78 research outputs found
Effect of histamine on rat gastric H(+)-K(+)-ATPase alpha-subunit expression
No full text The H(+)-K(+)-adenosinetriphosphatase (ATPase) is expressed in the parietal cell and is responsible for acid secretion by the stomach. Histamine binds to an H2 receptor and activates adenylate cyclase and intracellular calcium concentration ([Ca2+]i) elevation, stimulating acid secretion. It has been shown that omeprazole administered to rats increases serum gastrin and transiently increases the level of mRNA for the alpha-subunit of the pump, but this increase is blocked by the presence of the H2-receptor antagonist, famotidine [A. Tari, G. Yamamoto, K. Sumii, M. Sumii, Y. Takehara, K. Haruma, G. Kajiyama, V. Wu, G. Sachs, and J. H. Walsh. Am. J. Physiol. 265 (Gastrointest. Liver Physiol. 28): G752-G758, 1993]. These observations suggest that the release of histamine induced by gastrin is essential for the increase of the expression of mRNA induced by omeprazole. Infusion of histamine at 15 mumol.kg-1.h-1 i.v. for 1 h increased the alpha-subunit mRNA level by 144 +/- 2.4% and induced a stimulated morphological appearance of the parietal cell. These changes were inhibited completely by the competitive H2-receptor antagonist famotidine, which elevated gastric pH and serum gastrin. Famotidine also reduced the level of H(+)-K(+)-ATPase mRNA compared with control animals. No change in the expression of beta-actin mRNA was observed in any group of animals. These data provide direct evidence for histamine stimulation of H(+)-K(+)-ATPase alpha-subunit gene expression by activation of the H2 receptor. </jats:p
Sumii, Mrs. M.
No full textPassport photo of older woman. Negative scan.In 1922, Kinso Ninomiya opened the Ninomiya Studio in Little Tokyo, Los Angeles. Due to Executive Order 9066 in 1942, the studio was forced to close but was reopened by Kinso and his son, Elwin Ichiro, in 1949. The studio operated in Little Tokyo until its final closing in 1986. The Ninomiya Studio Collection captures slices of Japanese American life in Los Angeles from the 1950s through the 1980s. The collection contains formal portraiture and candid photography in black and white and color as well as commercial photography for local businesses and reproductions of older photographs. The negatives come in a variety of sizes, including 8 x 10 inch negatives and panoramic negatives on Cirkut film. Each negative scanned has been selected out of multiple negatives and prints from a set. The title of the negative scan reflects the purchaser’s name
Parametricity Versus the Universal Type
No full textThere has long been speculation in the scientific literature on how to dynamically enforce parametricity such as that yielded by System F. Almost 20 years ago, Sumii and Pierce proposed a formal compiler from System F into the cryptographic lambda calculus: an untyped lambda calculus extended with an idealised model of encryption. They conjectured that this compiler was fully abstract, i.e. that compiled terms are contextually equivalent if and only if the original terms were, a property that can be seen as a form of secure compilation. The conjecture has received attention in several other publications since then, but remains open to this day.
More recently, several researchers have been looking at gradually-typed languages that extend System F. In this setting it is natural to wonder whether embedding System F into these gradually-typed languages preserves contextual equivalence and thus parametricity.
In this paper, we answer both questions negatively. We provide a concrete counterexample: two System F terms whose contextual equivalence is not preserved by the Sumii-Pierce compiler, nor the embedding into the polymorphic blame calculus. This counterexample relies on the absence in System F of what we call a universal type, i.e., a type that all other types can be injected into and extracted from. As the languages in which System F is compiled have a universal type, the compilation cannot be fully abstract; this paper explains why.
