It is impossible to control another person`s motivation. But much of the instructor`s job involves stimulating learner motivation, and learning environments should ideally be designed toward this ...goal. Motivational Design for Learning and Performance introduces readers to the core concepts of motivation and motivational design and applies this knowledge to the design process in a systematic step-by-step format. The ARCS model-theoretically robust, rooted in best practices, and adaptable to a variety of practical uses-forms the basis of this problem-solving approach. Separate chapters cover each component of the model-attention, relevance, confidence, and satisfaction-and offer strategies for promoting each one in learners. From there, the motivational design process is explained in detail, supplemented by real-world examples and ready-to-use worksheets. The methods are applied to traditional and alternative settings, including gifted classes, elementary grades, self-directed learning, and corporate training. And the book is geared toward the non-specialist reader, making it accessible to those without a psychology or teaching background. With this guide, the reader learns how to: Identify motivation problems and goals Decide whether the environment or the learners need changing Generate attention, relevance, confidence, and satisfaction in learners Integrate motivational design and instructional design Select, develop, and evaluate motivational materials Plus a wealth of tables, worksheets, measures, and other valuable tools aid in the design process Comprehensive and enlightening, Motivational Design for Learning and Performance furnishes an eminently practical body of knowledge to researchers and professionals in performance technology and instructional design as well as educational psychologists, teachers and trainers. TOC:The Study of Motivation.- What is Motivational Design.- The ARCS Model of Motivational Design.- Generating and Sustaining Attention.- Establishing and Supporting Relevance.- Building Confidence.- Managing Outcomes for Satisfaction.- Identifying the Motivational Problems.- Identifying Motivational Goals and Tactics.- Integrating Motivational and Instructional Strategies.- Tools to Support Motivational Design.- Motivational Design Research and Development.
Prostate cancer (PCa) metastasizes selectively to bone through unknown mechanisms. In the current study, we identified exosome-mediated transfer of pyruvate kinase M2 (PKM2) from PCa cells into bone ...marrow stromal cells (BMSCs) as a novel mechanism through which primary tumor-derived exosomes promote premetastatic niche formation. We found that PKM2 up-regulates BMSC CXCL12 production in a HIF-1α-dependent fashion, which subsequently enhances PCa seeding and growth in the bone marrow. Furthermore, serum-derived exosomes from patients with either primary PCa or PCa metastasis, as opposed to healthy men, reveal that increased exosome PKM2 expression is associated with metastasis, suggesting clinical relevance of exosome PKM2 in PCa. Targeting the exosome-induced CXCL12 axis diminished exosome-mediated bone metastasis. In summary, primary PCa cells educate the bone marrow to create a premetastatic niche through primary PCa exosome-mediated transfer of PKM2 into BMSCs and subsequent up-regulation of CXCL12. This novel mechanism indicates the potential for exosome PKM2 as a biomarker and suggests therapeutic targets for PCa bone metastasis.
Heart development is exquisitely sensitive to the precise temporal regulation of thousands of genes that govern developmental decisions during differentiation. However, we currently lack a detailed ...understanding of how chromatin and gene expression patterns are coordinated during developmental transitions in the cardiac lineage. Here, we interrogated the transcriptome and several histone modifications across the genome during defined stages of cardiac differentiation. We find distinct chromatin patterns that are coordinated with stage-specific expression of functionally related genes, including many human disease-associated genes. Moreover, we discover a novel preactivation chromatin pattern at the promoters of genes associated with heart development and cardiac function. We further identify stage-specific distal enhancer elements and find enriched DNA binding motifs within these regions that predict sets of transcription factors that orchestrate cardiac differentiation. Together, these findings form a basis for understanding developmentally regulated chromatin transitions during lineage commitment and the molecular etiology of congenital heart disease.
Objective
Psychological distress is common in cancer patients, and awareness of its indicators is essential. We aimed to assess the prevalence of psychological distress and to identify problems ...indicative of high distress.
Methods
We used the distress thermometer (DT) and its 34‐item problem list to measure psychological distress in 3724 cancer patients (mean age 58 years; 57% women) across major tumor entities, enrolled in an epidemiological multicenter study. To identify distress‐related problems, we conducted monothetic analyses.
Results
We found high levels of psychological distress (DT ≥ 5) in 52% of patients. The most prevalent problems were fatigue (56%), sleep problems (51%), and problems getting around (47%). Sadness, fatigue, and sleep problems were most strongly associated with the presence of other problems. High distress was present in 81.4% of patients reporting all 3 of these problems (DT M = 6.4). When analyzing only the subset of physical problems, fatigue, problems getting around, and indigestion showed the strongest association with the remaining problems and 76.3% of patients with all 3 problems were highly distressed (DT M = 6.1).
Conclusions
Our results show a high prevalence of psychological distress in cancer patients, as well as a set of problems that indicate the likely presence of other problems and high distress and can help clinicians identify distressed patients even if no routine distress screening is available.
The ability to direct the differentiation of human pluripotent stem cells (hPSCs) to the different cardiomyocyte subtypes is a prerequisite for modeling specific forms of cardiovascular disease ...in vitro and for developing novel therapies to treat them. Here we have investigated the development of the human atrial and ventricular lineages from hPSCs, and we show that retinoic acid signaling at the mesoderm stage of development is required for atrial specification. Analyses of early developmental stages revealed that ventricular and atrial cardiomyocytes derive from different mesoderm populations that can be distinguished based on CD235a and RALDH2 expression, respectively. Molecular and electrophysiological characterization of the derivative cardiomyocytes revealed that optimal specification of ventricular and atrial cells is dependent on induction of the appropriate mesoderm. Together these findings provide new insights into the development of the human atrial and ventricular lineages that enable the generation of highly enriched, functional cardiomyocyte populations for therapeutic applications.
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•Human atrial and ventricular cardiomyocytes derive from distinct mesoderm populations•Atrial and ventricular mesoderm are distinguished by RALDH2 and CD235a expression•Atrial cardiomyocytes are specified by autocrine RA signaling•Efficient atrial/ventricular myocyte generation depends on mesoderm patterning
Keller, Protze, and colleagues show that atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. Molecular and functional analyses revealed that appropriate mesoderm patterning is required for generating enriched populations of atrial or ventricular cardiomyocytes from hPSCs. These findings provide important new insights for the derivation of populations for future therapeutic applications.
Centrifugal microfluidics has evolved into a mature technology. Several major diagnostic companies either have products on the market or are currently evaluating centrifugal microfluidics for product ...development. The fields of application are widespread and include clinical chemistry, immunodiagnostics and protein analysis, cell handling, molecular diagnostics, as well as food, water, and soil analysis. Nevertheless, new fluidic functions and applications that expand the possibilities of centrifugal microfluidics are being introduced at a high pace. In this review, we first present an up-to-date comprehensive overview of centrifugal microfluidic unit operations. Then, we introduce the term "process chain" to review how these unit operations can be combined for the automation of laboratory workflows. Such aggregation of basic functionalities enables efficient fluidic design at a higher level of integration. Furthermore, we analyze how novel, ground-breaking unit operations may foster the integration of more complex applications. Among these are the storage of pneumatic energy to realize complex switching sequences or to pump liquids radially inward, as well as the complete pre-storage and release of reagents. In this context, centrifugal microfluidics provides major advantages over other microfluidic actuation principles: the pulse-free inertial liquid propulsion provided by centrifugal microfluidics allows for closed fluidic systems that are free of any interfaces to external pumps. Processed volumes are easily scalable from nanoliters to milliliters. Volume forces can be adjusted by rotation and thus, even for very small volumes, surface forces may easily be overcome in the centrifugal gravity field which enables the efficient separation of nanoliter volumes from channels, chambers or sensor matrixes as well as the removal of any disturbing bubbles. In summary, centrifugal microfluidics takes advantage of a comprehensive set of fluidic unit operations such as liquid transport, metering, mixing and valving. The available unit operations cover the entire range of automated liquid handling requirements and enable efficient miniaturization, parallelization, and integration of assays.
Review on miniaturization, integration, and automation of laboratory processes within centrifugal microfluidic platforms. For efficient implementation of applications, building blocks are categorized into unit operations and process chains.
Patients with resectable lung cancer were assigned to neoadjuvant pembrolizumab or placebo plus chemotherapy and adjuvant pembrolizumab or placebo. Two-year event-free survival was 62.4% with ...pembrolizumab and 40.6% with placebo.
La reproduction recouvre l’ensemble des processus biologiques qui permettent d’assurer la survie d’une espèce grâce à la naissance de nouveaux individus. Cette propriété fondamentale et obligatoire ...du monde vivant repose sur un mécanisme efficace et extrêmement complexe. Chez les vertébrés, c’est l’axe hypothalamo-hypophyso-gonadique qui est le cadre anatomique responsable de la compétence reproductive et donc de la pérennité des espèces. La coordination de ce système biologique à trois étages repose sur le contrôle neuronal de libération de la « Gonadotrophin Releasing Hormone » (GnRH), système localisé dans la partie rostrale de l’hypothalamus. La libération de GnRH dans le système porte hypothalamo-hypophysaire stimule la sécrétion des gonadotropines hypophysaires qui sont impliquées dans le déclenchement de la puberté et la régulation de la fonction de reproduction. Cette revue fournit des éléments de compréhension sur le fonctionnement du contrôle neuroendocrine de l’axe hypothalamo-hypophyso-gonadique chez les mammifères, en particulier, sur les propriétés du système à GnRH, le contrôle neuroendocrinien des cycles ovariens, l’effet de neuropeptides hypothalamiques «kisspeptin » sur les neurones à GnRH, le déclenchement de la puberté, la saisonnalité et conclue sur les perspectives de recherche dans cette discipline de la neurobiologie.
Cell-tracing studies in the mouse indicate that the cardiac lineage arises from a population that expresses the vascular endothelial growth factor receptor 2 (VEGFR2, Flk-1), suggesting that it may ...develop from a progenitor with vascular potential. Using the embryonic stem (ES) cell differentiation model, we have identified a cardiovascular progenitor based on the temporal expression of the primitive streak (PS) marker
brachyury and Flk-1. Comparable progenitors could also be isolated from head-fold stage embryos. When cultured with cytokines known to function during cardiogenesis, individual cardiovascular progenitors generated colonies that displayed cardiomyocyte, endothelial, and vascular smooth muscle (VSM) potential. Isolation and characterization of this previously unidentified population suggests that the mammalian cardiovascular system develops from multipotential progenitors.
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