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105 results on '"Espeseth AS"'

1. Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Author

Boen, Rune, primary, Kaufmann, Tobias, additional, van der Meer, Dennis, additional, Frei, Oleksandr, additional, Agartz, Ingrid, additional, Ames, David, additional, Andersson, Micael, additional, Armstrong, Nicola J., additional, Artiges, Eric, additional, Atkins, Joshua R., additional, Bauer, Jochen, additional, Benedetti, Francesco, additional, Boomsma, Dorret I., additional, Brodaty, Henry, additional, Brosch, Katharina, additional, Buckner, Randy L., additional, Cairns, Murray J., additional, Calhoun, Vince, additional, Caspers, Svenja, additional, Cichon, Sven, additional, Corvin, Aiden P., additional, Crespo-Facorro, Benedicto, additional, Dannlowski, Udo, additional, David, Friederike S., additional, de Geus, Eco J.C., additional, de Zubicaray, Greig I., additional, Desrivières, Sylvane, additional, Doherty, Joanne L., additional, Donohoe, Gary, additional, Ehrlich, Stefan, additional, Eising, Else, additional, Espeseth, Thomas, additional, Fisher, Simon E., additional, Forstner, Andreas J., additional, Fortaner-Uyà, Lidia, additional, Frouin, Vincent, additional, Fukunaga, Masaki, additional, Ge, Tian, additional, Glahn, David C., additional, Goltermann, Janik, additional, Grabe, Hans J., additional, Green, Melissa J., additional, Groenewold, Nynke A., additional, Grotegerd, Dominik, additional, Grøntvedt, Gøril Rolfseng, additional, Hahn, Tim, additional, Hashimoto, Ryota, additional, Hehir-Kwa, Jayne Y., additional, Henskens, Frans A., additional, Holmes, Avram J., additional, Håberg, Asta K., additional, Haavik, Jan, additional, Jacquemont, Sebastien, additional, Jansen, Andreas, additional, Jockwitz, Christiane, additional, Jönsson, Erik G., additional, Kikuchi, Masataka, additional, Kircher, Tilo, additional, Kumar, Kuldeep, additional, Le Hellard, Stephanie, additional, Leu, Costin, additional, Linden, David E., additional, Liu, Jingyu, additional, Loughnan, Robert, additional, Mather, Karen A., additional, McMahon, Katie L., additional, McRae, Allan F., additional, Medland, Sarah E., additional, Meinert, Susanne, additional, Moreau, Clara A., additional, Morris, Derek W., additional, Mowry, Bryan J., additional, Mühleisen, Thomas W., additional, Nenadić, Igor, additional, Nöthen, Markus M., additional, Nyberg, Lars, additional, Ophoff, Roel A., additional, Owen, Michael J., additional, Pantelis, Christos, additional, Paolini, Marco, additional, Paus, Tomas, additional, Pausova, Zdenka, additional, Persson, Karin, additional, Quidé, Yann, additional, Marques, Tiago Reis, additional, Sachdev, Perminder S., additional, Sando, Sigrid B., additional, Schall, Ulrich, additional, Scott, Rodney J., additional, Selbæk, Geir, additional, Shumskaya, Elena, additional, Silva, Ana I., additional, Sisodiya, Sanjay M., additional, Stein, Frederike, additional, Stein, Dan J., additional, Straube, Benjamin, additional, Streit, Fabian, additional, Strike, Lachlan T., additional, Teumer, Alexander, additional, Teutenberg, Lea, additional, Thalamuthu, Anbupalam, additional, Tooney, Paul A., additional, Tordesillas-Gutierrez, Diana, additional, Trollor, Julian N., additional, van ’t Ent, Dennis, additional, van den Bree, Marianne B.M., additional, van Haren, Neeltje E.M., additional, Vázquez-Bourgon, Javier, additional, Völzke, Henry, additional, Wen, Wei, additional, Wittfeld, Katharina, additional, Ching, Christopher R.K., additional, Westlye, Lars T., additional, Thompson, Paul M., additional, Bearden, Carrie E., additional, Selmer, Kaja K., additional, Alnæs, Dag, additional, Andreassen, Ole A., additional, and Sønderby, Ida E., additional

Published
2024
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3. Evaluation of a stabilized RSV pre-fusion F mRNA vaccine: Preclinical studies and Phase 1 clinical testing in healthy adults

Author

Nussbaum, Jesse, primary, Cao, Xin, additional, Railkar, Radha A., additional, Sachs, Jeffrey R., additional, Spellman, Daniel S., additional, Luk, Julie, additional, Shaw, Christine A., additional, Cejas, Pedro J., additional, Citron, Michael P., additional, Al-Ibrahim, Mohamed, additional, Han, David, additional, Pagnussat, Sandra, additional, Stoch, S. Aubrey, additional, Lai, Eseng, additional, Bett, Andrew J., additional, and Espeseth, Amy S., additional

Published
2023
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5. Characterization of humoral and cell-mediated immunity induced by mRNA vaccines expressing influenza hemagglutinin stem and nucleoprotein in mice and nonhuman primates

Author

Jessica A, Flynn, Teresa, Weber, Pedro J, Cejas, Kara S, Cox, Sinoeun, Touch, Lauren A, Austin, Yangsi, Ou, Michael P, Citron, Bin, Luo, Marian E, Gindy, Kapil, Bahl, Giuseppe, Ciaramella, Amy S, Espeseth, and Lan, Zhang

Subjects
Primates, Immunity, Cellular, Vaccines, Synthetic, General Veterinary, General Immunology and Microbiology, Public Health, Environmental and Occupational Health, Hemagglutinin Glycoproteins, Influenza Virus, Antibodies, Viral, Immunity, Humoral, Mice, Influenza A Virus, H1N1 Subtype, Nucleoproteins, Infectious Diseases, Orthomyxoviridae Infections, Influenza Vaccines, Animals, Molecular Medicine, mRNA Vaccines
Abstract

In response to immune pressure, influenza viruses evolve, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response capable of recognizing multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the efficacy and immunogenicity of mRNA vaccines encoding either the conserved stem domain of a group 1 hemagglutinin (HA), a group 2 nucleoprotein (NP), or a combination of the two antigens in mice, as well as evaluated immunogenicity in naïve and influenza seropositive nonhuman primates (NHPs). HA stem-immunized animals developed a robust anti-stem antibody binding titer, and serum antibodies recognized antigenically distinct group 1 HA proteins. These antibodies showed little to no neutralizing activity in vitro but were active in an assay measuring induction of antibody-dependent cellular cytotoxicity. HA-directed cell-mediated immunity was weak following HA stem mRNA vaccination; however, robust CD4 and CD8 T cell responses were detected in both mice and NHPs after immunization with mRNA vaccines encoding NP. Both HA stem and NP mRNA vaccines partially protected mice from morbidity following lethal influenza virus challenge, and superior efficacy against two different H1N1 strains was observed when the antigens were combined. In vivo T cell depletion suggested that anti-NP cell-mediated immunity contributed to protection in the mouse model. Taken together, these data show that mRNA vaccines encoding conserved influenza antigens, like HA stem and NP in combination, induce broadly reactive humoral responses as well as cell-mediated immunity in mice and NHPs, providing protection against homologous and heterologous influenza infection in mice.

Published
2022

7. Preclinical immunogenicity and efficacy of a candidate COVID-19 vaccine based on a vesicular stomatitis virus-SARS-CoV-2 chimera

Author

Espeseth, Amy S., primary, Yuan, Maoli, additional, Citron, Michael, additional, Reiserova, Lucia, additional, Morrow, Gavin, additional, Wilson, Aaron, additional, Horton, Melanie, additional, Rukhman, Mark, additional, Kinek, Keith, additional, Hou, Fuxiang, additional, Li, Shui L., additional, Li, Fengsheng, additional, Choi, Yesle, additional, Heidecker, Gwen, additional, Luo, Bin, additional, Wu, Guoxin, additional, Zhang, Lan, additional, Strable, Erica, additional, DeStefano, Joanne, additional, Secore, Susan, additional, Mukhopadhyay, Tarit K., additional, Richardson, Douglas D., additional, Sayeed, Eddy, additional, Welch, Lisa S., additional, Bett, Andrew J., additional, Feinberg, Mark B., additional, Gupta, Swati B., additional, Cooper, Christopher L., additional, and Parks, Christopher L., additional

Published
2022
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8. Deep neural networks learn general and clinically relevant representations of the ageing brain

Author

Leonardsen, Esten H., primary, Peng, Han, additional, Kaufmann, Tobias, additional, Agartz, Ingrid, additional, Andreassen, Ole A., additional, Celius, Elisabeth Gulowsen, additional, Espeseth, Thomas, additional, Harbo, Hanne F., additional, Høgestøl, Einar A., additional, Lange, Ann-Marie de, additional, Marquand, Andre F., additional, Vidal-Piñeiro, Didac, additional, Roe, James M., additional, Selbæk, Geir, additional, Sørensen, Øystein, additional, Smith, Stephen M., additional, Westlye, Lars T., additional, Wolfers, Thomas, additional, and Wang, Yunpeng, additional

Published
2022
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9. Characterization of humoral and cell-mediated immunity induced by mRNA vaccines expressing influenza hemagglutinin stem and nucleoprotein in mice and nonhuman primates

Author

Flynn, Jessica A., primary, Weber, Teresa, additional, Cejas, Pedro J., additional, Cox, Kara S., additional, Touch, Sinoeun, additional, Austin, Lauren A., additional, Ou, Yangsi, additional, Citron, Michael P., additional, Luo, Bin, additional, Gindy, Marian E., additional, Bahl, Kapil, additional, Ciaramella, Giuseppe, additional, Espeseth, Amy S., additional, and Zhang, Lan, additional

Published
2022
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10. Upper and lower respiratory tract correlates of protection against respiratory syncytial virus following vaccination of nonhuman primates

Author

Zohar, Tomer, primary, Hsiao, Jeff C., additional, Mehta, Nickita, additional, Das, Jishnu, additional, Devadhasan, Anush, additional, Karpinski, Wiktor, additional, Callahan, Cheryl, additional, Citron, Michael P., additional, DiStefano, Daniel J., additional, Touch, Sinoeun, additional, Wen, Zhiyun, additional, Sachs, Jeffrey R., additional, Cejas, Pedro J., additional, Espeseth, Amy S., additional, Lauffenburger, Douglas A., additional, Bett, Andrew J., additional, and Alter, Galit, additional

