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Academic literature on the topic 'HSDH'

Author: Grafiati

Published: 9 March 2023

Last updated: 11 March 2023

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Journal articles on the topic "HSDH"

Gao, Miaomiao, Kaili Nie, Meng Qin, Haijun Xu, Fang Wang, and Luo Liu. "Molecular Mechanism Study on Stereo-Selectivity of α or β Hydroxysteroid Dehydrogenases." Crystals 11, no. 3 (February 25, 2021): 224. http://dx.doi.org/10.3390/cryst11030224.

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Hydroxysteroid dehydrogenases (HSDHs) are from two superfamilies of short-chain dehydrogenase (SDR) and aldo–keto reductase (AKR). The HSDHs were summarized and classified according to their structural and functional differences. A typical pair of enzymes, 7α–hydroxysteroid dehydrogenase (7α–HSDH) and 7β–hydroxysteroid dehydrogenase (7β–HSDH), have been reported before. Molecular docking of 7-keto–lithocholic acid(7–KLA) to the binary of 7β–HSDH and nicotinamide adenine dinucleotide phosphate (NADP+) was realized via YASARA, and a possible binding model of 7β–HSDH and 7–KLA was obtained. The α side of 7–KLA towards NADP+ in 7β–HSDH, while the β side of 7–KLA towards nicotinamide adenine dinucleotide (NAD+) in 7α–HSDH, made the orientations of C7–OH different in products. The interaction between Ser193 and pyrophosphate of NAD(P)+ [Ser193–OG⋯3.11Å⋯O1N–PN] caused the upturning of PN–phosphate group, which formed a barrier with the side chain of His95 to make 7–KLA only able to bind to 7β–HSDH with α side towards nicotinamide of NADP+. A possible interaction of Tyr253 and C24 of 7–KLA may contribute to the formation of substrate binding orientation in 7β–HSDH. The results of sequence alignment showed the conservation of His95, Ser193, and Tyr253 in 7β–HSDHs, exhibiting a significant difference to 7α–HSDHs. The molecular docking of other two enzymes, 17β–HSDH from the SDR superfamily and 3(17)α–HSDH from the AKR superfamily, has furtherly verified that the stereospecificity of HSDHs was related to the substrate binding orientation.

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Wang, Rui, Jiaquan Wu, David Kin Jin, Yali Chen, Zhijia Lv, Qian Chen, Qiwei Miao, Xiaoyu Huo, and Feng Wang. "Structure of NADP+-bound 7β-hydroxysteroid dehydrogenase reveals two cofactor-binding modes." Acta Crystallographica Section F Structural Biology Communications 73, no. 5 (April 26, 2017): 246–52. http://dx.doi.org/10.1107/s2053230x17004460.

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In mammals, bile acids/salts and their glycine and taurine conjugates are effectively recycled through enterohepatic circulation. 7β-Hydroxysteroid dehydrogenases (7β-HSDHs; EC 1.1.1.201), including that from the intestinal microbeCollinsella aerofaciens, catalyse the NADPH-dependent reversible oxidation of secondary bile-acid products to avoid potential toxicity. Here, the first structure of NADP+bound to dimeric 7β-HSDH is presented. In one active site, NADP+adopts a conventional binding mode similar to that displayed in related enzyme structures. However, in the other active site a unique binding mode is observed in which the orientation of the nicotinamide is different. Since 7β-HSDH has become an attractive target owing to the wide and important pharmaceutical use of its product ursodeoxycholic acid, this work provides a more detailed template to support rational protein engineering to improve the enzymatic activities of this useful biocatalyst, further improving the yield of ursodeoxycholic acid and its other applications.

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Ferreira, Renato Rodrigues, Ariane Vendemiatti, Lyndel Wayne Meinhardt, Peter John Lea, and Ricardo Antunes Azevedo. "Isolation of enzymes involved in threonine biosynthesis from sorghum seeds." Brazilian Journal of Plant Physiology 16, no. 2 (August 2004): 95–104. http://dx.doi.org/10.1590/s1677-04202004000200005.

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Cereal seeds are poor in essential amino acids, particularly lysine, tryptophan and threonine. The amino acids lysine and threonine are synthesized in the aspartate pathway. Although most of the enzymes of the aspartate pathway have been isolated and characterized in higher plant species, the metabolism of lysine and threonine is totally unknown in sorghum. We have isolated two enzymes, aspartate kinase (AK) and homoserine dehydrogenase (HSDH) from sorghum. Optimum assay conditions were established for the determination of AK and HSDH activities. The highest level of activity was observed in immature seeds. AK was shown to be inhibited by threonine and lysine indicating the existence of at least two isoenzymes, one sensitive to threonine inhibition and the other sensitive to lysine inhibition with the latter being predominant in sorghum seeds. HSDH was shown to be inhibited by threonine indicating the existence of a threonine-sensitive HSDH, however, most of the activity was not inhibited by threonine, suggesting the existence of a second predominant isoenzyme of HSDH resistant to threonine inhibition.

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Prabha, V., Meenakshi Gupta, and K. G. Gupta. "Kinetic properties of 7α-hydroxysteroid dehydrogenase from Escherichia coli 080." Canadian Journal of Microbiology 35, no. 12 (December 1, 1989): 1076–80. http://dx.doi.org/10.1139/m89-180.

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Results on the kinetics of 7α-hydroxysteroid dehydrogenase 7α-HSDH showed that this enzyme could oxidize all bile acids having an –OH group at the C-7 position. Lineweaver-Burk plots showed Michaelis constant (Km) values of 0.83 and 0.12 mM for cholic acid and chenodeoxycholic acid, respectively. The effect of enzyme concentration on the reaction velocity showed a constant increase in the enzyme activity with increase in enzyme-protein concentration. 7α-HSDH was activated by Na+, K+, Ca2+, and Mn2+ ions and by reducing agents having a thiol group (dithiothreitol, 2-mercaptoethanol). Co2+, Hg2+, Fe3+, Mg2+, Zn2+, Ba2+, and Cu2+ ions, chelating agents (potassium oxalate, heparin, EDTA), oxidizing agents (sodium perchlorate, sodium periodate, sodium persulphate), and detergents (Tween 20, Tween 40, Tween 80, Triton X-100, sodium lauryl sulphate) were inhibitory to 7α-HSDH activity.Key words: 7α-hydroxysteroid dehydrogenase, bile acids, NAD+, Escherichia coli 080, enzyme kinetics.

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Ji, Qingzhi, Bochu Wang, Chou Li, Jinglan Hao, and Wenjing Feng. "Co-immobilised 7α- and 7β-HSDH as recyclable biocatalyst: high-performance production of TUDCA from waste chicken bile." RSC Advances 8, no. 60 (2018): 34192–201. http://dx.doi.org/10.1039/c8ra06798h.

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Isogai, Shota, and Hiroshi Takagi. "Enhancement of lysine biosynthesis confers high-temperature stress tolerance to Escherichia coli cells." Applied Microbiology and Biotechnology 105, no. 18 (August 29, 2021): 6899–908. http://dx.doi.org/10.1007/s00253-021-11519-0.

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Abstract Lysine, a nutritionally important amino acid, is involved in adaptation and tolerance to environmental stresses in various organisms. Previous studies reported that lysine accumulation occurs in response to stress and that lysine supplementation enhances stress tolerance; however, the effect of lysine biosynthesis enhancement on stress tolerance has yet to be elucidated. In this study, we confirmed that lysine supplementation to the culture medium increased intracellular lysine content and improved cell growth of Escherichia coli at high temperature (42.5 °C). Lysine-overproducing strains were then isolated from the lysine analogue S-adenosylmethionine-resistant mutants by conventional mutagenesis and exhibited higher tolerance to high-temperature stress than the wild-type strain. We identified novel amino acid substitutions Gly474Asp and Cys554Tyr on ThrA, a bifunctional aspartate kinase/homoserine dehydrogenase (AK/HSDH), in the lysine-overproducing mutants. Interestingly, the Gly474Asp and Cys554Tyr variants of ThrA induced lysine accumulation and conferred high-temperature stress tolerance to E. coli cells. Enzymatic analysis revealed that the Gly474Asp substitution in ThrA reduced HSDH activity, suggesting that the intracellular level of aspartate semialdehyde, which is a substrate for HSDH and an intermediate for lysine biosynthesis, is elevated by the loss of HSDH activity and converted to lysine in E. coli. The present study demonstrated that both lysine supplementation and lysine biosynthesis enhancement improved the high-temperature stress tolerance of E. coli cells. Our findings suggest that lysine-overproducing strains have the potential as stress-tolerant microorganisms and can be applied to robust host cells for microbial production of useful compounds. Key points • Lysine supplementation improved the growth of E. coli cells at high temperature. • The G474D and C554Y variant ThrA increased lysine productivity in E. coli cells. • The G474D substitution in ThrA reduced homoserine dehydrogenase activity. • E. coli cells that overproduce lysine exhibited high-temperature stress tolerance.

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Tsachaki, Maria, Arne Meyer, Benjamin Weger, Denise V. Kratschmar, Janina Tokarz, Jerzy Adamski, Heinz-Georg Belting, Markus Affolter, Thomas Dickmeis, and Alex Odermatt. "Absence of 11-keto reduction of cortisone and 11-ketotestosterone in the model organism zebrafish." Journal of Endocrinology 232, no. 2 (February 2017): 323–35. http://dx.doi.org/10.1530/joe-16-0495.

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Zebrafish are widely used as model organism. Their suitability for endocrine studies, drug screening and toxicity assessements depends on the extent of conservation of specific genes and biochemical pathways between zebrafish and human. Glucocorticoids consist of inactive 11-keto (cortisone and 11-dehydrocorticosterone) and active 11β-hydroxyl forms (cortisol and corticosterone). In mammals, two 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 11β-HSD2) interconvert active and inactive glucocorticoids, allowing tissue-specific regulation of glucocorticoid action. Furthermore, 11β-HSDs are involved in the metabolism of 11-oxy androgens. As zebrafish and other teleost fish lack a direct homologue of 11β-HSD1, we investigated whether they can reduce 11-ketosteroids. We compared glucocorticoid and androgen metabolism between human and zebrafish using recombinant enzymes, microsomal preparations and zebrafish larvae. Our results provide strong evidence for the absence of 11-ketosteroid reduction in zebrafish. Neither human 11β-HSD3 nor the two zebrafish 11β-HSD3 homologues, previously hypothesized to reduce 11-ketosteroids, converted cortisone and 11-ketotestosterone (11KT) to their 11β-hydroxyl forms. Furthermore, zebrafish microsomes were unable to reduce 11-ketosteroids, and exposure of larvae to cortisone or the synthetic analogue prednisone did not affect glucocorticoid-dependent gene expression. Additionally, a dual-role of 11β-HSD2 by inactivating glucocorticoids and generating the main fish androgen 11KT was supported. Thus, due to the lack of 11-ketosteroid reduction, zebrafish and other teleost fish exhibit a limited tissue-specific regulation of glucocorticoid action, and their androgen production pathway is characterized by sustained 11KT production. These findings are of particular significance when using zebrafish as a model to study endocrine functions, stress responses and effects of pharmaceuticals.

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Husen, B., N. Psonka, M. Jacob-Meisel, C. Keil, and GM Rune. "Differential expression of 17beta-hydroxysteroid dehydrogenases types 2 and 4 in human endometrial epithelial cell lines." Journal of Molecular Endocrinology 24, no. 1 (February 1, 2000): 135–44. http://dx.doi.org/10.1677/jme.0.0240135.

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In the endometrium two enzymes are known to convert estradiol to its inactive metabolite estrone: microsomal 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) and peroxisomal 17beta-HSD4. In order to elucidate the particular function of each of these two different enzymes, the human endometrial epithelial cell lines HEC-1-A and RL95-2 were examined with respect to the expression of 17betaHSD isozymes. They were compared with human endometrium in vivo. Non-radioactive in situ hybridization revealed both enzymes in glandular epithelial cells of human endometrium. The two cell lines were screened for mRNA expression of 17beta-HSD 1-4 by RT-PCR and Northern blot. 17beta-HSD2 and 4 could be detected by either method, 17beta-HSD1 only by RT-PCR, 17beta-HSD3 not at all. Both cell lines were proven to have no receptor for progesterone which is known as a physiological inducer of several 17beta-HSD isozymes. To study the regulation of 17beta-HSD2 and 17betaHSD4, the concentration of fetal calf serum in the cell culture media was reduced stepwise to 0.3% by dilution with a defined serum replacement. This treatment led to an inhibition of 17beta-HSD2 mRNA expression and an increase in the mRNA expression of 17beta-HSD4. Concomitantly, distinct morphological changes were observed, such as a decrease in the number and length of microvilli and a decrease in the formation of domes on top of the monolayers. The endometrial epithelial cell lines HEC-1-A and RL95-2 represent a suitable in vitro model for further studies of the differential expression of the major endometrial HSD isozymes, independent of the effect of progesterone.

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Miro, P., M. L. Marin, and M. A. Miranda. "Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls." Organic & Biomolecular Chemistry 14, no. 9 (2016): 2679–83. http://dx.doi.org/10.1039/c5ob02561c.

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The aim of the present paper is to explore the potential of radical-mediated dehydrogenation of bile salts (BSs), which is reminiscent of the enzymatic action of hydroxysteroid dehydrogenase enzymes (HSDH).

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Zhou, L. Y., D. S. Wang, B. Senthilkumaran, M. Yoshikuni, Y. Shibata, T. Kobayashi, C. C. Sudhakumari, and Y. Nagahama. "Cloning, expression and characterization of three types of 17β-hydroxysteroid dehydrogenases from the Nile tilapia, Oreochromis niloticus." Journal of Molecular Endocrinology 35, no. 1 (August 2005): 103–16. http://dx.doi.org/10.1677/jme.1.01801.

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In order to elucidate the roles of 17β-HSDs in fish gonadal steroidogenesis, three types of 17β-HSDs (17β-HSD1, 17β-HSD8 and putative 17β-HSD12) were cloned and characterized from the Nile tilapia, Oreochromis niloticus. The cloned cDNAs of 17β-HSD type 1, 8 and 12 were 1504, 1006 and 1930 bp long, with open reading frames encoding proteins of 289, 256 and 314 aminoacids, respectively. Tissue distribution pattern analyzed by RT-PCR and Northern blot showed that 17β-HSD1 was dominantly expressed in the ovary, while the putative 17β-HSD12, one of the two duplicates found in fish, is a male specific enzyme and expressed exclusively in testis (detected by RT-PCR only). On the other hand, 17β-HSD8 was expressed in the brain, gill, heart, liver, intestine, gonad, kidney and muscle of both male and female. Enzymatic assays of the three types of 17β-HSDs were performed using recombinant proteins expressed in E. coli or HEK 293 cells. Tilapia 17β-HSD1 expressed in E. coli had the preference for NADP(H) as cofactor and could catalyze the inter-conversion between estrone and estradiol efficiently as well as the inter-conversion between androstenedione and testosterone, but less efficiently. Tilapia 17β-HSD8 recombinant protein expressed in HEK 293 cells could catalyze the conversion of testosterone to androstenedione, as well as the inter-conversion between estrone and estradiol. However, the putative 17β-HSD12 expressed in E. coli or in HEK 293 cells showed no conversion to any of the four substrates tested in this study. Based on enzyme characterization and tissue distribution, it is plausible to attribute crucial roles to 17β-HSDs in the gonadal steroidogenesis of teleosts.

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Dissertations / Theses on the topic "HSDH"

Argueso, Cristiana Morgado dos Guimarães Teixeira. "Identificação e purificação parcial de isoenzimas da aspartato quinase (AK) e homoserina desidrogenase (HSDH) de sementes de arroz (Oriza sativa) : evidencias para a existencia de um polipeptideo bifuncional com atividades de AK e HSDH." [s.n.], 1997. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317254.

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Orientador: RIcardo Antunes de Azevedo
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-07-23T00:01:31Z (GMT). No. of bitstreams: 1 Argueso_CristianaMorgadodosGuimaraesTeixeira_M.pdf: 7441540 bytes, checksum: 47e2d4385d38c27ba690c5c89a9ab5e0 (MD5) Previous issue date: 1997
Mestrado
Genetica de Plantas
Mestre em Ciências Biológicas

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BERTULETTI, SUSANNA. "EXPLOITING OXIDOREDUCTASES, HYDROLASES AND TRANSAMINASES AS STEREO- AND REGIO-SELECTIVE BIOCATALYSTS IN ORGANIC SYNTHESIS." Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/886073.

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The thesis concerns the use of different enzyme classes (namely, oxidoreductases, transferases, and hydrolases) as biocatalysts to achieve the chemo-, regio- and stereo-selective green synthesis of pharmaceutically relevant compounds. The main work has been done with hydroxysteroid dehydrogenases, redox enzymes that naturally work on steroids, which were studied with two main purposes: to shorten the synthesis of valuable bile acids already sold as drugs or with potential biomarker application, and to synthesize active pharmaceutical ingredients of non-steroidal nature. The work has been completed by the study on a peculiar, extremely resistant, redox enzyme, which was isolated from a metagenome in search for novel thermostable hydroxyxsteroid dehydrogenases.

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Baum, Oliver. "HSOH an elusive species with many different traits." Göttingen Cuvillier, 2008. http://d-nb.info/991202996/04.

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Pereira, Laura E. "11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2), molecular structure and regulation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0006/MQ32501.pdf.

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White, Christopher Iain. "Cardiovascular 11β-HSD1 : its role in myocardial physiology and pathophysiology." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23391.

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Glucocorticoid production by the adrenal gland is regulated by hypothalamicpituitary- adrenal (HPA) axis activity. Within cells, glucocorticoid levels are modulated by 11β-hydroxysteroid dehydrogenase (11β-HSD), which interconverts active and intrinsically inert glucocorticoids. Glucocorticoids have widespread physiological effects and, in the cardiovascular system, they play a crucial role in heart development and maturation, blood pressure control, and myocardial calcium cycling. Mice which are unable to regenerate the physiological glucocorticoid, corticosterone, from 11-dehydrocorticosterone due to deletion of the type 1 11β-HSD isozyme (11β-HSD1) have previously been shown to have smaller, lighter hearts but unaltered systolic function. Moreover, a single nucleotide polymorphism (SNP) in the Hsd11b1 gene has been associated with reduced left ventricular mass in humans, suggesting a role for 11β-HSD1 in regulating cardiac size. After myocardial infarction (MI), 11β-HSD1 deficient mice have an augmented inflammatory response, increased numbers of pro-reparative alternatively-activated macrophages in the heart, enhanced peri-infarct angiogenesis and improved cardiac function compared to C57BL/6 controls. However, the role of ‘cardiovascular’ 11β-HSD1 in the development of these phenotypes, both basally and after MI, is unknown. It was hypothesised that ‘cardiovascular’ 11β-HSD1 deficiency would result in smaller hearts, and that this selective deletion would lead to altered calcium handling protein expression and diastolic abnormalities. Furthermore, it was hypothesised that ‘cardiovascular’ 11β-HSD1 deletion would reproduce the beneficial post-MI phenotype previously seen in global 11β-HSD1 deficient mice. The first aim was to characterise the cardiac phenotype of mice with global deletion of 11β-HSD1 (DelI mice), and mice in which deletion is restricted to cardiomyocytes and vascular smooth muscle cells (SMAC mice). SMAC mice have ‘floxed’ 11β- HSD1 alleles and a Cre recombinase transgene inserted into the Sm22α gene. Sm22α is expressed in vascular smooth muscle cells, and transiently in cardiomyocytes during development. Thus, Cre expression in these cells results in deletion of exon three of the Hsd11b1 gene and gives rise to a non-functional protein. Controls for DelI mice were C57BL/6 mice, and controls for SMAC mice were their Cre- littermates. DelI, but not SMAC, mice have smaller, lighter hearts, which may be explained by their shorter cardiomyocytes measured following isolation using a Langendorff preparation. Cardiomyocyte cross-sectional area is unchanged. In vivo measurement of cardiac function using ultrasound imaging showed systolic function is comparable between DelI mice and SMAC mice and their respective controls. However, there is mild diastolic dysfunction in both DelI and SMAC mice, characterised by reduced E wave deceleration and an increased mitral valve deceleration time. This phenotype occurred following pharmacological inhibition of 11β-HSD1, by administration of UE2316, a selective 11β-HSD1 inhibitor, to adult C57BL6/SJL mice. While ventricular collagen content is unaltered in DelI, SMAC and UE2316-treated mice compared to their respective controls, expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA) is reduced, suggesting that altered calcium handling, rather than changes in stiffness, may underlie this phenotype. The second aim was to determine whether the beneficial acute outcomes seen previously in 11β-HSD1 deficient mice after MI could be reproduced by selective cardiovascular deletion of the enzyme. Seven days after MI, compared to Cre- littermate controls, SMAC mice have similar peri-infarct angiogenesis, total macrophage and alternatively-activated macrophage infiltration into the heart, infarct size, ventricular dilatation and systolic function. This suggests 11β-HSD1 deletion in another cell type, or types, is responsible for the phenotype seen in global 11β-HSD1 deficient mice. The final aim was to assess the impact of global 11β-HSD1 deficiency and ‘cardiovascular’ 11β-HSD1 deletion on the development of heart failure, using magnetic resonance imaging to determine structure and function. Eight weeks after MI, mice globally deficient in 11β-HSD1 have attenuated expression of ANP and β- MHC, RNA markers of heart failure, and show attenuated pulmonary oedema, reduced chamber dilatation, preserved systolic function and smaller infarcts compared to control. None of these parameters are altered in SMAC mice relative to control. In conclusion, the data presented in this thesis shows that cardiovascular 11β-HSD1 influences physiological cardiac function, potentially through regulation of calcium handling. 11β-HSD1 in other cells influences cardiomyocyte length, resulting in smaller hearts in its absence. Despite this, global 11β-HSD1 deficiency prevents heart failure development after MI, suggesting that pharmacological inhibition of 11β-HSD1 may be of benefit in treating this condition. Cardiovascular 11β-HSD1 does not, however, account for the changes in infarct healing or remodelling associated with this beneficial outcome, therefore these effects must be related to 11β-HSD1 deficiency elsewhere, such as fibroblasts or myeloid cells.

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Leiva, Martínez Rosana. "Polycyclic group optimization in 11β-HSD1 inhibitors and their pharmacological evaluation." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/457770.

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The present PhD Thesis evolves around the design, synthesis and pharmacological evaluation of novel 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors. Given that the enzyme active site includes a hydrophobic pocket to accommodate bulky lipophilic scaffolds, the main objective was focused on the study of new 11β-HSD1 inhibitors exploring different hydrophobic polycyclic substituents. 11β-HSD1 catalyzes the cortisol regeneration from its inactive form cortisone in tissues mainly expressing glucocorticoid (GC) receptors, such as liver, adipose and brain. GCs are well known hormones that play a major role in our organism. It is well accepted that the GC concentration in peripheral tissues not only depends on the adrenal secretion but also on the intracellular metabolism in these tissues, namely by 11β-HSD1. During the last years, both academia and industry have made great efforts to develop 11β-HSD1 inhibitors to target diseases such as type 2 diabetes and Alzheimer’s. The general structure of these molecules consists on a bulky lipophilic group –usually an adamantyl- linked by an amide core to a right-hand side (RHS) substituent. The first goal was the development of a new polycyclic amine, the 2-oxaadamantan-5- amine, to add to our library of polycyclic substituents (Chapter 3). The target amine was envisioned to contain an oxygen atom in its hydrophobic skeleton to mimic the structure of some hydroxylated adamantyl derivatives in development. Its synthesis involved consecutive Criegee rearrangements on 2-methyl-2-adamantanol to deliver the 2- oxaadamantane, which was then functionalized by C-H activation using phase-transfer catalysis. Finally, a Ritter reaction followed by deprotection with thiourea delivered the desired 2-oxaadamantan-5-amine. The second objective of the present thesis was the synthesis of a small series of 1- and 2-adamantyl-based 11β-HSD1 inhibitors, as most of the 11β-HSD1 inhibitors evaluated are 2-adamantyl substituted derivatives and no comparison with their C-1 isomers was available. Moreover, considering that very few heteroadamantanes have been studied in 11β-HSD1 inhibitors, we also evaluated the introduction of the previously synthesized 5-substituted 2-oxaadamantane (Chapter 4). 1 Focusing on the main goal, it is reported the exploration of other hydrophobic polycyclic substituents as replacement of adamantane with a design supported by molecular modeling studies in order to optimize the filling of the hydrophobic pocket in the binding site (Chapter 5). This work let us to a new family of potent 11β-HSD1 inhibitors featuring unexplored pyrrolidine-based polycyclic substituents. The in vitro biological profiling of the compounds permitted us to select a proper candidate for an in vivo study in a rodent model of cognitive dysfunction. The results supported the neuroprotective effect of 11β- HSD1 inhibition in cognitive decline related to the aging process, since the treatment prevented memory deficits through a reduction of neuroinflammation and oxidative stress, and an increase of the abnormal proteins degradation in the brain. An additional in vivo study in a model of cognitive dysfunction and metabolic disease is currently ongoing to study how 11β-HSD1 inhibition can modulate these two linked disorders, as so-called type 3 diabetes. Finally, the focus was on the exploration of different substituents in the RHS of the molecule to further improve potency, selectivity and metabolic stability. The endeavour started integrating different aromatic, heteroaromatic, heterocycloalkyl and branched alkyl substituents generating diversity to build some structure-activity relationship (SAR) information (Chapter 6). From this work we obtained potent nanomolar inhibitors but still without the needed selectivity and stability properties. In light of these results, we started a rational design of new substitution patterns in order to establish additional interactions that would deliver more potent and selective inhibitors (Chapter 7). The pharmacological tests revealed some low nanomolar activities together with good metabolic stabilities, although selectivity over the isoenzyme 11β-HSD2 remains a challenge to be accomplished.

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Craigie, Eilidh. "Investigating mechanisms of salt-sensitive hypertension in 11β-HSD2 heterozygote mice." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5565.

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The mineralocorticoid hormone, aldosterone, classically acts via the Mineralocorticoid Receptor (MR) to promote sodium transport in aldosterone target tissues, such as the kidney, thereby controlling long-term electrolyte homeostasis and blood pressure (BP). Aldosterone biosynthesis by the adrenal gland is regulated by a negative feedback loop called the Renin Angiotensin Aldosterone System (RAAS). The glucocorticoid cortisol (corticosterone in rodents), which has a very similar structure to aldosterone, shares with aldosterone an equal affinity for the MR. Typically, plasma cortisol levels are approximately 1000-fold higher than plasma aldosterone, and so the ligand specificity for aldosterone must be imposed on MR by other, non-structural, means. This specificity is important in order to retain electrolyte and BP balance within the control of the RAAS. The co-localisation of the enzyme 11β-Hydroxysteroid Dehydrogenase Type 2 (11β-HSD2) with the MR in aldosterone target tissues provides the MR with the aldosterone specificity it inherently lacks. 11β-HSD2 achieves this by converting active cortisol to its inactive 11-keto metabolite, cortisone (dehydrocorticosterone in rodents). In humans with the monogenetic Syndrome of Apparent Mineralocorticoid Excess (SAME), inactivating mutations in the HSD11B2 gene allows cortisol unregulated access to the MR. Resultant symptoms include severe hypertension and life-threatening hypokalemia. Individuals heterozygous for SAME display no overt phenotypes. However, some studies have associated SAME heterozygosity and loss-of-function polymorphisms within the HSD11B2 gene with essential and/or salt-sensitive hypertension in the general population. Targeted disruption of the Hsd11b2 gene in mice (Hsd11b2-/-) faithfully reproduces with all the major phenotypes of SAME patients. Mice heterozygote for the targeted gene (Hsd11b2+/-) have no phenotype and display a normal BP. In the present study, Hsd11b2+/- mice were used to explore the relationship between reduced 11β-HSD2 enzyme activity and salt-sensitive hypertension. On a high salt diet, Hsd11b2+/- mice were found to have increased BP and impaired natriuresis, compared to wild-type controls (Hsd11b2+/+). Further studies used pharmacological blockade of the Epithelial Sodium Channel (ENaC) and MR to ascertain the contributions of these pathways towards the observed phenotypes. These identified a deregulation of ENaC activity pertaining to an inability to regulate sodium appropriately. Investigations into the contributions of the RAAS and the Hypothalamus Pituitary Adrenal (HPA) axis have revealed valuable insights into their roles in this model. There is an implication that the RAAS has increased sensitivity in Hsd11b2+/-, further exacerbated by increased dietary sodium, and that the regulation of corticosteroids may also be altered. Novel observations have suggested that oxidative stress in response to a high salt diet could also be involved, as a study administering an antioxidant drug in conjunction with a high salt diet prevented the manifestation of a phenotype in Hsd11b2+/-. Finally, the generation of a floxed Hsd11b2 targeting construct for tissue-specific deletion of 11β-HSD2 will allow future studies into the contributions of specific 11β-HSD2 expression sites (such as the kidney) towards the phenotypes of both homozygous and heterozygous mice.

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Andres, Janin. "Untersuchungen über Regulationsmechanismen der 11beta-Hydroxysteroid Dehydrogenase Typ 1." Phd thesis, Universität Potsdam, 2008. http://opus.kobv.de/ubp/volltexte/2009/3303/.

