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Showing papers by "University of Basel published in 2012"


Journal ArticleDOI
TL;DR: In this paper, a set of models for solar metallicity, where the effects of rotation are accounted for in a homogeneous way, is presented, and a grid of 48 different stellar evolutionary tracks, both rotating and non-rotating, at Z ǫ = 0.014, spanning a wide mass range from 0.8 to 120 m ⊙.
Abstract: Aims. Many topical astrophysical research areas, such as the properties of planet host stars, the nature of the progenitors of different types of supernovae and gamma ray bursts, and the evolution of galaxies, require complete and homogeneous sets of stellar models at different metallicities in order to be studied during the whole of cosmic history. We present here a first set of models for solar metallicity, where the effects of rotation are accounted for in a homogeneous way.Methods. We computed a grid of 48 different stellar evolutionary tracks, both rotating and non-rotating, at Z = 0.014, spanning a wide mass range from 0.8 to 120 M ⊙ . For each of the stellar masses considered, electronic tables provide data for 400 stages along the evolutionary track and at each stage, a set of 43 physical data are given. These grids thus provide an extensive and detailed data basis for comparisons with the observations. The rotating models start on the zero-age main sequence (ZAMS) with a rotation rate υ ini /υ crit = 0.4. The evolution is computed until the end of the central carbon-burning phase, the early asymptotic giant branch (AGB) phase, or the core helium-flash for, respectively, the massive, intermediate, and both low and very low mass stars. The initial abundances are those deduced by Asplund and collaborators, which best fit the observed abundances of massive stars in the solar neighbourhood. We update both the opacities and nuclear reaction rates, and introduce new prescriptions for the mass-loss rates as stars approach the Eddington and/or the critical velocity. We account for both atomic diffusion and magnetic braking in our low-mass star models.Results. The present rotating models provide a good description of the average evolution of non-interacting stars. In particular, they reproduce the observed main-sequence width, the positions of the red giant and supergiant stars in the Hertzsprung-Russell (HR) diagram, the observed surface compositions and rotational velocities. Very interestingly, the enhancement of the mass loss during the red-supergiant stage, when the luminosity becomes supra-Eddington in some outer layers, help models above 15−20 M ⊙ to lose a significant part of their hydrogen envelope and evolve back into the blue part of the HR diagram. This result has interesting consequences for the blue to red supergiant ratio, the minimum mass for stars to become Wolf-Rayet stars, and the maximum initial mass of stars that explode as type II−P supernovae.

1,654 citations


Journal ArticleDOI
20 Mar 2012-BMJ
TL;DR: In European hospitals, improvement of hospital work environments might be a relatively low cost strategy to improve safety and quality in hospital care and to increase patient satisfaction.
Abstract: Objective To determine whether hospitals with a good organisation of care (such as improved nurse staffing and work environments) can affect patient care and nurse workforce stability in European countries. Design Cross sectional surveys of patients and nurses. Setting Nurses were surveyed in general acute care hospitals (488 in 12 European countries; 617 in the United States); patients were surveyed in 210 European hospitals and 430 US hospitals. Participants 33 659 nurses and 11 318 patients in Europe; 27 509 nurses and more than 120 000 patients in the US. Main outcome measures Nurse outcomes (hospital staffing, work environments, burnout, dissatisfaction, intention to leave job in the next year, patient safety, quality of care), patient outcomes (satisfaction overall and with nursing care, willingness to recommend hospitals). Results The percentage of nurses reporting poor or fair quality of patient care varied substantially by country (from 11% (Ireland) to 47% (Greece)), as did rates for nurses who gave their hospital a poor or failing safety grade (4% (Switzerland) to 18% (Poland)). We found high rates of nurse burnout (10% (Netherlands) to 78% (Greece)), job dissatisfaction (11% (Netherlands) to 56% (Greece)), and intention to leave (14% (US) to 49% (Finland, Greece)). Patients’ high ratings of their hospitals also varied considerably (35% (Spain) to 61% (Finland, Ireland)), as did rates of patients willing to recommend their hospital (53% (Greece) to 78% (Switzerland)). Improved work environments and reduced ratios of patients to nurses were associated with increased care quality and patient satisfaction. In European hospitals, after adjusting for hospital and nurse characteristics, nurses with better work environments were half as likely to report poor or fair care quality (adjusted odds ratio 0.56, 95% confidence interval 0.51 to 0.61) and give their hospitals poor or failing grades on patient safety (0.50, 0.44 to 0.56). Each additional patient per nurse increased the odds of nurses reporting poor or fair quality care (1.11, 1.07 to 1.15) and poor or failing safety grades (1.10, 1.05 to 1.16). Patients in hospitals with better work environments were more likely to rate their hospital highly (1.16, 1.03 to 1.32) and recommend their hospitals (1.20, 1.05 to 1.37), whereas those with higher ratios of patients to nurses were less likely to rate them highly (0.94, 0.91 to 0.97) or recommend them (0.95, 0.91 to 0.98). Results were similar in the US. Nurses and patients agreed on which hospitals provided good care and could be recommended. Conclusions Deficits in hospital care quality were common in all countries. Improvement of hospital work environments might be a relatively low cost strategy to improve safety and quality in hospital care and to increase patient satisfaction.

1,587 citations


Journal ArticleDOI
TL;DR: In response to the proliferation of ambiguous or unquantifiable terms in the literature on medication adherence, this research has resulted in a new conceptual foundation for a transparent taxonomy, focused on promoting consistency and quantification in terminology and methods.
Abstract: Interest in patient adherence has increased in recent years, with a growing literature that shows the pervasiveness of poor adherence to appropriately prescribed medications. However, four decades of adherence research has not resulted in uniformity in the terminology used to describe deviations from prescribed therapies. The aim of this review was to propose a new taxonomy, in which adherence to medications is conceptualized, based on behavioural and pharmacological science, and which will support quantifiable parameters. A systematic literature review was performed using MEDLINE, EMBASE, CINAHL, the Cochrane Library and PsycINFO from database inception to 1 April 2009. The objective was to identify the different conceptual approaches to adherence research. Definitions were analyzed according to time and methodological perspectives. A taxonomic approach was subsequently derived, evaluated and discussed with international experts. More than 10 different terms describing medication-taking behaviour were identified through the literature review, often with differing meanings. The conceptual foundation for a new, transparent taxonomy relies on three elements, which make a clear distinction between processes that describe actions through established routines (‘Adherence to medications’, ‘Management of adherence’) and the discipline that studies those processes (‘Adherence-related sciences’). ‘Adherence to medications’ is the process by which patients take their medication as prescribed, further divided into three quantifiable phases: ‘Initiation’, ‘Implementation’ and ‘Discontinuation’. In response to the proliferation of ambiguous or unquantifiable terms in the literature on medication adherence, this research has resulted in a new conceptual foundation for a transparent taxonomy. The terms and definitions are focused on promoting consistency and quantification in terminology and methods to aid in the conduct, analysis and interpretation of scientific studies of medication adherence.

1,339 citations


Journal ArticleDOI
TL;DR: All human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination, showing that CD47 is a commonly expressed molecule on all cancers, its function to blockphagocytosis is known, and blockade of its function leads to tumor cell phagcytosis and elimination.
Abstract: CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination CD47 is therefore a validated target for cancer therapies

1,206 citations


Journal ArticleDOI
TL;DR: Proof of principle is provided that microplastics are taken up into cells and cause significant effects on the tissue and cellular level, which can be assessed with standard cytochemical biomarkers and polarized light microscopy for microplastic tracking in tissue.
Abstract: In this study, we investigated if industrial high-density polyethylene (HDPE) particles, a model microplastic free of additives, ranging > 0–80 μm are ingested and taken up into the cells and tissue of the blue mussel Mytilus edulis L. The effects of exposure (up to 96 h) and plastic ingestion were observed at the cellular and subcellular level. Microplastic uptake into the gills and digestive gland was analyzed by a new method using polarized light microscopy. Mussel health status was investigated incorporating histological assessment and cytochemical biomarkers of toxic effects and early warning. In addition to being drawn into the gills, HDPE particles were taken up into the stomach and transported into the digestive gland where they accumulated in the lysosomal system after 3 h of exposure. Our results show notable histological changes upon uptake and a strong inflammatory response demonstrated by the formation of granulocytomas after 6 h and lysosomal membrane destabilization, which significantly inc...

1,109 citations


Journal ArticleDOI
TL;DR: A statistical framework to describe and compare environmental niches from occurrence and spatial environmental data and shows that niche overlap can be accurately detected with the framework when variables driving the distributions are known.
Abstract: Aim Concerns over how global change will influence species distributions, in conjunction with increased emphasis on understanding niche dynamics in evolutionary and community contexts, highlight the growing need for robust methods to quantify niche differences between or within taxa. We propose a statistical framework to describe and compare environmental niches from occurrence and spatial environmental data. Location Europe, North America and South America. Methods The framework applies kernel smoothers to densities of species occurrence in gridded environmental space to calculate metrics of niche overlap and test hypotheses regarding niche conservatism. We use this framework and simulated species with pre-defined distributions and amounts of niche overlap to evaluate several ordination and species distribution modelling techniques for quantifying niche overlap. We illustrate the approach with data on two well-studied invasive species. Results We show that niche overlap can be accurately detected with the framework when variables driving the distributions are known. The method is robust to known and previously undocumented biases related to the dependence of species occurrences on the frequency of environmental conditions that occur across geographical space. The use of a kernel smoother makes the process of moving from geographical space to multivariate environmental space independent of both sampling effort and arbitrary choice of resolution in environmental space. However, the use of ordination and species distribution model techniques for selecting, combining and weighting variables on which niche overlap is calculated provide contrasting results. Main conclusions The framework meets the increasing need for robust methods to quantify niche differences. It is appropriate for studying niche differences between species, subspecies or intra-specific lineages that differ in their geographical distributions. Alternatively, it can be used to measure the degree to which the environmental niche of a species or intra-specific lineage has changed over time.

1,095 citations


Journal ArticleDOI
TL;DR: It is shown that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities.

921 citations


Journal ArticleDOI
TL;DR: Careful selection of monitoring sites, examination of influential observations and skewed variable distributions were essential for developing stable LUR models, which are used to estimate air pollution concentrations at the home addresses of participants in the health studies involved in ESCAPE.
Abstract: Land Use Regression (LUR) models have been used increasingly for modeling small-scale spatial variation in air pollution concentrations and estimating individual exposure for participants of cohort studies. Within the ESCAPE project, concentrations of PM(2.5), PM(2.5) absorbance, PM(10), and PM(coarse) were measured in 20 European study areas at 20 sites per area. GIS-derived predictor variables (e.g., traffic intensity, population, and land-use) were evaluated to model spatial variation of annual average concentrations for each study area. The median model explained variance (R(2)) was 71% for PM(2.5) (range across study areas 35-94%). Model R(2) was higher for PM(2.5) absorbance (median 89%, range 56-97%) and lower for PM(coarse) (median 68%, range 32- 81%). Models included between two and five predictor variables, with various traffic indicators as the most common predictors. Lower R(2) was related to small concentration variability or limited availability of predictor variables, especially traffic intensity. Cross validation R(2) results were on average 8-11% lower than model R(2). Careful selection of monitoring sites, examination of influential observations and skewed variable distributions were essential for developing stable LUR models. The final LUR models are used to estimate air pollution concentrations at the home addresses of participants in the health studies involved in ESCAPE.

861 citations


Journal ArticleDOI
TL;DR: It is shown using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles, and evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells.
Abstract: Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.

855 citations


Journal ArticleDOI
17 May 2012-BMJ
TL;DR: Dietary interventions based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes and the overall evidence rating was low to very low for important outcomes such as pre-eclampsia, Gestational diabetes, gestational hypertension, and preterm delivery.
Abstract: Objective To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. Design Systematic review and meta-analysis. Data sources Major databases from inception to January 2012 without language restrictions. Study selection Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. Data synthesis Results summarised as relative risks for dichotomous data and mean differences for continuous data. Results We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference −50 g, −100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference −60 g, −120 to −10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. Conclusions Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.

750 citations


Journal ArticleDOI
16 Mar 2012-Science
TL;DR: It is shown that when analog climates are compared between regions, fewer than 15% of species have more than 10% of their invaded distribution outside their native climatic niche, revealing that substantial niche shifts are rare in terrestrial plant invaders.
Abstract: The assumption that climatic niche requirements of invasive species are conserved between their native and invaded ranges is key to predicting the risk of invasion. However, this assumption has been challenged recently by evidence of niche shifts in some species. Here, we report the first large-scale test of niche conservatism for 50 terrestrial plant invaders between Eurasia, North America, and Australia. We show that when analog climates are compared between regions, fewer than 15% of species have more than 10% of their invaded distribution outside their native climatic niche. These findings reveal that substantial niche shifts are rare in terrestrial plant invaders, providing support for an appropriate use of ecological niche models for the prediction of both biological invasions and responses to climate change.

Journal ArticleDOI
TL;DR: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage.
Abstract: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).

Journal ArticleDOI
TL;DR: In conclusion, straight sprinting is the most frequent action in goal situations within decisive situations in professional football and should be included in fitness testing and training.
Abstract: The present study aimed to analyse the influence of speed and power abilities in goal situations in professional football. During the second half of the season 2007/08, videos of 360 goals in the first German national league were analysed by visual inspection. For the assisting and the scoring player the situations immediately preceding the goal were evaluated. The observed actions were categorised as: no powerful action, rotation (around the body's centre-line), straight sprint, change-in-direction sprint, jump, or a combination of those categories. Two hundred and ninety-eight (83%) goals were preceded by at least one powerful action of the scoring or the assisting player. Most actions for the scoring player were straight sprints (n = 161, 45% of all analysed goals, P < 0.001) followed by jumps (n = 57, 16%), rotations and change-in-direction sprints (n = 22, 6% each). Most sprints were conducted without an opponent (n = 109, P < 0.001) and without the ball (n = 121, P < 0.001). Similarly, for ...

Journal ArticleDOI
TL;DR: A brief cognitive assessment for multiple sclerosis that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use is recommended.
Abstract: Background: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and spe...

Journal ArticleDOI
26 Oct 2012-Science
TL;DR: A bifunctional artificial metalloenzyme is created in which a glutamic acid or aspartic acid residue engineered into streptavidin acts in concert with a docked biotinylated rhodium(III) complex to enable catalytic asymmetric carbon-hydrogen (C–H) activation.
Abstract: Enzymes provide an exquisitely tailored chiral environment to foster high catalytic activities and selectivities, but their native structures are optimized for very specific biochemical transformations. Designing a protein to accommodate a non-native transition metal complex can broaden the scope of enzymatic transformations while raising the activity and selectivity of small-molecule catalysis. Here, we report the creation of a bifunctional artificial metalloenzyme in which a glutamic acid or aspartic acid residue engineered into streptavidin acts in concert with a docked biotinylated rhodium(III) complex to enable catalytic asymmetric carbon-hydrogen (C–H) activation. The coupling of benzamides and alkenes to access dihydroisoquinolones proceeds with up to nearly a 100-fold rate acceleration compared with the activity of the isolated rhodium complex and enantiomeric ratios as high as 93:7.

Journal ArticleDOI
TL;DR: The HR state for psychosis is associated with significant and widespread impairments in neurocognitive functioning and social cognition, and subsequent transition to psychosis is particularly associated with deficits in verbal fluency and memory functioning.
Abstract: Context A substantial proportion of people at clinical high risk (HR) of psychosis will develop a psychotic disorder over time. Cognitive deficits may predate the onset of psychosis and may be useful as markers of increased vulnerability to illness. Objective To quantitatively examine the cognitive functioning in subjects at HR in the literature to date. Data Sources Electronic databases were searched until January 2011. All studies reporting cognitive performance in HR subjects were retrieved. Study Selection Nineteen studies met the inclusion criteria, comprising a total of 1188 HR subjects and 1029 controls. Data Extraction Neurocognitive functioning and social cognition as well as demographic, clinical, and methodological variables were extracted from each publication or obtained directly from its authors. Data Synthesis Subjects at HR were impaired relative to controls on tests of general intelligence, executive function, verbal and visual memory, verbal fluency, attention and working memory, and social cognition. Processing speed domain was also affected, although the difference was not statistically significant. Later transition to psychosis was associated with even more marked deficits in the verbal fluency and memory domains. The studies included reported relatively homogeneous findings. There was no publication bias and a sensitivity analysis confirmed the robustness of the core results. Conclusions The HR state for psychosis is associated with significant and widespread impairments in neurocognitive functioning and social cognition. Subsequent transition to psychosis is particularly associated with deficits in verbal fluency and memory functioning.

Journal ArticleDOI
TL;DR: In this paper, the relative impact of brand communication on brand equity through social media as compared to traditional media was investigated in a juxtaposition of different industries, investigating whether both communication instruments have an impact on consumer-based brand equity; comparing the effect sizes of these two communication instruments; and separating the effects of firm created and user-generated social media communication.
Abstract: Purpose – The purpose of this paper is to investigate the relative impact of brand communication on brand equity through social media as compared to traditional media. In a juxtaposition of different industries it aims at: investigating whether both communication instruments have an impact on consumer‐based brand equity; comparing the effect sizes of these two communication instruments; and separating the effects of firm‐created and user‐generated social media communication.Design/methodology/approach – A total of 393 data sets from three different industries, namely tourism, telecommunications, and pharmaceuticals, were generated using a standardized online‐survey. Structural equation modeling was used in the analysis of the data obtained to investigate the interplay of social media and traditional media in general, as well as in an examination of industry‐specific differences.Findings – The results of the empirical study show that both traditional communications and social media communications have a si...

