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3. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author

Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., Räikkönen, K., Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., and Räikkönen, K.

Abstract

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Published
2022

4. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author

Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, Raikkonen, K, Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, and Raikkonen, K

Abstract

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Published
2022

9. The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance

Author

Bey, K., Weinhold, L., Gruetzmann, R., Heinzel, S., Kaufmann, C., Klawohn, J., Riesel, A., Lennertz, L., Schmid, M., Ramirez, A., Kathmann, N., Wagner, M., Bey, K., Weinhold, L., Gruetzmann, R., Heinzel, S., Kaufmann, C., Klawohn, J., Riesel, A., Lennertz, L., Schmid, M., Ramirez, A., Kathmann, N., and Wagner, M.

Abstract

Objective Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. Methods We derived PRS for OCD at severalP-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. Results Results showed that OCD PRS significantly predicted OCD status, with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multipleP-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. Conclusion Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.

Published
2020

13. Internet use: Personality and motivation behind using the Internet, and cross-cultural specifics

Author

Sariyska R., Lachmann B., Reuter M., Bey K., Sha P., Li M., Chen Y-F., Liu W-Y., Zhu Y-K., Li C-B., Suárez-Rivillas A., Feldmann M., Hellmann M., Keiper J., Markett S., Young K. S., Cheng C., Gnisci A., Kaliszewska-Czeremska K., Laconi S., Zhong S., Toraman, D. & Montag, Sariyska, R., Lachmann, B., Reuter, M., Bey, K., Sha, P., Li, M., Chen, Y-F., Liu, W-Y., Zhu, Y-K., Li, C-B., Suárez-Rivillas, A., Feldmann, M., Hellmann, M., Keiper, J., Markett, S., Young, K. S., Cheng, C., Gnisci, A., Kaliszewska-Czeremska, K., Laconi, S., Zhong, S., Toraman, and D., & Montag

Published
2016

16. Some results about Lipschitz p-Nuclear Operators

Author

Bey Khedidja and Belacel Amar

Subjects
isometries, lipschitz operators, lipschitz p-nuclear operators, pointed metric space, primary: 46a32, 46b04, 46b20, secondary: 46b28, 47b10, 47l20, Mathematics, QA1-939
Abstract

The aim of this paper is to study the onto isometries of the space of strongly Lipschitz p-nuclear operators, introduced by D. Chen and B. Zheng (Nonlinear Anal.,75, 2012). We give some new results about such isometrics and we focus, in particular, on the case F = ℓp*.

Published
2021
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27. Strongly Lipschitz up-Nuclear Operators

Author

Belacel Amar and Bey Khedidja

Subjects
lipschitz operators, strongly lipschitz p-summing, p-nuclear operators, strongly lipschitz up-nuclear, strongly lipschitz p-nuclear, factorization theorem, 46a32, 47b10, 47l22, Mathematics, QA1-939
Abstract

In this paper, we introduce the notion of strongly Lipschitz up-nuclear operators. Among other results, we prove an analog of the factorization theorem for these classes and characterize their conjugates.

Published
2019
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28. Finite element analysis of high speed compressible flows using mesh refinement/movement procedures

Author

Ramakrishnan, R, Thornton, E. A, and Bey, K. S

Subjects
Fluid Mechanics And Heat Transfer
Abstract

An adaptive mesh refinement procedure for analyzing high-speed inviscid and viscous compressible flows is described. The adaptation procedure which uses both quadrilateral and triangular elements is implemented with an explicit finite element formulation. Elements in regions of strong and weak gradients are refined or coarsened based on inviscid and viscous indicators. Nodal locations are also adaptively moved to better resolve flow features. The effectiveness of the finite element procedure is demonstrated by modeling flows with complex shock structure and viscous-inviscid interactions. Numerical results are compared with experimental data.

Published
1989

29. A New Finite Element Approach for Prediction of Aerothermal Loads: Progress in Inviscid Flow Computations

Author

Bey, K. S, Thornton, E. A, Dechaumphai, P, and Ramakrishnan, R

Subjects
Fluid Mechanics And Heat Transfer
Abstract

Recent progress in the development of finite element methodology for the prediction of aerothermal loads is described. Two dimensional, inviscid computations are presented, but emphasis is placed on development of an approach extendable to three dimensional viscous flows. Research progress is described for: (1) utilization of a commerically available program to construct flow solution domains and display computational results, (2) development of an explicit Taylor-Galerkin solution algorithm, (3) closed form evaluation of finite element matrices, (4) vector computer programming strategies, and (5) validation of solutions. Two test problems of interest to NASA Langley aerothermal research are studied. Comparisons of finite element solutions for Mach 6 flow with other solution methods and experimental data validate fundamental capabilities of the approach for analyzing high speed inviscid compressible flows.

Published
1985

30. Analytical prediction of aerothermal environment in a wing-elevon cove

Author

Bey, K. S

Subjects
Fluid Mechanics And Heat Transfer
Abstract

The fluid/thermal environment in the cove between the wing and elevon surfaces was a concern throughout the design and initial operational phases of the space shuttle. Experimenal and analytical investigations provided some understanding of the environmental in the wing-elevon cove. An incompressible finite element analysis of flow through straight parallel walls and curved parallel walls to determine the effects of cove geomtry on the fluid/thermal environment is described. Results from this analysis agree qualitatively with experimental data. The centerline gas temperatures and cold wall heating rates are virtually identical for the two cases indicating that the slight curvature has little effect on the overall thermal environment.

Published
1983

31. Aerothermal environment in control surface gaps in hypersonic flow - An overview

Author

Wieting, A. R, Walsh, J. L, and Bey, K. S

Subjects
Aerodynamics
Abstract

Experimental and analytical research by the NASA Langley Research Center to develop an understanding of the fluid and thermal environment in control surface gaps such as the spanwise gap of the wing elevon and chordwise gap of a split elevon configuration typical of the Space Shuttle are summarized. Although the experimental and analytical studies were initiated too late to significantly impact the basic Shuttle design they do provide a fundamental understanding of the basic fluid/thermal environment in control surface gaps and help to establish a firm data base for future vehicle design.

Published
1983

40. Analysis of genes involved in 6-deoxyhexose biosynthesis and transfer inSaccharopolyspora erythraea

Author

Doumith, M., Weingarten, P., Wehmeier, U. F., Salah-Bey, K., Benhamou, B., Capdevila, C., Michel, J.-M., Piepersberg, W., and Raynal, M.-C.

Abstract

Glycosylation represents an attractive target for protein engineering of novel antibiotics, because specific attachment of one or more deoxysugars is required for the bioactivity of many antibiotic and antitumour polyketides. However, proper assessment of the potential of these enzymes for such combinatorial biosynthesis requires both more precise information on the enzymology of the pathways and also improvedEscherichia coli-actinomycete shuttle vectors. New replicative vectors have been constructed and used to express independently thednmUgene ofStreptomyces peucetiusand theeryBVIIgene ofSaccharopolyspora erythraeain aneryBVIIdeletion mutant ofSac. erythraea.Production of erythromycin A was obtained in both cases, showing that both proteins serve analogous functions in the biosynthetic pathways to dTDP-L-daunosamine and dTDP-L-mycarose, respectively. Over-expression of both proteins was also obtained inS. lividans, paving the way for protein purification and in vitro monitoring of enzyme activity. In a further set of experiments, the putative desosaminyltransferase ofSac. erythraea, EryCIII, was expressed in the picromycin producerStreptomycessp. 20032, which also synthesises dTDP-D-desosamine. The substrate 3-α-mycarosylerythronolide B used for hybrid biosynthesis was found to be glycosylated to produce erythromycin D only when recombinant EryCIII was present, directly confirming the enzymatic role of EryCIII. This convenient plasmid expression system can be readily adapted to study the directed evolution of recombinant glycosyltransferases.

Published
2000
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42. A thermal parametric study of non-evaporative spray cooling process

Author

Otmani Abdessalam, Mzad Hocine, and Bey Kamel

Subjects
Engineering (General). Civil engineering (General), TA1-2040
Abstract

Ordinary water spray cooling is connected with very high temperatures where heat transfer during evaporation plays a key role. However, during cooling without phase change, the behaviour of the spray cooling parameters is rarely considered. The purpose of this paper is to study the influence of spray hydrodynamic parameters on heat transfer without liquid phase change during the cooling of an aluminium 3003-H18 plate at a temperature of 92 °C. First of all, the flow rate was varied from 0.497 up to 1 l/min. Then, the inlet pressure varied from 0.7 to 2.1 bars. The influence of nozzle-to-target distance is also tested since the simulations were carried out in a wide height range, from 100 mm to 505 mm. The present simulation was achieved using the version 5.2 of COMSOL Multiphysics code.

Published
2018
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43. A model of water-spray cooling effect on a continuous casting process

Author

Mzad Hocine, Otmani Abdessalam, Bey Kamel, and Łopata Stanisław

Subjects
Metal, Melting, Water-spray, Simulation, Heat transfer, Engineering (General). Civil engineering (General), TA1-2040
Abstract

The intention of this study is to give an idea about the influence of water-spray cooling on the solidification process of the liquid metal which enables to locate the shear region. The effect of spray heat transfer coefficient (hspray) during the liquid-to-solid transition through the cooled zone temperature and the metal latent heat of solidification are highlighted. A gray iron continuous casting process subjected to water-sprays cooling was simulated using the commercial code COMSOL MULTIPHYSICS 5.2. The obtained results show the great influence of hspray on the location of transition region as well as the relationship between hspray, wall outer temperature, latent heat dissipation, and the solidification time.

Published
2018
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