39 research outputs found
Claims on Housing Space in Nineteenth-Century Montreal
Space per person is a fundamental measure of equity in an urban society. From small samples of the Montreal population over the years 1861-1901, we infer substantial improvement in the average dwelling space available per person, but an extreme and persistent inequity in the distribution among households. The housing market remained polarised in terms of class and cultural identity. As crowding diminished, urban density increased, and the problem of working-class housing became, increasingly, one of collective rather than individual space. Families, through networks of kinship and neighbouring, found new ways to exert some control over vital urban micro-spaces. In a continuous, demanding process of adjustment of households to dwellings, the re-structuring of households was a factor as important as their moves from house to house
Residential Segregation in the Industrializing City: A Closer Look
This article maps and measures several dimensions of residential segregation in Montreal in 1881, thereby adding to our understanding of the social structure of the industrial city. Taking advantage of an unusual historical database—a historical geographic information system (H-GIS)—we locate 17,000 individual households with precision, and evaluate the dissimilarity of neighborhoods along several social dimensions and at various levels of spatial aggregation. The empirical findings suggest that Montreal was highly segregated along lines of ethnic identity as well as socioeconomic status; segregation values increased inversely with size of the spatial unit, but precision of unit boundaries have negligible effect. Coupling the highprecision GIS with a statistical model such as the classic index of dissimilarity lends new power to grasp the scale of phenomena, to inquire into behavioral choices of 19th-century households, and even to challenge our assumptions about the meaning of segregation or integration
Identification and Characterization of Novel Mutations in the Human Gene Encoding the Catalytic Subunit Calpha of Protein Kinase A (PKA)
The genes PRKACA and PRKACB encode the principal catalytic (C) subunits of protein kinase A (PKA) Cα and Cβ, respectively. Cα is expressed in all eukaryotic tissues examined and studies of Cα knockout mice demonstrate a crucial role for Cα in normal physiology. We have sequenced exon 2 through 10 of PRKACA from the genome of 498 Norwegian donors and extracted information about PRKACA mutations from public databases. We identified four interesting nonsynonymous point mutations, Arg45Gln, Ser109Pro, Gly186Val, and Ser263Cys, in the Cα1 splice variant of the kinase. Cα variants harboring the different amino acid mutations were analyzed for kinase activity and regulatory (R) subunit binding. Whereas mutation of residues 45 and 263 did not alter catalytic activity or R subunit binding, mutation of Ser109 significantly reduced kinase activity while R subunit binding was unaltered. Mutation of Cα Gly186 completely abrogated kinase activity and PKA type I but not type II holoenzyme formation. Gly186 is located in the highly conserved DFG motif of Cα and mutation of this residue to Val was predicted to result in loss of binding of ATP and Mg2+, which may explain the kinetic inactivity. We hypothesize that individuals born with mutations of Ser109 or Gly186 may be faced with abnormal development and possibly severe disease
Tumor Transcriptome Sequencing Reveals Allelic Expression Imbalances Associated with Copy Number Alterations
Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor
2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects
Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis
The role of plant functional groups mediating climate impacts on carbon and biodiversity of alpine grasslands
Plant removal experiments allow assessment of the role of biotic interactions among species or
functional groups in community assembly and ecosystem functioning. When replicated along climate
gradients, they can assess changes in interactions among species or functional groups with climate.
Across twelve sites in the Vestland Climate Grid (VCG) spanning 4°C in growing season temperature
and 2000 mm in mean annual precipitation across boreal and alpine regions of Western Norway, we
conducted a fully factorial plant functional group removal experiment (graminoids, forbs, bryophytes).
Over six years, we recorded biomass removed, soil microclimate, plant community composition
and structure, seedling recruitment, ecosystem carbon fuxes, and refectance in 384 experimental
and control plots. The dataset consists of 5,412 biomass records, 360 species-level biomass records,
1,084,970 soil temperature records, 4,771 soil moisture records, 17,181 plant records covering 206
taxa, 16,656 seedling records, 3,696 ecosystem carbon fux measurements, and 1,244 refectance
measurements. The data can be combined with longer-term climate data and plant population,
community, ecosystem, and functional trait data collected within the VCG.publishedVersio
Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing
Numerical Evaluation of T-stress under Mixed Mode Loading Through the Use of Coarse Meshes
The present paper investigates the employment of coarse meshes in evaluating the T-stress with the displacement method. Several finite element analyses have been carried out with different mesh refinements and accuracies. Mode I and mixed mode I/II loadings have been considered in finite element analyses. Under mode I loading, single and double edge notched geometries have been considered, while plate with central crack has been considerd for mixed mode loading condition. The analyses are compared with the results by the well-nown stress based approach, and showed that the displacement method permits the evaluation of the T-stress with the employment of coarse meshes. By the way, several precautions must be taken when dealing with coarse and very coarse meshes.Peer reviewe