Rapid Access to Azabicyclo[3.3.1]nonanes by a Tandem Diverted Tsuji–Trost Process

A three-step synthesis of the 2-azabicyclo[3.3.1]nonane ring system from simple pyrroles, employing a combined photochemical/palladium-catalyzed approach is reported. Substrate scope is broad, allowing the incorporation of a wide range of functionality relevant to medicinal chemistry. Mechanistic studies demonstrate that the process occurs via acid-assisted C-N bond ß-hydride elimination to form a reactive diene, demonstrating that efficient control of what might be considered off-cycle reactions can result in productive tandem catalytic processes. This represents a short and versatile route to the biologically important morphan scaffold

System Engineering Paper

The Iowa State University team, Team LunaCY, is composed of the following sub-teams: the main student organization, the Lunabotics Club; a senior mechanical engineering design course, ME 415; a senior multidisciplinary design course, ENGR 466; and a senior design course from Wartburg College in Waverly, Iowa. Team LunaCY designed and fabricated ART-E III, Astra Robotic Tractor- Excavator the Third, for the team's third appearance in the NASA Lunabotic Mining competition. While designing ART-E III, the team had four main goals for this year's competition:to reduce the total weight of the robot, to increase the amount of regolith simulant mined, to reduce dust, and to make ART-E III autonomous. After many designs and research, a final robot design was chosen that obtained all four goals of Team LunaCY. A few changes Team LunaCY made this year was to go to the electrical, computer, and software engineering club fest at Iowa State University to recruit engineering students to accomplish the task of making ART-E III autonomous. Team LunaCY chose to use LabView to program the robot and various sensors were installed to measure the distance between the robot and the surroundings to allow ART-E III to maneuver autonomously. Team LunaCY also built a testing arena to test prototypes and ART-E III in. To best replicate the competition arena at the Kennedy Space Center, a regolith simulant was made from sand, QuickCrete, and fly ash to cover the floor of the arena. Team LunaCY also installed fans to allow ventilation in the arena and used proper safety attire when working in the arena . With the additional practice in the testing arena and innovative robot design, Team LunaCY expects to make a strong appearance at the 2012 NASA Lunabotic Mining Competition.

Computed tomographic analysis of the quality of trunk muscles in asymptomatic and symptomatic lumbar discectomy patients

Background: No consensus exists on how rehabilitation programs for lumbar discectomy patients with persistent complaints after surgery should be composed. A better understanding of normal and abnormal postoperative trunk muscle condition might help direct the treatment goals. Methods: A three-dimensional CT scan of the lumbar spine was obtained in 18 symptomatic and 18 asymptomatic patients who had undergone a lumbar discectomy 42 months to 83 months (median 63 months) previously. The psoas muscle (PS), the paraspinal muscle mass (PA) and the multifidus muscle (MF) were outlined at the L3, L4 and L5 level. Of these muscles, fat free Cross Sectional Area (CSA) and fat CSA were determined. CSA of the lumbar erector spinae (LES = longissimus thoracis + iliocostalis lumborum) was calculated by subtracting MF CSA from PA CSA. Mean muscle CSA of the left and right sides was calculated at each level. To normalize the data for interpersonal comparison, the mean CSA was divided by the CSA of the L3 vertebral body (mCSA = normalized fat-free muscle CSA; fCSA = normalized fat CSA). Differences in CSA between the pain group and the pain free group were examined using a General Linear Model (GLM). Three levels were examined to investigate the possible role of the level of operation. Results: In lumbar discectomy patients with pain, the mCSA of the MF was significantly smaller than in pain-free subjects (p = 0.009) independently of the level. The mCSA of the LES was significantly smaller in pain patients, but only on the L3 slice (p = 0.018). No significant difference in mCSA of the PS was found between pain patients and pain-free patients (p = 0.462). The fCSA of the MF (p = 0.186) and of the LES (p = 0.256) were not significantly different between both populations. However, the fCSA of the PS was significantly larger in pain patients than in pain-free patients. (p = 0.012). The level of operation was never a significant factor. Conclusions: CT comparison of MF, LES and PS muscle condition between lumbar discectomy patients without pain and patients with protracted postoperative pain showed a smaller fat-free muscle CSA of the MF at all levels examined, a smaller fat-free muscle CSA of the LES at the L3 level, and more fat in the PS in patients with pain. The level of operation was not found to be of importance. The present results suggest a general lumbar muscle dysfunction in the pain group, in particular of the deep stabilizing muscle system

The Combination of BH3-Mimetic ABT-737 with the Alkylating Agent Temozolomide Induces Strong Synergistic Killing of Melanoma Cells Independent of p53

Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ) is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2 family members, has been found to enhance the efficacy of many conventional chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT-737 induced strong synergistic apoptosis in multiple human melanoma cell lines. When the drugs were used in combination in a mouse xenograft model, they drastically reduced tumor growth at concentrations where each individual drug had no significant effect. We found that TMZ treatment elevated p53 levels, and that the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells. Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT-737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer, demonstrated that p53 induction was sufficient for synergistic cell death with ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT-737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737 together induce Noxa in a p53-independent fashion. These results demonstrate that targeting anti-apoptotic Bcl-2 members is a promising method for treating metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are warranted

Self-harm in young people with perinatal HIV and HIV negative young people in England: cross sectional analysis.

BACKGROUND: Self-harm in adolescents is of growing concern internationally but limited evidence exists on the prevalence of self-harm in those living with HIV, who may be at higher risk of poor mental health outcomes. Therefore our aim was to determine the prevalence and predictors of self-harm among young people with perinatally-acquired HIV (PHIV) and HIV negative (with sibling or mother living with HIV) young people living in England. METHODS: 303 PHIV and 100 HIV negative young people (aged 12-23 years) participating in the Adolescents and Adults Living with Perinatal HIV cohort study completed an anonymous self-harm questionnaire, as well as a number of standardised mental-health assessments. Logistic regression investigated predictors of self-harm. RESULTS: The median age was 16.7 years in both groups, and 40.9% of the PHIV and 31.0% of the HIV negative groups were male. In total 13.9% (56/403) reported having ever self-harmed, with no difference by HIV status (p = 0.089). Multivariable predictors of self-harm were female sex (adjusted odds ratio (AOR) 5.3, (95% confidence interval 1.9, 14.1), p = 0.001), lower self-esteem (AOR 0.9 (0.8, 0.9) per 1 point increase, p < 0.001) and having ever used alcohol (AOR 3.8 (1.8, 7.8), p < 0.001). Self-esteem z-scores for both PHIV and HIV negative participants were 1.9 standard deviations below the mean for population norms. CONCLUSIONS: Self-harm is common among PHIV and HIV negative adolescents in England. Reassuringly however, they do not appear to be at an increased risk compared to the general adolescent population (15-19% lifetime prevalence). The low level of self-esteem (compared to available normative data) in both groups is worrying and warrants further attention

Nolanville Comprehensive Plan 2015-2030

Comprehensive plans are “the central organizing umbrella under which other plans, regulations, and initiatives exist.” They typically have long-range planning horizons between 20 and 30 years. These public documents, along with relevant zoning maps, can be used to guide, support, and justify city land use and decision-making in the future. A comprehensive plan should include the overall vision for the community, as well as a plan for the physical growth, development, and preservation of the land. Furthermore, an inclusive comprehensive plan should envision future growth in the various fields of transportation, community facilities and infrastructure, economy, parks and open spaces, natural and cultural resources, and housing.In the fall 2014, the City of Nolanville and Texas Target Communities partnered to create a planning task force to represent the community. The task force was integral to the planning process, contributing the thoughts, desires, and opinions of community members—as well as their enthusiasm about Nolanville’s future. This fourteen-month planning process ended in September 2015. All the material included in the plan is the result of work accomplished in four different graduate level classes spanning two semesters at Texas A&M University as part of the Master of Urban Planning program.The result of this collaboration is the City of Nolanville Comprehensive Plan 2015 - 2030, which is the official policy guide for the community’s growth over the next twenty years.Texas Target Communitie

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies

Sustainability of bioenergy – mapping the risks and benefits to inform future bioenergy systems

Bioenergy is widely included in energy strategies for its GHG mitigation potential. Bioenergy technologies will likely have to be deployed at scale to meet decarbonisation targets, and consequently biomass will have to be increasingly grown/mobilised. Sustainability risks associated with bioenergy may intensify with increasing deployment and where feedstocks are sourced through international trade. This research applies the Bioeconomy Sustainability Indicator Model (BSIM) to map and analyse the performance of bioenergy across 126 sustainability issues, evaluating 16 bioenergy case studies that reflect the breadth of biomass resources, technologies, energy vectors and bio-products. The research finds common trends in sustainability performance across projects that can inform bioenergy policy and decision making. Potential sustainability benefits are identified for People (jobs, skills, income, energy access); for Development (economy, energy, land utilisation); for Natural Systems (soil, heavy metals), and; for Climate Change (emissions, fuels). Also, consistent trends of sustainability risks where focus is required to ensure the viability of bioenergy projects, including for infrastructure, feedstock mobilisation, techno-economics and carbon stocks. Emission mitigation may be a primary objective for bioenergy, this research finds bioenergy projects can provide potential benefits far beyond emissions - there is an argument for supporting projects based on the ecosystem services and/or economic stimulation they may deliver. Also given the broad dynamics and characteristics of bioenergy projects, a rigid approach of assessing sustainability may be incompatible. Awarding ‘credit’ across a broader range of sustainability indicators in addition to requiring minimum performances in key areas, may be more effective at ensuring bioenergy sustainability

Sex Differences in Social Interaction Behavior Following Social Defeat Stress in the Monogamous California Mouse (Peromyscus californicus)

Stressful life experiences are known to be a precipitating factor for many mental disorders. The social defeat model induces behavioral responses in rodents (e.g. reduced social interaction) that are similar to behavioral patterns associated with mood disorders. The model has contributed to the discovery of novel mechanisms regulating behavioral responses to stress, but its utility has been largely limited to males. This is disadvantageous because most mood disorders have a higher incidence in women versus men. Male and female California mice (Peromyscus californicus) aggressively defend territories, which allowed us to observe the effects of social defeat in both sexes. In two experiments, mice were exposed to three social defeat or control episodes. Mice were then behaviorally phenotyped, and indirect markers of brain activity and corticosterone responses to a novel social stimulus were assessed. Sex differences in behavioral responses to social stress were long lasting (4 wks). Social defeat reduced social interaction responses in females but not males. In females, social defeat induced an increase in the number of phosphorylated CREB positive cells in the nucleus accumbens shell after exposure to a novel social stimulus. This effect of defeat was not observed in males. The effects of defeat in females were limited to social contexts, as there were no differences in exploratory behavior in the open field or light-dark box test. These data suggest that California mice could be a useful model for studying sex differences in behavioral responses to stress, particularly in neurobiological mechanisms that are involved with the regulation of social behavior