The formal [4+3] cycloaddition between donor-acceptor cyclobutanes and nitrones.

The formal [4+3] cycloaddition of 2-alkoxy-1,1-dicarboxylate activated donor-acceptor cyclobutanes with nitrones is disclosed. The reaction forms structurally unique oxazepines in moderate to high yield with a wide scope of nitrones. In most cases either a diastereomeric mixture or a single diastereomer may be formed, depending on the reaction conditions

Increased yields and simplified purification with a second-generation cobalt catalyst for the oxidative formation of trans-THF rings.

The synthesis of a second-generation cobalt catalyst for the formation of trans-THF products via the Mukaiyama aerobic oxidative cyclization is reported. Two procedures have been developed with the new water-soluble catalyst that give superior yields and greatly simplify purification compared to the previous catalysts

Oxidative cyclization of tertiary pentenol derivatives forming 2,5,5-trisubstituted THF rings and the total synthesis of cyclocapitelline

The synthesis of 2,5,5-trisubstituted tetrahydrofuran rings was accomplished via the Mukaiyama aerobic oxidative cyclization of tertiary 5-pentenols employing the Co(nmp)2catalyst. A variety of THFs were formed in moderate to good yield and diastereoselectivity. The method developed herein was successfully applied to an enantioselective total synthesis of cyclocapitelline

Geologic notes

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Know The Star, Know the Planet. IV. A Stellar Companion to the Host star of the Eccentric Exoplanet HD 8673b

HD 8673 hosts a massive exoplanet in a highly eccentric orbit (e=0.723). Based on two epochs of speckle interferometry a previous publication identified a candidate stellar companion. We observed HD 8673 multiple times with the 10 m Keck II telescope, the 5 m Hale telescope, the 3.63 m AEOS telescope and the 1.5m Palomar telescope in a variety of filters with the aim of confirming and characterizing the stellar companion. We did not detect the candidate companion, which we now conclude was a false detection, but we did detect a fainter companion. We collected astrometry and photometry of the companion on six epochs in a variety of filters. The measured differential photometry enabled us to determine that the companion is an early M dwarf with a mass estimate of 0.33-0.45 M?. The companion has a projected separation of 10 AU, which is one of the smallest projected separations of an exoplanet host binary system. Based on the limited astrometry collected, we are able to constrain the orbit of the stellar companion to a semi-major axis of 35{60 AU, an eccentricity ? 0.5 and an inclination of 75{85?. The stellar companion has likely strongly in uenced the orbit of the exoplanet and quite possibly explains its high eccentricity.Comment: Accepted to the Astronomical Journal, 6 Pages, 5 Figure

Committing to ecological restoration: Efforts around the globe need legal and policy clarification

At the September 2014 United Nations Climate Summit, governments rallied around an international agreement—the New York Declaration on Forests—that underscored restoration of degraded ecosystems as an auspicious solution to climate change. Ethiopia committed to restore more than one-sixth of its land. Uganda, the Democratic Republic of Congo, Guatemala, and Colombia pledged to restore huge areas within their borders. In total, parties committed to restore a staggering 350 million hectares by 2030.Fil: Suding, Kathering. State University Of Colorado-boulder; Estados UnidosFil: Higgs, Eric. University Of Victoria; CanadáFil: Palmer, Margaret. University of Maryland; Estados UnidosFil: Callicott, J. Baird. University Of North Texas; Estados UnidosFil: Anderson, Christopher Brian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Baker, Matthew. University Of Maryland; Estados UnidosFil: Gutrich, John J.. Southern Oregon University; Estados UnidosFil: Hondula, Kelly L.. University of Maryland; Estados UnidosFil: Lafevor, Matthew C.. University of Maryland; Estados UnidosFil: Larson, Brendon M. H.. University Of Waterloo; CanadáFil: Randall, Alan. Ohio State University; Estados Unidos. University Of Sidney; AustraliaFil: Ruhl, J. B.. Vanderbilt University; Estados UnidosFil: Schwartz, Katrina Z. S.. Woodrow Wilson International Center for Scholars; Estados Unido

Identification of PADI2 as a potential breast cancer biomarker and therapeutic target.

BACKGROUND: We have recently reported that the expression of peptidylarginine deiminase 2 (PADI2) is regulated by EGF in mammary cancer cells and appears to play a role in the proliferation of normal mammary epithelium; however, the role of PADI2 in the pathogenesis of human breast cancer has yet to be investigated. Thus, the goals of this study were to examine whether PADI2 plays a role in mammary tumor progression, and whether the inhibition of PADI activity has anti-tumor effects. METHODS: RNA-seq data from a collection of 57 breast cancer cell lines was queried for PADI2 levels, and correlations with known subtype and HER2/ERBB2 status were evaluated. To examine PADI2 expression levels during breast cancer progression, the cell lines from the MCF10AT model were used. The efficacy of the PADI inhibitor, Cl-amidine, was tested in vitro using MCF10DCIS cells grown in 2D-monolayers and 3D-spheroids, and in vivo using MCF10DCIS tumor xenografts. Treated MCF10DCIS cells were examined by flow-cytometry to determine the extent of apoptosis and by RT2 Profiler PCR Cell Cycle Array to detect alterations in cell cycle associated genes. RESULTS: We show by RNA-seq that PADI2 mRNA expression is highly correlated with HER2/ERBB2 (p = 2.2 x 106) in luminal breast cancer cell lines. Using the MCF10AT model of breast cancer progression, we then demonstrate that PADI2 expression increases during the transition of normal mammary epithelium to fully malignant breast carcinomas, with a strong peak of PADI2 expression and activity being observed in the MCF10DCIS cell line, which models human comedo-DCIS lesions. Next, we show that a PADI inhibitor, Cl-amidine, strongly suppresses the growth of MCF10DCIS monolayers and tumor spheroids in culture. We then carried out preclinical studies in nude (nu/nu) mice and found that Cl-amidine also suppressed the growth of xenografted MCF10DCIS tumors by more than 3-fold. Lastly, we performed cell cycle array analysis of Cl-amidine treated and control MCF10DCIS cells, and found that the PADI inhibitor strongly affects the expression of several cell cycle genes implicated in tumor progression, including p21, GADD45alpha, and Ki67. CONCLUSION: Together, these results suggest that PADI2 may function as an important new biomarker for HER2/ERBB2+ tumors and that Cl-amidine represents a new candidate for breast cancer therapy

The utility of 6-minute walk distance in predicting waitlist mortality for lung transplant candidates.

BACKGROUND The lung allocation score (LAS) has led to improved organ allocation for transplant candidates. At present, the 6-minute walk distance (6MWD) is treated as a binary categorical variable of whether or not a candidate can walk more than 150 feet in 6 minutes. In this study, we tested the hypothesis that 6MWD is presently under-utilized with respect to discriminatory power, and that, as a continuous variable, could better prognosticate risk of waitlist mortality. METHODS A retrospective cohort analysis was performed using the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) transplant database. Candidates listed for isolated lung transplant between May 2005 and December 2011 were included. The population was stratified by 6MWD quartiles and unadjusted survival rates were estimated. Multivariable Cox proportional hazards modeling was used to assess the effect of 6MWD on risk of death. The Scientific Registry of Transplant Recipients (SRTR) Waitlist Risk Model was used to adjust for confounders. The optimal 6MWD for discriminative accuracy in predicting waitlist mortality was assessed by receiver-operating characteristic (ROC) curves. RESULTS Analysis was performed on 12,298 recipients. Recipients were segregated into quartiles by distance walked. Waitlist mortality decreased as 6MWD increased. In the multivariable model, significant variables included 6MWD, male gender, non-white ethnicity and restrictive lung diseases. ROC curves discriminated 6-month mortality was best at 655 feet. CONCLUSIONS The 6MWD is a significant predictor of waitlist mortality. A cut-off of 150 feet sub-optimally identifies candidates with increased risk of mortality. A cut-off between 550 and 655 feet is more optimal if 6MWD is to be treated as a dichotomous variable. Utilization of the LAS as a continuous variable could further enhance predictive capabilities

The Effects of a Problem Solving-Based Intervention on Depressive Symptoms and HIV Medication Adherence Are Independent

Depression and depressive symptoms predict poor adherence to medical therapy, but the association is complex, nonspecific, and difficult to interpret. Understanding this association may help to identify the mechanism explaining the results of interventions that improve both medical therapy adherence and depressive symptoms as well as determine the importance of targeting depression in adherence interventions. We previously demonstrated that Managed Problem Solving (MAPS) focused on HIV medication adherence improved adherence and viral load in patients initiating a new antiretroviral regimen. Here, we assessed whether MAPS improved depressive symptoms and in turn, whether changes in depressive symptoms mediated changes in adherence and treatment outcomes. We compared MAPS to usual care with respect to presence of depressive symptoms during the trial using logistic regression. We then assessed whether MAPS' effect on depressive symptoms mediated the relationship between MAPS and adherence and virologic outcomes using linear and logistic regression, respectively. Mediation was defined by the disappearance of the mathematical association between MAPS and the outcomes when the proposed mediator was included in regression models. Although MAPS participants had a lower rate of depressive symptoms (OR = 0.45, 95% confidence interval 0.21-0.93), there was no evidence of mediation of the effects of MAPS on adherence and virological outcome by improvements in depression. Thus, interventions for medication adherence may not need to address depressive symptoms in order to impact both adherence and depression; this remains to be confirmed, however, in other data