Now showing items 5884-5903 of 7851

• #### Rab14 specifies the apical membrane through Arf6-mediated regulation of lipid domains and Cdc42

The generation of cell polarity is essential for the development of multi-cellular organisms as well as for the function of epithelial organs in the mature animal. Small GTPases regulate the establishment and maintenance of polarity through effects on cytoskeleton, membrane trafficking, and signaling. Using short-term 3-dimensional culture of MDCK cells, we find that the small GTPase Rab14 is required for apical membrane specification. Rab14 knockdown results in disruption of polarized lipid domains and failure of the Par/aPKC/Cdc42 polarity complex to localize to the apical membrane. These effects are mediated through tight control of lipid localization, as overexpression of the phosphatidylinositol 4-phosphate 5-kinase a [PtdIns(4) P5K] activator Arf6 or PtdIns(4) P5K alone, or treatment with the phosphatidylinositol 3-kinase (PtdInsI3K) inhibitor wortmannin, rescued the multiple-apical domain phenotype observed after Rab14 knockdown. Rab14 also co-immunoprecipitates and colocalizes with the small GTPase Cdc42, and Rab14 knockdown results in increased Cdc42 activity. Furthermore, Rab14 regulates trafficking of vesicles to the apical domain, mitotic spindle orientation, and midbody position, consistent with Rab14' s reported localization to the midbody as well as its effects upon Cdc42. These results position Rab14 at the top of a molecular cascade that regulates the establishment of cell polarity.
• #### Race and BMI modify associations of calcium and vitamin D intake with prostate cancer

Background: African Americans have disproportionately higher burden of prostate cancer compared to European Americans. However, the cause of prostate cancer disparities is still unclear. Several roles have been proposed for calcium and vitamin D in prostate cancer pathogenesis and progression, but epidemiologic studies have been conducted mainly in European descent populations. Here we investigated the association of calcium and vitamin D intake with prostate cancer in multiethnic samples. Methods: A total of 1,657 prostate cancer patients who underwent screening and healthy controls (888 African Americans, 620 European Americans, 111 Hispanic Americans, and 38 others) from Chicago, IL and Washington, D.C. were included in this study. Calcium and vitamin D intake were evaluated using food frequency questionnaire. We performed unconditional logistic regression analyses adjusting for relevant variables. Results: In the pooled data set, high calcium intake was significantly associated with higher odds for aggressive prostate cancer (ORQuartile (1 vs. Quartile) (4) = 1.98, 95% C.I.: 1.01-3.91), while high vitamin D intake was associated with lower odds of aggressive prostate cancer (ORQuartile 1 vs. Quartile (4) = 0.38, 95% C.I.: 0.18-0.79). In African Americans, the association between high calcium intake and aggressive prostate cancer was statistically significant (ORQuartile 1 vs. Quartile 4 = 4.28, 95% C.I.: 1.70-10.80). We also observed a strong inverse association between total vitamin D intake and prostate cancer in African Americans (ORQuartile 1 vs. Quartile 4 = 0.06, 95% C.I.: 0.02-0.54). In European Americas, we did not observe any significant associations between either calcium or vitamin D intake and prostate cancer. In analyses stratifying participants based on Body Mass Index (BMI), we observed a strong positive association between calcium and aggressive prostate cancer and a strong inverse association between vitamin D intake and aggressive prostate cancer among men with low BMI (<27.8 kg/m(2)), but not among men with high BMI (>= 27.8 kg/m(2)). Interactions of race and BMI with vitamin D intake were significant (P-Interaction < 0.05). Conclusion: Calcium intake was positively associated with aggressive prostate cancer, while vitamin D intake exhibited an inverse relationship. However, these associations varied by race/ethnicity and BMI. The findings from this study may help develop better prostate cancer prevention and management strategies.
• #### Race and Class: A Randomized Experiment with Prosecutors