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Die 11beta-HSD1 reguliert intrazellulär die Cortisolkonzentration durch Regeneration von Cortison z.B. aus dem Blutkreislauf, zu Cortisol. Daher stellt diese ein wichtiges Element in der Glucocorticoid-vermittelten Genregulation dar. Die 11beta-HSD1 wird ubiquitär exprimiert, auf hohem Niveau besonders in Leber, Fettgewebe und glatten Muskelzellen. Insbesondere die Bedeutung der 11beta-HSD1 in Leber und Fettgewebe konnte mehrfach nachgewiesen werden. In der Leber führte eine erhöhte Aktivität aufgrund einer Überexpression in Mäusen zu einer verstärkten Gluconeogeneserate. Des Weiteren konnte gezeigt werden, dass eine erhöhte Expression und erhöhte Enzymaktivität der 11beta-HSD1 im subkutanen und viszeralen Fettgewebe assoziiert ist mit Fettleibigkeit, Insulinresistenz und Dyslipidämie. Über die Regulation ist jedoch noch wenig bekannt. Zur Untersuchung der Promotoraktivität wurde der Promotorbereich von -3034 bis +188, vor und nach dem Translations- und Transkriptionsstart, der 11beta-HSD1 kloniert. 8 Promotorfragmente wurden mittels Dual-Luciferase-Assay in humanen HepG2-Zellen sowie undifferenzierten und differenzierten murinen 3T3-L1-Zellen untersucht. Anschließend wurde mittels nicht-radioaktiven EMSA die Bindung des TATA-Binding Proteins (TBP) sowie von CCAAT/Enhancer-Binding-Proteinen (C/EBP) an ausgewählte Promotorregionen analysiert. Nach der Charakterisierung des Promotors wurden spezifische endogene und exogene Regulatoren untersucht. Fettsäuren modifizieren die Entstehung von Adipositas und Insulinresistenz. Ihre Wirkung wird u.a. PPARgamma-abhängig vermittelt und kann durch das Inkretin (Glucose-dependent insulinotropic Peptide) GIP modifiziert werden. So wurden die Effekte von unterschiedlichen Fettsäuren, vom PPARgamma Agonisten Rosiglitazon sowie dem Inkretin GIP auf die Expression und Enzymaktivität der 11beta-HSD1 untersucht. Dies wurde in-vitro-, tierexperimentell und in humanen in-vivo-Studien realisiert. Zuletzt wurden 2 Single Nucleotide Polymorphismen (SNP) im Promotorbereich der 11beta-HSD1 in der Zellkultur im Hinblick auf potentielle Funktionalität analysiert sowie die Assoziation mit Diabetes mellitus Typ 2 und Körpergewicht in der MeSyBePo-Kohorte bei rund 1.800 Personen untersucht. Die Luciferase-Assays zeigten basal eine zell-spezifische Regulation der 11beta-HSD1, wobei in allen 3 untersuchten Zelltypen die Bindung eines Repressors nachgewiesen werden konnte. Zudem konnte eine mögliche Bindung des TBPs sowie von C/EBP-Proteinen an verschiedene Positionen gezeigt werden. Die Transaktivierungsassays mit den C/EBP-Proteinen -alpha, -beta und -delta zeigten eben-falls eine zellspezifische Regulation des 11beta-HSD1-Promotors. Die Aktivität und Expression der 11beta-HSD1 wurde durch die hier untersuchten endogenen und exogenen Faktoren spezifisch modifiziert, was sowohl in-vitro als auch in-vivo in unterschiedlichen Modellsystemen dargestellt werden konnte. Die Charakterisierung der MeSyBePo-Kohorte ergab keine direkten Assoziationen zwischen Polymorphismus und klinischem Phänotyp, jedoch Tendenzen für eine erhöhtes Körper-gewicht und Typ 2 Diabetes mellitus in Abhängigkeit des Genotyps. Der Promotor der 11beta-HSD1 konnte aufgrund der Daten aus den Luciferaseassays sowie den Daten aus den EMSA-Analysen näher charakterisiert werden. Dieser zeigt eine variable und zell-spezifische Regulation. Ein wichtiger Regulator stellen insbesondere in den HepG2-Zellen die C/EBP-Proteine -alpha, -beta und -delta dar. Aus den in-vivo-Studien ergab sich eine Regulation der 11beta-HSD1 durch endogene, exogene und pharmakologische Substanzen, die durch die Zellkulturversuche bestätigt und näher charakterisiert werden konnten.
The enzyme 11beta-HSD1 regulates intracellular the cortisol concentration by regeneration of cortisone to cortisol. Hence, 11beta-HSD1 is an important factor in glucocorticoid-mediated gene expression. It is ubiquitously expressed, but high levels have been specifically described in liver, adipose tissue and smooth muscle cells. A pivotal role for 11beta-HSD1 has been demonstrated with respect to metabolism in liver and adipose tissue. Thus, a liver-specific overexpression results in an elevated gluconeogenesis and hepatic glucose output. Furthermore, a fat-specific overexpression was associated with obesity, insulin resistance and dyslipidemia. Despite these intriguing data, the regulation of the human 11beta-HSD1 gene is still in its infancies. 8 promoter fragments from -3034 to +188 of 11beta-HSD1-gene were cloned to analyze promoter activity. Dual-Luciferase-Assay was used in humane HepG2 cells and in undifferentiated and differentiated 3T3-L1 cells. Furthermore, the region close to the transcription start was studied with a non-radioactive EMSA for binding of TATA-binding protein (TBP) and CCAAT/enhancer-binding-protein (C/EBP). The role of the endogenous and exogenous regulators fatty acids, PPARgamma and the incretin (Glucose-dependent insulinotropic Peptide) GIP was investigated in-vitro and in-vivo. Finally, the functional consequences of 2 Single Nucleotide Polymorphisms (SNP) within the promoter region were studied in cell culture and the MeSyBePo-cohorts for association with diabetes mellitus type 2 and body weight. The Luciferase-assay revealed a cell-specific regulation of 11beta-HSD1 and a repressor, which was active in all 3 cell models. Accordingly, a cell-specific regulation was observed in transactivation-assays with C/EBP-proteins -alpha, -beta and -delta. The 11beta-HSD1 enzyme expression and activity was specifically modified by the here investigated endogenous and exogenous factors, which was demonstrated in-vitro but also in-vivo in various experimental settings. The characterisation of the MeSyBePo-cohorte revealed no association between genotype and clinical phenotype, although a trend for an increased body weight and diabetes mellitus type 2 was detected. This work demonstrated a cell-specific regulation of the 11beta-HSD1 promoter. Furthermore, a binding site for TATA-binding proteins was detected in HepG2 and undifferentiated 3T3-L1 cells. A pivotal role in regulation of 11beta-HSD1 promoter activity was demonstrated for the C/EBP-proteins, especially in liver cells. The in-vivo-Studies revealed a regulation of enzyme expression and activity by endogenous, exogenous and pharmacological substances, which was confirmed and analyzed in more detail in cell culture experiments.

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Coutinho, Agnes Elizabeth. "Consequences of 11β-hydroxysteroid dehydrogenase deficiency during inflammatory responses." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4190.

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Glucocorticoids profoundly influence the immune system and pharmacological doses exert potent anti-inflammatory actions. During inflammation, glucocorticoids limit oedema and influence cell trafficking, differentiation programmes and gene transcription in glucocorticoid-sensitive leukocytes. Within cells, glucocorticoid action is modulated by a pre-receptor mechanism; glucocorticoid metabolism by the enzyme 11β- hydroxysteroid dehydrogenase (11β-HSD). Two 11β-HSD isozymes exist: 11β-HSD1, which catalyses amplification of glucocorticoid levels in intact cells by oxo-reduction of intrinsically inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone in rodents) and 11β-HSD2, which performs the opposite reaction. Thus, amplification of intracellular glucocorticoid levels by 11β-HSD1 may represent an endogenous anti-inflammatory mechanism. This hypothesis has been tested in Hsd11b1-/- mice (homozygous for a targeted disruption in the Hsd11b1 gene, encoding 11β-HSD1), using carageenan-induced pleurisy and experimental model of arthritis induced by injection of arthritogenic antibodies. In both models, Hsd11b1-/- mice showed more severe acute inflammation than control mice. During carrageenan-induced pleurisy, Hsd11b1-/- mice recruited more inflammatory cells to the pleural cavity than congenic controls, with a greater proportion of viable cells, at the onset and peak of pleurisy, suggesting a worse inflammatory response. Histological examination suggested impaired resolution of inflammation in Hsd11b1-/- mice with persistence of inflammation in the visceral pleura, activation of lymphoid aggregates, and uniquely in Hsd11b1-/- mice, formation of fibrous adhesions between lung lobes 48h after initiation of pleurisy. During experimental arthritis induced by injection of serum from arthritic K/BxN mice, clinical signs of inflammation occurred earlier in Hsd11b1-/- mice and were slower to resolve than in control mice. Histological assessment of the acute phase (2d) of arthritis showed no difference in joint pathology between genotypes, despite greater oedema and higher clinical scores in the Hsd11b1-/- mice. However, when the inflammation had resolved (21d following injection of serum), compared to control mice, Hsd11b1-/- mice showed more severe exostosis, intense periarticular inflammation, more collagen deposition and uniquely, ganglion cyst formation. At 21d, whereas basal (morning) plasma corticosterone levels were normal in control mice, they remained elevated in Hsd11b1-/- mice, suggesting ongoing inflammation and persistent activation of the hypothalamic-pituitary-adrenal axis. Mast cells are critical in the initiation of an inflammatory response and are essential in this model of arthritis. Mast cells expressed 11β-HSD1 (but not 11β-HSD2) mRNA and activity. Although mast cell number did not differ in joints or peritoneum of Hsd11b1-/- mice, 11-HSD1-deficient mast cells had a lower threshold for degranulation induced by K/BxN arthritogenic serum. As well as implicating a role for mast cell 11β-HSD1 in limiting initial inflammation in arthritis, these findings also have implications for infection, allergy and tolerance. Collectively, these data suggest that 11β-HSD1 deficiency worsens acute inflammation and results in slower resolution. Therefore, amplification of intracellular glucocorticoids levels, by 11β-HSD1, may represent an important mechanism to limit the acute inflammatory response and programme its subsequent resolution. Increasing leukocyte 11β-HSD1 or local delivery of substrate affords a novel approach for anti-inflammatory therapy.

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Zhang, Zhenguang. "Role of macrophage 11β-HSD1 in inflammation mediated angiogenesis, arthritis and obesity." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9553.

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11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by Hsd11b1) is an enzyme that predominantly converts inactive glucocorticoids (cortisone in human and most mammals, 11dehydro-corticosterone in mice and rats) into their active forms (cortisol and corticosterone, respectively). Thus 11β-HSD1 amplifies intracellular levels of glucocorticoids. Studies in globally 11β-HSD1 deficient mice have revealed changes in glucocorticoid-regulated physiological and pathological processes, including metabolism, aging, arthritis and angiogenesis. The function of macrophages, which play an important role in inflammation, is also altered. For example, 11β-HSD1 deficiency in macrophages causes a delay in their acquisition of phagocytic capacity. To dissect the role of macrophage 11β-HSD1 in angiogenesis, arthritis and obesity, both in vitro macrophage stimulation and in vivo functional assays in macrophage-specific 11β-HSD1 knockout mice, were conducted. Thioglycollate-elicited peritoneal macrophages from globally 11β-HSD1 deficient and control C57BL/6 mice were used for in vitro studies. In M1/M2 macrophage polarisation experiments, 11β-HSD1 deficient macrophages showed increased expression of mRNAs encoding pro-inflammatory factors upon lipopolysaccharide and interferon-ϒ treatment and decreased expression of pro-resolution genes with interleukin-4 stimulation. However, at cytokine or protein levels, there was little difference between the genotypes except for decrease IL12 p40 levels in 11β-HSD1 deficient macrophages. Hypoxic stress failed to show differences between genotypes in hypoxia-regulated gene expression. These data do not support a strong role for macrophage 11β-HSD1 in inflammation regulation, nor in response to hypoxia, at least when measured in vitro. The discrepancy between transcriptional and translational responses is currently unexplained, but may reflect altered posttranscriptional activity. To investigate the role of macrophage 11β-HSD1 in vivo, macrophage-specific Hsd11b1 knockout mice, LysM-Cre Hsd11b1 flox/flox (MKO) mice and Hsd11b1flox/flox littermate controls were generated. In MKO mice, 11β-HSD1 protein levels and enzyme activity were reduced by >80% in resident peritoneal macrophages. However, 11β-HSD1 protein and enzyme activity levels were unchanged or only modestly reduced in thioglycocollate-elicited peritoneal neutrophils, monocytes/macrophages, or in bone marrow-derived macrophages, despite >80% decrease in Hsd11b1 mRNA levels in these cells. A relatively long half-life of 11β-HSD1 protein compared to that of circulating myeloid cells may underlie this mismatch between transcriptional and translational expression. Furthermore, following 12 days of inflammatory arthritis induced by K/BxN serum transfer, the reduction in 11β-HSD1 protein levels in circulating neutrophils of MKO mice is consistently around 50%, which corroborates the above explanation. MKO mice and littermate controls were subjected to inflammatory models which may involve resident macrophages. First, to address the role of 11β-HSD1 in macrophages in angiogenesis, sponge implants were inserted subcutaneously into the flanks of adult male mice and harvested after 21 days. Chalkley counting on hematoxylin and eosin stained sponge sections showed significantly increased angiogenesis in MKO mice (scores: 5.2±1.0 versus 4.3±0.7; p<0.05, n=9-11). Cdh5 expression (encoding VE-cadherin, a marker of endothelial cells) was higher in sponges from MKO mice (relative expression: 1.5±0.9 versus 0.8±0.6; p<0.05), as was Il1b (encoding IL-1 beta, a marker of inflammation, relative expression: 6.5±6.4 versus 1.5±0.9; p<0.05). Vegfa mRNA (encoding vascular endothelial growth factor alpha) was unchanged, with a trend for higher Angpt1 (encoding angiopoietin 1, p=0.09) expression levels in the MKO group. These results suggest that lack of 11β- HSD1 in resident macrophages increases their pro-angiogenic activity, independently of VEGF-. The K/BxN serum transfer model of arthritis was used to investigate the role of macrophage 11β-HSD1 in arthritis. Adult male MKO and control mice received a single i.p. injection of 125μl K/BxN serum per mouse, followed by 21 days of clinical scoring to assess joint inflammation. The onset of inflammation (d1-8) was similar between MKO and control mice, but MKO mice exhibited greater clinical inflammation scores in the resolution phase of arthritis (d13-21; area-under-the-curve: 86.6±14.7 versus 60.1±13.4; p<0.005), indistinguishable from globally 11β-HSD1- deficient mice. Hematoxylin and eosin staining revealed pronounced fibroplasia predominantly in the supporting mesenchyme associated with the tenosynovium, with new bone and blood vessel formation. These results suggest that macrophage 11β-HSD1 deficiency is fully accountable for the worse arthritis resolution phenotype in the globally 11β-HSD1 deficient mice, but not the earlier onset of inflammation with global 11β-HSD1 deficiency. Macrophage activation states are closely linked with adipose insulin sensitivity. Globally 11β-HSD1 deficient mice are protected from high fat diet induced insulin resistance and adipose tissue hypoxia and fibrosis. To study the effect of macrophage 11β-HSD1 deficiency on insulin sensitivity, adult male MKO and control mice were given a 14 week high fat diet, which typically causes insulin resistance in control but not globally 11β-HSD1 KO mice. The level of fibrosis in subcutaneous adipose tissues was reduced as indicated by quantification of picrosirius red staining of collagen, though GTT data so far does not support protection from insulin resistance in MKO mice. In summary, in vitro macrophage polarisation experiments do not support a strong role of 11β-HSD in M1/M2 macrophage polarisations or response to hypoxia. However, MKO mice reveal, for the first time, an important in vivo role of macrophage 11β-HSD1 to promote angiogenesis and facilitate resolution of K/BxN serum transfer induced arthritis. Modulation of fibrosis is context dependent. Reduced adipose fibrosis may be one of the mechanisms that improve insulin sensitivity. Meanwhile, these findings suggest caution regarding the potential side effects of 11β-HSD1 inhibitors in treating metabolic disease in patients with inflammation-related co-morbidities, such as rheumatoid arthritis.

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Books on the topic "HSDH"

Kolltveit, Bård. I rute: HSD 125 år 1880-2005. Bergen: Vigmostad Bjørke, 2005.

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Bischoff, Joachim. Tatort HSH Nordbank: Über "Bankenrettungen", Landesbanken und Schlammschlachten. Hamburg: VSA-Verlag, 2010.

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Smith, Melanie A. Biochemical and biophysical characterisation of the domain structure of the HsdS subunit of EcoR124I. Portsmouth: University of Portsmouth, Institute of Biomedical and Biomolecular Sciences, 2000.

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Patel, Jaynish. The cloning, expression and mutagenesis of the recognition subunit, HsdS, from the EcoR124 R-M system. Portsmouth: University of Portsmouth, School of Biological Sciences, 1992.

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(Brazil), Programa Nacional de Doenças Sexualmente Transmissíveis/AIDS. Plano nacional de enfrentamento da epidemia de aids e das DST entre gays, HSH e travestis. Brasília: Ministério da Saúde, Secretaria de Vigilância em Saúde, Programa Nacional de DST e Aids, 2008.

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Toni, Reis, Harrad David, and Programa Nacional de Doenças Sexualmente Transmissíveis/AIDS (Brazil), eds. Projeto Somos: Desenvolvimento organizacional, Advocacy e intervenção para ONGs que trabalham com GAYS e outros HSH. Brasília, DF: Ministério da Saúde, Secretaria de Vigilância em Saúde, Programa Nacional de DST e Aids, 2005.

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Mateos, Rosa María Lara y. Vivir muriendo: La estigmatización a hombres que tienen sexo con hombres (HSH) seropositivos del puerto de Veracruz. México, D.F: Centro Nacional para la Prevención y el Control del SIDA, 2006.

