Effects of long-term growth hormone therapy on adrenal steroidogenesis in Turner syndrome

Nature's most potent molecules are produced by enzyme-catalysed reactions, coupled with the natural selection of those products that possess optimal biological activity. Combinatorial biocatalysis harnesses the natural diversity of enzymatic reactions for the iterative synthesis of organic libraries. Iterative reactions can be performed using isolated enzymes or whole cells, in natural and unnatural environments, and on substrates in solution or on a solid phase. Combinatorial biocatalysis is a powerful addition to the expanding array of combinatorial methods for the generation and optimization of lead compounds in drug discovery and development.     

Hemodynamic characteristics, myocardial kinetics and microvascular rheology of FS-069, a second-generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection

OBJECTIVES: We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. BACKGROUND: FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection. METHODS: Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular findings of FS-069 can explain its echocardiographic behavior during direct coronary injections. RESULTS: There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gamma-variate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification. CONCLUSIONS: FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.     

Effect of surface condition on the oxidation behaviour of MCrAlY coatings

Coatings of the MCrAlY type (M = Ni, Co) are commonly used as overlay coatings and as bond coats (BC's) for ceramic thermal barrier coatings (TBC's) in industrial gas turbines. During high temperature service the MCrAlY coatings form aluminium based surface oxide scales. The technologically most relevant properties of the oxide scales, growth rate and adherence do not only depend on the exact MCrAlY composition but also on the surface condition after coating manufacturing. Depending on the coating manufacturing process, the MCrAlY surfaces may substantially differ in roughness. In addition the coatings may be subjected to surface treatments (e.g. shot peening, grinding or smoothening prior to deposition of TBC). In the present work the effect of the surface roughness commonly prevailing in the case of vacuum plasma sprayed MCrAlY coatings on the morphology and composition of the alumina scales formed during high-temperature oxidation was studied. For this purpose free standing coatings with rough and polished surfaces were oxidised in the temperature range from 800 to 1100 °C with exposure times up to 1000 h. The surface scale composition and morphology were analysed by optical metallography and SEM. Fluorescence spectroscopy was used for stress measurements in the oxide scales. It has been found that the oxide scales formed on rough surfaces of MCrAlY coatings have an intrinsically different morphology and growth rate compared to those formed on the flat ground surfaces.     

Hydraulic behaviour and removal efficiencies of two H-SSF constructed wetlands for wastewater reuse with different operational life

This work focuses on the performance evaluation of two full-scale horizontal suburface flow constructed wetlands (H-SSF CWs) working in parallel, which have an almost equal surface area (about 2,000 m2) but with different operational lives: 8 and 3 years. Both H-SSF CWs, located in Southern Italy (Sicily), are used for tertiary treatment of the effluent of a conventional wastewater treatment plant. This study evaluates and compares H-SSF CW efficiency both in terms of water quality improvement (removal percentage) and achievement of Italian wastewater discharge and irrigation reuse limits. The mean removal percentage, for the overall operational life, of TSS, COD and BOD (80%, 63%, 58% obtained for H-SSF1 and 67%, 38%, 41% for H-SSF2), confirm the high reliability of CWs for wastewater treatment. However, despite the satisfactory removal of microbial indicators (the mean E. coli removal was up to 2.5 log unit for both beds), CWs didn't achieve the Italian limits for wastewater reuse. Information on hydraulic properties of the CWs were extracted from breakthrough curves of a non-reactive tracer (NaCl). By comparing the nominal (tau(n)) and actual residence time (tau), hydraulic behaviour was revealed.     

A Joint Numerical-Experimental Study on Impact Induced Intra-laminar and Inter-laminar Damage in Laminated Composites

The investigation of the mechanical response of fibre-reinforced composite laminates under impact loads can be very difficult due to the occurrence of simultaneous failure phenomena. Indeed, as a consequence of low velocity impacts, intra-laminar damages, like fibre and matrix cracking, and inter-laminar damages, such as delaminations, can take place simultaneously. These damage mechanisms can lead to significant reductions in strength and stability of the composite structure. In this paper a joint numerical-experimental study is proposed which, by means of non-destructive testing techniques (Ultra-sound and thermography) and non-linear explicit FEM analyses, aims to completely characterise the impact induced damage in composite laminates under low velocity impacts. Indeed the proposed numerical tool has been used to improve the understanding of the experimental data obtained by Non-Destructive Techniques. Applications on samples tested according to the AECMA (European Association of Aerospace Manufacturers) prEn6038 standard at three different impact energies are presented. The interaction between numerical and experimental investigation allowed to obtain an exhaustive insight on the different phases of the impact event considering the inter-laminar damage formation and evolution.     

