The resistive state in a superconducting wire: Bifurcation from the normal state

We study formally and rigorously the bifurcation to steady and time-periodic states in a model for a thin superconducting wire in the presence of an imposed current. Exploiting the PT-symmetry of the equations at both the linearized and nonlinear levels, and taking advantage of the collision of real eigenvalues leading to complex spectrum, we obtain explicit asymptotic formulas for the stationary solutions, for the amplitude and period of the bifurcating periodic solutions and for the location of their zeros or "phase slip centers" as they are known in the physics literature. In so doing, we construct a center manifold for the flow and give a complete description of the associated finite-dimensional dynamics

Abdominal aortic calcification on a plain X-ray and the relation with significant coronary artery disease in asymptomatic chronic dialysis patients

BACKGROUND: Coronary artery disease (CAD) is common in asymptomatic chronic dialysis patients and plays an important role in their poor survival. Early identification of these high-risk patients could improve treatment and reduce mortality. Abdominal aortic calcification (AAC) has previously been associated with CAD in autopsy studies. Since the AAC can be quantified easily using a lateral lumbar X-ray we hypothesized that the extent of AAC as assessed on a lateral lumbar X-ray might be predictive of the presence of significant CAD in dialysis patients. METHODS: All patients currently enrolled in the ICD2 trial without a history of CABG or a PCI with stent implantation were included in this study. All patients underwent CT-angiography (CTA) and a lateral X-ray of the abdomen. AAC on X-ray was quantified using a previously validated scoring system whereupon the association between AAC and the presence of significant CAD was assessed. RESULTS: A total of 90 patients were included in this study (71% male, 67 ± 7 years old). Forty-six patients were found to have significant CAD. AAC-score was significantly higher in patients with CAD (10.1 ± 4.9 vs 6.3 ± 4.6 (p < 0.05). Multivariate regression analysis revealed that AAC score is an independent predictor for the presence of CAD with a 1,2 fold higher risk per point increase (p < 0.01). The AAC score has a sensitivity of 85% and a specificity of 57% for the presence of significant CAD. CONCLUSION: This study shows that abdominal aortic calcification as assessed on a lateral lumbar X-ray is predictive for the presence of significant coronary artery disease in asymptomatic dialysis patients. This simple, non-invasive and cheap screening method could contribute to early identification of patients eligible for further screening of CAD. TRIAL REGISTRATION: NTR948, registered 10-4-2007 ; ISRCTN20479861, registered 2-5-200

Vitamin D Receptor Deficiency and Low Vitamin D Diet Stimulate Aortic Calcification and Osteogenic Key Factor Expression in Mice

Low levels of 25-hydroxy vitamin D (25(OH)D) are associated with cardiovascular diseases. Herein, we tested the hypothesis that vitamin D deficiency could be a causal factor in atherosclerotic vascular changes and vascular calcification. Aortic root sections of vitamin D receptor knockout (VDR−/−) mice that were stained for vascular calcification and immunostained for osteoblastic differentiation factors showed more calcified areas and a higher expression of the osteogenic key factors Msx2, Bmp2, and Runx2 than the wild-type mice (P<0.01). Data from LDL receptor knockout (LDLR−/−) mice that were fed western diet with either low (50 IU/kg), recommended (1,000 IU/kg), or high (10,000 IU/kg) amounts of vitamin D3 over 16 weeks revealed increasing plasma concentrations of 25(OH)D (P<0.001) with increasing intake of vitamin D, whereas levels of calcium and phosphorus in plasma and femur were not influenced by the dietary treatment. Mice treated with the low vitamin D diet had more calcified lesions and a higher expression of Msx2, Bmp2, and Runx2 in aortic roots than mice fed recommended or high amounts of vitamin D (P<0.001). Taken together, these findings indicate vitamin D deficiency as a risk factor for aortic valve and aortic vessel calcification and a stimulator of osteogenic key factor expression in these vascular areas

Glucolipotoxicity initiates pancreatic beta-cell death through TNFR5/CD40-mediated STAT1 and NF-kappa B activation

Funded by Diabetes UK, NovoNordisk UK Research Foundation, and St. Bartholomew’s & The Royal London Charitable Foundation grant awards

iTools: A Framework for Classification, Categorization and Integration of Computational Biology Resources

The advancement of the computational biology field hinges on progress in three fundamental directions – the development of new computational algorithms, the availability of informatics resource management infrastructures and the capability of tools to interoperate and synergize. There is an explosion in algorithms and tools for computational biology, which makes it difficult for biologists to find, compare and integrate such resources. We describe a new infrastructure, iTools, for managing the query, traversal and comparison of diverse computational biology resources. Specifically, iTools stores information about three types of resources–data, software tools and web-services. The iTools design, implementation and resource meta - data content reflect the broad research, computational, applied and scientific expertise available at the seven National Centers for Biomedical Computing. iTools provides a system for classification, categorization and integration of different computational biology resources across space-and-time scales, biomedical problems, computational infrastructures and mathematical foundations. A large number of resources are already iTools-accessible to the community and this infrastructure is rapidly growing. iTools includes human and machine interfaces to its resource meta-data repository. Investigators or computer programs may utilize these interfaces to search, compare, expand, revise and mine meta-data descriptions of existent computational biology resources. We propose two ways to browse and display the iTools dynamic collection of resources. The first one is based on an ontology of computational biology resources, and the second one is derived from hyperbolic projections of manifolds or complex structures onto planar discs. iTools is an open source project both in terms of the source code development as well as its meta-data content. iTools employs a decentralized, portable, scalable and lightweight framework for long-term resource management. We demonstrate several applications of iTools as a framework for integrated bioinformatics. iTools and the complete details about its specifications, usage and interfaces are available at the iTools web page http://iTools.ccb.ucla.edu

A data mining approach to evaluate suitability of dissolved oxygen sensor observations for lake metabolism analysis

Despite rapid growth in continuous monitoring of dissolved oxygen for lake metabolism studies, the current best practice still relies on visual assessment and manual data filtering of sensor observations by experienced scientists in order to achieve meaningful results. This time consuming approach is fraught with potential for inconsistency and individual subjectivity. An automated method to assure the quality of data for the purpose of metabolism modeling is clearly needed to obtain consistent results representative of collective expertise. We used a hybrid approach of expert panel and data mining for data filtration. Symbolic Aggregate approXimation (SAX) treats discretized numerical timeseries segments as symbolic indications, creating a series of strings which are literally comparable to human words and sentences. This conversion allows established text mining techniques, such as classification methods to be applied to timeseries data. Half‐hourly frequency surface dissolved oxygen data from 18 global lakes were used to create day‐long segments of the original time series data. Three hundred sets of 1‐d measurements were provided to a group of seven anonymous experts, experienced in manual filtering of oxygen data for metabolism modeling studies. The collective results were treated as expert panel decisions, and were used to rank the data by confidence level for use in metabolism calculations. While considerable variation occurred in the way the experts perceived the quality of the data, the model provides an objective and quantitative assessment method. The program output will assist the decision making process in determining whether data should be used for metabolism calculations. An R version of the program is available for download

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease