Bioluminescence Intensity Modeling and Sampling Strategy Optimization

The focus of this paper is on the development of methodology for short-term (1-3 days) oceanic bioluminescence (BL) predictions and the optimization of spatial and temporal bioluminescence sampling strategies. The approach is based on predictions of bioluminescence with an advection-diffusion-reaction (tracer) model with velocities and diffusivities from a circulation model. In previous research, it was shown that short-term changes in some of the salient features in coastal bioluminescence can be explained and predicted by using this approach. At the same time, it was demonstrated that optimization of bioluminescence sampling prior to the forecast is critical for successful short-term BL predictions with the tracer model. In the present paper, the adjoint to the tracer model is used to study the sensitivity of the modeled bioluminescence distributions to the sampling strategies for BL. The locations and times of bioluminescence sampling prior to the forecast are determined by using the adjoint-based sensitivity maps. The approach is tested with bioluminescence observations collected during August 2000 and 2003 in the Monterey Bay, California, area. During August 2000, BL surveys were collected during a strong wind relaxation event, while in August 2003, BL surveys were conducted during an extended (longer than a week) upwelling-favorable event. The numerical bioluminescence predictability experiments demonstrated a close agreement between observed and model-predicted short-term spatial and temporal changes of the coastal bioluminescence

Результаты наблюдательного исследования ТРАМПЛИН по оценке эффективности, безопасности и переносимости крема Травоген и крема Травокорт

The article describes the results of the TRAMPLIN clinical multi-center follow-up prospective study for evaluating the efficacy, safety and tolerance of the Travogen cream (isoconazole) and Travocort cream (isoconazole, diflucortolone) in patients suffering from combined (allergic, mycotic, bacterial) skin lesions of different etiology and localization in Moscow.Приведены результаты клинического многоцентрового наблюдательного проспективного исследования ТРАМПЛИН по оценке эффективности, безопасности и переносимости крема Травоген (изоконазол) и крема Травокорт (изоконазол, дифлукортолон) у больных с комбинированными (аллергическими, микотическими, бактериальными) поражениями кожи различной этиологии и локализации в Москве

Parkinson's disease age at onset genome-wide association study : Defining heritability, genetic loci, and α-synuclein mechanisms

Background Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age at onset are largely unknown. Objectives To identify the genetic determinants of PD age at onset. Methods Using genetic data of 28,568 PD cases, we performed a genome-wide association study based on PD age at onset. Results We estimated that the heritability of PD age at onset attributed to common genetic variation was similar to 0.11, lower than the overall heritability of risk for PD (similar to 0.27), likely, in part, because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni-corrected significant effect at other known PD risk loci, GBA, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. Notably, SNCA, TMEM175, SCARB2, BAG3, and GBA have all been shown to be implicated in alpha-synuclein aggregation pathways. Remarkably, other well-established PD risk loci, such as GCH1 and MAPT, did not show a significant effect on age at onset of PD. Conclusions Overall, we have performed the largest age at onset of PD genome-wide association studies to date, and our results show that not all PD risk loci influence age at onset with significant differences between risk alleles for age at onset. This provides a compelling picture, both within the context of functional characterization of disease-linked genetic variability and in defining differences between risk alleles for age at onset, or frank risk for disease. (c) 2019 International Parkinson and Movement Disorder SocietyPeer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Opportunities and challenges of China’s inquiry-based education reform in middle and high schools: Perspectives of science teachers and teacher educators

Consistent with international trends, an emergent interest in inquiry-based science teaching and learning in K-12 schools is also occurring in China. This study investigates the possibilities for and the barriers to enactment of inquiry-based science education in Chinese schools. Altogether 220 Chinese science teachers, science teacher educators and researchers (primarily from the field of chemistry education) participated in this study in August 2001. Participants represented 13 cities and provinces in China. We administered two questionnaires, one preceding and one following a 3-hour presentation by a US science educator and researcher about inquiry-based teaching and learning theories and practices. In each of three sites in which the study was conducted (Shanghai, Guangzhou and Beijing), questionnaires were administered, and four representative participants were interviewed. Our coding and analysis of quantifiable questionnaire responses (using a Likert scale), of open-ended responses, and of interview transcripts revealed enthusiastic interest in incorporating inquiry-based teaching and learning approaches in Chinese schools. However, Chinese educators face several challenges: (a) the national college entrance exam needs to align with the goals of inquiry-based teaching; (b) systemic reform needs to happen in order for inquiry-based science to be beneficial to students, including a change in the curriculum, curriculum materials, relevant resources, and teacher professional development; (c) class size needs to be reduced; and (d) an equitable distribution of resources in urban and rural schools needs to occur.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42933/1/10763_2005_Article_1517.pd

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies