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

Precision surveying using very long baseline interferometry

Radio interferometry measurements were used to measure the vector baselines between large microwave radio antennas. A 1.24 km baseline in Massachusetts between the 36 meter Haystack Observatory antenna and the 18 meter Westford antenna of Lincoln Laboratory was measured with 5 mm repeatability in 12 separate experiments. Preliminary results from measurements of the 3,928 km baseline between the Haystack antenna and the 40 meter antenna at the Owens Valley Radio Observatory in California are presented

Effective Temperatures of a Driven System Near Jamming

Fluctuations in a model of a sheared, zero-temperature foam are studied numerically. Five different quantities that reduce to the true temperature in an equilibrium thermal system are calculated. All five have the same shear-rate dependence, and three have the same value. Near the onset of jamming, the relaxation time is the same function of these three temperatures in the sheared system as of the true temperature in an unsheared system. These results imply that statistical mechanics is useful for the system and provide strong support for the concept of jamming.Comment: 4 pages, 4 postscript figure

Dissociative electron attachment to the H2O molecule. II. Nuclear dynamics on coupled electronic surfaces within the local complex potential model

We report the results of a first-principles study of dissociative electron attachment to H2O. The cross sections are obtained from nuclear dynamics calculations carried out in full dimensionality within the local complex potential model by using the multi-configuration time-dependent Hartree method. The calculations employ our previously obtained global, complex-valued, potential-energy surfaces for the three (doublet B1, doublet A1, and doublet B2) electronic Feshbach resonances involved in this process. These three metastable states of H2O- undergo several degeneracies, and we incorporate both the Renner-Teller coupling between the B1 and A1 states as well as the conical intersection between the A1 and B2 states into our treatment. The nuclear dynamics are inherently multidimensional and involve branching between different final product arrangements as well as extensive excitation of the diatomic fragment. Our results successfully mirror the qualitative features of the major fragment channels observed, but are less successful in reproducing the available results for some of the minor channels. We comment on the applicability of the local complex potential model to such a complicated resonant system.Comment: Corrected version of Phys Rev A 75, 012711 (2007

Gastroenterologists' Perceived Barriers to Optimal Pre-Colonoscopy Bowel Preparation: Results of a National Survey

Poor quality bowel preparation has been reported in almost one third of all colonoscopies. To better understand factors associated with poor bowel preparation, we explored perceived patient barriers to optimal pre-colonoscopy bowel preparation from the perspective of the gastroenterologist. A random sample of physician members of the American College of Gastroenterology was surveyed via the internet and postal mailing. Demographic and practice characteristics and practice-related and perceived patient barriers to optimal bowel preparation were assessed among 288 respondents. Lack of time, no patient education reimbursement, and volume of information were not associated with physician level of suboptimal bowel preparation. Those reporting greater than or equal to 10 % suboptimal bowel preparations were more likely to believe patients lack understanding of the importance of following instructions, have problems with diet, and experience trouble tolerating the purgative. Bowel preparation instruction communication and unmet patient educational needs contribute to suboptimal bowel preparation. Educational interventions should address both practice and patient-related factors

Split dose and MiraLAX-based purgatives to enhance bowel preparation quality becoming common recommendations in the US

Objectives: Rates of suboptimal bowel preparation up to 30% have been reported. Liberalized precolonoscopy diet, split dose purgative, and the use of MiraLAX-based bowel preparation (MBBP) prior to colonoscopy are recently developed measures to improve bowel preparation quality but little is known about the utilization prevalence of these measures. We examined the patterns of utilization of these newer approaches to improve precolonoscopy bowel preparation quality among American gastroenterologists. Methods: Surveys were distributed to a random sample of members of the American College of Gastroenterologists. Participants were queried regarding demographics, practice characteristics, and bowel preparation recommendations including recommendations for liberal dietary restrictions, split dose purgative, and the use of MBBP. Approaches were evaluated individually and in combination. Results: Of the 999 eligible participants, 288 responded; 15.2% recommended a liberal diet, 60.0% split dose purgative, and 37.4% MBBP. Diet recommendations varied geographically with gastroenterologists in the West more likely to recommend a restrictive diet (odds ratio [OR] 2.98, 95% confidence interval [CI] 1.16–7.67) and physicians in the Northeast more likely to recommend a liberal diet more likely. Older physicians more often recommended split dosing (OR 1.04, 95% CI 1.04–2.97). Use of MBBP was more common in suburban settings (OR 2.14, 95% CI 1.23–3.73). Evidence suggests that physicians in private practice were more likely to prescribe split dosing (p = 0.03) and less often recommended MBBP (p = 0.02). Likelihood of prescribing MBBP increased as weekly volume of colonoscopy increased (p = 0.03). Conclusions: To enhance bowel preparation quality American gastroenterologists commonly use purgative split dosing. The use of MBBP is becoming more prevalent while a liberalized diet is infrequently recommended. Utilization of these newer approaches to improve bowel preparation quality varies by physician and practice characteristics. Further evaluation of the patterns of usage of these measures is indicated

Optical pulse labeling studies reveal exogenous seeding slows α-synuclein clearance

The accumulation of α-synuclein (α-syn) in intracellular formations known as Lewy bodies (LBs) is associated with several neurodegenerative diseases including Parkinson's disease and Lewy Body Dementia. There is still limited understanding of how α-syn and LB formation is associated with cellular dysfunction and degeneration in these diseases. To examine the clearance and production dynamics of α-syn we transduced organotypic murine brain slice cultures (BSCs) with recombinant adeno-associated viruses (rAAVs) to express Dendra2-tagged human wild-type (WT) and mutant A53T α-syn, with and without the addition of exogenous α-syn fibrillar seeds and tracked them over several weeks in culture using optical pulse labeling. We found that neurons expressing WT or mutant A53T human α-syn show similar rates of α-syn turnover even when insoluble, phosphorylated Ser129 α-syn has accumulated. Taken together, this data reveals α-syn aggregation and overexpression, pSer129 α-syn, nor the A53T mutation affect α-syn dynamics in this system. Prion-type seeding with exogenous α-syn fibrils significantly slows α-syn turnover, in the absence of toxicity but is associated with the accumulation of anti-p62 immunoreactivity and Thiazin Red positivity. Prion-type induction of α-syn aggregation points towards a potential protein clearance deficit in the presence of fibrillar seeds and the ease of this system to explore precise mechanisms underlying these processes. This system facilitates the exploration of α-syn protein dynamics over long-term culture periods. This platform can further be exploited to provide mechanistic insight on what drives this slowing of α-syn turnover and how therapeutics, other genes or different α-syn mutations may affect α-syn protein dynamics