APOBEC3G levels predict rates of progression to AIDS

BACKGROUND: APOBEC3G (hA3G) is a newly discovered cellular factor of innate immunity that inhibits HIV replication in vitro. Whether hA3G conferrs protection against HIV in vivo is not known. To investigate the possible anti-HIV activity of hA3G in vivo, we examined hA3G mRNA abundance in primary human cells isolated from either HIV-infected or HIV-uninfected individuals, and found that hA3G mRNA levels follow a hierarchical order of long-term nonprogressors>HIV-uninfected>Progressors; and, hA3G mRNA abundance is correlated with surrogates of HIV disease progression: viral load and CD4 count. Another group later confirmed that HIV-infected subjects have lower hA3G mRNA levels than HIV-uninfected controls, but did not find correlations between hA3G mRNA levels and viral load or CD4 count. These conflicing results indicate that a more comprehensive, conclusive investigation of hA3G expression levels in various patient cohorts is urgently needed. PRESENTATION OF THE HYPOTHESIS: For exploring whether hA3G abundance might influence HIV disease progression, we have formulated a hypothesis that inlcudes two parts: a) in vivo, the basal hA3G mRNA expression level per PBMC is a constant – with minor physiologic fluctuations – determined by host genetic and epigenetic elements in a healthy individual; and that the basal hA3G mRNA expression levels in a population follow a Normal (or Gaussian) distribution; b) that although HIV infects randomly, it results in more rapid disease progression in those with lower hA3G mRNA levels, and slower disease progression in those with higher hA3G mRNA levels. TESTING THE HYPOTHESIS: This hypothesis could be tested by a straighforward set of experiments to compare the distribution of hA3G mRNA levels in HIV-uninfected healthy individuals and that in HIV-infected, antiretroviral therapy-naïve subjects who are at early and late stages of infection. IMPLICATION OF THE HYPOTHESIS: Testing this hypothesis will have significant implications for biomedical research. a) It will link hA3G to the mechanisms underlying slower disease progression in long-term nonprogressors. And, b) It may help to establiseh a new prognostic marker, the hA3G abundance measurement, for HIV-infected patients

Sympatho-Excitatory Response to Pulmonary Chemosensitive Spinal Afferent Activation in Anesthetized, Vagotomized Rats

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1-expressing afferent soma at the level of T1-T4 dorsal root ganglia pleura. This treatment abolished all sympatho-excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9-10 weeks post-RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli

A Natural Application for High Temperature Superconductors: a Bearing for the Azimuth Mount of a Lunar Telescope

A bearing for telescope mounts on the moon has to function in a cold dusty vacuum environment that impairs the operation of almost all traditional bearings, but it is a natural environment for bearings constructed out of magnets and high temperature superconductors. The challenge lies not so much in the weight of the telescope that has to be supported, but in the smoothness of forces required for precision positioning control over a long stretch of time without human intervention. In this paper, we present a design of hybrid superconductor magnet bearings intended for use on the azimuth mount of an altitude-azimuth telescope mount system. In addition to the general features of hybrid super conducting magnet bearings, we will address particular issues connected with the application of these bearings on a telescope mount

Tolerance limits and methodologies for IMRT measurement‐based verification QA: Recommendations of AAPM Task Group No. 218

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143649/1/mp12810_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143649/2/mp12810.pd

Southern Ocean mesocyclones and polar lows from manually tracked satellite mosaics

A new reference dataset of mesocyclone activity over the Southern Ocean has been developed from the manual analysis of high resolution infrared satellite mosaics for winter 2004. Of the total 1735 mesocyclones which were identified and analyzed about three quarters were classified as being ‘polar lows’ (i.e. intense systems; see Rasmussen and Turner 2003). The dataset includes mesocyclone track, size, associated cloud vortex type and background synoptic conditions. Maxima in track density were observed over the Bellingshausen Sea and around East Antarctica and are highly correlated with cyclogenesis regions. A comparison against QuikSCAT and reanalyses wind characteristics shows that the reanalyses, while capturing mesocyclone events, tend to considerably underestimate their wind speed (by up to 10 ms-1). This mesocyclone dataset is available as a reference for further analysis of mesocyclones and for the evaluation and development of cyclone-tracking algorithms