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Rosa María Lara y Mateos. Vivir muriendo: La estigmatización a hombres que tienen sexo con hombres (HSH) seropositivos del puerto de Veracruz. México, D.F: Centro Nacional para la Prevención y el Control del SIDA, 2006.

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Book chapters on the topic "HSDH"

Metze, Dieter, Vanessa F. Cury, Ricardo S. Gomez, Luiz Marco, Dror Robinson, Eitan Melamed, Alexander K. C. Leung, et al. "HSH." In Encyclopedia of Molecular Mechanisms of Disease, 857. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_8504.

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Tremblay, Y., B. Marcotte, and J. F. Strauss. "Differential Regulation of 3β-HSD and 17β-HSD Expression in Granulosa Cells." In Signaling Mechanisms and Gene Expression in the Ovary, 261–67. New York, NY: Springer New York, 1991. http://dx.doi.org/10.1007/978-1-4612-3200-1_26.

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Krapf, Jill M., John E. Buster, and Andrew T. Goldstein. "Management of Hypoactive Sexual Desire Disorder (HSDD)." In Management of Sexual Dysfunction in Men and Women, 233–49. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3100-2_21.

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Jiang, Xiao-Jian, Xian-Ling Mao, Bo-Si Feng, Xiaochi Wei, Bin-Bin Bian, and Heyan Huang. "HSDS: An Abstractive Model for Automatic Survey Generation." In Database Systems for Advanced Applications, 70–86. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-18576-3_5.

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Nguyen-Quoc, T., S. Nguyen-Hoai, and D. Mai-Duc. "Static Analysis of FG-CNTRC Plates Using C0-HSDT." In Proceedings of the International Conference on Advances in Computational Mechanics 2017, 357–67. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-10-7149-2_24.

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Ricaud, J. C., and F. Lavoisier. "Optimizing the Multiple Injection Settings on an HSDI Diesel Engine." In Thermo- and Fluid Dynamic Processes in Diesel Engines 2, 199–234. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-662-10502-3_11.

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Dong, Hui, Jianxi Fan, Baolei Cheng, Yan Wang, and Jingya Zhou. "Connectivity and Routing Algorithm of the Data Center Network HSDC." In Lecture Notes in Computer Science, 407–19. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-79478-1_35.

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Yoon, Jihun, Jiwon Lee, Sunghwan Heo, Hayeong Yu, Jayeon Lim, Chi Hyun Song, SeulGi Hong, et al. "hSDB-instrument: Instrument Localization Database for Laparoscopic and Robotic Surgeries." In Medical Image Computing and Computer Assisted Intervention – MICCAI 2021, 393–402. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-87202-1_38.

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Wu, Hao, Nenggan Zheng, Hong Li, and Zonghua Gu. "GA-Based Mapping and Scheduling of HSDF Graphs on Multiprocessor Platforms." In Green, Pervasive, and Cloud Computing, 323–33. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-15093-8_23.

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Chau-Dinh, Thanh, Huong Tran-Ngoc-Diem, and Jin-Gyun Kim. "Static Analysis of HSDT-Based FGM Plates Using ES-MITC3+ Elements." In Advances in Intelligent Systems and Computing, 375–87. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-62324-1_32.

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Conference papers on the topic "HSDH"

SaiRam, K., Jayanta Mukherjee, Amit Patra, and Partha Pratim Das. "HSD-CNN." In ICVGIP 2018: 11th Indian Conference on Computer Vision, Graphics and Image Processing. New York, NY, USA: ACM, 2018. http://dx.doi.org/10.1145/3293353.3293383.

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Zhang, Jingnan, Anna Ström, and Ingrid Undeland. "Creating functional protein ingredients by cross-processing herring co-products with lingonberry press-cake, shrimp shells or green seaweed." In 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/xogq1535.

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Cross-processing herring co-products with lingonberry press-cake, shrimp shells and green seaweed (hereafter referred to as €œhelpers€) was recently reported to mitigate lipid oxidation during pH-shift-based protein isolation but had the drawback to reduce protein yield. Here, four strategies to counteract this yield-reduction were studied; optimized solubilization and precipitation pHs, increased water to raw material ratio as well as application of high shear mechanical homogenization (HSMH) and ultrasonication (US). Beyond effects on protein yield, the impacts of the process conditions on the structural, rheological and functional properties of the recovered proteins were also investigated.Increasing solubilization pH from 11.5 to 12 and decreasing precipitation pH from 5.5 to 5.0 or 4.5, as well as increasing the water-to-raw material ratio significantly improved protein yield with all helpers. Rotor-stator (RS)-HSMH and US also improved protein yield by 5-12% with a more marked effect of the type of helper. Cross-processing herring co-products with antioxidant-rich helpers substantially improved water solubility and emulsification capacity of the protein isolates but the effects of RS-HSMH and US were highly dependent on the type of helper. RS-HSMH helped in mitigating the observed negative impact of cross-processing on gel-forming capacity of protein isolates produced in presence of all three helpers; results with lingonberry press-cake were particularly promising. Altogether, tuning processing conditions as well as adding RS-HSMH and US can help in maximizing protein yield during cross-processing of herring co-products with antioxidant-containing helpers. However, the effects of processing conditions on protein functionality are intimately linked to the type of helpers. The combination of herring co-products with lingonberry press-cake was the most promising and will be subject for further studies.

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Ashrafiuon, Hashem, Nabih M. Alem, and B. Joseph McEntire. "Effects of Head-Supported Devices on the Human and Manikin Necks." In ASME 1997 Design Engineering Technical Conferences. American Society of Mechanical Engineers, 1997. http://dx.doi.org/10.1115/detc97/vib-4193.

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Abstract A comprehensive study of the effect of Head-Supported Devices (HSDs) on the neck loading during helicopter accidents is presented. The new Articulated Total Body (ATB) model which treats the neck as a deformable segment was used for crash simulation. Different categories of human and manikin subjects were considered under several crash scenarios. Simulations were theoretically designed to include a wide range of HSDs by changing their weights and C. G. (center of gravity) locations relative to the head and studying the effects of these changes. HSDs were only included as added weight and inertia to the head and their possible detachment has not been modeled in the study. Hence, two typical detachable devices were modeled and selected simulations were repeated and compared not only to provide a theoretical measure of accuracy for the original results but also to see the effect of separation of these devices from the helmet.

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Garcés, Lina, Flávio Oquendo, and Elisa Yumi Nakagawa. "Uma arquitetura de referência para sistemas de casas inteligentes de apoio ao cuidado à saúde da perspectiva de Sistemas-de-sistemas." In Anais Estendidos do Simpósio Brasileiro de Computação Aplicada à Saúde. Sociedade Brasileira de Computação (SBC), 2019. http://dx.doi.org/10.5753/sbcas.2019.6287.

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Sistemas de casas inteligentes para o cuidado da saúde (em inglês Health- care Supportive Home ou HSH) podem prover serviços de saúde nas residências de pacientes diagnosticados com uma ou múltiplas doenças crônicas, visando princi- palmente a melhoria da qualidade de vida e da autonomia, bem como a diminuição dos custos dos sistemas públicos de saúde. Contudo, sistemas HSH apresentam gran- des desafios principalmente no tocante ao projeto de sua arquitetura e que preci- sam ser de fato tratados visando sua alta qualidade e viabilidade econômica. Além disso, sistemas de HSH são na maioria dos casos constituı́dos por diversos outros sistemas que são complexos, independentes, distribuı́dos e heterogêneos, como por exemplo dispositivos médicos, sistemas de saúde eletrônica (e-Health), sistemas de informação em saúde, entre outros. Dessa forma, eles não devem ser tratados como sistemas monolı́ticos (como atualmente os são), mas sim como Sistemas-de-Sistemas (do inglês, Systems-of-Systems ou SoS). Nesse cenário, o principal objetivo desta tese foi contribuir para o projeto arquitetural de HSH-SoS 1 ; para isso, foi estabelecida a HomecARe, uma arquitetura de referência que dá suporte ao reúso sistemático do conhecimento técnico e de domı́nio, facilitando o projeto e desenvolvimento de HSH-SoS. Para estabelecer a HomecARe, foi adotado um processo sistemático que apoia a engenharia de arquiteturas de referência. Visando analisar a viabilidade e relevância da HomecARe, foi conduzido um amplo estudo de caso no qual a Ho- mecARe foi utilizada para projetar o DiaManT@Home, um HSH-SoS de apoio a pacientes com diabetes mellitus para a autogestão de sua doença. Resultados obti- dos evidenciaram a relevância e viabilidade da HomecARe possibilitando construir HSH-SoS reusáveis, interoperáveis, confiáveis, seguros e adaptativos, sendo inclu- sive uma contribuição inédita para a área de saúde eletrônica, e trazendo avanços nas áreas de arquitetura de referência e SoS.

