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2. Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Author

Vollstedt, E.J., Schaake, S., Lohmann, K., Padmanabhan, S., Brice, A., Lesage, S., Tesson, C., Vidailhet, M., Wurster, I., Hentati, F., Mirelman, A., Giladi, N., Marder, K., Waters, C., Fahn, S., Kasten, M., Brüggemann, N., Borsche, M., Foroud, T., Tolosa, E., Garrido, A., Annesi, G., Gagliardi, M., Bozi, M., Stefanis, L., Ferreira, J.J., Guedes, L. Correia, Avenali, M., Petrucci, S., Clark, L., Fedotova, E.Y., Abramycheva, N.Y., Alvarez, V., Menéndez-González, M., Maestre, S. Jesús, Gómez-Garre, P., Mir, P., Belin, A.C., Ran, C., Lin, Chih-Yu, Kuo, M.C., Crosiers, D., Wszolek, Z.K., Ross, O.A., Jankovic, J., Nishioka, K., Funayama, M., Clarimon, J., Williams-Gray, C.H., Camacho, M., Cornejo-Olivas, M., Torres-Ramirez, L., Wu, Y.R., Lee-Chen, G.J., Morgadinho, A., Pulkes, T., Termsarasab, P., Berg, D., Kuhlenbäumer, G., Kühn, A.A., Borngräber, F., Michele, G. de, Rosa, A. De, Zimprich, A., Puschmann, A., Mellick, G.D., Dorszewska, J., Carr, J., Ferese, R., Gambardella, S., Chase, B., Markopoulou, K., Satake, W., Toda, T., Rossi, M., Merello, M., Lynch, T., Olszewska, D.A., Lim, S.Y., Ahmad-Annuar, A., Tan, A.H., Al-Mubarak, B., Hanagasi, H., Koziorowski, D., Ertan, S., Genç, G., Aguiar, P. de Carvalho, Barkhuizen, M., Pimentel, M.M.G., Saunders-Pullman, R., Warrenburg, B.P.C. van de, Bressman, S., Toft, M., Appel-Cresswell, S., Lang, A.E., Skorvanek, M., Boon, A.J., Krüger, R., Sammler, E.M., Tumas, V., et al., Vollstedt, E.J., Schaake, S., Lohmann, K., Padmanabhan, S., Brice, A., Lesage, S., Tesson, C., Vidailhet, M., Wurster, I., Hentati, F., Mirelman, A., Giladi, N., Marder, K., Waters, C., Fahn, S., Kasten, M., Brüggemann, N., Borsche, M., Foroud, T., Tolosa, E., Garrido, A., Annesi, G., Gagliardi, M., Bozi, M., Stefanis, L., Ferreira, J.J., Guedes, L. Correia, Avenali, M., Petrucci, S., Clark, L., Fedotova, E.Y., Abramycheva, N.Y., Alvarez, V., Menéndez-González, M., Maestre, S. Jesús, Gómez-Garre, P., Mir, P., Belin, A.C., Ran, C., Lin, Chih-Yu, Kuo, M.C., Crosiers, D., Wszolek, Z.K., Ross, O.A., Jankovic, J., Nishioka, K., Funayama, M., Clarimon, J., Williams-Gray, C.H., Camacho, M., Cornejo-Olivas, M., Torres-Ramirez, L., Wu, Y.R., Lee-Chen, G.J., Morgadinho, A., Pulkes, T., Termsarasab, P., Berg, D., Kuhlenbäumer, G., Kühn, A.A., Borngräber, F., Michele, G. de, Rosa, A. De, Zimprich, A., Puschmann, A., Mellick, G.D., Dorszewska, J., Carr, J., Ferese, R., Gambardella, S., Chase, B., Markopoulou, K., Satake, W., Toda, T., Rossi, M., Merello, M., Lynch, T., Olszewska, D.A., Lim, S.Y., Ahmad-Annuar, A., Tan, A.H., Al-Mubarak, B., Hanagasi, H., Koziorowski, D., Ertan, S., Genç, G., Aguiar, P. de Carvalho, Barkhuizen, M., Pimentel, M.M.G., Saunders-Pullman, R., Warrenburg, B.P.C. van de, Bressman, S., Toft, M., Appel-Cresswell, S., Lang, A.E., Skorvanek, M., Boon, A.J., Krüger, R., Sammler, E.M., and Tumas, V., et al.

