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.     

Light‐emitting polymers for full‐color display applications

The latest developments in light‐emitting‐polymer (LEP) technology at CDT continue to show steady progress. Device performance for blue, green, and red systems as well as a high‐performance yellow system in terms of device efficiency and stability will be described. Some of the issues associated with the commercialization of LEP technology including the development of direct‐patterning techniques enabling full‐color passive‐ and active‐matrix display will be discussed.     

The effect of heating shot peened sheets and thin plates of aluminium alloys

2024, 7075 and 7475 aluminium alloy sheet and thin plate specimens shot peened to various intensities and subsequently exposed for periods up to 500 h at temperatures up to 120 ° C showed significant decreases in the level of residual stress induced by the shot peening and significant changes in geometrical contour even for exposure temperatures as low as 80 ° C. The higher the intensity of the shot peening, the higher the temperature of exposure and the longer the period of exposure, the greater was the relief of residual stress. After 40 h at 120 ° C the level of residual stress was reduced by more than 60%. Specimens formed to a given curvature by shot peening tended to straighten out on exposure at elevated temperatures. Such significant effects were obtained at temperatures as low as 80 ° C, these increasing with duration and temperature of exposure. The results and the possible effect of a tendency to change the contour of a flight component in service are discussed. Metallurgical ameliorative measures for some of these effects are demonstrated.     

Clinical and instrumental diagnosis of pulmonary embolism

Pulmonary embolism shows a high mortality especially for the difficulty in establishing an early correct diagnosis. The pathophysiology and thus the clinical manifestations of pulmonary embolism (PE) are essentially conditioned by three factors: the size of the embolus, the pre-existing cardiorespiratory condition, the release caused by the embolus, of some substances or the activation of reflexes which tend to worsen the purely mechanical consequences of PE. The clinical manifestations resulting from the combination of these factors result in three clinical patterns: acute cor pulmonare, pulmonary infarction, acute dyspnea. PE symptoms may be absent in a moderate percentage of cases and if present, they are nonspecific. Some laboratory tests were shown to be of no diagnostic accuracy, as enzyme determination, a sign of necrosis, blood gas analysis, and determination of alveolar arterial oxygen gradient. Among blood coagulation tests, D-dimer determination was shown to be of some relevance. However, at present, it cannot be used to confirm the diagnostic suspicion of PE. Among the instrumental cardiologic procedures, while ECG has a poor diagnostic reliability, transesophageal echocardiography in central embolism may be able to visualize the embolus and to accurately assess the hemodynamic effects, supplying sufficient information for PE therapy. Even if imaging procedures as pulmonary angiography and more recently CT or MRI are the most reliable diagnostic tools, the diagnostic suspicion of PE in subjects at risk, the use of the examined methods and the search in these patients for the presence of lower limb deep vein thrombosis, often asymptomatic, may increase the number of treated patients thus decreasing the mortality of this disease.     

Radioimmunoassay of regulatory peptides in the presence of acetonitrile: marked improvement of cholecystokinin assays

Radioimmunoassay has made it possible to measure the levels of many hormones. However, samples for some hormones, such as cholecystokinin (CCK), need to be purified by reverse phase chromatography before assay. Usually, samples are eluted from cartridges or HPLC columns in about 50% acetonitrile, dried on a vacuum centrifuge, and then reconstituted in buffer. Drying and reconstituting samples is time consuming and introduces additional sources of error and peptide loss. The present study investigated the effect of acetonitrile on radioimmunoassays for CCK to see if samples containing acetonitrile could be assayed directly. The non-specific binding of a radiolabeled peptide, the zero binding (B0), and the fall in the presence of 2.5 fmol unlabeled CCK were determined in the presence of various proportions of acetonitrile with 0.1% TFA. Additionally, standard curves were compared in the presence and absence of 200microl of 50% acetonitrile, (n = 5). For assays using two separate CCK antisera, increasing amounts of acetonitrile gave progressively higher zero binding and fall, thereby increasing sensitivity and antibody titer. The use of 200microl 50% acetonitrile, chosen to represent typical sample conditions, increased antiserum titers by three to four-fold, as well as increasing sensitivity considerably. For one antiserum (CCK2), the IC20 was 0.36+/-0.02 fmol CCK/tube in the presence of acetonitrile and 1.45+/-0.08 fmol/tube in its absence (P< 0.001). For the other antiserum (Dino 7), the IC20 was 0.40+/-0.02 fmol CCK/tube in the presence of acetonitrile and 0.63+/-0.01 fmol/tube in its absence (P<0.001). A similar increase in sensitivity was seen with a gastrin assay. However, no significant change in the gastrin antibody titer was evident. Assays for several other hormones were unaffected by 200 microl of 50% acetonitrile. At volumes encountered in samples following chromatography, acetonitrile did not adversely affect radioimmunoassays for a number of hormones, and the sensitivity and antibody titer of the CCK assays were improved. Measurement of CCK samples without drying and reconstitution increases assay efficiency and sensitivity.     

