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1. Semantic agent framework for automated flood assessment using dynamic knowledge graphs

Author

Markus Hofmeister, Jiaru Bai, George Brownbridge, Sebastian Mosbach, Kok F. Lee, Feroz Farazi, Michael Hillman, Mehal Agarwal, Srishti Ganguly, Jethro Akroyd, and Markus Kraft

Subjects
derived information framework, digital twin, flood assessment, knowledge graph, ontology, Engineering (General). Civil engineering (General), TA1-2040
Abstract

This article proposes a framework of linked software agents that continuously interact with an underlying knowledge graph to automatically assess the impacts of potential flooding events. It builds on the idea of connected digital twins based on the World Avatar dynamic knowledge graph to create a semantically rich asset of data, knowledge, and computational capabilities accessible to humans, applications, and artificial intelligence. We develop three new ontologies to describe and link environmental measurements and their respective reporting stations, flood events, and their potential impact on population and built infrastructure as well as the built environment of a city itself. These coupled ontologies are deployed to dynamically instantiate near real-time data from multiple fragmented sources into the World Avatar. Sequences of autonomous agents connected via the derived information framework automatically assess consequences of newly instantiated data, such as newly raised flood warnings, and cascade respective updates through the graph to ensure up-to-date insights into the number of people and building stock value at risk. Although we showcase the strength of this technology in the context of flooding, our findings suggest that this system-of-systems approach is a promising solution to build holistic digital twins for various other contexts and use cases to support truly interoperable and smart cities.

Published
2024
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2. Quantification of functional abilities in Rett syndrome: a comparison between stages III and IV

Author

Monteiro CBM, Savelsbergh GJP, Smorenburg ARP, Graciani Z, Torriani-Pasin C, de Abreu LC, Valenti VE, and Kok F

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Carlos BM Monteiro,1 Geert JP Savelsbergh,2 Ana RP Smorenburg,3 Zodja Graciani,4 Camila Torriani-Pasin,5 Luiz Carlos de Abreu,6 Vitor E Valenti,7 Fernando Kok41School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil; 2MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University, Amsterdam, the Netherlands; 3Burke-Cornell Medical Research Institute, White Plains, NY, USA; 4Department of Neurology, University of São Paulo, São Paulo, Brazil; 5Motor Behavior Laboratory, University of São Paulo, São Paulo, Brazil; 6Laboratory of Scientific Writing, Department of Morphology and Physiology, School of Medicine of ABC, Santo Andre, Brazil; 7Department of Speech Language and Hearing Therapy, Faculty of Philosophy and Sciences, UNESP, Marilia, BrazilAbstract: We aimed to evaluate the functional abilities of persons with Rett syndrome (RTT) in stages III and IV. The group consisted of 60 females who had been diagnosed with RTT: 38 in stage III, mean age (years) of 9.14, with a standard deviation of 5.84 (minimum 2.2/maximum 26.4); and 22 in stage IV, mean age of 12.45, with a standard deviation of 6.17 (minimum 5.3/maximum 26.9). The evaluation was made using the Pediatric ­Evaluation of Disability Inventory, which has 197 items in the areas of self-care, mobility, and social function. The results showed that in the area of self-care, stage III and stage IV RTT persons had a level of 24.12 and 18.36 (P=0.002), respectively. In the area of mobility, stage III had 37.22 and stage IV had 14.64 (P

Published
2014

3. Growth characteristics of the mean shear layer in pipe bends with and without a guide vane.

Author

Kok, F. and Myose, R.

Abstract

The growth characteristics of two identical pipe bends with and without a guide vane are investigated by means of large eddy simulation. The two pipe bends, with a radius of curvature slightly above the separation threshold, are subjected to two fully developed upstream flow conditions, with a corresponding Reynolds number of 11 700 and 24 000. A precursor computation method is employed to provide the fully developed turbulence inflow conditions for all cases. The growth of the mean shear layer in this work is characterized by the local momentum thickness, which measures the extent of momentum deficit confined under the mean shear layer. For both pipe bends, the initial growth of momentum thickness is observed in the first quarter of the bend. The onset location is almost independent of the Reynolds numbers. However, a clear Reynolds number dependence is observed in the onset magnitude, which strongly defines the growth rate thereafter. By examining the mean momentum balance in the bend section, the results show that rather than the adverse pressure gradient, the overall growth characteristics of the mean shear layer, which include the onset location and the growth rate, are better described by the balance between the centrifugal force and the radial pressure gradient. This balance manifests itself as a change in the swirling intensity of the secondary flow. The presence of guide vane significantly suppresses the swirling intensity in the bend section, leading to a noticeable reduction in the overall momentum thickness growth and the production of turbulence in the flow downstream of the bend. Further inspection also indicates that the initial mechanism leading to the suppression of separation at the inner bend is linked to the increasing dominance of the small vortices at the near-wall vicinity relative to the local adverse pressure gradient. Certain aspects pertaining to the turbulent statistics are also discussed. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Economic rationality and political viability, prerequisites in economic reform? : a case study of China, 1978-1995

Author

Kok, F. Josephine B. de

Subjects
338.951, Economic policy, China
Abstract

To address the research questions - How has the Chinese government been able to produce a successful reform process and what logic has been behind it? - I develop a politico-economic framework that is largely based on a public choice model by Frey and Eichenberger (1992) and a politico-economic research methodology by Bates and Kreuger (1993). Its basic assumption is that all individuals, including bureaucrats and autocrats, maximise their own power and money subject to constraints. Secondly, it assumes that, when a new leadership rises to power, it will try to start an economic reform process in order to secure its power position. Per reform period, economic reform plans are analysed on their intended effect, implementation and actual results in pure economic terms as well as in political terms (leadership's power position). The framework hypothesises that during a reform process a government will perform a constant balancing act between the political viability with the economic rationality of each individual reform measure. This hypothesis is testedJand the Chinese reform period 1978-1995. The constraints Deng Xiaoping's leadership faces are the Communist Party's rule, a very strong bureaucracy, management of state enterprises and military, the command economy with an agricultural commune system and a revenue dependency on state owned enterprises. The hypothesis largely holds for China: agricultural reforms start with liberalisation to be later on largely retracted; real state owned enterprise reforms are never implemented; rural industrial reforms boom after tax revenues could be withheld at local level; the military's civilian industries is thriving. Unwanted results are quickly changed or retracted in the following period. Also identified is that despite these efforts, unintended interlinkage effects between the different reform measures become increasingly important and difficult to assess, resulting in a great loss of power for the leadership.

