An EIA method on single donor solubilized HLA antigens for the identification of anti-HLA antibodies

Primary biliary cirrhosis (PBC) is an immunologically mediated disease in which activated T lymphocytes attack and destroy epithelial cells in the small intralobular bile ducts of genetically susceptible patients. This article reviews the results of treatment of PBC with immunomodulatory agents. Results with drugs such as glucocorticoids, azathioprine, and chlorambucil have been disappointing because of either limited efficacy (azathioprine), toxicity (chlorambucil), or both (glucocorticoids). Colchicine improved tests of liver function in three prospective studies and was associated with improved survival for up to 4 years. However, survival benefits were lost at 8 years. Colchicine appears to slow the rate of progression of PBC but not to stop it. Preliminary results suggest that colchicine may have synergistic effects if used together with ursodeoxycholic acid, particularly in patients who are only partially responsive to ursodeoxycholic acid. Results with cyclosporine have been disappointing because of limited efficacy and predictable toxicity. The modest improvement in tests of liver function and survival are counterbalanced by the development of hypertension in some and worsening renal function in most. There is little beneficial effect on symptoms or histology. Results with methotrexate are promising. There are improvements in symptoms and tests of liver function that are equal to those seen with ursodeoxycholic acid and significant improvement in liver histology. Some patients, particularly those with striking inflammation and granulomas in portal triads, appear to have achieved sustained remission while on methotrexate. The effects of methotrexate are additive to those of ursodeoxycholic acid in patients whose blood tests have responded only partially to ursodeoxycholic acid. The most effective treatment of PBC will most likely use a combination of drugs such as ursodeoxycholic acid, colchicine, and methotrexate.     

Early detection of ageing in solder joints through laser probe thermal analysis of the peltier effect

We have recently developed an optical contactless method for testing the quality of solder joints during accelerated thermal cycling ageing processes.¹ The method was based upon the measurement of the dynamic thermal behaviour of the joint to short bursts of Joule heating. It has proved to be efficient in revealing the formation of cracks at the lead-solder interface. We present a method to evaluate ageing at a much earlier stage in the cycling process. We have observed in earlier work,¹ that before cracks appear, structural changes occur in the solder at the lead-solder interface. The thermal response of the solder joint is recorded over time to a Peltier heat perturbation produced by flowing a current pulse through the interface where structural changes occur. The key point in this method is to discriminate the Peltier effect from the Joule thermal response because both effects generate heat. The variation of the early Peltier response in the thermal cycling ageing tests is seen as a quantitative signature of the structural changes in the lead-solder interface.     

A variable radius roll adhesion test (VaRRAT) suitable for measuring the adhesion of paint to metal

Early trials and analysis of a new adhesion test are discussed. The test is designed for measuring the adhesion of paint to deformable steel sheets as used in building, automotive, and other cladding applications, and does not require detailed knowledge of the paint mechanical properties. A stiff overlay, such as an epoxy resin, is applied to the coating, and the steel substrate is peeled away using a roll of well-defined radius to which the steel substrate is constrained. The propagation of a crack within the paint or at some interface in the paint/metal system depends mostly on the mechanical properties and thickness of the overlay and the radius of the constraining roll. The test is shown to discriminate better than existing practical adhesion tests between paints of expected differing adhesion/cohesion, but also presents some inconsistencies that require further work to resolve. BHP Institute of Steel Processing and Products, Wollongong NSW 2522, Australia.     

Toward automatic phenotyping of developing embryos from videos.

We describe a trainable system for analyzing videos of developing C. elegans embryos. The system automatically detects, segments, and locates cells and nuclei in microscopic images. The system was designed as the central component of a fully automated phenotyping system. The system contains three modules 1) a convolutional network trained to classify each pixel into five categories: cell wall, cytoplasm, nucleus membrane, nucleus, outside medium; 2) an energy-based model, which cleans up the output of the convolutional network by learning local consistency constraints that must be satisfied by label images; 3) a set of elastic models of the embryo at various stages of development that are matched to the label images.     

Radiation damage induced in Si photodiodes by high-temperature neutron irradiation

Results are presented of a detailed study of the effects of high-temperature 4-MeV neutron irradiation on the performance degradation of Si pin photodiodes together with the radiation-induced defects, observed by deep level transient spectroscopy (DLTS). It was found that the dark current increases after irradiation, while the photocurrent decreases. After irradiation, two majority electron capture levels with (E _c–0.22 eV) and (E _c–0.40 eV) were induced in the n-Si substrate, while one minority hole capture level with (E _v+0.37 eV) was found. Additionally, the degradation of the device performance and the introduction rate of the lattice defects decreases with increasing irradiation temperature. For a 250 °C irradiation, the reduction of the reverse current is only 20% of the starting value. This result suggests that the creation and recovery of the radiation damage proceeds simultaneously at high temperatures.     

Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.     

Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8–12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior.     

Great enhancement of mechanical features in PLA based composites containing aligned few layer graphene (FLG), the effect of FLG loading,size, and dispersion on mechanical and thermal properties

Four series of polylactide (PLA) based composite films containing horizontally aligned few layer graphene (FLG) flakes of high aspect ratio and adsorbed albumin are prepared. The mechanical and thermal properties varies with percentage, dispersion degree and size of FLG flakes. Great improvement up to 290% and 360% of tensile modulus and strength respectively were obtained for the composite containing high lateral size of FLG at 0.17% wt, and up to 60% and 80% for the composite with very well dispersed 0.02% wt FLG. The composites of PLA and PEG-PLLA containing very well dispersed FLG flakes at 0.07% wt are ductile showing enhancement of elongation at break up to respectively 80% and 88%. Relatively high electrical conductivity, 5 × 10⁻³ S/cm, is measured for PLA film charged with 3% of FLG.     

Urban flood risk assessment using sewer flooding databases

Sustainable water management is a global challenge for the 21st century. One key aspect remains protection against urban flooding. The main objective is to ensure or maintain an adequate level of service for all inhabitants. However, level of service is still difficult to assess and the high-risk locations difficult to identify. In this article, we propose a methodology, which (i) allows water managers to measure the service provided by the urban drainage system with regard to protection against urban flooding; and (ii) helps stakeholders to determine effective strategies for improving the service provided. One key aspect of this work is to use a database of sewer flood event records to assess flood risk. Our methodology helps urban water managers to assess the risk of sewer flooding; this approach does not seek to predict flooding but rather to inform decision makers on the current level of risk and on actions which need to be taken to reduce the risk. This work is based on a comprehensive definition of risk, including territorial vulnerability and perceptions of urban water stakeholders. This paper presents the results and the methodological contributions from implementing the methodology on two case studies: the cities of Lyon and Mulhouse.