Dynamics and energetics of the South Pacific Convergence Zone during FGGE SOP-1 and South Pacific Convergence Zone and global-scale

Significant accomplishments (papers published, conference presentations, and education degrees) are presented. The focus of the current research is outlined. Plans for the coming year are discussed briefly

Single Synonymous Mutations in KRAS Cause Transformed Phenotypes in NIH3T3 Cells

Synonymous mutations in the KRAS gene are clustered at G12, G13, and G60 in human cancers. We constructed 9 stable NIH3T3 cell lines expressing KRAS, each with one of these synonymous mutations. Compared to the negative control cell line expressing the wild type human KRAS gene, all the synonymous mutant lines expressed more KRAS protein, grew more rapidly and to higher densities, and were more invasive in multiple assays. Three of the cell lines showed dramatic loss of contact inhibition, were more refractile under phase contrast, and their refractility was greatly reduced by treatment with trametinib. Codon usage at these glycines is highly conserved in KRAS compared to HRAS, indicating selective pressure. These transformed phenotypes suggest that synonymous mutations found in driver genes such as KRAS may play a role in human cancers

Inhibiting Lactate Dehydrogenase A Enhances the Cytotoxicity of the Mitochondria Accumulating Antioxidant, Mitoquinone, in Melanoma Cells

Limited options exist for inhibitors targeted against melanoma tumors with mutation subtypes other than BRAF. We investigated the cytotoxic activity of mitoquinone (MitoQ), an antioxidant and ubiquinone derivative, on various human melanoma cell lines, alone or in combination with other agents to perturb cellular bioenergetics. This lipophilic cation crosses the cell membrane, enters and accumulates in the mitochondria where it can disrupt mitochondrial function at micromolar concentrations or act as an antioxidant to preserve membrane integrity at nanomolar concentrations. Consistent with previous studies, cells treated with 12.5 μM MitoQ show significantly reduced viability versus control treatments. Although all melanoma cells were susceptible to cytotoxicity induced by MitoQ, cells with wild-type BRAF were responsive to lower doses, compared to cells with activating mutations in BRAF. Mechanistically, the positively charged lipophilic moiety of the MitoQ induced a dose-dependent collapse of the mitochondrial membrane potential (Δψm) and significantly reduced the mitochondrial ATP production and reduced oxygen consumption rate, suggesting mitochondrial dysfunction. We also combined MitoQ with a glycolytic lactate dehydrogenase A inhibitor (FX-11) and observed an enhanced reduction in viability, but not other therapies examined. To summarize, the data suggest that FX-11 enhances the cytotoxic effects of MitoQ in cells with wild-type BRAF

Dissection of the left main coronary artery after blunt thoracic trauma: Case report and literature review

Blunt chest trauma is commonly encountered by surgeons and is rarely associated with cardiac injuries. The incidence of cardiac injury is rare but can be rapidly fatal, requiring prompt recognition and treatment. We review the case of a 37 year-old male who was involved in a head-on motor vehicle collision at highway speed and was found to have an isolated left main coronary artery dissection. We then review the supporting literature for evaluation of blunt cardiac injuries and the treatment options for traumatic coronary dissection

Checks and cheques : implementing a population health and recall system to improve coverage of patients with diabetes in a rural general practice

Identification of all diabetic patients in the population is essential if diabetic care is to be effective in achieving the targets of the St Vincent Declaration.1 The challenge therefore is to establish population based monitoring and control systems by means of state of the art technology in order to achieve quality assurance in the provision of care for patients with diabetes. 2,3 Disease management receives extensive international support as the most appropriate approach to organising and delivering healthcare for chronic conditions like diabetes.4 This approach is achieved through a combination of guidelines for practice, patient education, consultations and follow up using a planned team approach and a strong focus on continuous quality improvement using information technology. 5,6 The current software (Medical Director) could not easily meet these requirements which led us to adopt a trial of Ferret. In designing this project we used change management7 and the plan, do, study, act cycle8 illustrated in Diagram 1.<br /

Comparison of Analysis, Simulation, and Measurement of Wire-to-Wire Crosstalk

In this investigation, we compare crosstalk analysis, simulation, and measurement results for electrically short configurations. Methods include hand calculations, PSPICE simulations, Microstripes transient field solver, and empirical measurement. In total, four representative physical configurations are examined, including a single wire over a ground plane, a twisted pair over a ground plane, generator plus receptor wires inside a cylindrical conduit, and a single receptor wire inside a cylindrical conduit. Part 1 addresses the first two cases, and Part 2 addresses the final two. Agreement between the analysis, simulation, and test data is shown to be very good

GIFTed Demons: deformable image registration with local structure-preserving regularization using supervoxels for liver applications.