Published
1996

6. Brain or Spinal Cord MRI in the Investigation of Hereditary Spastic Paraplegia? Brain First!

Author

Freua, F., Ripa, B., IMacedo-Souza, L., Paiva, A. B., and Kok, F.

Subjects
Magnetic resonance imaging -- Investigations -- Analysis, Learning disorders, Spastic paraplegia, Disabilities, Diagnostic imaging, Characterization, Paraplegia, Company legal issue, Health
Abstract

Byline: F. Freua, B. Ripa, L. IMacedo-Souza, A. B Paiva, F. Kok A 37-year-old woman presented with a previous history of learning disability, started when she was 23 years old, [...]

Published
2020

10. The effects of emoji in email marketing

Author

Kok, F., Kok, F., Kok, F., and Kok, F.

Abstract

The full text of this thesis is not available due to privacy or embargo reasons.

Published
2020

12. Dynamic control of district heating networks with integrated emission modelling: A dynamic knowledge graph approach

Author

Markus Hofmeister, Kok Foong Lee, Yi-Kai Tsai, Magnus Müller, Karthik Nagarajan, Sebastian Mosbach, Jethro Akroyd, and Markus Kraft

Subjects
Knowledge graph, Digital twin, Interoperability, Energy modelling, Emission dispersion, Electrical engineering. Electronics. Nuclear engineering, TK1-9971, Computer software, QA76.75-76.765
Abstract

This paper presents a knowledge graph-based approach for the dynamic control of a district heating network with integrated emission dispersion modelling. We propose an interoperable and extensible implementation to forecast the anticipated heat demand of a municipal heating network, minimise associated total generation cost based on a previously devised methodology, and couple it with dispersion simulations for induced airborne pollutants to provide automatic insights into air quality implications of various heat sourcing strategies. We create cross-domain interoperability in the nexus of energy and air quality via newly developed ontologies and semantic software agents, which can be chained together via The World Avatar dynamic knowledge graph to resemble the behaviour of complex systems. Furthermore, we integrate the City Energy Analyst into this ecosystem to provide building-level insights into energy demand and renewable generation potential to foster strategic analyses and scenario planning. Underlying calculations use building and weather data from the knowledge graph in place of inherent assumptions in the official software release, facilitating a more data-driven approach. All use cases are implemented for a mid-size town in Germany as a proof-of-concept, and a unified visualisation interface is provided, allowing for the examination of 3D buildings alongside their corresponding energy demand and supply time series, as well as emission dispersion data. With this work, we outline the potential of Semantic Web technologies to connect digital twins for holistic energy modelling in smart cities, thereby addressing the increasing complexity of interconnected energy systems.

Published
2024
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21. Heterogeneous pdgfrβ+ cells regulate coronary vessel development and revascularization during heart regeneration

Author

Hongjun Bai, Ying Huang, Matteo Pellegrini, Tyler Yoshida, Ching-Ling Lien, Harrison Mm, Fierros J, Kok F, Aguayo A, Peter F. Hitchcock, Wiens Km, Kapuria S, Nathan D. Lawson, Joycelyn K. Yip, Megan L. McCain, and Mikiko Nagashima

Subjects
biology, Heart development, Chemistry, Regeneration (biology), Coronary vessel, biology.protein, Atrioventricular canal, biology.organism_classification, Beta (finance), Zebrafish, Platelet-derived growth factor receptor, Mural cell, Cell biology
Abstract

Endothelial cells emerge from the atrioventricular canal (AVC) to form nascent coronary blood vessels in the juvenile zebrafish heart. We found that pdgfrβ is first expressed in the epicardium around the AVC and later becomes localized mainly in the mural cells. pdgfrβ mutant fish display severe defects in mural cell recruitment and coronary vessel development. pdgfrβ+ mural cells are heterogeneous and those associated with coronary arteries also express cxcl12b. Mural cells positive for both pdgfrβ and cxcl12b transgenic reporters had elevated expression of smooth muscle cell genes. Interestingly, these mural cells were associated with coronary arteries even in the absence of Pdgfrβ, although smooth muscle gene expression was downregulated in these cells. We found that pdgfrβ expression dynamically changes in the epicardium derived cells, which we found to be a heterogeneous population. mdka was identified as a gene upregulated in subpopulations of pdgfrβ+ cells during heart regeneration. However, pdgfrβ but not mdka mutants showed defects in heart regeneration. Our results demonstrated that pdgfrβ+ cells and Pdgfrβ signaling are essential for coronary development and heart regeneration.SUMMARY STATEMENTHeterogeneous pdgfrβ positive cells are present in developing and regenerating zebrafish hearts and are required for development of mural cells and their association with the nascent coronary vessels during zebrafish heart development and regeneration.

Published
2021

22. Vitamin D: do we get enough?: A discussion between vitamin D experts in order to make a step towards the harmonisation of dietary reference intakes for vitamin D across Europe

Author

Brouwer-Brolsma, E. M., Bischoff-Ferrari, H. A., Bouillon, R., Feskens, E. J. M., Gallagher, C. J., Hypponen, E., Llewellyn, D. J., Stoecklin, E., Dierkes, J., Kies, A. K., Kok, F. J., Lamberg-Allardt, C., Moser, U., Pilz, S., Saris, W. H., van Schoor, N. M., Weber, P., Witkamp, R., Zittermann, A., and de Groot, L. C. P. G. M.

