gebhart/patrepeval huggingface dataset:
Inhibition of guinea‐pig and human sensory nerve activity and the cough reflex in guinea‐pigs by cannabinoid (CB<sub>2</sub>) receptor activation (2003)

1. There is considerable interest in novel therapies for cough, since currently used agents such as codeine have limited beneficial value due to the associated side effects. Sensory nerves in the airways mediate the cough reflex via activation of C-fibres and RARs. Evidence suggests that cannabinoids may inhibit sensory nerve-mediated responses. 2. We have investigated the inhibitory actions of cannabinoids on sensory nerve depolarisation mediated by capsaicin, hypertonic saline and PGE2 on isolated guinea-pig and human vagus nerve preparations, and the cough reflex in conscious guinea-pigs. 3. The non-selective cannabinoid (CB) receptor agonist, CP 55940, and the selective CB2 agonist, JWH 133 inhibited sensory nerve depolarisations of the guinea-pig vagus nerve induced by hypertonic saline, capsaicin and PGE2. These responses were abolished by the CB2 receptor antagonist SR144528, and unaffected by the CB1 antagonist SR141716A. Similarly, JWH 133 inhibited capsaicin-evoked nerve depolarisations in the human vagus nerve, and was prevented by SR144528. 4. Using a guinea-pig in vivo model of cough, JWH 133 (10 mg kg-1, i.p., 20 min) significantly reduced citric acid-induced cough in conscious guinea pigs compared to those treated with the vehicle control. 5. These data show that activation of the CB2 receptor subtype inhibits sensory nerve activation of guinea-pig and human vagus nerve, and the cough reflex in guinea-pigs, suggesting that the development of CB2 agonists, devoid of CB1-mediated central effects, will provide a new and safe antitussive treatment for chronic cough.
New ideas for the dietary management of gastrointestinal tract disease (1994)

ABSTRACT Drugs are often given inappropriate precedence in the treatment of gastrointestinal tract diseases. Diet has a marked influence on gastrointestinal tract function and the manipulation of dietary composition provides clinicians with a powerful therapeutic tool. During acute gastroenteritis, a short period of fasting is recommended. ‘Feeding through’ diarrhoea (without a period of fasting) is recommended in human infants but has limited applicability in dogs and cats, primarily because different types of diarrhoea are commonly treated by veterinary surgeons compared to physicians. Following the fast, a change from the animal's regular food to a diet containing novel protein sources is advisable. This minimises the likelihood of acquired food allergies to staple proteins. Allergy avoidance may require special techniques such as rotation diets or protein hydrolysates. Dietary fat is usually kept to a minimum during gastrointestinal dysfunction as malabsorbed fatty acids and bile acids promote secretory diarrhoea in the large bowel. Recommendations to feed high fat rather than high carbohydrate diets to cats with diarrhoea need to be objectively examined. The type of fat fed may also prove to be an important consideration. Incorporation of omega‐3 fatty acids into the diet has been shown to have anti‐inflammatory effects on the gastrointestinal mucosa. In diseases of the small bowel, it is traditional to use low fibre diets. This recommendation needs re‐examination because the binding and gelling properties of fibre are of potential benefit in the treatment of small bowel diarrhoea. High fibre diets are useful in most large bowel diseases. Soluble (fermentable) fibres (eg, psyllium, oat bran and fibrim) rather than insoluble (non‐fermentable) fibres (eg, wheat bran) give better results in treating colitis. The benefits from soluble fibre probably relates to the binding of irritant bile acids and the generation of volatile fatty acids, such as butyrate, that nourish the colonic epithelium and encourage growth of normal bacterial flora.
Polystyrene foams. II. Structure–impact properties relationships (2003)

Abstract In the first part of this series of articles, the relations between the foaming conditions and the microstructure of expanded polystyrene (EPS) were explored. In this part, the effects of the foaming conditions and the microstructure of EPS on impact properties are discussed. Regression analysis was conducted on the data and expressions were developed to quantify these relationships. Moreover, the importance of the individual structural parameters was determined. Statistical analysis of the data showed that foaming time was the most important factor determining the impact strength, while foaming temperature was the most important factor controlling the specific impact strength. The deformation of cells at the crack tip, as a result of bending and/or buckling of cell walls, can increase the failure strain, which leads to an increase in failure energy. In expanded polymers, the majority of the absorbed energy during impact loading is dissipated as plastic work. The transition of plane stress conditions to plane strain conditions, due to expansion, can be considered as another source of toughening in EPS. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1421–1426, 2003
High time for high level ATPG (2005)

