Beet-ing Muscle Dysfunction and Exercise Intolerance in Pulmonary Hypertension

Indiana University-Purdue University Indianapolis (IUPUI)Background: Pulmonary Hypertension (PH) is a devastating disease characterized by pulmonary arterial remodeling, right ventricular dysfunction and ultimately right heart failure. Increased emphasis has been given to skeletal muscle dysfunction in PH, and to its implication in the severe exercise intolerance that is a hallmark of the condition. In this dissertation, skeletal muscle blood flow was measured via the microsphere technique at rest and during exercise (Aim 1), with an acute dose of dietary nitrate via beetroot juice (BRJ) gavage used to determine if supplementation could improve muscle blood flow and alter energetics (Aim 2). VO2max, voluntary running and grip strength tests were used to determine the effect of disease on performance, and to test for an ergogenic effect of BRJ vs. placebo (PL) in healthy and PH rats (Aim 3). Methods: A prospective, randomized, counterbalanced, placebo-controlled trial was used to examine the aforementioned aims across four groups; PH rats (induced with monocrotaline, MCT, 60mg/kg, s.q., 4 weeks) supplemented with BRJ (MCT BRJ, n=9); PH rats supplemented with placebo (MCT PL, n=9); healthy control rats (vehicle, s.q.) supplemented with BRJ (CON BRJ, n=8); healthy control rats supplemented with placebo (CON PL, n=9). Results: Monocrotaline induced a severe PH phenotype evidenced by increased RV wall thickness, RV hypertrophy, RVSP and reduced cardiac output and stroke volume compared to controls (p=<0.001). MCT rats demonstrated lower muscle blood flow at rest, and more prominently during exercise compared to controls (p=0.007-0.047), regardless of supplementation. MCT rats displayed a greater reliance on anaerobic metabolism, demonstrated by increased blood lactate accumulation (p=<0.001), and this was significantly related to reduced blood flow during exercise (r=-0.5879, p=0.001). BRJ supplementation resulted in increased plasma nitrate and nitrite compared to PL (p=<0.001), but at the skeletal muscle level, only nitrate was increased after BRJ. BRJ did not have a significant effect on blood flow, with no improvement during exercise shown vs. PL. Similarly, BRJ did not significantly improve exercise function in MCT or CON rats. Conclusion: MCT rats demonstrated a reduction in muscle blood flow, with BRJ supplementation not resulting in improved flow or exercise performance

Maternal Performance of First-Calf Crossbred Beef Cowns in Relation to Sire Expected Progeny Differency (EPDs)

Cumulative milk production of crossbred daughters of sires of several breeds was estimated using weigh-suckle-weigh procedures. Pooled-across-breed analyses were conducted to determine, in retrospect, relationships of sire expected progeny difference (EPD) values for milk and total maternal value to daughter milk yield and daughter\u27s offspring weaning weight. The pooled coefficient for regression of daughter 214-day milk yield sire milk EPD was 13.4 Ib/lb (residual correlation was .14). The overall mean estimated milk yield was 2,782 Ib, suggesting that a difference in sire milk EPD of 1 Ib corresponded to a difference of approximately 5% in cumulative daughter milk yield. The pooled coefficient for regression of daughter\u27s offspring 214-day weight on sire total maternal EPD was 1.1 8 Ib/lb (residual correlation was .17). Breeders who use sire milk and total maternal EPD values as selection tools should expect such selection to be effective, on average, but should also expect that a substantial proportion of individuals or small groups may not rank as predicted

Relationship of Beef Sire Birth Weight and Weaning Weight Expected Progeny Differences to Actual Performance of Crossbred Offspring

Performance records from 1982 to 1992 on 1365 calves for birth weight (BW) and 1492 calves for weaning weight (WW) were analyzed to estimate relationships of purebred sire expected progeny difference (EPD) values for BW and WW to actual crossbred progeny performance. Sires of the calves were Polled Hereford, Simmental, Angus, Salers, Tarentaise, or Charolais. The pooled-across-breed regressions (Ib/lb + SE) of BW and WW of calves on sire EPD were 1 .I 7 ±.31 and .75 + .28, respectively. Residual correlations of BW with BW EPD and WW with WW EPD were .I6 (P\u3c -01) and .05 (P= .10), respectively. Additional regression and residual correlation analyses were conducted in which records from progeny of low-accuracy sires (Acc. \u3c .50) were deleted. The reduced data set included 967 records for BW and 962 records for WW. The pooled-across-breed regressions (Ib/lb + SE) of BW and WW of calves on higher-accuracy sire EPD were 1.28 + .35 and .71 ± .31, respectively. Residual correlations using higher-accuracy sire data of BW with BW EPD and WW with WW EPD were .I8 (P\u3c.01) and .09 (P = .02). Breeders who use BW and WW EPDs as a selection tool should expect such selection to be effective, on average, and reasonably consistent with theoretical expectation. However, some sires and small progeny groups may not rank as expected based on sire EPDs

A MULTIBAND GENERALIZATION OF THE MULTIHARMONIC ANALYSIS OF VARIANCE PERIOD ESTIMATION ALGORITHM AND THE EFFECT OF INTER-BAND OBSERVING CADENCE ON PERIOD RECOVERY RATE

