An Energy-Minimization Finite-Element Approach for the Frank-Oseen Model of Nematic Liquid Crystals: Continuum and Discrete Analysis

This paper outlines an energy-minimization finite-element approach to the computational modeling of equilibrium configurations for nematic liquid crystals under free elastic effects. The method targets minimization of the system free energy based on the Frank-Oseen free-energy model. Solutions to the intermediate discretized free elastic linearizations are shown to exist generally and are unique under certain assumptions. This requires proving continuity, coercivity, and weak coercivity for the accompanying appropriate bilinear forms within a mixed finite-element framework. Error analysis demonstrates that the method constitutes a convergent scheme. Numerical experiments are performed for problems with a range of physical parameters as well as simple and patterned boundary conditions. The resulting algorithm accurately handles heterogeneous constant coefficients and effectively resolves configurations resulting from complicated boundary conditions relevant in ongoing research.Comment: 31 pages, 3 figures, 3 table

The thermodynamics of metabolism, cardiovascular performance and exercise, in health and diabetes: The objective of clinical markers

Extensive experience in UK National Health Service metabolic syndrome/type 2 diabetes clinics highlights the need for convenient clinical marker(s) which can be readily used to indicate the success or otherwise of alternative therapies. In this paper we study the metabolic context of the healthy and diseased states, which points to the haemodynamics being a possible key in identifying candidate markers. Human metabolism relates to two elemental thermodynamic systems, the individual cell and the human body in its entirety. The fundamental laws of thermodynamics apply to humans, animals, and their individual cells for both healthy and diseased conditions. as they are to classic heat engines. In compliance with the second law enhanced levels of heat are generated under exercise, heat itself being another factor modulating the cardiovascular response to physical exercise. Nutrients and oxygen uptake occurs via the digestive system and lungs, respectively, leading to ATP production by the established metabolic pathways: this is controlled by insulin. These are then delivered to the cells via the haemodynamic system to satisfy local metabolic need. The supply and demand of oxygen are finely regulated, in part, via oxygen-dependent release of ATP from the circulating erythrocytes. Energy supply and demand are regulated to sustain muscle activity resulting in the body’s output of measurable thermodynamic work—i.e. exercise. Recently a dynamic pathway model allowing quantification of ATP release from the erythrocytes and its contribution to oxygen supply regulation has been published. However, metabolic uptake is well known to be greatly affected by disease such as the highly prevalent diabetes type 2 with insulin resistance and beta cell dysfunction having mechanistic roles. In 2010, over 25% of residents above 65 in the USA had diabetes 2. The complexity of the metabolic pathways means that monitoring of patient-specific treatment would be beneficial from a diabetic marker which may be haemodynamic-related and traceable via the local fluid dynamics

Cancer immunology and canine malignant melanoma: a comparative review

Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current “gold standard” treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics

A metastatic secretory gastric plasmacytoma with aberrant CD3 expression in a dog

A 10-year-old crossbred dog was presented with a 6-week history of hematemesis, melena, anorexia, and lethargy. Clinical evaluation revealed a gastric mass with a regional lymphadenomegaly as well as a monoclonal gammopathy manifesting as hyperglobulinemia. Cytologic and histopathologic analyses were consistent with a round cell neoplasm; neoplastic cells showed nuclear immunoreactivity for MUM1 and diffuse cytoplasmic reactivity for CD3. Polymerase chain reactions performed on fixed and fresh tissue identified a clonal rearrangement with an IgH primer set. An extramedullary plasmacytoma (EMP) was confirmed by cellular morphology and molecular diagnostics. Following an objective response to chemotherapy, the dog was euthanized 8 months after diagnosis, and a postmortem examination confirmed the clinical findings. This is the first reported case of a monoclonal gammopathy secondary to a gastric EMP coupled with aberrant expression of CD3 in an aggressive plasmacytic tumor, and highlights the utility of molecular diagnostics for classifying atypical hemolymphoid neoplasms

Nutrient modulation in the management of disease-induced muscle wasting: evidence from human studies

Purpose of review: In addition to being essential for movement, skeletal muscles act as both a store and source of key macronutrients. As such, muscle is an important tissue for whole body homeostasis, undergoing muscle wasting in times of starvation, disease, and stress, for example, to provide energy substrates for other tissues. Yet, muscle wasting is also associated with disability, comorbidities, and mortality. As nutrition is so crucial to maintaining muscle homeostasis 'in health', it has been postulated that muscle wasting in cachexia syndromes may be alleviated by nutritional interventions. This review will highlight recent work in this area in relation to muscle kinetics, the acute metabolic (e.g. dietary protein), and longer-term effects of dietary interventions. Recent findings: Whole body and skeletal muscle protein synthesis invariably exhibit deranged kinetics (favouring catabolism) in wasting states; further, many of these conditions harbour blunted anabolic responses to protein nutrition compared with healthy controls. These derangements underlie muscle wasting. Recent trials of essential amino acid and protein-based nutrition have shown some potential for therapeutic benefit. Summary: Nutritional modulation, particularly of dietary amino acids, may have benefits to prevent or attenuate disease-induced muscle wasting. Nonetheless, there remains a lack of recent studies exploring these key concepts to make conclusive recommendations

Recent developments in deuterium oxide tracer approaches to measure rates of substrate turnover: implications for protein, lipid, and nucleic acid research

Purpose of review: Methods that inform on dynamic metabolism that can be applied to clinical populations to understand disease progression and responses to therapeutic interventions are of great importance. This review perspective will highlight recent advances, development, and applications of the multivalent stable isotope tracer deuterium oxide (D2O) to the study of substrate metabolism with particular reference to protein, lipids, and nucleic acids, and how these methods can be readily applied within clinical and pharmaceutical research. Recent findings: Advances in the application of D2O techniques now permit the simultaneous dynamic measurement of a range of substrates (i.e. protein, lipid, and nucleic acids, along with the potential for OMICs methodologies) with minimal invasiveness further creating opportunities for long-term ‘free living’ measures that can be used in clinical settings. These techniques have recently been applied to ageing populations and further in cancer patients revealing altered muscle protein metabolism. Additionally, the efficacy of numerous drugs in improving lipoprotein profiles and controlling cellular proliferation in leukaemia have been revealed. Summary: D2O provides opportunities to create a more holistic picture of in-vivo metabolic phenotypes, providing a unique platform for development in clinical applications, and the emerging field of personalized medicine