Mechanism for generation of left isomerism in Ccdc40 mutant embryos

Leftward fluid flow in the mouse node is generated by cilia and is critical for initiating asymmetry of the left-right axis. Coiled-coil domain containing-40 (Ccdc40) plays an evolutionarily conserved role in the assembly of motile cilia and establishment of the left-right axis. Approximately one-third of Ccdc40lnks mutant embryos display situs defects and here we investigate the underlying mechanism. Ccdc40lnks mutants show delayed induction of markers of the left-lateral plate mesoderm (L-LPM) including Lefty1, Lefty2 and Nodal. Consistent with defective cilia motility compromising fluid flow across the node, initiation of asymmetric perinodal Cerberus like-2 (Cerl2) expression is delayed and then randomized. This is followed by delayed and then randomized asymmetric Nodal expression around the node. We propose a model to explain how left isomerism arises in a proportion of Ccdc40lnks mutants. We postulate that with defective motile cilia, Cerl2 expression remains symmetric and Nodal is antagonized equally on both sides of the node. This effectively reduces Nodal activation bilaterally, leading to reduced and delayed activation of Nodal and its antagonists in the LPM. This model is further supported by the failure to establish Nodal expression in the left-LPM with reduced Nodal gene dosage in Ccdc40lnks/lnks;NodalLacZ/+ mutants causing a predominance of right not left isomerism. Together these results suggest a model where cilia generated fluid flow in the node functions to ensure robust Nodal activation and a timely left-sided developmental program in the LPM

Profiling a New Breed of Learning Executive

In May 2005, The Graduate School of Education and The Wharton School of the University of Pennsylvania held a summit of approximately 40 chief learning officers from Fortune 500 companies and other large organizations. Polling the group about their backgrounds uncovered what is mirrored in this article: people took many paths to become CLOs, but there is no clear credentialing track. While chief learning officers are responsible for the professional educational development of millions of people, there is no school with a curriculum to prepare this group of powerful and influential individuals. Penn’s business and education schools are joining forces to develop a credentialing program for CLOs. Targeting newly appointed CLOs, experienced CLOs, and those aspiring to the position, the modular program will offer executive education and applied research opportunities—and may ultimately lead to a doctoral degree in education. Focusing on business strategy and management, leadership, instructional design, technological integration, and problem solving, the program defines the path for a potential CLO, supports and develops the current CLO, and increases the public’s understanding of this role

Immunocytochemical localization of the neuron-specific form of the c-src gene product, pp60c-src(+), in rat brain

Neurons express high levels of a variant form of the c-src gene product, denoted pp60c-src(+), which contains a 6 amino acid insert in the amino-terminal half of the c-src protein. We have determined the localization of pp60c-src(+) in neurons using an affinity-purified anti-peptide antibody, referred to as affi-SB12, that exclusively recognizes this neuron-specific form of the c-src gene product. Using affi-SB12, we examined the distribution of pp60c-src(+) by immunoperoxidase staining of sections through adult rat brains, pp60c-src(+) was widely distributed in rat brain and appeared to be differentially expressed in subpopulations of neurons. The majority of immunoreactive neurons was found in the mesencephalon, cerebellum, pons, and medulla. Telencephalic structures that contained substantial populations of pp60c-src(+)-immunoreactive neurons included layer V of the cerebral cortex and the ventral pallidum. Within individual neurons, pp60c-src(+) immunoreactivity was localized to the cell soma and dendritic processes, while labeling of axons and nerve terminals (puncta) was not as readily detected. Dense accumulations of immunoreactive axons were rare, being most prominent in portions of the inferior and superior olive, and in the spinal trigeminal nucleus. While the regional distribution of pp60c-src(+) immunoreactivity does not correlate with any specific neuronal cell type or first messenger system, this unique pattern of expression of pp60c-src(+) suggests the existence of a previously uncharacterized functional organization within the brain. Furthermore, the localization of this neuron-specific tyrosine kinase in functionally important areas of the nerve cell, namely, dendritic processes, axons, and nerve terminals, suggests that pp60c-src(+) may regulate pleiotropic functions in specific classes of neurons in the adult central nervous system

Comparison and Uncertainty Quantification of Two-Fluid Models forBubbly Flows with NEPTUNE_CFD and STAR-CCM+

International audienceThe nuclear industry is interested in better understanding the behavior of turbulent boiling flowsand in using modern computational tools for the design and analysis of advanced fuels and reactorsand for simulation and study of mitigation strategies in accident scenarios. Such interests serve asdrivers for the advancement of the 3-dimensional multiphase Computational Fluid Dynamicsapproach. A pair of parallel efforts have been underway in Europe and in the United States, theNEPTUNE and CASL programs respectively, that aim at delivering advanced simulation tools thatwill enable improved safety and economy of operations of the reactor fleet. Results from acollaboration between these two efforts, aimed at advancing the understanding of multiphaseclosures for pressurized water reactor (PWR) application, are presented. Particular attention is paidto the assessment and analysis of the different physical models implemented in NEPTUNE_CFDand STAR-CCM+ codes used in the NEPTUNE and the CASL programs respectively, forapplication to turbulent two-phase bubbly flows. The experiments conducted by Liu and Bankoff(Liu, 1989; Liu and Bankoff 1993a and b) are selected for benchmarking, and predictions from thetwo codes are presented for a broad range of flow conditions and with void fractions varyingbetween 0 and 50percent. Comparison of the CFD simulations and experimental measurements revealsthat a similar level of accuracy is achieved in the two codes. The differences in both sets of closuremodels are analyzed, and their capability to capture the main features of the flow over a wide rangeof experimental conditions are discussed. This analysis paves the way for future improvements ofexisting two-fluid models. The benchmarks are further leveraged for a systematic study of thepropagation of model uncertainties. This provides insights into mechanisms that lead to complexinteractions between individual closures (of the different phenomena) in the multiphase CFDapproach. As such, it is seen that the multi-CFD-code approach and the principled uncertaintyquantification approach are both of great value in assessing the limitations and the level of maturityof multiphase hydrodynamic closures

Transcript of The Dory Derby Accident

This story is an excerpt from a longer interview that was collected as part of the Launching through the Surf: The Dory Fleet of Pacific City project. In this story, Don Grotjohn recounts an accident that occurred during a Dory Derby competition

Establishing position papers by the WSES

A position paper (PP) should establish a unified voice in areas where controversy occurs based upon multiple practices and/or therapeutic choices. Typically, a position paper should elucidate the knowledge gap, followed by an evidence-based review of options, leading to an "endorsed position." A position paper should represent more than the opinion or consensus of the authors but should present current opinions and practices supported by the World Society of Emergency Surgery (WSES). Accordingly, position papers should require the approval of an expert group of WSES and in parallel be presented at an annual meeting prior to submission for publication. It is important that a unified approach for drafting of position papers be established and endorsed by WSES in order to establish credibility and prevent misunderstandings during a smooth transition to publication. The purpose of this article is to suggest a uniform process for the development of WSES guidelines.Peer reviewe