We present a new method of extending the single band Analysis of Variance period estimation algorithm to multiple bands. We use SDSS Stripe 82 RR Lyrae to show that in the case of low number of observations per band and non-simultaneous observations, improvements in period recovery rates of up to $\approx$60\% are observed. We also investigate the effect of inter-band observing cadence on period recovery rates. We find that using non-simultaneous observation times between bands is ideal for the multiband method, and using simultaneous multiband data is only marginally better than using single band data. These results will be particularly useful in planning observing cadences for wide-field astronomical imaging surveys such as LSST. They also have the potential to improve the extraction of transient data from surveys with few ($\lesssim 30$) observations per band across several bands, such as the Dark Energy Survey.Comment: Submitted to ApJL, comments welcome at [email protected]

The first dental visit: knowledge, attitudes, and behaviors of North Carolina dentists regarding physician referral guidelines

The purpose of this cross-sectional study was to (1) assess the knowledge, attitudes and behaviors of North Carolina (NC) dentists regarding infant and toddler dental referral guidelines of the American Academy of Pediatrics, and (2) to determine factors among this population that influence embracement of these guidelines. One thousand general dentists in NC were randomly selected to participate. The primary outcome variable was acceptance of children referred for the age one dental visit, therefore allowing physicians to comply with referral guidelines. Significant predictors of referral acceptance included correct knowledge about the guideline (OR = 2.0, 95%CI 1.2-3.3), increased confidence in providing preventive care to infants and toddlers (OR = 2.6, 95%CI 1.3 - 4.9), and agreement that parents see importance in dental referrals (OR = 2.1, 95%CI 1.2-3.6). This study identifies factors that influence acceptance of physician referrals for the age one dental visit among NC dentists, that can lead to development of interventions to maximize availability of a dental home for young children

Potential Inhibitory Influence of miRNA 210 on Regulatory T Cells during Epicutaneous Chemical Sensitization

Toluene diisocyanate (TDI) is a potent low molecular weight chemical sensitizer and a leading cause of chemical-induced occupational asthma. The regulatory potential of microRNAs (miRNAs) has been recognized in a variety of disease states, including allergic disease; however, the roles of miRNAs in chemical sensitization are largely unknown. In a previous work, increased expression of multiple miRNAs during TDI sensitization was observed and several putative mRNA targets identified for these miRNAs were directly related to regulatory T-cell (Treg) differentiation and function including Foxp3 and Runx3. In this work, we show that miR-210 expression is increased in the mouse draining lymph node (dLN) and Treg subsets following dermal TDI sensitization. Alterations in dLN mRNA and protein expression of Treg related genes/putative miR-210 targets (foxp3, runx3, ctla4, and cd25) were observed at multiple time points following TDI exposure and in ex vivo systems. A Treg suppression assay, including a miR-210 mimic, was utilized to investigate the suppressive ability of Tregs. Cells derived from TDI sensitized mice treated with miR-210 mimic had less expression of miR-210 compared to the acetone control suggesting other factors, such as additional miRNAs, might be involved in the regulation of the functional capabilities of these cells. These novel findings indicate that miR-210 may have an inhibitory role in Treg function during TDI sensitization. Because the functional roles of miRNAs have not been previously elucidated in a model of chemical sensitization, these data contribute to the understanding of the potential immunologic mechanisms of chemical induced allergic disease

A comparison of computational and experimental lift-off heights of coflow laminar diffusion flames

As a sensitive marker of changes in flame structure, the number densities of excited-state CH (denoted CH*), and excited-state OH (denoted OH*) are imaged in coflow laminar diffusion flames. Measurements are made both in normal gravity and on the NASA KC-135 reduced-gravity aircraft. The spatial distribution of these radicals provides information about flame structure and lift-off heights that can be directly compared with computational predictions. Measurements and computations are compared over a range of buoyancy and fuel dilution levels. Results indicate that the lift-off heights and flame shapes predicted by the computations are in excellent agreement with measurement for both normal gravity (1g) and reduced gravity flames at low dilution levels. As the fuel mixture is increasingly diluted, however, the 1g lift-off heights become underpredicted. This trend continues until the computations predict stable flames at highly dilute fuel mixtures beyond the 1g experimental blow-off limit. To better understand this behavior, an analysis was performed, which indicates that the lift-off height is sensitive to the laminar flame speed of the corresponding premixed mixture at the flame edge. By varying the rates of two key "flame speed" controlling reactions, we were able to modify the predicted lift-off heights so as to be in closer agreement with the experiments. The results indicate that reaction sets that work well in low dilution systems may need to be modified to accommodate high dilution flames

James Webb Space Telescope Optical Simulation Testbed I: Overview and First Results

The James Webb Space Telescope (JWST) Optical Simulation Testbed (JOST) is a tabletop workbench to study aspects of wavefront sensing and control for a segmented space telescope, including both commissioning and maintenance activities. JOST is complementary to existing optomechanical testbeds for JWST (e.g. the Ball Aerospace Testbed Telescope, TBT) given its compact scale and flexibility, ease of use, and colocation at the JWST Science & Operations Center. We have developed an optical design that reproduces the physics of JWST's three-mirror anastigmat using three aspheric lenses; it provides similar image quality as JWST (80% Strehl ratio) over a field equivalent to a NIRCam module, but at HeNe wavelength. A segmented deformable mirror stands in for the segmented primary mirror and allows control of the 18 segments in piston, tip, and tilt, while the secondary can be controlled in tip, tilt and x, y, z position. This will be sufficient to model many commissioning activities, to investigate field dependence and multiple field point sensing & control, to evaluate alternate sensing algorithms, and develop contingency plans. Testbed data will also be usable for cross-checking of the WFS&C Software Subsystem, and for staff training and development during JWST's five- to ten-year mission.Comment: Proceedings of the SPIE, 9143-150. 13 pages, 8 figure