gebhart/patrepeval huggingface dataset:
Electrophysiological Responses of Angiotensin Peptides on the Rat Isolated Nodose Ganglion (1992)

Previous autoradiographic studies have identified angiotensin II (AII) binding sites over the nodose ganglion and along the vagal afferent neurons. In the present study, we examined whether these binding sites are functional receptors by measuring d.c. potential changes by extracellular recording techniques in the rat isolated nodose ganglion preparation in response to superfusion of angiotensin peptides. It was found that AII, as well as AI and AIII elicited concentration-dependent depolarisation of the nodose ganglion. However, the amino terminal angiotensin heptapeptide, A(1-7), failed to evoke any significant response. The AII receptor antagonist, saralasin had no intrinsic activity, but caused a concentration-dependent blockade of AII-induced depolarisation. This study provides evidence for direct neuronal effects of angiotensin peptides on rat vagal afferent neurons. Moreover, this preparation is a relatively convenient one in which to study functional neuronal AII receptor mechanisms on central or peripheral terminals of vagal sensory neurons.
Prevalence of headache syndromes in panic disorder (1999)

We investigated the prevalence of headache in a group of patients attending a psychiatric clinic because suffering from panic disorder, according to DSM-IV criteria. The psychopathological assessment was performed with the 'Panic Disorder/Agoraphobia Questionnaire' and the presence of headache was evaluated according to the criteria of the International Headache Society. The results showed that two-thirds of patients met the criteria for a diagnosis of headache, with migraine without aura being the most frequent form, followed by tension headache, while two patients only were affected by migraine with aura. When we compared panic patients with and without headache, those with headache had a longer duration of panic disorder, a higher number of attacks and a heavier family loading for panic disorder and headache. This suggests that the comorbidity of headache with panic disorder renders this condition more severe and possibly responsive to different treatments compared to panic disorder alone.
Issues in the design of a logic simulator: element modelling for efficiency (1996)

A unique method of using inertial cancellation in the detection of set-up and hold-time violations in flip-flops and other memory-like elements is described, together with an effective technique of modelling sources so that each queues at most one event at any time. Results are presented showing a test circuit failing to operate correctly as a result of timing violations, correctly simulated by these modelling techniques.
Iron acquisition and virulence in Helicobacter pylori: a major role for FeoB, a high‐affinity ferrous iron transporter (2000)

The genome sequence of Helicobacter pylori suggests that this bacterium possesses several Fe acquisition systems, including both Fe2+- and Fe3+-citrate transporters. The role of these transporters was investigated by generating insertion mutants in feoB, tonB, fecA1 and fecDE. Fe transport in the feoB mutant was approximately 10-fold lower than in the wild type (with 0.5 microM Fe), irrespective of whether Fe was supplied in the Fe2+ or Fe3+ form. In contrast, transport rates were unaffected by the other mutations. Complementation of the feoB mutation fully restored both Fe2+ and Fe3+ transport. The growth inhibition exhibited by the feoB mutant in Fe-deficient media was relieved by human holo-transferrin, holo-lactoferrin and Fe3+-dicitrate, but not by FeSO4. The feoB mutant had less cellular Fe and was more sensitive to growth inhibition by transition metals in comparison with the wild type. Biphasic kinetics of Fe2+ transport in the wild type suggested the presence of high- and low-affinity uptake systems. The high-affinity system (apparent Ks = 0.54 microM) is absent in the feoB mutant. Transport via FeoB is highly specific for Fe2+ and was inhibited by FCCP, DCCD and vanadate, indicating an active process energized by ATP. Ferrozine inhibition of Fe2+ and Fe3+ uptake implied the concerted involvement of both an Fe3+ reductase and FeoB in the uptake of Fe supplied as Fe3+. Taken together, the results are consistent with FeoB-mediated Fe2+ uptake being a major pathway for H. pylori Fe acquisition. feoB mutants were unable to colonize the gastric mucosa of mice, indicating that FeoB makes an important contribution to Fe acquisition by H. pylori in the low-pH, low-O2 environment of the stomach.
Inapproximability Results for Sparsest Cut, Optimal Linear Arrangement, and Precedence Constrained Scheduling (2007)