High level ATPG does not make the test problem any easy. In fact, there are several design-flow-related complications it creates. Also, the fault models used in high level ATPG are not suitable. Gate level ATPG has dominated for over 20 years and continue to do so. And there are enough challenging unsolved problems in gate level ATPG and there is no evidence that high level ATPG provides any help to these challenging problems.
Mutational Activation of the K-<i>ras</i>Oncogene (1987)

To define the role of cellular oncogenes in human cancers, we studied the prevalence of mutational activation of ras oncogenes in untreated non-small-cell lung cancer. Genomic DNA was extracted from 39 tumor specimens obtained by thoracotomy and was examined for activating point mutations in codons 12, 13, and 61 of the H-ras, K-ras, and N-ras genes. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. The K-ras gene was found to be activated by point mutations in codon 12 in 5 of 10 adenocarcinomas. Two of these tumors were less than 2 cm in size and had not metastasized. No ras gene mutations were observed in 15 squamous-cell carcinomas, 10 large-cell carcinomas, 1 carcinoid, 2 metastatic adenocarcinomas from primary tumors outside the lung, and 1 small-cell carcinoma. An approximately 20-fold amplification of the unmutated K-ras gene was observed in a tumor that proved to be a solitary lung metastasis of a rectal carcinoma. We conclude that mutational K-ras activation may be an important early event in the pathogenesis of adenocarcinoma of the lung but that amplification of ras genes or mutational activation of H-ras or N-ras does not play a major part in non-small-cell lung cancer.
An Efficient Multigram Synthesis of Monomers for the Preparation of Novel Oligonucleotides Containing Isosteric Non-Phosphorous Backbones (1997)

Abstract The facile preparation of two novel classes of nucleoside analogs for the inclusion as dimeric non-phosphorous containing subunits in chimeric backbones has been accomplished. The concise preparation of 3′-formylnucleosides and 5′-O-(N-methylhydroxylamino)-nucleosides is reported.
Integrated querying of XML data in RDBMSs (2003)

This paper proposes a way to integrate cleanly relational databases and XML documents. The main idea is to draw a clear line of demarcation between the two concepts by modelling XML documents as a new atomic SQL type. The standardised XML tools like XPath, XQuery, XSLT are then user-defined functions that operate on this type. Well-defined interoperability is guaranteed by, on the one hand, defining a standard way to markup SQL relations as XML documents and, thus, to make them accessible to the XML tools; on the other hand, XPath and XQuery queries run against the XML portion of the database can use the same predefined schema to make their results accessible to the SQL language for further processing. Additionally, a method for set-oriented evaluation of regular path expressions is presented that integrates into our implementation framework.
Design of database and secure communication protocols for Internet-of-things-based smart home system (2017)

Recently, the implementation of IoT technology development has been growing rapidly. One of IoT applications is smart home system. In this system, in-home hardwares are connected to the internet. Thus, residents can access them using any internet-connected devices, such as mobile phones. Since the main concern of the IoT system is communication, the design of an efficient and secure communication protocol and database becomes very important. In this paper, we design an AMQP communication protocol with the existence of queuing data queuing scheme. For ensuring security, the entire communication process is encrypted using RSA and AES encryption algorithms, while the database is stored in MySQL RDBMS.
Aerobic Nickel-Catalyzed Hydroxysulfonylation of Alkenes Using Sodium Sulfinates (2015)

Nickel-catalyzed hydroxysulfonylation of alkenes was achieved using sodium sulfinates under air atmosphere. The procedure enabled the selective synthesis of β-hydroxysulfones in good yields and suppressed the formation of β-ketosulfones. On the contrary, sulfonylation of alkynes with sodium sulfonates afforded only β-ketosulfones.
Arteriogenesis Proceeds via ICAM-1/Mac-1- Mediated Mechanisms (2004)

Monocyte adhesion to shear stress-activated endothelium stands as an important initial step during arteriogenesis (collateral artery growth). Using multiple approaches, we tested the hypothesis that monocyte adhesion via intercellular adhesion molecule-1 (ICAM-1) and selectin interactions is essential for adaptive arteriogenesis. Forty-eight New Zealand White rabbits received either solvent, monocyte chemoattractant protein-1 (MCP-1) alone, MCP-1 plus ICAM-mab, or MCP-1 plus an IgG2a isotype control via osmotic minipumps. After 7 days, collateral conductance was evaluated: solvent 4.01 (mL/min per 100 mm Hg), MCP-1 plus ICAM-mab 8.04 (versus solvent P=NS), and MCP-1 alone 33.11 (versus solvent P<0.05). Furthermore, the right femoral arteries of ICAM-1-/-, Mac-1-/- and mice having defective selectin interactions (FT4/7-/-) as well as their corresponding controls were ligated. One week later, perfusion ratios were determined by the use of fluorescent microspheres. FT4/7-/- mice did not show any significant difference in perfusion restoration whereas ICAM-1-/- and Mac-1-/- mice had a significant reduction in arteriogenesis as compared with matching controls (FT4/7-WT 37+/-9%, FT4/7-/- 32+/-3%, P=0.31; C57BL/6J 59+/-9%, ICAM-1-/- 36+/-8%, P<0.05; Mac-1-/- 42+/-3%, P<0.05). ICAM-1/Mac-1-mediated monocyte adhesion to the endothelium of collateral arteries is an essential step for arteriogenesis, whereas this process can proceed via selectin interaction independent mechanisms. Furthermore, in vivo treatment with monoclonal antibodies against ICAM-1 totally abolishes the stimulatory effect of MCP-1 on collateral artery growth, suggesting that the mechanism of the MCP-1-induced arteriogenesis proceeds via the localization of monocytes rather than the action of the MCP-1 molecule itself.
Integrated circuit design with NEM relays (2008)

To overcome the energy-efficiency limitations imposed by finite sub-threshold slope in CMOS transistors, this paper explores the design of integrated circuits based on nano-electro-mechanical (NEM) relays. A dynamical Verilog-A model of the NEM relay is described and correlated to device measurements. Using this model we explore NEM relay design strategies for digital logic and I/O that can significantly improve the energy efficiency of the whole VLSI system. By exploiting the low effective threshold voltage and zero leakage achievable with these relays, we show that NEM relay-based adders can achieve an order of magnitude or more improvement in energy efficiency over CMOS adders with ns-range delays and with no area penalty. By applying parallelism, this improvement in energy-efficiency can be achieved at higher throughputs as well, at the cost of increased area. Similar improvements in high-speed I/O energy are also predicted by making use of the relays to implement highly energy-efficient digital-to-analog and analog-to-digital converters.
Detection of Legionella antigenuria by reverse passive agglutination (1982)

A reverse passive agglutination method was developed to detect soluble antigens of Legionella spp. By this method Legionella antigens were detected in urine specimens from 14 of 15 antigenuric patients with clinically diagnosed Legionnaires disease and in none of 263 urine samples from healthy subjects or patients with urinary tract infections. Intra-genus cross-reactivity was observed only between L. pneumophila serogroups 2, 3, and 6. The Legionella reverse passive agglutination method was also evaluated with reference to reagent concentrations, test conditions, and subjectivity of reading test results. The method is rapid and does not require special equipment.
The FET3 Gene Product Required for High Affinity Iron Transport in Yeast Is a Cell Surface Ferroxidase (1995)

The yeast FET3 gene is required for high affinity iron transport (Askwith, C., Eide, D., Ho, A. V., Bernard, P. S., Li, L., Davis-Kaplan, S., Sipe, D. M., and Kaplan, J. (1994) Cell 76, 403-410). The gene has extensive sequence homology to the family of multi-copper oxidases. In this communication, we demonstrate that the gene product is a cell surface ferroxidase involved in iron transport. Cells that contain a functional FET3 gene product exhibited an iron-dependent non-mitochondrial increase in oxygen consumption. Comparison of the rate of iron oxidation to O2 consumption yielded an approximate value of 4:1, as predicted for a ferroxidase. Spheroplasts obtained from cells grown under low iron conditions also displayed an iron-dependent increase in O2 consumption. Treatment of spheroplasts with trypsin or affinity-purified antibodies directed against the putative external ferroxidase domain of Fet3 had no effect on basal O2 consumption but inhibited the iron-dependent increase in O2 consumption. Anti-peptide antibodies directed against the cytosolic domain of Fet3 had no effect on O2 consumption. These studies indicate that Fet3 is a plasma membrane ferroxidase required for high affinity iron uptake, in which the ferroxidase-containing domain is localized on the external cell surface.
Effect of <i>Candida glabrata FKS1</i> and <i>FKS2</i> Mutations on Echinocandin Sensitivity and Kinetics of 1,3-β- <scp>d</scp> -Glucan Synthase: Implication for the Existing Susceptibility Breakpoint (2009)

