Open system effects on slow light and electromagnetically induced transparency

The coherence properties of a three-level $\Lambda$-system influenced by a Markovian environment are analyzed. A coherence vector formalism is used and a vector form of the Lindblad equation is derived. Together with decay channels from the upper state, open system channels acting on the subspace of the two lower states are investigated, i.e., depolarization, dephasing, and amplitude damping channels. We derive an analytic expression for the coherence vector and the concomitant optical susceptibility, and analyze how the different channels influence the optical response. This response depends non-trivially on the type of open system interaction present, and even gain can be obtained. We also present a geometrical visualization of the coherence vector as an aid to understand the system response.Comment: Several changes; journal reference adde

Genes with Relevance for Early to Late Progression of Colon Carcinoma Based on Combined Genomic and Transcriptomic Information from the Same Patients

Background: Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression. Methods: Tumor and normal colon tissue were obtained at primary operations from 24 patients selected by chance. DNA, RNA and microRNAs were extracted from the same biopsy material in all individuals and analyzed by oligo-nucleotide array-based comparative genomic hybridization (CGH), mRNA- and microRNA oligo-arrays. Statistical analyses were performed to assess statistical interactions (correlations, co-variations) between DNA copy number changes and significant alterations in gene and microRNA expression using appropriate parametric and non-parametric statistics. Results: Main DNA alterations were located on chromosome 7, 8, 13 and 20. Tumor DNA copy number gain increased with tumor progression, significantly related to increased gene expression. Copy number loss was not observed in Dukes A tumors. There was no significant relationship between expressed genes and tumor progression across Dukes A–D tumors; and no relationship between tumor stage and the number of microRNAs with significantly altered expression. Interaction analyses identified overall 41 genes, which discriminated early Dukes A plus B tumors from late Dukes C plus D tumor; 28 of these genes remained with correlations between genomic and transcriptomic alterations in Dukes C plus D tumors and 17 in Dukes D. One microRNA (microR-663) showed interactions with DNA alterations in all Dukes A-D tumors. Conclusions: Our modeling confirms that colon cancer progression is related to genomic instability and altered gene expression. How- ever, early invasive tumor growth seemed rather related to transcriptomic alterations, where changes in microRNA may be an early phenomenon, and less to DNA copy number changes

The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. <p/>Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. <p/>Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. <p/>Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL

The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge

BACKGROUND AND AIM:The first genome-wide association study on birth weight was recently published and the most significant associated birth weight lowering variant was the rs900400 C-allele located near LEKR1 and CCNL1. We aimed to replicate the association with birth weight in the Danish Inter99 study and furthermore to evaluate associations between rs900400 and indices of insulin secretion and insulin sensitivity obtained by oral glucose tolerance tests in adults from the Danish Inter99 study and the Finnish, Metabolic Syndrome in Men (METSIM) sample. METHODS:For 4,744 of 6,784 Inter99 participants, midwife journals were traced through the Danish State Archives and association of rs900400 with birth weight was examined. Associations between rs900400 and fasting serum insulin, fasting plasma glucose, insulinogenic index, homeostasis model assessment of insulin resistance (HOMA-IR) and disposition index were studied in 5,484 Danish and 6,915 Finnish non-diabetic individuals and combined in meta-analyses. RESULTS:The C-allele of rs900400 was associated with a 22.1 g lower birth weight ([-41.3;-3.0], P = 0.024) per allele. Moreover, in combined analyses of the Danish Inter99 study and the Finnish METSIM study we found that the birth weight lowering allele was associated with increased insulin release measured by the insulinogenic index (β = 2.25% [0.59; 3.91], P = 0.008) and with an increased disposition index (β = 1.76% [0.04; 3.49], P = 0.05). CONCLUSION:The birth weight lowering effect of the C-allele of rs900400 located near LEKR1 and CCNL1 was replicated in the Danish population. Furthermore the C-allele was associated with increased insulin response following oral glucose stimulation in a meta-analysis based on Danish and Finnish non-diabetic individuals

Clinical Use and Effectiveness of Lipid Lowering Therapies in Diabetes Mellitus—An Observational Study from the Swedish National Diabetes Register

OBJECTIVES: To describe the use and evaluate the effectiveness of different lipid lowering therapies in unselected patients with type 1 and type 2 diabetes in clinical practice. DESIGN: Observational population-based study using the personal identification number to link information from the National Diabetes Register, the Prescribed Drug Register and the Patient register in Sweden. All patients in the NDR aged 18-75 years with diabetes more than one year were eligible, but only patients starting any lipid lowering treatment with at least three prescriptions 1 July 2006-30 June 2007 were included (n = 37,182). The mean blood lipid levels in 2008 and reductions in LDL cholesterol were examined. RESULTS: Blood lipid levels were similar in patients treated with simvastatin, atorvastatin and rosuvastatin, showing similar lipid lowering effect as currently used. Users of pravastatin, fluvastatin, ezetimib and fibrate more seldom reach treatment goals. Moderate daily doses of the statins were used, with 76% of simvastatin users taking 20 mg or less, 48% of atorvastatin users taking 10 mg, 55% of pravastatin users taking 20 mg, and 76% of rosuvastatin users taking 5 or 10 mg. CONCLUSIONS: This observational study shows that the LDL-C levels in patients taking simvastatin, atorvastatin or rosuvastatin are very similar as currently used, as well as their LDL-C lowering abilities. There is potential to intensify lipid lowering treatment to reduce the remaining high residual risk and achieve better fulfilment of treatment goals, since the commonly used doses are only low to moderate

