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1. Effect of experimental type 2 diabetes complicated by pyelonephritis on ltrastructural changes in the choroid, retina and nephrons

Author

Borisov S. O., Kostiev F. I., Borisov O. V., Dekhtiar Yu. M., Vit V. V., Molchaniuk N. I., Mikheytseva I. M., Kolomiichuk S. G., and Amaied Ahmed

Subjects
ultrastructure, pyelonephritis, type 2 diabetes, choroid, retina, renal glomeruli and tubules, Internal medicine, RC31-1245
Abstract

Background: The clinical and morphological picture of diabetic microangiopathy is rather specific. Diabetic retinal ischemia can lead to irreversible damage to retinal neural elements and choroidal capillaries. Diabetic nephropathy can lead to progressive renal dysfunction and chronic renal failure. Choroidal and retinal capillaries are structurally and functionally similar to those of the intestinal mucosa and renal tissue. Purpose: To assess vascular ultrastructural changes in the choroid, retina, and renal glomerular and tubular system in a rat model of pyelonephritis in the presence of type 2 diabetes. Material and Methods: Samples were obtained from 95 Wistar rats divided into three groups: group 1 (or control group) of 30 intact animals; group 2 of 15 animals with type 2 diabetes induced by intraperitoneal streptozotocin 15.0 mg/kg for 5 consecutive days; and group 3 of 50 animals with acute pyelonephritis in the presence of type 2 diabetes (streptozotocin 35.0 mg/kg on 2 days spaced by a week). Acute pyelonephritis was induced by Escherichia coli administration (107 CFU/kg) rectally. The ultrastructure of rat choroidal, retinal and renal glomerular-and-tubular vessels was examined with electron microscopy (PEM-100-01 electron microscope). Results: In rats with induced type 2 diabetes, the most significant ocular vascular changes and renal vascular changes were found in endothelial cells. These changes included findings of vacuolar degeneration in some epithelial cells, basal membrane thickening and focal necrosis of individual epithelial cells. Vessel lumens appeared focally narrowed or expanded, with red blood cells forming clumps or sludge in lumens. Some capillaries were obliterated. These changes obviously caused secondary changes in the surrounding structures. Common ocular changes included focal destruction in retinal pigment epithelium cells, destruction of retinal photoreceptor inner segments and choroidal stromal edema. Common renal changes included destruction of the podocytes of the glomerular capillary network and homogenization of the basal membrane. Vascular ultrastructural changes in the renal glomerular system were more marked in rats with experimental type 2 diabetes and pyelonephritis than in those with type 2 diabetes only. Conclusion: Electron microscopy micrographs demonstrated the ultrastructural changes in the retinal and uveal vascular systems which were of a similar type to those in the renal glomerular-and-tubular system in rats with experimental pyelonephritis in the presence of type 2 diabetes.

Published
2022
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2. Geometry-Based Output Robust Tracking Control of a Quadrotor

Author

Borisov, O. I., Kakanov, M. A., Zhivitckii, A. Iu., and Pyrkin, A. A.

Subjects
Electrical Engineering and Systems Science - Systems and Control
Abstract

The paper solves the problem of tracking control of a quadrotor with unmeasurable pitch and roll angles based on the geometric approach with the use of the enhanced extended observer and the internal model. The proposed approach makes it possible to ensure the movement of a quadrotor in a horizontal plane along a trajectory given in the form of a sinusoidal or second-order polynomial function with semiglobal asymptotic convergence of the tracking errors to zero., Comment: in Russian

Published
2021

3. Robust Control of a Surface Vessel with Adaptive Rejection of Disturbances with Unknown Parameters

Author

Borisov, O. I., Gromova, F. B., Zhivitckii, A. Iu., and Pyrkin, A. A.

Subjects
Electrical Engineering and Systems Science - Systems and Control
Abstract

This paper solves the problem of station-keeping control of a surface vessel under conditions of sinusoidal disturbances with unknown parameters. The proposed control algorithm is based on the geometric approach with the use of the adaptive internal model and the extended observer. The paper analytically proves the boundedness of the trajectories of the system and their semiglobal convergence to an arbitrarily small set. The performance of the algorithm is illustrated by computer simulation., Comment: in Russian

Published
2021

7. DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity

Author

Turner, D. C., Gorski, P. P., Maasar, M. F., Seaborne, R. A., Baumert, P., Brown, A. D., Kitchen, M. O., Erskine, R. M., Dos-Remedios, I., Voisin, S., Eynon, N., Sultanov, R. I., Borisov, O. V., Larin, A. K., Semenova, E. A., Popov, D. V., Generozov, E. V., Stewart, C. E., Drust, B., Owens, D. J., Ahmetov, I. I., and Sharples, A. P.

Published
2020
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8. A precise measurement of 180 GeV muon energy losses in iron

Author

Amaral, P, Amorim, A, Anderson, K, Artikov, A, Benetta, R, Berglund, S, Biscarat, C, Blanch, O, Blanchot, G, Bogush, A, Bohm, C, Boldea, V, Borisov, O, Bosman, M, Bromberg, C, Bravo, S, Budagov, J, Burdin, S, Caloba, L, Camarena, F, Carvalho, J, Castillo, MV, Cavalli-Sforza, M, Cavasinni, V, Cerqueira, AS, Chadelas, R, Chirikov-Zorin, I, Chlachidze, G, Cobal, M, Cogswell, F, Cologna, S, Constantinescu, S, Costanzo, D, Cowan, B, Crouau, M, Daudon, F, David, M, Davidek, T, Dawson, J, De, K, Delfino, M, Del Prete, T, De Santo, A, Di Girolamo, B, Dita, S, Downing, R, Engström, M, Errede, D, Errede, S, Fassi, F, Fenyuk, A, Ferrer, A, Flaminio, V, Flix, J, Garabik, R, Gil, I, Gildemeister, O, Glagolev, V, Gomes, A, Gonzalez, V, González De La Hoz, S, Grabski, V, Grenier, P, Hakopian, H, Haney, M, Hellman, S, Henriques, A, Hebrard, C, Higon, E, Holik, P, Holmgren, S, Hruska, I, Huston, J, Jon-And, K, Kakurin, S, Karyukhin, A, Khubua, J, Kopikov, S, Krivkova, P, Kukhtin, V, Kulchitsky, Y, Kuzmin, M, Lami, S, Lapin, V, Lazzeroni, C, Lebedev, A, Leitner, R, Li, J, Lomakin, Y, Lomakina, O, Lokajicek, M, Lopez Amengual, JM, Maio, A, Malyukov, S, Marroquin, F, Mataix, L, Mazzoni, E, Merritt, F, Miller, R, and Minashvili, I

Subjects
Nuclear & Particles Physics, Quantum Physics, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Atomic, Molecular, Nuclear, Particle and Plasma Physics
Abstract

The energy loss spectrum of 180 GeV muons has been measured with the 5.6 m long finely segmented Module 0 of the ATLAS hadron Tile Calorimeter at the CERN SPS. The differential probability dP/dv per radiation length of a fractional energy loss v = ΔΕμ/Εμ has been measured in the range 0.025 ≤ v ≤ 0.97; it is compared with theoretical predictions for energy losses due to bremsstrahlung, production of electron-positron pairs, and energetic knock-on electrons. The iron elastic form factor correction ΔelFe = 1.63 ± 0.17stat ± 0.23Syst±0.200.14theor to muon bremsstrahlung in the region of no screening of the nucleus by atomic electrons has been measured for the first time, and is compared with different theoretical predictions.

Published
2001

9. Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores.

Author

Ishorst, N., Henschel, L., Thieme, F., Drichel, D., Sivalingam, S., Mehrem, S.L., Fechtner, A.C., Fazaal, J., Welzenbach, J., Heimbach, A., Maj, C., Borisov, O., Hausen, J., Raff, R., Hoischen, A., Dixon, M., Rada-Iglesias, A., Bartusel, M., Rojas-Martinez, A., Aldhorae, K., Braumann, B., Kruse, T., Kirschneck, C., Spanier, G., Reutter, H., Nowak, S., Gölz, L., Knapp, M., Buness, A., Krawitz, P., Nöthen, M.M., Nothnagel, M., Becker, T., Ludwig, K.U., Mangold, E., Ishorst, N., Henschel, L., Thieme, F., Drichel, D., Sivalingam, S., Mehrem, S.L., Fechtner, A.C., Fazaal, J., Welzenbach, J., Heimbach, A., Maj, C., Borisov, O., Hausen, J., Raff, R., Hoischen, A., Dixon, M., Rada-Iglesias, A., Bartusel, M., Rojas-Martinez, A., Aldhorae, K., Braumann, B., Kruse, T., Kirschneck, C., Spanier, G., Reutter, H., Nowak, S., Gölz, L., Knapp, M., Buness, A., Krawitz, P., Nöthen, M.M., Nothnagel, M., Becker, T., Ludwig, K.U., and Mangold, E.

Abstract

Item does not contain fulltext, BACKGROUND: Nonsyndromic cleft lip with/without cleft palate (nsCL/P) is a congenital malformation of multifactorial etiology. Research has identified >40 genome-wide significant risk loci, which explain less than 40% of nsCL/P heritability. Studies show that some of the hidden heritability is explained by rare penetrant variants. METHODS: To identify new candidate genes, we searched for highly penetrant de novo variants (DNVs) in 50 nsCL/P patient/parent-trios with a low polygenic risk for the phenotype (discovery). We prioritized DNV-carrying candidate genes from the discovery for resequencing in independent cohorts of 1010 nsCL/P patients of diverse ethnicities and 1574 population-matched controls (replication). Segregation analyses and rare variant association in the replication cohort, in combination with additional data (genome-wide association data, expression, protein-protein-interactions), were used for final prioritization. CONCLUSION: In the discovery step, 60 DNVs were identified in 60 genes, including a variant in the established nsCL/P risk gene CDH1. Re-sequencing of 32 prioritized genes led to the identification of 373 rare, likely pathogenic variants. Finally, MDN1 and PAXIP1 were prioritized as top candidates. Our findings demonstrate that DNV detection, including polygenic risk score analysis, is a powerful tool for identifying nsCL/P candidate genes, which can also be applied to other multifactorial congenital malformations.

