Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease

AIM: Prostaglandin G/H synthase 2 (PTGS2 or COX2) is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases (IBD). In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS: We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTGS2 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5 exonuclease assay (TaqMan). New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS: Allele 5209G was weakly associated with Crohn's disease (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57), and allele 8473T with ulcerative colitis (OR 1.50, 95%CI 1.00-2.27). The haplotype including both alleles showed a strong association with IBD (OR 13.15, 95%CI 3.17-116.15). This haplotype, while rare (-0.3%) in the general population, is found more frequently in patients (3.5%). CONCLUSION: Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD

Multidisciplinary Experience In The Selection Of Patients For Tubal Sterilization.

Results of the use of a special protocol for evaluation of patients requiring tubal ligation is presented after applied by a multidisciplinary group. The authors conclude that the use of defined parameters of age, parity, marital union duration, number of children alive and the presence of maternal clinical pathology are useful to identify patients with smaller chances of regret after surgery.27% of reproductive-age women in Brazil have chosen surgical sterilization as their contraceptive method. Most of these women who have undergone tubal sterilization opted for cesarean surgery. However, given the young ages of many of these women, many regret having been sterilized. This paper summarizes the experience of a multidisciplinary group in evaluating women who apply for surgical sterilization at the Department of Tocogynecology, Faculdade de Ciencas Medicas, Universidade Estadual de Campinas in Sao Paulo. Detailed descriptions are presented of the medical and social characteristics of cases seen between June 1988 and July 1989. The authors conclude that the use of the defined parameters of age, parity, marital union duration, number of living children, and the presence of maternal clinical pathology are useful in identifying the patients who are least likely to regret undergoing surgical sterilization.113171572

Efficacy and Tolerability of Lapatinib in the Management of Breast Cancer

Approximately 20%–25% of all breast cancers over express a key cell surface growth factor receptor known as HER2. HER2 plays a key role in cell growth and proliferation and is linked to worse clinical outcomes, making it a logical therapeutic target. The first HER2 targeted drug to be approved by the FDA, was the humanized monoclonal antibody trastuzumab, after it showed improvements in survival in the adjuvant setting, and delayed time to progression in the metastatic setting. Although highly effective, for reasons that are not clear, some patients display resistance to trastuzumab. Lapatinib is an oral, small molecule tyrosine kinase inhibitor, that inhibits both the HER1 ahd HER2 receptors and may be able to overcome trastuzumab resistance. Lapatinib is approved in the second line setting for use in combination with capecitabine or with letrozole. In this review, we will discuss the indications, concerns or any issues with regards to the drug

First results on light readout from the 1-ton ArDM liquid argon detector for dark matter searches

ArDM-1t is the prototype for a next generation WIMP detector measuring both the scintillation light and the ionization charge from nuclear recoils in a 1-ton liquid argon target. The goal is to reach a minimum recoil energy of 30\,keVr to detect recoiling nuclei. In this paper we describe the experimental concept and present results on the light detection system, tested for the first time in ArDM on the surface at CERN. With a preliminary and incomplete set of PMTs, the light yield at zero electric field is found to be between 0.3-0.5 phe/keVee depending on the position within the detector volume, confirming our expectations based on smaller detector setups.Comment: 14 pages, 10 figures, v2 accepted for publication in JINS

Characterization of large area photomultipliers and its application to dark matter search with noble liquid detectors

There is growing interest in the use of noble liquid detectors to study particle properties and search for new phenomena. In particular, they are extremely suitable for performing direct searches for dark matter. In this kind of experiments, the light produced after an interaction within the sensitive volume is usually read-out by photomultipliers. The need to go to masses in the tonne scale to explore deeper regions of the parameter space, calls for the use of large area photomultipliers. In this paper we address the need to perform laboratory calibration measurements of these large photomultipliers, in particular to characterize its behaviour at cryogenic temperatures where no reference from the manufacturer is available. We present comparative tests of phototubes from two companies. The tests are performed in conditions similar to those of operation in a real experiment. Measurements of the most relevant phototube parameters (quantum efficiency, gain, linearity, etc.) both at room and liquid Argon temperatures are reported. The results show that the studied phototubes comply with the stringent requirements posed by current dark matter searches performed with noble-liquid detectors.This work has been supported by CICYT Grants FPA-2006-00684, FPA-2002-01835 and FPA- 2005-07605-C02-01

Functional dissection of the chickpea (Cicer arietinum l.) stay-green phenotype associated with molecular variation at an ortholog of mendel’s i gene for cotyledon color: Implications for crop production and carotenoid biofortification

“Stay-green” crop phenotypes have been shown to impact drought tolerance and nutritional content of several crops. We aimed to genetically describe and functionally dissect the particular stay-green phenomenon found in chickpeas with a green cotyledon color of mature dry seed and investigate its potential use for improvement of chickpea environmental adaptations and nutritional value. We examined 40 stay-green accessions and a set of 29 BC2F4-5 stay-green introgression lines using a stay-green donor parent ICC 16340 and two Indian elite cultivars (KAK2, JGK1) as recurrent parents. Genetic studies of segregating populations indicated that the green cotyledon trait is controlled by a single recessive gene that is invariantly associated with the delayed degreening (extended chlorophyll retention). We found that the chickpea ortholog of Mendel’s I locus of garden pea, encoding a SGR protein as very likely to underlie the persistently green cotyledon color phenotype of chickpea. Further sequence characterization of this chickpea ortholog CaStGR1 (CaStGR1, for carietinum stay-green gene 1) revealed the presence of five different molecular variants (alleles), each of which is likely a loss-of-function of the chickpea protein (CaStGR1) involved in chlorophyll catabolism. We tested the wild type and green cotyledon lines for components of adaptations to dry environments and traits linked to agronomic performance in different experimental systems and different levels of water availability. We found that the plant processes linked to disrupted CaStGR1 gene did not functionality affect transpiration efficiency or water usage. Photosynthetic pigments in grains, including provitaminogenic carotenoids important for human nutrition, were 2–3-fold higher in the stay-green type. Agronomic performance did not appear to be correlated with the presence/absence of the stay-green allele. We conclude that allelic variation in chickpea CaStGR1 does not compromise traits linked to environmental adaptation and agronomic performance, and is a promising genetic technology for biofortification of provitaminogenic carotenoids in chickpea

Tribological performance of an H-DLC coating prepared by PECVD

Carbon-based coatings are of wide interest due to their application in machine elements subjected to continuous contact where fluid lubricant films are not permitted. This paper describes the tribological performance under dry conditions of duplex layered H-DLC coating sequentially deposited by microwave excited plasma enhanced chemical vapour deposition on AISI 52100 steel. The architecture of the coating comprised Cr, WC, and DLC (a-C:H) with a total thickness of 2.8 μm and compressive residual stress very close to 1 GPa. Surface hardness was approximately 22 GPa and its reduced elastic modulus around 180 GPa. Scratch tests indicated a well adhered coating achieving a critical load of 80 N. The effect of normal load on the friction and wear behaviours were investigated with steel pins sliding against the actual coating under dry conditions at room temperature (20 ± 2°C) and 35-50% RH. The results show that coefficient of friction of the coating decreased from 0.21 to 0.13 values with the increase in the applied loads (10-50 N). Specific wear rates of the surface coating also decrease with the increase in the same range of applied loads. Maximum and minimum values were 14 × 10-8 and 5.5 × 10-8 mm-3/N m, respectively. Through Raman spectroscopy and electron microscopy it was confirmed the carbon-carbon contact, due to the tribolayer formation on the wear scars of the coating and pin. In order to further corroborate the experimental observations regarding the graphitisation behaviour, the existing mathematical relationships to determine the graphitisation temperature of the coating/steel contact as well as the flash temperature were used