Concurrent level set and fiber orientation optimization of composite structures

By adjusting both the structural shape and fiber orientation, this research aims to optimize the design of Fiber Reinforced Composite structures. The structural geometry is represented by a level set function, which is approximated by quadratic B-spline functions. The fiber orientation field is parameterized with quadratic/cubic B-splines on hierarchically refined meshes. Different levels for B-spline mesh refinement for the level set and fiber orientation fields are studied to obtain a smooth fiber layout. To facilitate FRC manufacturing, the parallel alignment, and smoothness of fiber paths are enforced by introducing penalty terms referred to as "misalignment penalty and curvature penalty", which are incorporated into the optimization process. A geometric interpretation of the penalties is provided. The material behavior of the FRCs is modeled by the Mori-Tanaka homogenization scheme and the macroscopic structure response is modeled by linear elasticity under static mutiloading conditions. The Governing equations are discretized by a Heaviside-enriched eXtended IsoGeometric Analysis to avoid the need to generate conformal meshes. Instabilities in XIGA are mitigated by the facet-oriented ghost stabilization technique. This work considers mass and strain energy in the formulation of the optimization objective, along with misalignment and curvature penalties and additional regularization terms. Constraints are imposed on the volume of the structure. The resulting optimization problems are solved by a gradient-based algorithm. The design sensitivities are computed by the adjoint method. Numerical examples demonstrate with two-dimensional and three-dimensional configurations that the proposed method is efficient in simultaneously optimizing the macroscopic shape and the fiber layout while improving manufacturability by promoting parallel and smooth fiber paths

The Intentional Use of Service Recovery Strategies to Influence Consumer Emotion, Cognition and Behaviour

Service recovery strategies have been identified as a critical factor in the success of. service organizations. This study develops a conceptual frame work to investigate how specific service recovery strategies influence the emotional, cognitive and negative behavioural responses of . consumers., as well as how emotion and cognition influence negative behavior. Understanding the impact of specific service recovery strategies will allow service providers' to more deliberately and intentionally engage in strategies that result in positive organizational outcomes. This study was conducted using a 2 x 2 between-subjects quasi-experimental design. The results suggest that service recovery has a significant impact on emotion, cognition and negative behavior. Similarly, satisfaction, negative emotion and positive emotion all influence negative behavior but distributive justice has no effect

Appraisal of health care: from patient value to societal benefit

Aim: This paper summarizes the deficiencies and weaknesses of the most frequently used methods for the allocation of health-care resources. New, more transparent and practical methods for optimizing the allocation of these resources are proposed. Method: The examples of quality-adjusted life years (QALYs) and efficiency frontier (EF) are analyzed to describe weaknesses and problems in decisions regulating health-care provision. After conducting a literature search and discussions with an international group of professionals, three groups of professionals were formed to discuss the assessment and appraisal of health-care services and allocation of available resources. Results: At least seven essential variables were identified that should be heeded when applying the concept of QALYs for decisions concerning health-care provision. The efficiency frontier (EF) concept can be used to set a ceiling price and perform a cost-benefit analysis of provision, but different stakeholders—a biostatistician (efficacy), an economist (costs), a clinician (effectiveness), and the patient (value)—could provide a fairer appraisal of health-care services. Efficacy and costs are often based on falsifiable data. Effectiveness and value depend on the success with which a particular clinical problem has been solved. These data cannot be falsified. The societal perspective is generated by an informal cost-benefit analysis including appraisals by the above-mentioned stakeholders and carried out by an authorized institution. Conclusion: Our analysis suggests that study results expressed in QALYs or as EF cannot be compared unless the variables included in the calculation are specified. It would be far more objective and comprehensive if an authorized institution made an informal decision based on formal assessments of the effectiveness of health-care services evaluated by health-care providers, of the value assessed by consumers, of efficacy described by biostatisticians, and of costs calculated by economists

Detection and Verification of Mammalian Mirtrons by Northern Blotting

microRNAs (miRNAs) have vital roles in regulating gene expression—contributing to major diseases like cancer and heart disease. Over the last decade, thousands of miRNAs have been discovered through high throughput sequencing-based annotation. Different classes have been described, as well as a great dynamic range of expression levels. While sequencing approaches provide insight into biogenesis and allow confident identification, there is a need for additional methods for validation and characterization. Northern blotting was one of the first techniques used for studying miRNAs, and remains one of the most valuable as it avoids enzymatic manipulation of miRNA transcripts. Blotting can also provide insight into biogenesis by revealing RNA processing intermediates. Compared to sequencing, however, northern blotting is a relatively insensitive technology. This creates a challenge for detecting low expressed miRNAs, particularly those produced by inefficient, non-canonical pathways. In this chapter, we describe a strategy to study such miRNAs by northern blotting that involves ectopic expression of both miRNAs and miRNA-binding Argonaute (Ago) proteins. Through use of epitope tags, this strategy also provides a convenient method for verification of small RNA competency to be loaded into regulatory complexes

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

First Sagittarius A* Event Horizon Telescope Results. I. The Shadow of the Supermassive Black Hole in the Center of the Milky Way

We present the first Event Horizon Telescope (EHT) observations of Sagittarius A* (Sgr A*), the Galactic center source associated with a supermassive black hole. These observations were conducted in 2017 using a global interferometric array of eight telescopes operating at a wavelength of lambda = 1.3 mm. The EHT data resolve a compact emission region with intrahour variability. A variety of imaging and modeling analyses all support an image that is dominated by a bright, thick ring with a diameter of 51.8 +/- 2.3 mu as (68% credible interval). The ring has modest azimuthal brightness asymmetry and a comparatively dim interior. Using a large suite of numerical simulations, we demonstrate that the EHT images of Sgr A* are consistent with the expected appearance of a Kerr black hole with mass similar to 4 x 10(6) M (circle dot), which is inferred to exist at this location based on previous infrared observations of individual stellar orbits, as well as maser proper-motion studies. Our model comparisons disfavor scenarios where the black hole is viewed at high inclination (i > 50 degrees), as well as nonspinning black holes and those with retrograde accretion disks. Our results provide direct evidence for the presence of a supermassive black hole at the center of the Milky Way, and for the first time we connect the predictions from dynamical measurements of stellar orbits on scales of 10(3)-10(5) gravitational radii to event-horizon-scale images and variability. Furthermore, a comparison with the EHT results for the supermassive black hole M87* shows consistency with the predictions of general relativity spanning over three orders of magnitude in central mass