Light-ion production in the interaction of 175 MeV quasi-mono-energetic neutrons with iron and with bismuth

Nuclear data for neutron-induced reactions in the intermediate energy range of 20 to 200 MeV are of great importance for the development of nuclear reaction codes since little data exist in that range. Also several different applications benefit from such data, notably accelerator-driven incineration of nuclear waste. The Medley setup was used for a series of measurements of p, d, t, $^3$He and $\alpha$-particle production by 175 MeV quasi-mono-energetic neutrons on various target nuclei. The measurements were performed at the The Svedberg Laboratory in Uppsala, Sweden. Eight detector telescopes placed at angles between 20$^\circ$ and 160$^\circ$ were used. Medley uses the $\Delta E$-$\Delta E$-$E$ technique to discriminate among the particle types and is able to measure double-differential cross sections over a wide range of particle energies. This paper briefly describes the experimental setup, summarizes the data analysis and reports on recent changes in the previously reported preliminary data set on bismuth. Experimental data are compared with INCL4.5-Abla07, MCNP6 using CEM03.03, TALYS and PHITS model calculations as well as with nuclear data evaluations. The models agree fairly well overall but in some cases systematic differences are found.Comment: 16 pages, 19 figures; submitted to Phys. Rev.

Pattern Recognition in Pulmonary Tuberculosis Defined by High Content Peptide Microarray Chip Analysis Representing 61 Proteins from M. tuberculosis

Background: Serum antibody-based target identification has been used to identify tumor-associated antigens (TAAs) for development of anti-cancer vaccines. A similar approach can be helpful to identify biologically relevant and clinically meaningful targets in M.tuberculosis (MTB) infection for diagnosis or TB vaccine development in clinically well defined populations. Method: We constructed a high-content peptide microarray with 61 M.tuberculosis proteins as linear 15 aa peptide stretches with 12 aa overlaps resulting in 7446 individual peptide epitopes. Antibody profiling was carried with serum from 34 individuals with active pulmonary TB and 35 healthy individuals in order to obtain an unbiased view of the MTB epitope pattern recognition pattern. Quality data extraction was performed, data sets were analyzed for significant differences and patterns predictive of TB+/2. Findings: Three distinct patterns of IgG reactivity were identified: 89/7446 peptides were differentially recognized (in 34/34 TB+ patients and in 35/35 healthy individuals) and are highly predictive of the division into TB+ and TB2, other targets were exclusively recognized in all patients with TB (e.g. sigmaF) but not in any of the healthy individuals, and a third peptide set was recognized exclusively in healthy individuals (35/35) but no in TB+ patients. The segregation between TB+ and TB2 does no

Barriers and facilitators to implementing community outreach work, and inter-professional collaboration with regional partners

Abstract : Objective. Community outreach workers support individuals in accessing the health and community services they require through various forms of proximity approaches. Even though community outreach has been available in the province of Quebec (Canada) for the past 40 years, it is still difficult to implement and sustain, especially with families of young children. The aim of this study was to document barriers and facilitators to implementing community outreach practices, and to describe how such workers collaborate with sectoral (e.g. health care) and inter-sectoral (e.g. municipalities, community organizations, schools) partners. Methodology. We performed a content analysis on 55 scientific and grey literature documents, and transcriptions of 24 individual interviews and 3 focus groups with stakeholders including parents, community outreach workers, health care employees, and inter-sectoral partners. Results. This study reveals four categories of barriers and facilitators to the implementation of community outreach work (i.e. organizational factors, nature of the work and worker-related factors, family-related factors, external factors). With regards to collaboration, community outreach workers deal with various partners. Good inter-professional collaboration is achieved through positive interactions and communication, shared or co-developed activities for the families, co-intervention with families, and strategies to enhance role awareness and inter-sectoral meetings. Conclusion. Results highlighted that many factors interact and can either influence, positively or negatively, the opportunity to implement community outreach work. The collaborative practices identified may help to maximize facilitators and overcome barriers. Advocacy and a better understanding of how to integrate community outreach work within health services while maintaining the workers’ flexibility are needed to sustain this practice

Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content

Defects in the mRNA export scaffold protein GANP, encoded by the MCM3AP gene, cause autosomal recessive early-onset peripheral neuropathy with or without intellectual disability. We extend here the phenotypic range associated with MCM3AP variants, by describing a severely hypotonic child and a sibling pair with a progressive encephalopathic syndrome. In addition, our analysis of skin fibroblasts from affected individuals from seven unrelated families indicates that disease variants result in depletion of GANP except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants. Patient fibroblasts showed transcriptome alterations that suggested intron content-dependent regulation of gene expression. For example, all differentially expressed intronless genes were downregulated, including ATXN7L3B, which couples mRNA export to transcription activation by association with the TREX-2 and SAGA complexes. Our results provide insight into the molecular basis behind genotype-phenotype correlations in MCM3AP-associated disease and suggest mechanisms by which GANP defects might alter RNA metabolism.Peer reviewe