Deformable image registration, a key component of motion correction in medical imaging, needs to be efficient and provides plausible spatial transformations that reliably approximate biological aspects of complex human organ motion. Standard approaches, such as Demons registration, mostly use Gaussian regularization for organ motion, which, though computationally efficient, rule out their application to intrinsically more complex organ motions, such as sliding interfaces. We propose regularization of motion based on supervoxels, which provides an integrated discontinuity preserving prior for motions, such as sliding. More precisely, we replace Gaussian smoothing by fast, structure-preserving, guided filtering to provide efficient, locally adaptive regularization of the estimated displacement field. We illustrate the approach by applying it to estimate sliding motions at lung and liver interfaces on challenging four-dimensional computed tomography (CT) and dynamic contrast-enhanced magnetic resonance imaging datasets. The results show that guided filter-based regularization improves the accuracy of lung and liver motion correction as compared to Gaussian smoothing. Furthermore, our framework achieves state-of-the-art results on a publicly available CT liver dataset

The effect of European starlings and ambient air temperature on \u3ci\u3eSalmonella enterica\u3c/i\u3e contamination within cattle feed bunks

European starlings (Sturnus vulgaris) are a known risk factor for the occurrence of microorganisms that are pathogenic to cattle and humans in concentrated animal feeding operations (CAFOs). Starling use of CAFOs is known to vary in response to weather; starling control operations on CAFOs often are timed to coincide with favorable environmental conditions to maximize take. The totality of this information suggests that disease risks in CAFOs associated with starlings may be influenced by environmental factors, such as temperature. In this study, we assessed the risk of Salmonella enterica contamination of cattle feed by modeling the interaction between starling numbers and ambient air temperatures using data previously reported from Texas CAFOs. We compared these interaction models to the previously published additive models for S. enterica contamination of cattle feed using an information-theoretic approach to model selection that ranked and weighted models in terms of their support by the data, using bias-adjusted Akaike’s Information Criterion (AICc) and Akaike weights (Wi). Our results indicate that the interaction between European starlings and ambient air temperature better explained the occurrence of S. enterica in cattle feed than any of the previously reported models. Specifically, the risk of S. enterica contamination of cattle feed by starlings was greatest when winter temperatures were highest (10°C). Thus, we conclude that the risk of S. enterica contamination of cattle feed by starlings will be worst on the few winter days when daytime high temperatures are above freezing and large numbers of birds are present. Because these conditions will be most common in the late winter and early spring, we recommend that starling control operations on feedlots and dairies be conducted as early in the winter as possible to mitigate the risks of disease created by large foraging flocks of starlings

Inhibition of inducible nitric oxide synthase limits nitric oxide production and experimental aneurysm expansion

AbstractPurpose: Nitric oxide (NO), frequently cited for its protective role, can also generate toxic metabolites known to degrade elastin. Both abdominal aortic aneurysms (AAAs) and inducible nitric oxide synthase (iNOS) are associated with inflammatory states, yet the relationship between NO production by iNOS and AAA development is unknown. The current study examines iNOS expression, NO production, and the effects of selective inhibition of iNOS by aminoguanidine in experimental AAA. Methods: An intra-aortic elastase infusion model was used. Control rats received intra-aortic saline infusion and postoperative intraperitoneal saline injections (Group 1). In the remaining groups, intra-aortic elastase infusion was used to induce aneurysm formation. These rats were treated with intraperitoneal injections of saline postoperatively (Group 2), aminoguanidine postoperatively (Group 3), or aminoguanidine preoperatively and postoperatively (Group 4). Aortic diameter and plasma nitrite/nitrate levels were measured on the day of surgery and postoperative day 7. Aortas were harvested for biochemical and histologic analysis on postoperative day 7. Results: Infusion of elastase produced AAAs (P <.001) with significant production of iNOS (P <.05) and nitrite/nitrate (P <.003) compared with controls. Selective inhibition of iNOS with aminoguanidine in elastase-infused aortas significantly reduced aneurysm size (P <.01) compared with elastase infusion alone. Aminoguanidine-treated rats displayed suppression of iNOS expression and plasma nitrite/nitrate production not significantly different from the control group. Histologic evaluation revealed equivalent inflammatory infiltrates in elastase-infused groups. Conclusion: Expression of iNOS is induced and plasma nitrite/nitrate levels are increased in experimental AAA. Inhibition of iNOS limits NO production and iNOS expression, resulting in smaller aneurysm size. NO production by iNOS plays an important role with detrimental effects during experimental aneurysm development. (J Vasc Surg 2001;33:579-86.