The 10 Meter South Pole Telescope Carlstrom, J. E.; Ade, P. A. R.; Aird, K. A. ...
Publications of the Astronomical Society of the Pacific,
05/2011, Letnik:
123, Številka:
903
Journal Article
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The South Pole Telescope (SPT) is a 10 m diameter, wide-field, offset Gregorian telescope with a 966 pixel, multicolor, millimeter-wave, bolometer camera. It is located at the Amundsen-Scott South ...Pole station in Antarctica. The design of the SPT emphasizes careful control of spillover and scattering, to minimize noise and false signals due to ground pickup. The key initial project is a large-area survey at wavelengths of 3, 2, and 1.3 mm, to detect clusters of galaxies via the Sunyaev-Zel’dovich effect and to measure the small-scale angular power spectrum of the cosmic microwave background (CMB). The data will be used to characterize the primordial matter power spectrum and to place constraints on the equation of state of dark energy. A second-generation camera will measure the polarization of the CMB, potentially leading to constraints on the neutrino mass and the energy scale of inflation.
Race, Ethnicity, and NIH Research Awards Ginther, Donna K.; Schaffer, Walter T.; Schnell, Joshua ...
Science,
08/2011, Letnik:
333, Številka:
6045
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We investigated the association between a U.S. National Institutes of Health (NIH) R01 applicant's self-identified race or ethnicity and the probability of receiving an award by using data from the ...NIH IMPAC II grant database, the Thomson Reuters Web of Science, and other sources. Although proposals with strong priority scores were equally likely to be funded regardless of race, we find that Asians are 4 percentage points and black or African-American applicants are 13 percentage points less likely to receive NIH investigator-initiated research funding compared with whites. After controlling for the applicant's educational background, country of origin, training, previous research awards, publication record, and employer characteristics, we find that black applicants remain 10 percentage points less likely than whites to be awarded NIH research funding. Our results suggest some leverage points for policy intervention.
The RAS family of proto-oncogenes are among the most commonly mutated genes in human cancers and predict poor clinical outcome. Several mechanisms underlying oncogenic RAS transformation are well ...documented, including constitutive signaling through the RAF-MEK-ERK proproliferative pathway as well as the PI3K-AKT prosurvival pathway. Notably, control of redox balance has also been proposed to contribute to RAS transformation. However, how homeostasis between reactive oxygen species (ROS) and antioxidants, which have opposing effects in the cell, ultimately influence RAS-mediated transformation and tumor progression is still a matter of debate and the mechanisms involved have not been fully elucidated. Here, we show that oncogenic KRAS protects fibroblasts from oxidative stress by enhancing intracellular GSH levels. Using a whole transcriptome approach,we discovered that this is attributable to transcriptional up-regulation of xCT, the gene encoding the cystine/glutamate antiporter. This is in line with the function of xCT, which mediates the uptake of cystine, a precursor for GSH biosynthesis. Moreover, our results reveal that the ETS-1 transcription factor downstream of the RAS-RAF-MEK-ERK signaling cascade directly transactivates the xCT promoter in synergy with the ATF4 endoplasmic reticulum stress-associated transcription factor. Strikingly, xCT was found to be essential for oncogenic KRAS-mediated transformation in vitro and in vivo bymitigating oxidative stress, as knockdown of xCT strongly impaired growth of tumor xenografts established from KRAS-transformed cells. Overall, this study uncovers a mechanism by which oncogenic RAS preserves intracellular redox balance and identifies an unexpected role for xCT in supporting RAS-induced transformation and tumorigenicity.
Cerebral blood flow (CBF) reductions in Alzheimer's disease patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences for ...Alzheimer's disease pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to in wild-type animals, largely due to neutrophils that had adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to both an immediate increase in CBF and rapidly improved performance in spatial and working memory tasks. This study identified a previously uncharacterized cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of Alzheimer's disease and demonstrated that improving CBF rapidly enhanced short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a strategy for improving cognition in Alzheimer's disease patients.
Adeno-associated viral vectors are highly safe and efficient gene delivery vehicles. However, numerous challenges in vector design remain, including neutralizing antibody responses, tissue transport ...and infection of resistant cell types. Changes must be made to the viral capsid to overcome these problems; however, very often insufficient information is available for rational design of improvements. We therefore applied a directed evolution approach involving the generation of large mutant capsid libraries and selection of adeno-associated virus (AAV) 2 variants with enhanced properties. High-throughput selection processes were designed to isolate mutants within the library with altered affinities for heparin or the ability to evade antibody neutralization and deliver genes more efficiently than wild-type capsid in the presence of anti-AAV serum. This approach, which can be extended to additional gene delivery challenges and serotypes, directs viral evolution to generate 'designer' gene delivery vectors with specified, enhanced properties.
Operative eligibility thresholds based on body mass index (BMI) alone may risk restricting access to improved pain control, function, and quality of life. This study evaluated the use of BMI-cutoffs ...to offering TKA in avoiding: 1) 90-day readmission, 2) one-year mortality, and 3) failure to achieve clinically important one-year PROMS improvement (MCID).
A total of 4126 primary elective unilateral TKA patients from 2015 to 2018 were prospectively collected. For specific BMI(kg/m2) cutoffs: 30, 35, 40, 45, and 50, the positive predictive value (PPV) for 90-day readmission, one-year mortality, and failure to achieve one-year MCID were calculated. The number of patients denied complication-free postoperative courses per averted adverse outcome/failed improvement was estimated.
Rates of 90-day readmission and one-year mortality were similar across BMI categories (P > .05, each). PPVs for preventing 90-day readmission and one-year mortality were low across all models of BMI cutoffs. The highest PPV for 90-day readmission and one-year mortality was detected at cutoffs of 45 (6.4%) and 40 (0.87%), respectively. BMI cutoff of 40 would deny 18 patients 90-day readmission-free, and 194 patients one-year mortality-free postoperative courses for each averted 90-day readmission/one-year mortality. Such cutoff would also deny 11 patients an MCID per avoided failure. Implementing BMI thresholds alone did not influence the rate of improvements in KOOS-PS, KRQOL, or VR-12.
Utilizing BMI cutoffs as the sole determinants of TKA ineligibility may deny patients complication-free postoperative courses and clinically important improvements. Shared decision-making supported by predictive tools may aid in balancing the potential benefit TKA offers to obese patients with the potentially increased complication risk and cost of care provision.
We report constraints on cosmological parameters from the angular power spectrum of a cosmic microwave background (CMB) gravitational lensing potential map created using temperature data from 2500 ...deg2 of South Pole Telescope (SPT) data supplemented with data from Planck in the same sky region, with the statistical power in the combined map primarily from the SPT data. We fit the lensing power spectrum to a model including cold dark matter and a cosmological constant ( ), and to models with single-parameter extensions to . We find constraints that are comparable to and consistent with those found using the full-sky Planck CMB lensing data, e.g., = 0.598 0.024 from the lensing data alone with weak priors placed on other parameters. Combining with primary CMB data, we explore single-parameter extensions to . We find or < 0.70 eV at 95% confidence, in good agreement with results including the lensing potential as measured by Planck. We include two parameters that scale the effect of lensing on the CMB: , which scales the lensing power spectrum in both the lens reconstruction power and in the smearing of the acoustic peaks, and , which scales only the amplitude of the lensing reconstruction power spectrum. We find × = 1.01 0.08 for the lensing map made from combined SPT and Planck data, indicating that the amount of lensing is in excellent agreement with expectations from the observed CMB angular power spectrum when not including the information from smearing of the acoustic peaks.
As the organ shortage continues to grow, the creation of social media communities by transplant hospitals and the public is rapidly expanding to increase the number of living donors. Social media ...communities are arranged in myriad ways and without standardization, raising concerns about transplant candidates’ and potential donors’ autonomy and quality of care. Social media communities magnify and modify extant ethical issues in deceased and living donation related to privacy, confidentiality, professionalism, and informed consent, and increase the potential for undue influence and coercion for potential donors and transplant candidates. Currently, no national ethical guidelines have been developed in the United States regarding the use of social media to foster organ transplantation. We provide an ethical framework to guide transplant stakeholders in using social media for public and patient communication about transplantation and living donation, and offer recommendations for transplant clinical practice and future research.
In an effort to guide transplant stakeholders in using social media for public and patient communication about transplantation and living donation, this article provides an ethical framework and offers recommendations for transplant clinical practice and future research.
Abstract Alzheimer's disease (AD) is among the most prevalent forms of dementia affecting the aging population, and pharmacological therapies to date have not been successful in preventing disease ...progression. Future therapeutic efforts may benefit from the development of models that enable basic investigation of early disease pathology. In particular, disease-relevant models based on human pluripotent stem cells (hPSCs) may be promising approaches to assess the impact of neurotoxic agents in AD on specific neuronal populations and thereby facilitate the development of novel interventions to avert early disease mechanisms. We implemented an efficient paradigm to convert hPSCs into enriched populations of cortical glutamatergic neurons emerging from dorsal forebrain neural progenitors, aided by modulating Sonic hedgehog (Shh) signaling. Since AD is generally known to be toxic to glutamatergic circuits, we exposed glutamatergic neurons derived from hESCs to an oligomeric pre-fibrillar forms of Aβ known as “globulomers”, which have shown strong correlation with the level of cognitive deficits in AD. Administration of such Aβ oligomers yielded signs of the disease, including cell culture age-dependent binding of Aβ and cell death in the glutamatergic populations. Furthermore, consistent with previous findings in postmortem human AD brain, Aβ-induced toxicity was selective for glutamatergic rather than GABAeric neurons present in our cultures. This in vitro model of cortical glutamatergic neurons thus offers a system for future mechanistic investigation and therapeutic development for AD pathology using human cell types specifically affected by this disease.
To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents.
Individually linked health data in Denmark (2000−2012), Finland (2005–2014), ...Iceland (2004–2017), Norway (2005–2015), Sweden (2006–2015), Germany (2006–2015), Australia (New South Wales, 2004–2012), Hong Kong (2001–2015), UK (2006–2016), and the US (Medicaid, 2000–2013, and IBM MarketScan, 2012–2015) were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated with the use of antipsychotics.
We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries, prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries.
Antipsychotic use during pregnancy varied considerably between populations, partly explained by varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population.
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