The influence of pacing rate and autonomic blockade on human primary and secondary atrial pacemakers

Current gene therapy protocols designed to treat adenosine deaminase (ADA) deficiency and other metabolic disorders suffer from low-efficiency delivery to target cells and a lack of long-term stability in expression of the therapeutic proteins. These problems may be resolved by use of an in vivo dominant selection. The multidrug transporter (MDR1) has been suggested as a useful selective marker for gene therapy. In this work, we co-expressed ADA and MDR1 cDNA in a retroviral vector using an internal ribosome entry site (IRES) from encephalomyocarditis virus. This system produced a bicistronic mRNA containing both ADA and MDR1, which enables co-expression of ADA and MDR1, and also allows the two proteins to be translated separately. After in vitro selection using a cytotoxic MDR1 substrate, vincristine, we demonstrated that functional ADA was co-expressed with MDR1 in proportion to the expression level of MDR1, whereas MDR1 expression was proportional to the stringency of the vincristine selection. Because the efficiency of IRES-dependent translation was much lower than that of cap-dependent translation in this system, we observed lower expression of the genes positioned after the IRES. This asymmetric expression caused a lower viral titer when MDR1 was placed downstream from the IRES, but it also provided a way of modulating the relative expression of ADA and MDR1. The retroviral system described in this work may serve as a useful tool to evaluate the strategies involving in vivo dominant selection for gene therapy of ADA-deficient patients.     

Solid state reactions in the Fe2O3-CaCO3-In2O3 system

The kinetics of solid-state reactions of powdered reactants were investigated by X-ray and by differential thermogravimetry in a magnetic field. Measurements revealed mutual diffusion of the Fe³⁺ and In³⁺ ions in the Fe₂O₃-In₂O₃ system heat treated for 3 h at 700 to 1400° C. Diffusion of indium into the Fe₂O₃ lattice caused a shift of the Curie temperature of the antiferromagnetic iron oxide towards lower temperatures. Only Caln₂O₄ was found between CaCO₃ and In₂O₃ up to 1400° C. Also, in the Fe₂O₃-CaCO₃-In₂O₃in system, the reaction started with the mutual diffusion of iron and indium and the forming of CaFe₂O₄. End-products were the magnetic -Ca₄Fe₁₄O₂₅ and CaFe₄O₇, and the non-magnetic CaFe₅O₇, depending on the In³⁺ concentration. Indium stabilized the magnetic calcium-iron oxide structures, shifting their Curie temperatures towards lower values.     

PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.     

Modeling of Intercritical Heat Treatment of DP and TRIP Steels

The final microstructure of DP and TRIP assisted steels can evolve after hot working (hot rolling) or during post heat treatment process. In the formation of the final structure a number of different technological parameters have important roles, e.g. end temperature of rolling, cooling rates, temperature of intercritical annealing, etc. As a result of the individual factors and their combinations a lot of product technology routes are feasible. The effect of the different combinations of these technological parameters on the microstructure can be mapped by the special Jominy end-quench test (so called intercritical Jominy end-quench test) described in this paper. Unlike the traditional Jominy test, in this case there is a partial anstenizing between A1 and A3 temperatures which results in a given amount of ferrite in the microstructure before quenching. The method developed can be applied for mapping DP and TRIP assisted steels' microstructure in a wide range of technological parameters. The analysis of measured and calculated data can help us find the technological parameters optimal from the microstructural point of view.     

On Efficiency of Multi-job Grid Allocation Based on Statistical Trace Data

The ever growing number of computation-intensive applications calls for utilizing large-scale, potentially interoperable distributed infrastructures. Nowadays, such distributed systems enable the management of heterogeneous scientific workflows of considerable sizes, where job scheduling and resource management is a crucial issue. In this paper we focus on the challenges of scheduling parameter sweep applications, a specific and commonly used type of workflows where ordering of job executions is irrelevant. A parameter sweep has a large set of independent job instances, called a multi-job, submitted for execution in a single step. In order to cope with the high uncertainty and unpredictable load of resources, and the simultaneous submissions of multi-job instances, we propose a statistics-based brokering approach for allocating jobs to resources so that the makespan is minimised. Earlier studies claim that users’ predictions on job runtime are inaccurate and unusable for scheduling. Our aim is to examine, whether statistical trace data for the same purpose is efficient compared to randomized allocation.     

Quality through Managed Improvement and Measurement (QMIM): Towards a Phased Development and Implementation of a Quality Management System for a Software Company

The paper describes results of a longitudinal study of developments in the area of software product and process quality improvement within a Hungarian software company, IQSOFT Ltd. This company has been active in this area since 1993, trying to build, introduce and maintain an efficiently working quality management system which, e.g., fulfils the ISO 9001 requirements, allows steady software process improvement and, at the same time, conforms to company's own needs. Over the last eight years five phases could be distinguished. Each phase is described shortly, following the same structure, namely: basic starting points, key problem areas, literature consulted, activities and design executed, reflections on what happened and why. The lessons resulting from the analysis of this case have been formulated in terms of guidelines. We feel that these are applicable to any low maturity software development organisation embarking on a product or process quality improvement endeavour. These guidelines are developed around a framework containing the basic issues of software production (project management, technical processes and products). The guidelines advocate a careful step-by-step development of definitions, quality characteristics, and metrics related to these objects while at the same time developing and introducing the associated process.     

Degree-constrained decompositions of graphs: Bounded treewidth and planarity

We study the problem of decomposing the vertex set V$V$ of a graph into two nonempty parts _V1,_V2$V_1,V_2$ which induce subgraphs where each vertex v∈_V1$v\in V_1$ has degree at least a(v)$a(v)$ inside _V1$V_1$ and each v∈_V2$v\in V_2$ has degree at least b(v)$b(v)$ inside _V2$V_2$. We give a polynomial-time algorithm for graphs with bounded treewidth which decides if a graph admits a decomposition, and gives such a decomposition if it exists. This result and its variants are then applied to designing polynomial-time approximation schemes for planar graphs where a decomposition does not necessarily exist but the local degree conditions should be met for as many vertices as possible.