Characterizing the Unsteady Dynamics of Cylinder-Induced Shock Wave/Transitional Boundary Layer Interactions Using Non-Intrusive Diagnostics

The objectives of this study were to provide time-resolved (1) characterizations of shock wave/transitional boundary layer interactions using schlieren flow visualization, and (2) correlations of unsteady shock motion to boundary layer features. The characteristics of cylinder-induced shock wave/transitional boundary layer interactions in a Mach 2 freestream flowfield were studied experimentally. The Reynolds number in the Mach 2 facility was 30,000,000 m-1. Incoming boundary layers were in transitional and fully turbulent states. Characterizing the shock wave motion was based on tracking the position of the shock wave on the model surface in schlieren images. The motion of the shock waves revealed an high-intensity resonance. When analysis of high-speed schlieren images were combined with unsteady pressure-sensitive paint studies, it was concluded that upstream scaling exhibited characteristics of laminar flow interactions, whereas the downstream separation mirrored turbulent interactions. This high-intensity resonance was duplicated using a blunt fin shock generator and an axisymmetric model. Furthermore, the unsteady dynamics of a boundary layer separation precursor upstream of the separation shock was highly correlated to the motion of the upstream influence (UI) shock and separation shock. The motion of the UI shock, separation shock and boundary layer separation precursor suggest that the unsteadiness in transitional interactions was driven by instabilities in the boundary layer. An initial characterization with changing Reynolds number and edge Mach number was made in the appendix

A study of sex ratio in native (Orconectes virilis) and invasive (Orconectes rusticus) crayfish species in Burt Lake, Michigan

Student PaperSex ratio theory has led to numerous studies that both support current ideas and investigate and explain deviations from the expected 1:1 male to female tertiary sex ratio. Crustaceans have been shown to have aberrant sex ratios (Wenner 1972). This study tests the hypothesis that these results apply to crayfish species. In this study native (O. virilis) and invasive (O. rusticus) species were sampled in Burt Lake in Cheboygan County, Michigan to determine the sex ratios of both populations. Crayfish were captured at 4 sites using dip nets and sex and species were visually determined by examination of the genital pore and color indicators. Carapace length and total length were also measured. The chi-squared tests of the data showed a statistically significant deviation from expected 1:1 sex ratios for O. virilis. In this case there was a female bias with 52 female individuals to only 20 male individuals. O. rusticus samples did not differ significantly from the expected sex ratio. This sex ratio bias in O. virilis could be the result of differential movement or mortality as well as interactions between native and invasive crayfish species.http://deepblue.lib.umich.edu/bitstream/2027.42/57415/1/Lash_Elizabeth_2007.pd

Nondestructive Evaluation of the J-2X Direct Metal Laser Sintered Gas Generator Discharge Duct

The J-2X program at NASA's Marshall Space Flight Center (MSFC) procured a direct metal laser sintered (DMLS) gas generator discharge duct from Pratt & Whitney Rocketdyne and Morris Technologies for a test program that would evaluate the material properties and durability of the duct in an engine-like environment. DMLS technology was pursued as a manufacturing alternative to traditional techniques, which used off nominal practices to manufacture the gas generator duct's 180 degree turn geometry. MSFC's Nondestructive Evaluation (NDE) Team performed radiographic, ultrasonic, computed tomographic, and fluorescent penetrant examinations of the duct. Results from the NDE examinations reveal some shallow porosity but no major defects in the as-manufactured material. NDE examinations were also performed after hot-fire testing the gas generator duct and yielded similar results pre and post-test and showed no flaw growth or development

Ladarixin, a dual CXCR1/2 inhibitor, attenuates experimental melanomas harboring different molecular defects by affecting malignant cells and tumor microenvironment.

CXCR1 and CXCR2 chemokine receptors and their ligands (CXCL1/2/3/7/8) play an important role in tumor progression. Tested to date CXCR1/2 antagonists and chemokine-targeted antibodies were reported to affect malignant cells in vitro and in animal models. Yet, redundancy of chemotactic signals and toxicity hinder further clinical development of these approaches. In this pre-clinical study we investigated the capacity of a novel small molecule dual CXCR1/2 inhibitor, Ladarixin (LDX), to attenuate progression of experimental human melanomas. Our data showed that LDX-mediated inhibition of CXCR1/2 abrogated motility and induced apoptosis in cultured cutaneous and uveal melanoma cells and xenografts independently of the molecular defects associated with the malignant phenotype. These effects were mediated by the inhibition of AKT and NF-kB signaling pathways. Moreover, systemic treatment of melanoma-bearing mice with LDX also polarized intratumoral macrophages to M1 phenotype, abrogated intratumoral de novo angiogenesis and inhibited melanoma self-renewal. Collectively, these studies outlined the pre-requisites of the successful CXCR1/2 inhibition on malignant cells and demonstrated multifactorial effects of Ladarixin on cutaneous and uveal melanomas, suggesting therapeutic utility of LDX in treatment of various melanoma types

Human cardiac mesenchymal stem cell like cells, a novel cell population with therapeutic potential.

