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.     

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.     

Fentanyl but Not Morphine or Buprenorphine Improves the Severity of Necrotizing Acute Pancreatitis in Rats

Opioids are widely used for the pain management of acute pancreatitis (AP), but their impact on disease progression is unclear. Therefore, our aim was to study the effects of clinically relevant opioids on the severity of experimental AP. Various doses of fentanyl, morphine, or buprenorphine were administered as pre- and/or post-treatments in rats. Necrotizing AP was induced by the intraperitoneal injection of L-ornithine-HCl or intra-ductal injection of Na-taurocholate, while intraperitoneal caerulein administration caused edematous AP. Disease severity was determined by laboratory and histological measurements. Mu opioid receptor (MOR) expression and function was assessed in control and AP animals. MOR was expressed in both the pancreas and brain. The pancreatic expression and function of MOR were reduced in AP. Fentanyl post-treatment reduced necrotizing AP severity, whereas pre-treatment exacerbated it. Fentanyl did not affect the outcome of edematous AP. Morphine decreased vacuolization in edematous AP, while buprenorphine pre-treatment increased pancreatic edema during AP. The overall effects of morphine on disease severity were negligible. In conclusion, the type, dosing, administration route, and timing of opioid treatment can influence the effects of opioids on AP severity. Fentanyl post-treatment proved to be beneficial in AP. Clinical studies are needed to determine which opioids are best in AP.     

Wear Performance of Laser Processed Tantalum Coatings

This first generation investigation evaluates the in vitro tribological performance of laser-processed Ta coatings on Ti for load-bearing implant applications. Linear reciprocating wear tests in simulated body fluid showed one order of magnitude less wear rate, of the order of 10(-4)mm(3)(N.m)(-1), for Ta coatings compared to Ti. Our results demonstrate that Ta coatings can potentially minimize the early-stage bone-implant interface micro-motion induced wear debris generation due to their excellent bioactivity comparable to that of hydroxyapatite (HA), high wear resistance and toughness compared to popular HA coatings.     

Nonresonant referenced laser-induced thermal acoustics thermometry in air

We report a detailed investigation of nonresonant laser-induced thermal acoustics (LITA) for the single-shot measurement of the speed of sound (v(S)) in an oven containing room air. A model for the speed of sound that includes important acoustic relaxation effects is used to convert the speed of sound into temperature. A reference LITA channel is used to reduce uncertainties in v(S). Comparing thermocouple temperatures with temperatures deduced from our v(S) measurements and model, we find the mean temperature difference from 300 to 650 K to be 1% (+/-2sigma). The advantages of using a reference LITA channel are discussed.     

Asymptotic behavior of certain Riccati difference equations

Matrix Riccati difference equations are investigated on the infinite index set. Under natural assumptions an existence and uniqueness theorem is proven. The existence of the asymptotic expansion of the solution and computability of its coefficients are shown, provided the coefficients of the equation have such an expansion.     

Dynamic denoising studies in wideband radio channel measurement and modeling

The fixed level and dynamic denoising method was studied based on indoor-to-outdoor measured channel impulse responses ORs） at 5.25 GHz with radio frequency （RF） 100 MHz bandwidth. It is found that the dynamic ranges, peak powers and noise floors of the IRs are with close correlations. The comparisons with different denoising methods are given by deriving the power delay profiles （PDPs）, root mean square （RMS） delay spread （RMS DS）, number of paths （NOPs） and Ricean K-factors. It is concluded that the traditional fixed level noise cut is under estimate of DS and NOPs. The Ricean K-factors are of little sensitive to noise cut irrespective of what kind of methods applied. The PDPs are not very sensitive to the fixed level noise cut, however, obvious changes can be found by dynamic noise cut. The dynamic noise cut is preferred when clear noise floors is observed and decided from the measured IRs, it＇s of importance in data post processing for wideband radio channel measurements as well as the relevant modeling work.     

Reversal of liver failure in sickle cell vaso-occlusive crisis

Issues concerning patient advocacy and nursing advocacy are explored in relation to the nurse's role and the UKCC code of conduct. The author's personal experiences of being an advocate are described. Potential conflict between the nurse's role and doctor's role in relation to advocacy is identified. The best person to take on the role of patient advocate is discussed.