Disparities in criminal justice outcomes are well known, and prior observational research has shown correlations between the race of defendants and prosecutors' decisions about how to charge and resolve cases. Yet causation is questionable: other factors, including unobserved variation in case facts, may account for some of the disparity. Disparities may also be driven by socioeconomic class differences, which are highly correlated with race. This article presents the first blinded, randomized controlled experiment that tests for race and class effects in prosecutors' charging decisions. Case vignettes are manipulated between subjects in five conditions to test effcts of defendants' race and class status. In the control condition, race and class are omitted, which allows baseline measures for bias and pilot testing of a blinding reform. Primary outcome variables included whether the prosecutor charged a felony, whether the prosecutor would pursue a fine or imprisonment, and the amounts thereof. With 467 actual prosecutors participating nationwide, we found that race and class did not have detectable prejudicial effects on prosecutorial decisions. This finding, contrary to the majority of observational studies, suggests that other causes drive known disparities in criminal justice outcomes.
• #### Racial and Ethnic Disparities in Renal Cell Carcinoma: An Analysis of Clinical Characteristics

Racial/ethnic minority groups, including Hispanic Americans (HAs) and Native Americans (NAs), have a heavier burden of kidney cancer than European Americans (EAs). We investigated variations in clinical characteristics of HA and NA patients with renal cell carcinoma (RCC) who were previously underrepresented. Clinical records of 294 patients with RCC (151 EAs, 95 HAs, 22 NAs, and 26 others) without prior diagnosis of cancer were reviewed. Logistic regression analysis was performed to understand patients' clinical characteristics. HAs had about 5 years younger average age at diagnosis than EAs (55.8 vs. 60.5 years) and an almost 3-fold increased odds of diagnosis before age 50 years (odds ratio [OR], 2.77; 95% confidence interval [CI], 1.39-5.54). The mean age of diagnosis among NAs was 49.7 years, and NAs had an over 6-fold higher odds of diagnosis at a younger age (OR, 6.23; 95% CI, 2.00-19.46). Clear-cell RCC (ccRCC) was more common in HAs and NAs than EAs. Over 90% of HA patients had ccRCC, whereas only 78.8% of EA patients had ccRCC. HAs had increased odds of diagnosis with ccRCC compared with EAs (OR, 2.79; 95% CI, 1.15-6.80). Among HAs, older patients and patients who spoke Spanish as their primary language were more likely to have advanced stage RCC at diagnosis (OR, 10.48; 95% CI, 1.69-64.89 and OR, 4.61; 95% CI, 1.38-15.40). HA and NA patients with RCC had different clinical characteristics than EA patients. It is necessary to better understand the clinical characteristics of these underserved HA and NA populations with high kidney cancer burden.
• #### Racial and ethnic disparities in the control of cardiovascular disease risk factors in Southwest American veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study

BACKGROUND:Racial/ethnic disparities in cardiovascular disease complications have been observed in diabetic patients. We examined the association between race/ethnicity and cardiovascular disease risk factor control in a large cohort of insulin-treated veterans with type 2 diabetes.METHODS:We conducted a cross-sectional observational study at 3 Veterans Affairs Medical Centers in the American Southwest. Using electronic pharmacy databases, we randomly selected 338 veterans with insulin-treated type 2 diabetes. We collected medical record and patient survey data on diabetes control and management, cardiovascular disease risk factors, comorbidity, demographics, socioeconomic factors, psychological status, and health behaviors. We used analysis of variance and multivariate linear regression to determine the effect of race/ethnicity on glycemic control, insulin treatment intensity, lipid levels, and blood pressure control.RESULTS:The study cohort was comprised of 72 (21.3%) Hispanic subjects (H), 35 (10.4%) African Americans (AA), and 226 (67%) non-Hispanic whites (NHW). The mean (SD) hemoglobin A1c differed significantly by race/ethnicity: NHW 7.86 (1.4)%, H 8.16 (1.6)%, AA 8.84 (2.9)%, p = 0.05. The multivariate-adjusted A1c was significantly higher for AA (+0.93%, p = 0.002) compared to NHW. Insulin doses (unit/day) also differed significantly: NHW 70.6 (48.8), H 58.4 (32.6), and AA 53.1 (36.2), p < 0.01. Multivariate-adjusted insulin doses were significantly lower for AA (-17.8 units/day, p = 0.01) and H (-10.5 units/day, p = 0.04) compared to NHW. Decrements in insulin doses were even greater among minority patients with poorly controlled diabetes (A1c greater than or equal to] 8%). The disparities in glycemic control and insulin treatment intensity could not be explained by differences in age, body mass index, oral hypoglycemic medications, socioeconomic barriers, attitudes about diabetes care, diabetes knowledge, depression, cognitive dysfunction, or social support. We found no significant racial/ethnic differences in lipid or blood pressure control.CONCLUSION:In our cohort, insulin-treated minority veterans, particularly AA, had poorer glycemic control and received lower doses of insulin than NHW. However, we found no differences for control of other cardiovascular disease risk factors. The diabetes treatment disparity could be due to provider behaviors and/or patient behaviors or preferences. Further research with larger sample sizes and more geographically diverse populations are needed to confirm our findings.
• #### Racial disparities in the incidence of colon cancer in patients with inflammatory bowel disease

