Predicting preferential DNA vector insertion sites: implications for functional genomics and gene therapy

Viral and transposon vectors have been employed in gene therapy as well as functional genomics studies. However, the goals of gene therapy and functional genomics are entirely different; gene therapists hope to avoid altering endogenous gene expression (especially the activation of oncogenes), whereas geneticists do want to alter expression of chromosomal genes. The odds of either outcome depend on a vector's preference to integrate into genes or control regions, and these preferences vary between vectors. Here we discuss the relative strengths of DNA vectors over viral vectors, and review methods to overcome barriers to delivery inherent to DNA vectors. We also review the tendencies of several classes of retroviral and transposon vectors to target DNA sequences, genes, and genetic elements with respect to the balance between insertion preferences and oncogenic selection. Theoretically, knowing the variables that affect integration for various vectors will allow researchers to choose the vector with the most utility for their specific purposes. The three principle benefits from elucidating factors that affect preferences in integration are as follows: in gene therapy, it allows assessment of the overall risks for activating an oncogene or inactivating a tumor suppressor gene that could lead to severe adverse effects years after treatment; in genomic studies, it allows one to discern random from selected integration events; and in gene therapy as well as functional genomics, it facilitates design of vectors that are better targeted to specific sequences, which would be a significant advance in the art of transgenesis

Teaching Basic Counseling Skills to Aspiring School Leaders: Active Listening Skills as Critical Components of Team Building and Collaboration

The preparation of school leaders in educational leadership programs provides multiple challenges in terms of a set course of study with discrete skills for the leader. Programs in educational leadership have been criticized for curricular disarray (Levine, 2005). Deficiencies cited by an American Enterprise Institute study of 31 educational leadership programs found that a small percentage of instruction in those programs focused on issues such as data analysis, public relations, marketing, and parent and school board relations (Hess & Kelly, 2005). A Southern Regional Education Board (SREB) study of educational leadership programs found that the majority of universities “fall short of implementing the conditions necessary to create high quality programs centered on preparing principals who can lead improvement in student achievement” (Southern Regional Education Board, 2005, p. 8). A move away from curricula organized along those lines began in the 1980s with a new emphasis on skills required of an instructional leader (Hallinger, 2003; Jason, 2001)

The Neural Representation Of Duration In Event Concepts

Little is known about the neural basis of temporal concepts. Some have suggested that temporal concepts are grounded in spatial or temporal processes. Here we aimed to examine the representation of duration of event concepts, and compare them with judgments of object size, which may entail spatial processing. A 2x2 block design used event and object nouns as stimuli that were presented during functional imaging. Participants made judgments about event duration, object size, and event and object valence. In addition to whole-brain analyses, we examined activations in areas known to be involved in temporal processing and spatial processing. Knowledge of events compared to objects activated a distributed network with large clusters in bilateral angular gyri, precuneus, middle temporal lobules and prefrontal cortices in whole-brain analyses. The whole-brain analyses of duration minus valence revealed a right hemispheric preference for processing of semantic duration information compared to valence tasks. Peak activation of clusters for duration were located in the right dorsomedial prefrontal cortex, precuneus, lingual gyrus, SMG, left middle MTG/ITG, parahippocampal gyrus and bilateral angular gyri. ROI analyses of angular gyri suggested the processing of semantic information of duration occurred mainly the right AG and left PGp. ROI analyses of temporal perception areas suggested a role of the right SMG in the representation of duration. Additionally, temporal ROIs suggested that the right pSTS and left SMG were involved in event processing relative to objects. IPS ROI revealed that the right middle IPS was activated for event duration minus event valence and object size minus object valance. Additionally, PPA ROI revealed that event duration compared to event valence and object size compared to object valence activated the PPA. Thus, we found that event concepts were supported by bilateral inferior parietal and anterior and middle temporal cortex, as well as precuneus and posterior cingulate. This is consistent with the role of AG in integrating temporal sequences. Conceptual duration processing is grounded in both temporal perception (right SMG) and space (IPS and PPA)

Medicine and surgery residents\u27 perspectives on the impact of COVID-19 on graduate medical education.

The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisis-related stressors on residents\u27 professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after \u3e6 weeks of a modified schedule. The primary outcome was to determine which factors or resident characteristics were related to stress during the pandemic. Our secondary goals were to examine which resident characteristics were related to survey responses. Data were analyzed with regression analyses. Ninety-six of 205 residents completed the survey (47% response rate). For our primary outcome, anxiety about PP

Masters of the Universe: Bid Rigging by Private Equity Firms in Multibillion Dollar LBOs

In the first successful case of its kind, a class action alleging widespread collusion in the market for leveraged buyouts, some of the world’s largest private equity firms settled Dahl v. Bain Capital Partners, LLC for $590.5 million. The case was unique not only for its size and the fact that it involved complex financial transactions instead of a typical commodity, but also because the claimants used auction theory to demonstrate both the “plus” factors required to prove antitrust injury and the resulting damages. Economic analyses show that the cost to shareholders of collusion in the eight litigated multi-billion dollar leveraged buyout transactions approached$12 billion. The use of empirical economic analysis in antitrust litigation is now de rigueur. Courts expect it, and litigants have an array of econometricians available who understand both how to work with data and antitrust doctrine. In “ordinary” commodities price fixing cases, plaintiffs and defendants are expected to engage experts who gather transaction data and apply regression theory and other economic analyses to contest whether it is possible to demonstrate injury, impact, and damages. Dahl was not an ordinary case in that it involved neither a commodity nor a sellers’ cartel. Instead, it involved a buyers’ cartel which, Plaintiffs alleged, conspired to drive down the price of a number of unique, large LBOs during the mid-2000s. Additionally, the case was notable because of the Plaintiffs’ decision to use the auction theory to demonstrate the existence of antitrust violations and the extent of damage

Generalised Geometry for M-Theory

Generalised geometry studies structures on a d-dimensional manifold with a metric and 2-form gauge field on which there is a natural action of the group SO(d,d). This is generalised to d-dimensional manifolds with a metric and 3-form gauge field on which there is a natural action of the group $E_{d}$. This provides a framework for the discussion of M-theory solutions with flux. A different generalisation is to d-dimensional manifolds with a metric, 2-form gauge field and a set of p-forms for $p$ either odd or even on which there is a natural action of the group $E_{d+1}$. This is useful for type IIA or IIB string solutions with flux. Further generalisations give extended tangent bundles and extended spin bundles relevant for non-geometric backgrounds. Special structures that arise for supersymmetric backgrounds are discussed.Comment: 31 page

Intelligence within BAOR and NATO's Northern Army Group

During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict