La Importancia del diseñador instruccional en el diseño de cursos en línea

El número de ofrecimientos de educación a distancia (en la modalidad en línea) ha aumentando considerablemente en los últimos años. Este aumento requiere desarrollar estándares para la creación, aplicación e implementación de la enseñanza en línea. Para lograr este objetivo se requiere la participación de un diseñador instruccional con rol de consultor, diseñador, arquitecto y, en ocasiones, como consejero

Search for axion-like particles using a variable baseline photon regeneration technique

We report the first results of the GammeV experiment, a search for milli-eV mass particles with axion-like couplings to two photons. The search is performed using a "light shining through a wall" technique where incident photons oscillate into new weakly interacting particles that are able to pass through the wall and subsequently regenerate back into detectable photons. The oscillation baseline of the apparatus is variable, thus allowing probes of different values of particle mass. We find no excess of events above background and are able to constrain the two-photon couplings of possible new scalar (pseudoscalar) particles to be less than 3.1x10^{-7} GeV^{-1} (3.5x10^{-7} GeV^{-1}) in the limit of massless particles.Comment: 5 pages, 4 figures. This is the version accepted by PRL and includes updated limit

Physico-chemical foundations underpinning microarray and next-generation sequencing experiments

Hybridization of nucleic acids on solid surfaces is a key process involved in high-throughput technologies such as microarrays and, in some cases, next-generation sequencing (NGS). A physical understanding of the hybridization process helps to determine the accuracy of these technologies. The goal of a widespread research program is to develop reliable transformations between the raw signals reported by the technologies and individual molecular concentrations from an ensemble of nucleic acids. This research has inputs from many areas, from bioinformatics and biostatistics, to theoretical and experimental biochemistry and biophysics, to computer simulations. A group of leading researchers met in Ploen Germany in 2011 to discuss present knowledge and limitations of our physico-chemical understanding of high-throughput nucleic acid technologies. This meeting inspired us to write this summary, which provides an overview of the state-of-the-art approaches based on physico-chemical foundation to modeling of the nucleic acids hybridization process on solid surfaces. In addition, practical application of current knowledge is emphasized

The PAK-U.S. alliance in the fight against terrorism: a cost-benefit analysis

The cost-benefit equation of the Pak-U.S. alliance, in the fight against terrorism, reflects a direct correlation between the fluctuating patterns of U.S. assistance and their direct and indirect implications for Pakistan. While the U.S. strives to achieve a better return on its investment through military-oriented support, Pakistan seeks to adopt an approach that suits both the U.S. and its own domestic and regional interests. This research traces the trend of Pak-U.S. relations, highlights the impact of the fluctuating U.S. aid in shaping perceptions, and provides a game theoretical analysis on the issue. Besides highlighting measures to achieve cost effectiveness through micro alliances, decentralization, accountability, and transparency in fund management, the study supports development of entrepreneurial culture and micro-alliances in Pakistan. More importantly, it provides an in-depth analysis of the military and population-centric approaches and their associated costs and benefits for the two countries. The research concludes by suggesting a more population-centric U.S. approach towards Pakistan to achieve a better return on investment besides laying foundation for a long-term strategic alliance. It suggests future research on the prospects and methodology of achieving a long-term partnership between the two nations.http://archive.org/details/thepakuslliancei1094510631Pakistan Air Force autho

Pre-processing and differential expression analysis of Agilent microRNA arrays using the AgiMicroRna Bioconductor library

<p>Abstract</p> <p>Background</p> <p>The main research tool for identifying microRNAs involved in specific cellular processes is gene expression profiling using microarray technology. Agilent is one of the major producers of microRNA arrays, and microarray data are commonly analyzed by using R and the functions and packages collected in the Bioconductor project. However, an analytical package that integrates the specific characteristics of microRNA Agilent arrays has been lacking.</p> <p>Results</p> <p>This report presents the new bioinformatic tool <it>AgiMicroRNA </it>for the pre-processing and differential expression analysis of Agilent microRNA array data. The software is implemented in the open-source statistical scripting language R and is integrated in the Bioconductor project (<url>http://www.bioconductor.org</url>) under the GPL license. For the pre-processing of the microRNA signal, <it>AgiMicroRNA </it>incorporates the <it>robust multiarray average algorithm</it>, a method that produces a summary measure of the microRNA expression using a linear model that takes into account the probe affinity effect. To obtain a normalized microRNA signal useful for the statistical analysis, <it>AgiMicroRna </it>offers the possibility of employing either the processed signal estimated by the <it>robust multiarray average algorithm </it>or the processed signal produced by the Agilent image analysis software. The <it>AgiMicroRNA </it>package also incorporates different graphical utilities to assess the quality of the data. <it>AgiMicroRna </it>uses the linear model features implemented in the <it>limma </it>package to assess the differential expression between different experimental conditions and provides links to the <it>miRBase </it>for those microRNAs that have been declared as significant in the statistical analysis.</p> <p>Conclusions</p> <p><it>AgiMicroRna </it>is a rational collection of Bioconductor functions that have been wrapped into specific functions in order to ease and systematize the pre-processing and statistical analysis of Agilent microRNA data. The development of this package contributes to the Bioconductor project filling the gap in microRNA array data analysis.</p

Performance evaluation of commercial miRNA expression array platforms

<p>Abstract</p> <p>Background</p> <p>microRNAs (miRNA) are short, endogenous transcripts that negatively regulate the expression of specific mRNA targets. The relative abundance of miRNAs is linked to function <it>in vivo </it>and miRNA expression patterns are potentially useful signatures for the development of diagnostic, prognostic and therapeutic biomarkers.</p> <p>Finding</p> <p>We compared the performance characteristics of four commercial miRNA array technologies and found that all platforms performed well in separate measures of performance.</p> <p>Conclusions</p> <p>The Ambion and Agilent platforms were more accurate, whereas the Illumina and Exiqon platforms were more specific. Furthermore, the data analysis approach had a large impact on the performance, predominantly by improving precision.</p

Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment

Distinct Pools of β-Amyloid in Alzheimer Disease-Affected Brain: A Clinicopathologic Study

Objective: To determine whether β-amyloid (Aβ) peptides segregated into distinct biochemical compartments would differentially correlate with clinical severity of Alzheimer disease (AD). Design: Clinicopathologic correlation study. Participants: Twenty-seven patients from a longitudinal study of AD and 13 age- and sex-matched controls without a known history of cognitive impairment or dementia were included in this study. Interventions: Temporal and cingulate neocortex were processed using a 4-step extraction, yielding biochemical fractions that are hypothesized to be enriched with proteins from distinct anatomical compartments: TRIS (extracellular soluble), Triton (intracellular soluble), sodium dodecyl sulfate (SDS) (membrane associated), and formic acid (extracellular insoluble). Levels of Aβ₄₀ and Aβ₄₂ were quantified in each biochemical compartment by enzyme-linked immunosorbent assay. Results: The Aβ₄₂ level in all biochemical compartments was significantly elevated in patients with AD vs controls (P < .01). The Aβ₄₀ levels in the TRIS and formic acid fractions were elevated in patients with AD (temporal, P < .01; cingulate, P = .03); however, Triton and SDS Aβ₄₀ levels were similar in patients with AD and in controls. Functional impairment proximal to death correlated with Triton Aβ₄₂ (r = 0.48, P = .02) and SDS Aβ₄₂ (r = 0.41, P = .04) in the temporal cortex. Faster cognitive decline was associated with elevated temporal SDS Aβ₄₂ levels (P < .001), whereas slower decline was associated with elevated cingulate formic acid Aβ₄₂ and SDS Aβ₄₂ levels (P = .02 and P = .01, respectively). Conclusion: Intracellular and membrane-associated Aβ, especially Aβ₄₂ in the temporal neocortex, may be more closely related to AD symptoms than other measured Aβ species

Lineage-based identification of cellular states and expression programs

We present a method, LineageProgram, that uses the developmental lineage relationship of observed gene expression measurements to improve the learning of developmentally relevant cellular states and expression programs. We find that incorporating lineage information allows us to significantly improve both the predictive power and interpretability of expression programs that are derived from expression measurements from in vitro differentiation experiments. The lineage tree of a differentiation experiment is a tree graph whose nodes describe all of the unique expression states in the input expression measurements, and edges describe the experimental perturbations applied to cells. Our method, LineageProgram, is based on a log-linear model with parameters that reflect changes along the lineage tree. Regularization with L1 that based methods controls the parameters in three distinct ways: the number of genes change between two cellular states, the number of unique cellular states, and the number of underlying factors responsible for changes in cell state. The model is estimated with proximal operators to quickly discover a small number of key cell states and gene sets. Comparisons with existing factorization, techniques, such as singular value decomposition and non-negative matrix factorization show that our method provides higher predictive power in held, out tests while inducing sparse and biologically relevant gene sets.National Institutes of Health (U.S.) (P01-NS055923)National Institutes of Health (U.S.) (1-UL1-RR024920