Background: Studies have explored the relationship between inflammatory bowel disease (IBD) [ulcerative colitis (UC) and Crohn's disease (CD)] and colon cancer (CC). Additionally, racial disparities in the incidence of CC is well known. However, the impact of racial disparity in IBD patients who develop CC remains unclear. The aim of this study is to address the knowledge gap in this particular group of patients. Methods: A retrospective analysis was done using the National Inpatient Sample (NIS) database from 2011. We included patients with IBD over age >= 18 years with a diagnosis of CC. Patients were stratified by race, gender, age, presence of IBD and CC. Statistical analysis was performed to compare the groups. Results: A total of 57,542 patients were included (CD: 36,357, UC: 21,001). Of all patients with and without IBD, advanced age, Black and Asian race conferred an increased risk of developing CC, whereas female gender, Hispanic and Native American race conferred a protective effect. In patients with IBD, advanced age conferred an increased risk for developing CC while female gender conferred a protective effect. In this subset of patients, black race conferred a protective effect. Conclusions: Racial disparity exists in the overall incidence of CC and among patients with IBD who develop CC. Interestingly, black race conferred a protective effect for patients with IBD, contrary to what is seen in the general population. These findings could be attributed to the environmental factors and genetic makeup between racial groups. Further studies are warranted to better understand these disparities.
• #### Racial/ethnic disparities in renal cell carcinoma: Increased risk of early-onset and variation in histologic subtypes

Background Racial/ethnic minority groups have a higher burden of renal cell carcinoma (RCC), but RCC among Hispanic Americans (HAs) and American Indians and Alaska Natives (AIs/ANs) are clinically not well characterized. We explored variations in age at diagnosis and frequencies of RCC histologic subtypes across racial/ethnic groups and Hispanic subgroups using National Cancer Database (NCDB) and Arizona Cancer Registry Data. Methods Adult RCC cases with known race/ethnicity were included. Logistic regression analysis was performed to estimate odds and 95% confidence interval (CI) of early-onset (age at diagnosis <50 years) and diagnosis with clear cell RCC (ccRCC) or papillary RCC. Results A total of 405 073 RCC cases from NCDB and 9751 cases from ACR were identified and included. In both datasets, patients from racial/ethnic minority groups had a younger age at diagnosis than non-Hispanic White (NHW) patients. In the NCDB, AIs/ANs had twofold increased odds (OR, 2.21; 95% CI, 1.88-2.59) of early-onset RCC compared with NHWs. HAs also had twofold increased odds of early-onset RCC (OR, 2.14; 95% CI, 1.79-2.55) in the ACR. In NCDB, ccRCC was more prevalent in AIs (86.3%) and Mexican Americans (83.5%) than NHWs (72.5%). AIs/ANs had twofold increased odds of diagnosis with ccRCC (OR, 2.18; 95% CI, 1.85-2.58) in the NCDB, but the association was stronger in the ACR (OR, 2.83; 95% CI, 2.08-3.85). Similarly, Mexican Americans had significantly increased odds of diagnosis with ccRCC (OR, 2.00; 95% CI, 1.78-2.23) in the NCDB. Conclusions This study reports younger age at diagnosis and higher frequencies of ccRCC histologic subtype in AIs/ANs and Hispanic subgroups. These variations across racial/ethnic groups and Hispanic subgroups may have potential clinical implications.
• #### Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation

PURPOSE. The purpose of this study was to quantify the biomechanical response of human posterior ocular tissues from donors of various racioethnic groups to better understand how differences in these properties may play a role in the racioethnic health disparities known to exist in glaucoma. METHODS. Sequential digital image correlation (S-DIC) was used to measure the pressure-induced surface deformations of 23 normal human posterior poles from three racioethnic groups: African descent (AD), European descent (ED), and Hispanic ethnicity (HIS). Regional in-plane principal strains were compared across three zones: the optic nerve stump (ONS), the peripapillary (PP) sclera, and non-PP sclera. RESULTS. The PP scleral tensile strains were found to be lower for ED eyes compared with AD and HIS eyes at 15 mm Hg (P = 0.024 and 0.039, respectively). The mean compressive strains were significantly higher for AD eyes compared with ED eyes at 15 mm Hg (P = 0.018). We also found that the relationship between tensile strain and pressure was significant for those of ED and HIS eyes (P < 0.001 and P = 0.004, respectively), whereas it was not significant for those of AD (P = 0.392). CONCLUSIONS. Our results suggest that, assuming glaucomatous nerve loss is caused by mechanical strains in the vicinity of the optic nerve head, the mechanism of increased glaucoma prevalence may be different in those of AD versus HIS. Our ONS strain analysis also suggested that it may be important to account for ONS geometry and material properties in future scleral biomechanical analysis.
• #### Radar Reflectivity as a Proxy for the Dust Content of Individual Layers in the Martian North Polar Layered Deposits

The stratigraphy of the north polar layered deposits (NPLD) of Mars is believed to contain a climate record of the recent Amazonian period. However, full utilization of this record is difficult without detailed information regarding the physical properties of the constituent layers. Here we present a method for determining the fractional dust content of individual layers using a combination of orbital radar reflectivity measurements and physical modeling. We apply this method to the upper 500 m of the NPLD at 10 study sites and compare the results to a cap-wide radar-mapped surface. Our results show that reflectivity can vary drastically both geographically and with depth, a result we attribute to changing dust content, though the impact of variable layer thickness cannot be totally discounted. These findings imply large-scale regional patterns in ice and dust accumulation do not remain consistent through time. We also find that current models of Mars's dust cycle and polar ice accumulation consistently underpredict the dust content of layers, indicating that our understanding of dust transport, dust sequestration, or dust preservation remains incomplete. Comparisons of study sites on the NPLD also show that some locations contain fewer radar reflectors than others, meaning they may contain a less complete record of the planet's recent paleoclimate, and any future efforts to use the polar layered deposits as a climate proxy, including in situ measurements, should take this into account by choosing study sites wisely.

• #### Radial abundance gradients in the outer Galactic disk as traced by main-sequence OB stars

Context. Elemental abundance gradients in galactic disks are important constraints for models of how spiral galaxies form and evolve. However, the abundance structure of the outer disk region of the Milky Way is poorly known, which hampers our understanding of the spiral galaxy that is closest to us and that can be studied in greatest detail. Young OB stars are good tracers of the present-day chemical abundance distribution of a stellar population and because of their high luminosities they can easily be observed at large distances, making them suitable to explore and map the abundance structure and gradients in the outer regions of the Galactic disk. Aims. Using a sample of 31 main-sequence OB stars located between galactocentric distances 8.4-15.6 kpc, we aim to probe the present-day radial abundance gradients of the Galactic disk. Methods. The analysis is based on high-resolution spectra obtained with the MIKE spectrograph on the Magellan Clay 6.5-m telescope on Las Campanas. We used a non-NLTE analysis in a self-consistent semi-automatic routine based on TLUSTY and SYNSPEC to determine atmospheric parameters and chemical abundances. Results. Stellar parameters (effective temperature, surface gravity, projected rotational velocity, microturbulence, and macroturbulence) and silicon and oxygen abundances are presented for 28 stars located beyond 9 kpc from the Galactic center plus three stars in the solar neighborhood. The stars of our sample are mostly on the main-sequence, with effective temperatures between 20800-31300 K, and surface gravities between 3.23-4.45 dex. The radial oxygen and silicon abundance gradients are negative and have slopes of -0.07 dex kpc(-1) and -0.09 dex kpc(-1), respectively, in the region 8.4 <= R-G <= 15.6 kpc. Conclusions. The obtained gradients are compatible with the present-day oxygen and silicon abundances measured in the solar neighborhood and are consistent with radial metallicity gradients predicted by chemodynamical models of Galaxy Evolution for a subsample of young stars located close to the Galactic plane.
• #### Radial Evolution of Stochastic Heating in Low-β Solar Wind

We consider the radial evolution of perpendicular ion heating due to the violation of magnetic moment conservation caused by Alfven and kinetic Alfven wave turbulence. This process, referred to as stochastic heating (SH), can be quantified by the ratio between the average velocity fluctuations at the ion gyroradius and the perpendicular ion thermal speed epsilon delta v/v(t perpendicular to). Using 17 yr of Helios observations, we constrain how much energy could be dissipated by this mechanism between 0.29 and 0.98 au. We find that SH likely operates throughout the entire inner heliosphere, but that its radial dependence is steeper than that of empirically derived dissipation rates, with r(-2.5) being compared with r(-2.08). This difference is significantly increased in fast solar wind streams to r(-3.1) compared with r(-1.8).
• #### Radial velocities of K–M dwarfs and local stellar kinematics

Aims. The goal of this paper is to present complete radial-velocity data for the spectroscopically selected McCormick sample of nearby K-M dwarfs and, based on these and supplementary data, to determine the space-velocity distributions of late-type stars in the solar neighborhood. Methods. We analyzed nearly 3300 measurements of radial velocities for 1049 K-M dwarfs, that we obtained during the past decade with a CORAVEL-type instrument, with a primary emphasis on detecting and eliminating from kinematic calculations the spectroscopic binaries and binary candidates. Combining radial-velocity data with HIPPARCOS/Tycho-2 astrometry we calculated the space-velocity components and parameters of the galactic orbits in a three-component model potential for the stars in the sample, that we use for kinematical analysis and for the identification of possible candidate members of nearby stellar kinematic groups. Results. We present the catalog of our observations of radial velocities for 959 stars which are not suspected of velocity variability, along with the catalog of U, V, W velocities and Galactic orbital parameters for a total of 1088 K-M stars which are used in the present kinematic analysis. Of these, 146 stars were identified as possible candidate members of the known nearby kinematic groups and suspected subgroups. The distributions of space-velocity components, orbital eccentricities, and maximum distances from the Galactic plane are consistent with the presence of young, intermediate-age and old populations of the thin disk and a small fraction (similar to 3%) of stars with the thick disk kinematics. The kinematic structure gives evidence that the bulk of K-M type stars in the immediate solar vicinity represents a dynamically relaxed stellar population. The star MCC 869 is found to be on a retrograde Galactic orbit (V = -262 km s(-1)) of low inclination (4 degrees) and can be a member of stellar stream of some dissolved structure. The Sun's velocity with respect to the Local Standard of Rest, derived from the distributions of space-velocity components, is (U-circle dot, V-circle dot, W-circle dot) = (9.0 +/- 1.4, 13.1 +/- 0.6, 7.2 +/- 0.8) km s(-1). The radial solar motion derived via the Stromberg's relation, V-circle dot = 14.2 +/- 0.8 km s(-1), agrees within the errors with the value obtained directly from the V distribution of stars on nearly circular orbits.
• #### Radial Velocity Discovery of an Eccentric Jovian World Orbiting at 18 au

