251 research outputs found
Novel variants in genes related to vesicle-mediated-transport modify Parkinson's disease risk
No full textObjectives: VPS35 and VPS13 have been associated with Parkinson's disease (PD), and their shared phenotype in yeast when reduced in function is abnormal vacuolar transport. We aim to test if additional potentially deleterious variants in other genes that share this phenotype can modify the risk for PD. Methods: 77 VPS and VPS-related genes were analyzed using whole-genome-sequencing data from 202 PD patients of Ashkenazi Jewish (AJ) ancestry. Filtering was done based on quality and functionality scores. Ten variants in nine genes were further genotyped in 1200 consecutively recruited unrelated AJ-PD patients, and allele frequencies and odds ratio calculated compared to gnomAD-AJ-non-neuro database, in un-stratified (n = 1200) and stratified manner (LRRK2-G2019S-PD patients (n = 145), GBA-PD patients (n = 235), and non-carriers of these mutations (NC, n = 787)). Results: Five variants in PIK3C3, VPS11, AP1G2, HGS and VPS13D were significantly associated with PD-risk. PIK3C3-R768W showed a significant association in an un-stratified (all PDs) analysis, as well as in stratified (LRRK2, GBA, and NC) analyses (Odds ratios = 2.71, 5.32, 3.26. and 2.19 with p = 0.0015, 0.002, 0.0287, and 0.0447, respectively). AP1G2-R563W was significantly associated in LRRK2-carriers (OR = 3.69, p = 0.006) while VPS13D-D2932N was significantly associated in GBA-carriers (OR = 5.45, p = 0.0027). VPS11-C846G and HGS-S243Y were significantly associated in NC (OR = 2.48 and 2.06, with p = 0.022 and 0.0163, respectively). Conclusions: Variants in genes involved in vesicle-mediated protein transport and recycling pathways, including autophagy and mitophagy, may differentially modify PD-risk in LRRK2-carriers, GBA carriers, or NC. Specifically, PIK3C3-R768W is a PD-risk allele, with the highest effect size in LRRK2-G2019S carriers. These results suggest oligogenic effect that may depends on the genetic background of the patient. An unbiased burden of mutations approach in these genes should be evaluated in additional PD and control groups. The mechanisms by which these novel variants interact and increase PD-risk should be researched in depth for better tailoring therapeutic intervention for PD prevention or slowing disease progression
Privacy by Design by Regulation: The Case Study of Ontario
No full textThis article presents the findings of a case study examining the role of the regulator in
facilitating Privacy by Design (“PbD”) solutions. With the introduction of PbD into
the new European Union General Data Protection Regulation, it is important to
understand the conditions under which PbD can succeed and the role which regulators
can play (if at all) in promoting such success. Two initiatives with similar technology
are examined: first, a PbD success, the introduction of facial recognition technology
into existing cameras in casinos in Ontario, and second, a PbD failure, the expanded
deployment of cameras within the public transit system of Toronto. The findings are
organized into three overarching themes: PbD-focused findings, leadership and
organizational findings, and regulator-focused findings. The article argues that privacy
continues to persist as an engineering problem despite PbD, that (related to that) there is
growing recognition of privacy as an issue of organizational change and leadership, and
consequently, that the role of the regulator must evolve if PbD is to become a meaningful
regulatory tool, an evolution that carries with it both risks and opportunities for privacy.Not peer reviewe
Job search by employed workers : the effects of restrictions
No full textWithin the framework of a general equilibrium search model, the authors study the effect of institutional restrictions on workers'job mobility. The model generates endogenuous job searches on the job and off the job with two forms of labor contracts emerging and coexisting in equilibrium. One form of contract involves the workers'long-term commitment to the firm ("reversed tenure"): some firms offer high wages in return for their workers'commitment not to search for better jobs. The other is a short-term contract requiring no such commitment: some firms that cannot afford to pay wages that guarantee lifetime attachment pay lower wages, have lower turn-over costs, but impose no restrictions on searches for better jobs. The authors study the effects on employment of exogenous restrictions on mobility - in the form of a transfer from the quitting worker, made either to the employer or to a third party. These transfers, the separation bonds, are typically the benefits lost by the quitting worker, such as vested pension. Restrictions of this type, by crowding out the firms that allow on-the-job searches for employment directly increase unemployment. When restrictions on workers'mobility take the form of a zero-sum transfer, there is no real effect so long as the transfer is below some bound - the worker loses nothing. When the separation bond is prohibitively large, or when it is forfeited to a third party, employment among all types of workers falls.Health Monitoring&Evaluation,Health Economics&Finance,Environmental Economics&Policies,Economic Theory&Research,Labor Markets
