1,811 research outputs found

    Molecular and cellular dynamics of the 26S proteasome

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    In eukaryotic cells, the ubiquitin-proteasome system serves to remove proteins that are either dysfunctional or no longer needed. The 26S proteasome is a 2.5 MDa multisubunit complex comprising the 20S core particle, where degradation is executed, and one or two regulatory particles which prepare substrates for degradation. Whereas the 20S core particles of several species had been studied extensively by X-ray crystallography, the 26S holocomplex structure had remained elusive for a long time. Recent advances in single-particle cryo-electron microscopy have changed the situation and provided atomic resolution models of this intriguing molecular machine and its dynamics. Besides, cryo-electron tomography enables structural studies in situ, providing molecular resolution images of macromolecules inside pristinely preserved cellular environments. This has greatly contributed to our understanding of proteasome dynamics in the context of cells

    One-dimensional semirelativity for electrons in carbon nanotubes

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    It is shown that the band structure of single-wall semiconducting carbon nanotubes (CNT) is analogous to relativistic description of electrons in vacuum, with the maximum velocity uu= 10810^8cm/s replacing the light velocity. One-dimensional semirelativistic kinematics and dynamics of electrons in CNT is formulated. Two-band k.p Hamiltonian is employed to demonstrate that electrons in CNT experience a Zitterbewegung (trembling motion) in absence of external fields. This Zitterbewegung should be observable much more easily in CNT than its analogue for free relativistic electrons in vacuum.Comment: 4 pages no figure

    Protective efficacy of malaria case management for preventing malaria mortality in children: a systematic review for the Lives Saved Tool

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    <p>Abstract</p> <p>Background</p> <p>The Lives Saved Tool (LiST) model was developed to estimate the impact of the scale-up of child survival interventions on child mortality. New advances in antimalarials have improved their efficacy of treating uncomplicated and severe malaria. Artemisinin-based combination therapies (ACTs) for uncomplicated <it>Plasmodium falciparum</it> malaria and parenteral or rectal artemisinin or quinine for severe malaria syndromes have been shown to be very effective for the treatment of malaria in children. These interventions are now being considered for inclusion in the LiST model. However, for obvious ethical reasons, their protective efficacy (PE) compared to placebo is unknown and their impact on reducing malaria-attributable mortality has not been quantified.</p> <p>Methods</p> <p>We performed systematic literature reviews of published studies in <it>P. falciparum</it> endemic settings to determine the protective efficacy (PE) of ACT treatment against malaria deaths among children with uncomplicated malaria, as well as the PE of effective case management including parenteral quinine against malaria deaths among all hospitalized children. As no randomized placebo-controlled trials of malaria treatment have been conducted, we used multiple data sources to ascertain estimates of PE, including a previously performed Delphi estimate for treatment of uncomplicated malaria.</p> <p>Results</p> <p>Based on multiple data sources, we estimate the PE of ACT treatment of uncomplicated <it>P. falciparum</it> malaria on reducing malaria mortality in children 1–23 months to be 99% (range: 94-100%), and in children 24-59 months to be 97% (range: 86-99%). We estimate the PE of treatment of severe <it>P. falciparum</it> malaria with effective case management including intravenous quinine on reducing malaria mortality in children 1-59 months to be 82% (range: 63-94%) compared to no treatment.</p> <p>Conclusions</p> <p>This systematic review quantifies the PE of ACT used for treating uncomplicated malaria and effective case management including parenteral quinine for treating severe <it>P. falciparum</it> malaria for preventing malaria mortality in children <5. These data will be used in the Lives Saved Tool (LiST) model for estimating the impact of scaling-up these interventions against malaria. However, in order to estimate the reduction in child mortality due to scale-up of these interventions, it is imperative to develop standardized indicators to measure population coverage of these interventions.</p

    Is the Scale Up of Malaria Intervention Coverage Also Achieving Equity?

