259 research outputs found

    Efficient Mixing at low Reynolds numbers using polymer additives

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    Mixing in fluids is a rapidly developing field of fluid mechanics \cite{Sreen,Shr,War}, being an important industrial and environmental problem. The mixing of liquids at low Reynolds numbers is usually quite weak in simple flows, and it requires special devices to be efficient. Recently, the problem of mixing was solved analytically for a simple case of random flow, known as the Batchelor regime \cite{Bat,Kraich,Fal,Sig,Fouxon}. Here we demonstrate experimentally that very viscous liquids at low Reynolds number, ReRe. Here we show that very viscous liquids containing a small amount of high molecular weight polymers can be mixed quite efficiently at very low Reynolds numbers, for a simple flow in a curved channel. A polymer concentration of only 0.001% suffices. The presence of the polymers leads to an elastic instability \cite{LMS} and to irregular flow \cite{Ours}, with velocity spectra corresponding to the Batchelor regime \cite{Bat,Kraich,Fal,Sig,Fouxon}. Our detailed observations of the mixing in this regime enable us to confirm sevearl important theoretical predictions: the probability distributions of the concentration exhibit exponential tails \cite{Fal,Fouxon}, moments of the distribution decay exponentially along the flow \cite{Fouxon}, and the spatial correlation function of concentration decays logarithmically.Comment: 11 pages, 5 figure

    HOIL-1L Interacting Protein (HOIP) as an NF-κB Regulating Component of the CD40 Signaling Complex

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    The tumor necrosis factor receptor (TNFR) superfamily mediates signals critical for regulation of the immune system. One family member, CD40, is important for the efficient activation of antibody-producing B cells and other antigen-presenting cells. The molecules and mechanisms that mediate CD40 signaling are only partially characterized. Proteins known to interact with the cytoplasmic domain of CD40 include members of the TNF receptor-associated factor (TRAF) family, which regulate signaling and serve as links to other signaling molecules. To identify additional proteins important for CD40 signaling, we used a combined stimulation/immunoprecipitation procedure to isolate CD40 signaling complexes from B cells and characterized the associated proteins by mass spectrometry. In addition to known CD40-interacting proteins, we detected SMAC/DIABLO, HTRA2/Omi, and HOIP/RNF31/PAUL/ZIBRA. We found that these previously unknown CD40-interacting partners were recruited in a TRAF2-dependent manner. HOIP is a ubiquitin ligase capable of mediating NF-κB activation through the ubiquitin-dependent activation of IKKγ. We found that a mutant HOIP molecule engineered to lack ubiquitin ligase activity inhibited the CD40-mediated activation of NF-κB. Together, our results demonstrate a powerful approach for the identification of signaling molecules associated with cell surface receptors and indicate an important role for the ubiquitin ligase activity of HOIP in proximal CD40 signaling

    Patient Reported Outcomes in Sickle Cell Disease Examined Within a Conceptual Model

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    Objective: To examine the relations between patient reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 – 45 years enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD related factors and barriers to care would independently contribute to functioning as measured using the PRO domains. Additionally, pain and other SCD related complications are expected to impact the relation between the variables. Methods: Participants completed a 48-item survey that included socio-demographics and PRO measures, such as social functioning, pain impact emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency, timing and severity, and barriers to medical care. Healthcare utilization was obtained from medical records abstractions. Results: Higher pain frequency and severity and history of treatment for depression were associated with higher odds of worse outcomes in almost all PRO domains, controlling for age and gender for the 2,054 participants. Such social determinants of health as lower household income and unemployment, particularly due to disability status, were associated with higher odds of worse outcomes. Reports of fewer individual barriers to care were associated with better outcomes in emotion, social, cognitive and fatigue domains, while reports of fewer self-reported SCD complications/treatments were associated with better outcomes in emotion and sleep impact domains. Conclusions: Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes. @font-face {font-family: Cambria Math ; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face {font-family:Times; panose-1:2 0 5 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:-536870145 1342185562 0 0 415 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent: ; margin:0in; mso-pagination:widow-orphan; font-size:12.0pt; font-family: Times New Roman ,serif; mso-fareast-font-family: Times New Roman ;}.MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-family: Calibri ,sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Calibri; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family: Times New Roman ; mso-bidi-theme-font:minor-bidi;}div.WordSection1 {page:WordSection1;

    Accepting splicing systems with permitting and forbidding words

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    Abstract: In this paper we propose a generalization of the accepting splicingsystems introduced in Mitrana et al. (Theor Comput Sci 411:2414?2422,2010). More precisely, the input word is accepted as soon as a permittingword is obtained provided that no forbidding word has been obtained sofar, otherwise it is rejected. Note that in the new variant of acceptingsplicing system the input word is rejected if either no permitting word isever generated (like in Mitrana et al. in Theor Comput Sci 411:2414?2422,2010) or a forbidding word has been generated and no permitting wordhad been generated before. We investigate the computational power ofthe new variants of accepting splicing systems and the interrelationshipsamong them. We show that the new condition strictly increases thecomputational power of accepting splicing systems. Although there areregular languages that cannot be accepted by any of the splicing systemsconsidered here, the new variants can accept non-regular and even non-context-free languages, a situation that is not very common in the case of(extended) finite splicing systems without additional restrictions. We alsoshow that the smallest class of languages out of the four classes definedby accepting splicing systems is strictly included in the class of context-free languages. Solutions to a few decidability problems are immediatelyderived from the proof of this result

    Comparative Effectiveness of Guidelines for the Management of Hyperlipidemia and Hypertension for Type 2 Diabetes Patients

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    Background: Several guidelines to reduce cardiovascular risk in diabetes patients exist in North America, Europe, and Australia. Their ability to achieve this goal efficiently is unclear. Methods and Findings: Decision analysis was used to compare the efficiency and effectiveness of international contemporary guidelines for the management of hypertension and hyperlipidemia for patients aged 40-80 with type 2 diabetes. Measures of comparative effectiveness included the expected probability of a coronary or stroke event, incremental medication costs per event, and number-needed-to-treat (NNT) to prevent an event. All guidelines are equally effective, but they differ significantly in their medication costs. The range of NNT to prevent an event was small across guidelines (6.5-7.6 for males and 6.5-7.5 for females); a larger range of differences were observed for expected cost per event avoided (ranges, 117,269117,269-157,186 for males and 115,999115,999-163,775 for females). Australian and U.S. guidelines result in the highest and lowest expected costs, respectively. Conclusions: International guidelines based on the same evidence and seeking the same goal are similar in their effectiveness; however, there are large differences in expected medication costs. © 2011 Shah et al

    Correlation of Serotype-Specific Dengue Virus Infection with Clinical Manifestations

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    Dengue virus (DENV) causes disease in millions of people annually and disproportionately affects those in the developing world. DENVs may be divided into four serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) and a geographical region may be affected by one or more DENV serotypes simultaneously. Infection with DENV may cause life-threatening disease such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), but more often causes less severe manifestations affecting a wide range of organs. Although many previous reports have explored the role of the different DENV serotypes in the development of severe manifestations, little attention has focused on the relative role of each DENV serotype in the development of cutaneous, respiratory, gastrointestinal, musculoskeletal, and neurological manifestations. We recruited a large group of participants from four countries in South America to compare the prevalence of more than 30 manifestations among the four different DENV serotypes. We found that certain DENV serotypes were often associated with a higher prevalence of a certain manifestation (e.g., DENV-3 and diarrhea) or manifestation group (e.g., DENV-4 and cutaneous manifestations)

    When Incentives Work too well: Locally Implemented Pay for Performance (P4P) and Adverse Sanctions towards Home Birth in Tanzania - A Qualitative Study.

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    Despite limited evidence of its effectiveness, performance-based payments (P4P) are seen by leading policymakers as a potential solution to the slow progress in reaching Millennium Development Goal 5: improved maternal health. This paper offers insights into two of the aspects that are lacking in the current literature on P4P, namely what strategies health workers employ to reach set targets, and how the intervention plays out when implemented by local government as part of a national programme that does not receive donor funding. A total of 28 in-depth interviews (IDIs) with 25 individuals were conducted in Mvomero district over a period of 15 months in 2010 and 2011, both before and after P4P payments. Seven facilities, including six dispensaries and one health centre, were covered. Informants included 17 nurses, three clinical officers, two medical attendants, one lab technician and two district health administrators. Health workers reported a number of strategies to increase the number of deliveries at their facility, including health education and cooperation with traditional health providers. The staff at all facilities also reported that they had told the women that they would be sanctioned if they gave birth at home, such as being fined or denied clinical cards and/or vaccinations for their babies. There is a great uncertainty in relation to the potential health impacts of the behavioural changes that have come with P4P, as the reported strategies may increase the numbers, but not necessarily the quality. Contrary to the design of the P4P programme, payments were not based on performance. We argue that this was due in part to a lack of resources within the District Administration, and in part as a result of egalitarian fairness principles. Our results suggest that particular attention should be paid to adverse effects when using external rewards for improved health outcomes, and secondly, that P4P may take on a different form when implemented by local implementers without the assistance of professional P4P specialists

    Autocrine Regulation of Pulmonary Inflammation by Effector T-Cell Derived IL-10 during Infection with Respiratory Syncytial Virus

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    Respiratory syncytial virus (RSV) infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection
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