Privacy by design by regulation: The case study of Ontario
No full textThis article presents the findings of a case study examining the role of the regulator in facilitating Privacy by Design (“PbD”) solutions. With the introduction of PbD into the new European Union General Data Protection Regulation, it is important to understand the conditions under which PbD can succeed and the role which regulators can play (if at all) in promoting such success. Two initiatives with similar technology are examined: first, a PbD success, the introduction of facial recognition technology into existing cameras in casinos in Ontario, and second, a PbD failure, the expanded deployment of cameras within the public transit system of Toronto. The findings are organized into three overarching themes: PbD-focused findings, leadership and organizational findings, and regulator-focused findings. The article argues that privacy continues to persist as an engineering problem despite PbD, that (related to that) there is growing recognition of privacy as an issue of organizational change and leadership, and consequently, that the role of the regulator must evolve if PbD is to become a meaningful regulatory tool, an evolution that carries with it both risks and opportunities for privacy.Not peer reviewe
Reciprocity in a Two-Part Dictator Game
No full textWe conduct a dictator game experiment in which recipients in an initial game become dictators in a second game. When the subjects paired remain the same, the amount sent back is strongly correlated with the amount received, despite the fact that the interaction is anonymous and is known to be one-time and zero-sum in nature. When the initial recipient is instead paired with a third subject, a less significant and lower-valued correlation between amounts received and sent is exhibited. Intelligence and personality test results, gender, and other characteristics also help to predict sending behavior and degree of reciprocity.reciprocity, dictator game, cognition, personality, altruism
Robust inter-subject audiovisual decoding in functional magnetic resonance imaging using high-dimensional regression
No full textMajor methodological advancements have been recently made in the field of neural decoding, which is concerned with the reconstruction of mental content from neuroimaging measures. However, in the absence of a large-scale examination of the validity of the decoding models across subjects and content, the extent to which these models can be generalized is not clear. This study addresses the challenge of producing generalizable decoding models, which allow the reconstruction of perceived audiovisual features from human magnetic resonance imaging (fMRI) data without prior training of the algorithm on the decoded content. We applied an adapted version of kernel ridge regression combined with temporal optimization on data acquired during film viewing (234 runs) to generate standardized brain models for sound loudness, speech presence, perceived motion, face-to-frame ratio, lightness, and color brightness. The prediction accuracies were tested on data collected from different subjects watching other movies mainly in another scanner. Substantial and significant (QFDR<0.05) correlations between the reconstructed and the original descriptors were found for the first three features (loudness, speech, and motion) in all of the 9 test movies (R¯=0.62, R¯ = 0.60, R¯ = 0.60, respectively) with high reproducibility of the predictors across subjects. The face ratio model produced significant correlations in 7 out of 8 movies (R¯=0.56). The lightness and brightness models did not show robustness (R¯=0.23, R¯ = 0). Further analysis of additional data (95 runs) indicated that loudness reconstruction veridicality can consistently reveal relevant group differences in musical experience. The findings point to the validity and generalizability of our loudness, speech, motion, and face ratio models for complex cinematic stimuli (as well as for music in the case of loudness). While future research should further validate these models using controlled stimuli and explore the feasibility of extracting more complex models via this method, the reliability of our results indicates the potential usefulness of the approach and the resulting models in basic scientific and diagnostic contexts
A cuspidality criterion for the functorial product on GL(2) × GL(3) with a cohomological application
No full textA strong impetus for this paper came, at least for the first author, from a question of Avner Ash, asking whether one can construct non-selfdual, nonmonomial cuspidal cohomology classes for suitable congruence subgroups Γ of SL(n, Z), say for n = 6. Such a construction, in special examples, ha
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