Published
2023

10. Dissecting the genetic heterogeneity of gastric cancer

Author

Hess, T., Maj, C., Gehlen, J., Borisov, O., Haas, S. L., Gockel, I., Vieth, M., Piessen, G., Alakus, H., Vashist, Y., Pereira, C., Knapp, M., Schuller, V., Quaas, A., Grabsch, H. I., Trautmann, J., Malecka-Wojciesko, E., Mokrowiecka, A., Speller, J., Mayr, A., Schroder, J., Hillmer, A. M., Heider, D., Lordick, F., Perez-Aisa, A., Campo, R., Espinel, J., Geijo, F., Thomson, C., Bujanda, L., Sopena, F., Lanas, A., Pellise, M., Pauligk, C., Goetze, T. O., Zelck, C., Reingruber, J., Hassanin, E., Elbe, P., Alsabeah, S., Lindblad, M., Nilsson, M., Kreuser, N., Thieme, R., Tavano, F., Pastorino, Roberta, Arzani, D., Persiani, Roberto, Jung, J. -O., Nienhuser, H., Ott, K., Schumann, R. R., Kumpf, O., Burock, S., Arndt, V., Jakubowska, A., Lawniczak, M., Moreno, V., Martin, V., Kogevinas, M., Pollan, M., Dabrowska, J., Salas, A., Cussenot, O., Boland-Auge, A., Daian, D., Deleuze, J. -F., Salvi, E., Teder-Laving, M., Tomasello, G., Ratti, M., Senti, C., De Re, V., Steffan, A., Holscher, A. H., Messerle, K., Bruns, C. J., Sivins, A., Bogdanova, I., Skieceviciene, J., Arstikyte, J., Moehler, M., Lang, H., Grimminger, P. P., Kruschewski, M., Vassos, N., Schildberg, C., Lingohr, P., Ridwelski, K., Lippert, H., Fricker, N., Krawitz, P., Hoffmann, Christian Pieter, Nothen, M. M., Veits, L., Izbicki, J. R., Mostowska, A., Martinon-Torres, F., Cusi, D., Adolfsson, R., Cancel-Tassin, G., Hoblinger, A., Rodermann, E., Ludwig, M., Keller, G., Metspalu, A., Brenner, H., Heller, J., Neef, M., Schepke, M., Dumoulin, F. L., Hamann, L., Cannizzaro, Rino, Ghidini, Maria Candida, Plassmann, D., Geppert, M., Malfertheiner, P., Gehlen, O., Skoczylas, T., Majewski, M., Lubinski, J., Palmieri, O., Boccia, Stefania, Latiano, A., Aragones, N., Schmidt, T., Dinis-Ribeiro, M., Medeiros, R., Al-Batran, S. -E., Leja, M., Kupcinskas, J., Garcia-Gonzalez, M. A., Venerito, M., Schumacher, J., Pastorino R. (ORCID:0000-0001-5013-0733), Persiani R. (ORCID:0000-0002-1537-5097), Hoffmann P., Cannizzaro R., Ghidini M., Boccia S. (ORCID:0000-0002-1864-749X), Hess, T., Maj, C., Gehlen, J., Borisov, O., Haas, S. L., Gockel, I., Vieth, M., Piessen, G., Alakus, H., Vashist, Y., Pereira, C., Knapp, M., Schuller, V., Quaas, A., Grabsch, H. I., Trautmann, J., Malecka-Wojciesko, E., Mokrowiecka, A., Speller, J., Mayr, A., Schroder, J., Hillmer, A. M., Heider, D., Lordick, F., Perez-Aisa, A., Campo, R., Espinel, J., Geijo, F., Thomson, C., Bujanda, L., Sopena, F., Lanas, A., Pellise, M., Pauligk, C., Goetze, T. O., Zelck, C., Reingruber, J., Hassanin, E., Elbe, P., Alsabeah, S., Lindblad, M., Nilsson, M., Kreuser, N., Thieme, R., Tavano, F., Pastorino, Roberta, Arzani, D., Persiani, Roberto, Jung, J. -O., Nienhuser, H., Ott, K., Schumann, R. R., Kumpf, O., Burock, S., Arndt, V., Jakubowska, A., Lawniczak, M., Moreno, V., Martin, V., Kogevinas, M., Pollan, M., Dabrowska, J., Salas, A., Cussenot, O., Boland-Auge, A., Daian, D., Deleuze, J. -F., Salvi, E., Teder-Laving, M., Tomasello, G., Ratti, M., Senti, C., De Re, V., Steffan, A., Holscher, A. H., Messerle, K., Bruns, C. J., Sivins, A., Bogdanova, I., Skieceviciene, J., Arstikyte, J., Moehler, M., Lang, H., Grimminger, P. P., Kruschewski, M., Vassos, N., Schildberg, C., Lingohr, P., Ridwelski, K., Lippert, H., Fricker, N., Krawitz, P., Hoffmann, Christian Pieter, Nothen, M. M., Veits, L., Izbicki, J. R., Mostowska, A., Martinon-Torres, F., Cusi, D., Adolfsson, R., Cancel-Tassin, G., Hoblinger, A., Rodermann, E., Ludwig, M., Keller, G., Metspalu, A., Brenner, H., Heller, J., Neef, M., Schepke, M., Dumoulin, F. L., Hamann, L., Cannizzaro, Rino, Ghidini, Maria Candida, Plassmann, D., Geppert, M., Malfertheiner, P., Gehlen, O., Skoczylas, T., Majewski, M., Lubinski, J., Palmieri, O., Boccia, Stefania, Latiano, A., Aragones, N., Schmidt, T., Dinis-Ribeiro, M., Medeiros, R., Al-Batran, S. -E., Leja, M., Kupcinskas, J., Garcia-Gonzalez, M. A., Venerito, M., Schumacher, J., Pastorino R. (ORCID:0000-0001-5013-0733), Persiani R. (ORCID:0000-0002-1537-5097), Hoffmann P., Cannizzaro R., Ghidini M., and Boccia S. (ORCID:0000-0002-1864-749X)

Abstract

Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular me

Published
2023

21. Development, creation, and startup of the DC-110 heavy ion cyclotron complex for industrial production of track membranes

Author

Gikal, B. N., Dmitriev, S. N., Gul’bekyan, G. G., Apel’, P. Yu., Bogomolov, S. L., Borisov, O. N., Buzmakov, V. A., Verevochkin, V. A., Efremov, A. A., Ivanenko, I. A., Ivanov, G. N., Kazarinov, N. Yu., Kazacha, V. I., Kalagin, I. V., Kolesov, I. V., Kononov, V. M., Korolev, A. A., Kostyrev, V. A., Lomovtsev, A. M., Mel’nikov, V. N., Mironov, V. I., Pashchenko, S. V., Sokolov, V. A., Osipov, N. F., Tikhomirov, A. V., Fateev, A. A., and Khabarov, M. V.