Abstract

Item does not contain fulltext, BACKGROUND: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. OBJECTIVE: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. METHODS: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. RESULTS: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. CONCLUSIONS: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward

Published
2023

3. Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD cohort

Author

Ertan, Fatoş Sibel (ORCID 0000-0003-1339-243X & YÖK ID 112829), Vollstedt, E.J.; Schaake, S.; Lohmann, K.; Padmanabhan, S.; Brice, A.; Lesage, S.; Tesson, C.; Vidailhet, M.; Wurster, I.; Hentati, F.; Mirelman, A.; Giladi, N.; Marder, K.; Waters, C.; Fahn, S.; Kasten, M.; Brüggemann, N.; Borsche, M.; Foroud, T.; Tolosa, E.; Garrido, A.; Annesi, G.; Gagliardi, M.; Bozi, M.; Stefanis, L.; Ferreira, J.J.; Guedes, L.C.; Avenali, M.; Petrucci, S.; Clark, L.; Fedotova, E.Y.; Abramycheva, N.Y.; Alvarez, V.; Menéndez-González, M.; Maestre, SJ.; Gómez-Garre, P.; Mir, P.; Belin, A.C.; Ran, C.; Lin, C.H.; Kuo, M.C.; Crosiers, D.; Wszolek, Z.K.; Ross, O.A.; Jankovic, J.; Nishioka, K.; Funayama, M.; Clarimon, J.; Williams-Gray, C.H.; Camacho, M.; Cornejo-Olivas, M.; Torres-Ramirez, L.; Wu, YR.; Lee-Chen, G.J.; Morgadinho, A.; Pulkes, T.; Termsarasab, P.; Berg, D.; Kuhlenbäumer, G.; Kühn, A.A.; Borngräber, F.; de Michele, G.; De Rosa, A.; Zimprich, A.; Puschmann, A.; Mellick, GD.; Dorszewska, J.; Carr, J.; Ferese, R.; Gambardella, S.; Chase, B.; Markopoulou, K.; Satake, W.; Toda, T.; Rossi, M.; Merello, M.; Lynch, T.; Olszewska, D.A.; Lim, S.Y.; Ahmad-Annuar, A.; Tan, A.H.; Al-Mubarak, B.; Hanagasi, H.; Koziorowski, D.; Genç, G.; Aguiar, P.D.; Barkhuizen, M.; Pimentel, M.M.G.; Saunders-Pullman, R.; van de Warrenburg, B.; Bressman, S.; Toft, M.; Appel-Cresswell, S.; Lang, A.E.; Skorvanek, M.; Boon, A.J.W.; Krüger, R.; Sammler, E.M.; Tumas, V.; Zhang, B.R.; Garraux, G.; Chung, SJ.; Kim, Y.J.; Winkelmann, J.; Sue, C.M.; Tan, E.K.; Damásio, J.; Klivényi, P.; Kostic, V.S.; Arkadir, D.; Martikainen, M.; Borges, V.; Hertz, J.M.; Brighina, L.; Spitz, M.; Suchowersky, O.; Riess, O.; Das, P.; Mollenhauer, B.; Gatto, E.M.; Petersen, M.S.; Hattori, N.; Wu, R.M.; Illarioshkin, S.N.; Valente, E.M.; Aasly, J.O.; Aasly, A.; Alcalay, R.N.; Thaler, A.; Farrer, M.J.; Brockmann, K.; Corvol, J.C.; Klein, C., School of Medicine, Ertan, Fatoş Sibel (ORCID 0000-0003-1339-243X & YÖK ID 112829), Vollstedt, E.J.; Schaake, S.; Lohmann, K.; Padmanabhan, S.; Brice, A.; Lesage, S.; Tesson, C.; Vidailhet, M.; Wurster, I.; Hentati, F.; Mirelman, A.; Giladi, N.; Marder, K.; Waters, C.; Fahn, S.; Kasten, M.; Brüggemann, N.; Borsche, M.; Foroud, T.; Tolosa, E.; Garrido, A.; Annesi, G.; Gagliardi, M.; Bozi, M.; Stefanis, L.; Ferreira, J.J.; Guedes, L.C.; Avenali, M.; Petrucci, S.; Clark, L.; Fedotova, E.Y.; Abramycheva, N.Y.; Alvarez, V.; Menéndez-González, M.; Maestre, SJ.; Gómez-Garre, P.; Mir, P.; Belin, A.C.; Ran, C.; Lin, C.H.; Kuo, M.C.; Crosiers, D.; Wszolek, Z.K.; Ross, O.A.; Jankovic, J.; Nishioka, K.; Funayama, M.; Clarimon, J.; Williams-Gray, C.H.; Camacho, M.; Cornejo-Olivas, M.; Torres-Ramirez, L.; Wu, YR.; Lee-Chen, G.J.; Morgadinho, A.; Pulkes, T.; Termsarasab, P.; Berg, D.; Kuhlenbäumer, G.; Kühn, A.A.; Borngräber, F.; de Michele, G.; De Rosa, A.; Zimprich, A.; Puschmann, A.; Mellick, GD.; Dorszewska, J.; Carr, J.; Ferese, R.; Gambardella, S.; Chase, B.; Markopoulou, K.; Satake, W.; Toda, T.; Rossi, M.; Merello, M.; Lynch, T.; Olszewska, D.A.; Lim, S.Y.; Ahmad-Annuar, A.; Tan, A.H.; Al-Mubarak, B.; Hanagasi, H.; Koziorowski, D.; Genç, G.; Aguiar, P.D.; Barkhuizen, M.; Pimentel, M.M.G.; Saunders-Pullman, R.; van de Warrenburg, B.; Bressman, S.; Toft, M.; Appel-Cresswell, S.; Lang, A.E.; Skorvanek, M.; Boon, A.J.W.; Krüger, R.; Sammler, E.M.; Tumas, V.; Zhang, B.R.; Garraux, G.; Chung, SJ.; Kim, Y.J.; Winkelmann, J.; Sue, C.M.; Tan, E.K.; Damásio, J.; Klivényi, P.; Kostic, V.S.; Arkadir, D.; Martikainen, M.; Borges, V.; Hertz, J.M.; Brighina, L.; Spitz, M.; Suchowersky, O.; Riess, O.; Das, P.; Mollenhauer, B.; Gatto, E.M.; Petersen, M.S.; Hattori, N.; Wu, R.M.; Illarioshkin, S.N.; Valente, E.M.; Aasly, J.O.; Aasly, A.; Alcalay, R.N.; Thaler, A.; Farrer, M.J.; Brockmann, K.; Corvol, J.C.; Klein, C., and School of Medicine

Abstract

Background: as gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: the objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: we conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: we collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward, Open Access funding enabled and organized by Projekt DEAL. Funding text 1: Carolyn M. Sue: Intellectual Property Rights: WO 2015/157794 A1. Advisory Boards: AbbVie. Employment: Northern Sydney Local Health District, Sydney, Australia. Honoraria: The International Movement Disorder Society for course directorships and invited lectures. Patents: WO 2015/157794 A1. Grants: 2018–22 NHMRC Partnership grant (APP1151906); 2018–22 MRFF NHMRC Practitioner Fellowship (App1136800); 2020–2025 NHMRC Partnership grant (APP11179029); 2020–2023 NHMRC Ideas Grant (APP1184403); 2021–5 MRFF 2020 Genomics Health Futures Mission Grant (APP2007959); 2021–23 ASAP Project grant ; Funding text 2: Natalya Y. Abramycheva: Employment: Research Center of Neurology, Ministry of Science and Higher Education of the Russian Federation, Moscow, Russia. Grants: Russian Science Foundation ; Funding text 3: Rachel Saunders?Pullman: Employment: Icahn School of Medicine at Mount Sinai, New York City, New York, USA. Grants: NIH 1U01NS107016?01A1; Bigglesworth Family Foundation. Others: Bachmann?Strauss Chair ; Funding text 4: Zbigniew K. Wszolek: Advisory Boards: Vigil Neuroscience, Inc. Employment: Mayo Clinic, Jacksonville, Florida, USA. Grants: NIH/NIA and NIH/NINDS (1U19AG063911, FAIN: U19AG063911), Mayo Clinic Center for Regenerative Medicine, PI or co?PI on Biohaven Pharmaceuticals, Inc. (BHV4157?206 and BHV3241?301), Neuraly, Inc. (NLY01?PD?1), and Vigil Neuroscience, Inc. (VGL101?01.001 and VGL101?01.002). He also serves as the co?PI of the Mayo Clinic APDA Center for Advanced Research. Others: Donations from the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation ; Funding text 5: Vladimir S. Kostic: Employment: School of Medicine, University of Belgrade, Serbia. Grants: Project No 175090 Ministry of Education, Science and Technological Development of Serbia. Project ??28 Serbian Academy of S

