Effect of surface waviness on a supercritical laminar-flow-control airfoil

Calculations were made of the effects of surface waviness on the external pressure of a supercritical airfoil at design conditions. Wave parameters varied include amplitude, wavelength, phase, and number of cycles. Effects of single and multiple waves are calculated at various chordwise locations. General trends of surface waviness effects on pressure distribution are determined and these solutions are reported. Contour deviations are imposed on the upper surface of the airfoil. Results are presented in a manner designed to facilitate ready comparison with the ideal contour static pressure distribution

Simulation studies of improved sounding systems

Two instrument designs for indirect satellite sounding of the atmosphere in the infrared are represented by the High Resolution Infra-Red Sounder, Model 2 (HIRS-2) and by the Advanced Meteorological Temperature Sounder (AMTS). The relative capabilities of the two instruments were tested by simulating satellite measurements from a group of temperature soundings, allowing the two participants to retrieve the temperature profiles from the simulated data, and comparing the results with the original temperature profiles. Four data sets were produced from radiosondes data extrapolated to a suitable altitude, representing continents and oceans, between 30S and 30N. From the information available, temperature profiles were retrieved by two different methods, statistical regression and inversion of the radiative transfer equation. Results show the consequence of greater spectral purity, concomitant increase in the number of spectral intervals, and the better spatial resolution in partly clouded areas. At the same time, the limitation of the HIRS-2 without its companion instrument leads to some results which should be ignored in comparing the two instruments. A clear superiority of AMTS results is shown

IMPROVEMENT OF CIRCUlATION USING THE RADIAL APPLIANCE

The purpose of this study was to determine if a subtle energy device, the Cayce Radial Appliance, could improve circulation in the extremities. There were two aspects to the study: a doubleblind, placebo-controlled experiment and a small clinical investigation. In the experiment, 30 subjects were selected for cold extremities, with the criterion that either the hands or the feet had to be below 800 F during the initial measurement session. To measure improvement of circulation, we used digital thermometers to record the temperatures of the thumbs and big toes on both hands and feet. Subjects were instructed to use the appliance 16 times; laboratory measurements were taken during the 1st, 4th and 16th sessions. Skin temperature turned our to be a difficult variable to work with, due to the wide variability in temperature apparently unrelated to the experimental siruation. The strongest results were observed in the 4th session. During session baseline, differences between hand and foot temperatures of the experimental group were significantly greater than those of the control group (t [13,11] 2.49, p '" .02). The 16th session did not yield significant differences between the experimental and control groups. However, in the experimental group, there was a correlation of r (9) -.56 (p '" .07) of hand temperarure increase with the number of days it took to complete the 16 sessions. That is, those subjects who were more consistent in using the appliance may have obtained better results, though statistically the result is only suggestive due to the small sample size. In contrast, in a clinical follow-up study with five subjects and no control group, we found that all subjects had a substantial increase in hand temperature following three sessions on the appliance (Mean increase'" 8.40 F, SO = 3.3). This increase was well in excess of that seen in either the experimental or control groups in the previous study. One important difference was that in the clinical study, use of the appliance was closely supervised, whereas in the blind study most of the appliance sessions were conducted by the subjects alone in their homes

TREATMENT OF PARKINSON'S DISEASE USING THE CAYCE WET CELL BATTERY

Parkinson's disease, a condition involving progressive deterioration of the nervous system, is at present incurable by conventional medicine. Here we report on a study in which we have evidence of clinical improvement from using a treatment modality recommended by Edgar Cayce, a subtle energy device known as the wet cell battery. Cayce said that the wet cell would transfer vibratory energy into the body, and specifically recommended it for neurological disorders, but there have been no previous clinical studies of this modality. T en participants with Parkinson's disease used the wet cell, a chemical battery, with gold and silver solutions, for a four-month treatment period at home. Nine of the ten people followed the protocol consistently (but none completely or perfectly). They averaged slight to moderate improvement in Parkinson's disease symptoms over four months, based on observations by researchers and subjective questionnaires. Over the long term (three years), one participant obtained almost complete remission of his Parkinson's disease symptoms. Since there was no control group the placebo effect cannot be ruled out. However, many minor symptoms showed interesting improvement in several individuals. For example, two people reported regaining their sense of smell, and one had improved color vision. Several people had more facial emotional expressiveness, and reported reduced tremors

Muscle-specific ablation of glucose transporter 1 (GLUT1) does not impair basal or overload-stimulated skeletal muscle glucose uptake

Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle

Microenvironmental Influence on Pre-Clinical Activity of Polo-Like Kinase Inhibition in Multiple Myeloma: Implications for Clinical Translation

Polo-like kinases (PLKs) play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM). We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM) and rapid (commitment to cell death <24 hrs) in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM and other cancers

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

(Un)becoming women: Indian factory women's counternarratives of gender

This paper portrays the life stories of five factory workers in Delhi whose life trajectories run counter to normative femininity. As daughters and wives, they are neglected, abandoned or rejected by their families; they live alone, with their parents past the age that is their natal right, with siblings, or with families and men who are not related to them. I explore the circulation of their counternarratives and how their gender transgressions go public through ordinary forms of talk, such as gossip and rumor. I argue that their move out of the normative is not produced by, but produces, their gender politics; that their agency emerges cognitively from the telling of their stories in tandem with their interlocutors' credulity and uptake; and that the site of gender politics for working class Indian women lies in the informal subaltern publics that are formed by the circulation of their stories. Contrary to the notion of a stable unitary subject that precedes the political, these women's counternarratives demonstrate the subject‐in‐process as a political effect. Their alterity does not exist outside the heteronormative gender order but demarcates the boundaries of its historicity, hinting at both the internal contradictions of existing gender relations and their future possibilities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112196/1/j.1467-954X.2011.02026.x.pd

Genetically Increasing Flux Through b-Oxidation in Skeletal Muscle Increases Mitochondrial Reductive Stress and Glucose Intolerance

Elevated mitochondrial hydrogen peroxide (H(2)O(2)) emission and an oxidative shift in cytosolic redox environment have been linked to high-fat-diet-induced insulin resistance in skeletal muscle. To test specifically whether increased flux through mitochondrial fatty acid oxidation, in the absence of elevated energy demand, directly alters mitochondrial function and redox state in muscle, two genetic models characterized by increased muscle β-oxidation flux were studied. In mice overexpressing peroxisome proliferator-activated receptor-α in muscle (MCK-PPARα), lipid-supported mitochondrial respiration, membrane potential (ΔΨ(m)), and H(2)O(2) production rate (JH(2)O(2)) were increased, which coincided with a more oxidized cytosolic redox environment, reduced muscle glucose uptake, and whole body glucose intolerance despite an increased rate of energy expenditure. Similar results were observed in lipin-1-deficient, fatty-liver dystrophic mice, another model characterized by increased β-oxidation flux and glucose intolerance. Crossing MCAT (mitochondria-targeted catalase) with MCK-PPARα mice normalized JH(2)O(2) production, redox environment, and glucose tolerance, but surprisingly, both basal and absolute insulin-stimulated rates of glucose uptake in muscle remained depressed. Also surprising, when placed on a high-fat diet, MCK-PPARα mice were characterized by much lower whole body, fat, and lean mass as well as improved glucose tolerance relative to wild-type mice, providing additional evidence that overexpression of PPARα in muscle imposes more extensive metabolic stress than experienced by wild-type mice on a high-fat diet. Overall, the findings suggest that driving an increase in skeletal muscle fatty acid oxidation in the absence of metabolic demand imposes mitochondrial reductive stress and elicits multiple counterbalance metabolic responses in an attempt to restore bioenergetic homeostasis. NEW & NOTEWORTHY Prior work has suggested that mitochondrial dysfunction is an underlying cause of insulin resistance in muscle because it limits fatty acid oxidation and therefore leads to the accumulation of cytotoxic lipid intermediates. The implication has been that therapeutic strategies to accelerate β-oxidation will be protective. The current study provides evidence that genetically increasing flux through β-oxidation in muscle imposes reductive stress that is not beneficial but rather detrimental to metabolic regulation