Published
2014
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23. Polygenic risk scores for hypertension risk stratification

Author

Borisov, O, Salvi, E, Citterio, L, Lanzani, C, Barlassina, C, Glorioso, N, Krawitz, P, Cusi, D, Manunta, P, Maj, C, Borisov, O, Salvi, E, Citterio, L, Lanzani, C, Barlassina, C, Glorioso, N, Krawitz, P, Cusi, D, Manunta, P, and Maj, C

Published
2020

27. Multimodal Machine Learning Workflows for Prediction of Psychosis in Patients With Clinical High-Risk Syndromes and Recent-Onset Depression

Author

Koutsouleris, N, Dwyer, DB, Degenhardt, F, Maj, C, Urquijo-Castro, MF, Sanfelici, R, Popovic, D, Oeztuerk, O, Haas, SS, Weiske, J, Ruef, A, Kambeitz-Ilankovic, L, Antonucci, LA, Neufang, S, Schmidt-Kraepelin, C, Ruhrmann, S, Penzel, N, Kambeitz, J, Haidl, TK, Rosen, M, Chisholm, K, Riecher-Rossler, A, Egloff, L, Schmidt, A, Andreou, C, Hietala, J, Schirmer, T, Romer, G, Walger, P, Franscini, M, Traber-Walker, N, Schimmelmann, BG, Fluckiger, R, Michel, C, Rossler, W, Borisov, O, Krawitz, PM, Heekeren, K, Buechler, R, Pantelis, C, Falkai, P, Salokangas, RKR, Lencer, R, Bertolino, A, Borgwardt, S, Noethen, M, Brambilla, P, Wood, SJ, Upthegrove, R, Schultze-Lutter, F, Theodoridou, A, Meisenzahl, E, Koutsouleris, N, Dwyer, DB, Degenhardt, F, Maj, C, Urquijo-Castro, MF, Sanfelici, R, Popovic, D, Oeztuerk, O, Haas, SS, Weiske, J, Ruef, A, Kambeitz-Ilankovic, L, Antonucci, LA, Neufang, S, Schmidt-Kraepelin, C, Ruhrmann, S, Penzel, N, Kambeitz, J, Haidl, TK, Rosen, M, Chisholm, K, Riecher-Rossler, A, Egloff, L, Schmidt, A, Andreou, C, Hietala, J, Schirmer, T, Romer, G, Walger, P, Franscini, M, Traber-Walker, N, Schimmelmann, BG, Fluckiger, R, Michel, C, Rossler, W, Borisov, O, Krawitz, PM, Heekeren, K, Buechler, R, Pantelis, C, Falkai, P, Salokangas, RKR, Lencer, R, Bertolino, A, Borgwardt, S, Noethen, M, Brambilla, P, Wood, SJ, Upthegrove, R, Schultze-Lutter, F, Theodoridou, A, and Meisenzahl, E

Abstract

IMPORTANCE: Diverse models have been developed to predict psychosis in patients with clinical high-risk (CHR) states. Whether prediction can be improved by efficiently combining clinical and biological models and by broadening the risk spectrum to young patients with depressive syndromes remains unclear. OBJECTIVES: To evaluate whether psychosis transition can be predicted in patients with CHR or recent-onset depression (ROD) using multimodal machine learning that optimally integrates clinical and neurocognitive data, structural magnetic resonance imaging (sMRI), and polygenic risk scores (PRS) for schizophrenia; to assess models' geographic generalizability; to test and integrate clinicians' predictions; and to maximize clinical utility by building a sequential prognostic system. DESIGN, SETTING, AND PARTICIPANTS: This multisite, longitudinal prognostic study performed in 7 academic early recognition services in 5 European countries followed up patients with CHR syndromes or ROD and healthy volunteers. The referred sample of 167 patients with CHR syndromes and 167 with ROD was recruited from February 1, 2014, to May 31, 2017, of whom 26 (23 with CHR syndromes and 3 with ROD) developed psychosis. Patients with 18-month follow-up (n = 246) were used for model training and leave-one-site-out cross-validation. The remaining 88 patients with nontransition served as the validation of model specificity. Three hundred thirty-four healthy volunteers provided a normative sample for prognostic signature evaluation. Three independent Swiss projects contributed a further 45 cases with psychosis transition and 600 with nontransition for the external validation of clinical-neurocognitive, sMRI-based, and combined models. Data were analyzed from January 1, 2019, to March 31, 2020. MAIN OUTCOMES AND MEASURES: Accuracy and generalizability of prognostic systems. RESULTS: A total of 668 individuals (334 patients and 334 controls) were included in the analysis (mean [SD] age, 25.1 [5.