Published
2022
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13. Aluminium plates with geometrical defects subjected to low-velocity impact: Experiments and simulations

Author

Vetle Espeseth, Tore Børvik, and Odd Sture Hopperstad

Subjects
Mechanics of Materials, Mechanical Engineering, Automotive Engineering, Aerospace Engineering, Ocean Engineering, Safety, Risk, Reliability and Quality, Civil and Structural Engineering
Abstract

In this paper, an experimental and numerical program investigating impact in the low-velocity regime ( m/s) on 1.5 mm thick AA6016 aluminium plates in three different heat treatments (T4/T6/T7) is presented. The tests were carried out in a drop tower where the force was continuously monitored by a strain-gauge instrumented striker. Results from both intact plates and plates with geometrical defects in the form of pre-cut slits are presented. The heat treatments result in materials with different strength, work-hardening and ductility. It was observed that the intact plates in high-strength material are more resilient to low-velocity impact whereas high ductility is preferred for the plates with pre-cut slits as the crack growth is more restrained. Quasi-static tests on the same plates showed a significant reduction in force only for plates in temper T6 and T7. The experiments are complemented by nonlinear finite element simulations using linear brick elements in Abaqus/Explicit. A von Mises plasticity model was calibrated from notched tension tests. The global response from single edge notch tension (SENT) tests was used to calibrate the failure criterion. The numerical model was able to sufficiently predict the force response and deformation of the intact plates, and the global response and crack propagation of the SENT tests. While the force response in the dynamic simulation of low-velocity impact on plates with slits was in agreement with the observed quasi-static response for all tempers, it was in general underestimated for temper T6 and T7 when compared to the data from the dynamic experiments. For plates in temper T4, the predicted response also agreed with the dynamic experiments.

Published
2022

14. Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis

Author

Maas, Brian M., primary, Lommerse, Jos, additional, Plock, Nele, additional, Railkar, Radha A., additional, Cheung, S.Y. Amy, additional, Caro, Luzelena, additional, Chen, Jingxian, additional, Liu, Wen, additional, Zhang, Ying, additional, Huang, Qinlei, additional, Gao, Wei, additional, Qin, Li, additional, Meng, Jie, additional, Witjes, Han, additional, Schindler, Emilie, additional, Guiastrennec, Benjamin, additional, Bellanti, Francesco, additional, Spellman, Daniel S., additional, Roadcap, Brad, additional, Kalinova, Mariya, additional, Fok-Seang, Juin, additional, Catchpole, Andrew P., additional, Espeseth, Amy S., additional, Stoch, S. Aubrey, additional, Lai, Eseng, additional, Vora, Kalpit A., additional, Aliprantis, Antonios O., additional, and Sachs, Jeffrey R., additional

Published
2021
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15. Upper and Lower Respiratory Tract Correlates of Protection Against RSV Following Vaccination of Non-Human Primates

Author

Michael P. Citron, Zhiyun Wen, Nickita Mehta, Galit Alter, Amy S. Espeseth, Daniel J. DiStefano, Jishnu Das, Sinoeun Touch, Cheryl Callahan, Jeffrey R. Sachs, Tomer Zohar, Paloma Cejas, Andrew J. Bett, Anush Devadhasan, Douglas A. Lauffenburger, and Wiktor Karpinski

Subjects
Innate immune system, biology, business.industry, Virus, Vaccination, medicine.anatomical_structure, Immunity, Immunology, biology.protein, medicine, Antibody, Respiratory system, business, Viral load, Respiratory tract
Abstract

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory illness in both young infants and the elderly. While antibodies represent key correlates of protection, the antibody mechanisms remain poorly understood. Emerging data point to additional humoral Fc-mediated mechanisms of action beyond neutralization. Therefore, to map the humoral correlates of immunity against RSV, antibody responses were profiled in a highly controlled non-human primate challenge model. Six different vaccine platforms were tested in African Green Monkeys, which post-challenge, yielded distinct antibody profiles and viral loads in both upper and lower respiratory tracts. Machine learning was then used to determine antibody features associated with protection. Upper respiratory control involved virus specific IgA levels, neutralization, and complement whereas lower respiratory control involved Fc-mediated mechanisms. These data highlight a collaborative Fab and Fc protective signature, induced selectively by distinct vaccine platforms, and provides mechanistic insights for the rational development of vaccines.

Published
2021

16. A numerical study of a size-dependent finite-element based unit cell with primary and secondary voids

Author

Espeseth, Vetle, Morin, David, Faleskog, Jonas, Borvik, Tore, Hopperstad, Odd Sture, Espeseth, Vetle, Morin, David, Faleskog, Jonas, Borvik, Tore, and Hopperstad, Odd Sture

Abstract

Aluminium alloys contain various types of intermetallic particles with different sizes, such as constituent particles and dispersoids. The main mechanism of ductile fracture in these materials is assumed to be nucleation of voids around the constituent particles, which grow during plastic deformation and eventually coalesce, resulting in material failure. The role of the dispersoids is less certain, but they are assumed to contribute in the last stages of the ductile fracture process. While the constituent particles are in the range of a couple of microns, the size of dispersoids is normally one order of magnitude smaller. To disclose the possible effects of the dispersoids on the ductile fracture process in aluminium alloys, this paper presents a numerical study of a finiteelement based unit cell, which consists of a single spherical void embedded in a matrix material represented by a porous plasticity model with void size effects. Accordingly, the single, primary void of the unit cell is assumed to have nucleated on a constituent particle, whereas the matrix porosity is assumed to account for secondary, smaller voids nucleated on dispersoids. The effects of the intrinsic length scale of the matrix material on the void growth and coalescence are studied for a range of stress states, while the initial primary and secondary void volume fractions are kept constant. The secondary voids have a substantial effect on the behaviour of the unit cell when their size is large compared to the intrinsic material length scale, but they were not found to influence the growth of the primary void. Instead, the growth of the secondary voids promotes strain softening and influences the coalescence process of the primary voids, which gradually changes mode from internal necking to loss of load-carrying capacity of the inter-void ligament., QC 20211103

Published
2021
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18. Upper and lower respiratory tract correlates of protection against respiratory syncytial virus following vaccination of nonhuman primates

Author

Tomer Zohar, Jeff C. Hsiao, Nickita Mehta, Jishnu Das, Anush Devadhasan, Wiktor Karpinski, Cheryl Callahan, Michael P. Citron, Daniel J. DiStefano, Sinoeun Touch, Zhiyun Wen, Jeffrey R. Sachs, Pedro J. Cejas, Amy S. Espeseth, Douglas A. Lauffenburger, Andrew J. Bett, and Galit Alter

Subjects
Primates, Vaccination, Respiratory Syncytial Virus Infections, Viral Load, Antibodies, Viral, Antibodies, Neutralizing, Microbiology, Immunity, Innate, Immunoglobulin A, Respiratory Syncytial Virus, Human, Virology, Chlorocebus aethiops, Respiratory Syncytial Virus Vaccines, Animals, Humans, Parasitology, Lung, Biomarkers
Abstract

Respiratory syncytial virus (RSV) infection is a major cause of respiratory illness in infants and the elderly. Although several vaccines have been developed, none have succeeded in part due to our incomplete understanding of the correlates of immune protection. While both T cells and antibodies play a role, emerging data suggest that antibody-mediated mechanisms alone may be sufficient to provide protection. Therefore, to map the humoral correlates of immunity against RSV, antibody responses across six different vaccines were profiled in a highly controlled nonhuman primate-challenge model. Viral loads were monitored in both the upper and lower respiratory tracts, and machine learning was used to determine the vaccine platform-agnostic antibody features associated with protection. Upper respiratory control was associated with virus-specific IgA levels, neutralization, and complement activity, whereas lower respiratory control was associated with Fc-mediated effector mechanisms. These findings provide critical compartment-specific insights toward the rational development of future vaccines.

Published
2022

19. Effect of wind direction and incidence angle on polarimetric SAR observations of slicked and unslicked sea surfaces

Author

Cathleen E. Jones, Benjamin Holt, Stine Skrunes, Martine M. Espeseth, and Camilla Brekke

Subjects
Synthetic aperture radar, 010504 meteorology & atmospheric sciences, Correlation coefficient, 0211 other engineering and technologies, Polarimetry, Soil Science, SNR, 02 engineering and technology, 01 natural sciences, VDP::Mathematics and natural science: 400::Physics: 430, Standard deviation, Computers in Earth Sciences, 021101 geological & geomatics engineering, 0105 earth and related environmental sciences, Remote sensing, VDP::Matematikk og Naturvitenskap: 400::Fysikk: 430, Oil spill, Geology, Wind direction, Racing slick, Noise floor, Relative wind, Synthetic aperture radar (SAR), Incidence angle, Ocean scattering, Imaging geometry
Abstract

Accepted manuscript version, licensed CC BY-NC-ND 4.0. Published version available at https://doi.org/10.1016/j.rse.2018.05.001. The objective of this paper is to investigate the dependency of oil spill observations in polarimetric SAR data on imaging geometry, i.e., on incidence angle and look direction relative to the wind. The study is based on quad-polarization data acquired by the Uninhabited Aerial Vehicle Synthetic Aperture Radar over experimental oil slicks under relatively high winds of 10–12 m/s over an 8-hour period. The data is collected over a wide range of incidence angles and alternates between looking upwind (UW) and downwind (DW). The unique time series enables a detailed study of the behavior of multipolarization parameters over clean sea and oil slicks under varying imaging geometry to be carried out for the first time. For clean sea backscatter, our findings are in agreement with previous studies, showing decreasing backscatter as the incidence angle increases and from UW to DW, with the highest sensitivity in the HH channel. We also find similar variations in oil covered areas. The results suggest that the oil slick backscatter is slightly more sensitive to the relative wind direction than the clean sea, and higher oil-sea damping ratios are found in DW than in UW cases, particularly in the HH channel. All multipolarization features investigated have some degree of dependency on imaging geometry. The lowest sensitivities are found in the magnitude of the copolarization correlation coefficient, the standard deviation of the copolarized phase difference, the polarization difference, the mean scattering angle and the entropy. Several features clearly change behavior when the signal approaches the sensor noise floor, and we find that the measurements and derived parameters may be affected at even higher signal-to-noise ratio (SNR) levels than previously proposed, i.e., closer to 7–9 dB above the sensor noise floor. Overall, the polarization difference is clearly identified as the most interesting parameter for oil spill observation, producing high oil-sea contrast in addition to low sensitivity to imaging geometry. The results show that both the relative wind direction and the incidence angle, in combination with the SNR, should be taken into account when developing operational methods based on multipolarization SAR data.