We consider (uniform) sparsest cut, optimal linear arrangement and the precedence constrained scheduling problem 1 |prec| Sigmaw <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j</sub> C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j</sub> -So far, these three notorious NP-hard problems have resisted all attempts to prove inapproximability results. We show that they have no polynomial time approximation scheme (PTAS), unless NP-complete pmblems can be solved in randomized subexponential time. Furthermore, we prove that the scheduling problem is as-hard to approximate as vertex cover when the so-called fixed cost, that is present in all feasible solutions, is subtracted from the objective function.
Study of protein adsorption on glass surfaces with a hydrophobic fluorescent probe. (1984)

The relationship between the affinity of proteins for glass surfaces in a water medium and the fluorescence intensity of a probe [7-(p-methoxybenzylamino)-4-nitrobenz-2-oxa-1, 3-diazole (MBD)] of hydrophobic areas on proteins was studied. Proteins displaying a weak affinity for glass surfaces, such as bovine serum albumin and horse-radish peroxidase, showed stronger fluorescence than those displaying a stronger affinity for glass surfaces, such as serum globulin and fibrinogen. Compatible results were obtained in the chromatography of protein mixtures, such as serum or extract of liver, on porous glass columns. These results suggest that hydrophobic interactions do not participate in the adsorption of proteins on glass surfaces.
Authoritative Sources in a Hyperlinked Environment (2011)

. The network structure of a hyperlinked environment can be a rich source of information about the content of the environment, provided we have effective means for understanding it. We develop a set of algorithmic tools for extracting information from the link structures of such environments, and report on experiments that demonstrate their effectiveness in a variety of contexts on the World Wide Web. The central issue we address within our framework is the distillation of broad search topics, through the discovery of &amp;quot;authoritative&amp;quot; information sources on such topics. We propose and test an algorithmic formulation of the notion of authority, based on the relationship between a set of relevant authoritative pages and the set of &amp;quot;hub pages&amp;quot; that join them together in the link structure. Our formulation has connections to the eigenvectors of certain matrices associated with the link graph; these connections in turn motivate additional heuristics for link-based analysis. Categories and S...
Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. (1998)

Weekly paclitaxel therapy is active and well tolerated in patients with metastatic breast cancer. Weekly therapy should be considered as a current clinical option for these patients and should be incorporated into future comparative clinical trials.
Increased reactivity to myelin oligodendrocyte glycoprotein peptides and epitope mapping in HLA DR2(15)+ multiple sclerosis (1998)

Multiple sclerosis (MS) is a central nervous system-specific inflammatory and demyelinating disease where a myelin-directed autoimmune response is thought to be pathogenetically relevant. Myelin oligodendrocyte glycoprotein (MOG) is a surface-exposed minor myelin component that is a prime candidate autoantigen. We have investigated peripheral blood lymphocyte responses to synthetic 15-26 amino acids long overlapping MOG peptides in 20 MS patients and 14 healthy controls with the MS-associated HLA haplotype DR2(15). There were significantly increased responses, in terms of numbers of cells secreting IFN-gamma detected by Elispot in response to several MOG-derived peptides in the MS patients, but not the healthy controls. MOG peptide 63-87 evoked the strongest response, and the stimulatory property of this peptide was confirmed in additional DR2(15)+ MS patients where a peptide concentration-dependent proliferative response, which was inhibited by the addition of anti-HLA class II antibodies, was observed. This is the first work detailing putative immunodominant T cell epitopes of MOG in DR2(15)+ MS patients.
Isolation and Structure of Cytostatic Steroidal Saponins from the African Medicinal Plant Balanites aegyptica (1991)

Bioactivity-guided separation of a CH2Cl2/MeOH extract of Balanites aegyptica afforded four new cytostatic saponins, named balanitins 4 [1], 5 [2], 6 [3], and 7 [4]. On the basis of enzymatic hydrolyses and glycosidation nmr chemical shifts employing the peracetates, structures 1-4 were established as yamogenin 3 beta-O-beta-D-glucopyranosyl-(1----3)-beta-D-glucopyranosyl-(1----4)-[al pha- L-rhamnopyranosyl-(1----2)]-beta-D-glucopyranoside [1], yamogenin 3 beta-O-alpha-L-rhamnopyranosyl-(1----3)-beta-D-glucopyranosyl-(1----4)- [alpha-L-rhamnopyranosyl-(1----2)]-beta-D-glucopyranoside [2], yamogenin 3 beta-O-beta-D-glucopyranosyl-(1----4)-[alpha-L- rhamnopyranosyl-(1----2)]-beta-D-glucopyranoside [3], and diosgenin 3 beta-O-beta-D-xylopyranosyl-(1----3)-beta-D-glucopyranosyl-(1----4)-[alp ha- L-rhamnopyranosyl-(1----2)]-beta-D-glucopyranoside [4].
Dual FRET molecular beacons for mRNA detection in living cells (2004)

