Gamma-Ray Bursts from Primordial Quark Objects in Space

We investigate the possibility that gamma-ray bursts originate in a concentric spherical shell with a given average redshift and find that this is indeed compatible with the data from the third BATSE (3B) catalog. It is also shown that there is enough freedom in the choice of unknown burst properties to allow even for extremely large distances to the majority of bursts. Therefore, we speculate about an early, and very energetic, origin of bursts, and suggest that they come from phase transitions in massive objects of pure quark matter, left over from the Big Bang.Comment: 11 pages, Latex, 3 postscript figures, to be publ in the Proc of the Joint Meeting of the Networks 'The Fundamental Structure of Matter' and 'Tests of the Electroweak Symmetry Breaking', Ouranoupolis, Greece, May 199

Preliminary X-ray crystallographic analysis of the secreted chorismate mutase from Mycobacterium tuberculosis: a tricky crystallization problem solved

A method is presented that allowed the diffraction limit of crystals of the secreted chorismate mutase from M. tuberculosis to be improved from approximately 3.5 to 1.3 Å. To obtain large well diffracting crystals, it was critical to initiate crystallization at higher precipitant concentration and then transfer the drops to lower precipitant concentrations within 5–15 min

Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.

In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24 <sup>Gag</sup> vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI. All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log <sub>10</sub> -transformed VL (VE <sup>VL</sup> ) or CD4 count (VE <sup>CD4</sup> ). A lower fold-change of CD4+ T-cell proliferation was associated with VE <sup>CD4</sup> at week 48 (p=0.036, multiplicity adjusted q=0.036) and week 52 (p=0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VE <sup>VL</sup> at week 44 (p=0.047, q=0.07). A higher fold-change of TNF-α was associated with VE <sup>VL</sup> at week 44 (p=0.045, q=0.070), week 48 (p=0.028, q=0.070), and week 52 (p=0.037, q=0.074). A higher fold-change of IL-6 was associated with VE <sup>VL</sup> at week 48 (p=0.017, q=0.036). TNF-α levels (>median) were associated with VE <sup>CD4</sup> at week 48 (p=0.009, q=0.009). These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies

Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia

B-cell chronic lymphocytic leukaemia (B-CLL) is characterised by the progressive accumulation of monoclonal CD5+ B cells. In a previous study, we have analysed the expression profile of apoptosis-regulating genes using a cDNA-based microarray and found overexpression of the antiapoptotic bcl-2 family member, bfl-1, in B-CLL cells with an apoptosis-resistant phenotype. In this study, bfl-1 mRNA levels have been determined by competitive PCR in an extended population of B-CLL patients to characterise its role in disease progression and development of chemoresistance. bfl-1 levels were significantly higher in patients with no response (NR) to last chemotherapy than in patients responding (partial response (PR)) to last chemotherapy (P<0.05) and in patients who had not required treatment (P<0.05). We found no correlation between bfl-1 mRNA levels and disease progression, IGHV mutational status or other clinical parameters. In addition, bfl-1 mRNA levels were inversely correlated with apoptotic response to in vitro fludarabine treatment of B-CLL cells. Specific downregulation of bfl-1 using siRNA induced apoptosis in resistant cells. Our data suggest that bfl-1 contributes to chemoresistance and might be a therapeutic target in B-CLL

Neuroadaptations in Human Chronic Alcoholics: Dysregulation of the NF-κB System

Anna Ökvist is with Karolinska Institute, Sofia Johansson is with Karolinska Institute, Alexander Kuzmin is with Karolinska Institute, Igor Bazov is with Karolinska Institute, Roxana Merino-Martinez is with Karolinska Institute, Igor Ponomarev is with UT Austin, R. Dayne Mayfield is with UT Austin, R. Adron Harris is with UT Austin, Donna Sheedy is with University of Sydney, Therese Garrick is with University of Sydney, Clive Harper is with University of Sydney, Yasmin L. Hurd is with Mount Sinai School of Medicine, Lars Terenius is with Karolinska Institute, Tomas J. Ekström is with Karolinska Institute, Georgy Bakalkin is with Karolinska Institute and Uppsala University, Tatjana Yakovleva is with Karolinska Institute and Uppsala University.Background -- Alcohol dependence and associated cognitive impairments apparently result from neuroadaptations to chronic alcohol consumption involving changes in expression of multiple genes. Here we investigated whether transcription factors of Nuclear Factor-kappaB (NF-κB) family, controlling neuronal plasticity and neurodegeneration, are involved in these adaptations in human chronic alcoholics. Methods and Findings -- Analysis of DNA-binding of NF-κB (p65/p50 heterodimer) and the p50 homodimer as well as NF-κB proteins and mRNAs was performed in postmortem human brain samples from 15 chronic alcoholics and 15 control subjects. The prefrontal cortex involved in alcohol dependence and cognition was analyzed and the motor cortex was studied for comparison. The p50 homodimer was identified as dominant κB binding factor in analyzed tissues. NF-κB and p50 homodimer DNA-binding was downregulated, levels of p65 (RELA) mRNA were attenuated, and the stoichiometry of p65/p50 proteins and respective mRNAs was altered in the prefrontal cortex of alcoholics. Comparison of a number of p50 homodimer/NF-κB target DNA sites, κB elements in 479 genes, down- or upregulated in alcoholics demonstrated that genes with κB elements were generally upregulated in alcoholics. No significant differences between alcoholics and controls were observed in the motor cortex. Conclusions -- We suggest that cycles of alcohol intoxication/withdrawal, which may initially activate NF-κB, when repeated over years downregulate RELA expression and NF-κB and p50 homodimer DNA-binding. Downregulation of the dominant p50 homodimer, a potent inhibitor of gene transcription apparently resulted in derepression of κB regulated genes. Alterations in expression of p50 homodimer/NF-κB regulated genes may contribute to neuroplastic adaptation underlying alcoholism.This work was supported by grants from the AFA Forsäkring to AK, YLH, TJE and GB, the Research Foundation of the Swedish Alcohol Retail Monopoly (SRA) and Karolinska Institutet to AK, TJE and GB, and the Swedish Science Research Council and the Swedish National Drug Policy Coordinator to GB. The Australian Brain Donor Programs NSW Tissue Resource Centre was supported by The University of Sydney, National Health and Medical Research Council of Australia, Neuroscience Institute of Schizophrenia and Allied Disorders, National Institute of Alcohol Abuse and Alcoholism and NSW Department of Health.Waggoner Center for Alcohol and Addiction Researc

The sleep of little children and their parents

Background: How small children sleep influence the whole family. Sleeping problems, could influence children physical, mental, emotionally, cognitive and socially. When parents get waked by the children, who wake by themselves in the middle of the night, the parents do not always now what to do. Aim: The aim of this study was how children sleep and how it influence their parents sleep habit. The question formulation was threefold: Firstly. To describe the sleeping habit of children aged 0-3 years and their parents. Secondly, how usual are sleeping problems and which are the differences concerning sleep between those who experience problems and those who do not? Thirdly, witch help has the parents searched and received concerning sleeping problems. Method: The study was empirical and a questionnaire was constructed. This was delivered to three children care centres. 51 questionnaires were answered and analysed. Results: The parents who believed that they sometimes had problem with the sleep, felt more irascible. They also believed that the children were more frequently sick. The parents talked more with district nurse, and they had more frequently at least two children

Erfarenhetsåterföring och uppföljning av ÄTA : Ett beställarperspektiv

Validerat; 20140226 (global_studentproject_submitter

Det är en utmaning. Men den är ju viktig. : En kvalitativ undersökning av planeringen för representativa medborgardialoger

ABSTRACTThe aim with this study was to examine how a municipality plans for representative citizens dialogues, by investigating the motives, how they understand and have planned for representativity. This has been done through a case study with the case Skövde tätorter, a project that has been initiated to encourage urban development in Skövde municipality.This study’s analysis has been accomplished by a directed content analysis. This means that previous scientific research and theories has formed the analytic framework in the form of a coding scheme. To get a greater understanding of how the municipality’s in-house project group has reasoned and planned for representativity, interviews have been done with the planners in charge of the project. In addition to this, studies of project specific guidelines, presentations and memos from project meetings has been made.The study shows that Skövde has good intentions when planning for representative citizen dialogues. They state that representativity has been permeating the project since it started. The municipality have had a vision that the citizen dialogues should generate participation, representativity and a consensus. In other words, it needs to be inclusive, but with an aim to reach consensus. This is possible goals, but it becomes difficult to claim that representativity has been the dialogues focus. An important conclusion from the interviews is that the expectation on the dialogues is that they automatically will generate representativity, and not something the municipality actively have to plan for. This indicates that Skövde did not have a concrete plan, which according to Madureira, is a necessity to success

Effektivisera genom att planera - gör mer med mindre

Validerat; 20101217 (root