Journal ArticleDOI
TL;DR: It is demonstrated that glutamine in combination with leucine activates mammalian TORC1 (mTORC1) by enhancing glutaminolysis and α-ketoglutarate production and this may provide an explanation for glutamine addiction in cancer cells.

Journal ArticleDOI
TL;DR: The results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self- esteem are not mere epiphenomena of success and failure in important life domains.
Abstract: We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants—children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains.

Journal ArticleDOI
13 Jan 2012-Science
TL;DR: It is shown that antiferromagnetic nanostructures, composed of just a few Fe atoms on a surface, exhibit two magnetic states, the Néel states, that are stable for hours at low temperature.
Abstract: Control of magnetism on the atomic scale is becoming essential as data storage devices are miniaturized. We show that antiferromagnetic nanostructures, composed of just a few Fe atoms on a surface, exhibit two magnetic states, the Neel states, that are stable for hours at low temperature. For the smallest structures, we observed transitions between Neel states due to quantum tunneling of magnetization. We sensed the magnetic states of the designed structures using spin-polarized tunneling and switched between them electrically with nanosecond speed. Tailoring the properties of neighboring antiferromagnetic nanostructures enables a low-temperature demonstration of dense nonvolatile storage of information.

Journal ArticleDOI
31 Aug 2012-Cell
TL;DR: Analysis of histone methyltransferases showed that elimination of two HMTs, MET-2 and SET-25, mimics the loss of SAM synthetase, abrogating the perinuclear attachment of heterochromatic transgenes and of native chromosomal arms rich in histone H3 lysine 9 methylation.

Journal ArticleDOI
TL;DR: Standards for performance of the basic clinical mfERG test with a stimulus array of 61 or 103 hexagons, as well as for reporting the results, are specified.
Abstract: The multifocal electroretinogram (mfERG) is an electrophysiological test that allows the function of multiple discrete areas of the retina to be tested simultaneously. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV standard for clinical mfERG and defines minimum protocols for basic clinical mfERG recording and reporting so that responses can be recognized and compared from different laboratories worldwide. The major changes compared with the previous mfERG standard relate to the minimum length of m-sequences used for recording, reporting of results and a change in document format, to be more consistent with other ISCEV standards.

Journal ArticleDOI
26 Oct 2012-Cell
TL;DR: This rich resource provides the first comprehensive reference for all RNA and most protein concentrations in a eukaryote under two key physiological conditions: cellular proliferation and quiescence.

Journal ArticleDOI
TL;DR: This is the first comprehensive estimation of how economic resources are lost to headache in Europe, and it is hoped that this will help clarify the financial costs of headaches in Europe.
Abstract: Background and purpose: Headache disorders are very common, but their monetary costs in Europe are unknown. We performed the first comprehensive estimation of how economic resources are lost to headache in Europe. Methods: From November 2008 to August 2009, a cross-sectional survey was conducted in eight countries representing 55% of the adult EU population. Participation rates varied between 11% and 59%. In total, 8412 questionnaires contributed to this analysis. Using bottom-up methodology, we estimated direct (medications, outpatient health care, hospitalization and investigations) and indirect (work absenteeism and reduced productivity at work) annual per-person costs. Prevalence data, simultaneously collected and, for migraine, also derived from a systematic review, were used to impute national costs. Results: Mean per-person annual costs were €1222 for migraine (95% CI 1055–1389; indirect costs 93%), €303 for tension-type headache (TTH, 95% CI 230–376; indirect costs 92%), €3561 for medication-overuse headache (MOH, 95% CI 2487–4635; indirect costs 92%), and €253 for other headaches (95% CI 99–407; indirect costs 82%). In the EU, the total annual cost of headache amongst adults aged 18–65 years was calculated, according to our prevalence estimates, at €173 billion, apportioned to migraine (€111 billion; 64%), TTH (€21 billion; 12%), MOH (€37 billion; 21%) and other headaches (€3 billion; 2%). Using the 15% systematic review prevalence of migraine, calculated costs were somewhat lower (migraine €50 billion, all headache €112 billion annually). Conclusions: Headache disorders are prominent health-related drivers of immense economic losses for the EU. This has immediate implications for healthcare policy. Health care for headache can be both improved and cost saving.

Journal ArticleDOI
TL;DR: A systematic review and meta-analysis finds that sanitation is associated with a reduced risk of transmission of helminthiases to humans.
Abstract: Background In countries of high endemicity of the soil-transmitted helminth parasites Ascaris lumbricoides, Trichuris trichiura, and hookworm, preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations) is the main strategy to control morbidity. However, rapid reinfection of humans occurs after successful deworming, and therefore effective preventive measures are required to achieve public health goals with optimal efficiency and sustainability.

Journal ArticleDOI
TL;DR: In this paper, the authors examined magnetorotationally driven supernovae as sources of r-process elements in the early Galaxy and found that the peak distribution of Ye in the ejecta is shifted from 0.15 to 0.17 and broadened toward higher Ye due to neutrino absorption.
Abstract: We examine magnetorotationally driven supernovae as sources of r-process elements in the early Galaxy. On the basis of thermodynamic histories of tracer particles from a three-dimensional magnetohydrodynamical core-collapse supernova model with approximated neutrino transport, we perform nucleosynthesis calculations with and without considering the effects of neutrino absorption reactions on the electron fraction (Ye ) during post-processing. We find that the peak distribution of Ye in the ejecta is shifted from ~0.15 to ~0.17 and broadened toward higher Ye due to neutrino absorption. Nevertheless, in both cases, the second and third peaks of the solar r-process element distribution can be reproduced well. The rare progenitor configuration that was used here, characterized by a high rotation rate and a large magnetic field necessary for the formation of bipolar jets, could naturally provide a site for the strong r-process in agreement with observations of the early Galactic chemical evolution.

Journal ArticleDOI
TL;DR: Mammalian target of rapamycin complex 2 regulates hepatic glucose and lipid metabolism via insulin-induced Akt signaling to control whole-body metabolic homeostasis and has implications for emerging drug therapies that target mTORC2.

Journal ArticleDOI
TL;DR: In this paper, a plethora of genes have been identified that are critical for epithelial-mesenchymal transition (EMT) and metastasis formation, which not only induces increased cancer cell motility and invasiveness but also allows cancer cells to avoid apoptosis, anoikis, oncogene addiction, cellular, senescence and general immune defense.

Journal ArticleDOI
TL;DR: These findings support a role for compensatory evolution in the global epidemics of MDR TB and show that M. tuberculosis strains harboring these compensatory mutations showed a high competitive fitness in vitro and were associated with high fitness in vivo.
Abstract: Epidemics of drug-resistant bacteria emerge worldwide, even as resistant strains frequently have reduced fitness compared to their drug-susceptible counterparts. Data from model systems suggest that the fitness cost of antimicrobial resistance can be reduced by compensatory mutations; however, there is limited evidence that compensatory evolution has any significant role in the success of drug-resistant bacteria in human populations. Here we describe a set of compensatory mutations in the RNA polymerase genes of rifampicin-resistant M. tuberculosis, the etiologic agent of human tuberculosis (TB). M. tuberculosis strains harboring these compensatory mutations showed a high competitive fitness in vitro. Moreover, these mutations were associated with high fitness in vivo, as determined by examining their relative clinical frequency across patient populations. Of note, in countries with the world's highest incidence of multidrug-resistant (MDR) TB, more than 30% of MDR clinical isolates had this form of mutation. Our findings support a role for compensatory evolution in the global epidemics of MDR TB.

Journal ArticleDOI
TL;DR: DeGradFP as discussed by the authors is a genetically encoded method for direct and fast depletion of target green fluorescent protein (GFP) fusions in any eukaryotic genetic system, which relies on an evolutionarily highly conserved EKaryotic function, the ubiquitin pathway.
Abstract: The use of genetic mutations to study protein functions in vivo is a central paradigm of modern biology. Recent advances in reverse genetics such as RNA interference and morpholinos are widely used to further apply this paradigm. Nevertheless, such systems act upstream of the proteic level, and protein depletion depends on the turnover rate of the existing target proteins. Here we present deGradFP, a genetically encoded method for direct and fast depletion of target green fluorescent protein (GFP) fusions in any eukaryotic genetic system. This method is universal because it relies on an evolutionarily highly conserved eukaryotic function, the ubiquitin pathway. It is traceable, because the GFP tag can be used to monitor the protein knockout. In many cases, it is a ready-to-use solution, as GFP protein-trap stock collections are being generated in Drosophila melanogaster and in Danio rerio.