Published
2018

20. A novel method for strict intranasal delivery of non-replicating RSV vaccines in cotton rats and non-human primates

Author

Sinoeun Touch, Chinedu G. Orekie, Cameron M. Douglas, Walter Knapp, Jane Fontenot, Amy S. Espeseth, Zhiyun Wen, Michael P. Citron, Ioan Petrescu, Mona Purcell, Cheryl Callahan, Xiaoping Liang, Sai Prasanth Chamarthy, Manishkumar Patel, Paul McQuade, Daniel Rubins, Shu-An Lin, Alexa Gleason, and Matthew Pine

Subjects
0301 basic medicine, Drug Evaluation, Preclinical, Respiratory Syncytial Virus Infections, 03 medical and health sciences, 0302 clinical medicine, Immune system, 030225 pediatrics, Chlorocebus aethiops, Respiratory Syncytial Virus Vaccines, medicine, Animals, Sigmodontinae, Cotton rat, Administration, Intranasal, General Veterinary, General Immunology and Microbiology, biology, business.industry, Respiratory disease, Public Health, Environmental and Occupational Health, medicine.disease, biology.organism_classification, Vaccination, Pneumonia, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Immunization, Bronchiolitis, Respiratory Syncytial Virus, Human, Models, Animal, Immunology, Molecular Medicine, Female, business, Respiratory tract
Abstract

Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis and pneumonia in children twelve months of age or younger and a significant cause of lower respiratory disease in older adults. As various clinical and preclinical candidates advance, cotton rats (Sigmodon hispidus) and non-human primates (NHP) continue to play a valuable role in RSV vaccine development, since both animals are semi-permissive to human RSV (HRSV). However, appropriate utilization of the models is critical to avoid mis-interpretation of the preclinical findings. Using a multimodality imaging approach; a fluorescence based optical imaging technique for the cotton rat and a nuclear medicine based positron emission tomography (PET) imaging technique for monkeys, we demonstrate that many common practices for intranasal immunization in both species result in inoculum delivery to the lower respiratory tract, which can result in poor translation of outcomes from the preclinical to the clinical setting. Using these technologies we define a method to limit the distribution of intranasally administered vaccines solely to the upper airway of each species, which includes volume restrictions in combination with injectable anesthesia. We show using our newly defined methods for strict intranasal immunization that these methods impact the immune responses and efficacy observed when compared to vaccination methods resulting in distribution to both the upper and lower respiratory tracts. These data emphasize the importance of well-characterized immunization methods in the preclinical assessment of intranasally delivered vaccine candidates.

Published
2018

21. A numerical study of a size-dependent finite-element based unit cell with primary and secondary voids

Author

Vetle Espeseth, David Morin, Tore Børvik, Odd Sture Hopperstad, and Jonas Faleskog

Subjects
Coalescence (physics), Void (astronomy), Materials science, Mechanical Engineering, Astrophysics::Cosmology and Extragalactic Astrophysics, 02 engineering and technology, Plasticity, urologic and male genital diseases, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, 010305 fluids & plasmas, Stress (mechanics), Mechanics of Materials, 0103 physical sciences, Particle, Material failure theory, Composite material, 0210 nano-technology, Porosity, Necking
Abstract

Aluminium alloys contain various types of intermetallic particles with different sizes, such as constituent particles and dispersoids. The main mechanism of ductile fracture in these materials is assumed to be nucleation of voids around the constituent particles, which grow during plastic deformation and eventually coalesce, resulting in material failure. The role of the dispersoids is less certain, but they are assumed to contribute in the last stages of the ductile fracture process. While the constituent particles are in the range of a couple of microns, the size of dispersoids is normally one order of magnitude smaller. To disclose the possible effects of the dispersoids on the ductile fracture process in aluminium alloys, this paper presents a numerical study of a finite-element based unit cell, which consists of a single spherical void embedded in a matrix material represented by a porous plasticity model with void size effects. Accordingly, the single, primary void of the unit cell is assumed to have nucleated on a constituent particle, whereas the matrix porosity is assumed to account for secondary, smaller voids nucleated on dispersoids. The effects of the intrinsic length scale of the matrix material on the void growth and coalescence are studied for a range of stress states, while the initial primary and secondary void volume fractions are kept constant. The secondary voids have a substantial effect on the behaviour of the unit cell when their size is large compared to the intrinsic material length scale, but they were not found to influence the growth of the primary void. Instead, the growth of the secondary voids promotes strain softening and influences the coalescence process of the primary voids, which gradually changes mode from internal necking to loss of load-carrying capacity of the inter-void ligament.

Published
2021

22. Upper and Lower Respiratory Tract Correlates of Protection Against RSV Following Vaccination of Non-Human Primates

Author

Zohar, Tomer, primary, Mehta, Nickita, additional, Das, Jishnu, additional, Devadhasan, Anush, additional, Karpinski, Wiktor, additional, Callahan, Cheryl, additional, Citron, Michael P., additional, DiStefano, Daniel J., additional, Touch, Sinoeun, additional, Wen, Zhiyun, additional, Sachs, Jeffrey R., additional, Cejas, Pedro J., additional, Espeseth, Amy S., additional, Lauffenburger, Douglas, additional, Bett, Andrew J., additional, and Alter, Galit, additional

Published
2021
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24. Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis

Author

Francesco Bellanti, Antonios O. Aliprantis, Juin Fok-Seang, Wen Liu, Jeffrey R. Sachs, Radha Railkar, Brad Roadcap, Kalpit A. Vora, Qinlei Huang, Li Qin, Nele Plock, W. Gao, Eseng Lai, Daniel S. Spellman, Jingxian Chen, Andrew P. Catchpole, Emilie Schindler, Mariya Kalinova, Amy S. Espeseth, Jie Meng, S. Y. Amy Cheung, Luzelena Caro, S. Aubrey Stoch, Benjamin Guiastrennec, Jos Lommerse, Brian M. Maas, Ying Zhang, and Han Witjes

Subjects
Adult, Male, Medicine (General), Research paper, Adolescent, medicine.drug_class, Premedication, Monoclonal Antibody, Force of infection, Respiratory Syncytial Virus Infections, Antibodies, Viral, Monoclonal antibody, medicine.disease_cause, Placebo, General Biochemistry, Genetics and Molecular Biology, Virus, Translational Research, Biomedical, Young Adult, R5-920, Modelling and Simulation, Clinical endpoint, Humans, Medicine, Aged, RSV, Meta-analysis, Clinical Trials as Topic, biology, business.industry, Incidence, Antibodies, Monoclonal, Human Challenge Study, General Medicine, Middle Aged, Models, Theoretical, Antibodies, Neutralizing, Clinical trial, Respiratory syncytial virus (RSV), Respiratory Syncytial Virus, Human, Immunology, biology.protein, Female, Seasons, Respiratory Syncytial Virus, Antibody, business, Algorithms
Abstract

Background Neutralizing mAbs can prevent communicable viral diseases. MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) under development to prevent RSV infection in infants. Development and validation of methods to predict efficacious doses of neutralizing antibodies across patient populations exposed to a time-varying force of infection (i.e., seasonal variation) are necessary. Methods Five decades of clinical trial literature were leveraged to build a model-based meta-analysis (MBMA) describing the relationship between RSV serum neutralizing activity (SNA) and clinical endpoints. The MBMA was validated by backward translation to animal challenge experiments and forward translation to predict results of a recent RSV mAb trial. MBMA predictions were evaluated against a human trial of 70 participants who received either placebo or one of four dose-levels of MK-1654 and were challenged with RSV [NCT04086472]. The MBMA was used to perform clinical trial simulations and predict efficacy of MK-1654 in the infant target population. Findings The MBMA established a quantitative relationship between RSV SNA and clinical endpoints. This relationship was quantitatively consistent with animal model challenge experiments and results of a recently published clinical trial. Additionally, SNA elicited by increasing doses of MK-1654 in humans reduced RSV symptomatic infection rates with a quantitative relationship that approximated the MBMA. The MBMA indicated a high probability that a single dose of ≥ 75 mg of MK-1654 will result in prophylactic efficacy (> 75% for 5 months) in infants. Interpretation An MBMA approach can predict efficacy of neutralizing antibodies against RSV and potentially other respiratory pathogens.

Published
2021

28. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author

Lee, Phil H., primary, Anttila, Verneri, additional, Won, Hyejung, additional, Feng, Yen-Chen A., additional, Rosenthal, Jacob, additional, Zhu, Zhaozhong, additional, Tucker-Drob, Elliot M., additional, Nivard, Michel G., additional, Grotzinger, Andrew D., additional, Posthuma, Danielle, additional, Wang, Meg M.-J., additional, Yu, Dongmei, additional, Stahl, Eli A., additional, Walters, Raymond K., additional, Anney, Richard J.L., additional, Duncan, Laramie E., additional, Ge, Tian, additional, Adolfsson, Rolf, additional, Banaschewski, Tobias, additional, Belangero, Sintia, additional, Cook, Edwin H., additional, Coppola, Giovanni, additional, Derks, Eske M., additional, Hoekstra, Pieter J., additional, Kaprio, Jaakko, additional, Keski-Rahkonen, Anna, additional, Kirov, George, additional, Kranzler, Henry R., additional, Luykx, Jurjen J., additional, Rohde, Luis A., additional, Zai, Clement C., additional, Agerbo, Esben, additional, Arranz, M.J., additional, Asherson, Philip, additional, Bækvad-Hansen, Marie, additional, Baldursson, Gísli, additional, Bellgrove, Mark, additional, Belliveau, Richard A., additional, Buitelaar, Jan, additional, Burton, Christie L., additional, Bybjerg-Grauholm, Jonas, additional, Casas, Miquel, additional, Cerrato, Felecia, additional, Chambert, Kimberly, additional, Churchhouse, Claire, additional, Cormand, Bru, additional, Crosbie, Jennifer, additional, Dalsgaard, Søren, additional, Demontis, Ditte, additional, Doyle, Alysa E., additional, Dumont, Ashley, additional, Elia, Josephine, additional, Grove, Jakob, additional, Gudmundsson, Olafur O., additional, Haavik, Jan, additional, Hakonarson, Hakon, additional, Hansen, Christine S., additional, Hartman, Catharina A., additional, Hawi, Ziarih, additional, Hervás, Amaia, additional, Hougaard, David M., additional, Howrigan, Daniel P., additional, Huang, Hailiang, additional, Kuntsi, Jonna, additional, Langley, Kate, additional, Lesch, Klaus-Peter, additional, Leung, Patrick W.L., additional, Loo, Sandra K., additional, Martin, Joanna, additional, Martin, Alicia R., additional, McGough, James J., additional, Medland, Sarah E., additional, Moran, Jennifer L., additional, Mors, Ole, additional, Mortensen, Preben B., additional, Oades, Robert D., additional, Palmer, Duncan S., additional, Pedersen, Carsten B., additional, Pedersen, Marianne G., additional, Peters, Triinu, additional, Poterba, Timothy, additional, Poulsen, Jesper B., additional, Ramos-Quiroga, Josep Antoni, additional, Reif, Andreas, additional, Ribasés, Marta, additional, Rothenberger, Aribert, additional, Rovira, Paula, additional, Sánchez-Mora, Cristina, additional, Satterstrom, F. Kyle, additional, Schachar, Russell, additional, Artigas, Maria Soler, additional, Steinberg, Stacy, additional, Stefansson, Hreinn, additional, Turley, Patrick, additional, Walters, G. Bragi, additional, Werge, Thomas, additional, Zayats, Tetyana, additional, Arking, Dan E., additional, Bettella, Francesco, additional, Buxbaum, Joseph D., additional, Christensen, Jane H., additional, Collins, Ryan L., additional, Coon, Hilary, additional, De Rubeis, Silvia, additional, Delorme, Richard, additional, Grice, Dorothy E., additional, Hansen, Thomas F., additional, Holmans, Peter A., additional, Hope, Sigrun, additional, Hultman, Christina M., additional, Klei, Lambertus, additional, Ladd-Acosta, Christine, additional, Magnusson, Pall, additional, Nærland, Terje, additional, Nyegaard, Mette, additional, Pinto, Dalila, additional, Qvist, Per, additional, Rehnström, Karola, additional, Reichenberg, Abraham, additional, Reichert, Jennifer, additional, Roeder, Kathryn, additional, Rouleau, Guy A., additional, Saemundsen, Evald, additional, Sanders, Stephan J., additional, Sandin, Sven, additional, St Pourcain, Beate, additional, Stefansson, Kari, additional, Sutcliffe, James S., additional, Talkowski, Michael E., additional, Weiss, Lauren A., additional, Willsey, A. Jeremy, additional, Agartz, Ingrid, additional, Akil, Huda, additional, Albani, Diego, additional, Alda, Martin, additional, Als, Thomas D., additional, Anjorin, Adebayo, additional, Backlund, Lena, additional, Bass, Nicholas, additional, Bauer, Michael, additional, Baune, Bernhard T., additional, Bellivier, Frank, additional, Bergen, Sarah E., additional, Berrettini, Wade H., additional, Biernacka, Joanna M., additional, Blackwood, Douglas H.R., additional, Bøen, Erlend, additional, Budde, Monika, additional, Bunney, William, additional, Burmeister, Margit, additional, Byerley, William, additional, Byrne, Enda M., additional, Cichon, Sven, additional, Clarke, Toni-Kim, additional, Coleman, Jonathan R.I., additional, Craddock, Nicholas, additional, Curtis, David, additional, Czerski, Piotr M., additional, Dale, Anders M., additional, Dalkner, Nina, additional, Dannlowski, Udo, additional, Degenhardt, Franziska, additional, Di Florio, Arianna, additional, Elvsåshagen, Torbjørn, additional, Etain, Bruno, additional, Fischer, Sascha B., additional, Forstner, Andreas J., additional, Forty, Liz, additional, Frank, Josef, additional, Frye, Mark, additional, Fullerton, Janice M., additional, Gade, Katrin, additional, Gaspar, Héléna A., additional, Gershon, Elliot S., additional, Gill, Michael, additional, Goes, Fernando S., additional, Gordon, Scott D., additional, Gordon-Smith, Katherine, additional, Green, Melissa J., additional, Greenwood, Tiffany A., additional, Grigoroiu-Serbanescu, Maria, additional, Guzman-Parra, José, additional, Hauser, Joanna, additional, Hautzinger, Martin, additional, Heilbronner, Urs, additional, Herms, Stefan, additional, Hoffmann, Per, additional, Holland, Dominic, additional, Jamain, Stéphane, additional, Jones, Ian, additional, Jones, Lisa A., additional, Kandaswamy, Radhika, additional, Kelsoe, John R., additional, Kennedy, James L., additional, Joachim, Oedegaard Ketil, additional, Kittel-Schneider, Sarah, additional, Kogevinas, Manolis, additional, Koller, Anna C., additional, Lavebratt, Catharina, additional, Lewis, Cathryn M., additional, Li, Qingqin S., additional, Lissowska, Jolanta, additional, Loohuis, Loes M.O., additional, Lucae, Susanne, additional, Maaser, Anna, additional, Malt, Ulrik F., additional, Martin, Nicholas G., additional, Martinsson, Lina, additional, McElroy, Susan L., additional, McMahon, Francis J., additional, McQuillin, Andrew, additional, Melle, Ingrid, additional, Metspalu, Andres, additional, Millischer, Vincent, additional, Mitchell, Philip B., additional, Montgomery, Grant W., additional, Morken, Gunnar, additional, Morris, Derek W., additional, Müller-Myhsok, Bertram, additional, Mullins, Niamh, additional, Myers, Richard M., additional, Nievergelt, Caroline M., additional, Nordentoft, Merete, additional, Adolfsson, Annelie Nordin, additional, Nöthen, Markus M., additional, Ophoff, Roel A., additional, Owen, Michael J., additional, Paciga, Sara A., additional, Pato, Carlos N., additional, Pato, Michele T., additional, Perlis, Roy H., additional, Perry, Amy, additional, Potash, James B., additional, Reinbold, Céline S., additional, Rietschel, Marcella, additional, Rivera, Margarita, additional, Roberson, Mary, additional, Schalling, Martin, additional, Schofield, Peter R., additional, Schulze, Thomas G., additional, Scott, Laura J., additional, Serretti, Alessandro, additional, Sigurdsson, Engilbert, additional, Smeland, Olav B., additional, Stordal, Eystein, additional, Streit, Fabian, additional, Strohmaier, Jana, additional, Thorgeirsson, Thorgeir E., additional, Treutlein, Jens, additional, Turecki, Gustavo, additional, Vaaler, Arne E., additional, Vieta, Eduard, additional, Vincent, John B., additional, Wang, Yunpeng, additional, Witt, Stephanie H., additional, Zandi, Peter, additional, Adan, Roger A.H., additional, Alfredsson, Lars, additional, Ando, Tetsuya, additional, Aschauer, Harald, additional, Baker, Jessica H., additional, Bencko, Vladimir, additional, Bergen, Andrew W., additional, Birgegård, Andreas, additional, Perica, Vesna Boraska, additional, Brandt, Harry, additional, Burghardt, Roland, additional, Carlberg, Laura, additional, Cassina, Matteo, additional, Clementi, Maurizio, additional, Courtet, Philippe, additional, Crawford, Steven, additional, Crow, Scott, additional, Crowley, James J., additional, Danner, Unna N., additional, Davis, Oliver S.P., additional, Degortes, Daniela, additional, DeSocio, Janiece E., additional, Dick, Danielle M., additional, Dina, Christian, additional, Docampo, Elisa, additional, Egberts, Karin, additional, Ehrlich, Stefan, additional, Espeseth, Thomas, additional, Fernández-Aranda, Fernando, additional, Fichter, Manfred M., additional, Foretova, Lenka, additional, Forzan, Monica, additional, Gambaro, Giovanni, additional, Giegling, Ina, additional, Gonidakis, Fragiskos, additional, Gorwood, Philip, additional, Mayora, Monica Gratacos, additional, Guo, Yiran, additional, Halmi, Katherine A., additional, Hatzikotoulas, Konstantinos, additional, Hebebrand, Johannes, additional, Helder, Sietske G., additional, Herpertz-Dahlmann, Beate, additional, Herzog, Wolfgang, additional, Hinney, Anke, additional, Imgart, Hartmut, additional, Jiménez-Murcia, Susana, additional, Johnson, Craig, additional, Jordan, Jennifer, additional, Julià, Antonio, additional, Kaminská, Deborah, additional, Karhunen, Leila, additional, Karwautz, Andreas, additional, Kas, Martien J.H., additional, Kaye, Walter H., additional, Kennedy, Martin A., additional, Kim, Youl-Ri, additional, Klareskog, Lars, additional, Klump, Kelly L., additional, Knudsen, Gun Peggy S., additional, Landén, Mikael, additional, Le Hellard, Stephanie, additional, Levitan, Robert D., additional, Li, Dong, additional, Lichtenstein, Paul, additional, Maj, Mario, additional, Marsal, Sara, additional, McDevitt, Sara, additional, Mitchell, James, additional, Monteleone, Palmiero, additional, Monteleone, Alessio Maria, additional, Munn-Chernoff, Melissa A., additional, Nacmias, Benedetta, additional, Navratilova, Marie, additional, O’Toole, Julie K., additional, Padyukov, Leonid, additional, Pantel, Jacques, additional, Papezova, Hana, additional, Rabionet, Raquel, additional, Raevuori, Anu, additional, Ramoz, Nicolas, additional, Reichborn-Kjennerud, Ted, additional, Ricca, Valdo, additional, Roberts, Marion, additional, Rujescu, Dan, additional, Rybakowski, Filip, additional, Scherag, André, additional, Schmidt, Ulrike, additional, Seitz, Jochen, additional, Slachtova, Lenka, additional, Slof-Op‘t Landt, Margarita C.T., additional, Slopien, Agnieszka, additional, Sorbi, Sandro, additional, Southam, Lorraine, additional, Strober, Michael, additional, Tortorella, Alfonso, additional, Tozzi, Federica, additional, Treasure, Janet, additional, Tziouvas, Konstantinos, additional, van Elburg, Annemarie A., additional, Wade, Tracey D., additional, Wagner, Gudrun, additional, Walton, Esther, additional, Watson, Hunna J., additional, Wichmann, H-Erich, additional, Woodside, D. Blake, additional, Zeggini, Eleftheria, additional, Zerwas, Stephanie, additional, Zipfel, Stephan, additional, Adams, Mark J., additional, Andlauer, Till F.M., additional, Berger, Klaus, additional, Binder, Elisabeth B., additional, Boomsma, Dorret I., additional, Castelao, Enrique, additional, Colodro-Conde, Lucía, additional, Direk, Nese, additional, Docherty, Anna R., additional, Domenici, Enrico, additional, Domschke, Katharina, additional, Dunn, Erin C., additional, Foo, Jerome C., additional, de. Geus, E.J.C., additional, Grabe, Hans J., additional, Hamilton, Steven P., additional, Horn, Carsten, additional, Hottenga, Jouke-Jan, additional, Howard, David, additional, Ising, Marcus, additional, Kloiber, Stefan, additional, Levinson, Douglas F., additional, Lewis, Glyn, additional, Magnusson, Patrik K.E., additional, Mbarek, Hamdi, additional, Middeldorp, Christel M., additional, Mostafavi, Sara, additional, Nyholt, Dale R., additional, Penninx, Brenda WJH., additional, Peterson, Roseann E., additional, Pistis, Giorgio, additional, Porteous, David J., additional, Preisig, Martin, additional, Quiroz, Jorge A., additional, Schaefer, Catherine, additional, Schulte, Eva C., additional, Shi, Jianxin, additional, Smith, Daniel J., additional, Thomson, Pippa A., additional, Tiemeier, Henning, additional, Uher, Rudolf, additional, van der Auwera, Sandra, additional, Weissman, Myrna M., additional, Alexander, Madeline, additional, Begemann, Martin, additional, Bramon, Elvira, additional, Buccola, Nancy G., additional, Cairns, Murray J., additional, Campion, Dominique, additional, Carr, Vaughan J., additional, Cloninger, C. Robert, additional, Cohen, David, additional, Collier, David A., additional, Corvin, Aiden, additional, DeLisi, Lynn E., additional, Donohoe, Gary, additional, Dudbridge, Frank, additional, Duan, Jubao, additional, Freedman, Robert, additional, Gejman, Pablo V., additional, Golimbet, Vera, additional, Godard, Stephanie, additional, Ehrenreich, Hannelore, additional, Hartmann, Annette M., additional, Henskens, Frans A., additional, Ikeda, Masashi, additional, Iwata, Nakao, additional, Jablensky, Assen V., additional, Joa, Inge, additional, Jönsson, Erik G., additional, Kelly, Brian J., additional, Knight, Jo, additional, Konte, Bettina, additional, Laurent-Levinson, Claudine, additional, Lee, Jimmy, additional, Lencz, Todd, additional, Lerer, Bernard, additional, Loughland, Carmel M., additional, Malhotra, Anil K., additional, Mallet, Jacques, additional, McDonald, Colm, additional, Mitjans, Marina, additional, Mowry, Bryan J., additional, Murphy, Kieran C., additional, Murray, Robin M., additional, O’Neill, F. Anthony, additional, Oh, Sang-Yun, additional, Palotie, Aarno, additional, Pantelis, Christos, additional, Pulver, Ann E., additional, Petryshen, Tracey L., additional, Quested, Digby J., additional, Riley, Brien, additional, Sanders, Alan R., additional, Schall, Ulrich, additional, Schwab, Sibylle G., additional, Scott, Rodney J., additional, Sham, Pak C., additional, Silverman, Jeremy M., additional, Sim, Kang, additional, Steixner, Agnes A., additional, Tooney, Paul A., additional, van Os, Jim, additional, Vawter, Marquis P., additional, Walsh, Dermot, additional, Weiser, Mark, additional, Wildenauer, Dieter B., additional, Williams, Nigel M., additional, Wormley, Brandon K., additional, Zhang, Fuquan, additional, Androutsos, Christos, additional, Arnold, Paul D., additional, Barr, Cathy L., additional, Barta, Csaba, additional, Bey, Katharina, additional, Bienvenu, O. Joseph, additional, Black, Donald W., additional, Brown, Lawrence W., additional, Budman, Cathy, additional, Cath, Danielle, additional, Cheon, Keun-Ah, additional, Ciullo, Valentina, additional, Coffey, Barbara J., additional, Cusi, Daniele, additional, Davis, Lea K., additional, Denys, Damiaan, additional, Depienne, Christel, additional, Dietrich, Andrea, additional, Eapen, Valsamma, additional, Falkai, Peter, additional, Fernandez, Thomas V., additional, Garcia-Delgar, Blanca, additional, Geller, Daniel A., additional, Gilbert, Donald L., additional, Grados, Marco A., additional, Greenberg, Erica, additional, Grünblatt, Edna, additional, Hagstrøm, Julie, additional, Hanna, Gregory L., additional, Hartmann, Andreas, additional, Hedderly, Tammy, additional, Heiman, Gary A., additional, Heyman, Isobel, additional, Hong, Hyun Ju, additional, Huang, Alden, additional, Huyser, Chaim, additional, Ibanez-Gomez, Laura, additional, Khramtsova, Ekaterina A., additional, Kim, Young Key, additional, Kim, Young-Shin, additional, King, Robert A., additional, Koh, Yun-Joo, additional, Konstantinidis, Anastasios, additional, Kook, Sodahm, additional, Kuperman, Samuel, additional, Leventhal, Bennett L., additional, Lochner, Christine, additional, Ludolph, Andrea G., additional, Madruga-Garrido, Marcos, additional, Malaty, Irene, additional, Maras, Athanasios, additional, McCracken, James T., additional, Meijer, Inge A., additional, Mir, Pablo, additional, Morer, Astrid, additional, Müller-Vahl, Kirsten R., additional, Münchau, Alexander, additional, Murphy, Tara L., additional, Naarden, Allan, additional, Nagy, Peter, additional, Nestadt, Gerald, additional, Nestadt, Paul S., additional, Nicolini, Humberto, additional, Nurmi, Erika L., additional, Okun, Michael S., additional, Paschou, Peristera, additional, Piras, Fabrizio, additional, Piras, Federica, additional, Pittenger, Christopher, additional, Plessen, Kerstin J., additional, Richter, Margaret A., additional, Rizzo, Renata, additional, Robertson, Mary, additional, Roessner, Veit, additional, Ruhrmann, Stephan, additional, Samuels, Jack F., additional, Sandor, Paul, additional, Schlögelhofer, Monika, additional, Shin, Eun-Young, additional, Singer, Harvey, additional, Song, Dong-Ho, additional, Song, Jungeun, additional, Spalletta, Gianfranco, additional, Stein, Dan J., additional, Stewart, S Evelyn, additional, Storch, Eric A., additional, Stranger, Barbara, additional, Stuhrmann, Manfred, additional, Tarnok, Zsanett, additional, Tischfield, Jay A., additional, Tübing, Jennifer, additional, Visscher, Frank, additional, Vulink, Nienke, additional, Wagner, Michael, additional, Walitza, Susanne, additional, Wanderer, Sina, additional, Woods, Martin, additional, Worbe, Yulia, additional, Zai, Gwyneth, additional, Zinner, Samuel H., additional, Sullivan, Patrick F., additional, Franke, Barbara, additional, Daly, Mark J., additional, Bulik, Cynthia M., additional, McIntosh, Andrew M., additional, O’Donovan, Michael C., additional, Zheutlin, Amanda, additional, Andreassen, Ole A., additional, Børglum, Anders D., additional, Breen, Gerome, additional, Edenberg, Howard J., additional, Fanous, Ayman H., additional, Faraone, Stephen V., additional, Gelernter, Joel, additional, Mathews, Carol A., additional, Mattheisen, Manuel, additional, Mitchell, Karen S., additional, Neale, Michael C., additional, Nurnberger, John I., additional, Ripke, Stephan, additional, Santangelo, Susan L., additional, Scharf, Jeremiah M., additional, Stein, Murray B., additional, Thornton, Laura M., additional, Walters, James T.R., additional, Wray, Naomi R., additional, Geschwind, Daniel H., additional, Neale, Benjamin M., additional, Kendler, Kenneth S., additional, and Smoller, Jordan W., additional

Published
2019
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29. Mitochondrial transcription factor A (TFAM) rs1937 and AP endonuclease 1 (APE1) rs1130409 alleles are associated with reduced cognitive performance

Author

Ivar Reinvang, Tone Tønjum, Per Selnes, Thomas Espeseth, Tormod Fladby, Vidar Stenset, Meryl S. Lillenes, Mari Støen, and Clara-Cecilie Günther

Subjects
0301 basic medicine, Heterozygote, Mitochondrial DNA, DNA Repair, DNA repair, DNA damage, tau Proteins, DNA-Directed DNA Polymerase, Mitochondrion, Polymorphism, Single Nucleotide, AP endonuclease, Mitochondrial Proteins, 03 medical and health sciences, Alzheimer Disease, MUTYH, DNA-(Apurinic or Apyrimidinic Site) Lyase, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Aged, Aged, 80 and over, Genetics, Amyloid beta-Peptides, biology, General Neuroscience, Base excision repair, Middle Aged, TFAM, DNA Polymerase gamma, DNA-Binding Proteins, 030104 developmental biology, Case-Control Studies, biology.protein, Cognition Disorders, Reactive Oxygen Species, Biomarkers, DNA Damage, Transcription Factors
Abstract

Mitochondrial dysfunction and DNA damage is intimately connected to ageing and neurodegeneration, including Alzheimer’s disease (AD). A particular culprit in this context is oxidative stress, which is a result of increased reactive oxygen species (ROS) due to hyperactive or dysfunctional mitochondria and/or reduced DNA repair capacity. Base excision repair (BER) is the major pathway for repairing oxidative damage events in chromosomal and mitochondrial DNA. Defects in BER have been detected in ageing and neurodegeneration. Mitochondrial transcription factor A (TFAM) plays an important role in the maintenance of mitochondrial DNA integrity. The present study investigated single nucleotide polymorphisms (SNPs) in the genes encoding the BER components MutYH, OGG1, APE1, PolB and PolG and the gene encoding mitochondrial TFAM in a cohort of 161 AD patients, 96 non-AD patient controls (PC) and 192 healthy controls (HC). Notably, the minor allele carriers of APE1 rs1130409 and the common allele carriers of TFAM rs1937 were associated with reduced mini-mental state examination score in AD patients, PC and HC, with no distinction of SNP frequencies in either of these sub-groups. Collectively, the results suggest an association between DNA maintenance and decline in cognitive function. These studies enlighten the normal brain aging process and point to potential new biomarkers for cognitive function and impairment.

Published
2017

30. Pupillary and behavioral markers of alerting and orienting: An individual difference approach

Author

Thomas Espeseth, Bruno Laeng, Thomas Hagen, and Samira Aminihajibashi

Subjects
Cognitive Neuroscience, Individuality, Experimental and Cognitive Psychology, Posner cueing task, Affect (psychology), 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), Reaction Time, Developmental and Educational Psychology, Humans, Attention, 0501 psychology and cognitive sciences, Cued speech, 05 social sciences, Individual difference, Pupil, Cognition, Uncorrelated, Alertness, Neuropsychology and Physiological Psychology, Locus coeruleus, Cues, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract

Measuring task-evoked pupillary (TEP) responses as an index of phasic activity in the locus coeruleus (LC), we examined two competing hypotheses regarding the alerting and orienting mechanisms of attention. According to a dual mechanism account (Fernandez-Duque & Posner, 1997), two separate noradrenergic and cholinergic mechanisms modulate, respectively, the alerting and orienting effects. However, Corbetta and colleagues (2008) proposed that LC phasic activity may also be involved in orienting effect through its functional relationship with the ventral attentional network. We recruited seventy-five healthy Norwegian participants to perform a Posner cueing task. Both behavioral and pupillary responses revealed the alerting effect. Also, both behavioral and pupillary responses indicated that cued attention is affected by age. Behavioral responses also revealed orienting effect However, we found no TEP differences between valid, invalid, and neutral conditions, suggesting that TEP effects were driven by the alerting effect of cue presentation. Moreover, both behavioral and pupillary estimates of alertness and orienting were uncorrelated. Finally, individual differences in general cognitive abilities did not appear to affect the orienting and alerting mechanisms. This pattern of results is consistent with the dual mechanism account of attention. However, the LC involvement in the (re)orienting attention may be driven by state-specific factors.

Published
2020

31. Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

Author

Yao, Shuyang, primary, Kuja-Halkola, Ralf, additional, Martin, Joanna, additional, Lu, Yi, additional, Lichtenstein, Paul, additional, Norring, Claes, additional, Birgegård, Andreas, additional, Yilmaz, Zeynep, additional, Hübel, Christopher, additional, Watson, Hunna, additional, Baker, Jessica, additional, Almqvist, Catarina, additional, Thornton, Laura M., additional, Magnusson, Patrik K., additional, Bulik, Cynthia M., additional, Larsson, Henrik, additional, Adan, Roger, additional, Ando, Tetsuya, additional, Bergen, Andrew, additional, Berrettini, Wade, additional, Boni, Claudette, additional, Boraska Perica, Vesna, additional, Brandt, Harry, additional, Burghardt, Roland, additional, Cassina, Matteo, additional, Cesta, Carolyn, additional, Clementi, Maurizio, additional, Coleman, Joni, additional, Cone, Roger, additional, Courtet, Philippe, additional, Crawford, Steven, additional, Crow, Scott, additional, Crowley, James, additional, Danner, Unna, additional, Davis, Oliver, additional, de Zwaan, Martina, additional, Dedoussis, George, additional, Degortes, Daniela, additional, DeSocio, Janiece, additional, Dick, Danielle, additional, Dikeos, Dimitris, additional, Dmitrzak-Weglarz, Monika, additional, Docampo, Elisa, additional, Egberts, Karin, additional, Ehrlich, Stefan, additional, Escaramís, Geòrgia, additional, Esko, Tõnu, additional, Estivill, Xavier, additional, Favaro, Angela, additional, Fernández-Aranda, Fernando, additional, Fichter, Manfred, additional, Finan, Chris, additional, Fischer, Krista, additional, Föcker, Manuel, additional, Foretova, Lenka, additional, Forzan, Monica, additional, Franklin, Christopher, additional, Gaspar, Héléna, additional, Gonidakis, Fragiskos, additional, Gorwood, Philip, additional, Gratacos, Monica, additional, Guillaume, Sébastien, additional, Guo, Yiran, additional, Hakonarson, Hakon, additional, Halmi, Katherine, additional, Hatzikotoulas, Konstantinos, additional, Hauser, Joanna, additional, Hebebrand, Johannes, additional, Helder, Sietske, additional, Hendriks, Judith, additional, Herpertz-Dahlmann, Beate, additional, Herzog, Wolfgang, additional, Hilliard, Christopher, additional, Hinney, Anke, additional, Huckins, Laura, additional, Hudson, James, additional, Huemer, Julia, additional, Imgart, Hartmut, additional, Inoko, Hidetoshi, additional, Jiménez-Murcia, Susana, additional, Johnson, Craig, additional, Jordan, Jenny, additional, Juréus, Anders, additional, Kalsi, Gursharan, additional, Kaminska, Debora, additional, Kaplan, Allan, additional, Kaprio, Jaakko, additional, Karhunen, Leila, additional, Karwautz, Andreas, additional, Kas, Martien, additional, Kaye, Walter, additional, Kennedy, James, additional, Kennedy, Martin, additional, Keski-Rahkonen, Anna, additional, Kiezebrink, Kirsty, additional, Kim, Youl-Ri, additional, Klump, Kelly, additional, Knudsen, Gun Peggy, additional, Koeleman, Bobby, additional, Koubek, Doris, additional, La Via, Maria, additional, Landén, Mikael, additional, Levitan, Robert, additional, Li, Dong, additional, Lilenfeld, Lisa, additional, Lissowska, Jolanta, additional, Magistretti, Pierre, additional, Maj, Mario, additional, Mannik, Katrin, additional, Martin, Nicholas, additional, McDevitt, Sara, additional, McGuffin, Peter, additional, Merl, Elisabeth, additional, Metspalu, Andres, additional, Meulenbelt, Ingrid, additional, Micali, Nadia, additional, Mitchell, James, additional, Mitchell, Karen, additional, Monteleone, Palmiero, additional, Monteleone, Alessio Maria, additional, Mortensen, Preben, additional, Munn-Chernoff, Melissa, additional, Nacmias, Benedetta, additional, Nilsson, Ida, additional, Ntalla, Ioanna, additional, O’Toole, Julie, additional, Pantel, Jacques, additional, Papezova, Hana, additional, Parker, Richard, additional, Rabionet, Raquel, additional, Raevuori, Anu, additional, Rajewski, Andrzej, additional, Ramoz, Nicolas, additional, Rayner, N. William, additional, Reichborn-Kjennerud, Ted, additional, Ricca, Valdo, additional, Ripke, Stephan, additional, Ritschel, Franziska, additional, Roberts, Marion, additional, Rotondo, Alessandro, additional, Rybakowski, Filip, additional, Santonastaso, Paolo, additional, Scherag, André, additional, Schmidt, Ulrike, additional, Schork, Nicholas, additional, Schosser, Alexandra, additional, Seitz, Jochen, additional, Slachtova, Lenka, additional, Slagboom, P. Eline, additional, Slof-Op’t Landt, Margarita, additional, Slopien, Agnieszka, additional, Smith, Tosha, additional, Sorbi, Sandro, additional, Strengman, Eric, additional, Strober, Michael, additional, Sullivan, Patrick, additional, Szatkiewicz, Jin, additional, Szeszenia-Dabrowska, Neonila, additional, Tachmazidou, Ioanna, additional, Tenconi, Elena, additional, Thornton, Laura, additional, Tortorella, Alfonso, additional, Tozzi, Federica, additional, Treasure, Janet, additional, Tsitsika, Artemis, additional, Tziouvas, Konstantinos, additional, van Elburg, Annemarie, additional, van Furth, Eric, additional, Wade, Tracey, additional, Wagner, Gudrun, additional, Walton, Esther, additional, Woodside, D. Blake, additional, Yao, Shuyang, additional, Zeggini, Eleftheria, additional, Zerwas, Stephanie, additional, Zipfel, Stephan, additional, Alfredsson, Lars, additional, Andreassen, Ole, additional, Aschauer, Harald, additional, Barrett, Jeffrey, additional, Bencko, Vladimir, additional, Carlberg, Laura, additional, Cichon, Sven, additional, Cohen-Woods, Sarah, additional, Dina, Christian, additional, Ding, Bo, additional, Espeseth, Thomas, additional, Floyd, James, additional, Gallinger, Steven, additional, Gambaro, Giovanni, additional, Giegling, Ina, additional, Herms, Stefan, additional, Janout, Vladimir, additional, Julià, Antonio, additional, Klareskog, Lars, additional, Le Hellard, Stephanie, additional, Leboyer, Marion, additional, Lundervold, Astri, additional, Marsal, Sara, additional, Mattingsdal, Morten, additional, Navratilova, Marie, additional, Ophoff, Roel, additional, Palotie, Aarno, additional, Pinto, Dalila, additional, Ripatti, Samuli, additional, Rujescu, Dan, additional, Scherer, Stephen, additional, Scott, Laura, additional, Sladek, Robert, additional, Soranzo, Nicole, additional, Southam, Lorraine, additional, Steen, Vidar, additional, Wichmann, H-Erich, additional, Widen, Elisabeth, additional, Breen, Gerome, additional, and Bulik, Cynthia, additional

Published
2019
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33. Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways

Author

Lam, Max, primary, Hill, W. David, additional, Trampush, Joey W., additional, Yu, Jin, additional, Knowles, Emma, additional, Davies, Gail, additional, Stahl, Eli, additional, Huckins, Laura, additional, Liewald, David C., additional, Djurovic, Srdjan, additional, Melle, Ingrid, additional, Sundet, Kjetil, additional, Christoforou, Andrea, additional, Reinvang, Ivar, additional, DeRosse, Pamela, additional, Lundervold, Astri J., additional, Steen, Vidar M., additional, Espeseth, Thomas, additional, Räikkönen, Katri, additional, Widen, Elisabeth, additional, Palotie, Aarno, additional, Eriksson, Johan G., additional, Giegling, Ina, additional, Konte, Bettina, additional, Hartmann, Annette M., additional, Roussos, Panos, additional, Giakoumaki, Stella, additional, Burdick, Katherine E., additional, Payton, Antony, additional, Ollier, William, additional, Chiba-Falek, Ornit, additional, Attix, Deborah K., additional, Need, Anna C., additional, Cirulli, Elizabeth T., additional, Voineskos, Aristotle N., additional, Stefanis, Nikos C., additional, Avramopoulos, Dimitrios, additional, Hatzimanolis, Alex, additional, Arking, Dan E., additional, Smyrnis, Nikolaos, additional, Bilder, Robert M., additional, Freimer, Nelson A., additional, Cannon, Tyrone D., additional, London, Edythe, additional, Poldrack, Russell A., additional, Sabb, Fred W., additional, Congdon, Eliza, additional, Conley, Emily Drabant, additional, Scult, Matthew A., additional, Dickinson, Dwight, additional, Straub, Richard E., additional, Donohoe, Gary, additional, Morris, Derek, additional, Corvin, Aiden, additional, Gill, Michael, additional, Hariri, Ahmad R., additional, Weinberger, Daniel R., additional, Pendleton, Neil, additional, Bitsios, Panos, additional, Rujescu, Dan, additional, Lahti, Jari, additional, Le Hellard, Stephanie, additional, Keller, Matthew C., additional, Andreassen, Ole A., additional, Deary, Ian J., additional, Glahn, David C., additional, Malhotra, Anil K., additional, and Lencz, Todd, additional

Published
2019
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34. Antibody responses to crucial functional epitopes as a novel approach to assess immunogenicity of vaccine adjuvants

Author

Awasthi, Sita, primary, Hook, Lauren M., additional, Swaminathan, Gokul, additional, Cairns, Tina M., additional, Brooks, Benjamin, additional, Smith, Jeffrey S., additional, Ditto, Noah T., additional, Gindy, Marian E., additional, Bett, Andrew J., additional, Espeseth, Amy S., additional, Cohen, Gary H., additional, and Friedman, Harvey M., additional

Published
2019
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38. F5. Brain Disorders are Associated With Increased Brain Age

Author

Ole A. Andreassen, N. Trung Doan, Jan Egil Nordvik, Thomas Espeseth, Andreas Papassotiropoulos, Deanna Barch, Martina J. Lund, Helena Fatouros-Bergmann, Andreas Meyer-Lindenberg, Klaus-Peter Lesch, Erik G. Joensson, Karin Persson, Ingrid Agartz, Marco Papalino, Pasquale Di Carlo, Vidar M. Steen, Alessandro Bertolino, Tobias Kaufmann, Emanuel Schwarz, Srdjan Djurovic, Annette Conzelmann, Torbjørn Elvsåshagen, Stefan Borgwardt, Dag Alnæs, Ingrid Melle, Lena Flyckt, Stephanie Le Hellard, Paul Pauli, Nils Inge Landrø, Giulio Pergola, Ulrik Fredrik Malt, Barbara Franke, Asta Håberg, Lars T. Westlye, Geir Selbæk, Peter Kirsch, Lars Nyberg, Erlend Bøen, and Dennis van der Meer

Subjects
Biological Psychiatry
Published
2018

39. Proactive and reactive modes of cognitive control can operate independently and simultaneously

Author

Thomas Hagen, Thomas Espeseth, and Verónica Mäki-Marttunen

Subjects
Adult, Male, media_common.quotation_subject, Control (management), Experimental and Cognitive Psychology, Context (language use), Neuropsychological Tests, 050105 experimental psychology, Task (project management), Young Adult, 03 medical and health sciences, Web-based experiments, Cognition, 0302 clinical medicine, Reward, Arts and Humanities (miscellaneous), Perception, Reaction Time, Developmental and Educational Psychology, Humans, Attention, 0501 psychology and cognitive sciences, Situational ethics, media_common, Motivation, 05 social sciences, General Medicine, Female, Psychology, 030217 neurology & neurosurgery, Cognitive load, Cognitive psychology
Abstract

Cognitive control enables optimal biasing of attention, perception, and actions in the service of mental or behavioral goals. To understand the variability of applied cognitive control, we need to unravel the relation between two underlying mechanisms: proactive and reactive modes. During proactive cognitive control, goal-relevant information is selected before the occurrence of a cognitively demanding event, and is actively maintained for as long as required by the task. During reactive mode, cognitive control is transiently activated only after the cognitively demanding event has occurred. Mechanistically, proactive and reactive control modes may be at least semi-independent and engaged simultaneously, but this has so far not been demonstrated empirically. Situational demands and an individual's cognitive capacity and motivation may bias behavior towards one or the other mode. Reward induces more proactive processing in the AX-CPT task, whereas context load induces reactive processing. We combined these manipulations to investigate the extent to which proactive and reactive control modes can operate independently and simultaneously. The results replicated already published effects of reward incentives and context load. Most importantly, these effects were essentially independent of each other, suggesting that proactive and reactive cognitive control modes depend on separate information-processing and neural mechanisms. The results also show that while proactive processing is influenced by reward, reactive processing seems independent of such factor. These findings have implications for our understanding of the structure of cognitive control and cognitive motivation, and are relevant for the design of interventions to improve cognitive control in various developmental and neuropsychiatric groups.

Published
2019

41. F5. Brain Disorders are Associated With Increased Brain Age

Author

Kaufmann, Tobias, primary, van der Meer, Dennis, additional, Doan, N. Trung, additional, Schwarz, Emanuel, additional, Lund, Martina J., additional, Agartz, Ingrid, additional, Alnæs, Dag, additional, Barch, Deanna, additional, Bertolino, Alessandro, additional, Bøen, Erlend, additional, Borgwardt, Stefan, additional, Conzelmann, Annette, additional, Di Carlo, Pasquale, additional, Djurovic, Srdjan, additional, Elvsåshagen, Torbjørn, additional, Espeseth, Thomas, additional, Fatouros-Bergmann, Helena, additional, Flyckt, Lena, additional, Franke, Barbara, additional, Håberg, Asta, additional, Jönsson, Erik G., additional, Kirsch, Peter, additional, Landrø, Nils I., additional, Le Hellard, Stephanie, additional, Lesch, Klaus-Peter, additional, Malt, Ulrik F., additional, Melle, Ingrid, additional, Meyer-Lindenberg, Andreas, additional, Nordvik, Jan Egil, additional, Nyberg, Lars, additional, Papalino, Marco, additional, Papassotiropoulos, Andreas, additional, Pauli, Paul, additional, Pergola, Giulio, additional, Persson, Karin, additional, Selbæk, Geir, additional, Steen, Vidar M., additional, Andreassen, Ole A., additional, and Westlye, Lars T., additional

Published
2018
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42. A novel method for strict intranasal delivery of non-replicating RSV vaccines in cotton rats and non-human primates

Author

Citron, Michael P., primary, Patel, Manishkumar, additional, Purcell, Mona, additional, Lin, Shu-An, additional, Rubins, Daniel J., additional, McQuade, Paul, additional, Callahan, Cheryl, additional, Gleason, Alexa, additional, Petrescu, Ioan, additional, Knapp, Walter, additional, Orekie, Chinedu, additional, Chamarthy, Sai, additional, Wen, Zhiyun, additional, Touch, Sinoeun, additional, Pine, Matthew, additional, Fontenot, Jane, additional, Douglas, Cameron, additional, Liang, Xiaoping, additional, and Espeseth, Amy S., additional

Published
2018
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43. F50. Genetic Architecture of Hippocampal Subfield Volumes: Shared and Specific Influences

Author

van der Meer, Dennis, primary, Kaufmann, Tobias, additional, Córdova-Palomera, Aldo, additional, Bettella, Francesco, additional, Frei, Oleksandr, additional, Doan, N. Trung, additional, Alnæs, Dag, additional, Moberget, Torgeir, additional, Agartz, Ingrid, additional, Bertolino, Alessandro, additional, Brandt, Christine L., additional, Buitelaar, Jan K., additional, Djurovic, Srdjan, additional, Dørum, Erlend D., additional, Espeseth, Thomas, additional, Faraone, Stephen V., additional, Franke, Barbara, additional, Håberg, Asta, additional, Haatveit, Beathe C., additional, Hartman, Catharina, additional, Le Hellard, Stephanie, additional, Heslenfeld, Dirk, additional, Hoekstra, Pieter, additional, Jönsson, Erik G., additional, Kolskår, Knut, additional, Lund, Martina J., additional, Melle, Ingrid, additional, Norbom, Linn B., additional, Nordvik, Jan E., additional, Nyberg, Lars, additional, Oosterlaan, Jaap, additional, Papassotiropoulos, Andreas, additional, Pergola, Giulio, additional, Richard, Genevieve, additional, Sanders, Anne-Marthe, additional, Steen, Vidar M., additional, Ulrichsen, Kristine M., additional, Andreassen, Ole, additional, and Westlye, Lars T., additional

Published
2018
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44. Network-specific effects of age and in-scanner subject motion: A resting-state fMRI study of 238 healthy adults

Author

Athanasia M. Mowinckel, Lars T. Westlye, and Thomas Espeseth

Subjects
Adult, Male, Cognitive aging, Aging, Rest, Cognitive Neuroscience, Sensory system, Developmental psychology, Motion, Young Adult, Frontal regions, Image Interpretation, Computer-Assisted, Neural Pathways, medicine, Humans, Default mode network, Aged, Aged, 80 and over, Brain Mapping, medicine.diagnostic_test, Resting state fMRI, Functional connectivity, Age Factors, Brain, Cognition, Middle Aged, Magnetic Resonance Imaging, Neurology, Female, Artifacts, Functional magnetic resonance imaging, Psychology, Neuroscience
Abstract

Cognitive aging is accompanied by a range of structural and functional differences in the brain, even in the absence of neurodegenerative disease. Functional magnetic resonance imaging (fMRI) studies have reported increased bilateral activation during task performance in elderly participants compared to their younger counterparts, particularly in frontal regions. Alterations have also been observed in the functional architecture of the resting brain, suggesting that aging is associated with changes in the organization of the networks of the brain. However, previous studies have largely focused on the default mode network, and little is known about the effects of age on other resting state-networks (RSNs). The aim of the present study was to investigate age-differences in resting state functional connectivity (RSFC) using fMRI data obtained during rest from 238 healthy participants aged 21–80 years. Using independent component analysis (ICA) and dual-regression, the results revealed age-related increases in RSFC across a range of RSNs, including task-positive networks in frontal and parietal regions. In contrast, age-related reductions in the default mode network and occipital visual networks were observed. Furthermore, whereas the effects of age on the various RSNs were found independent of age-related decreases in gray matter volume, sex and subject motion, we report strong positive and widespread effects of estimated subject motion on the RSFC across RSNs. The results provide support for the notion of network-specific effects in aging, manifested as increased tonic activation of task-positive networks, supporting higher-order cognitive functions and cognitive control, along with reduced task-negative default mode network and sensory visual networks during rest. The present results also corroborate recent evidence of strong influence of subject motion on estimated functional connectivity measures and strongly suggest that studies using RSFC measures as imaging phenotypes should adjust for individual differences in in-scanner subject motion.

