Novel pericyclic routes to strained organic molecules: Theoretical and experimental studies

The chemistry of cyclobutyne (20) and 1,2-cyclobutadiene (21) has been investigated. Research efforts were focused on attempting to independently generate and trap these highly reactive species. The trapping experiments were inconclusive in each case. Calculations using MCSCF theory indicate that perfluorination of cyclobutyne will have a profound effect that stabilizes the cyclobutyne relative to rearrangement. However, experiments designed to generate and trap perfluorocyclobutyne (73) did not provide evidence for this compound. The development of new routes to strained organic compounds through the extension of known pericyclic reactions is described. These novel pericyclic reactions have been investigated by ab initio calculations and flash vacuum pyrolysis (FVP) experiments. MP4/6-31G*//MP2/6-31G* calculations support the possibility that strained six-membered rings can be prepared by replacement of a double bond with a triple bond in the prototypical Diels/Alder cycloaddition eq. (1) or electrocyclic reaction eq. (7). The novel cycloadditions explored involve the replacement of the traditional 1,3-butadiene component of (4+2) cycloadditions with vinylacetylene (19), 1,3-butadiyne (160), and strans-butadiene (233). Electrocyclic reactions of 1,2,3-cyclohexatriene (167), 1,2,4-cyclohexatriene (166), cyclohexen-3-yne (247), and 1,2,3,4-cyclohexatetraene (243) have been investigated. Experimental evidence is presented for the first example of intramolecular diyne + alkene and diyne + alkyne cycloadditions. The latter process is believed to give an o-benzyne intermediate, which is subsequently reduced to indan. This cycloaddition is unique in that it may be considered a cycloaromatization because an aromatic ring is directly generated. The mechanism and generality of diyne cycloadditions is examined

Solving Congestion and Safety Issues with Roundabouts

The Plainfield Road corridor is a major commuter route in Blue Ash, Ohio. This corridor is plagued by extreme peak hour congestion and intersection crash rates that are the largest in the city. The City intends to construct a series of roundabouts to address both congestion and safety issues. This presentation summarizes the evaluation process used to identify roundabouts as the preferred alternative to address both issues

Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al

Species-specific responses to atmospheric carbon dioxide and tropospheric ozone mediate changes in soil carbon

We repeatedly sampled the surface mineral soil (0–20 cm depth) in three northern temperate forest communities over an 11-year experimental fumigation to understand the effects of elevated carbon dioxide (CO 2 ) and/or elevated phyto-toxic ozone (O 3 ) on soil carbon (C). After 11 years, there was no significant main effect of CO 2 or O 3 on soil C. However, within the community containing only aspen ( Populus tremuloides Michx.), elevated CO 2 caused a significant decrease in soil C content. Together with the observations of increased litter inputs, this result strongly suggests accelerated decomposition under elevated CO 2. In addition, an initial reduction in the formation of new (fumigation-derived) soil C by O 3 under elevated CO 2 proved to be only a temporary effect, mirroring trends in fine root biomass. Our results contradict predictions of increased soil C under elevated CO 2 and decreased soil C under elevated O 3 and should be considered in models simulating the effects of Earth’s altered atmosphere.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78639/1/j.1461-0248.2009.01380.x.pd

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

Survival Data and Predictors of Functional Outcome an Average of 15 Years after the Fontan Procedure: The Pediatric Heart Network Fontan Cohort