Hiding behind Writing: Communication in Offering Process and MBS Performance

Abstract Securities Offering Reform (SOR) in 2005 formalized free writing prospectus (FWP) as permittable written communication in the offering process by securities issuers. Using non-agency mortgage deals securitized following SOR, we find the surprising result that MBS deals with more usage of FWPs sufferred up to 20% higher cumulative net loss. Using textual analysis as an identification strategy, we attribute our finding to the more aggressive sales tactic associated with more FWP usage being employed for deals with more adverse information withholding. Consequently, the cumulative net loss on these deals are worse than their reported characteristics. Lending support to this explanation, we find that the FWP effect persists even after controlling for deal initial yield spreads and credit enhancements, and higher usage of FWPs are associated with increased content ambiguity in the final prospectus. The latter is a tactic often used to hedge litigation risk on undisclosed information. Keywords: Written Communication, Free Writing Prospectus, Information withholding, Uncertain Text, MBS Performance * We thank Zhonglan Dai, Jun Li, Tim Loughran, and Han Xia for helpful comments. All three authors are from Naveen Jindal School of Management, University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas, 75080, email: [email protected], [email protected], [email protected] "In many ways, mortgage products such as RMBS were ground zero in the financial crisis. Misrepresentations in connection with the creation and sale of mortgage securities contributed greatly to the tremendous losses suffered by investors once the U.S. housing market collapsed.&quot

An epigenome-wide association study identifies multiple DNA methylation markers of exposure to endocrine disruptors

Background: Exposure to environmental endocrine disrupting chemicals (EDCs) may play an important role in the epidemic of metabolic diseases. Epigenetic alterations may functionally link EDCs with gene expression and metabolic traits. Objectives: We aimed to evaluate metabolic-related effects of the exposure to endocrine disruptors including five parabens, three bisphenols, and 13 metabolites of nine phthalates as measured in 24-hour urine on epigenome-wide DNA methylation. Methods: A blood-based epigenome-wide association study was performed in 622 participants from the Lifelines DEEP cohort using Illumina Infinium HumanMethylation450 methylation data and EDC excretions in 24-hour urine. Out of the 21 EDCs, 13 compounds were detected in >75% of the samples and, together with bisphenol F, were included in these analyses. Furthermore, we explored the putative function of identified methylation markers and their correlations with metabolic traits. Results: We found 20 differentially methylated cytosine-phosphate-guanines (CpGs) associated with 10 EDCs at suggestive p-value < 1 × 10−6, of which four, associated with MEHP and MEHHP, were genome-wide significant (Bonferroni-corrected p-value < 1.19 × 10−7). Nine out of 20 CpGs were significantly associated with at least one of the tested metabolic traits, such as fasting glucose, glycated hemoglobin, blood lipids, and/or blood pressure. 18 out of 20 EDC-associated CpGs were annotated to genes functionally related to metabolic syndrome, hypertension, obesity, type 2 diabetes, insulin resistance and glycemic traits. Conclusions: The identified DNA methylation markers for exposure to the most common EDCs provide suggestive mechanism underlying the contributions of EDCs to metabolic health. Follow-up studies are needed to unravel the causality of EDC-induced methylation changes in metabolic alterations

Hiding behind Writing: Communication in the Offering Process of Mortgage-Backed Securities

Abstract Securities Offering Reform (SOR) in 2005 formalized free writing prospectus (FWP) as permittable written communication in the offering process by securities issuers. Using non-agency mortgage deals securitized following SOR, we find the surprising result that MBS deals with more FWP usage suffered up to 2% higher cumulative net loss, accounting for almost 18% of the deal average loss. Examining the contents of FWPs, we uncover that textual FWPs rather than loan data tape played a more significant role for the larger deal losses. More FWPs are associated with increased uncertain text usage in the final prospectus supplements, a tactic often used to hedge litigation risk on undisclosed information. Our findings provide evidence that MBS issuers may have hidden information behind writing for their financial benefits. Keywords: Written Communication, Free Writing Prospectus, Information Withholding, Uncertain Text * We thank Dion Bongaerts, Zhonglan Dai, Kathleen Weiss Hanley, Jun Li, Tim Loughran, Han Xia, and the seminar participants at Erasmus University for helpful comments. All three authors are from Naveen Jindal School of Management, University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas, 75080, email: [email protected], [email protected], [email protected] &quot;In many ways, mortgage products such as RMBS were ground zero in the financial crisis. Misrepresentations in connection with the creation and sale of mortgage securities contributed greatly to the tremendous losses suffered by investors once the U.S. housing market collapsed.&quot