3,3'-diethylthiatricarbocyanine iodide: a highly sensitive chiroptical reporter of DNA helicity and sequence

Using UV-vis absorption and circular dichroism (CD) spectroscopies, we explored the binding interactions of 3,3'-diethylthiatricarbocyanine iodide (Cy7) with polynucleotides of different sequences and helicity. CD showed to be a very diagnostic tool giving different spectroscopic chiroptical signatures for all explored DNA sequences upon Cy7 binding. Cy7 was able to spectroscopically discriminate between the right handed B-DNA of poly(dG-dC)(2) and its left handed Z-DNA counterpart induced by spermine or Co(III)hexamine via nearly opposite induced circular dichroic signal.     

The muscarinic M1 agonist xanomeline increases soluble amyloid precursor protein release from Chinese hamster ovary-m1 cells

The functionally selective M1 agonist xanomeline, which is currently undergoing clinical trials as a therapy for Alzheimer's disease, was compared to the muscarinic agonist carbachol for effects on secretion of soluble amyloid precursor protein (APPs) from Chinese hamster ovary cells transfected with the human m1 receptor (CHO-m1). Release of APPs from CHO-m1 cells was increased maximally (4-10 fold) by 100 microM carbachol (EC50 = 11 microM) and by 100 nM xanomeline (EC50 = 10 nM). Stimulation of APPs secretion by xanomeline and carbachol was blocked by preincubation with 1 microM atropine. Carbachol did not stimulate APPs secretion from non-transfected CHO cells. Pilocarpine at 1 mM also increased APPs release. The efficacy of carbachol, xanomeline and pilocarpine for stimulating APPs secretion did not differ significantly. Activation of protein kinase C (PKC) in m1 transfected cell lines by 1 microM phorbol dibutyrate (PDBu) increased APPs release, and this was inhibited 97% by the PKC inhibitor bisindolemalemide. The PKC inhibitor decreased xanomeline and carbachol-stimulated APPs secretion by only 25-30%. These results demonstrate that xanomeline increased APPs release by activation of m1 muscarinic receptors and support the possibility that cholinergic replacement therapy for Alzheimer's Disease may reduce amyloid deposition.     

Research contributions to improving managed health care outcomes.

Managed health care programs are beginning to look to findings from psychotherapy outcome research to help set policy, suggesting the need to consider outcomes research from the standpoint of usability or utility. It also provides an opportunity to integrate science and practice. Considering and applying outcomes in this context requires cooperation between scientists and practitioners, the willingness of each group to set aside guild agenda, and giving up favored but insupportable beliefs and practices on the parts of those in both scientist and practitioner camps. This type of cooperation may have mutual payoffs. This article considers some of the obstacles to this type of sacrifice and evaluates some of the potential costs of cooperating. It also provides perspectives on the new roles of psychological assessment and methods of outcome research that would provide a scientific basis for the function of managed health care. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

True Color Correction of Autonomous Underwater Vehicle Imagery

This paper presents an automated approach to recovering the true color of objects on the seafloor in images collected from multiple perspectives by an autonomous underwater vehicle (AUV) during the construction of three‐dimensional (3D) seafloor models and image mosaics. When capturing images underwater, the water column induces several effects on light that are typically negligible in air, such as color‐dependent attenuation and backscatter. AUVs must typically carry artificial lighting when operating at depths below 20‐30 m; the lighting pattern generated is usually not spatially consistent. These effects cause problems for human interpretation of images, limit the ability of using color to identify benthic biota or quantify changes over multiple dives, and confound computer‐based techniques for clustering and classification. Our approach exploits the 3D structure of the scene generated using structure‐from‐motion and photogrammetry techniques to provide basic spatial data to an underwater image formation model. Parameters that are dependent on the properties of the water column are estimated from the image data itself, rather than using fixed in situ infrastructure, such as reflectance panels or detailed data on water constitutes. The model accounts for distance‐based attenuation and backscatter, camera vignetting and the artificial lighting pattern, recovering measurements of the true color (reflectance) and thus allows us to approximate the appearance of the scene as if imaged in air and illuminated from above. Our method is validated against known color targets using imagery collected in different underwater environments by two AUVs that are routinely used as part of a benthic habitat monitoring program.     

双功能化、双重响应聚（N-异丙基丙烯酰胺）基微凝胶的研究

为制备具有特殊层次结构的多功能化微凝胶,利用N-异丙基丙烯酰胺（NIPAM）为温敏性单体、甲基丙烯酸（MAA）为pH敏感单体、聚乙二醇甲基丙烯酸酯（PEGMA）为反应性稳定剂,通过沉淀聚合合成了内部富含羧基、表面富含羟基的一系列共聚物微凝胶。利用滴定法测定了微凝胶中羧基的含量。透射电镜和动态光散射表明得到的微凝胶几乎是单分散的。变温动态光散射和浊度测定结果表明,所制备的微凝胶具有良好的pH-响应性,随温度改变呈现两级体积相转变。     

Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O₂·⁻) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O₂·⁻ in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O₂·⁻ in the MnPO contributes to the development of chronic AngII-dependent hypertension.     

Tobacco industry litigation position on addiction: continued dependence on past views

This paper reviews the tobacco industry's litigation strategy for addressing the addiction issue through trial testimony by its experts, and opening and closing statements by its lawyers. Despite the fact that several companies now claim to accept, in varying degrees, the conclusions of the Surgeon General concerning tobacco addiction, the tobacco industry litigation strategy pertaining to addiction is essentially unchanged since that of the early 1980s when the issue emerged as crucial. The industry uses its experts and the process of cross-examination of plaintiff's experts to imply that the addictiveness of tobacco and nicotine are more comparable to substances such as caffeine, chocolate, and even milk, than to heroin, cocaine and alcohol. Furthermore, the tobacco industry contends that the definition of addiction has now become so broadened as to include carrots and caffeine and hence that any concurrence that smoking is addictive, does not imply that cigarettes are addictive to the standards that drugs such as heroin and cocaine are addictive. Finally, the industry has continuously asserted that tobacco users assumed the risks of tobacco since they understood that quitting could be difficult when they began to use, and moreover, that the main barrier to cessation is lack of desire or motivation to quit and not physical addiction. These positions have been maintained through the 2004-2005 US Government litigation that was ongoing as the time of this writing.     

Comparison of byproduct formation in waters treated with chlorine and iodine: relevance to point-of-use treatment

Due to their efficacy in deactivating a range of microbial pathogens, particularly amoebic cysts, iodine-based disinfectants have been a popular option for point-of-use (POU) drinking water disinfection by campers, the military, and rural consumers in developing countries. Recently, concerns regarding the formation of cytotoxic and genotoxic iodinated disinfection byproducts (I-DBPs) have arisen during chloramine disinfection of iodide-containing waters in the developed world; similar concerns should pertain to iodine-based POU disinfection. Because there are alternative POU disinfection techniques, including chlorine-based disinfectants, this paper compared disinfection byproduct formation from a range of iodine-based disinfectants at their recommended dosages to chlorination and chloramination under overdosing conditions. Just as chloroform was the predominant trihalomethane (THM) forme during chlorination or chloramination, iodoform was the predominant THM formed during iodination. Conditions fostering THM formation were similar between these treatments, except that THM formation during chlorination increased with pH, while it was slightly elevated at circumneutral pH during iodination. Iodoform formation during treatment with iodine tincture was higher than during treatment with iodine tablets. On a molar basis, iodoform formation during treatment with iodine tincture was 20-60% of the formation of chloroform during chlorination, and total organic iodine (TOI) formation was twice that of total organic chlorine (TOCl), despite the 6-fold higher oxidant dose during chlorination. Based upon previous measurements of chronic mammalian cell cytotoxicity for the individual THMs, consumers of two waters treated with iodine tincture would receive the same THM-associated cytotoxic exposure in 4-19 days as a consumer of the same waters treated with a 6-fold higher dose of chlorine over 1 year. Iodoacetic acid, diiodoacetic acid, and other iodo-acids were also formed with iodine tincture treatment, but at levels <11% of iodoform. However, testing of a Lifestraw Personal POU device, which combines an iodinated anion exchange resin with activated carbon post-treatment, indicated minimal formation of I-DBPs and no iodine residual. Although N-nitrosamines have been associated with oxidant contact with anion exchange resins, N-nitrosamine formation rapidly declined to low levels (4 ng/L) using the Lifestraw device after the first few flushes of water.