We believe this paper thus sheds light on recent results in the field of gradually typed languages and it provides a perspective for further research into secure compilation of polymorphic languages.sponsorship: (Dominique Devriese holds a Postdoctoral fellowship from the Research Foundation Flanders (FWO). This research is partially funded by project grants from the Research Fund KU Leuven, and from the Research Foundation Flanders (FWO). This work was partially supported by the German Federal Ministry of Education and Research (BMBF) through funding for the CISPA-Stanford Center for Cybersecurity (FKZ: 13N1S0762). The authors thank Phil Wadler for interesting comments and suggestions.)status: Publishe
Semantics for Prolog with Cut – Revisited
No full textThis paper revisits the semantics for Prolog with cut from the perspective of formulating a semantic base that is amenable to abstract interpretation. It argues that such a semantics should separate the question of divergence from questions pertaining to the number of answers and determinacy. It also shows how to replace prefix ordering, that is classically used in these semantics, with a domain that is setup for abstraction, whilst simultaneously retaining a fixpoint construction, albeit one in a stratified form
Discovering Key Activation Hotspots in the M₂ Muscarinic Receptor
No full textアセチルコリン受容体活性化の鍵を発見 --次世代薬剤設計の可能性を拡げるGPCRメカニズム解明の新たな一歩-- . 京都大学プレスリリース. 2025-03-17.The M₂ muscarinic receptor (M₂R) is a prototypical G protein-coupled receptor (GPCR) that serves as a model system for understanding ligand recognition and GPCR activation. Here, using vibrational spectroscopy, we identify the mechanisms governing M₂R activation by its native agonist, acetylcholine. Combined with mutagenesis, computational chemistry, and organic synthetic chemistry, our analyses found that the precise distance between acetylcholine and Asn404, one of the amino acids constituting the ligand-binding site, is important for M₂R activation and that the N404Q mutant undergoes partial active state-like conformational changes. We discovered that a water molecule bridging acetylcholine and Asn404 forms a precise and flexible hydrogen bond network, triggering the outward movement of transmembrane helix 6 in M₂R. Consistent with this observation, disruptions in this hydrogen bond network via chemical modification at the α- or β-position of acetylcholine failed to activate M₂R. Collectively, our findings pinpoint Asn404 as a critical residue that both senses acetylcholine binding and induces M₂R activation
A generic operational metatheory for algebraic effects
No full textWe provide a syntactic analysis of contextual preorder and equivalence for a polymorphic programming language with effects. Our approach applies uniformly across a range of algebraic effects, and incorporates, as instances: errors, input/output, global state, nondeterminism, probabilistic choice, and combinations thereof. Our approach is to extend Plotkin and Power’s structural operational semantics for algebraic effects (FoSSaCS 2001) with a primitive “basic preorder” on ground type computation trees. The basic preorder is used to derive notions of contextual preorder and equivalence on program terms. Under mild assumptions on this relation, we prove fundamental properties of contextual preorder (hence equivalence) including extensionality properties and a characterisation via applicative contexts, and we provide machinery for reasoning about polymorphism using relational parametricity
Evidence that endogenous GRP in rat stomach mediates omeprazole-induced hypergastrinemia
No full text To investigate the physiological role of endogenous gastrin-releasing peptide (GRP) in regulating the release of gastrin, we evaluated the response of intragastric pH, gastrin, and GRP after omeprazole treatment in rats. A significant elevation of the plasma level of GRP (P< 0.01) and a significant reduction of the antral content of GRP (P <0.05) were observed after the administration of 100 mg/kg omeprazole. The antral content of GRP was significantly decreased 12 h after omeprazole administration and thereafter gradually returned to control levels. Peak values for intragastric pH and plasma GRP were observed 3 h after omeprazole administration and before the peak of serum gastrin. The bombesin antagonist [D-Phe6]-bombesin-(6,13)-methyl ester significantly inhibited gastrin release after omeprazole treatment (P < 0.05). These observations indicate that omeprazole-induced inhibition of acid secretion stimulates the release of GRP and suggest that the secretion of GRP induced by omeprazole may stimulate the secretion of gastrin, at least in the early phase. </jats:p
The Serum Levels of Endothelium Nitric Oxide Synthase in Positive Cases for Helicobacter pylori Stool Antigen
No full textBackground & Objectives: Endothelium nitric oxide synthase (eNOS) is a type of enzyme
which produces an endogenous factor called nitric oxide (NO). NO plays important role in
progress of euplastic diseases. In chronic gastritis, the increased level of NO causes damages
to DNA. The aim of present study is to evaluate eNOS concentration in sera of healthy people
and those infected by Helicobacter pylori.
Methods: The sera and stool specimens from 84 voluntaries (Female: 58.3%, Males 41.6%)
were collected. Helicobacter pylori antigen in the stool specimens and eNOS levels in sera
were determined using ELISA. Obtained data were analyzed using Excell software.
Results: The age range was from 1 to 78 years old (Mean: 30 years old). In terms of special
diseases, 70.2% did not have any special diseases, but 29.76% showed at least one special
disease, mainly thyroid disease and hypertension. The results for H. pylori stool antigen
detection showed that 16.6%, 29.76% and 53.57% of collected specimens were equivocal,
Helicobacter pylori negative and positive respectively. Comparison of sera concentrations of
eNOS showed that there is no significant change among these three groups.
Conclusion: As mentioned in results, the eNOS sera concentrations showed no significant
change in Helicobacter pylori positive and negative groups. Albeit the other studies showed
the significant increase in serum concentration of Helicobacter pylori positive patient, this
controversy may arise from race and variations in Helicobacter pylori pathogenic islands such
as those containing VacA and CagA. We propose to conduct a similar study in Ardabil to
focus on the pathogenic islands of H. pylori strains in this province
Studies of Halogen Bonding Induced by Pentafluorosulfanyl Aryl Iodides: A Potential Group of Halogen Bond Donors in a Rational Drug Design
No full textThe activation of halogen bonding by the substitution of the pentafluoro-λ6-sulfanyl (SF5) group was studied using a series of SF5-substituted iodobenzenes. The simulated electrostatic potential values of SF5-substituted iodobenzenes, the ab initio molecular orbital calculations of intermolecular interactions of SF5-substituted iodobenzenes with pyridine, and the 13C-NMR titration experiments of SF5-substituted iodobenzenes in the presence of pyridine or tetra (n-butyl) ammonium chloride (TBAC) indicated the obvious activation of halogen bonding, although this was highly dependent on the position of SF5-substitution on the benzene ring. It was found that 3,5-bis-SF5-iodobenzene was the most effective halogen bond donor, followed by o-SF5-substituted iodobenzene, while the m- and p-SF5 substitutions did not activate the halogen bonding of iodobenzenes. The similar ortho-effect was also confirmed by studies using a series of nitro (NO2)-substituted iodobenzenes. These observations are in good agreement with the corresponding Mulliken charge of iodine. The 2:1 halogen bonding complex of 3,5-bis-SF5-iodobenzene and 1,4-diazabicyclo[2.2.2]octane (DABCO) was also confirmed. Since SF5-containing compounds have emerged as promising novel pharmaceutical and agrochemical candidates, the 3,5-bis-SF5-iodobenzene unit may be an attractive fragment of rational drug design capable of halogen bonding with biomolecules
Linking Unit Tests and Properties
No full textQuickCheck allows us to verify software against particular proper- ties. A property can be regarded as an abstraction over many unit tests. QuickCheck uses generated random input data to test such properties. If a counterexample is found, it becomes immediately clear what we have tested. This is not the case when all tests pass, since we do not (and shall not) see the actual generated test cases. How can we be sure about what is tested? QuickCheck has the ability to gather statistics about the test cases, which is insightful. But still it does not tell us whether the particular unit test scenarios we have in mind are included. For this reason, we have developed a tool that can answer this question. It checks if a given unit test can be generated by a property, making it easier to judge the property’s quality. We have applied our tool to an industrial use case of testing the AUTOSAR basic software modules and shows that it can handle complex models and large unit tests
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