Published
2013
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24. Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

Author

Hoed, J. den, Boer, E. de, Voisin, N., Dingemans, A.J.M., Guex, N., Wiel, L.J.M. van de, Nellaker, C., Amudhavalli, S.M., Banka, S., Bena, F.S., Ben-Zeev, B., Bonagura, V.R., Bruel, A.L., Brunet, T., Brunner, H.G., Chew, H.B., Chrast, J., Cimbalistienė, L., Coon, H., Délot, E.C., Démurger, F., Denommé-Pichon, A.S., Depienne, C., Donnai, D., Dyment, D.A., Elpeleg, O., Faivre, L., Gilissen, C.F., Granger, L., Haber, B., Hachiya, Y., Abedi, Y.H., Hanebeck, J., Hehir-Kwa, J.Y., Horist, B., Itai, T., Jackson, A., Jewell, R., Jones, K.L., Joss, S., Kashii, H., Kato, M., Kattentidt-Mouravieva, A.A., Kok, F., Kotzaeridou, U., Krishnamurthy, V., Kučinskas, V., Kuechler, A., Lavillaureix, A., Liu, P, Manwaring, L., Matsumoto, N., Mazel, B., McWalter, K., Meiner, V., Mikati, M.A., Miyatake, S., Mizuguchi, T., Moey, L.H., Mohammed, S, Mor-Shaked, H., Mountford, H., Newbury-Ecob, R., Odent, S., Orec, L., Osmond, M., Palculict, T.B., Parker, M., Petersen, A.K., Pfundt, R.P., Preikšaitienė, E., Radtke, K., Ranza, E., Rosenfeld, J.A., Santiago-Sim, T., Schwager, C., Sinnema, M., Snijders Blok, L., Spillmann, R.C., Stegmann, A.P.A., Thiffault, I., Tran, L., Vaknin-Dembinsky, A., Vedovato-Dos-Santos, J.H., Schrier Vergano, S.A., Vilain, E., Vitobello, A., Wagner, M., Waheeb, A., Willing, M., Zuccarelli, B., Kini, U., Newbury, D.F., Kleefstra, T., Reymond, A., Fisher, S.E., Vissers, L.E.L.M., Hoed, J. den, Boer, E. de, Voisin, N., Dingemans, A.J.M., Guex, N., Wiel, L.J.M. van de, Nellaker, C., Amudhavalli, S.M., Banka, S., Bena, F.S., Ben-Zeev, B., Bonagura, V.R., Bruel, A.L., Brunet, T., Brunner, H.G., Chew, H.B., Chrast, J., Cimbalistienė, L., Coon, H., Délot, E.C., Démurger, F., Denommé-Pichon, A.S., Depienne, C., Donnai, D., Dyment, D.A., Elpeleg, O., Faivre, L., Gilissen, C.F., Granger, L., Haber, B., Hachiya, Y., Abedi, Y.H., Hanebeck, J., Hehir-Kwa, J.Y., Horist, B., Itai, T., Jackson, A., Jewell, R., Jones, K.L., Joss, S., Kashii, H., Kato, M., Kattentidt-Mouravieva, A.A., Kok, F., Kotzaeridou, U., Krishnamurthy, V., Kučinskas, V., Kuechler, A., Lavillaureix, A., Liu, P, Manwaring, L., Matsumoto, N., Mazel, B., McWalter, K., Meiner, V., Mikati, M.A., Miyatake, S., Mizuguchi, T., Moey, L.H., Mohammed, S, Mor-Shaked, H., Mountford, H., Newbury-Ecob, R., Odent, S., Orec, L., Osmond, M., Palculict, T.B., Parker, M., Petersen, A.K., Pfundt, R.P., Preikšaitienė, E., Radtke, K., Ranza, E., Rosenfeld, J.A., Santiago-Sim, T., Schwager, C., Sinnema, M., Snijders Blok, L., Spillmann, R.C., Stegmann, A.P.A., Thiffault, I., Tran, L., Vaknin-Dembinsky, A., Vedovato-Dos-Santos, J.H., Schrier Vergano, S.A., Vilain, E., Vitobello, A., Wagner, M., Waheeb, A., Willing, M., Zuccarelli, B., Kini, U., Newbury, D.F., Kleefstra, T., Reymond, A., Fisher, S.E., and Vissers, L.E.L.M.

Abstract

Contains fulltext : 231687.pdf (Publisher’s version ) (Closed access), Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.

