocytes. Inhibition is specific to plasmids containing a triplex formation target and sensitive to sequence alteration in the triplex forming target site. Inhibition of gene expression was nearly complete when oligonucleotide and plasmid were mixed together prior to injection. Inhibition was partial when oligonucleotide was injected first and not evident when plasmid was injected and allowed to form chromatin prior to oligonucleotide injection. Thus, access to DNA is a determining factor in effective triplex inhibition of gene expression.
Genetic Classification of “Norwalk‐like Viruses” (2000)

Reverse transcription-polymerase chain reaction has been used worldwide for the diagnosis of Norwalk-like virus (NLV) infection, yet a commonly accepted genetic classification scheme has not been established. Amino acid sequences from four regions of open-reading frame 2 (ORF2) were used to analyze 101 NLV strains, including 2 bovine strains. On the basis of this analysis, a genetic classification scheme is proposed that differentiates 99 human strains into 2 major genetic groups consisting of 5 and 10 genetic clusters, respectively. The 2 bovine strains constitute a newly defined third major genetic group composed of 2 putative clusters represented by each strain. This classification scheme is well supported by the analysis of the entire ORF2 sequences from 38 strains selected to represent the genetic diversity of the human strains used above. This scheme should provide a firm scientific basis for the unified classification of NLV strains detected around the world.
Hepatocyte and immune system: acute phase reaction as a contribution to early defence mechanisms. (1994)

Hepatocyte and immune system: acute phase reaction as a contribution to early defence mechanisms Cytokines, a variety of hormone-like molecules, include a group of soluble factors -the interferons, interleukins, and hematopoietic growth factors. They build a complex net- work of interactive signals and are important for the regulation of hematopoesis and many immune reactions. The interaction of the hepatocyte with the immune system may occur at different levels (Fig 1 ). For example viral infections often induce interferon (IFN) production, but can also stimulate synthesis of class II molecules, tumour necrosis factor and interleukin (IL) 2.1 2 IFN activates other cytokines directly by interacting with IFN sequence motifs in their promotors.3 Little information exists on the role of cytokines in the initiation and perpetuation of liver diseases. The level and activity of different cytokines such as IL 6 can be abnormal and may contribute to the injury in immunologically mediated liver diseases.4 Another mechanism is the 'acute phase response', in which a panel of cytokines regulates different liver specific genes. There is detailed knowledge on how the signals of these cytokines are transduced from the surface of the hepatocyte membrane to the promotor of the liver specific gene: the mechanisms will be reviewed in this article.
Analysis of responses to the Rho-kinase inhibitor Y-27632 in the pulmonary and systemic vascular bed of the rat (2010)

Responses to the Rho kinase inhibitor Y-27632 were investigated in the anesthetized rat. Under baseline conditions intravenous injections of Y-27632 decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressures were enhanced when baseline tone was increased with U-46619, and under elevated tone conditions Y-27632 produced similar percent decreases in pulmonary and systemic arterial pressures. Injections of Y-27632 prevented and reversed the hypoxic pulmonary vasoconstrictor response. The increase in pulmonary arterial pressure in response to ventilation with a 10% O(2)-90% N(2) gas mixture was not well maintained during the period of hypoxic exposure. Treatment with the nitric oxide (NO) synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME) increased pulmonary arterial pressure and prevented the decline or fade in the hypoxic pulmonary vasoconstrictor response. The hypoxic pulmonary vasoconstrictor response was reversed by Y-27632 in control and in l-NAME-treated animals. The Rho kinase inhibitor attenuated increases in pulmonary arterial pressures in response to intravenous injections of serotonin, angiotensin II, and Bay K 8644. Y-27632, sodium nitrite, and BAY 41-8543, a guanylate cyclase stimulator, decreased pulmonary and systemic arterial pressures and vascular resistances in monocrotaline-treated rats. These data suggest that Rho kinase is involved in the regulation of baseline tone and in the mediation of pulmonary vasoconstrictor responses. The present data suggest that the hypoxic pulmonary vasoconstrictor response is modulated by the release of NO that mediates the nonsustained component of the response in the anesthetized rat. These data suggest that Rho kinase and NOS play important roles in the regulation of vasoconstrictor tone in physiological and pathophysiological states and that monocrotaline-induced pulmonary hypertension can be reversed by agents that inhibit Rho kinase, generate NO, or stimulate soluble guanylate cyclase.
Converting Phenylacetone Monooxygenase into Phenylcyclohexanone Monooxygenase by Rational Design: Towards Practical Baeyer–Villiger Monooxygenases (2005)

Abstract A homology model of the most frequently used, but thermally somewhat labile, Baeyer–Villiger monooxygenase, cyclohexanone monooxygenase (CHMO) has been derived on the basis of the recently published crystal structure of the thermally stable phenylacetone monooxygenase (PAMO). This has led to the identification of a structural element crucial for substrate acceptance and stereoselectivity, namely an arginine‐interacting loop near the active site. A bulge in this loop occurring in PAMO (but not in CHMO) has been eliminated by mutation, enhancing the range of substrate acceptance and enantioselectivity of Baeyer–Villiger reactions while maintaining high thermal stability.
Hierarchical Representations for Efficient Architecture Search (2017)

