255 research outputs found

    An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.

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    Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease

    CO Florida 2012, A MOVES-Based, Near-Road, Screening Model

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    Citizens in the United States are fortunate to have an excellent system of roadways and the affluence with which to afford automobiles. The flexibility of travel on demand for most allows for a variety of lifestyles, assists with conducting business, and contributes to the feeling of freedom that most citizens enjoy. The current vehicle fleet, which is primarily powered by internal combustion engines burning fossil fuels, does however contribute to the deterioration of air quality. This effect is particularly significant in metropolitan areas. Motor vehicle exhausts contain several combustion bi-products that pose harmful effects to the environment and human health, in particular. The United States Environmental Protection Agency (EPA) and the Federal Highway Administration (FHWA) have selected carbon monoxide (CO) as the air pollutant on which it has based its guidelines for assessing potential air quality impacts from roadway construction (EPA 1992). The design of roadway networks must consider traffic flows, Level of Service (LOS), cost, and National Ambient Air Quality Standards (NAAQS) requirements. In light of the environmental standards it is necessary to model to estimate potential future near-road concentrations of CO. This modeling has two aspects, first determining the rate of pollutant emissions, and second determining how those pollutants disperse near the road. Obtaining a precise, realistic estimate of the near-road CO concentrations under a wide variety of weather and traffic patterns is a potentially huge undertaking. With budgetary constraints in mind, the development of a screening model is appropriate. CO Florida 2012 (COFL2012) is such a model that uses conservative assumptions to predict worst-case, near-road CO concentration. Projects that pass a COFL2012 model run do not require additional air quality modeling. Projects that fail a COFL2012 model run, however, may still be viable, but will require additional, detailed modeling and possibly project modifications. COFL2012 uses tables of emission factors (EFs) that were derived from numerous runs of the EPA\u27s MOtor Vehicle Emission Simulator (MOVES2010a), which is indicated as the preferred model for near-road modeling of CO.(EPA 2009) COFL2012 then inputs the EFs, along with assumed link configurations, geographical assumptions, and user-inputted traffic information into input files that are run through CAL3QHC Version 2.0 (CAL3QHC2), the EPA\u27s approved near-road dispersion model (EPA 1995). COFL2012 is a brand new Florida CO screening model, written from scratch. This author has written the computer code for COFL2012 in Visual Basic, using Microsoft Visual Studios 2010. Visual Studios utilizes the .net Framework 4. COFL2012 is easy to learn, quick to operate, and has been written to allow for future updates simply and easily, whenever the EPA releases updates to the databases that feed MOVES2010a

    Profile, organizational involvement and perception of leadership responsibility among selected members of boards of directors

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    The study addressed whether volunteers would stay within the same organization in order to rise to its highest level of leadership; their motivation and commitment to board activity, and their perception of the characteristics of effective leadership. The volume of literature covering the administrative volunteer and the non-profit voluntary agency is comparatively sparse. Few empirical studies have focused on the complexities of board members and the agency to which they commit themselves. However, many authors reflect on the ubiquitous nature of voluntary action. The respondents were men and women who have been or are currently serving on a board of directors of a United Way agency. They either live or work within the San Fernando Valley, a part of metropolitan Los Angeles. The data collected was categorized into five segments: profile of respondents, motivation for voluntary efforts, leadership involvement, skills and characteristics of board responsibility, and characteristics of an ideal type of board assignment. The data indicates a substantial and enduring level of leadership involvement by the respondents. The majority of the volunteers stayed primarily within the same organization for many years although some served on more than one board. They represented a homogenous, well-established community leadership group. The majority of volunteers were motivated by feeling a commitment to "help others," "doing something to benefit the community" and/or "personal satisfaction." Ideal voluntary board assignments centered around tasks motivated by a personal commitment. Effective board leadership was identified by setting agency and board objectives, making management and program decisions, and having a sound knowledge of the organization.California State University, Northridge. Department of Recreation and Leisure Studies.Includes bibliographical references (pages 70-72

    Facebook: Use, personality, and well-being

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    As our society moves toward greater integration with technology we are seeing more social interactions conducted through electronic means. An understanding of how individual factors affect use of communication mediated by social networking platforms, and the role of this communication in our global social interactions, is important in assessing the impact of our changing options for social contact. Within the present study, a total of 270 participants were recruited through links posted on the social networking site Facebook. The age of participants ranged from 18 to 67, with a mean age of 25.6. The majority of participants reported residing in the United States (n=244), identified as female (n=189), White (n=222) and as students (n=196, ranging from high school to graduate school). Interactions were found between personality traits and content the user uploads to the site, motivations for using Facebook, and consumption of content on the site. Additionally associations between well-being and receiving directed communication from other users were found

    The Coptic Wizard's Hoard

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    This is the publisher's version, also available electronically from http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=7824067&fileId=S0017816000030224.Within the large collection of ancient manuscripts at the University of Michigan there is a group of Coptic papyri which appears to have been a hoard or library of ancient magical texts. Produced by five copyists sometime in the fourth through seventh centuries and originating from a now unknown location in Egypt, the collection was brought to the British Museum by Sir E. A. Wallis Budge in February 1921 for restoration by C. T. Lamacraft; in August of that year, it underwent philological examination by the Coptic lexicographer Walter E. Crum, and was later forwarded to the University of Michigan

    miR-125b Promotes Early Germ Layer Specification through Lin28/let-7d and Preferential Differentiation of Mesoderm in Human Embryonic Stem Cells

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    Unlike other essential organs, the heart does not undergo tissue repair following injury. Human embryonic stem cells (hESCs) grow indefinitely in culture while maintaining the ability to differentiate into many tissues of the body. As such, they provide a unique opportunity to explore the mechanisms that control human tissue development, as well as treat diseases characterized by tissue loss, including heart failure. MicroRNAs are small, non-coding RNAs that are known to play critical roles in the regulation of gene expression. We profiled the expression of microRNAs during hESC differentiation into myocardial precursors and cardiomyocytes (CMs), and determined clusters of human microRNAs that are specifically regulated during this process. We determined that miR-125b overexpression results in upregulation of the early cardiac transcription factors, GATA4 and Nkx2-5, and accelerated progression of hESC-derived myocardial precursors to an embryonic CM phenotype. We used an in silico approach to identify Lin28 as a target of miR-125b, and validated this interaction using miR-125b knockdown. Anti-miR-125b inhibitor experiments also showed that miR-125b controls the expression of miRNA let-7d, likely through the negative regulatory effects of Lin28 on let-7. We then determined that miR-125b overexpression inhibits the expression of Nanog and Oct4 and promotes the onset of Brachyury expression, suggesting that miR-125b controls the early events of human CM differentiation by inhibiting hESC pluripotency and promoting mesodermal differentiation. These studies identified miR-125b as an important regulator of hESC differentiation in general, and the development of hESC-derived mesoderm and cardiac muscle in particular. Manipulation of miR-125b-mediated pathways may provide a novel approach to directing the differentiation of hESC-derived CMs for cell therapy applications
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