Published
2021

25. SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females

Author

Radio, F.C., Pang, K., Ciolfi, A., Levy, M.A., Hernández-García, A., Pedace, L., Pantaleoni, F., Liu, Z, Boer, E. de, Jackson, A., Bruselles, A., McConkey, H., Stellacci, E., Cicero, S. Lo, Motta, M., Carrozzo, R., Dentici, M.L., McWalter, K., Desai, M., Monaghan, K.G., Telegrafi, A., Philippe, C., Vitobello, A., Au, M., Grand, K., Sanchez-Lara, P.A., Baez, J., Lindstrom, K., Kulch, P., Sebastian, J., Madan-Khetarpal, S., Roadhouse, C., MacKenzie, J.J., Monteleone, B., Saunders, C.J., Cuevas, J.K. Jean, Cross, L., Zhou, D., Hartley, T., Sawyer, S.L., Monteiro, F.P., Secches, T.V., Kok, F., Schultz-Rogers, L.E., Macke, E.L., Morava, E., Klee, E.W., Kemppainen, J., Iascone, M., Selicorni, A., Tenconi, R., Amor, D.J., Pais, L., Gallacher, L., Turnpenny, P.D., Stals, K., Ellard, S., Cabet, S., Lesca, G., Pascal, J., Steindl, K., Ravid, S., Weiss, K., Castle, A.M.R., Carter, M.T., Kalsner, L., Vries, B.B.A. de, Bon, B.W. van, Wevers, M.R., Pfundt, R.P., Stegmann, A.P.A., Kerr, B., Kingston, H.M., Chandler, K.E., Sheehan, W., Elias, A.F., Shinde, D.N., Towne, M.C., Robin, N.H., Goodloe, D., Vanderver, A., Sherbini, O., Bluske, K., Hagelstrom, R.T., Zanus, C., Faletra, F., Musante, L., Kurtz-Nelson, E.C., Earl, R.K., Anderlid, B.M., Morin, G., Slegtenhorst, M. van, Diderich, K.E.M., Brooks, A.S., Gribnau, J., Boers, R.G., Finestra, T.R., Carter, L.B., Rauch, A., Gasparini, P., Vissers, L.E.L.M., Lloyd Holder, J., Tartaglia, M., Radio, F.C., Pang, K., Ciolfi, A., Levy, M.A., Hernández-García, A., Pedace, L., Pantaleoni, F., Liu, Z, Boer, E. de, Jackson, A., Bruselles, A., McConkey, H., Stellacci, E., Cicero, S. Lo, Motta, M., Carrozzo, R., Dentici, M.L., McWalter, K., Desai, M., Monaghan, K.G., Telegrafi, A., Philippe, C., Vitobello, A., Au, M., Grand, K., Sanchez-Lara, P.A., Baez, J., Lindstrom, K., Kulch, P., Sebastian, J., Madan-Khetarpal, S., Roadhouse, C., MacKenzie, J.J., Monteleone, B., Saunders, C.J., Cuevas, J.K. Jean, Cross, L., Zhou, D., Hartley, T., Sawyer, S.L., Monteiro, F.P., Secches, T.V., Kok, F., Schultz-Rogers, L.E., Macke, E.L., Morava, E., Klee, E.W., Kemppainen, J., Iascone, M., Selicorni, A., Tenconi, R., Amor, D.J., Pais, L., Gallacher, L., Turnpenny, P.D., Stals, K., Ellard, S., Cabet, S., Lesca, G., Pascal, J., Steindl, K., Ravid, S., Weiss, K., Castle, A.M.R., Carter, M.T., Kalsner, L., Vries, B.B.A. de, Bon, B.W. van, Wevers, M.R., Pfundt, R.P., Stegmann, A.P.A., Kerr, B., Kingston, H.M., Chandler, K.E., Sheehan, W., Elias, A.F., Shinde, D.N., Towne, M.C., Robin, N.H., Goodloe, D., Vanderver, A., Sherbini, O., Bluske, K., Hagelstrom, R.T., Zanus, C., Faletra, F., Musante, L., Kurtz-Nelson, E.C., Earl, R.K., Anderlid, B.M., Morin, G., Slegtenhorst, M. van, Diderich, K.E.M., Brooks, A.S., Gribnau, J., Boers, R.G., Finestra, T.R., Carter, L.B., Rauch, A., Gasparini, P., Vissers, L.E.L.M., Lloyd Holder, J., and Tartaglia, M.

Abstract

Contains fulltext : 231702.pdf (Publisher’s version ) (Closed access), Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.

Published
2021

28. A dynamic knowledge graph approach to distributed self-driving laboratories

Author

Jiaru Bai, Sebastian Mosbach, Connor J. Taylor, Dogancan Karan, Kok Foong Lee, Simon D. Rihm, Jethro Akroyd, Alexei A. Lapkin, and Markus Kraft

Subjects
Science
Abstract

Abstract The ability to integrate resources and share knowledge across organisations empowers scientists to expedite the scientific discovery process. This is especially crucial in addressing emerging global challenges that require global solutions. In this work, we develop an architecture for distributed self-driving laboratories within The World Avatar project, which seeks to create an all-encompassing digital twin based on a dynamic knowledge graph. We employ ontologies to capture data and material flows in design-make-test-analyse cycles, utilising autonomous agents as executable knowledge components to carry out the experimentation workflow. Data provenance is recorded to ensure its findability, accessibility, interoperability, and reusability. We demonstrate the practical application of our framework by linking two robots in Cambridge and Singapore for a collaborative closed-loop optimisation for a pharmaceutically-relevant aldol condensation reaction in real-time. The knowledge graph autonomously evolves toward the scientist’s research goals, with the two robots effectively generating a Pareto front for cost-yield optimisation in three days.

Published
2024
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29. Retrospective database analysis for clinical diagnoses commonly associated with pneumococcal diseases in the Malaysian healthcare system over a 3-year period (2013–2015)

Author

Saravanan S. R. Sundaramurthy, Kristen E. Allen, Mark A. Fletcher, Kok Fui Liew, Boekhtiar Borhanuddin, Mohammad Ali, Graciela Morales, Bradford Gessner, Jerusha Naidoo, and Jo Southern

Subjects
Pneumococcal, Pneumonia, Meningitis, Septicaemia, Bacteraemia, Malaysia, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015. Methods This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region. Results A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged

Published
2024
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31. Royal academy of medicine in Ireland international conference on homocysteine metabolism from basic science to clinical medicine: Proceedings of meeting held at Dromoland Castle, Co. Clare on July 2nd–6th, 1995