Based on two decades of radial velocity (RV) observations using Keck/High Resolution Echelle Spectrometer (HIRES) and McDonald/Tull, and more recent observations using the Automated Planet Finder, we found that the nearby star HR 5183 (HD 120066) hosts a 3 ${M}_{{\rm{J}}}$ minimum mass planet with an orbital period of ${74}_{-22}^{+43}$ yr. The orbit is highly eccentric (e sime 0.84), shuttling the planet from within the orbit of Jupiter to beyond the orbit of Neptune. Our careful survey design enabled high cadence observations before, during, and after the planet's periastron passage, yielding precise orbital parameter constraints. We searched for stellar or planetary companions that could have excited the planet's eccentricity, but found no candidates, potentially implying that the perturber was ejected from the system. We did identify a bound stellar companion more than 15,000 au from the primary, but reasoned that it is currently too widely separated to have an appreciable effect on HR 5183 b. Because HR 5183 b's wide orbit takes it more than 30 au (1'') from its star, we also explored the potential of complimentary studies with direct imaging or stellar astrometry. We found that a Gaia detection is very likely, and that imaging at 10 μm is a promising avenue. This discovery highlights the value of long-baseline RV surveys for discovering and characterizing long-period, eccentric Jovian planets. This population may offer important insights into the dynamical evolution of planetary systems containing multiple massive planets.
• #### Radial Velocity Measurements of HR 8799 b and c with Medium Resolution Spectroscopy

High-contrast medium resolution spectroscopy has been used to detect molecules such as water and carbon monoxide in the atmospheres of gas giant exoplanets. In this work, we show how it can be used to derive radial velocity (RV) measurements of directly imaged exoplanets. Improving upon the traditional cross-correlation technique, we develop a new likelihood based on joint forward modeling of the planetary signal and the starlight background (i.e., speckles). After marginalizing over the starlight model, we infer the barycentric RV of HR 8799 b and c in 2010 yielding ?9.20.5 km s(?1) and ?11.60.5 km s(?1), respectively. These RV measurements help to constrain the 3D orientation of the orbit of the planet by resolving the degeneracy in the longitude of an ascending node. Assuming coplanar orbits for HR 8799 b and c, but not including d and e, we estimate Omega = 89 degrees(27)(-17+) and i = 20 degrees.8(-3.7)(+4.5).
• #### A radial velocity survey of the Carina Nebula's O-type stars

We have obtained multi-epoch observations of 31 O-type stars in the Carina Nebula using the CHIRON spectrograph on the CTIO/SMARTS 1.5-m telescope. We measure their radial velocities to 1-2 km s(-1) precision and present new or updated orbital solutions for the binary systems HD 92607, HD 93576, HDE 303312, and HDE 305536. We also compile radial velocities from the literature for 32 additional O-type and evolved massive stars in the region. The combined data set shows a mean heliocentric radial velocity of 0.6 km s(-1). We calculate a velocity dispersion of <= 9.1 km s(-1), consistent with an unbound, substructured OB association. The Tr 14 cluster shows a marginally significant 5 km s(-1) radial velocity offset from its neighbour Tr 16, but there are otherwise no correlations between stellar position and velocity. The O-type stars in Cr 228 and the South Pillars region have a lower velocity dispersion than the region as a whole, supporting a model of distributed massive star formation rather than migration from the central clusters. We compare our stellar velocities to the Carina Nebula's molecular gas and find that Tr 14 shows a close kinematic association with the Northern Cloud. In contrast, Tr 16 has accelerated the Southern Cloud by 10-15 km s(-1), possibly triggering further massive star formation. The expansion of the surrounding HII region is not symmetric about the O-type stars in radial velocity space, indicating that the ionized gas is constrained by denser material on the far side.