Cryptic post-transition state bifurcations that reduce the efficiency of lactone-forming Rh-carbenoid C-H insertions.

Byproducts of chemical reactions are generally thought to result from the competition between two reaction pathways, each with its own rate-determining transition state structure. We show here, however, that pathways with a single transition state structure followed by a post-transition state bifurcation may also be a source of undesired products, especially those whose appearance is unexpected. The viability of this scenario for intramolecular C-H insertion reactions affording β-lactones via Rh-carbenoid intermediates is assessed through quantum chemical calculations on potential energy surfaces and quasi-classical molecular dynamics simulations. It appears that, in these cases, the rhodium catalyst is to blame for the accessibility of a second, unintended, pathway following the transition state structure for β-lactone formation that leads to fragmentation to a ketene and carbonyl compound. If an unexpected product is formed via a post-transition state bifurcation, conventional strategies for suppressing its formation are unlikely to succeed. Guidelines for recognizing the presence of a post-transition state bifurcation are described here, along with hints at means for controlling product distributions

Monitoring Self & World: A Novel Network Model of Hallucinations in Schizophrenia

Schizophrenia (Sz) is a psychotic disorder characterized by multifaceted symptoms including hallucinations (e.g. vivid perceptions that occur in the absence of external stimuli). Auditory hallucinations are the most common type of hallucination in Sz; roughly 70 percent of Sz patients report hearing voices specifically (e.g. auditory verbal hallucinations). Prior functional magnetic resonance imaging (fMRI) studies have provided initial insights into the neural mechanisms underlying hallucinations, implicating an anatomically-distributed network of cortical (sensory, insular, and inferior frontal cortex) and subcortical (hippocampal, striatal) regions. Yet, it remains unclear how this distributed network gives rise to hallucinations impacting different sensory modalities. The insular cortex is a central hub of a larger functional network called the salience network. By regulating default-mode network activity (associated with internally-directed thought), and fronto-parietal network activity (associated with externally-directed attention), the salience network is able to orient our attention to the most pressing matters (e.g. bodily pain, environmental threats, etc.). Abnormal salience monitoring is thought to underlie Sz symptoms; improper monitoring of salient internal events (e.g. auditory-verbal imagery, visual images) plausibly generates hallucinations, but no prior study has directly tested this hypothesis by exploring how sensory networks interact with the salience network in the context of hallucinations in Sz. This dissertation project combined exploratory and hypothesis-driven approaches to delineate functional neural markers of Sz symptoms. The first analysis explored the relationship between Sz symptom expression and altered functional communication between salience and default-mode networks. The second analysis explored fMRI signal fluctuations associated with modality-dependent (e.g. auditory, visual) hallucinations. The final analysis tested the hypothesis that abnormal functional communication between salience and sensory (e.g. auditory, visual) networks underlies hallucinations in Sz. The results suggest that there are three key players in the generation of auditory hallucinations in Sz: auditory cortex, hippocampus, and salience network. A novel functional network model of auditory hallucinations is proposed to account for these findings

A Transcendental Phenomenological Study of Mental Health Symptoms and Awareness in the College Student Population

The purpose of this transcendental phenomenological study was to understand mental health concerns and the services provided within the college population located at an on-ground campus in the United States. The theories guiding this study were Schlossberg’s transition theory and self-efficacy theory, which play a major role in understanding the concerns and heightened symptoms students faced when transitioning into the college setting. The transcendental phenomenological study focused on gathering data from sophomore students enrolled at Rose College who have recently faced the transition from high school or undergraduate settings. The setting took place virtually due to restrictions and limitations of COVID-19. Student samples were collected by reaching out to students via an institutional research marketing platform where this researcher’s marketing flyer was posted throughout Liberty University’s campus. In addition, two rounds of marking e-mails were sent to students to request participation from sophomore students who endorsed the criteria for experiencing various mental health symptoms while enrolled in the higher education setting, such as: depression, anxiety, and general adjustment symptoms. The data collection process consisted of individual interviews with (N= 10) student participants, a student artifact collection questionnaire, a student letter to self, and a final focus group that allowed a space for all students willing to share their lived experiences regarding their transition into higher education. Research findings indicated students who utilized various support systems and artifacts as an added source of coping, benefitted from successfully finishing their first year of college

Duty, death and the Republic: The career of Maurice Papon from Vichy France to the Algerian War.

This thesis examines the career of Maurice Papon from his appointment as secretary-general of the prefecture of the Gironde in 1942, through his terms as a prefect in Morocco and Algeria, to the end of the Algerian War in 1962 when he was prefect of police in Paris. Throughout this period, Papon's career was marked by controversy: in the Gironde on account of his involvement in the detaining and deportation of Jews, which led to his conviction in 1998 for crimes against humanity; in North Africa on account of the use of torture and summary execution by units of the army within his jurisdiction; and in Paris on account of the harsh methods used by the police to suppress the Algerian nationalist movement. Papon, who was extensively interviewed for the thesis, regarded himself as a loyal civil servant who was simply doing his duty. The thesis carefully examines his relations to the State, his actions and the circumstances in which he carried them out. In doing so, it presents an historical portrait of Papon and the State which employed him, and an assessment of what both understood by the concept of a civil servant's duty to obey

Solidarity: For Sale? The Social Dimension of the New European Economic Governances. Europe in Dialogue 2012/01

The Europeans can be proud as they look back on fifty years of peaceful integration. Nowadays many people in the world see the European Union as a model of how states and their citizens can work together in peace and in freedom. However, this achievement does not automatically mean that the EU has the ability to deal with the problems of the future in a rapidly changing world. For this reason the European Union needs to keep developing its unity in diversity in a dynamic way, be it with regard to energy issues, the euro, climate change or new types of conflict. Self-assertion and solidarity are the fundamental concepts which will shape the forthcoming discourse. "Europe in Dialogue" wishes to make a contribution to this open debate. The analyses in this series subject political concepts, processes and institutions to critical scrutiny and suggest ways of reforming internal and external European policymaking so that it is fit for the future. However, "Europe in Dialogue" is not merely trying to encourage an intra- European debate, and makes a point of including authors from non-EU states. Looking at an issue from a different angle or from a distance often helps to facilitate the crucial change of perspective which in turn makes it possible to continue to develop Europe in a meaningful way and to engage in a critical and yet courteous discourse with other civilizations and continents

Interactive molecular dynamics in virtual reality for accurate flexible protein-ligand docking

Simulating drug binding and unbinding is a challenge, as the rugged energy landscapes that separate bound and unbound states require extensive sampling that consumes significant computational resources. Here, we describe the use of interactive molecular dynamics in virtual reality (iMD-VR) as an accurate low-cost strategy for flexible protein-ligand docking. We outline an experimental protocol which enables expert iMD-VR users to guide ligands into and out of the binding pockets of trypsin, neuraminidase, and HIV-1 protease, and recreate their respective crystallographic protein-ligand binding poses within 5 - 10 minutes. Following a brief training phase, our studies shown that iMD-VR novices were able to generate unbinding and rebinding pathways on similar timescales as iMD-VR experts, with the majority able to recover binding poses within 2.15 Angstrom RMSD of the crystallographic binding pose. These results indicate that iMD-VR affords sufficient control for users to carry out the detailed atomic manipulations required to dock flexible ligands into dynamic enzyme active sites and recover crystallographic poses, offering an interesting new approach for simulating drug docking and generating binding hypotheses.Comment: PLOS ON

Sur un théorème de Poncelet et sa généralisation par M. Horvarth

Most chemical transformations (reactions or conformational changes) that are of interest to researchers have many degrees of freedom, usually too many to visualize without reducing the dimensionality of the system to include only the most important atomic motions. In this article, we describe a method of using Principal Component Analysis (PCA) for analyzing a series of molecular geometries (e.g., a reaction pathway or molecular dynamics trajectory) and determining the reduced dimensional space that captures the most structural variance in the fewest dimensions. The software written to carry out this method is called PathReducer, which permits (1) visualizing the geometries in a reduced dimensional space, (2) determining the axes that make up the reduced dimensional space, and (3) projecting the series of geometries into the low-dimensional space for visualization. We investigated two options to represent molecular structures within PathReducer: aligned Cartesian coordinates and matrices of interatomic distances. We found that interatomic distance matrices better captured non-linear motions in a smaller number of dimensions. To demonstrate the utility of PathReducer, we have carried out a number of applications where we have projected molecular dynamics trajectories into a reduced dimensional space defined by an intrinsic reaction coordinate. The visualizations provided by this analysis show that dynamic paths can differ greatly from the minimum energy pathway on a potential energy surface. Viewing intrinsic reaction coordinates and trajectories in this way provides a quick way to gather qualitative information about the pathways trajectories take relative to a minimum energy path. Given that the outputs from PCA are linear combinations of the input molecular structure coordinates (i.e., Cartesian coordinates or interatomic distances), they can be easily transferred to other types of calculations that require the definition of a reduced dimensional space (e.g., biased molecular dynamics simulations)

Good practice in food-related neuroimaging

The use of neuroimaging tools, especially functional magnetic resonance imaging, in nutritional research has increased substantially over the past 2 decades. Neuroimaging is a research tool with great potential impact on the field of nutrition, but to achieve that potential, appropriate use of techniques and interpretation of neuroimaging results is necessary. In this article, we present guidelines for good methodological practice in functional magnetic resonance imaging studies and flag specific limitations in the hope of helping researchers to make the most of neuroimaging tools and avoid potential pitfalls. We highlight specific considerations for food-related studies, such as how to adjust statistically for common confounders, like, for example, hunger state, menstrual phase, and BMI, as well as how to optimally match different types of food stimuli. Finally, we summarize current research needs and future directions, such as the use of prospective designs and more realistic paradigms for studying eating behavior