Published
2023

14. The large-scale in situ PRACLAY heater test: first observations on the in situ thermo-hydro-mechanical behaviour of Boom Clay

Author

Dizier A., Chen G.J., Levasseur S., Li X.L., Sillen X., Verstricht J., Dizier A., Chen G.J., Levasseur S., Li X.L., Sillen X., and Verstricht J.

Abstract

The PRACLAY long-term in-situ heating test in the Boom Clay started in 2014 at the HADES underground research facility in Mol (Belgium). The test will study the thermo-hydro-mechanical behaviour of the clay both within the excavation damaged zone and in the heated gallery of the high level waste storage chamber. Results after four years of heating at 80 degrees C at the gallery lining/Boom Clay interface show that the zone in which the temperature is affected by heating extends to about 20 m and is growing slowly. The pore water pressures also evolved smoothly, reaching 2.8 MPa in the backfilled part of the heated gallery and a maximum of 3MPa in the Boom Clay. Changes of pore water pressure were seen up to 22 m away from the axis of the heated gallery while the temperature had still not increased at this location. The initial observations confirm the results of smaller scale experiments, particularly that the effects of the mechanical anisotropic properties of the clay affect the pore water pressure. It is concluded that after four years of heating at the lining-clay interface, the conditions in and around the test behaved as expected and the Boom clay can withstand the thermal load., The PRACLAY long-term in-situ heating test in the Boom Clay started in 2014 at the HADES underground research facility in Mol (Belgium). The test will study the thermo-hydro-mechanical behaviour of the clay both within the excavation damaged zone and in the heated gallery of the high level waste storage chamber. Results after four years of heating at 80 degrees C at the gallery lining/Boom Clay interface show that the zone in which the temperature is affected by heating extends to about 20 m and is growing slowly. The pore water pressures also evolved smoothly, reaching 2.8 MPa in the backfilled part of the heated gallery and a maximum of 3MPa in the Boom Clay. Changes of pore water pressure were seen up to 22 m away from the axis of the heated gallery while the temperature had still not increased at this location. The initial observations confirm the results of smaller scale experiments, particularly that the effects of the mechanical anisotropic properties of the clay affect the pore water pressure. It is concluded that after four years of heating at the lining-clay interface, the conditions in and around the test behaved as expected and the Boom clay can withstand the thermal load.

Published
2021

17. Coupled thermohydromechanical modeling of the full-scale in situ test 'Prototype Repository'

Author

Chen, G.J. and Ledesma, A.

Subjects
Thermodynamics -- Research, Radioactive waste disposal in the ground -- Research, Numerical analysis -- Methods, Bentonite -- Mechanical properties, Rock mechanics -- Research, Earth sciences, Engineering and manufacturing industries, Science and technology
Abstract

The Prototype Repository project represents a full-scale in situ test of the Swedish concept for high level radioactive waste disposal in deep geological repositories, being conducted at the underground Aspo Hard Rock Laboratory and managed by SKB (Swedish Agency for Radioactive Waste Disposal). Instead of canisters with radioactive material, heaters installed in cylindrical containers surrounded by compacted bentonite have been used in the test. A large number of thermohydromechanical parameters for materials used in the test were carefully determined based on the latest laboratory experiments and site investigation. After comparison among six simulation models, some valuable conclusions are made about the interaction effects of six deposition holes and the effects of thermohydrogas--mechanical coupling. A three-dimensional coupled thermohydraulic model was selected for the prediction of temperature, whereas an axisymmetric two-dimensional coupled thermohydromechanical model was selected for the prediction of relative humidity and stresses for the system of heater--bentonite--near rock. Selected results of temperature, relative humidity, and total stress are presented and discussed, and the agreement between the compared variables highlights the ability of the developed models to reproduce the complex coupled processes involved in the test. CE Database subject headings: Radioactive wastes; Coupling; Numerical analysis; Rocks; Backfill; Comparative studies; Predictions; Bentonite.

