5,877 research outputs found
Androgen-regulated processing of the oncomir MiR-27a, which targets Prohibitin in prostate cancer
Publication and patent analysis of European researchers in the field of production technology and manufacturing systems
This paper develops a structured comparison among a sample of European researchers in the field of Production Technology and Manufacturing Systems, on the basis of scientific publications and patents. Researchers are evaluated and compared by a variegated set of indicators concerning (1) the output of individual researchers and (2) that of groups of researchers from the same country. While not claiming to be exhaustive, the results of this preliminary study provide a rough indication of the publishing and patenting activity of researchers in the field of interest, identifying (dis)similarities between different countries. Of particular interest is a proposal for aggregating analysis results by means of maps based on publication and patent indicators. A large amount of empirical data are presented and discusse
Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density
Rationale:
In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI).
Objective:
To characterize RyR functional properties in relation to TT proximity, at baseline and after MI.
Methods:
Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category.
Results:
In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI.
Conclusion:
TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves
Negative discriminant states in N=4 supersymmetric string theories
Single centered BPS black hole solutions exist only when the charge carried
by the black hole has positive discriminant. On the other hand the exact dyon
spectrum in heterotic string theory compactified on T^6 is known to contain
states with negative discriminant. We show that all of these negative
discriminant states can be accounted for as two centered black holes. Thus
after the contribution to the index from the two centered black holes is
subtracted from the total microscopic index, the index for states with negative
discriminant vanishes even for finite values of charges, in agreement with the
results from the black hole side. Bound state metamorphosis -- which requires
us to identify certain apparently different two centered configurations
according to a specific set of rules -- plays a crucial role in this analysis.
We also generalize these results to a class of CHL string theories.Comment: LaTeX file, 32 pages; v2: reference added; v3: added new section 3.
Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys
Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland.
Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data.
Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy.
Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy
The extraordinary evolutionary history of the reticuloendotheliosis viruses
The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events
Logarithmic Corrections to Extremal Black Hole Entropy from Quantum Entropy Function
We evaluate the one loop determinant of matter multiplet fields of N=4
supergravity in the near horizon geometry of quarter BPS black holes, and use
it to calculate logarithmic corrections to the entropy of these black holes
using the quantum entropy function formalism. We show that even though
individual fields give non-vanishing logarithmic contribution to the entropy,
the net contribution from all the fields in the matter multiplet vanishes. Thus
logarithmic corrections to the entropy of quarter BPS black holes, if present,
must be independent of the number of matter multiplet fields in the theory.
This is consistent with the microscopic results. During our analysis we also
determine the complete spectrum of small fluctuations of matter multiplet
fields in the near horizon geometry.Comment: LaTeX file, 52 pages; v2: minor corrections, references adde
Emergency and critical care services in Tanzania: a survey of ten hospitals.
While there is a need for good quality care for patients with serious reversible disease in all countries in the world, Emergency and Critical Care tends to be one of the weakest parts of health systems in low-income countries. We assessed the structure and availability of resources for Emergency and Critical Care in Tanzania in order to identify the priorities for improving care in this neglected specialty. Ten hospitals in four regions of Tanzania were assessed using a structured data collection tool. Quality was evaluated with standards developed from the literature and expert opinion. Important deficits were identified in infrastructure, routines and training. Only 30% of the hospitals had an emergency room for adult and paediatric patients. None of the seven district and regional hospitals had a triage area or intensive care unit for adults. Only 40% of the hospitals had formal systems for adult triage and in less than one third were critically ill patients seen by clinicians more than once daily. In 80% of the hospitals there were no staff trained in adult triage or critical care. In contrast, a majority of equipment and drugs necessary for emergency and critical care were available in the hospitals (median 90% and 100% respectively. The referral/private hospitals tended to have a greater overall availability of resources (median 89.7%) than district/regional hospitals (median 70.6). Many of the structures necessary for Emergency and Critical Care are lacking in hospitals in Tanzania. Particular weaknesses are infrastructure, routines and training, whereas the availability of drugs and equipment is generally good. Policies to improve hospital systems for the care of emergency and critically ill patients should be prioritised
Spin-orbit density wave induced hidden topological order in URu2Si2
The conventional order parameters in quantum matters are often characterized
by 'spontaneous' broken symmetries. However, sometimes the broken symmetries
may blend with the invariant symmetries to lead to mysterious emergent phases.
The heavy fermion metal URu2Si2 is one such example, where the order parameter
responsible for a second-order phase transition at Th = 17.5 K has remained a
long-standing mystery. Here we propose via ab-initio calculation and effective
model that a novel spin-orbit density wave in the f-states is responsible for
the hidden-order phase in URu2Si2. The staggered spin-orbit order 'spontaneous'
breaks rotational, and translational symmetries while time-reversal symmetry
remains intact. Thus it is immune to pressure, but can be destroyed by magnetic
field even at T = 0 K, that means at a quantum critical point. We compute
topological index of the order parameter to show that the hidden order is
topologically invariant. Finally, some verifiable predictions are presented.Comment: (v2) Substantially modified from v1, more calculation and comparison
with experiments are include
Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity
MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors
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