Thirteen Candida glabrata strains harboring a range of mutations in hot spot regions of FKS1 and FKS2 were studied. The mutations were linked to an echinocandin reduced susceptibility phenotype. Sequence alignments showed that 11 out of the 13 mutants harbored a mutation in FKS1 or FKS2 not previously implicated in echinocandin reduced susceptibility in C. glabrata. A detailed kinetic characterization demonstrated that amino acid substitutions in Fks1p and Fks2p reduced drug sensitivity in mutant 1,3-beta-D-glucan synthase by 2 to 3 log orders relative to that in wild-type enzyme. These mutations were also found to reduce the catalytic efficiency of the enzyme (Vmax) and to influence the relative expression of FKS genes. In view of the association of FKS mutations and reduced susceptibility of 1,3-beta-D-glucan synthase, an evaluation of the new CLSI echinocandin susceptibility breakpoint was conducted. Only 3 of 13 resistant fks mutants (23%) were considered anidulafungin or micafungin nonsusceptible (MIC > 2 microg/ml) by this criterion. In contrast, most fks mutants (92%) exceeded a MIC of >2 microg/ml with caspofungin. However, when MIC determinations were performed in the presence of 50% serum, all C. glabrata fks mutants showed MICs of > or = 2 microg/ml for the three echinocandin drugs. As has been observed with Candida albicans, the kinetic inhibition parameter 50% inhibitory concentration may be a better predictor of FKS-mediated resistance. Finally, the close association between FKS1/FKS2 hot spot mutations provides a basis for understanding echinocandin resistance in C. glabrata.
Relationship Between Tumor Gene Expression and Recurrence in Four Independent Studies of Patients With Stage II/III Colon Cancer Treated With Surgery Alone or Surgery Plus Adjuvant Fluorouracil Plus Leucovorin (2010)

RT-qPCR of FPE colon cancer tissue applied to four large independent populations has been used to develop multigene algorithms for estimating recurrence risk and benefit from FU/LV. These algorithms are being independently validated, and their clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR) study.
Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain. (1989)

Dopamine receptor types D1 and D2 can oppose or enhance each other's actions for electrical, biochemical, and psychomotor effects. We report a D1-D2 interaction in homogenized tissue as revealed by ligand binding. D2 agonists lowered the binding of [3H]raclopride to D2 receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D1-selective antagonist SCH 23390 prevented the agonist-induced decrease in [3H]raclopride binding to D2 sites in the striatum but not in the anterior pituitary, which has no D1 receptors. Conversely, a dopamine-induced reduction in the binding of [3H]SCH 23390 to D1 receptors could be prevented by the D2-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D1-D2 interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D2 receptors in the high-affinity state. Thus, the D1-D2 link may be mediated by guanine nucleotide-binding protein components. The link may underlie D1-D2 interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata.
Activation of Nitric Oxide Release and Oxidative Metabolism by Leukotrienes B4, C4, and D4 in Human Polymorphonuclear Leukocytes (1999)

Because arachidonate metabolites are potent mediators of inflammation, we have studied the effects of leukotriene B4(LTB4) and the cysteinyl leukotrienes C4 and D4 (LTC4 and LTD4) on the release of nitric oxide (NO), in vitro, by human polymorphonuclear granulocytes (PMN). Two independent and highly sensitive real-time methods were used for these studies, ie, the NO-dependent oxidation of oxyhemoglobin (HbO2) to methemoglobin and a NO-sensitive microelectrode. When activated with LTB4, LTC4, or LTD4, but not with other lipoxygenase products such as 5S-HETE, 5-oxo-ETE or 5S,12S-diHETE, PMN produced NO in a stimulus- and concentration-dependent manner. The rank order of potency was LTB4 = LTC4 &gt; LTD4, corresponding to 232 ± 50 pmol of NO/106 PMN for 100 nmol/L LTB4 after 30 minutes. The kinetic properties of the responses were similar for all three leukotrienes with a maximum response at 13 ± 3 minutes. Cysteinyl leukotriene and LTB4 antagonists inhibited the agonist-induced NO production by 70%, and treatment with Bordetella pertussis toxin, or chelation of cytosolic Ca2+, [Ca2+]i, also efficiently inhibited this response. In contrast, treatment of PMN with cytochalasin B (5 μg/mL) enhanced the LTB4-induced NO formation by 86%. Thus, this is the first demonstration that the cysteinyl leukotrienes LTC4 and LTD4, as well as LTB4, activate NO release from human PMN by surface receptor, G-protein and [Ca2+]i-dependent mechanisms. This effect differs from activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, for which only LTB4is an activator.
Effect of Pantothenic Acid and Ascorbic Acid Supplementation on Human Skin Wound Healing Process (1995)