Cardiac stem/progenitors are being used in the clinic to treat patients with a range of cardiac pathologies. However, improvements in heart function following treatment have been reported to be variable, with some showing no response. This discrepancy in response remains unresolved. MSCs have been highlighted as a regenerative tool as these cells display both immunomodulatory and pro-regenerative activity. The purpose of this study was to derive a cardiac MSC population to provide an alternative/support to current therapies. We derived human cardiac-mesenchymal-stem-cell-like-cells (CMSCLC) so named as they share some MSC characteristics. However, CMSCLC lack the MSC tri-lineage differentiation capacity, being capable of only rare adipogenic differentiation and demonstrating low/no osteogenic or chondrogenic potential, a phenotype that may have advantages following transplantation. Further, CMSCLC expressed low levels of p16, high levels of MHCI and low levels of MHCII. A lack of senescent cells would also be advantageous for cells to be used therapeutically, as would the ability to modulate the immune response. Crucially, CMSCLC display a transcriptional profile which includes genes associated with cardio-protective/cardio-beneficial effects. CMSCLC are also secretory and multipotent, giving rise to cardiomyocytes and endothelial cells. Our findings support CMSCLC as a novel cell population suitable for use for transplantation

Radiation protection of the gastrointestinal tract and growth inhibition of prostate cancer xenografts by a single compound.

Normal tissue toxicity markedly reduces the therapeutic index of genotoxic anticancer agents, including ionizing radiation. Countermeasures against tissue damage caused by radiation are limited by their potential to also protect malignant cells and tissues. Here, we tested a panel of signal transduction modifiers for selective radioprotection of normal but not tumor tissues. These included three inhibitors of GSK3 (LiCl, SB216763, and SB415286) and two inhibitors of NF-κB (ethyl pyruvate and RTA 408). Among these, the thiol-reactive triterpenoid RTA 408 emerged as a robust and effective protector of multiple organ systems (gastrointestinal, skin, and hemopoietic) against lethal doses of radiation. RTA 408 preserved survival and proliferation of intestinal crypt cells in lethally irradiated mice while reducing apoptosis incidence in crypts and villi. In contrast, RTA 408 uniformly inhibited growth of established CWR22Rv1, LNCaP/C4-2B, PC3, and DU145 xenografts either alone or combined with radiation. Antitumor effects in vivo were associated with reduced proliferation and intratumoral apoptosis and with inhibition of NF-κB-dependent transcription in PC3 cells. Selective protection of normal tissue compartments by RTA 408 critically depended on tissue context and could not be replicated in vitro. Collectively, these data highlight the potential of RTA 408 as a cytoprotective agent that may be safely used in chemoradiation approaches

Prototyping and the New Spirit of Policy-Making

This conceptual paper discusses the use of co-design approaches in the public realm by examining the emergence of a design practice, prototyping, in public policy-making. We argue that changes in approaches to management and organisation over recent decades have led towards greater flexibility, provisionality and anticipation in responding to public issues. These developments have co-emerged with growing interest in prototyping. Synthesising literatures in design, management and computing, and informed by our participant observation of teams inside government, we propose the defining characteristics of prototyping in policymaking and review the implications of using this approach. We suggest that such activities engender a ‘new spirit’ of policymaking. However this development is accompanied by the further encroachment of market logics into government, with the danger of absorbing critiques of capitalism and resulting in reinforced power structures

Development of a Clinical Prediction Score Including Monocyte-to-Lymphocyte Ratio to Inform Tuberculosis Treatment Among Children With HIV: A Multicountry Study

BACKGROUND: Clinical pediatric tuberculosis (TB) diagnosis may lead to overdiagnosis particularly among children with human immunodeficiency virus (CHIV). We assessed the performance of monocyte-lymphocyte ratio (MLR) as a diagnostic biomarker and constructed a clinical prediction score to improve specificity of TB diagnosis in CHIV with limited access to microbiologic testing. METHODS: We pooled data from cohorts of children aged ≤13 years from Vietnam, Cameroon, and South Africa to validate the use of MLR ≥0.378, previously found as a TB diagnostic marker among CHIV. Using multivariable logistic regression, we created an internally validated prediction score for diagnosis of TB disease in CHIV. RESULTS: The combined cohort had 601 children (median age, 1.9 [interquartile range, 0.9-5.3] years); 300 (50%) children were male, and 283 (47%) had HIV. Elevated MLR ≥0.378 had sensitivity of 36% (95% confidence interval [CI], 23%-51%) and specificity of 79% (95% CI, 71%-86%) among CHIV in the validation cohort. A model using MLR ≥0.28, age ≥4 years, tuberculin skin testing ≥5 mm, TB contact history, fever >2 weeks, and chest radiograph suggestive of TB predicted active TB disease in CHIV with an area under the receiver operating characteristic curve of 0.85. A prediction score of ≥5 points had a sensitivity of 94% and specificity of 48% to identify confirmed TB, and a sensitivity of 82% and specificity of 48% to identify confirmed and unconfirmed TB groups combined. CONCLUSIONS: Our score has comparable sensitivity and specificity to algorithms including microbiological testing and should enable clinicians to rapidly initiate TB treatment among CHIV when microbiological testing is unavailable

Modelling Volatilities and Conditional Correlations in Futures Markets with a Multivariate t Distribution

This paper considers a multivariate t version of the Gaussian dynamic conditional correlation (DCC) model proposed by Engle (2002), and suggests the use of devolatized returns computed as returns standardized by realized volatilities rather than by GARCH type volatility estimates. The t-DCC estimation procedure is applied to a portfolio of daily returns on currency futures, government bonds and equity index futures. The results strongly reject the normal-DCC model in favour of a t-DCC specification. The t-DCC model also passes a number of VaR diagnostic tests over an evaluation sample. The estimation results suggest a general trend towards a lower level of return volatility, accompanied by a rising trend in conditional cross correlations in most markets; possibly reflecting the advent of euro in 1999 and increased interdependence of financial markets