Published
2012

45. A cognitive phenotype for a polymorphism in the nicotinic receptor gene CHRNA4

Author

Raja Parasuraman, Thomas Espeseth, and Pamela M. Greenwood

Subjects
Genotype, Brain activity and meditation, Cognitive Neuroscience, Brain, Genetic Variation, Cognition, Stimulation, Receptors, Nicotinic, Phenotype, Behavioral Neuroscience, Neuropsychology and Physiological Psychology, Nicotinic agonist, Visual Perception, Humans, SNP, Attention, Allele, Psychology, Receptor, Neuroscience, Psychomotor Performance
Abstract

Drawing on converging behavioral, electrophysiological, and imaging evidence, we advance an hypothesis for a cognitive phenotype of a SNP in the CHRNA4 gene encoding the α(4) subunit of α(4)β(2) nicotinic receptors. First, we review evidence that visuospatial attention can be decomposed into several component processes. Secondly, we consider evidence that one component, redirection of attention, is modulated by the nicotinic cholinergic system. Third, we review evidence that nicotinic stimulation exerts effects at the network level. Fourth, we consider evidence that normal variation in this SNP exerts nicotine-like modulatory effects on visuospatial attention. Fifth, we hypothesize that the cognitive phenotype of the CHRNA4 rs1044396 SNP is characterized by greater ability of T allele carriers to preferentially process events in the attentional focus compared to events outside the attentional focus. Finally, we consider effects of the CHNRA4 rs1044396 SNP on brain activity and cognition in light of our hypothesized cognitive phenotype. This hypothesis makes an important contribution to the development of cognitive phenomics by arguing for a cognitive phenotype of CHRNA4.

Published
2012

46. Generalizing parametric models by introducing trial-by-trial parameter variability: The case of TVA

Author

Søren Kyllingsbæk, Thomas Espeseth, Claus Bundesen, and Mads Dyrholm

Subjects
Generalization, Computer science, Applied Mathematics, media_common.quotation_subject, Model selection, Bayesian inference, Empirical research, Perception, Parametric model, Statistics, Visual attention, General Psychology, Selection (genetic algorithm), media_common
Abstract

We identify two biases in the traditional use of Bundesen’s Theory of Visual Attention (TVA) and show that they can be substantially reduced by introducing trial-by-trial variability in the model. We analyze whole and partial report data from a comprehensive empirical study with 347 participants and elaborate on Bayesian model selection theory for quantifying the advantage of trial-by-trial generalization in general. The analysis provides strong evidence of trial-by-trial variation in both the VSTM capacity parameter and perceptual threshold parameter of TVA. On average, the VSTM capacity bias was found to be at least half an item, while the perceptual threshold parameter was found to be underestimated by about 2 ms.

Published
2011

47. Working memory deficits in healthy APOE epsilon 4 carriers

Author

Inger Lise Winjevoll, Thomas Espeseth, Helge Rootwelt, and Ivar Reinvang

Subjects
Adult, Male, Apolipoprotein E, Genotype, Cognitive Neuroscience, Apolipoprotein E4, Experimental and Cognitive Psychology, Neuropsychological Tests, Developmental psychology, Behavioral Neuroscience, Sex Factors, Gene Frequency, medicine, Humans, Memory disorder, Allele, Episodic memory, Aged, Analysis of Variance, Memory Disorders, medicine.diagnostic_test, Working memory, Cognitive disorder, Cognition, Neuropsychological test, Middle Aged, medicine.disease, Memory, Short-Term, Pattern Recognition, Visual, Female, Psychology, Neuroscience, Photic Stimulation
Abstract

Studies on the cognitive effects of APOE allele variation in healthy persons have mainly focused on episodic memory performance as most sensitive to genetic effects. The present study focuses on working memory performance, measured both in an experimental paradigm, the AX-Continuous Performance Task (AX-CPT), and in neuropsychological test paradigms of span capacity and interference control. In a highly functioning healthy group (N = 186) of mean age 64.5 years we found evidence of reduced working memory performance in APOE ɛ4 carriers, with sex and ɛ4 dose as modifying variables. Several aspects of capacity and control in working memory were affected, while genetic effects were not present for measures of episodic memory. The pattern of results suggests that response inhibition is sensitive to genetic effects. In healthy individuals the broad range of neurobiological mechanisms associated with APOE is consistent with effects on non-memory cognitive subsystems, and gender effects may be modulated by interaction of APOE with myelination, androgen mechanisms, or broad patterns of age-related changes in gene expression.

Published
2010

48. Increased sensitivity to effects of normal aging and Alzheimer's disease on cortical thickness by adjustment for local variability in gray/white contrast: A multi-sample MRI study

Author

Douglas N. Greve, Lars T. Westlye, Bruce Fischl, Naftali Raz, Ingrid Agartz, Anders M. Dale, Thomas Espeseth, Kristine B. Walhovd, Anders M. Fjell, and Ivar Reinvang

Subjects
Adult, Male, Aging, Pathology, medicine.medical_specialty, Cognitive Neuroscience, media_common.quotation_subject, Disease, Sensitivity and Specificity, Article, White matter, Young Adult, Imaging, Three-Dimensional, Alzheimer Disease, Image Interpretation, Computer-Assisted, medicine, Humans, Contrast (vision), Sensitivity (control systems), Pathological, media_common, Cerebral Cortex, medicine.diagnostic_test, business.industry, Reproducibility of Results, Magnetic resonance imaging, Middle Aged, Image Enhancement, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Cerebral cortex, Female, Alzheimer's disease, Psychology, Nuclear medicine, business, Algorithms
Abstract

MRI-based estimates of cerebral morphometric properties, e.g. cortical thickness, are pivotal to studies of normal and pathological brain changes. These measures are based on automated or manual segmentation procedures, which utilize the tissue contrast between gray and white matter on T(1)-weighted MR images. Tissue contrast is unlikely to remain a constant property across groups of different age and health. An important question is therefore how the sensitivity of cortical thickness estimates is influenced by variability in WM/GM contrast. The effect of adjusting for variability in WM/GM contrast on age sensitivity of cortical thickness was tested in 1189 healthy subjects from six different samples, enabling evaluation of consistency of effects within and between sites and scanners. Further, the influence of Alzheimer's disease (AD) diagnosis on cortical thickness with and without correction for contrast was tested in an additional sample of 96 patients. In healthy controls, regional increases in the sensitivity of the cortical thickness measure to age were found after correcting for contrast. Across samples, the strongest effects were observed in frontal, lateral temporal and parietal areas. Controlling for contrast variability also increased the cortical thickness estimates' sensitivity to AD, thus replicating the finding in an independent clinical sample. The results showed increased sensitivity of cortical estimates to AD in areas earlier reported to be compromised in AD, including medial temporal, inferior and superior parietal regions. In sum, the findings indicate that adjusting for contrast can increase the sensitivity of MR morphometry to variables of interest.

Published
2009

49. Discovery of aminoheterocycles as a novel β-secretase inhibitor class: pH dependence on binding activity part 1

Author

Beth Pietrak, Hemaka A. Rajapakse, Dennis Colussi, Paul Zuck, Hong Zhu, Kristen L.G. Jones, Adam J. Simon, Samuel L. Graham, Shawn J. Stachel, M. Katharine Holloway, Diane M. Rush, Joseph P. Vacca, Amy S. Espeseth, Tim J. Allison, Ming-Tain Lai, Craig A. Coburn, Abigail Wolfe, and Sanjeev Munshi

Subjects
Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Plasma protein binding, Crystallography, X-Ray, Biochemistry, Structure-Activity Relationship, Heterocyclic Compounds, Drug Discovery, Hydrolase, Amyloid precursor protein, Structure–activity relationship, Enzyme Inhibitors, Molecular Biology, chemistry.chemical_classification, biology, Ligand binding assay, Organic Chemistry, Hydrogen-Ion Concentration, Enzyme binding, Enzyme, chemistry, Enzyme inhibitor, Drug Design, biology.protein, Molecular Medicine, Amyloid Precursor Protein Secretases, Protein Binding
Abstract

We have developed a novel series of heteroaromatic BACE-1 inhibitors. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile, we have discovered a pH dependent effect on the binding affinity as a result of the intrinsic pK(a) of these inhibitors and the pH of the BACE-1 enzyme binding assay.

Published
2009

50. Individual variation in a cholinergic receptor gene modulates attention

Author

Ivar Reinvang, Thomas Espeseth, Helge Rootwelt, Astri J. Lundervold, and Eike Wehling

Subjects
Adult, Male, Aging, Single-nucleotide polymorphism, Neuropsychological Tests, Receptors, Nicotinic, Polymorphism, Single Nucleotide, Young Adult, Memory, Genetic variation, Humans, Attention, Allele, Receptor, Aged, Aged, 80 and over, General Neuroscience, Memoria, Neuropsychology, Middle Aged, Nicotinic agonist, Cholinergic, Female, Psychology, Neuroscience, Psychomotor Performance
Abstract

Cholinergic influences on attention are well documented and recent evidence indicates that genetic variation in the alpha4beta2 nicotinic receptor affects attentional networks of the brain. Several behavioral and electrophysiological studies have shown that a common polymorphism in the CHRNA4 gene (rs1044396) affects aspects of visual and auditory attentional processing. We examined genetic effects on neuropsychological measures of memory and attention in an adult life-span sample (N=488). TT homozygotes perform speed and attention tasks more slowly than TC or CC allele carriers, with stronger effects on complex attention tasks in participant 70-79 years of age. There are no parallel effects on memory function. The results are consistent with clinical studies indicating that reduction in nicotinic receptor efficiency affects attention and speed, but not memory. Both normal age-related changes in receptor function and incipient pathology may have contributed to the results.

Published
2009

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