A coordinated multiorgan metabolic response contributes to human mitochondrial myopathy

Mitochondrial diseases are a heterogeneous group of monogenic disorders that result from impaired oxidative phosphorylation (OXPHOS). As neuromuscular tissues are highly energy-dependent, mitochondrial diseases often affect skeletal muscle. Although genetic and bioenergetic causes of OXPHOS impairment in human mitochondrial myopathies are well established, there is a limited understanding of metabolic drivers of muscle degeneration. This knowledge gap contributes to the lack of effective treatments for these disorders. Here, we discovered fundamental muscle metabolic remodeling mechanisms shared by mitochondrial disease patients and a mouse model of mitochondrial myopathy. This metabolic remodeling is triggered by a starvation-like response that evokes accelerated oxidation of amino acids through a truncated Krebs cycle. While initially adaptive, this response evolves in an integrated multiorgan catabolic signaling, lipid store mobilization, and intramuscular lipid accumulation. We show that this multiorgan feed-forward metabolic response involves leptin and glucocorticoid signaling. This study elucidates systemic metabolic dyshomeostasis mechanisms that underlie human mitochondrial myopathies and identifies potential new targets for metabolic intervention

Novel Serial Positive Enrichment Technology Enables Clinical Multiparameter Cell Sorting

A general obstacle for clinical cell preparations is limited purity, which causes variability in the quality and potency of cell products and might be responsible for negative side effects due to unwanted contaminants. Highly pure populations can be obtained best using positive selection techniques. However, in many cases target cell populations need to be segregated from other cells by combinations of multiple markers, which is still difficult to achieve – especially for clinical cell products. Therefore, we have generated low-affinity antibody-derived Fab-fragments, which stain like parental antibodies when multimerized via Strep-tag and Strep-Tactin, but can subsequently be removed entirely from the target cell population. Such reagents can be generated for virtually any antigen and can be used for sequential positive enrichment steps via paramagnetic beads. First protocols for multiparameter enrichment of two clinically relevant cell populations, CD4high/CD25high/CD45RAhigh ‘regulatory T cells’ and CD8high/CD62Lhigh/CD45RAneg ‘central memory T cells’, have been established to determine quality and efficacy parameters of this novel technology, which should have broad applicability for clinical cell sorting as well as basic research

THE ROLE OF PSYCHOLOGY IN DEVELOPMENT AND DEALING OF FEAR IN HUMANS.

Fear is a simple basic emotion experienced by every single being. It is a fundamental survival mechanism that indicates humans to respond in danger with a ght or ight response in order to keep us safe. Every human body reacts in a different way when it encounters fear. This paper examines the reasons for the growth and prevalence of fear in relation to the mind and the role of psychological intervention in dealing with it. Literature search was done on Google scholar which included the use of keywords ‘fear’, ‘phobias’, ‘psychological intervention’ or ‘emotions. Reference lists having similar titles were also taken into consideration. Available literature search shows that hormones have a vital role in functioning of fear and phobias. Everyone has a different way of dealing with it. An abnormality in processing of fear could potentially lead to psychiatric disorders. Psychology based therapy is an effective way of dealing with it. Fear being an exaggerated emotion needs a plan that works towards the development of its belief. Psychological intervention involving Cognitive behavioural therapy, Rational emotive behaviour therapy, Systematic desensitization and many others have been proved to overcome fears and phobias.</jats:p

Design for Manufacture and Assembly Lean and Product Development Through Industrial Case Study

Lean is a key process that understands customer value and its goal is to provide perfect value to the customer by engaging a process cycle that minimizes waste. This paper focuses on the implementation of Lean in the Design and Manufacturing Industries. The complex interactions of the financial, logistical, and geological processes that are involved in developing a product and then handing it over to customers are driving forces in today’s industries. Hence, if industries do not implement Lean, product cost will rise. Lean design involves identifying wastage in the processes of product manufacturing/production. This means, specifically, eliminating waste and non-value-added activities in design, production, marketing, supply chain integration and customer interactions by making product flow through the Value Stream without any interruption. Our goal is to minimize production resources by eliminating non-value-added activities, thus saving time in production and improving product quality. The basic goal behind this paper is to reduce product cost by eliminating unnecessary elements that increase final product cost. This will be demonstrated by way of manufacturing a fuel tank by removing or redesigning the parts now used by the current industry. The paper also will show how Virtual Reality plays a key role in helping students and engineers to learn applications and to understand simulation more effectively. It is a powerful learning tool for both engineers and students. The paper will emphasize the development of active learning experiences in relation to Lean Product Development. The different models that are developed in this paper will help students and engineers to gain knowledge in various streams like Engineering, Business and Sciences, with the aid of Virtual Reality. This paper concentrates mainly on undergraduate and graduate students. Solid Works, one of the more common and available tools in most U.S. schools, is utilized as a software that allows users to change product designs on their own, so as to get better results. After learning these tools, users will be able to apply their skills in various industries to reduce non-value-added activities. Developing Lean Manufacturing models using Virtual Reality will increase any user’s capability, quality and efficiency in Product Development.</jats:p

Computerized Three-Dimensional Finite Element Reconstruction of the Left Ventricle from Cross-Sectional Echocardiograms

A computerized method for the generation of a three-dimensional finite element mesh of left ventricular geometry is presented. The technique employs two dimensional echocardiographic images of the left ventricle. The echocardiographic transducer is attached to an articulated, computerassisted, position registration arm with six degrees-of-freedom. These six degrees-of-freedom record the location and orientation of the transducer, when images are obtained, referenced to an external point. Eence, the images are digitized and aligned relative to one another, then several interpolation and curve fitting steps are used to reconstruct a threedimensional finite element model of the left ventricle. The finite element model can be used for volume determination, stress analysis, material property identification, and other applications. </jats:p