BLIMPK/Streamline Surface Catalytic Heating Predictions on the Space Shuttle Orbiter

This paper describes the results of an analysis of localized catalytic heating effects to the U.S. Space Shuttle Orbiter Thermal Protection System (TPS). The analysis applies to the High-temperature Reusable Surface Insulation (HRSI) on the lower fuselage and wing acreage, as well as the critical Reinforced Carbon-Carbon on the nose cap, chin panel and the wing leading edge. The object of the analysis was to use a modified two-layer approach to predict the catalytic heating effects on the Orbiter windward HRSI tile acreage, nose cap, and wing leading edge assuming localized highly catalytic or fully catalytic surfaces. The method incorporated the Boundary Layer Integral Matrix Procedure Kinetic (BLIMPK) code with streamline inputs from viscous Navier-Stokes solutions to produce heating rates for localized fully catalytic and highly catalytic surfaces as well as for nominal partially catalytic surfaces (either Reinforced Carbon-Carbon or Reaction Cured Glass) with temperature-dependent recombination coefficients. The highly catalytic heating results showed very good correlation with Orbiter Experiments STS-2, -3, and -5 centerline and STS-5 wing flight data for the HRSI tiles. Recommended catalytic heating factors were generated for use in future Shuttle missions in the event of quick-time analysis of damaged or repaired TPS areas during atmospheric reentry. The catalytic factors are presented along the streamlines as well as a function of stagnation enthalpy so they can be used for arbitrary trajectories

Racial Differences in Vascular Function in Response to Mental Stress

African Americans (AA) have a higher prevalence of hypertension and other cardiovascular (CV) complications compared to other populations. While the reasons for this elevated CV disease risk are multifactorial, vascular dysfunction is a key contributing factor. It has been previously shown that mental stress, induced by mental arithmetic, results in a significant increase in forearm blood flow (FBF). This response has been predominantly attributed to the release and vasodilatory effect of Nitric Oxide (NO). In this regard, a previous study has reported that AA have an attenuated increase in FBF as compared to Caucasians (CA) in response to mental stress, which may be related to impaired vascular function and thus elevated CV disease risk in AA. However, this study was conducted in a middle-age cohort (mid to late 40’s). Whether this attenuation is present in a young relatively healthy population is unknown. PURPOSE: The purpose of this study was to test the hypothesis that the vasodilatory response to mental stress is blunted in a relatively young and healthy AA population. METHODS: 6 relatively healthy young AA and 6 CA males (AA age: 22 + 2.6, CA age: 23 + 4.6) participated in this study. All measurements were obtained in the morning following an overnight fast. Brachial artery diameter and blood velocity were assessed using high resolution duplex ultrasound. Mental stress was induced by asking subjects to subtract 7 continuously from a 3-digit number while attempting to report answers at a pace set by a 60 bpm metronome. The 3-digit number was changed at 20 second intervals. FBF was measured during a two minute baseline followed by 3 minutes of mental stress. Vascular function was assessed as the absolute peak blood flow response (ml/min) as well as peak conductance (ml/min/mmHg) during the mental stress. RESULTS: The absolute peak flow (AA: 183 + 39 ml/min, CA: 307 + 127 ml/min; P = 0.05) were significantly greater in CA compared to AA. The maximum increase in conductance (AA: 2.03 + 0.32 ml/min/mmHg, CA: 3.69 + 1.39 ml/min/mmHg; P = .02) was also significantly higher in CA as compared to AA. CONCLUSION: This preliminary data supports our hypothesis that vascular function in response to mental stress is attenuated in young healthy AA as compared to their CA counterparts

Cerebrovascular Dysfunction is Related to Depressive Symptom Severity in Young Adults