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    Malaria in Africa is most severe in young children and pregnant women, particularly in rural and poor households. In many countries, malaria intervention coverage rates have increased as a result of scale up; but this may mask limited coverage in these highest-risk populations. Reports were reviewed from nationally representative surveys in African malaria-endemic countries from 2006 through 2008 to understand how reported intervention coverage rates reflect access by the most at-risk populations.Reports were available from 27 Demographic and Health Surveys (DHSs), Multiple Indicator Cluster Surveys (MICSs), and Malaria Indicator Surveys (MISs) during this interval with data on household intervention coverage by urban or rural setting, wealth quintile, and sex. Household ownership of insecticide-treated mosquito nets (ITNs) varied from 5% to greater than 60%, and was equitable by urban/rural and wealth quintile status among 13 (52%) of 25 countries. Malaria treatment rates for febrile children under five years of age varied from less than 10% to greater than 70%, and while equitable coverage was achieved in 8 (30%) of 27 countries, rates were generally higher in urban and richest quintile households. Use of intermittent preventive treatment in pregnant women varied from 2% to more than 60%, and again tended to be higher in urban and richest quintile households. Across all countries, there were no significant male/female inequalities seen for children sleeping under ITNs or receiving antimalarial treatment for febrile illness. Parasitemia and anemia rates from eight national surveys showed predominance in poor and rural populations.Recent efforts to scale up malaria intervention coverage have achieved equity in some countries (especially with ITNs), but delivery methods in other countries are not addressing the most at-risk populations. As countries seek universal malaria intervention coverage, their delivery systems must reach the rural and poor populations; this is not a small task, but it has been achieved in some countries

    The Utility Of The Pectoralis Myocutaneous Flap In The Management Of Select Cervical Esophageal Anastomotic Complications

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    AbstractObjective: The majority of cervical esophageal anastomotic complications can be successfully managed nonoperatively. A small group of patients may have anastomotic strictures or leakage and fistula formation that are chronic and resistant to nonoperative therapy. The purpose of this study was to review our experience with the use of the pectoralis myocutaneous flap to treat these patients. Methods: Since April 1992, four patients have undergone pectoralis myocutaneous flap repair of cervical esophageal anastomotic complications at our institution. Two patients had chronic strictures, one patient underwent prophylactic repair with a pectoralis myocutaneous flap to prevent stricture formation, and one patient had a chronic anastomotic fistula. The pectoralis myocutaneous flap was harvested in the standard fashion. The technique of anastomotic repair is described. The medical records were retrospectively reviewed to determine patient characteristics and our results. Results: Two suture line leaks developed: one small, contained leak required no intervention, and the other resolved with cervical drainage. Pneumonia, seroma at the site of the pectoralis myocutaneous flap donor, transient hoarseness, and partial skin graft loss occurred in one case each. There were no deaths. Hospital stay ranged from 12 to 22 days. A good functional result was obtained in three patients. Conclusion: Our results show that pectoralis myocutaneous flap repair of select cervical anastomotic complications is safe and well tolerated even in patients with complicated problems. (J Thorac Cardiovasc Surg 1998;115:1250-4

    Genetic Profiling Reveals Cross-Contamination and Misidentification of 6 Adenoid Cystic Carcinoma Cell Lines: ACC2, ACC3, ACCM, ACCNS, ACCS and CAC2

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    Adenoid cystic carcinoma (ACC) is the second most common malignant neoplasm of the salivary glands. Most patients survive more than 5 years after surgery and postoperative radiation therapy. The 10 year survival rate, however, drops to 40%, due to locoregional recurrences and distant metastases. Improving long-term survival in ACC requires the development of more effective systemic therapies based on a better understanding of the biologic behavior of ACC. Much preclinical research in this field involves the use of cultured cells and, to date, several ACC cell lines have been established. Authentication of these cell lines, however, has not been reported. We performed DNA fingerprint analysis on six ACC cell lines using short tandem repeat (STR) examinations and found that all six cell lines had been contaminated with other cells. ACC2, ACC3, and ACCM were determined to be cervical cancer cells (HeLa cells), whereas the ACCS cell line was composed of T24 urinary bladder cancer cells. ACCNS and CAC2 cells were contaminated with cells derived from non-human mammalian species: the cells labeled ACCNS were mouse cells and the CAC2 cells were rat cells. These observations suggest that future studies using ACC cell lines should include cell line authentication to avoid the use of contaminated or non-human cells
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