Retrogression and reaging and the role of dislocations in the stress corrosion of 7000-type aluminum alloys

The 7000-type aluminum alloys in the T6 temper are known to be highly susceptible to stress-corrosion cracking (SCC). Some years ago, a heat treatment known as retrogression and reaging (RR) was developed by one of the authors (B.C.), providing for enhanced stress-corrosion resistance without any sacrifice of yield or tensile strength in 7075 aluminum alloy. The idea behind the process was based on the suggestion that dislocations developed during quenching from the solution treatment were responsible for susceptibility to stress corrosion. In spite of considerable practical development of the RR process, the above basic hypothesis as to the role of dislocations has never been investigated. In the present work, the effect of the RR treatments on the dislocation structure of 7000-type aluminum alloys was studied using transmission electron microscopy (TEM). A clear relationship has been found between the presence of dislocations adjacent to grain boundaries and the susceptibility to stress corrosion of 7000-type aluminum alloys. The beneficial effect of the RR treatment on the SCC of 7000-type aluminum alloys in the T6 temper is believed to be due to the disappearance of the above dislocations as a result of RR treatment.     

Color Doppler US of intrahepatic vascular system

Aim of this article is an up-dating of the state of the art of color Doppler US in the assessment of intrahepatic vascularization. Recent reports are reviewed, based on already acquired certainties to better the knowledge of the physiology and pathophysiology of hepatic circulation to investigate new clinical applications of color Doppler US.     

Firearm-related hunting fatalities in North Carolina: impact of the 'Hunter Orange' Law

In the decade spanning 1983 through 1992, 68 people were killed by firearms while hunting in North Carolina (average of 1.66 fatalities/100,000 licenses issued). Of these, 58 deaths involved two parties, a shooter and a victim. In 22% of the incidents the victims were mistaken for game. During the 1987-1988 hunting season a "Hunter Orange" law was initially enforced. This law requires sportsmen to wear an article of bright orange clothing while hunting. After enactment of this law, a reduction in the incidence of hunters being killed because they were "mistaken for game" has proven statistically significant. The present study documents that legally mandating bright orange clothing has resulted in fewer firearms-related fatalities due to the victim's being mistaken for game while hunting. The North Carolina experience implies that governmental intervention can influence the incidence of accidental deaths during recreational hunting.     

Fractography of unidirectional CFRP composites

The morphology of fracture surfaces of unidirectional carbon fibre reinforced plastic composites has been studied to categorize the fractographic characteristics for several types of loading. Specimens were tested in compression and in tension, both in the axial and the transverse direction, in bending and in interlaminar shear. The influence of prior exposure to moisture and to elevated temperature on the fracture morphology of specimens tested at elevated temperature has also been studied. Optical and scanning electron microscopy were used for the fracture surface analyses. Fractographic features characteristic of each mode of stressing and directionality of specimen were identified.     

Nanocrystalline γ-Alumina Synthesized by Sonohydrolysis of Alkoxide Precursor in the Presence of Organic Acids: Structure and Morphological Properties

γ-Al₂O₃ nanoparticles with an average size of 5 nm were synthesized by the hydrolysis of aluminum triisopropoxide under the influence of power ultrasound (100 W/cm²) and in the presence of formic or oxalic acids as peptizers, followed by calcination. The structural and morphological properties of the as-prepared precursor hydroxides and calcined nanocrystalline powders were characterized by XRD, SEM, TEM, TGA, IR, and BET. The ultrasound-driven cavitation process has been shown to affect the agglomeration of the precursor nanoparticles by condensation of interparticle hydroxyls. The oxalate anions were strongly adsorbed on the surface of the precursor nanoparticles and thus retarded the ultrasound-driven condensation of interparticle hydroxyls. Formic acid showed a lesser degree of adsorption on the surface of the precursor particles. The ultrasound-driven agglomeration of the primary particles as well as the role of organic modifiers on the microstructural properties of the precursor and the target alumina phases have been discussed.