243 research outputs found

    Pseudo-Dirac Scenario for Neutrino Oscillations

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    We argue how pseudo-Dirac scenario for neutrinos leads to rich neutrino oscillation phenomena, including oscillation inside each generation. The pseudo-Dirac scenario is generalized by incorporating generation mixings and formulae for the various neutrino oscillations are derived. As the application we compare the formulae with the corresponding data. We find that observed pattern of mixings, such as almost maximal mixing in the atmospheric neutrino oscillation, is naturally explained in the generalized Pseudo-Dirac scenario with small generation mixings. We, however, also point out that there remain some problems to be settled for this scenario to be viable. The possible theoretical framework to realize the pseudo-Dirac scenario is also briefly commented on.Comment: 17 pages, LaTeX fil

    Alanine Racemase Mutants of Burkholderia pseudomallei and Burkholderia mallei and Use of Alanine Racemase as a Non-Antibiotic-Based Selectable Marker

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    Burkholderia pseudomallei and Burkholderia mallei are category B select agents and must be studied under BSL3 containment in the United States. They are typically resistant to multiple antibiotics, and the antibiotics used to treat B. pseudomallei or B. mallei infections may not be used as selective agents with the corresponding Burkholderia species. Here, we investigated alanine racemase deficient mutants of B. pseudomallei and B. mallei for development of non-antibiotic-based genetic selection methods and for attenuation of virulence. The genome of B. pseudomallei K96243 has two annotated alanine racemase genes (bpsl2179 and bpss0711), and B. mallei ATCC 23344 has one (bma1575). Each of these genes encodes a functional enzyme that can complement the alanine racemase deficiency of Escherichia coli strain ALA1. Herein, we show that B. pseudomallei with in-frame deletions in both bpsl2179 and bpss0711, or B. mallei with an in-frame deletion in bma1575, requires exogenous d-alanine for growth. Introduction of bpsl2179 on a multicopy plasmid into alanine racemase deficient variants of either Burkholderia species eliminated the requirement for d-alanine. During log phase growth without d-alanine, the viable counts of alanine racemase deficient mutants of B. pseudomallei and B. mallei decreased within 2 hours by about 1000-fold and 10-fold, respectively, and no viable bacteria were present at 24 hours. We constructed several genetic tools with bpsl2179 as a selectable genetic marker, and we used them without any antibiotic selection to construct an in-frame ΔflgK mutant in the alanine racemase deficient variant of B. pseudomallei K96243. In murine peritoneal macrophages, wild type B. mallei ATCC 23344 was killed much more rapidly than wild type B. pseudomallei K96243. In addition, the alanine racemase deficient mutant of B. pseudomallei K96243 exhibited attenuation versus its isogenic parental strain with respect to growth and survival in murine peritoneal macrophages

    Functional outcome after sacrospinous hysteropexy for uterine descensus

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    The study aimed to evaluate urogenital symptoms, defecatory symptoms and quality of life before and after a sacrospinous hysteropexy for uterovaginal prolapse. Seventy-two women with symptomatic uterovaginal prolapse were treated with sacrospinous hysteropexy. Before and after surgery, urogenital and defecatory symptoms and quality of life were assessed with a validated questionnaire. Anatomical outcome was assessed by means of pelvic examination before and after surgery. The mean follow-up time was 12.7 months. Scores on all domains of urogenital symptoms and defecatory symptoms, except for the pain and fecal incontinence domain, improved significantly. Also, quality of life improved on all domains. No major complications were encountered

    A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: A study protocol of a quasi-experimental design

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    <p>Abstract</p> <p>Background</p> <p>Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted.</p> <p>Methods/design</p> <p>A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome), patient perception regarding pain (secondary outcome), together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention.</p> <p>Discussion</p> <p>Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that evidence-based guidelines targeting this patient group's pain will be implemented more widely.</p> <p>Trial Registration Number</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01313234">NCT01313234</a></p

    Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase

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    Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the bla[subscript NDM] gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.Kinship Foundation. Searle Scholars ProgramMassachusetts Institute of Technology. Department of Chemistr

    In Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS

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    Apolipoprotein E (ApoE) is the strongest genetic risk factor for Alzheimer’s disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4) each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer’s disease (AD). Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ) peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS), we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis

    Identification of Hyaloperonospora arabidopsidis Transcript Sequences Expressed during Infection Reveals Isolate-Specific Effectors

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    Biotrophic plant pathogens secrete effector proteins that are important for infection of the host. The aim of this study was to identify effectors of the downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa) that are expressed during infection of its natural host Arabidopsis thaliana. Infection-related transcripts were identified from Expressed Sequence Tags (ESTs) derived from leaves of the susceptible Arabidopsis Ws eds1-1 mutant inoculated with the highly virulent Hpa isolate Waco9. Assembly of 6364 ESTs yielded 3729 unigenes, of which 2164 were Hpa-derived. From the translated Hpa unigenes, 198 predicted secreted proteins were identified. Of these, 75 were found to be Hpa-specific and six isolate Waco9-specific. Among 42 putative effectors identified there were three Elicitin-like proteins, 16 Cysteine-rich proteins and 18 host-translocated RXLR effectors. Sequencing of alleles in different Hpa isolates revealed that five RXLR genes show signatures of diversifying selection. Thus, EST analysis of Hpa-infected Arabidopsis is proving to be a powerful method for identifying pathogen effector candidates expressed during infection. Delivery of the Waco9-specific protein RXLR29 in planta revealed that this effector can suppress PAMP-triggered immunity and enhance disease susceptibility. We propose that differences in host colonization can be conditioned by isolate-specific effectors
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