Genetic alteration and gene expression modulation during cancer progression

Cancer progresses through a series of histopathological stages. Progression is thought to be driven by the accumulation of genetic alterations and consequently gene expression pattern changes. The identification of genes and pathways involved will not only enhance our understanding of the biology of this process, it will also provide new targets for early diagnosis and facilitate treatment design. Genomic approaches have proven to be effective in detecting chromosomal alterations and identifying genes disrupted in cancer. Gene expression profiling has led to the subclassification of tumors. In this article, we will describe the current technologies used in cancer gene discovery, the model systems used to validate the significance of the genes and pathways, and some of the genes and pathways implicated in the progression of preneoplastic and early stage cancer

Public Databases and Software for the Pathway Analysis of Cancer Genomes

The study of pathway disruption is key to understanding cancer biology. Advances in high throughput technologies have led to the rapid accumulation of genomic data. The explosion in available data has generated opportunities for investigation of concerted changes that disrupt biological functions, this in turns created a need for computational tools for pathway analysis. In this review, we discuss approaches to the analysis of genomic data and describe the publicly available resources for studying biological pathways

Zeros, chaotic ratios and the computational complexity of approximating the independence polynomial

The independence polynomial originates in statistical physics as the partition function of the hard-core model. The location of the complex zeros of the polynomial is related to phase transitions, and plays an important role in the design of efficient algorithms to approximately compute evaluations of the polynomial.In this paper we directly relate the location of the complex zeros of the independence polynomial to computational hardness of approximating evaluations of the independence polynomial. We do this by moreover relating the location of zeros to chaotic behaviour of a naturally associated family of rational functions; the occupation ratios

Soluble Guanylate Cyclase Generation of cGMP Regulates Migration of MGE Neurons

Here we have provided evidence that nitric oxide-cyclic GMP (NO-cGMP) signaling regulates neurite length and migration of immature neurons derived from the medial ganglionic eminence (MGE). Dlx1/2(-/-) and Lhx6(-/-) mouse mutants, which exhibit MGE interneuron migration defects, have reduced expression of the gene encoding the alpha subunit of a soluble guanylate cyclase (Gucy1A3). Furthermore, Dlx1/2(-/-) mouse mutants have reduced expression of NO synthase 1 (NOS1). Gucy1A3(-/-) mice have a transient reduction in cortical interneuron number. Pharmacological inhibition of soluble guanylate cyclase and NOS activity rapidly induces neurite retraction of MGE cells in vitro and in slice culture and robustly inhibits cell migration from the MGE and caudal ganglionic eminence. We provide evidence that these cellular phenotypes are mediated by activation of the Rho signaling pathway and inhibition of myosin light chain phosphatase activity

Lessons Learned: Recruiting Aging Adults for Research

Aging adults are the fastest-growing population in the United States, but they are underrepresented in health care research. Evidence-based decisions for aging adults need to be made using research done with this population. However, recruiting aging adults into research has many challenges. This article presents multiple cases of recruiting aging adults into nutrition research studies in 3 different US geographic locations. The challenges, successes, and lessons learned are presented. The lessons learned can provide guidance to others already doing research with aging adults and those clinical and community dietitians who want to start doing research with aging adults

Aggregating energy supply and demand

Energy usage in general, and electricity usage in particular, are major concerns internationally due to the increased cost of providing energy supplies and the environmental impacts of electricity generation using carbon-based fuels. If a "systems" approach is taken to understanding energy issues then both supply and demand need to be considered holistically. This paper examines two research projects in the energy area with IT tools as key deliverables, one examining supply issues and the other studying demand side issues. The supply side project used hard engineering methods to build the models and software, while the demand side project used a social science approach. While the projects are distinct, there was an overlap in personnel. Comparing the knowledge extraction, model building, implementation and interface issues of these two deliverables identifies both interesting contrasts and commonalities

Spitting cobra (Naja nigricincta nigricincta) bites complicated by rhabdomyolysis, possible intravascular haemolysis, and coagulopathy

Zebra snake (Naja nigricincta nigricincta) bite is a significant health problem in Namibia. Although fatalities are thought to be rare, the severe cytotoxic effects and debilitating consequences of neglected bites are well documented. The focus of our treatment has always been the urgent treatment of necrosis. Although there have been a few reports of infant fatalities, acute renal failure and mild coagulation problems, systemic effects after envenomation were not well documented. Three case reports of patients with rhabdomyolysis, intravascular haemolysis and coagulopathy following N. n. nigricincta bites are presented

Lee-Yang Zeros of the antiferromagnetic Ising Model

We investigate the location of zeros for the partition function of the anti-ferromagnetic Ising Model, focusing on the zeros lying on the unit circle. We give a precise characterization for the class of rooted Cayley trees, showing that the zeros are nowhere dense on the most interesting circular arcs. In contrast, we prove that when considering all graphs with a given degree bound, the zeros are dense in a circular sub-arc, implying that Cayley trees are in this sense not extremal. The proofs rely on describing the rational dynamical systems arising when considering ratios of partition functions on recursively defined trees

Evaluation of influenza vaccine effectiveness and description of circulating strains in outpatient settings in South Africa, 2014

The effectiveness of the trivalent seasonal influenza vaccine during the 2014 season in South Africa was assessed using a test-negative case–control study design including 472 cases and 362 controls. Influenza A(H3N2) was the dominant strain circulating. The overall vaccine effectiveness estimate, adjusted for age and underlying conditions, was43.1% (95% CI: 26.8-74.5). 2014 H3N2 viruses from South Africa were mainly in sublineage 3C.3 with accumulation of amino acid changes that differentiate them from the vaccine strain in 3C.1