The Photooxidation of Hexabromorhenate(IV) in Ethyl Bromide

Irradiation at 254 or 313 nm of solutions of (Bu4N)2[ReBr6] in ethyl bromide exposed to air causes complete conversion of the hexabromorhenate(IV) to perrhenate ion. The rate of the reaction is linearly dependent on the incident light intensity and on a combination of the fraction of light absorbed by the rhenium complex and the fraction absorbed by the ethyl bromide. The experimental results are consistent with a mechanism in which the peroxy radical CH3CH(Br)OO, produced in both the solvent-initiated and metal-initiated pathways, oxidizes [ReBr6]2− by electron transfer

A Psychological Flexibility-based Intervention for Modulating the Impact of Stigma and Prejudice: A Descriptive Review of Empirical Evidence

In recent years, there have been growing efforts to understand and modulate stigma and prejudice from the standpoint of the psychological flexibility model, a pragmatic model of complex human behavior. The present paper provides an overview of the empirical evidence on the applicability of the psychological flexibility model, and its applied strategy, acceptance and commitment therapy (ACT), to stigma and prejudice. Preliminary findings suggest that the psychological flexibility model and ACT are promising avenues for reducing stigma and prejudice; however, further investigation and refinement of the model and ACT are crucial for significantly ameliorating human suffering related to stigma and prejudice

Precise Re–Os ages of organic-rich mudrocks and the Os isotope composition of Jurassic seawater

Rhenium and osmium isotope and abundance data have been obtained on precisely-located samples from three suites of immature, organic-rich mudrocks from Jurassic coastal outcrops in England, The data provide accurate whole-rode ages of 207 +/- 12 Ma, 181 +/- 13 Ma and 155 +/- 4.3 Ma for suites of Hettangian, Toarcian (exaratum Subzone) and Kimmeridgian (sensu anglico, wheatleyensis Subzone) samples. These new Re-Os ages are indistinguishable, within the assigned analytical uncertainties, from interpolated depositional ages estimated from published geological timescales, and establish the importance of the Re-Os dating technique for chronostratigraphic studies. Early-diagenetic pyrite nodules possess levels of Re and Os which are similar to 1-2 orders of magnitude lower than in the enclosing organic-rich mudrocks, indicating that these elements had already been removed from sediment pore waters at the time of nodule formation. Thus the Re-Os isotope system in these organic-rich mudrocks has been closed since, or from very soon after, the time of sediment deposition. Because most of the Re (98+%) and Os (95-99.8+%) in the mudrocks is shown to be hydrogenous, the Os-187/Os-188((i)) of the samples is interpreted to be that of contemporaneous seawater. The data thereby provide the first estimates of the Os isotope composition of Jurassic seawater. During the earliest Jurassic (Hettangian), the seawater Os-187/Os-188 ratio was extremely unradiogenic (similar to 0.15); it had increased to similar to 0.8 at the end of the Early Jurassic (Toarcian) similar to 20 Ma later, while in the Late Jurassic (Kimmeridgian) the seawater Os-187/Os-188 ratio was similar to 0.59. The most likely explanation for the unradiogenic Os isotope composition of Hettangian seawater is that the contribution of unradiogenic Os to the oceans from the hydrothermal alteration of oceanic crust greatly exceeded the input of radiogenic Os from the continents at that time. This interpretation is in Line with observations suggesting that global weathering rates were low in the Hettangian, and that increased hydrothermal and volcanic activity preceded the break-up of Pangea. The Re/Os ratios of Hettangian mudrocks (and by inference, of contemporaneous seawater) are similar to those of mudrocks deposited at later times during the Jurassic, and argues against the unradiogenic Os in Hettangian seawater being derived from extraterrestrial meteoritic sources

Vascular smooth muscle Sirtuin-1 protects against aortic dissection during Angiotensin II-induced hypertension

BACKGROUND: Sirtuin-1 (SirT1), a nicotinamide adenine dinucleotide(+)-dependent deacetylase, is a key enzyme in the cellular response to metabolic, inflammatory, and oxidative stresses; however, the role of endogenous SirT1 in the vasculature has not been fully elucidated. Our goal was to evaluate the role of vascular smooth muscle SirT1 in the physiological response of the aortic wall to angiotensin II, a potent hypertrophic, oxidant, and inflammatory stimulus. METHODS AND RESULTS: Mice lacking SirT1 in vascular smooth muscle (ie, smooth muscle SirT1 knockout) had drastically high mortality (70%) caused by aortic dissection after angiotensin II infusion (1 mg/kg per day) but not after an equipotent dose of norepinephrine, despite comparable blood pressure increases. Smooth muscle SirT1 knockout mice did not show any abnormal aortic morphology or blood pressure compared with wild-type littermates. Nonetheless, in response to angiotensin II, aortas from smooth muscle SirT1 knockout mice had severely disorganized elastic lamellae with frequent elastin breaks, increased oxidant production, and aortic stiffness compared with angiotensin II-treated wild-type mice. Matrix metalloproteinase expression and activity were increased in the aortas of angiotensin II-treated smooth muscle SirT1 knockout mice and were prevented in mice overexpressing SirT1 in vascular smooth muscle or with use of the oxidant scavenger tempol. CONCLUSIONS: Endogenous SirT1 in aortic smooth muscle is required to maintain the structural integrity of the aortic wall in response to oxidant and inflammatory stimuli, at least in part, by suppressing oxidant-induced matrix metalloproteinase activity. SirT1 activators could potentially be a novel therapeutic approach to prevent aortic dissection and rupture in patients at risk, such as those with hypertension or genetic disorders, such as Marfan's syndrome.R01 HL098028 - NHLBI NIH HHS; HL098028 - NHLBI NIH HHS; HL105287 - NHLBI NIH HHS; T32 HL07224 - NHLBI NIH HH

