A large field CCD system for quantitative imaging of microarrays

We describe a charge-coupled device (CCD) imaging system for microarrays capable of acquiring quantitative, high dynamic range images of very large fields. Illumination is supplied by an arc lamp, and filters are used to define excitation and emission bands. The system is linear down to fluorochrome densities ≪1 molecule/µm(2). The ratios of the illumination intensity distributions for all excitation wavelengths have a maximum deviation ∼±4% over the object field, so that images can be analyzed without computational corrections for the illumination pattern unless higher accuracy is desired. Custom designed detection optics produce achromatic images of the spectral region from ∼ 450 to ∼750 nm. Acquisition of a series of images of multiple fluorochromes from multiple arrays occurs under computer control. The version of the system described in detail provides images of 20 mm square areas using a 27 mm square, 2K × 2K pixel, cooled CCD chip with a well depth of ∼10(5) electrons, and provides ratio measurements accurate to a few percent over a dynamic range in intensity >1000. Resolution referred to the sample is 10 µm, sufficient for obtaining quantitative multicolor images from >30 000 array elements in an 18 mm × 18 mm square

Relational legacies impacting on veteran transition from military to civilian life: trajectories of acquisition, loss and re-formulation of a sense of belonging

The veteran cohort has been inextricably linked in the general public's mind by media generated perceptions of high risk and fear of crime, echoed in wider contemporary debates linking issues of place, social identity, social exclusion (Pain 2000) and a loss of belonging in wider communities (Walklate 1998). Despite the growing interest in the longer term outcomes of transition from military to civilian life from policy-makers, practitioners and academics, few qualitative studies explore the social and relational impacts of this transitional experience on those who have experienced it. Tensions and frustrations expressed by ex-forces personnel, engaging in addictions services with a history of engagement in the criminal justice sector, are explored through the lens of belongingness, loss and related citizenship frameworks to expose temporal impacts on the acquisition, loss and reformulation of a sense of belonging across the life course. The relevance of a significant loss of belonging in the transition from military to civilian life is useful, given the widely accepted damaging consequences of having this need thwarted. This paper concludes that a broader understanding of this largely disenfranchised grief (Doka, 2002) can enable more informed reflexive opportunities to facilitate a valued military veteran citizenship status and thereby contribute to the formulation of current policy debates concerning the veteran question

On EPR paradox, Bell's inequalities and experiments which prove nothing

This article shows that the there is no paradox. Violation of Bell's inequalities should not be identified with a proof of non locality in quantum mechanics. A number of past experiments is reviewed, and it is concluded that the experimental results should be re-evaluated. The results of the experiments with atomic cascade are shown not to contradict the local realism. The article points out flaws in the experiments with down-converted photons. The experiments with neutron interferometer on measuring the "contextuality" and Bell-like inequalities are analyzed, and it is shown that the experimental results can be explained without such notions. Alternative experiment is proposed to prove the validity of local realism.Comment: 27 pages, 8 figures. I edited a little the text and abstract I corrected equations (49) and (50

Interplay between telecommunications and face-to-face interactions - a study using mobile phone data

In this study we analyze one year of anonymized telecommunications data for over one million customers from a large European cellphone operator, and we investigate the relationship between people's calls and their physical location. We discover that more than 90% of users who have called each other have also shared the same space (cell tower), even if they live far apart. Moreover, we find that close to 70% of users who call each other frequently (at least once per month on average) have shared the same space at the same time - an instance that we call co-location. Co-locations appear indicative of coordination calls, which occur just before face-to-face meetings. Their number is highly predictable based on the amount of calls between two users and the distance between their home locations - suggesting a new way to quantify the interplay between telecommunications and face-to-face interactions

Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard

Drug abuse robs individuals of their jobs, their families, and their free will as they succumb to addiction; but may cost even more: a life of disability or even life lost due to stroke. Many illicit drugs have been linked to major cardiovascular events and other comorbidities, including cocaine, amphetamines, ecstasy, heroin, phencyclidine, lysergic acid diethylamide, and marijuana. This review focuses on available epidemiological data, mechanisms of action, particularly those leading to cerebrovascular events, and it is based on papers published in English in PubMed during 1950 through February 2011. Each drug's unique interactions with the brain and vasculature predispose even young, healthy people to ischemic or hemorrhagic stroke. Cocaine and amphetamines have the strongest association with stroke. However, the level of evidence firmly linking other drugs to stroke pathogenesis is weak. Large epidemiological studies and systematic evaluation of each drug's action on the brain and cardiovascular system are needed to reveal the full impact of drug use on the population

Holocentric Chromosomes of Luzula elegans Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

The structure of holocentric chromosomes was analyzed in mitotic cells of Luzula elegans. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, L. elegans chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to Arabidopsis-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability. Copyright (C) 2011 S. Karger AG, Base

Between proper and strong edge-colorings of subcubic graphs

In a proper edge-coloring the edges of every color form a matching. A matching is induced if the end-vertices of its edges induce a matching. A strong edge-coloring is an edge-coloring in which the edges of every color form an induced matching. We consider intermediate types of edge-colorings, where edges of some colors are allowed to form matchings, and the remaining form induced matchings. Our research is motivated by the conjecture proposed in a recent paper of Gastineau and Togni on S-packing edge-colorings (On S-packing edge-colorings of cubic graphs, Discrete Appl. Math. 259 (2019), 63-75) asserting that by allowing three additional induced matchings, one is able to save one matching color. We prove that every graph with maximum degree 3 can be decomposed into one matching and at most 8 induced matchings, and two matchings and at most 5 induced matchings. We also show that if a graph is in class I, the number of induced matchings can be decreased by one, hence confirming the above-mentioned conjecture for class I graphs

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response