The ability to visualize in real-time the expression level and localization of specific endogenous RNAs in living cells can offer tremendous opportunities for biological and disease studies. Here we demonstrate such a capability using a pair of molecular beacons, one with a donor and the other with an acceptor fluorophore that hybridize to adjacent regions on the same mRNA target, resulting in fluorescence resonance energy transfer (FRET). Detection of the FRET signal significantly reduced false positives, leading to sensitive imaging of K-ras and survivin mRNAs in live HDF and MIAPaCa-2 cells. FRET detection gave a ratio of 2.25 of K-ras mRNA expression in stimulated and unstimulated HDF, comparable to the ratio of 1.95 using RT-PCR, and in contrast to the single-beacon result of 1.2. We further revealed intriguing details of K-ras and survivin mRNA localization in living cells. The dual FRET molecular beacons approach provides a novel technique for sensitive RNA detection and quantification in living cells.
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib (2005)

Our results suggest that treatment decisions regarding use of these kinase inhibitors might be improved by determining the mutational status of both EGFR and KRAS.
Impact of Misclassification in Genotype-Exposure Interaction Studies: Example of N-Acetyltransferase 2 (NAT2), Smoking, and Bladder Cancer (2004)

Errors in genotype determination can lead to bias in the estimation of genotype effects and gene-environment interactions and increases in the sample size required for molecular epidemiologic studies. We evaluated the effect of genotype misclassification on odds ratio estimates and sample size requirements for a study of NAT2 acetylation status, smoking, and bladder cancer risk. Errors in the assignment of NAT2 acetylation status by a commonly used 3-single nucleotide polymorphism (SNP) genotyping assay, compared with an 11-SNP assay, were relatively small (sensitivity of 94% and specificity of 100%) and resulted in only slight biases of the interaction parameters. However, use of the 11-SNP assay resulted in a substantial decrease in sample size needs to detect a previously reported NAT2-smoking interaction for bladder cancer: 1,121 cases instead of 1,444 cases, assuming a 1:1 case-control ratio. This example illustrates how reducing genotype misclassification can result in substantial decreases in sample size requirements and possibly substantial decreases in the cost of studies to evaluate interactions.
Comparative study of clinical, histological, and immunological responses to interferon therapy in type non-A, non-B, and type B chronic hepatitis. (1990)

Nineteen patients with chronic non-A, non-B hepatitis (CH-NANB) and 24 patients with chronic hepatitis B (CH-B) were treated with interferons, and the therapeutic and biological responses of the two groups (CH-NANB and CH-B) were compared. All patients had had sustained elevations in serum glutamic pyruvic transaminase (sGPT) levels for more than 6 months and were proven to have chronic hepatitis by liver biopsy. alpha-Interferon (IFN-alpha) or beta-interferon (IFN-beta) was administered in low doses of 3 to 6 mega international units (MIU) daily for 4 wk. Liver biopsies were taken from 13 CH-NANB and 14 CH-B subjects just before and immediately after treatment, and histological findings were assessed by the histology activity index (HAI) score. SGPT levels decreased much more rapidly and markedly in CH-NANB than in CH-B during IFN therapy (p less than 0.01). The HAI score decreased 3.5 points in CH-NANB and 1.0 point in CH-B between pretreatment and posttreatment. Serum beta 2-microglobulin (beta 2-MG) increased in both types of chronic hepatitis during treatment, but the rate of elevation was significantly less in CH-NANB than in CH-B (p less than 0.001). beta 2-MG expression on hepatocytes stained by the PAP method was almost identical in CH-NANB before and after treatment, whereas it increased steadily in CH-B. The serum 2',5'-oligoadenylate synthetase level increased in both types of hepatitis on IFN administration. These results suggest that, in IFN treatment for CH-NANB, the antiviral actions of IFNs may play a very important role in reducing the activity of chronic hepatitis.
Prediction of Hearing Aid Benefit (1994)

The listening level chosen by a hearing aid wearer for receiving amplified speech in noise has a substantial impact on the benefit that the hearing aid can provide. Chosen listening levels determine (1) the extent to which audibility of speech cues is improved by amplification, (2) the in situ distortion generated by the hearing aid, and sometimes (3) the auditory resolution abilities available to the hearing-impaired listener. All of these variables have been shown to affect hearing aid benefit. Thus, to predict benefit in any particular listening environment, the listening level that the wearer would choose in that setting must be known with some precision. This paper reports two studies of chosen, or preferred, listening levels. We present evidence to show that preferred listening levels vary with changes in the listening environment, especially when the signal-to-noise ratio is favorable. We describe a method for predicting preferred listening level changes in some environments that differ in talker levels and/or signal-to-noise ratios.
Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent (2017)

Transdermal delivery of peptides and other biological macromolecules is limited due to skin's inherent low permeability. Here, the authors report the use of a deep eutectic solvent, choline and geranate (CAGE), to enhance topical delivery of proteins such as bovine serum albumin (BSA, molecular weight: ≈66 kDa), ovalbumin (OVA, molecular weight: ≈45 kDa) and insulin (INS, molecular weight: 5.8 kDa). CAGE enhances permeation of BSA, OVA, and insulin into porcine skin ex vivo, penetrating deep into the epidermis and dermis. Studies using tritium-labeled BSA and fluorescein isothiocyanate labeled insulin show significantly enhanced delivery of proteins into and across porcine skin, penetrating the skin in a time-dependent manner. Fourier transform IR spectra of porcine stratum corneum (SC) samples before and after incubation in CAGE show a reduction in peak area attributed to SC lipid content, suggesting lipid extraction from the SC. Circular dichroism confirms that CAGE does not affect insulin's secondary conformation. In vivo studies in rats show that topical application of 10 U insulin dispersed in CAGE (25 U kg<sup>-1</sup> insulin dose) leads to a highly significant 40% drop in blood glucose levels in 4 h that is relatively sustained for 12 h. Taken together, these studies demonstrate that CAGE is a promising vehicle for transdermal delivery of therapeutic proteins; specifically, as a noninvasive delivery alternative to injectable insulin for the treatment of diabetes.
Genetic Map Refinement Using a Comparative Genomic Approach (2009)

Following various genetic mapping techniques conducted on different segregating populations, one or more genetic maps are obtained for a given species. However, recombination analyzes and other methods for gene mapping often fail to resolve the ordering of some pairs of neighboring markers, thereby leading to sets of markers ambiguously mapped to the same position. Each individual map is thus a partial order defined on the set of markers, and can be represented as a Directed Acyclic Graph (DAG). In this article, given a phylogenetic tree with a set of DAGs labeling each leaf (species), the goal is to infer, at each leaf, a single combined DAG that is as resolved as possible, considering the complementary information provided by individual maps, and the phylogenetic information provided by the species tree. After combining the individual maps of a leaf into a single DAG, we order incomparable markers by using two successive heuristics for minimizing two distances on the species tree: the breakpoint distance, and the Kemeny distance. We apply our algorithms to the plant species represented in the Gramene database, and we evaluate the simplified maps we obtained.
Characterization of the rat salivary-gland B1-immunoreactive proteins (1998)

The B1-immunoreactive proteins (B1-IPs) are major secretory products of rat submandibular gland acinar-cell progenitors, and are also produced by neonatal and adult rat sublingual and parotid glands. In order to characterize the B1-IPs, we have previously isolated cDNA clones encoding rat parotid secretory protein (PSP; the predominant parotid B1-IP) and the related clone ZZ3, which is developmentally regulated in the neonatal submandibular gland. The remainder of the B1-IPs were uncharacterized. This report demonstrates that all of the B1-IPs are derived from the PSP and ZZ3 transcripts. Molecular cloning and Western-blot analyses using PSP- and ZZ3-specific antisera show that, of the B1-IPs, only PSP and neonatal submandibular gland protein A (SMGA) are products of the Psp gene. This finding corrects our previous assertion that SMGA is derived from ZZ3. Neonatal submandibular gland proteins B1 and B2, as well as apparent Mr 26000-28000 and Mr 18000-20000 forms in submandibular, sublingual and parotid glands, are derived from the gene encoding ZZ3 by differential N-glycosylation and by proteolytic cleavage. The apparent Mr 18000-20000 proteolytic products are significant in secretion product collected in vitro, but rare in gland homogenate and submandibular/sublingual saliva. The gene encoding ZZ3 has been named Smgb. Psp and Smgb are regulated similarly in the developing submandibular gland, but differently in the sublingual and parotid glands. The expression pattern of Psp is conserved between rat and mouse. However, no evidence for proteins derived from an Smgb-like gene was observed in neonatal mouse submandibular or sublingual glands.
p14ARF Triggers G2 Arrest Through ERK-Mediated Cdc25C Phosphorylation, Ubiquitination and Proteasomal Degradation (2006)

The Cdc25C phosphatase is a key regulator of mitotic entry which activity is tightly regulated by phosphorylation. In response to DNA damage, phosphorylation at serine 216 induces the cytosolic retention of Cdc25C through 14-3-3 binding. We previously reported the ability of the p14ARF tumor suppressor to induce the accumulation of inactive phospho-Cdc25C(Ser216) protein as well as a decrease of Cdc25C steady state level and correlated these events with a p53-independent G2 arrest. The aim of this study was to investigate the cellular signaling pathways involved in this process. By using specific pharmacological inhibitors, we demonstrate that activation of the ERK1/2 MAP kinases pathway is involved in the p53-independent G2 checkpoint induced by p14ARF Moreover, we show that activated P-ERK1/2 bind and phosphorylate Cdc25C on its ser216 residue following p14ARF expression, thereby identifying Cdc25C as a new ERK1/2 target. Importantly, we further show that phosphorylation at Ser216 by phospho-ERK1/2 promotes Cdc25C ubiquitination and proteasomal degradation, suggesting that Cdc25C proteolysis is required for a sustained G2 arrest in response to p14ARF. Taken together, these results demonstrate that the MAPK ERK signaling pathway contributes to the p53-independent antiproliferative functions of p14ARF. Furthermore, they identify a new mechanism by which phosphorylation at serine 216 participates to Cdc25C inactivation.
Complete amino acid sequence of human placental 17β‐hydroxysteroid dehydrogenase deduced from cDNA (1988)

cDNA clones for 17 beta-hydroxysteroid dehydrogenase (17-HSD; EC 1.1.1.62) were isolated from a placental lambda gt11 expression library using polyclonal antibodies against placental 17-HSD. The largest cDNA contained 1325 nucleotides, consisting of a short 5'-noncoding segment, a coding segment of 987 nucleotides terminated by a TAA codon, and a 329 nucleotide long 3'-noncoding segment. The open reading frame encoded a polypeptide of 327 amino acid residues with a predicted Mr of 34853. The amino acid sequence of 23 N-terminal amino acids determined from purified 17-HSD agreed with the sequence deduced from cDNA. The deduced amino acid sequence also contained two peptides previously characterized from the proposed catalytic area of placental 17-HSD.
Infection with Mycobacterium avium induces production of interleukin-10 (IL-10), and administration of anti-IL-10 antibody is associated with enhanced resistance to infection in mice (1993)

Organisms of the Mycobacterium avium complex are associated with disseminated infection in patients with AIDS. The mechanisms that account for the survival of the intracellular bacteria are unknown. We document here that infection of C57BL/6 black mice with M. avium 101 triggered interleukin-10 (IL-10) production. The synthesis of IL-10 peaked after 2 weeks of infection and remained elevated throughout the period of infection. Treatment of M. avium-infected peritoneal macrophages with recombinant IL-10 suppressed the stimulatory effect of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. To confirm the possible role of IL-10 in the infection in vivo, mice were infected with M. avium 101 and simultaneously received treatment with neutralizing anti-IL-10 antibody. After 4 weeks the animals were harvested and the numbers of viable bacteria were quantitated in the liver, spleen, and blood. The liver and spleen of animals receiving anti-IL-10 antibody had 2 to 3 log units fewer bacteria than did those of control animals. These results suggest a role for IL-10 in the pathogenesis of M. avium infection.