Cerebral vasodilatory responsiveness is blunted in older adults (~70 yrs) with depressive disorders and is thought to contribute to the link between depressive symptomology and increased risk for neurocognitive (e.g., dementia) and cerebral vascular (e.g., stroke) diseases. In young adults with major depressive disorder (MDD), peripheral vascular endothelial dysfunction is present and graded in relation to the severity of depressive symptoms; however, to date, limited investigations have examined cerebral vasodilatory function in young otherwise healthy adults with MDD. PURPOSE: We tested the hypothesis that cerebral vasodilatory responsiveness to a hypercapnic stimulus would be blunted in young otherwise healthy adults with MDD compared to healthy non-depressed adults (HA). Further, we hypothesized, that the magnitude of impairment in cerebrovascular function would be related to depressive symptom severity. METHODS: Ten HA (7 women; 22±2yrs) and 10 adults with MDD (8 women; 22±2yrs; n=5 tested during a major depressive episode) participated. Depressive symptom severity was evaluated with the Patient Health History Questionnaire-9 (PHQ-9) in both HA and adults with MDD. Beat-to-beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), and end-tidal carbon dioxide concentration (PETCO2; capnograph) were continuously measured during baseline (i.e., normocapnia) and rebreathing-induced hypercapnia. Cerebral vascular conductance index (CVCi=MCAv•MAP-1) was calculated at baseline and at the highest common magnitude of hypercapnia achieved by all subjects during rebreathing (∆PETCO2 = 9 Torr). RESULTS: At baseline, there were no differences in MAP or CVCi between groups (both p\u3e0.05). During hypercapnia, there were no group differences in the increase in MAP (∆3±3 HA vs. ∆4±3 mmHg MDD; p=0.78). Further, neither the hypercapnia-induced increase in MCAv (∆29±7 HA vs. ∆26±8 cm•s-1 MDD; p=0.37) nor the increase in CVCi (∆39±12 HA vs. ∆30±12 %baseline MDD; p=0.13) were different between groups. However, greater severity of depressive symptoms was negatively related to cerebral vasodilatory responsiveness (R2=0.219, p=0.04). CONCLUSION: These preliminary data suggest that cerebral vasodilatory responsiveness to hypercapnia is not impaired in young adults with MDD, despite a negative relation between depressive symptom severity and the magnitude of hypercapnia-induced cerebral vasodilation

Central Blood Pressure and Peripheral Reactive Vasodilation in Plant-Based and Typical Dieting African Americans

African American individuals (AA) face higher mortality rates from cardiovascular disease than Americans from other racial/ethnic backgrounds. The cause of this health disparity is multifactorial and is in part related to impaired vascular function as well as other variables including diet and numerous socioeconomic factors. Diets rich in whole plant foods and low in animal products may protect blood vessels through their high antioxidant capacity and low inflammatory load. PURPOSE: The purpose of this study was to test the hypothesis that AA adhering to a 100% plant-based (vegan) diet (PBD) would have a more favorable dietary intake of several key nutrients and more optimal blood cholesterol, which would contribute to better blood pressure and peripheral reactive vasodilation relative to AA following a typical American diet (TAD). METHODS: Seventeen AA participated in the study. Of them, 8 (5 female; age: 25±2 years; BMI: 23.4±1.4 kg/m2) were following a PBD for 2.5±0.3 years and 9 (5 female; age: 21±1 years; BMI: 25.3±2.1 kg/m2) were following a TAD. A fasting venous blood draw was performed to assess blood lipids. Participants completed a comprehensive diet questionnaire (DHQIII, NIH). Peripheral and central blood pressures were measured via the SphygmoCor system (AtCor Medical). Brachial artery flow-mediated dilation (FMD) and reactive hyperemia (RH) were assessed via well-established procedures. Briefly, 2 min baseline measurements of brachial artery diameter and blood velocity were taken via Doppler ultrasound before a forearm cuff was inflated to 220 mmHg for 5 min. Post-occlusion data were recorded for 3 min. Measurement of baseline to peak post-occlusion brachial artery diameter and blood velocity were performed by pairing a video capture system (Elgato) with edge-detection and blood velocity-tracking software (Quipu). RESULTS: PBD AA consumed more dark green vegetables and whole grains and less cholesterol than TAD AA (p\u3c.05 for all). Consumption of sodium, potassium, and vitamins C & E was not different between groups (p\u3e.05 for all). Total (TC) and low-density lipoprotein (LDL-C) blood cholesterol concentrations were lower in PBD AA relative to TAD AA (TC: 136±9 vs. 174±12 mg/dl; LDL-C: 77±6 vs. 106±11 mg/dl; respectively; p\u3c.05 for both). Resting brachial (b) and central (c) mean arterial blood pressures (MAP) were lower in PBD AA relative to TAD AA (bMAP: 85±2 vs. 91±2 mmHg; cMAP: 80±2 vs. 87±2 mmHg; respectively; p\u3c.05 for both). There were no differences between groups in FMD nor RH (p\u3e.05 for all). FMD and FMD/shear rate were 7.7±0.8% and 0.33±0.05 au in PBD AA and 6.2±0.9% and 0.27±0.03 au in TAD AA, respectively. For RH, the percentage change in blood velocity and flow were 1441±479% and 1425±466% in PBD AA and 707±495% and 671±76% in TAD AA, respectively. CONCLUSION: These preliminary data suggest that a diet rich in whole plant foods but devoid of animal products may be associated with healthier blood cholesterol and peripheral and central blood pressures in AA but that these differences may not yet be translating to differences in peripheral reactive vasodilation

