2,526 research outputs found

    Effects of Dietary Sodium Intake on Blood Flow Regulation During Exercise in Salt Resistant Individuals

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    PURPOSE: Dietary sodium intake guidelines is ā‰¤2,300 mg/day, yet is exceeded by 90% of Americans. This study examined the impact of a high sodium diet on blood flow regulation during exercise. METHODS: Six males (25 Ā± 2 years) consumed dietary sodium intake guidelines for two weeks, with one week salt-capsule supplemented (HS: 6,900 mg/day of sodium) and the other week placebo-capsule supplemented (LS: 2,300 mg/day of sodium). At the end of each week, peripheral hemodynamic measurements [blood flow (BF), shear rate (SR), and flow mediated dilation (FMD)/SR)] of the brachial and superficial femoral artery were taken during handgrip (HG) and plantar flexion (PF) exercise, respectively. Each exercise workload was 3 minutes and progressed by 8 kilograms until exhaustion. RESULTS: There were no differences between LS and HS in blood pressure (82 Ā± 4 v 80 Ā± 5 mmHg; p = 0.3) or heart rate (56 Ā± 6 v 59 Ā± 10 bpm; p = 0.4). HG and PF exercise increased BF, SR, and FMD/SR across workload (p \u3c 0.03 for all), but no difference between diets (p \u3e 0.05 for all). CONCLUSION: Despite previous reports that HS impairs resting vascular function, this study revealed that peripheral vascular function and blood flow regulation during exercise is not impacted by a HS diet.https://scholarscompass.vcu.edu/gradposters/1082/thumbnail.jp

    A Whole-Body Model for Glycogen Regulation Reveals a Critical Role for Substrate Cycling in Maintaining Blood Glucose Homeostasis

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    Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active) and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile) cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into ā€œwhole-bodyā€ contextual models that mimic in vivo conditions

    The chicken type III GnRH receptor homologue is predominantly expressed in the pituitary, and exhibits similar ligand selectivity to the type I receptor

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    Two GnRH isoforms (cGnRH-I and GnRH-II) and two GnRH receptor subtypes (cGnRH-R-I and cGnRH-R-III) occur in chickens. Differential roles for these molecules in regulating gonadotrophin secretion or other functions are unclear. To investigate this we cloned cGnRH-R-III from a broiler chicken and compared its structure, expression and pharmacological properties with cGnRH-R-I. The broiler cGnRH-R-III cDNA was 100% identical to the sequence reported in the red jungle fowl and white leghorn breed. Pituitary cGnRH-R-III mRNA was āˆ¼1400-fold more abundant than cGnRH-R-I mRNA. Northern analysis indicated a single cGnRH-R-III transcript. A pronounced sex and age difference existed, with higher pituitary transcript levels in sexually mature females versus juvenile females. In contrast, higher expression levels occurred in juvenile males versus sexually mature males. Functional studies in COS-7 cells indicated that cGnRH-R-III has a higher binding affinity for GnRH-II than cGnRH-I (Kd: 0Ā·57 vs 19Ā·8ā€ŠnM) with more potent stimulation of inositol phosphate production (ED50: 0Ā·8 vs 4Ā·38ā€ŠnM). Similar results were found for cGnRH-R-I, (Kd: 0Ā·51 vs 10Ā·8ā€ŠnM) and (ED50: 0Ā·7 vs 2Ā·8ā€ŠnM). The initial rate of internalisation was faster for cGnRH-R-III than cGnRH-R-I (26 vs 15Ā·8%/min). Effects of GnRH antagonists were compared at the two receptors. Antagonist #27 distinguished between cGnRH-R-I and cGnRH-R-III (IC50: 2Ā·3 vs 351ā€ŠnM). These results suggest that cGnRH-R-III is probably the major mediator of pituitary gonadotroph function, that antagonist #27 may allow delineation of receptor subtype function in vitro and in vivo and that tissue-specific recruitment of cGnRH-R isoforms has occurred during evolution

    Probing Cosmology with Weak Lensing Minkowski Functionals

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    In this paper, we show that Minkowski Functionals (MFs) of weak gravitational lensing (WL) convergence maps contain significant non-Gaussian, cosmology-dependent information. To do this, we use a large suite of cosmological ray-tracing N-body simulations to create mock WL convergence maps, and study the cosmological information content of MFs derived from these maps. Our suite consists of 80 independent 512^3 N-body runs, covering seven different cosmologies, varying three cosmological parameters Omega_m, w, and sigma_8 one at a time, around a fiducial LambdaCDM model. In each cosmology, we use ray-tracing to create a thousand pseudo-independent 12 deg^2 convergence maps, and use these in a Monte Carlo procedure to estimate the joint confidence contours on the above three parameters. We include redshift tomography at three different source redshifts z_s=1, 1.5, 2, explore five different smoothing scales theta_G=1, 2, 3, 5, 10 arcmin, and explicitly compare and combine the MFs with the WL power spectrum. We find that the MFs capture a substantial amount of information from non-Gaussian features of convergence maps, i.e. beyond the power spectrum. The MFs are particularly well suited to break degeneracies and to constrain the dark energy equation of state parameter w (by a factor of ~ three better than from the power spectrum alone). The non-Gaussian information derives partly from the one-point function of the convergence (through V_0, the "area" MF), and partly through non-linear spatial information (through combining different smoothing scales for V_0, and through V_1 and V_2, the boundary length and genus MFs, respectively). In contrast to the power spectrum, the best constraints from the MFs are obtained only when multiple smoothing scales are combined.Comment: 19 pages, 9 figures, 5 table

    New tunnel diode for zero-bias direct detection for millimeter-wave imagers

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    High-resolution passive millimeter wave imaging cameras require per pixel detector circuitry that is simple, has high sensitivity, low noise, and low power. Detector diodes that do not require bias or local oscillator input, and have high cutoff frequencies are strongly preferred. In addition, they must be manufacturable in large quantities with reasonable uniformity and reproducibility. Such diodes have not been obtainable for W-band and above. We are developing zero-bias square-law detector diodes based on InAs/Alsb/GaAlSb heterostructures which for the first time offer a cost-effective solution for large array formats. The diodes have a high frequency response and are relatively insensitive to growth and process variables. The large zero- bias non-linearity in current floor necessary for detection arises from interband tunneling between the InAs and the GaAlSb layers. Video resistance can be controlled by varying an Alsb tunnel barrier layer thickness. Our analysis shows that capacitance can be further decreased and sensitivity increased by shrinking the diode area, as the diode can have very high current density. DC and RF characterization of these devices and an estimate of their ultimate frequency performance in comparison with commercially available diodes are presented

    Transformation of SV40-immortalized human uroepithelial cells by 3-methylcholanthrene increases IFN- and Large T Antigen-induced transcripts

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    <p>Abstract</p> <p>Background</p> <p>Simian Virus 40 (SV40) immortalization followed by treatment of cells with 3-methylcholanthrene (3-MC) has been used to elicit tumors in athymic mice. 3-MC carcinogenesis has been thoroughly studied, however gene-level interactions between 3-MC and SV40 that could have produced the observed tumors have not been explored. The commercially-available human uroepithelial cell lines were either SV40-immortalized (HUC) or SV40-immortalized and then 3-MC-transformed (HUC-TC).</p> <p>Results</p> <p>To characterize the SV40 - 3MC interaction, we compared human gene expression in these cell lines using a human cancer array and confirmed selected changes by RT-PCR. Many viral Large T Antigen (Tag) expression-related changes occurred in HUC-TC, and it is concluded that SV40 and 3-MC may act synergistically to transform cells. Changes noted in <it>IFP 9-27, 2'-5' OAS, IF 56, MxA </it>and <it>MxAB </it>were typical of those that occur in response to viral exposure and are part of the innate immune response. Because interferon is crucial to innate immune host defenses and many gene changes were interferon-related, we explored cellular growth responses to exogenous IFN-Ī³ and found that treatment impeded growth in tumor, but not immortalized HUC on days 4 - 7. Cellular metabolism however, was inhibited in <it>both </it>cell types. We conclude that IFN-Ī³ <it>metabolic </it>responses were functional in both cell lines, but IFN-Ī³ <it>anti-proliferative </it>responses functioned only in tumor cells.</p> <p>Conclusions</p> <p>Synergism of SV40 with 3-MC or other environmental carcinogens may be of concern as SV40 is now endemic in 2-5.9% of the U.S. population. In addition, SV40-immortalization is a generally-accepted method used in many research materials, but the possibility of off-target effects in studies carried out using these cells has not been considered. We hope that our work will stimulate further study of this important phenomenon.</p

    Limits of Earthquake Early Warning Accuracy and Best Alerting Strategy

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    We explore how accurate earthquake early warning (EEW) can be, given our limited ability to forecast expected shaking even if the earthquake source is known. Because of the strong variability of ground motion metrics, such as peak ground acceleration (PGA) and peak ground velocity (PGV), we find that correct alerts (i.e., alerts that accurately estimate the ground motion will be above a predetermined damage threshold) are not expected to be the most common EEW outcome even when the earthquake magnitude and location are accurately determined. Infrequently, ground motion variability results in a user receiving a false alert because the ground motion turned out to be significantly smaller than the system expected. More commonly, users will experience missed alerts when the system does not issue an alert but the user experiences potentially damaging shaking. Despite these inherit limitations, EEW can significantly mitigate earthquake losses for false-alert-tolerant users who choose to receive alerts for expected ground motions much smaller than the level that could cause damage. Although this results in many false alerts (unnecessary alerts for earthquakes that do not produce damaging ground shaking), it minimizes the number of missed alerts and produces overall optimal performance
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