CHL1 encodes a component of the low-affinity nitrate uptake system in Arabidopsis and shows cell type-specific expression in roots

The Arabidopsis CHL1 (AtNRT1) gene confers sensitivity to the herbicide chlorate and encodes a nitrate-regulated nitrate transporter. However, how CHL1 participates in nitrate uptake in plants is not yet clear. In this study, we examined the in vivo function of CHL1 with in vivo uptake measurements and in situ hybridization experiments. Under most conditions tested, the amount of nitrate uptake by a chl1 deletion mutant was found to be significantly less than that of the wild type. This uptake deficiency was reversed when a CHL1 cDNA clone driven by the cauliflower mosaic virus 35S promoter was expressed in transgenic chl1 plants. Furthermore, tissue-specific expression patterns showed that near the root tip, CHL1 mRNA is found primarily in the epidermis, but further from the root tip, the mRNA is found in the cortex or endodermis. These results are consistent with the involvement of CHL1 in nitrate uptake at different stages of root cell development. A functional analysis in Xenopus oocytes indicated that CHL1 is a low-affinity nitrate transporter with a K(m) value of approximately 8.5 mM for nitrate. This finding is consistent with the chlorate resistance phenotype of chl1 mutants. However, these results do not fit the current model of a single, constitutive component for the low-affinity uptake system. To reconcile this discrepancy and the complex uptake behavior observed, we propose a "two-gene" model for the low-affinity nitrate uptake system of Arabidopsis.     

Tests for comparing images based on randomization and permutation methods

Tests comparing image sets can play a critical role in PET research, providing a yes-no answer to the question "Are two image sets different?" The statistical goal is to determine how often observed differences would occur by chance alone. We examined randomization methods to provide several omnibus test for PET images and compared these tests with two currently used methods. In the first series of analyses, normally distributed image data were simulated fulfilling the requirements of standard statistical tests. These analyses generated power estimates and compared the various test statistics under optimal conditions. Varying whether the standard deviations were local or pooled estimates provided an assessment of a distinguishing feature between the SPM and Montreal methods. In a second series of analyses, we more closely simulated current PET acquisition and analysis techniques. Finally, PET images from normal subjects were used as an example of randomization. Randomization proved to be a highly flexible and powerful statistical procedure. Furthermore, the randomization test does not require extensive and unrealistic statistical assumptions made by standard procedures currently in use.     

Diagnosis of the industrial systems by fuzzy classification

The aim of this paper is to present a classifier based on a fuzzy inference system. For this classifier, we propose a parametrization method which is not necessarily based on an iterative training. This approach can be seen as a pre-parametrization which allows the determination of the rules base and the parameters of the membership functions. We also present a continuous and derivable version of the previous classifier and suggest an iterative learning algorithm based on a gradient method. An example using the learning basis IRIS, which is a benchmark for classification problems, is presented showing the performances of this classifier. Finally this classifier is applied to the diagnosis of a dc motor showing the effectiveness of this method.     

Biocompatibility and cutaneous reactivity of cellulosic polysaccharide film in induced skin wounds in rats

The development of a skin substitute suitable for immediately performing the function of the lost dermis and epidermis could result in a positive impact on the treatment of patients with extensive skin lesions. A biopolymer film was applied to skin wounds to investigate the biocompatibility and cutaneous reaction and to test its activity as a mechanical barrier and conductor in the healing process. Forty Wistar rats of both sexes were used in the present study. Two excisions were performed in the dorsal part of the skin flaps. The polysaccharide film was applied over one of the incisions and other incision was washed with saline. The time spent for complete healing of both lesions was virtually the same in both groups, during 21 days of observation. The film remained attached to the bed of the exposed wound for an average period of 6 days. There were no statistically significant differences with regard to lesion measurement area at assessment times of 2nd, 7th and 14th postoperative days. At day 21, the scar area showed a significant difference (0.0229). After 40 days, all wounds were completely healed. No statistically significant differences were found between the histological parameters assessed in the experimental and control groups. The cellulosic polysaccharide film integrated well with the tissue showing high biocompatibility and low skin reactivity.