Author

Björkegren, K., Bergmark, C., de Faire, U., Mansoor, M. Azam, Svardal, A., Bostom, A. G., Roubenoff, R., Dellaripa, P., Nadeau, M. R., Sutherland, P., Wilson, P. W. F., Jacques, P. F., Selhub, J., Rosenberg, I. H., Bostom, A. G., Brosnan, J. T., Hall, B., Nadeau, M. R., Selhub, J., Bostom, A. G., Shemin, D., Lapane, K. L., Sutherland, P., Nadeau, M. R., Wilson, P. W. F., Selhub, J., Bostom, A. G., Shemin, D., Nadeau, M. R., Selhub, J., Bostom, A. G., Selhub, J., Jacques, P. F., Nadeau, M. R., Williams, R. R., Ellison, R. C., Cuskelly, G. J., McNulty, H., Strain, J. J., McPartlin, J. M., Scott, J. M., Chadefaux-Vekemans, B., Coudé, M., Aupetit, J., Kamoun, P., Coudé, M., Aral, B., Zabot, M. T., Aupetit, J., Kamoun, P., Chadefaux-Vekemans, B., Calaf, R., Ghiringelli, O., Barlatier, A., Charpiot, P., Rolland, P. H., Garçon, D., Charpiot, P., Augier, T., Chareyre, C., Rolland, P. H., Garçon, D., Chango, A., Hodez, F., Tronel, H., Nuel, G., Michel, F., Frémont, S., Méjean, L., Nicolas, J. P., Candito, M., Chambon, P., Gibelin, P., Amsellem, J., Baudouy, M., Morand, P., Candito, M., Chambon, P., Pringuey, D., Aubin-Brunet, V., Beaulieu, F., Darcourt, G., Bedoucha, P., Alchaar, H., Chatel, M., Candito, M., de Valk, H. W., van der Griend, R., Eeden, M. K. G. van, de Groot, E., Duran, M., Smeitink, J. A. M., de Klerk, J. B. C., Wittebol-Post, D., Rolland, M. -O., Haas, F. J. L. M., Meuwissen, O. J. A. Th., Banga, J. D., Poll-The, B. T., de Vries, J. I. P., Dekker, G. A., van Geijn, H. P., Huigens, P. C., Jakobs, C., von Blomberg, B. M. E., Deulofeu, R., Giralt, M., Aibar, C., Bauchet, C., Ballesta, A. M., Varela, G., Vila, N., Chamorro, A., Casals, F. J., Cremades, J. Diaz, Daly, L., Meleady, R., Graham, I., den Heijer, M., Brouwer, I. A., Gerrits, W. B. J., Bos, G. M. J., Blom, H. J., den Heijer, M., Bos, G. M. J., Koster, T., Vandenbroucke, J. P., Blom, H. J., Briët, E., Rosendaal, F. R., Fischer, G., Behrend, C., Bartholmes, P., Fermo, I., Paroni, R., Vigano, S., D’Angelo, A., Fermo, I., Paroni, R., Vigano, S., D’Angelo, A., Franken, D. G., Boers, G. H. J., Blom, H. J., Hamel, B. C. J., Franken, D. G., Boers, G. H. J., Blom, H. J., Ruijs, J. H. J., Franken, D. G., Blom, H. J., Boers, G. H. J., Tangerman, A., Guttormsen, A. B., Ueland, P. M., Refsum, H., Svarstad, E., Gao, W., Goldman, E., Jakubowski, H., Sebastio, G., Sperandeo, M. P., de Franchis, R., Andria, G., Garrow, T. A., Hladovec, J., Sommerova, Z., Písariková, A., Halsted, C. H., Villanueva, J., Chandler, C. J., Stabler, S. P., Allen, R. H., Muskhelishvili, L., James, S. J., Poirer, L., Jacobsen, D. W., Savon, S. R., DiCorleto, P. E., Jourdheuil-Rahmani, D., Rolland, P. H., Garçon, D., Joosten, E., Riezler, R., Allen, R., Joosten, E., Riezler, R., Allen, R., Marquardt, T., Ullrich, K., Harms, E., Koch, H. G., Koch, H. G., Evers, S., Grotemeyer, K. H., Vogelpohl, L., von Eckardstein, A., Ullrich, K., Deufel, T., Kraus, J., Harms, E., Kozich, V., Janosik, M., Sokolová, J., Bukovská, G., Kraus, J. P., Kluitmans, L. A. J., van den Heuvel, L. P., Stevens, E., Trubels, J. M. F., Blom, H. J., Boers, G. H. J., van Oost, B. A., Kraus, J. P., Kittner, S., Macko, R., Hebel, J. R., Rohr, J., Malinow, M. R., Upson, B., Buchholz, D., Earley, C., Johnson, C., Price, T. R., Rosario, J., Sloan, M., Stern, B., Wityk, R., Wozniak, M., Sherwin, R., Stolley, P., Kluijtmans, L., Heuvel, L. van den, Stevens, E., Trijbels, F., Blom, H., Boers, G., van Oost, B., den Heijer, M., Rozen, R., Löhrer, F., Angst, C., Fowler, B., Zaugg, M., Brunner, F., Haefeli, W. E., Nedrebø, B., Ericsson, U. -B., Ueland, P. M., Refsum, H., Lien, E. A., London, J., Paly, E., Paul, V., Paris, D., Kamoun, P., Chassé, J. F., Møller, J., Rasmussen, K., Meleady, R., Graham, I., Daly, L., Verhoef, P., Meleady, R., Graham, I., Daly, L., McMartin, K. E., Phifer, T. J., Alexander, J. S., Middlebrooks, M., Childress, L. E., Nicolas, J. P., Tronel, H., Chango, A., Fremont, S., Felden, F., Guerci, B., Creton, C., Drouin, P., Oakley, G. P., Elias, P. R. P., Hann, A. C., Curtis, C. G., Rose, F. A., Tudball, N., Parrot-Roulaud, F., Cochet, C., Catargi, B., Leprat, F., Latapie, J. -L., Perna, A. F., De