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Zhang, Jian, Yu Chen, and Ji-feng Guo. "HSBH Algorithm Based on Chaotic Map." In 2008 Congress on Image and Signal Processing. IEEE, 2008. http://dx.doi.org/10.1109/cisp.2008.288.

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Sanguley, Leeladhar, and Samarth Purohit. "Haziness in HSD: Temperature Effect on Soluble Water Content." In ASME 2019 India Oil and Gas Pipeline Conference. American Society of Mechanical Engineers, 2019. http://dx.doi.org/10.1115/iogpc2019-4570.

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Quality parameters in petroleum products HSD/SKO/MS are being ascertained on the basis of IS standards and accordingly every OMC produces petroleum product. These products are transferred from refinery to receiving terminals through, rail, road or cross country pipelines. In a particular instance, one of the pipeline fed location in BPCL were continuously getting Haziness in diesel batches. This location was Kota terminal in Rajasthan state and the scenario was such that receipts taken through their MMBPL pipeline was Hazy in appearance. The hazy batches were required to keep ideal for almost 3–4 days to clear its appearance, however all other parameters were meeting the QC guidelines / IS standards. The peculiar behavior depicted in HSD batches was only at their end pipeline location (Kota), on other intermediate locations at upstream of Kota location, the same HSD batches were passing the appearance test. The study was undertaken to know the root cause for such phenomenon and on the basis of RCA , corrective action were implemented for altering the manufacturing process of HSD.

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Jahwari, Farooq Al, and Hani E. Naguib. "Experimental and Numerical Analysis on the Buckling Behavior of Functionally Graded Cellular Media With Extension-Capable C1 Higher Order Plate Theory." In ASME 2014 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/imece2014-39090.

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Abstract:

Polymeric cellular materials were primarily developed as means to reduce density of solid polymers and thus saving cost for applications where mechanical strength is not required like the packaging industry. Nevertheless, functionally graded cellular materials showed an attractive mechanical behavior in experimental studies. The fatigue life of porous polycarbonate (PC) with above 90% relative density is reported to be as much as four times that of a solid PC, and greater impact strength with relative density over 60%. The focus of this paper is on fabricating bio-polymeric-based functionally graded porous material with polylactic acid (PLA) and analyze the buckling behavior of their plate-like structures. The analysis includes numerical modeling supported with experimental findings. The modeling is carried out with a higher order shear deformation plate theory (HSDT) accounting for extension in the transverse direction. The proposed HSDT satisfies the constraint on the consistency of transverse shear strain energy a priori in addition to the traction conditions on plate surfaces. Few theories in the area satisfy both conditions. Finite element is used to implement the HSDT with C1 continuity using conforming elements. The through-thickness varying properties are homogenized at planar-level with the generalized self-consistent scheme. The graded cellular structure is manufactured to vary through the plate thickness while being uniform on-average for the other two planar dimensions. Constrained foaming process is adopted to control the pores’ size and structure through the plate thickness.

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Herzog, Peter. "Where is The HSDI Diesel Engine Going?" In SIAT 2004. 400 Commonwealth Drive, Warrendale, PA, United States: SAE International, 2004. http://dx.doi.org/10.4271/2004-28-0065.

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Yao, Lulu, Jing Liu, Yan Zhang, Yuejun Wang, Haiying Sun, Qingsheng Wang, Dehui Du, and Xiaohong Chen. "HSD: Hybrid MARTE Sequence Diagram." In 2015 IEEE International Conference on Software Quality, Reliability and Security (QRS). IEEE, 2015. http://dx.doi.org/10.1109/qrs.2015.35.

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Khattri, Hareesh, Narasimha Kumar V. Mangipudi, and Salvador Mandujano. "HSDL: A Security Development Lifecycle for hardware technologies." In 2012 IEEE International Symposium on Hardware-Oriented Security and Trust (HOST). IEEE, 2012. http://dx.doi.org/10.1109/hst.2012.6224330.

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Reports on the topic "HSDH"

Pfahl, Ulrich, Peter Herzog, Michael Weissbaeck, and Masashi Uchiyama. TIER II Emission Reduction Strategies for US HSDI Diesels. Warrendale, PA: SAE International, May 2005. http://dx.doi.org/10.4271/2005-08-0111.

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Markley, R. E., J. L. Elarton, and C. T. Allen. High-speed digital project, HSD test capability. Office of Scientific and Technical Information (OSTI), April 1994. http://dx.doi.org/10.2172/10146570.

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Fontanesi, Stefano, Vincenzo Gagliardi, Simone Malaguti, and Enrico Mattarelli. CFD parametric analysis of the combustion chamber shape in a small HSDI Diesel engine. Warrendale, PA: SAE International, October 2005. http://dx.doi.org/10.4271/2005-32-0094.

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Santee, William R., and Robert F. Wallace. Evaluation of Weather Service Heat Indices Using the USARIEM Heat Strain Decision Aid (HSDA) Model. Fort Belvoir, VA: Defense Technical Information Center, June 2003. http://dx.doi.org/10.21236/ada416195.

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Dubick, Michael A., Gary M. Zaucha, Don W. Korte, Wade Jr., and Charles E. Acute and Subacute Toxicity of 7.5% Hypertonic Saline/6% Dextran-70 (HSD) in Dogs. Fort Belvoir, VA: Defense Technical Information Center, November 1991. http://dx.doi.org/10.21236/ada244808.

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Dubick, M. A., J. J. Summary, J. Y. Greene, J. W. Holcroft, and C. E. Wade. Assessment of 7.5% NaCl /6% Dextran-70 (HSD) Effects on Serum or Plasma Protein Determinations. Fort Belvoir, VA: Defense Technical Information Center, December 1990. http://dx.doi.org/10.21236/ada232833.

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Cantore, Giuseppe, Stefano Fontanesi, Vincenzo Gagliardi, and Simone Malaguti. Effects of relative port orientation on the in-cylinder flow patterns in a small unit displacement HSDI Diesel Engine. Warrendale, PA: SAE International, October 2005. http://dx.doi.org/10.4271/2005-32-0093.

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Dubick, M. A., A. F. Kilani, J. J. Summary, J. Y. Greene, and C. E. Wade. Further Evaluation of the Effects of 7.5% NaCl/6% Dextran-70 (HSD) administration on Coagulation and Platelet Aggregation in Hemorrhaged and Euvolemic Swine. Fort Belvoir, VA: Defense Technical Information Center, April 1993. http://dx.doi.org/10.21236/ada266477.

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Qiao, Lijun, Yiqiang Xie, Xiujuan Xie, Hongming Hu, Tianpeng Ma, Brian Oliver, and Hui Che. The efficacy of adjunctive therapy using Huanshao Dan (HSD) in patients with dementia: A protocol for systematic review and meta-analysis of randomized controlled trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, December 2020. http://dx.doi.org/10.37766/inplasy2020.12.0082.

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Auerbach, Scott, Chad Blystone, B. Alex Merrick, Georgia Roberts, Daniel Morgan, John Bucher, Michael DeVito, et al. NTP Research Report on In Vivo Repeat Dose Biological Potency Study of Triphenyl Phosphate (CAS No. 115-86-6) in Male Sprague Dawley Rats (Hsd: Sprague Dawley SD) (Gavage Studies). NIEHS, October 2018. http://dx.doi.org/10.22427/ntp-rr-8.

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