Simulation of a finishing operation : milling of a turbine blade and influence of damping

Milling is used to create very complex geometries and thin parts, such as turbine blades. Irreversible geometric defects may appear during finishing operations when a high surface quality is expected. Relative vibrations between the tool and the workpiece must be as small as possible, while tool/workpiece interactions can be highly non-linear. A general virtual machining approach is presented and illustrated. It takes into account the relative motion and vibrations of the tool and the workpiece. Both deformations of the tool and the workpiece are taken into account. This allows predictive simulations in the time domain. As an example the effect of damping on the behavior during machining of one of the 56 blades of a turbine disk is analysed in order to illustrate the approach potential

A guide to chemokines and their receptors

The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G‐protein coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells (leukocytes). Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behaviour, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many non‐leukocytic cell types. Chemokines are profoundly affected by post‐translational modification, by interaction with the extracellular matrix (ECM), and by binding to heptahelical ‘atypical’ chemokine receptors that regulate chemokine localisation and abundance. This guide gives a broad overview of the chemokine and chemokine receptor families; summarises the complex physical interactions that occur in the chemokine network; and, using specific examples, discusses general principles of chemokine function, focussing particularly on their ability to direct leukocyte migration

How do undergraduate medical students perceive social accountability?

Aim: The concept of social accountability within undergraduate training is embedded within the remit of medical schools. Little is known of how medical students perceive social accountability, recognize aspects of their training contributing to the development of this concept and cultivate the underpinning values. Methods: Students nearing graduation were recruited to participate in focus groups designed to explore their perceptions of social accountability, which curricular aspects had contributed to their understanding, and to investigate the implications of individual variations in training. Results: Students expressed limited appreciation of the concept of social accountability and acknowledged little explicit teaching around underpinning core concepts such as awareness of local health needs, advocacy and nurturing of altruism. However, participants recognized numerous aspects of the course and learning initiatives as impacting on their attitudes towards this concept implicitly. Conclusion: This study highlights areas of their undergraduate training that students recognize as having the greatest impact on their development into socially accountable professionals. It poses some significant challenges for health care educators in addressing unintended consequences, including an outcome-driven educational approach, in reducing students’ capacity or willingness to engage in curricular challenges often designed to embed this concept

Ontology mapping for semantically enabled applications

In this review, we provide a summary of recent progress in ontology mapping (OM) at a crucial time when biomedical research is under a deluge of an increasing amount and variety of data. This is particularly important for realising the full potential of semantically enabled or enriched applications and for meaningful insights, such as drug discovery, using machine-learning technologies. We discuss challenges and solutions for better ontology mappings, as well as how to select ontologies before their application. In addition, we describe tools and algorithms for ontology mapping, including evaluation of tool capability and quality of mappings. Finally, we outline the requirements for an ontology mapping service (OMS) and the progress being made towards implementation of such sustainable services

The EG95 Antigen of Echinococcus spp. Contains Positively Selected Amino Acids, which May Influence Host Specificity and Vaccine Efficacy

Echinococcosis is a worldwide zoonotic parasitic disease of humans and various herbivorous domestic animals (intermediate hosts) transmitted by the contact with wild and domestic carnivores (definitive hosts), mainly foxes and dogs. Recently, a vaccine was developed showing high levels of protection against one parasite haplotype (G1) of Echinococcus granulosus, and its potential efficacy against distinct parasite variants or species is still unclear. Interestingly, the EG95 vaccine antigen is a secreted glycosylphosphatydilinositol (GPI)-anchored protein containing a fibronectin type III domain, which is ubiquitous in modular proteins involved in cell adhesion. EG95 is highly expressed in oncospheres, the parasite life cycle stage which actively invades the intermediate hosts. After amplifying and sequencing the complete CDS of 57 Echinococcus isolates belonging to 7 distinct species, we uncovered a large amount of genetic variability, which may influence protein folding. Two positively selected sites are outside the vaccine epitopes, but are predicted to alter protein conformation. Moreover, phylogenetic analyses indicate that EG95 isoform evolution is convergent with regard to the number of beta-sheets and alpha-helices. We conclude that having a variety of EG95 isoforms is adaptive for Echinococcus parasites, in terms of their ability to invade different hosts, and we propose that a mixture of isoforms could possibly maximize vaccine efficacy

Determination of the response function for the Portsmouth Gaseous Diffusion Plant criticality accident alarm system neutron detectors

Neutron-sensitive radiation detectors are used in the Portsmouth Gaseous Diffusion Plant`s (PORTS) criticality accident alarm system (CAAS). The CAAS is composed of numerous detectors, electronics, and logic units. It uses a telemetry system to sound building evacuation horns and to provide remote alarm status in a central control facility. The ANSI Standard for a CAAS uses a free-in-air dose rate to define the detection criteria for a minimum accident-of-concern. Previously, the free-in-air absorbed dose rate from neutrons was used for determining the areal coverge of criticality detection within PORTS buildings handling fissile materials. However, the free-in-air dose rate does not accurately reflect the response of the neutron detectors in use at PORTS. Because the cost of placing additional CAAS detectors in areas of questionable coverage (based on a free-in-air absorbed dose rate) is high, the actual response function for the CAAS neutron detectors was determined. This report, which is organized into three major sections, discusses how the actual response function for the PORTS CAAS neutron detectors was determined. The CAAS neutron detectors are described in Section 2. The model of the detector system developed to facilitate calculation of the response function is discussed in Section 3. The results of the calculations, including confirmatory measurements with neutron sources, are given in Section 4

Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).

We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome

Gas gangrene and osteomyelitis of the foot in a diabetic patient treated with tea tree oil

Diabetic foot wounds represent a class of chronic non-healing wounds that can lead to the development of soft tissue infections and osteomyelitis. We reviewed the case of a 44-year-old female with a diabetic foot wound who developed gas gangrene while treating her wound with tea tree oil, a naturally derived antibiotic agent. This case report includes images that represent clinical examination and x-ray findings of a patient who required broad-spectrum antibiotics and emergent surgical consultation. Emergency Department (ED) detection of these complications may prevent loss of life or limb in these patients

Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension

BACKGROUND: Renovascular hypertension (RVH) impairs cardiac structure and left ventricular (LV) function, but whether mitochondrial injury is implicated in RVH-induced myocardial damage and dysfunction has not been defined. We hypothesized that cardiac remodeling in swine RVH is partly attributable to cardiac mitochondrial injury. METHODS AND RESULTS: After 12 weeks of hypercholesterolemic (HC)-RVH or control (n=14 each), pigs were treated for another 4 weeks with vehicle or with the mitochondrial-targeted peptide (MTP), Bendavia (0.1 mg/kg subcutaneously, 5 days/week), which stabilizes mitochondrial inner-membrane cardiolipin (n=7 each). Cardiac function was subsequently assessed by multidetector-computed tomography and oxygenation by blood-oxygen-level-dependent magnetic resonance imaging. Cardiolipin content, mitochondrial biogenesis, as well as sarcoplasmic-reticulum calcium cycling, myocardial tissue injury, and coronary endothelial function were assessed ex vivo. Additionally, mitochondrial cardiolipin content, oxidative stress, and bioenergetics were assessed in rat cardiomyocytes incubated with tert-butyl hydroperoxide (tBHP) untreated or treated with MTP. Chronic mitoprotection in vivo restored cardiolipin content and mitochondrial biogenesis. Thapsigargin-sensitive sarcoplasmic reticulum Ca(2+)-ATPase activity that declined in HC-RVH normalized in MTP-treated pigs. Mitoprotection also improved LV relaxation (E/A ratio) and ameliorated cardiac hypertrophy, without affecting blood pressure or systolic function. Myocardial remodeling and coronary endothelial function improved only in MTP-treated pigs. In tBHP-treated cardiomyocytes, mitochondrial targeting attenuated a fall in cardiolipin content and bioenergetics. CONCLUSIONS: Chronic mitoprotection blunted myocardial hypertrophy, improved LV relaxation, and attenuated myocardial cellular and microvascular remodeling, despite sustained HC-RVH, suggesting that mitochondrial injury partly contributes to hypertensive cardiomyopathy

Discourses of student orientation to medical education programs

Background: Although medical students’ initial orientation is an important point of transition in medical education, there is a paucity of literature on the subject and major variations in the ways that different institutions orient incoming medical students to their programs. Methods: We conducted a discourse analysis of medical education orientation in the literature and on data from a survey of peer institutions’ approaches to orientation. Results: These two discourses of orientation had clear similarities, in particular, the critical role of ceremony and symbols, and the focus on developing professionalism and physician identities. There were also differences between them, in particular, in the way that the discourse in the literature focused on the symbolic and professional aspects of orientation; something we have called ‘cultural orientation’. Meanwhile, those who were responsible for orientation in their own institutions tended to focus on the practical and social dimensions. Conclusion: By examining how orientation has been described and discussed, we identify three domains of orientation: cultural, social, and practical. These domains are relatively distinct in terms of the activities associated with them, and in terms of who is involved in organizing and running these activities. We also describe orientation as a liminal activity system on the threshold of medical school where incoming students initially cross into the profession. Interestingly, this state of ambiguity also extends to the scholarship of orientation with only some of its aspects attracting formal enquiry, even though there is a growing interest in transitions in medical education as a whole. We hope, therefore, that this study can help to legitimize enquiry into orientation in all its forms and that it can begin to situate the role of orientation more firmly within the firmament of medical education practice and research