We explore efficient neural architecture search methods and show that a simple yet powerful evolutionary algorithm can discover new architectures with excellent performance. Our approach combines a novel hierarchical genetic representation scheme that imitates the modularized design pattern commonly adopted by human experts, and an expressive search space that supports complex topologies. Our algorithm efficiently discovers architectures that outperform a large number of manually designed models for image classification, obtaining top-1 error of 3.6% on CIFAR-10 and 20.3% when transferred to ImageNet, which is competitive with the best existing neural architecture search approaches. We also present results using random search, achieving 0.3% less top-1 accuracy on CIFAR-10 and 0.1% less on ImageNet whilst reducing the search time from 36 hours down to 1 hour.
GvpCs with reduced numbers of repeating sequence elements bind to and strengthen cyanobacterial gas vesicles (1995)

We have previously shown that the gas-vesicle protein GvpC is present on the outer surface of the gas vesicle, can be reversibly removed and rebound to the surface, and increases the critical collapse pressure of the gas vesicle. The GvpC molecule, which contains five partially conserved repeats of 33 amino acids (33-RR) sandwiched between 18 N-terminal and 10 C-terminal amino acids, is present in a ratio of 1:25 with the GvpA molecule, which forms the ribs of the gas vesicle. By using recombinant techniques we have now made modified versions of GvpC that contain only the first two, three or four of the 33-amino-acid repeats. All of these proteins bind to and strengthen gas vesicles that have been stripped of their native GvpC. Recombinant proteins containing three or four repeats bind in amounts that give the same ratio of 33-RR:GvpA (i.e. 1:5) as the native protein, and they restore much of the strength of the gas vesicle; the protein containing only two repeats binds at a lower ratio (1:7.7), however, and restores less of the strength. Ancestral proteins with only two, three or four of the 33-amino-acid repeats would have been functional in strengthening the gas vesicle but the progressive increase in number of repeats would have provided strength with increased efficiency.
The Roles of Human Sucrose Nonfermenting Protein 2 Homologue in the Tumor-Promoting Functions of Rsf-1 (2008)

Rsf-1 interacts with human sucrose nonfermenting protein 2 homologue (hSNF2H) to form a chromatin remodeling complex that participates in several biological processes. We have previously shown that Rsf-1 gene amplification was associated with the most aggressive type of ovarian cancer and cancer cells with Rsf-1 overexpression depended on Rsf-1 to survive. In this report, we determine if formation of the Rsf-1/hSNF2H complex could be one of the mechanisms contributing to tumor cell survival and growth in ovarian carcinomas. Based on immunohistochemistry, we found that Rsf-1 and hSNF2H were co-upregulated in ovarian cancer tissues. Ectopic expression of Rsf-1 in SKOV3 ovarian cancer cells with undetectable endogenous Rsf-1 expression enhanced hSNF2H protein levels and promoted SKOV3 tumor growth in a mouse xenograft model. Our studies also indicated that induction of Rsf-1 expression affected the molecular partnership of hSNF2H and translocated hSNF2H into nuclei where it colocalized with Rsf-1. Furthermore, analysis of Rsf-1 deletion mutants showed that the Rsf-D4 fragment contained the hSNF2H binding site based on coimmunoprecipitation and in vitro competition assays. As compared with other truncated mutants, expression of Rsf-D4 resulted in remarkable growth inhibition in ovarian cancer cells with Rsf-1 gene amplification and overexpression, but not in those without detectable Rsf-1 expression. The above findings suggest that interaction between Rsf-1 and hSNF2H may define a survival signal in those tumors overexpressing Rsf-1.
Identification of Common Differentially Expressed Genes in Urinary Bladder Cancer (2011)

The identification of the common DE genes among BC samples of different histology can provide further insight into the discovery of new putative markers.
Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer's disease (2002)

Interleukin-1 (IL-1), a key molecule in systemic immune responses in health and disease, has analogous roles in the brain where it may contribute to neuronal degeneration. Numerous findings suggest that this is the case. For example, IL-1 overexpression in the brain of Alzheimer patients relates directly to the development and progression of the cardinal neuropathological changes of Alzheimer's disease, i.e., the genesis and accumulation of beta-amyloid (Abeta) plaques and the formation and accumulation of neurofibrillary tangles in neurons, both of which contribute to neuronal dysfunction and demise. Several genetic studies show that inheritance of a specific IL-1A gene polymorphism increases risk for development of Alzheimer's disease by as much as sixfold. Moreover, this increased risk is associated with earlier age of onset of the disease. Homozygosity for this polymorphism in combination with another in the IL-1B gene further increases risk.
Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo‐controlled study of infliximab therapy in early rheumatoid arthritis (2004)

The delay or reversal of inflammatory and joint-destructive mechanisms in patients with early RA was already apparent following 18 weeks of treatment with infliximab + MTX and was reflected in radiologic changes at 54 weeks.
Once-Daily vs. Continuous Aminoglycoside Dosing: Efficacy and Toxicity in Animal and Clinical Studies of Gentamicin, Netilmicin, and Tobramycin (1983)

The dosing frequency of aminoglycoside antibiotics may alter efficacy and toxicity independent of total daily dose. Once-daily tobramycin dosing was compared with continuous infusion in three models of efficacy. Acute pneumonia due to Pseudomonas aeruginosa in guinea pigs responded better to once-daily dosing, and chronic pneumonia in rats and endocarditis in rabbits responded equally to both regimens. Dogs given gentamicin, tobramycin, or netilmicin once daily, with maximum serum concentrations of greater than 100 mg/liter, had less nephrotoxicity than dogs given continuous infusions. Tobramycin was given once daily or continuously to 52 patients with cystic fibrosis who in 10 days had no change in creatinine clearance or hearing despite maximum serum tobramycin concentrations of 40 mg/liter. Intermittent dosing of aminoglycosides, causing infrequent large maximum serum concentrations, may be less toxic and equally efficacious as frequent dosing.
Coronary artery disease after heart transplantation: non-invasive evaluation with exercise thallium scintigraphy (1993)

In order to assess the value of exercise thallium scintigraphy for the detection and prognosis of graft coronary artery disease, 50 heart transplant patients (mean age 46.7 +/- 11.5 years) were studied within 48 h of their scheduled yearly coronary angiography and subsequently followed up for a mean of 13 +/- 3 months. Angiography revealed normal coronary arteries in 35 patients, and coronary artery disease in 15 (two with type A lesions, seven with type B lesions and six with both). Seven patients had one or more stenoses > or = 50%. Exercise thallium scintigraphy was negative in all patients with normal coronary arteries (100% specificity), and abnormal in 10 of 15 patients with coronary artery disease (67% sensitivity). Fixed defects were seen in six cases, transient defects in two and both in two; the results of the test were abnormal in all seven patients with > or = 50% lesions. During follow-up, none of the patients with a normal exercise thallium scintigraphy experienced any cardiac event; in the group with abnormal results, four cardiac events occurred. Although further studies are needed to confirm these results, exercise thallium scintigraphy seems to be useful in evaluating post-transplant coronary artery disease: it is accurate in detecting the most severe stenoses and provides some prognostic information.
Dose-Dependent Entrainment of Rat Circadian Rhythms by Daily Injection of Melatonin (1986)

Previous work in our laboratory has shown that daily injection of large doses of the pineal hormone melatonin entrains the free-running locomotor rhythms of rats held in constant darkness and synchronizes the disrupted patterns of rats maintained in constant bright light. The present experiments determined the dose-response characteristics of entrainment to daily melatonin injections and made preliminary biochemical estimates of blood melatonin levels and half-lives after two critical doses of the hormone. The data indicated that the median effective dose for melatonin as an entraining agent in free-running rats was 5.45 +/- 1.33 micrograms/kg, considerably lower than doses previously employed and lower than doses employed in reproductive and metabolic studies in rats and hamsters. The data further indicated that the response to melatonin was quantal; rats either entrained to melatonin or they did not. No "partial entrainment" was evident, nor were there differences in phase angle, activity, or period among all effective doses. Biochemical estimates of blood melatonin after either 1 mg/kg or 1 microgram/kg of melatonin indicated that all effective doses resulted in supraphysiological levels of blood melatonin, although doses of 1 microgram/kg resulted in blood levels that were within one order of magnitude of normal nighttime values. Together, the data suggest that the rat circadian system is sensitive to the pineal hormone melatonin at or below doses required to effect rodent reproduction. Whether this sensitivity reflects a role for the pineal gland in rat circadian organization, however, still remains to be determined.
Fabrication of Sub-50-nm Solid-State Nanostructures on the Basis of Dip-Pen Nanolithography (2002)

The fabrication of arrays of sub-50-nm gold dots and line structures with deliberately designed 12−100-nm gaps is reported. These structures were made by initially using dip-pen nanolithography to pattern the etch resist, 16-mercaptohexadecanoic acid, on Au/Ti/SiOx/Si substrates and then using wet-chemical etching to remove the exposed gold.
The 39-kilodalton protein of Borrelia burgdorferi: a target for bactericidal human monoclonal antibodies (1993)

Three human monoclonal immunoglobulin M antibodies against Borrelia burgdorferi, obtained from in vitro-stimulated peripheral blood lymphocytes, reacted in Western blots (immunoblots) with a prominent 39-kDa peptide and a faint band of approximately 66 kDa. Two of these antibodies showed bactericidal activity without addition of complement. All three antibodies were reactive in an enzyme immunoassay with cloned P39 (W.J. Simpson, M.E. Schrumpf, and T.G. Schwan, J. Clin. Microbiol. 28:1329-1337, 1990), suggesting that the target molecule of these antibodies is identical to the P39 protein. In addition, the majority of supernatants from human lymphocytes stimulated in vitro with crude B. burgdorferi antigen reacted in this assay, demonstrating that P39, although a minor component of B. burgdorferi, is an immunodominant antigen in these spirochetes. A fourth monoclonal antibody, reacting with OspA, also exhibited bactericidal activity.