ObjectiveMulticenter longitudinal outcome data for Fontan patients surviving into adulthood are lacking. The aim of this study was to better understand contemporary outcomes in Fontan survivors by collecting follow‐up data in a previously well‐characterized cohort.DesignBaseline data from the Fontan Cross‐Sectional Study (Fontan 1) were previously obtained in 546 Fontan survivors aged 11.9 ± 3.4 years. We assessed current transplant‐free survival status in all subjects 6.8 ± 0.4 years after the Fontan 1 study. Anatomic, clinical, and surgical data were collected along with socioeconomic status and access to health care.ResultsThirty subjects (5%) died or underwent transplantation since Fontan 1. Subjects with both an elevated (>21 pg/mL) brain natriuretic peptide and a low Child Health Questionnaire physical summary score (<44) measured at Fontan 1 were significantly more likely to die or undergo transplant than the remainder, with a hazard ratio of 6.2 (2.9–13.5). Among 516 Fontan survivors, 427 (83%) enrolled in this follow‐up study (Fontan 2) at 18.4 ± 3.4 years of age. Although mean scores on functional health status questionnaires were lower than the general population, individual scores were within the normal range in 78% and 88% of subjects for the Child Health Questionnaire physical and psychosocial summary score, and 97% and 91% for the SF‐36 physical and mental aggregate score, respectively. Since Fontan surgery, 119 (28%) had additional cardiac surgery; 55% of these (n = 66) in the interim between Fontan 1 and Fontan 2. A catheter intervention occurred in 242 (57%); 32% of these (n = 78) after Fontan 1. Arrhythmia requiring treatment developed in 118 (28%) after Fontan surgery; 58% of these (n = 68) since Fontan 1.ConclusionsWe found 95% interim transplant‐free survival for Fontan survivors over an average of 7 years of follow‐up. Continued longitudinal investigation into adulthood is necessary to better understand the determinants of long‐term outcomes and to improve functional health status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110738/1/chd12193.pd

Disgust Sensitivity and the Neurophysiology of Left- Right Political Orientations

Disgust has been described as the most primitive and central of emotions. Thus, it is not surprising that it shapes behaviors in a variety of organisms and in a variety of contexts—including homo sapien politics. People who believe they would be bothered by a range of hypothetical disgusting situations display an increased likelihood of displaying right-of-center rather than left-of-center political orientations. Given its primal nature and essential value in avoiding pathogens disgust likely has an effect even without registering in conscious beliefs. In this article, we demonstrate that individuals with marked involuntary physiological responses to disgusting images, such as of a man eating a large mouthful of writhing worms, are more likely to self-identify as conservative and, especially, to oppose gay marriage than are individuals with more muted physiological responses to the same images. This relationship holds even when controlling for the degree to which respondents believe themselves to be disgust sensitive and suggests that people’s physiological predispositions help to shape their political orientations

Origins of Spatial Working Memory Deficits in Schizophrenia: An Event-Related fMRI and Near-Infrared Spectroscopy Study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased ‘false memory’ errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased “false memory” errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research

Ecosystem nitrogen retention is regulated by plant community trait interactions with nutrient status in an alpine meadow

Biotic nitrogen (N) retention is an important ecosystem function in the context of ongoing land-use intensification, N deposition and global warming. However, a paucity of experimental evidence limits understanding of how different plant community components influence N retention in terrestrial ecosystems. In this investigation, we conducted a 15 N labelling experiment to test how plant community properties, including plant species richness/diversity, dominance and functional traits, influence plant N uptake and retention under different nutrient availabilities. A 3-year experiment examined the effects of adding N (10 g N m −2  year −1 ) and phosphorus (P) (5 g P m −2  year −1 ) to an alpine meadow on the Qinghai-Tibetan Plateau. Results show that 15 N retention increased with the addition of N and P; the addition of P produced the largest increase of 15 N retention in plant and soil N pools. Changes in soil nutrient conditions also facilitated different plant community controls on ecosystem N retention. Ecosystem 15 N retention was influenced by species richness and root biomass in the control plots; whereas the N addition treatment showed an important effect of community-weighted means (CWM) of specific leaf area, and plots with additional P recorded lower CWM of root nitrogen content (root N) and larger CWM root:shoot ratios as important determinants. Synthesis. Ecosystem N retention was influenced by conservative and exploitative plant species and/or their traits under N deficient and abundant conditions, respectively, whereas species richness and community plant biomass were most influential under middle condition. The discovery of an interaction between plant community traits and nutrient biogeochemistry as a mechanism for ecosystem N retention offers a means to predict how vegetation in alpine meadow ecosystems will respond to expected global change