Quantifying the Reconfiguration of Intrinsic Networks during Working Memory

Rapid, flexible reconfiguration of connections across brain regions is thought to underlie successful cognitive control. Two intrinsic networks in particular, the cingulo-opercular (CO) and fronto-parietal (FP), are thought to underlie two operations critical for cognitive control: task-set maintenance/tonic alertness and adaptive, trial-by-trial updating. Using functional magnetic resonance imaging, we directly tested whether the functional connectivity of the CO and FP networks was related to cognitive demands and behavior. We focused on working memory because of evidence that during working memory tasks the entire brain becomes more integrated. When specifically probing the CO and FP cognitive control networks, we found that individual regions of both intrinsic networks were active during working memory and, as expected, integration across the two networks increased during task blocks that required cognitive control. Crucially, increased integration between each of the cognitive control networks and a task-related, non-cognitive control network (the hand somatosensory-motor network; SM) was related to increased accuracy. This implies that dynamic reconfiguration of the CO and FP networks so as to increase their inter-network communication underlies successful working memory

Trends in Availability and Prices of Subsidized ACT over the First Year of the AMFm: Evidence from Remote Regions of Tanzania

Background: The Affordable Medicines Facility for malaria (AMFm) is a pilot supra-national subsidy program that aims to increase access and affordability of artemisinin combination therapy (ACT) in public sector clinics and private retail shops. It is unclear to what extent the AMFm model will translate into wide scale availability and price reductions in ACT, particularly for rural, remote areas where disparities in access to medicines often exist. This study is the first to rigorously examine the availability and price of subsidized ACT during the first year of the AMFm, measured through retail audits in remote regions of Tanzania. Methods: Periodic retail audits of Accredited Drug Dispensing Outlets (ADDOs) were conducted in two remote regions of Tanzania (Mtwara and Rukwa). Temporal and spatial variation in ACT availability and pricing were explored. A composite measure of ADDO remoteness, using variables, such as distance to suppliers and towns, altitude and population density, was used to explore whether ACT availability and price vary systematically with remoteness. Results: Between February 2011 and January 2012, the fraction of ADDOs stocking AMFm-ACT increased from 25% to 88% in Mtwara and from 3% to 62% in Rukwa. Availability was widespread, though diffusion throughout the region was achieved more quickly in Mtwara. No significant relationship was found between ACT availability and remoteness. Adult doses of AMFm-ACT were much more widely available than any other age/weight band. Average prices fell from 1529 TZS (1.03 USD) to 1272 TZS (0.81 USD) over the study period, with prices in Rukwa higher than Mtwara. The government recommended retail price for AMFm- ACT is 1,000 TZS ($0.64 USD). The median retail ACT price in the final round of data collection was 1,000 TZS. Conclusions: The AMFm led to large increases in availability of low priced ACT in Tanzania, with no significant variation in availability based on remoteness. Availability did remain lower and prices remained higher in Rukwa, which is a more remote region overall. Low availability of child and adolescent ACT doses could be due in part to lower quantities of non-adult packs imported into Tanzania. Future research will explore whether increased availability and affordability persists and whether it translates into higher ACT use in Tanzania

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery

Trends in availability and prices of subsidized ACT over the first year of the AMFm: evidence from remote regions of Tanzania

Abstract Background The Affordable Medicines Facility for malaria (AMFm) is a pilot supra-national subsidy program that aims to increase access and affordability of artemisinin combination therapy (ACT) in public sector clinics and private retail shops. It is unclear to what extent the AMFm model will translate into wide scale availability and price reductions in ACT, particularly for rural, remote areas where disparities in access to medicines often exist. This study is the first to rigorously examine the availability and price of subsidized ACT during the first year of the AMFm, measured through retail audits in remote regions of Tanzania. Methods Periodic retail audits of Accredited Drug Dispensing Outlets (ADDOs) were conducted in two remote regions of Tanzania (Mtwara and Rukwa). Temporal and spatial variation in ACT availability and pricing were explored. A composite measure of ADDO remoteness, using variables, such as distance to suppliers and towns, altitude and population density, was used to explore whether ACT availability and price vary systematically with remoteness. Results Between February 2011 and January 2012, the fraction of ADDOs stocking AMFm-ACT increased from 25% to 88% in Mtwara and from 3% to 62% in Rukwa. Availability was widespread, though diffusion throughout the region was achieved more quickly in Mtwara. No significant relationship was found between ACT availability and remoteness. Adult doses of AMFm-ACT were much more widely available than any other age/weight band. Average prices fell from 1529 TZS (1.03 USD) to 1272 TZS (0.81 USD) over the study period, with prices in Rukwa higher than Mtwara. The government recommended retail price for AMFm- ACT is 1,000 TZS ($0.64 USD). The median retail ACT price in the final round of data collection was 1,000 TZS. Conclusions The AMFm led to large increases in availability of low priced ACT in Tanzania, with no significant variation in availability based on remoteness. Availability did remain lower and prices remained higher in Rukwa, which is a more remote region overall. Low availability of child and adolescent ACT doses could be due in part to lower quantities of non-adult packs imported into Tanzania. Future research will explore whether increased availability and affordability persists and whether it translates into higher ACT use in Tanzania.http://deepblue.lib.umich.edu/bitstream/2027.42/112716/1/12936_2012_Article_2494.pd