Expansion and Consolidation: The Associate Committee and the Division of Medical Research of the NRC, 1938-1959

The federal government took on the responsibility for the funding and coordination of medical research in 1938 with the creation of the Associate Committee on Medical Research of the National Research Council of Canada. The Associate Committee and its successor, the Division of Medical Research, developed policies and practices which promoted the growth of original investigation in the medical sciences through the Second World War and the post-war expansion. Their work helped to stimulate and institutionalize medical research on a national basis.C’est en 1938, par la création du Comité associé sur la recherche médicale du Conseil national de recherches du Canada, que le gouvernement fédéral prit en charge le financement et la coordination de la recherche médicale. Le comité associé et son successeur la Division de recherche médicale, ont mis au point des politiques et des pratiques qui ont favorisé la croissance de nouvelles recherches en sciences médicales pendant la Seconde guerre mondiale et au cours de la période de croissance qui suivit. L’action de ces comités a stimulé et favorisé l’institutionnalisation de la recherche médicale à l’échelle nationale

Numerical Simulation Based Targeting of the Magushan Skarn Cu-Mo Deposit, Middle-Lower Yangtze Metallogenic Belt, China

The Magushan Cu–Mo deposit is a skarn deposit within the Nanling–Xuancheng mining district of the Middle-Lower Yangtze River Metallogenic Belt (MLYRMB), China. This study presents the results of a new numerical simulation that models the ore-forming processes that generated the Magushan deposit and enables the identification of unexplored areas that have significant exploration potential under areas covered by thick sedimentary sequences that cannot be easily explored using traditional methods. This study outlines the practical value of numerical simulation in determining the processes that operate during mineral deposit formation and how this knowledge can be used to enhance exploration targeting in areas of known mineralization. Our simulation also links multiple subdisciplines such as heat transfer, pressure, fluid flow, chemical reactions, and material migration. Our simulation allows the modeling of the formation and distribution of garnet, a gangue mineral commonly found within skarn deposits (including within the Magushan deposit). The modeled distribution of garnet matches the distribution of known mineralization as well as delineating areas that may well contain high garnet abundances within and around a concealed intrusion, indicating this area should be considered a prospective target during future mineral exploration. Overall, our study indicates that this type of numerical simulation-based approach to prospectivity modeling is both effective and economical and should be considered an additional tool for future mineral exploration to reduce exploration risks when targeting mineralization in areas with thick and unprospective sedimentary cover sequences

Draft Genome Sequences of Propionibacterium acnes Type Strain ATCC6919 and Antibiotic-Resistant Strain HL411PA1.

Propionibacterium acnes is a major skin commensal and is associated with acne vulgaris, the most common skin disease. Here we report the draft genome sequences of two P. acnes strains, the type strain ATCC6919 and an antibiotic-resistant strain, HL411PA1

Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells

In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells.In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas9 will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD.National Institutes of Health (U.S.) (Grant R01-AG047661

Exploiting lattice structures in shape grammar implementations

The ability to work with ambiguity and compute new designs based on both defined and emergent shapes are unique advantages of shape grammars. Realizing these benefits in design practice requires the implementation of general purpose shape grammar interpreters that support: (a) the detection of arbitrary subshapes in arbitrary shapes and (b) the application of shape rules that use these subshapes to create new shapes. The complexity of currently available interpreters results from their combination of shape computation (for subshape detection and the application of rules) with computational geometry (for the geometric operations need to generate new shapes). This paper proposes a shape grammar implementation method for three-dimensional circular arcs represented as rational quadratic Bézier curves based on lattice theory that reduces this complexity by separating steps in a shape computation process from the geometrical operations associated with specific grammars and shapes. The method is demonstrated through application to two well-known shape grammars: Stiny's triangles grammar and Jowers and Earl's trefoil grammar. A prototype computer implementation of an interpreter kernel has been built and its application to both grammars is presented. The use of Bézier curves in three dimensions opens the possibility to extend shape grammar implementations to cover the wider range of applications that are needed before practical implementations for use in real life product design and development processes become feasible

Functional characterization improves associations between rare non-synonymous variants in CHRNB4 and smoking behavior

Smoking is the leading cause of preventable death worldwide. Accordingly, effort has been devoted to determining the genetic variants that contribute to smoking risk. Genome-wide association studies have identified several variants in nicotinic acetylcholine receptor genes that contribute to nicotine dependence risk. We previously undertook pooled sequencing of the coding regions and flanking sequence of the CHRNA5, CHRNA3, CHRNB4, CHRNA6 and CHRNB3 genes and found that rare missense variants at conserved residues in CHRNB4 are associated with reduced risk of nicotine dependence among African Americans. We identified 10 low frequency (<5%) non-synonymous variants in CHRNB4 and investigated functional effects by co-expression with normal α3 or α4 subunits in human embryonic kidney cells. Voltage-clamp was used to obtain acetylcholine and nicotine concentration-response curves and qRT-PCR, western blots and cell-surface ELISAs were performed to assess expression levels. These results were used to functionally weight genetic variants in a gene-based association test. We find that there is a highly significant correlation between carrier status weighted by either acetylcholine EC50 (β = -0.67, r2 = 0.017, P = 2 × 10(-4)) or by response to low nicotine (β = -0.29, r2 = 0.02, P = 6 × 10(-5)) when variants are expressed with the α3 subunit. In contrast, there is no significant association when carrier status is unweighted (β = -0.04, r2 = 0.0009, P = 0.54). These results highlight the value of functional analysis of variants and the advantages to integrating such data into genetic studies. They also suggest that an increased sensitivity to low concentrations of nicotine is protective from the risk of developing nicotine dependence

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease.

OBJECTIVES: To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. METHODS: 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers' ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. RESULTS: Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. CONCLUSIONS: The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM