147 research outputs found

    Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

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    It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

    Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

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    Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

    Neuroanatomical Variability of Religiosity

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    We hypothesized that religiosity, a set of traits variably expressed in the population, is modulated by neuroanatomical variability. We tested this idea by determining whether aspects of religiosity were predicted by variability in regional cortical volume. We performed structural magnetic resonance imaging of the brain in 40 healthy adult participants who reported different degrees and patterns of religiosity on a survey. We identified four Principal Components of religiosity by Factor Analysis of the survey items and associated them with regional cortical volumes measured by voxel-based morphometry. Experiencing an intimate relationship with God and engaging in religious behavior was associated with increased volume of R middle temporal cortex, BA 21. Experiencing fear of God was associated with decreased volume of L precuneus and L orbitofrontal cortex BA 11. A cluster of traits related with pragmatism and doubting God's existence was associated with increased volume of the R precuneus. Variability in religiosity of upbringing was not associated with variability in cortical volume of any region. Therefore, key aspects of religiosity are associated with cortical volume differences. This conclusion complements our prior functional neuroimaging findings in elucidating the proximate causes of religion in the brain

    Atmospheric retrieval of exoplanets

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    Exoplanetary atmospheric retrieval refers to the inference of atmospheric properties of an exoplanet given an observed spectrum. The atmospheric properties include the chemical compositions, temperature profiles, clouds/hazes, and energy circulation. These properties, in turn, can provide key insights into the atmospheric physicochemical processes of exoplanets as well as their formation mechanisms. Major advancements in atmospheric retrieval have been made in the last decade, thanks to a combination of state-of-the-art spectroscopic observations and advanced atmospheric modeling and statistical inference methods. These developments have already resulted in key constraints on the atmospheric H2O abundances, temperature profiles, and other properties for several exoplanets. Upcoming facilities such as the JWST will further advance this area. The present chapter is a pedagogical review of this exciting frontier of exoplanetary science. The principles of atmospheric retrievals of exoplanets are discussed in detail, including parametric models and statistical inference methods, along with a review of key results in the field. Some of the main challenges in retrievals with current observations are discussed along with new directions and the future landscape

    The Anaphase-Promoting Complex or Cyclosome Supports Cell Survival in Response to Endoplasmic Reticulum Stress

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    The anaphase-promoting complex or cyclosome (APC/C) is a multi-subunit ubiquitin ligase that regulates exit from mitosis and G1 phase of the cell cycle. Although the regulation and function of APC/CCdh1 in the unperturbed cell cycle is well studied, little is known of its role in non-genotoxic stress responses. Here, we demonstrate the role of APC/CCdh1 (APC/C activated by Cdh1 protein) in cellular protection from endoplasmic reticulum (ER) stress. Activation of APC/CCdh1 under ER stress conditions is evidenced by Cdh1-dependent degradation of its substrates. Importantly, the activity of APC/CCdh1 maintains the ER stress checkpoint, as depletion of Cdh1 by RNAi impairs cell cycle arrest and accelerates cell death following ER stress. Our findings identify APC/CCdh1 as a regulator of cell cycle checkpoint and cell survival in response to proteotoxic insults

    Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon

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    <p>Abstract</p> <p>Background</p> <p>Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB) on formation of aberrant crypt foci (ACF) in colons of male Fisher F344 rats (inbred strain). However, effects of BB on colon tumors and in both genders are unknown.</p> <p>Methods</p> <p>We examined efficacy of BB in inhibition of azoxymethane (AOM)-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain). Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults.</p> <p>Results</p> <p>Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (<it>P </it>< 0.05) ACF numbers within the distal colon of female but not male rats. There was a significant (<it>P </it>< 0.05) diet by gender interaction with respect to total colon ACF number. Colon and duodenum tumor incidences were less in females than males at 17 weeks after AOM. BB tended (0.1 > <it>P </it>> 0.05) to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (<it>P </it>> 0.1) by BB. There was a tendency (0.1 > <it>P </it>> 0.05) for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas) in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (<it>P </it>< 0.05). BB favored (<it>P </it>< 0.05) fewer adenocarcinomas and more adenomatous polyps (as a proportion of total tumor number) in female rat small intestine.</p> <p>Conclusion</p> <p>Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma) by BB.</p

    Comparison of methods for the identification of microorganisms isolated from blood cultures

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    BACKGROUND: Bloodstream infections are responsible for thousands of deaths each year. The rapid identification of the microorganisms causing these infections permits correct therapeutic management that will improve the prognosis of the patient. In an attempt to reduce the time spent on this step, microorganism identification devices have been developed, including the VITEK(®) 2 system, which is currently used in routine clinical microbiology laboratories. METHODS: This study evaluated the accuracy of the VITEK(®) 2 system in the identification of 400 microorganisms isolated from blood cultures and compared the results to those obtained with conventional phenotypic and genotypic methods. In parallel to the phenotypic identification methods, the DNA of these microorganisms was extracted directly from the blood culture bottles for genotypic identification by the polymerase chain reaction (PCR) and DNA sequencing. RESULTS: The automated VITEK(®) 2 system correctly identified 94.7 % (379/400) of the isolates. The YST and GN cards resulted in 100 % correct identifications of yeasts (15/15) and Gram-negative bacilli (165/165), respectively. The GP card correctly identified 92.6 % (199/215) of Gram-positive cocci, while the ANC card was unable to correctly identify any Gram-positive bacilli (0/5). CONCLUSIONS: The performance of the VITEK(®) 2 system was considered acceptable and statistical analysis showed that the system is a suitable option for routine clinical microbiology laboratories to identify different microorganisms
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