148 research outputs found

    A Comprehensive Economic Stimulus for our Failing Economy

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    This paper presents a comprehensive plan to fix the ailing American economy, through a five-step approach. First, the Federal Reserve must continue to broaden the scope of monetary policy, by purchasing and selling long-term securities. Manipulating expectations through FOMC statements is another tool at the Federal Reserve’s disposal. Secondly, the government must enact fiscal stimulus to stabilize the economy in the short and medium runs, through investment in infrastructure projects, green technology, fusion technology, and science education. Additionally, the new fiscal policy must tackle the mortgage meltdown, which is weighing down the entire economy. Third, the regulatory system must be changed to reduce the likelihood of another financial collapse, starting with the nationalization of the ratings agencies. Ratings should be updated faster, with a numeric grading system rather than the pre-existing letter grades. Fourth, our globalized economy insures that a coordinated globalized response is necessary to recover. Global cooperation to reduce inflation and avoid protectionist policies is vital. Finally, the American bailout policy must be made clear, only giving bailouts to companies that are sound but financially strapped and those that are too big to fail

    Molecular analysis of endocrine disruption in hornyhead turbot at wastewater outfalls in southern california using a second generation multi-species microarray.

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    Sentinel fish hornyhead turbot (Pleuronichthysverticalis) captured near wastewater outfalls are used for monitoring exposure to industrial and agricultural chemicals of ~ 20 million people living in coastal Southern California. Although analyses of hormones in blood and organ morphology and histology are useful for assessing contaminant exposure, there is a need for quantitative and sensitive molecular measurements, since contaminants of emerging concern are known to produce subtle effects. We developed a second generation multi-species microarray with expanded content and sensitivity to investigate endocrine disruption in turbot captured near wastewater outfalls in San Diego, Orange County and Los Angeles California. Analysis of expression of genes involved in hormone [e.g., estrogen, androgen, thyroid] responses and xenobiotic metabolism in turbot livers was correlated with a series of phenotypic end points. Molecular analyses of turbot livers uncovered altered expression of vitellogenin and zona pellucida protein, indicating exposure to one or more estrogenic chemicals, as well as, alterations in cytochrome P450 (CYP) 1A, CYP3A and glutathione S-transferase-α indicating induction of the detoxification response. Molecular responses indicative of exposure to endocrine disruptors were observed in field-caught hornyhead turbot captured in Southern California demonstrating the utility of molecular methods for monitoring environmental chemicals in wastewater outfalls. Moreover, this approach can be adapted to monitor other sites for contaminants of emerging concern in other fish species for which there are few available gene sequences

    The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure-Activity Relationships at TRPMPZQ Orthologs.

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    The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPMPZQ, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes. Here we interrogate whether the different activities of praziquantel analogs against different parasites are also reflected by unique structure-activity relationships at the TRPMPZQ channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPMPZQ channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPMPZQ orthologs, providing further support for TRPMPZQ as the therapeutically relevant target of praziquantel

    Bioaccessibility Tests Accurately Estimate Bioavailability Of Lead To Quail

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    Hazards of soil-borne lead (Pb) to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, the authors measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from 5 Pb-contaminated Superfund sites had relative bioavailabilities from 33% to 63%, with a mean of approximately 50%. Treatment of 2 of the soils with phosphorus (P) significantly reduced the bioavailability of Pb. Bioaccessibility of Pb in the test soils was then measured in 6 in vitro tests and regressed on bioavailability: the relative bioavailability leaching procedure at pH 1.5, the same test conducted at pH 2.5, the Ohio State University in vitro gastrointestinal method, the urban soil bioaccessible lead test, the modified physiologically based extraction test, and the waterfowl physiologically based extraction test. All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the relative bioavailability leaching procedure at pH 2.5 and Ohio State University in vitro gastrointestinal tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter (24%), or present as Pb sulfate (18%). Additional Pb was associated with P (chloropyromorphite, hydroxypyromorphite, and tertiary Pb phosphate) and with Pb carbonates, leadhillite (a lead sulfate carbonate hydroxide), and Pb sulfide. The formation of chloropyromorphite reduced the bioavailability of Pb, and the amendment of Pb-contaminated soils with P may be a thermodynamically favored means to sequester Pb

    Effects of bardoxolone methyl on body weight, waist circumference and glycemic control in obese patients with type 2 diabetes mellitus and stage 4 chronic kidney disease

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    AimsObesity is associated with progression of chronic kidney disease (CKD). Treatment with bardoxolone methyl in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate (eGFR) with concurrent reductions in body weight. We performed post-hoc analyses to further characterize reductions in body weight with bardoxolone methyl.MethodsEligible patients with type 2 diabetes (T2DM) and CKD stage 4 (eGFR 15 to <30 mL/min/1.73 m2) were randomized 1:1 to receive once-daily oral dose of bardoxolone methyl (20 mg) or placebo.ResultsBEACON enrolled 2185 patients. Patients randomized to bardoxolone methyl experienced significant reductions in body weight from baseline relative to patients randomized to placebo (-5.7 kg; 95% CI: -6.0 to -5.3 kg; p < 0.001). In patients randomized to bardoxolone methyl, rate and magnitude of body weight loss were proportional to baseline BMI. Bardoxolone methyl resulted in significant reductions in waist circumference and improved glycemic control.ConclusionsBardoxolone methyl resulted in significant weight loss in a generally obese patient population with T2DM and stage 4 CKD, with the magnitude and rate dependent on baseline BMI
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