Santo, N. G., Ingrosso, D., Galletti, P., Zappia, V., Parrot-Roulaud, F., Sassoust, G., Boissieras, P., Blom, H. J., Majors, A. K., Ehrhart, L. A., Pezacka, E. H., Perry, I. J., Morris, R. W., Ebrahim, S. B., Shaper, A. G., Refsum, H., Ueland, P. M., Pietrzik, K., Dierkes, J., Kroesen, M., Bung, P., Rasmussen, K., Moller, J., Rasmussen, K., Remacha, A., Garcia-Die, F., Cadafalch, J., Barceló, H. J., Parellada, H., Regland, B., Gottfries, C. -G., Andersson, M., Bagby, J., Dyrehag, L. -E., Abrahamsson, L., Ronge, E., Kjellman, B., Frosst, P., Christensen, B., Goyette, P., Rosenblatt, D. S., Genest, J., Rozen, R., Riedel, B., Ueland, P. M., Svardal, A. M., Silberberg, J., Crooks, R., Fryer, J., Ray, C., Guo, X. W., Xie, L., Dudman, N., Silberberg, J., Crooks, R., Fryer, J., Ray, C., Guo, X. W., Xie, L., Dudman, N., Silberberg, J., Crooks, R., Fryer, J., Ray, C., Guo, X., Xie, L., Dudman, N., Smith, B., Kohlman-Trigoboff, D., Simsir, S., Stabler, S. P., Allen, R. H., Strydom, A. J. C., Schlüssel, E., Preibisch, G., Elstner, E. F. E., Pütter, S., Spuijbroek, M. D. E. H., Goddijn-Wessel, T. A. W., Wouters, M. G. A. J., Molen, E. F. v. d., Blom, H. J., Boers, G. H. J., Steegers-Theunissen, R. P. M., Trijbels, J. M. F., Thomas, C. M. G., Eskes, T. K. A. B., Tsai, M. Y., Hanson, N., Key, N., Schwichtenberg, K., Garg, U., Todesco, L., Fowler, B., Pollaert, N., Haefeli, W. E., Thorand, B., Hages, M., Pietrzik, K., Bung, P., Holzgreve, W., Vila, N., Chamorro, A., Deulofeu, R., Aibar, C., Giralt, M., Ballesta, A. M., van der Mooren, M. J., Wouters, M. G. A. J., Schellekens, L. A., Eskes, T. K. A. B., Rolland, R., Blom, H. J., Put, N. v. d., Trijbels, F., Heuvel, L. v. d., Blom, H., Eskes, T., Steegers-Theunissen, R., Mariman, E., Heyer, M. d., Rozen, R., Daher, R., Van Lente, F., Vilkovsky, A. B., Maev, I. V., Richter, E. L., Kirnus, M. D., Varela-Moreiras, G., Alonso-Aperte, E., Rubio, M., Gassó, M., Deulofeu, R., Alvarez, L., Caballeria, J., Rodés, J., Mato, J. M., van Aerts, L. A. G. J. M., Peereboom-Stegeman, J. H. J. Copius, Noordhoek, J., Eskes, T. K. A. B., Molen, E. F. v. d., Spuijbroek, M. D. E. H., Eskes, T. K. A. B., Heuvel, L. P. v. d., Monnens, L. A. H., Blom, H. J., van Guidener, C., Janssen, M. J. F. M., Surachno, J., Stehouwer, C. D. A., van den Berg, M., Bierdrager, E., Rauwerda, J. A., Wilcken, B., Hammond, J., Wouters, M. G. A. J., Hamilton, C. J. C. M., Blom, H. J., Boers, G. H. J., Thomas, C. M. G., Borm, G. F., Eskes, T. K. A. B., Wang, H., Tsai, J. -C., Perrella, M. A., Yoshizumi, M., Sibinga, N. E. S., Haber, E., Chang, T. H. -T., Schlegel, R., Lee, M. -E., Woodside, J., McMaster, D., Yarnell, J., Young, I., Mercer, C., Byrne, K., Evans, A., Gey, F., Gao, X. M., Dougan, G., Wordsworth, P., McMichael, A., Young, P. B., Kennedy, D. G., Molloy, A. M., Scott, J. M., Ward, P., Naughten, E., Cahalane, S., Murphy, D., Mayne, P., Chauveau, P., Chadefaux-Vekemans, B., Coudé, M., Aupetit, J., Kamoun, P., Jungers, P., van Asselt, D. Z. B., Blom, H. J., de Wild, G. M., van Staveren, W. A., Hoefnagels, W. H. L., Naruszewicz, M., Staniewicz, A., Dziewanowski, K., Evrovski, J., Cole, D. E. C., Callaghan, Michael, Lindgren, A., Brattström, L., Hultberg, B., Verhoef, P., Hennekens, C. H., Allen, R. H., Stabler, S. P., Willett, W. C., Stampfer, M. J., Frantzen, F., Sundrehagen, E., Verhoef, P., Kok, F. J., Stampfer, M. J., Willett, W. C., Gaziano, J. M., Hennekens, C. H., Allen, R. H., Stabler, S. P., Reynolds, R. D., Hsu, R. -J., Shane, B., Robinson, K., Kottke-Marchant, K., Green, R., Gupta, A., Jacobsen, D., Robinson, K., Mayer, E., Gupta, A., Miller, D., Marchant, K., Green, R., Jacobsen, D., Greene, R., Chong, Y. -Y., Jacobsen, D., Robinson, K., Gupta, M., Sheppard, C. A., Matthews, R. G., Goyette, P., Frosst, P., Rozen, R., Verhoef, P., Kok, F. J., Kruyssen, H. A. C. M., Witteman, J. C. M., Ueland, P. M., Boushey, C., Beresford, S., Omenn, G., Motulsky, A. G., Nygard, O., Vollset, S. E., Kvale, G., Stensvold, I., Ueland, P. M., Refsum, H., Fiskerstrand, T., Ueland, P. M., Refsum, H., Bugge, K. H., Oshaug, A., Bjønnes, C. H., Refsum, H., Wu, J. T., Wu, L. L., and Wilson, L. W.