This study aimed at testing human skin wound healing improvement by a 21-day supplementation of 1.0 g ascorbic acid (AA) and 0.2 g pantothenic acid (PA). 49 patients undergoing surgery for tattoos, by the successive resections procedure, entered a double-blind, prospective and randomized study. Tests performed on both skin and scars determined: hydroxyproline concentrations, number of fibroblasts, trace element contents and mechanical properties. In the 18 supplemented patients, it was shown that in skin (day 8) Fe increased (p < 0.05) and Mn decreased (p < 0.05); in scars (day 21), Cu (p = 0.07) and Mn (p < 0.01) decreased, and Mg (p < 0.05) increased; the mechanical properties of scars in group A were significantly correlated to their contents in Fe, Cu and Zn, whereas no correlation was shown in group B. In blood, AA increased after surgery with supplementation, whereas it decreased in controls. Although no major improvement of the would healing process could be documented in this study, our results suggest that the benefit of AA and PA supplementation could be due to the variations of the trace elements, as they are correlated to mechanical properties of the scars.
Synthesis and Evaluation of CC-1065 and Duocarmycin Analogs Incorporating the 1,2,3,4,11,11a-Hexahydrocyclopropa[<i>c</i>]naphtho[2,1-<i>b</i>]azepin-6-one (CNA) Alkylation Subunit:  Structural Features that Govern Reactivity and Reaction Regioselectivity (1997)

The synthesis of 1,2,3,4,11,11a-hexahydrocyclopropa[c]naphtho[2,1−b]azepin-6-one (CNA), a seven-membered C-ring analog of the alkylation subunits of CC-1065 and the duocarmycins, is detailed. The core structure of CNA was prepared through the implementation of an intramolecular Heck reaction for assemblage of the key tricyclic tetrahydronaphtho[2,1−b]azepine skeleton and a final Winstein Ar-3' spirocyclization for introduction of the reactive cyclopropane. A study of the solvolysis reactivity of N-BOC-CNA revealed that incorporation of the seven-membered fused C-ring system increased the reactivity 4750× compared to the corresponding five-membered C-ring analog. Solvolysis occurs with SN2 nucleophilic attack at the more substituted carbon of the activated cyclopropane to afford exclusively the abnormal ring expansion product in a reaction that was shown to proceed with complete inversion of configuration at the reaction center. Single crystal X-ray structure analyses of N-CO2Me-CNA (29) and CNA (11) and their comparisons with X-ray structures of the corresponding five- and six-membered C-ring analogs revealed the structural origins of the solvolysis regioselectivity and reactivity. The regioselectivity may be attributed to the stereoelectronic alignment of the two available cyclopropane bonds with the cyclohexadienone π-system which for 29 resides with the bond that extends to the more substituted cyclopropyl carbon. The increased reactivity may be due in part to the geometric alignment of the cyclopropane but more significantly is linked to a twist in the N2 amide. X-ray analysis provides documentation of the disruption in the vinylogous amide stabilization as measured by a lengthening of the diagnostic C−N bond that accompanies the twist in the χ1 dihedral angle of the N2 amide. As the cross-conjugated vinylogous amide stabilization is diminished, the cyclopropane conjugation, bond lengths, and resulting reactivity increase. The unusual stability of the five-membered C-ring bearing alkylation subunits characteristic of the natural products is intimately linked to the extent of this vinylogous amide conjugation, and the studies support the proposal that catalysis for the DNA alkylation reaction may be due to a DNA binding-induced conformational change in the agents which serves to twist the linking N2 amide, disrupting the vinylogous amide stabilization, and activating the agents for SN2 nucleophilic attack.