Published
2009

18. The effect of extracts from ginger rhizome on inflammatory mediator production

Author

Lantz, R.C., Chen, G.J., Sarihan, M., Solyom, A.M., Jolad, S.D., and Timmermann, B.N.

Subjects
Materia medica, Vegetable -- Composition -- Health aspects, Lung diseases, Obstructive -- Drug therapy, Anti-inflammatory drugs -- Composition -- Health aspects, Ginger -- Composition -- Health aspects, Rheumatoid arthritis -- Drug therapy, Plant extracts -- Composition -- Health aspects, Asthma -- Drug therapy, Biological sciences, Health, Science and technology
Abstract

Abstract Compounds from rhizomes of Zingiber officinale, commonly called ginger, have been purported to have anti-inflammatory actions. We have used an in vitro test system to test the anti-inflammatory activity [...]

Published
2007

24. The effect of turmeric extracts on inflammatory mediator production

Author

Lantz, R.C., Chen, G.J., Solyom, A.M., Jolad, S.D., and Timmermann, B.N.

Subjects
Cytokines -- Health aspects, Prostaglandins -- Health aspects, Turmeric -- Health aspects, Materia medica, Vegetable -- Health aspects, Plant extracts -- Health aspects, Biological sciences, Health, Science and technology, Health aspects
Abstract

Abstract Major compounds of several commonly used botanicals, including turmeric, have been purported to have anti-inflammatory actions. In order to test the anti-inflammatory activity of compounds isolated from rhizomes of [...]

Published
2005

31. 'SAIL' high temperature superconductors digital logic: improvements and analysis

Author

Schwarzbek, S.M., Chen, G.J., Luine, J.A., Schneier, N.J., Fischer, G.R., and Davidheiser, R.A.

Subjects
Logic circuitry -- Research, High temperature superconductors -- Usage, Business, Electronics, Electronics and electrical industries
Abstract

The feasibility of using high temperature superconductor (HTS) step-edge junctions to enhance the performance of the Series Array Interferometer Logic (SAIL) circuit was evaluated. HTS-based SAIL gates were tested for their current-voltage characteristics at cryo-cooler temperatures and voltages of 100 microvolts. Results show that the incorporation of the HTS junctions in the design process enhanced the voltage and temperature performance of the SAIL circuit.

Published
1993

32. Nondestructive readout architecture for a kinetic inductance memory cell

Author

Chen, G.J., Beasley, M.R., Horowitz, M., Rosenthal, P., and Whiteley, S.

Subjects
Ferroelectric devices -- Research, Induction, Electromagnetic -- Usage, Information storage and retrieval systems -- Innovations, Business, Electronics, Electronics and electrical industries
Abstract

A conceptual kinetic inductance non-destructive-read-out memory cell for electronic data storage is presented. The cell consists of a single-junction superconducting quantum interference device (SJ SQUID) containing a kinetic inductor and a nonlinear resistor. It relies on the SJ SQUID's voltage-biased clockwise and counter-clockwise states for data storage. The proposed memory cell provides a means for accessing stored data in spite of the loss of magnetic control.

Published
1993

43. Effects of exogenous fibrolytic enzyme supplementation to diets with different NFC/NDF ratios on the growth performance, nutrient digestibility and ruminal fermentation in Chinese domesticated black goats

Author

Song, S.D., primary, Chen, G.J., additional, Guo, C.H., additional, Rao, K.Q., additional, Gao, Y.H., additional, Peng, Z.L., additional, Zhang, Z.F., additional, Bai, X., additional, Wang, Y., additional, Wang, B.X., additional, Chen, Z.H., additional, Fu, X.S., additional, and Zhu, W.L., additional

Published
2018
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