Published
2021

28. DC-350 accelerator complex

Author

Gulbekyan, G. G., Dmitriev, S. N., Gikal, B. N., Bogomolov, S. L., Borisov, O. N., Verevochkin, V. A., Efremov, A. A., Ivanenko, I. A., Ivanov, G. N., Kazarinov, N. Yu., Kazacha, V. I., Kalagin, I. V., Kolesov, I. V., Pashchenko, S. V., Sazonov, M. N., Tikhomirov, A. V., Franko, J., Khabarov, M. V., Kadyrzhanov, K. K., and Tuleushev, A. Zh.

Published
2010
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30. IC-100 accelerator complex for scientific and applied research

Author

Gikal, B. N., Dmitriev, S. N., Gul’bekyan, G. G., Apel’, P. Yu., Bashevoi, V. V., Bogomolov, S. L., Borisov, O. N., Buzmakov, V. A., Ivanenko, I. A., Ivanov, O. M., Kazarinov, N. Yu., Kolesov, I. V., Mironov, V. I., Papash, A. I., Pashchenko, S. V., Skuratov, V. A., Tikhomirov, A. V., Khabarov, M. V., Cherevatenko, A. P., and Yazvitskii, N. Yu.

Published
2008
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35. Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma

Author

Dong, J., Maj, C., Tsavachidis, S., Ostrom, Q.T., Gharahkhani, P., Anderson, L.A., Wu, A.H., Ye, W., Bernstein, L., Borisov, O., Schröder, J., Chow, W.H., Gammon, M.D., Liu, G., Caldas, C., Pharoah, P.D., Risch, H.A., May, A., Gerges, C., Anders, M., Venerito, M., Schmidt, T., Izbicki, J.R., Hölscher, A.H., Schumacher, B., Vashist, Y., Neuhaus, H., Rösch, T., Knapp, M., Krawitz, P., Böhmer, A., Iyer, P.G., Reid, B.J., Lagergren, J., Shaheen, N.J., Corley, D.A., Gockel, I., Fitzgerald, R.C., Cook, M.B., Whiteman, D.C., Vaughan, T.L., Schumacher, J., Thrift, A.P., Dong, J., Maj, C., Tsavachidis, S., Ostrom, Q.T., Gharahkhani, P., Anderson, L.A., Wu, A.H., Ye, W., Bernstein, L., Borisov, O., Schröder, J., Chow, W.H., Gammon, M.D., Liu, G., Caldas, C., Pharoah, P.D., Risch, H.A., May, A., Gerges, C., Anders, M., Venerito, M., Schmidt, T., Izbicki, J.R., Hölscher, A.H., Schumacher, B., Vashist, Y., Neuhaus, H., Rösch, T., Knapp, M., Krawitz, P., Böhmer, A., Iyer, P.G., Reid, B.J., Lagergren, J., Shaheen, N.J., Corley, D.A., Gockel, I., Fitzgerald, R.C., Cook, M.B., Whiteman, D.C., Vaughan, T.L., Schumacher, J., and Thrift, A.P.

Abstract

Contains fulltext : 229320.pdf (Publisher’s version ) (Closed access), BACKGROUND & AIMS: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored. METHODS: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits. RESULTS: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, P(BONF) = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, P(BONF) = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals. CONCLUSIONS: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.

Published
2020

50. Моделирование многофункционального терморезистивного преобразователя, использующего технологию теплообмена

Author

Osinov, S. M., Zavorotnyi, V. F., Lupyna, B. I., and Borisov, O. V.

Subjects
621.383, thermoresistive primary transduser, микроэлектромеханическая система, thermoanemometric and conductometric measurement method, microelectromechanical system, термоанемометрические и кондуктометрический метод измерения, термоанемо-метричний і кондуктометричний метод вимірювання, терморезистивный первичный преобразователь, мікроелектромеханічна система, терморезистивний первинний перетворювач
Abstract

У роботі проведено аналіз електронних, теплових і гідродинамічних фізичних процесів, характерних для структур первинних перетворювачів, виготовлених за технологією кремнієвої мікроелектромеханіки. Розглянуто фізико-технічні характеристики, структурні та топологічні аспекти функціонування мікромеханічних терморезисторних теплоізольованих структур активного нагрівання, які можуть бути основою для синтезу бібліотеки елементів первинних перетворювачів в системах автоматизованого проектування пристроїв інформаційної електроніки. Особливістю уніфікованої теплоізольованої структури є її багатофункціональність, що надає можливість на базі єдиного модельного підходу до функціонування терморезисторного первинного перетворювача активного нагрівання розробити низку сенсорів фізичних величин: абсолютного та диференційного тиску газового середовища, лінійної швидкості та масових витрат флюїду, потужності електромагнітного випромінювання тощо. Всі перетворювачі засновані на єдиній структурі MEMS (Micro Electro Mechanical System) і відрізняються за функціональністю за рахунок різних режимів роботи і різних принципів визначення параметрів рідини. Це дозволяє розробляти багатофункціональні датчики на основі єдиного обладнання, що включає в себе типову структуру МЕМС і мікропроцесор масового виробництва, наприклад, PSoC (Programmable System On Chip). В роботі розвинено запропоновану авторами в попередніх роботах математичну модель поверхневого терморезисторного первинного перетворювача лінійної швидкості потоку на діелектричній мембрані, вмонтованого в стінку потокоформуючого каналу прямокутного поперечного перерізу. Проведено поглиблений аналіз теплообмінних процесів між елементами теплоізольованої структури, оточуючим флюїдом і елементами корпусу. В запропонованій моделі реальної структури первинного перетворювача враховано геометричні і теплофізичні параметри мембрани, потокоформуючого каналу, геометрії теплоізолюючої порожнини травлення кремнію. Отримано рівняння, яке описує такі процеси в квазістатичному наближенні, наведено його розв’язок, виконано чисельний розрахунок залежності профілю температури теплоізольованої структури від швидкості потоку рідини в потокоформуючому каналі. Наведений в роботі аналітичний розв’язок надає можливість оптимізації чутливості первинного перетворювача до лінійної швидкості потоку флюїду в каналі та його вимірювального діапазону з врахуванням параметрів геометрії теплоізольованої структури і каналу. Запропонована модель може бути використаною у відкритих системах автоматизованого проектування типу COMSOL для розрахунку конструкції та аналізу фізичних засад функціонування пристроїв на основі теплоізольованих резисторних структур активного нагрівання з використання теплообмінних процесів у конструкціях міліметрових, мікронних та субмікронних розмірів. The physical and technical characteristics, structural and topological aspects of the micromechanical thermo-resistor active heating transdusers synthesis for fluid (gas and liquid) parameters determination are considered. All transducers are based on a single MEMS (Micro Electro Mechanical System) structure and differ in functionality due to different operating modes and different principles for determining fluid parameters. It allows the development of multifunctional sensors based on a single hardware, which includes a typical MEMS structure and mass production microprocessor, for example, PSoC (Programmable System On Chip). The transducers mathematical models acceptable for the COMSOL simulation library and designing of information electronics devices with the registration of various physical parameters are proposed. The analytical calculations on the basis of the proposed models for a gas flow sensor of the temperature dependence from the fluid flow velocity in the MEMS structure was performed. The proposed models can be used for the operation analytical description and computing of devices based on the use of thermoelectric processes in micro-scale structures. В работе рассмотрена систематизация электронных, тепловых и гидродинамических физических моделей, характерных для процессов в структурах первичных преобразователей, изготовленных по технологии кремниевой микроелектромеханикы. Рассмотрены физико-технические характеристики, структурные и топологические аспекты синтеза микромеханических терморезисторов активного нагрева для определения параметров среды (газа и жидкости). Предложена математическая модель, которая является основой для синтеза библиотеки элементов системы САПР и проектирования устройств информационной электроники для регистрации различных физических параметров. Проведен аналитический расчет температурной зависимости от скорости потока жидкости в структуре МЭМС на основе предложенной модели для датчика газового потока. Предложенные модели могут быть использованы в открытых системах САПР типа COMSOL для расчета и описания работы устройств на основе использования термоэлектрических процессов в малогабаритных конструкциях.

Published
2019

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