Published
1995
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33. 3rd IANA (International Academy on Nutrition and Aging) Meeting Nutrition, Exercise & Alzheimer and Clinical Trials on Sarcopenia August 1–2, 2008 Hyatt Regency Tamaya Resort 1300 Tuyuna Trail Santa Ana Pueblo, NM USA

Author

Andrieu, S., Barberger-Gateau, P., Raffaitin, C., Berr, C., Tzourio, C., Dartigues, J. -F., Gin, H., Fitten, L. J., Ortiz, F., Fairbanks, L., Bartzokis, G., Lu, P., Ringman, J., Heyn, P. C., Locher, J. L., Salvà, A., Andrieu, S., Fernández, E., Vellas, B., van de Rest, O., Geleijnse, J. M., Kok, F. J., van Staveren, W. A., Beekman, A. T. F., Hoefnagels, W. H. L., de Groot, C. P. G. M., Angevaren, M., Aufdemkampe, G., Verhaar, H. J. J., Aleman, A., Vannees, L., Arkin, S., Florez, H., Gerstein, H., Sheridan, P., Bosch, J., Goldberg, R., Kaspar, K. M., Drawert, S. M., Marcus, R. L., Kidde, J., Dibble, L., Addison, O., LaStayo, P. C., Scarmeas, N., Stern, Y., Schupf, N., Luchsinger, J. A., Sharkey, J. R., Laditka, J. N., Laditka, S. B., Liu, R., Hochhalter, A., Robare, J. F., Türner, N., Judge, M., Foster, T. C., Erdos, B., Cudykier, I., Scarpace, P. J., Weiss, L. A., Bergstrom, J., Kritz-Silverstein, D., Barrett-Connor, Elizabeth, Yurko-Mauro, K., Nelson, E., Quinn, J., Sattler, F. R., Castaneda-Sceppa, C., Binder, E. F., Schroeder, E. T., Wang, Y., Bhasin, S., Kawakubo, M., Stewart, Y., Hahn, C., Colletti, P., Roubenoff, R., Yarasheski, K. E., Azen, S. P., Aoki, Y., Yamamoto, T., Otuka, T., Blanc-Bisson, C., Bourdel-Marchasson, I., Bocock, M. A., Keller, H. H., Bowman, G., Baxter, J., Oken, B., Frei, B., Traber, M., Leonard, S., Kaye, J., Shannon, J., Quinn, J., Carlsson, M., Gustafson, Y., Eriksson, S., Littbrand, H., Håglin, L., Danthiir, V., Wilson, C., Nettelbeck, T., Burns, N., Wittert, G., Noakes, M., Clifton, P., DiMaria-Ghalili, R. A., Grieger, J. A., Nowson, C. A., Wattanapenpaiboon, N. T., Holstein, J., Robinson, C., Hartmann, C., Rueb, S., Heffel, L., Dintaman, S., Reynolds, J., Fleming, L., Crull, M., Goldey, J., Serper, L. L., Hubbard, R., Westengard, J., Horning, M., Ishige, Y., Aoki, Y., Keller, H. H., Keller, H. H., LaStayo, P. C., Marcus, R. L., Smith, S., Kidde, J., Dibble, L., Butler, C., Hill, M., LaStayo, P. C., Marcus, R. L., Dibble, L., Kidde, J., Peters, C., Meier, W., Laughlin, G. A., Kritz-Silverstein, D., von Muhlen, D., Barrett-Connor, E., Olariu, L., Petcu, M., Tulcan, C., Pup, M., Otilingam, P., Gate, M., Pasinetti, G. M., Ray, B., Chauhan, N. B., Bailey, J. A., Lahiri, D. K., Shatenstein, B., Kergoat, M. -J., Reid, I., Chicoine, M. -E., Vaz, L., Stewart, R., Sabbah, W., Tsakos, G., D’Aiuto, F., Watt, R. G., Sturman, M., Kelly, J., Fleischman, D., Leurgans, S., Bennett, D., Morris, M. C., Suominen, M. H., Muurinen, S., Soini, H., Pitkälä, K. H., Yamamoto, T., Fujinoki, C., and Aoki, Y.

Published
2008
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34. Urban Vulnerability Assessment of Sea Level Rise in Singapore through the World Avatar

Author

Shin Zert Phua, Kok Foong Lee, Yi-Kai Tsai, Srishti Ganguly, Jingya Yan, Sebastian Mosbach, Trina Ng, Aurel Moise, Benjamin P. Horton, and Markus Kraft

Subjects
sea level rise, knowledge graph, multi-perspective visualisation, vulnerability assessment, integrated spatial planning, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

This paper explores the application of The World Avatar (TWA) dynamic knowledge graph to connect isolated data and assess the impact of rising sea levels in Singapore. Current sea level rise vulnerability assessment tools are often regional, narrow in scope (e.g., economic or cultural aspects only), and are inadequate in representing complex non-geospatial data consistently. We apply TWA to conduct a multi-perspective impact assessment of sea level rise in Singapore, evaluating vulnerable buildings, road networks, land plots, cultural sites, and populations. We introduce OntoSeaLevel, an ontology to describe sea level rise scenarios, and its impact on broader elements defined in other ontologies such as buildings (OntoBuiltEnv ontology), road networks (OpenStreetMap ontology), and land plots (Ontoplot and Ontozoning ontology). We deploy computational agents to synthesise data from government, industry, and other publicly accessible sources, enriching buildings with metadata such as property usage, estimated construction cost, number of floors, and gross floor area. An agent is applied to identify and instantiate the impacted sites using OntoSeaLevel. These sites include vulnerable buildings, land plots, cultural sites, and populations at risk. We showcase these sea level rise vulnerable elements in a unified visualisation, demonstrating TWA’s potential as a planning tool against sea level rise through vulnerability assessment, resource allocation, and integrated spatial planning.

Published
2024
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37. Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy

Author

Chatron, N, Becker, F, Morsy, H, Schmidts, M, Hardies, K, Tuysuz, B, Roselli, S, Najafi, M, Alkaya, DU, Ashrafzadeh, F, Nabil, A, Omar, T, Maroofian, R, Karimiani, EG, Hussien, H, Kok, F, Ramos, L, Gunes, N, Bilguvar, K, Labalme, A, Alix, E, Sanlaville, D, de Bellescize, J, Poulat, A-L, EuroEpinomics-RES consortium AR working group, Moslemi, A-R, Lerche, H, May, P, Lesca, G, Weckhuysen, S, Tajsharghi, H, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], and University of Luxembourg: High Performance Computing - ULHPC [research center]

Subjects
cleft palate, Epilepsy, Hypsarrhythmia, omphalocele, GAD1, Suppression-burs, Developmental Syndrome, Genetics & genetic processes [F10] [Life sciences], Génétique & processus génétiques [F10] [Sciences du vivant], arthrogryposis
Abstract

Developmental and Epileptic Encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathies caused by bi-allelic loss of function variants in GAD1, as presented by eleven patients from 6 independent consanguineous families. Seizure onset occurred in the two first months of life in all patients. All 10 patients from whom early disease history was available, presented seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early electroencephalography showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before four years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyzes the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.

Published
2020

39. Loss of TNR causes a nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus

Author

Wagner, M., Levy, J., Jung-Klawitter, S., Bakhtiari, S., Monteiro, F., Maroofian, R., Bierhals, T., Hempel, M., Elmaleh-Berges, M., Kitajima, J.P., Kim, C.A., Salomao, J.G., Amor, D.J., Cooper, M.S., Perrin, L., Pipiras, E., Neu, A., Doosti, M., Karimiani, E.G., Toosi, M.B., Houlden, H., Jin, S.C., Si, Y.C., Rodan, L.H., Venselaar, H., Kruer, M.C., Kok, F., Hoffmann, G.F., Strom, T.M., Wortmann, S.B., Tabet, A.C., Opladen, T., Wagner, M., Levy, J., Jung-Klawitter, S., Bakhtiari, S., Monteiro, F., Maroofian, R., Bierhals, T., Hempel, M., Elmaleh-Berges, M., Kitajima, J.P., Kim, C.A., Salomao, J.G., Amor, D.J., Cooper, M.S., Perrin, L., Pipiras, E., Neu, A., Doosti, M., Karimiani, E.G., Toosi, M.B., Houlden, H., Jin, S.C., Si, Y.C., Rodan, L.H., Venselaar, H., Kruer, M.C., Kok, F., Hoffmann, G.F., Strom, T.M., Wortmann, S.B., Tabet, A.C., and Opladen, T.

Abstract

Contains fulltext : 220941.pdf (Publisher’s version ) (Closed access), PURPOSE: TNR, encoding Tenascin-R, is an extracellular matrix glycoprotein involved in neurite outgrowth and neural cell adhesion, proliferation and migration, axonal guidance, myelination, and synaptic plasticity. Tenascin-R is exclusively expressed in the central nervous system with highest expression after birth. The protein is crucial in the formation of perineuronal nets that ensheath interneurons. However, the role of Tenascin-R in human pathology is largely unknown. We aimed to establish TNR as a human disease gene and unravel the associated clinical spectrum. METHODS: Exome sequencing and an online matchmaking tool were used to identify patients with biallelic variants in TNR. RESULTS: We identified 13 individuals from 8 unrelated families with biallelic variants in TNR sharing a phenotype consisting of spastic para- or tetraparesis, axial muscular hypotonia, developmental delay, and transient opisthotonus. Four homozygous loss-of-function and four different missense variants were identified. CONCLUSION: We establish TNR as a disease gene for an autosomal recessive nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus and highlight the role of central nervous system extracellular matrix proteins in the pathogenicity of spastic disorders.

Published
2020

47. PRMT1 acts as a suppressor of MHC-I and anti-tumor immunity

Author

Tirta M. Djajawi, Lizzy Pijpers, Akash Srivaths, David Chisanga, Kok Fei Chan, Simon J. Hogg, Liam Neil, Sarahi Mendoza Rivera, Nenad Bartonicek, Sarah L. Ellis, Terry C.C. Lim Kam Sian, Pouya Faridi, Yang Liao, Bhupinder Pal, Andreas Behren, Wei Shi, Stephin J. Vervoort, Ricky W. Johnstone, and Conor J. Kearney

Subjects
CP: Cancer, CP: Immunology, Biology (General), QH301-705.5
Abstract

Summary: Cancer immunotherapies have demonstrated remarkable success; however, the majority of patients do not respond or develop resistance. Here, we conduct epigenetic gene-targeted CRISPR-Cas9 screens to identify epigenomic factors that limit CD8+ T cell-mediated anti-tumor immunity. We identify that PRMT1 suppresses interferon gamma (Ifnγ)-induced MHC-I expression, thus dampening CD8+ T cell-mediated killing. Indeed, PRMT1 knockout or pharmacological targeting of type I PRMT with the clinical inhibitor GSK3368715 enhances Ifnγ-induced MHC-I expression through elevated STAT1 expression and activation, while re-introduction of PRMT1 in PRMT1-deficient cells reverses this effect. Importantly, loss of PRMT1 enhances the efficacy of anti-PD-1 immunotherapy, and The Cancer Genome Atlas analysis reveals that PRMT1 expression in human melanoma is inversely correlated with expression of human leukocyte antigen molecules, infiltration of CD8+ T cells, and overall survival. Taken together, we identify PRMT1 as a negative regulator of anti-tumor immunity, unveiling clinical type I PRMT inhibitors as immunotherapeutic agents or as adjuncts to existing immunotherapies.

Published
2024
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48. Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome

Author

Suzuki, O.T., Sertie, A.L., Der Kaloustian, V.M., Kok, F., Carpenter, M., Murray, J., Czeizel, A.E., Kliemann, S.E., Rosemberg, S., Monteiro, M., Olsen, B.R., and Passos-Bueno, M.R.

Subjects
Collagen -- Genetic aspects, Collagen -- Physiological aspects, Gene mutations -- Physiological aspects, Genetic disorders -- Physiological aspects, Biological sciences
Published
2002

50. A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features

Author

Molin, A-M, Andrieux, J, Koolen, D A, Malan, V, Carella, M, Colleaux, L, Cormier-Daire, V, David, A, de Leeuw, N, Delobel, B, Duban-Bedu, B, Fischetto, R, Flinter, F, Kjaergaard, S, Kok, F, Krepischi, A C, Le Caignec, C, Ogilvie, C Mackie, Maia, S, Mathieu-Dramard, M, Munnich, A, Palumbo, O, Papadia, F, Pfundt, R, Reardon, W, Receveur, A, Rio, M, Ronsbro Darling, L, Rosenberg, C, Sá, J, Vallee, L, Vincent-Delorme, C, Zelante, L, Bondeson, M-L, and Annerén, G

Published
2012
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