Sympathetically-Mediated Cutaneous Vasoconstriction Is Similar Between Non-Hispanic Black and White Individuals

Cardiovascular disease (CVD) prevalence is highest in non-Hispanic Black (BL) individuals compared to any other race. The mechanisms responsible remain incompletely understood and can be impacted by several environmental, psychosocial, and socioeconomic factors. A major contributing factor to elevated CVD risk/prevalence in the BL population is altered vascular function, which could be attributed to an exaggerated vasoconstrictor response to efferent sympathetic activity (i.e., sympathetic vascular transduction). Previous data from our group demonstrates heightened sympathetic vascular transduction in the peripheral vasculature of BL males. However, whether sympathetically-mediated vasoconstriction is exaggerated in the cutaneous circulation of BL individuals remains unknown. PURPOSE: This study tested the hypothesis that BL individuals exhibit exaggerated vasoconstriction to intra-dermal infusions of the α-adrenoreceptor agonist norepinephrine (NE) relative to White (WH) individuals. METHODS: In this study, young, healthy college-aged BL (n=13; 6 females) and WH (n=10; 4 females) individuals participated. Participants were instrumented with an intradermal microdialysis membrane in the dorsal forearm. Red blood cell flux was continuously assessed via laser Doppler flowmetry before (baseline) and during incrementally stronger infusions of NE (10-8 M – 10-2 M; 6 min/dose). Data were analyzed as a relative (i.e., percent) reduction in cutaneous vascular conductance (CVC: flux/MAP) compared to the pre-infusion baseline. RESULTS: NE caused a dose-dependent reduction in CVC in both groups (P\u3c0.001). There was no difference between the BL and WH individuals (P=0.37) nor was there a race x dose interaction (P=0.84). Similarly, when the data were separated by sex there was no difference between BL and WH males (P=0.56) or females (P=0.26). CONCLUSION: Vasoconstrictor responsiveness to α-adrenoreceptor activation was similar between BL and WH individuals. These data suggest that the cutaneous circulation may exhibit divergent sympathically-mediated vasoconstrictor responsiveness relative to other peripheral vascular beds in BL individuals

Peripheral blood catalase in patients undergoing renal transplantation

Oxygen free radicals are mediators of tissue injury and catalase is an enzyme which is involved in limiting this process. We examined peripheral blood catalase activity (PBCA) to assess its value as a marker in detecting tissue injury related to renal allograft rejection. Thirty-one consecutive recipients of kidney (n = 29) or simultaneous kidney/pancreas (n = 2) transplants and 10 normal volunteers were studied. Catalase activity, measured by the disk-flotation method, was expressed as Sigma units x 10-3/ml (SU/ml) of whole blood. Normal PBCA was determined to be greater than 76 SU/ml. Twenty-nine episodes of renal allograft rejection (diagnosed by clinical criteria +/- biopsy [79%]) were observed in 26 patients. PBCA (mean +/- SEM) was found to be low (64 +/- 1 SU/ml) in 28/29 episodes ([chi]2 = 46.3, P < 0.001), and the decrease (at least two consecutive daily catalase values < 76 SU/ml) occurred 2 days prior to the clinical/biopsy diagnosis of rejection in 26/28 episodes. The sensitivity of PBCA as a discriminant of rejection was 97%, specificity was 96%, and test accuracy was 96%. PBCA less than 50 SU/ml on two or more occasions occurred in five cases and transplant nephrectomy was required in four of these because of uncontrollable rejection. Nine episodes of cyclosporine nephrotoxicity occurred in 7 patients and none of these episodes was associated with a decreased PBCA. Our data suggest that decreased PBCA is a sensitive and specific indicator of renal allograft rejection. PBCA remains normal during episodes of cyclosporine nephrotoxicity and therefore provides a rapid and inexpensive discriminant from allograft rejection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27320/1/0000343.pd

Quantitative scintigraphy with deconvolutional analysis for the dynamic measurement of hepatic function

A mathematical technique known as deconvolutional analysis was used to provide a critical and previously missing element in the computations required to quantitate hepatic function scintigraphically. This computer-assisted technique allowed for the determination of the time required, in minutes, of a labeled bilirubin analog (99mTc-disofenin) to enter the liver via blood and exit via bile. This interval was referred to as the mean transit time (MTT). The critical process provided for by deconvolution is the mathematical simulation of a bolus injection of tracer directly into the afferent blood supply of the liver. The raw data required for this simulation are obtained from the intravenous injection of labeled disofenin, a member of the HIDA family of radiopharmaceuticals. In this study, we perform experiments which document that the simulation process itself is accurate. We then calculate the MTT under a variety of experimental conditions involving progressive hepatic ischemia/reperfusion injury and correlate these results with the results of simultaneously performed BSP determinations and hepatic histology. The experimental group with the most pronounced histologic findings (necrosis, vacuolization, disorganization of hepatic cords) also have the most prolonged MTT and BSP half-life. However, both quantitative imaging and BSP testing are able to identify milder degrees of hepatic ischemic injury not reflected in the histologic evaluation. Quantitative imaging with deconvolutional analysis is a technique easily adaptable to the standard nuclear medicine minicomputer. It provides rapid results and appears to be a sensitive monitor of hepatic functional disturbances resulting from ischemia and reperfusion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26699/1/0000247.pd

Risk Factors for Ocular Infection with Chlamydia trachomatis in Children 6 Months following Mass Treatment in Tanzania

Trachoma control programs aim for high coverage of endemic communities with oral azithromycin to reduce the pool of infection with Chlamydia trachomatis. However, even with high coverage, infection is seen following treatment. In four communities in Tanzania, we followed every child aged under ten years from baseline through treatment to six months post-treatment. We determined who had infection at baseline and who still had or developed infection six months later. Coverage was over 95% in children in these communities, and infection in these children decreased by over 50% at six months. The study found that, at baseline, uninfected children who were treated had prevalence of infection at 6 months of 6%, but infected children who were treated had prevalence of infection of 22% at 6 months. Other risk factors for infection at 6 months included living in a household with other infected children, and living in a household with untreated children. Our data suggest that households with untreated children might be targeted for more intensive follow up to increase coverage and reduce subsequent infection in the community

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors