Tuning of Collagen Scaffold Properties Modulates Embedded Endothelial Cell Regulatory Phenotype in Repair of Vascular Injuries In Vivo

Perivascularly implanted matrix embedded endothelial cells (MEECs) are potent regulators of inflammation and intimal hyperplasia following vascular injuries. Endothelial cells (ECs) in collagen scaffolds adopt a reparative phenotype with significant therapeutic potential. Although the biology of MEECs is increasingly understood, tuning of scaffold properties to control cell-substrate interactions is less well-studied. It is hypothesized that modulating scaffold degradation would change EC phenotype. Scaffolds with differential degradation are prepared by cross-linking and predegradation. Vascular injury increases degradation and the presence of MEECs retards injury-mediated degradation. MEECs respond to differential scaffold properties with altered viability in vivo, suppressed smooth muscle cell (SMC) proliferation in vitro, and altered interleukin-6 and matrix metalloproteinase-9 expression. When implanted perivascularly to a murine carotid wire injury, tuned scaffolds change MEEC effects on vascular repair and inflammation. Live animal imaging enables real-time tracking of cell viability, inflammation, and scaffold degradation, affording an unprecedented understanding of interactions between cells, substrate, and tissue. MEEC-treated injuries improve endothelialization and reduce SMC hyperplasia over 14 d. These data demonstrate the potent role material design plays in tuning MEEC efficacy in vivo, with implications for the design of clinical therapies.National Institutes of Health (U.S.) (Grant R01 GM 49039

Extraction and correlation of total phenolic and flavonoid contents in seaweeds collected from Rameshwaram during pre- and post- monsoon period using different solvent systems with their antioxidant activity

The present study was carried out to compare and correlate the phenolic and flavonoid contents of Turbinaria sp., Sargassum sp. and Gracilaria sp. extracted using different solvents including methanol, isopropyl alcohol, acetone, acetonitrile, ethyl acetate and hexane, and elucidated for their anti-oxidant activity. The total phenolic and flavonoid contents of the solvent extracts were determined using the Folin-Ciocalteau assay and aluminium chloride colorimetric assay with gallic acid and quercetin as standards, respectively. The anti-oxidant activity in phenolic and flavonoid content was also estimated by phosphomolybdenum method and was compared with gallic acid and quercetin standard. The quantitative analysis of flavonoid content reveals that methanolic extract of Sargassum sp. (9.56±0.38 mg QE/g during pre-monsoon and 9.44±0.48 mg QE/g during post-monsoon season); acetone extract of Gracilaria sp. (2.16±0.11 mg QE/g during pre-monsoon and 2.12±0.07 mg QE/g during post-monsoon season) and methanolic extract of Turbinaria sp. (4.11±0.12 mg QE/g during pre-monsoon and 4.22±0.15 mg QE/g during post-monsoon season) had higher concentration of flavonoid content. However, the quantitative analysis of phenolic content was found to be lower in all the seaweed extracts as compared to flavonoids. The anti-oxidant activity of a phenolic content and flavonoid content were also found to be correlated. The findings of the current study conclusively demonstrate the content of phenolic and flavonoid compounds significantly correlate with anti-oxidant activity

Affordable Development and Demonstration of a Small NTR Engine and Stage: How Small is Big Enough?

The Nuclear Thermal Rocket (NTR) derives its energy from fission of uranium-235 atoms contained within fuel elements that comprise the engine's reactor core. It generates high thrust and has a specific impulse potential of approximately 900 seconds - a 100% increase over today's best chemical rockets. The Nuclear Thermal Propulsion (NTP) project, funded by NASA's AES program, includes five key task activities: (1) Recapture, demonstration, and validation of heritage graphite composite (GC) fuel (selected as the "Lead Fuel" option); (2) Engine Conceptual Design; (3) Operating Requirements Definition; (4) Identification of Affordable Options for Ground Testing; and (5) Formulation of an Affordable Development Strategy. During FY'14, a preliminary DDT&E plan and schedule for NTP development was outlined by GRC, DOE and industry that involved significant system-level demonstration projects that included GTD tests at the NNSS, followed by a FTD mission. To reduce cost for the GTD tests and FTD mission, small NTR engines, in either the 7.5 or 16.5 klbf thrust class, were considered. Both engine options used GC fuel and a "common" fuel element (FE) design. The small approximately 7.5 klbf "criticality-limited" engine produces approximately 157 megawatts of thermal power (MWt) and its core is configured with parallel rows of hexagonal-shaped FEs and tie tubes (TTs) with a FE to TT ratio of approximately 1:1. The larger approximately 16.5 klbf Small Nuclear Rocket Engine (SNRE), developed by LANL at the end of the Rover program, produces approximately 367 MWt and has a FE to TT ratio of approximately 2:1. Although both engines use a common 35 inch (approximately 89 cm) long FE, the SNRE's larger diameter core contains approximately 300 more FEs needed to produce an additional 210 MWt of power. To reduce the cost of the FTD mission, a simple "1-burn" lunar flyby mission was considered to reduce the LH2 propellant loading, the stage size and complexity. Use of existing and flight proven liquid rocket and stage hardware (e.g., from the RL10B-2 engine and Delta Cryogenic Second Stage) was also maximized to further aid affordability. This paper examines the pros and cons of using these two small engine options, including their potential to support future human exploration missions to the Moon, near Earth asteroids, and Mars, and recommends a preferred size. It also provides a preliminary assessment of the key activities, development options, and schedule required to affordably build, ground test and fly a small NTR engine and stage within a 10-year timeframe

Effect of Humic Acid on Seed Germination of Raphanus sativus L

Abstract: In the present study, we have tested the effect of humic acid on seed germination of Radish (Raphanus sativus). Seeds were soaked in various concentrations (0.1%, 0.25%, 0.5%, 0.75% and 1%) of humic acid at different time periods (10, 60, 120, 180 and 240 minutes). After 7 days, the seeds were analysed for their germination capacity, root and shoot length. The study infers that humic acid with the concentration of 0.25% showed maximum seed germination (100%) and the optimum shoot and root length was recorded as 6.175cm and 11.46cm respectively after 60 minutes soaking

Arterial microanatomy determines the success of energy-based renal denervation in controlling hypertension

Renal denervation (RDN) is a treatment option for patients with hypertension resistant to conventional therapy. Clinical trials have demonstrated variable benefit. To understand the determinants of successful clinical response to this treatment, we integrated porcine and computational models of intravascular radiofrequency RDN. Controlled single-electrode denervation resulted in ablation zone geometries that varied in arc, area, and depth, depending on the composition of the adjacent tissue substructure. Computational simulations predicted that delivered power density was influenced by tissue substructure, and peaked at the conductivity discontinuities between soft fatty adventitia and water-rich tissues (media, lymph nodes, etc.), not at the electrode-tissue interface. Electrode irrigation protected arterial wall tissue adjacent to the electrode by clearing heat that diffuses from within the tissue, without altering periarterial ablation. Seven days after multielectrode treatments, renal norepinephrine and blood pressure were reduced. Blood pressure reductions were correlated with the size-weighted number of degenerative nerves, implying that the effectiveness of the treatment in decreasing hypertension depends on the extent of nerve injury and ablation, which in turn are determined by the tissue microanatomy at the electrode site. These results may explain the variable patient response to RDN and suggest a path to more robust outcomes.National Institutes of Health (U.S.) (NIH grant R01 GM-49039

Bloch-Wall Phase Transition in the Spherical Model

The temperature-induced second-order phase transition from Bloch to linear (Ising-like) domain walls in uniaxial ferromagnets is investigated for the model of D-component classical spin vectors in the limit D \to \infty. This exactly soluble model is equivalent to the standard spherical model in the homogeneous case, but deviates from it and is free from unphysical behavior in a general inhomogeneous situation. It is shown that the thermal fluctuations of the transverse magnetization in the wall (the Bloch-wall order parameter) result in the diminishing of the wall transition temperature T_B in comparison to its mean-field value, thus favouring the existence of linear walls. For finite values of T_B an additional anisotropy in the basis plane x,y is required; in purely uniaxial ferromagnets a domain wall behaves like a 2-dimensional system with a continuous spin symmetry and does not order into the Bloch one.Comment: 16 pages, 2 figure

Adrenal-permissive HSD3B1 genetic inheritance and risk of estrogen-driven postmenopausal breast cancer.

BACKGROUNDGenetics of estrogen synthesis and breast cancer risk has been elusive. The 1245A→C missense-encoding polymorphism in HSD3B1, which is common in White populations, is functionally adrenal permissive and increases synthesis of the aromatase substrate androstenedione. We hypothesized that homozygous inheritance of the adrenal-permissive HSD3B1(1245C) is associated with postmenopausal estrogen receptor-positive (ER-positive) breast cancer.METHODSA prospective study of postmenopausal ER-driven breast cancer was done for determination of HSD3B1 and circulating steroids. Validation was performed in 2 other cohorts. Adrenal-permissive genotype frequency was compared between postmenopausal ER-positive breast cancer, the general population, and postmenopausal ER-negative breast cancer.RESULTSProspective and validation studies had 157 and 538 patients, respectively, for the primary analysis of genotype frequency by ER status in White female breast cancer patients who were postmenopausal at diagnosis. The adrenal-permissive genotype frequency in postmenopausal White women with estrogen-driven breast cancer in the prospective cohort was 17.5% (21/120) compared with 5.4% (2/37) for ER-negative breast cancer (P = 0.108) and 9.6% (429/4451) in the general population (P = 0.0077). Adrenal-permissive genotype frequency for estrogen-driven postmenopausal breast cancer was validated using Cambridge and The Cancer Genome Atlas data sets: 14.4% (56/389) compared with 6.0% (9/149) for ER-negative breast cancer (P = 0.007) and the general population (P = 0.005). Circulating androstenedione concentration was higher with the adrenal-permissive genotype (P = 0.03).CONCLUSIONAdrenal-permissive genotype is associated with estrogen-driven postmenopausal breast cancer. These findings link genetic inheritance of endogenous estrogen exposure to estrogen-driven breast cancer.FUNDINGNational Cancer Institute, NIH (R01CA236780, R01CA172382, and P30-CA008748); and Prostate Cancer Foundation Challenge Award

Effects of boundary conditions on magnetization switching in kinetic Ising models of nanoscale ferromagnets

Magnetization switching in highly anisotropic single-domain ferromagnets has been previously shown to be qualitatively described by the droplet theory of metastable decay and simulations of two-dimensional kinetic Ising systems with periodic boundary conditions. In this article we consider the effects of boundary conditions on the switching phenomena. A rich range of behaviors is predicted by droplet theory: the specific mechanism by which switching occurs depends on the structure of the boundary, the particle size, the temperature, and the strength of the applied field. The theory predicts the existence of a peak in the switching field as a function of system size in both systems with periodic boundary conditions and in systems with boundaries. The size of the peak is strongly dependent on the boundary effects. It is generally reduced by open boundary conditions, and in some cases it disappears if the boundaries are too favorable towards nucleation. However, we also demonstrate conditions under which the peak remains discernible. This peak arises as a purely dynamic effect and is not related to the possible existence of multiple domains. We illustrate the predictions of droplet theory by Monte Carlo simulations of two-dimensional Ising systems with various system shapes and boundary conditions.Comment: RevTex, 48 pages, 13 figure

Plasma Dynamics

Contains reports on ten research projects split into two sections.National Science Foundation (Grant ENG77-00340)U.S. Department of Energy (Contract EY-76-S-02-2766)U.S. Air Force - Office of Scientific Research (Grant AFOSR-77-3143)U.S. Department of Energy (Contract ET-78-C-01-3019)U.S. Department of Energy (Contract ET-78-S-02-4681)U.S. Department of Energy (Contract ET-78-S-02-4682)U.S. Department of Energy (Grant EG-77-G-01-4107)U.S. Department of Energy (Contract ET-78-S-02-4714)U.S. Department of Energy (Contract ET-78-S-02-4886)U.S. Department of Energy (Contract ET-78-S-02-4690

Plasma Dynamics

Contains reports on ten research projects divided into two sections.National Science Foundation (Grant ENG79-07047)U.S. Air Force - Office of Scientific Research (Grant AFOSR-77-3143)U.S. Department of Energy (Contract DE-ACO2-78ET51013)U.S. Department of Energy (Contract DE-ASO2-78ET53073.AO02)U.S. Department of Energy (Contract ET-78-S-02-4682)U.S. Department of Energy (Contract DE-AS02-78ET53074)U.S. Department of Energy (Contract DE-ASO2-78ET53050)U.S. Department of Energy (Contract DE-AS02-78ET51002)U.S. Department of Energy (Contract DE-ASO2-78ET53076