The [4+2]‐Cycloaddition of α‐Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero‐Diels–Alder Reactions—Experimental and Computational Studies

The [4+2]‐cycloadditions of α‐nitrosoalkenes with thiochalcones occur with high selectivity at the thioketone moiety of the dienophile providing styryl‐substituted 4H‐1,5,2‐oxathiazines in moderate to good yields. Of the eight conceivable hetero‐Diels–Alder adducts only this isomer was observed, thus a prototype of a highly periselective and regioselective cycloaddition has been identified. Analysis of crude product mixtures revealed that the α‐nitrosoalkene also adds competitively to the thioketone moiety of the thiochalcone dimer affording bis‐heterocyclic [4+2]‐cycloadducts. The experiments are supported by high‐level DFT calculations that were also extended to related hetero‐Diels–Alder reactions of other nitroso compounds and thioketones. These calculations reveal that the title cycloadditions are kinetically controlled processes confirming the role of thioketones as superdienophiles. The computational study was also applied to the experimentally studied thiochalcone dimerization, and showed that the 1,2‐dithiin and 2H‐thiopyran isomers are in equilibrium with the monomer. Again, the DFT calculations indicate kinetic control of this process

Reconciling Semiclassical and Bohmian Mechanics: II. Scattering states for discontinuous potentials

In a previous paper [J. Chem. Phys. 121 4501 (2004)] a unique bipolar decomposition, Psi = Psi1 + Psi2 was presented for stationary bound states Psi of the one-dimensional Schroedinger equation, such that the components Psi1 and Psi2 approach their semiclassical WKB analogs in the large action limit. Moreover, by applying the Madelung-Bohm ansatz to the components rather than to Psi itself, the resultant bipolar Bohmian mechanical formulation satisfies the correspondence principle. As a result, the bipolar quantum trajectories are classical-like and well-behaved, even when Psi has many nodes, or is wildly oscillatory. In this paper, the previous decomposition scheme is modified in order to achieve the same desirable properties for stationary scattering states. Discontinuous potential systems are considered (hard wall, step, square barrier/well), for which the bipolar quantum potential is found to be zero everywhere, except at the discontinuities. This approach leads to an exact numerical method for computing stationary scattering states of any desired boundary conditions, and reflection and transmission probabilities. The continuous potential case will be considered in a future publication.Comment: 18 pages, 8 figure

Intra-arterial adenoviral mediated tumor transfection in a novel model of cancer gene therapy

BACKGROUND: The aim of the present study was to develop and characterize a novel in vivo cancer gene therapy model in which intra-arterial adenoviral gene delivery can be characterized. In this model, the rat cremaster muscle serves as the site for tumor growth and provides convenient and isolated access to the tumor parenchyma with discrete control of arterial and venous access for delivery of agents. RESULTS: Utilizing adenovirus encoding the green fluorescent protein we demonstrated broad tumor transfection. We also observed a dose dependant increment in luciferase activity at the tumor site using an adenovirus encoding the luciferase reporter gene. Finally, we tested the intra-arterial adenovirus dwelling time required to achieve optimal tumor transfection and observed a minimum time of 30 minutes. CONCLUSION: We conclude that adenovirus mediated tumor transfection grown in the cremaster muscle of athymic nude rats via an intra-arterial route could be achieved. This model allows definition of the variables that affect intra-arterial tumor transfection. This particular study suggests that allowing a defined intra-tumor dwelling time by controlling the blood flow of the affected organ during vector infusion can optimize intra-arterial adenoviral delivery

Mars Relay Lander and Orbiter Overflight Profile Estimation

This software allows science and mission operations to view graphs of geometric overflights of satellites and landers within the Mars (or other planetary) networks. It improves on the MaROS Web interface within any modern Web browser, in that it adds new capabilities to the MaROS suite. The profile for an overflight is an important element for selecting communication/ overflight opportunities between the landers and orbiters within the Mars network. Unfortunately, determining these estimates is very computationally expensive and difficult to compute by hand. This software allows the user to select different overflights (via the existing MaROS Web interface) and specify the smoothness of the estimation. Estimates for the geometric relationship between a lander and an orbiter are determined based upon the orbital conditions of the orbiter at the moment the orbiter rises above the horizon from the perspective of the lander. It utilizes 2-body orbital equations to propagate the trajectory through the duration of the view period, and returns profiles that represent the range between the two vehicles, and the elevation and azimuth angles of the orbiter as measured from the lander s position. The algorithms assume a 2-body relationship with an ideal, spherical planetary body, so therefore can see errors less than 2% at polar landing sites on Mars. These algorithms are being implemented to provide rough estimates rapidly for the geometry of a geometric view period where more complete data is unavailable, such as for planning purposes. While other software for this task exists, each at the time of this reporting has been contained within a much more complicated package. This tool allows science and mission operations to view the estimates with a few clicks of the mouse

Relationships Between Problem-Gambling Severity and Psychopathology as Moderated by Income

Background and aims Problem and pathological gambling have been associated with elevated rates of both Axis-I and Axis-II psychiatric disorders. Although both problem gambling and psychiatric disorders have been reported as being more prevalent among lower income vs. middle/higher income groups, how income might moderate the relationship between problem-gambling severity and psychopathology is incompletely understood. To examine the associations between problem-gambling severity and psychopathology in lower income and middle/higher income groups. Methods Data from the first wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (n = 43,093) were analyzed in adjusted logistic regression models to investigate the relationships between problem-gambling severity and psychiatric disorders within and across income groups. Results Greater problem-gambling severity was associated with increased odds of multiple psychiatric disorders for both lower income and middle/higher income groups. Income moderated the association between problem/pathological gambling and alcohol abuse/dependence, with a stronger association seen among middle/higher income respondents than among lower income respondents. Discussion and conclusions The findings that problem-gambling severity is related to psychopathology across income groups suggest a need for public health initiatives across social strata to reduce the impact that problem/pathological gambling may have in relation to psychopathology. Middle/higher income populations, perhaps owing to the availability of more “disposable income,” may be at greater risk for co-occurring gambling and alcohol-use psychopathology and may benefit preferentially from interventions targeting both gambling and alcohol use

An evaluation of Gout visits in the United States for the years 2007 to 2011

Abstract Background This study analyzed visits for and factors associated with gout and gout medication treatment trends for the years 2007–2011 in the United States given the introduction of febuxostat, the first new treatment option for gout in over 40 years, which was introduced to the market in 2009. Methods This study was a retrospective, cross-sectional, observational study of patients age 20 and older seen by providers who participated in the National Ambulatory Medical Care Survey (NAMCS), the National Hospital Ambulatory Medical Care Survey Outpatient Department (NHAMCS-OPD) or Emergency Department (NHAMCS-ED) in the United States. The outcome of interest was visits for gout diagnosis and visits where a gout medication was prescribed. Results Approximately 1.2% of visits had a diagnosis of gout. There was a significant increase in the percentage of visits with a diagnosis of gout in years 2009–2011 compared to 2007–2008, which remained after adjusting for covariates of interest. Groups more likely to have a visit with gout included those ≥65 and 45–64 (both as compared to those 20–44), the African-American and ‘Other’ race groups (as compared to Caucasians) and those on a diuretic. Groups less likely to have a visit with gout included females, Hispanic/Latinos, those with insurance type of ‘Other’ and Medicaid (both as compared to private insurance) and visits to a hospital emergency setting (as compared to physician’s office visits). Conclusion Although there was a significant increase in visits where gout is diagnosed across study years, the overall percentage of visits with a gout diagnosis is low in the US population. Treatment trends over the study years has remained consistent, with the introduction of febuxostat appearing to have little impact for the study years through 2011

Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas

Background and aims: We tested the hypothesis that the actual or predicted consequences of mutations in the cystic fibrosis transmembrane regulator gene correlate with the pancreatic phenotype and with measures of quantitative exocrine pancreatic function. Methods: We assessed 742 patients with cystic fibrosis for whom genotype and clinical data were available. At diagnosis, 610 were pancreatic insufficient, 110 were pancreatic sufficient, and 22 pancreatic sufficient patients progressed to pancreatic insufficiency after diagnosis. Results: We identified mutations on both alleles in 633 patients (85.3%), on one allele in 95 (12.8%), and on neither allele in 14 (1.9%). Seventy six different mutations were identified. The most common mutation was ΔF508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G→T (1.2%), and W1282X (1.2%). Patients were categorized into five classes according to the predicted functional consequences of each mutation. Over 95% of patients with severe class I, II, and III mutations were pancreatic insufficient or progressed to pancreatic insufficiency. In contrast, patients with mild class IV and V mutations were consistently pancreatic sufficient. In all but four cases each genotype correlated exclusively with the pancreatic phenotype. Quantitative data of acinar and ductular secretion were available in 93 patients. Patients with mutations belonging to classes I, II, and III had greatly reduced acinar and ductular function compared with those with class IV or V mutations. Conclusion: The predicted or known functional consequences of specific mutant alleles correlate with the severity of pancreatic disease in cystic fibrosis.published_or_final_versio