The role of MUC1 and MUC3 in the biology and prognosis of colorectal cancer

BACKGROUND: MUC1 and MUC3 are from a large family of glycoproteins with an aberrant expression profile in various malignancies. Much interest has been focused on the role of these proteins in the development and progression of colorectal cancer; however, no previous studies have included the highly confounding variable of vascular invasion in their survival analysis. Using high throughput tissue microarray technology we assessed the prognostic value of MUC1 and MUC3 expression in the largest cohort of colorectal cancer patients to date. We propose that tumours lacking expression of MUC1 and MUC3 will be more likely to metastasise, due to previously observed loss of cell-cell adhesion, and this will therefore lead to more aggressive cancers with poorer prognosis. METHODS: A tissue micro-array was prepared from tumour samples of 462 consecutive patients undergoing resection of a primary colorectal cancer. A comprehensive prospectively recorded data base with mean follow up of 75 months was collected and included common clinicopathological variables and disease specific survival. Immunohistochemical analysis of MUC1 and MUC3 expression was performed using antibodies NCL-MUC1 and 1143/B7 respectively, results were correlated with the variables within the database. RESULTS: Positive expression of MUC1 and MUC3 was seen in 32% and 74% of tumours respectively. On univariate analysis no correlation was seen with either MUC1 or MUC3 and any of the clinicopathological variables including tumour grade and stage, vascular invasion and tumour type. Kaplan-Meier analysis demonstrated a significant reduction in disease specific survival with MUC1 positive tumours (p = 0.038), this was not seen with MUC3 (p = 0.552). On multivariate analysis, using Cox proportional hazards model, MUC1 expression was shown to be an independent marker of prognosis (HR 1.339, 95%CI 1.002–1.790, p = 0.048). CONCLUSION: MUC1 expression in colorectal cancer is an independent marker of poor prognosis, even when vascular invasion is included in the analysis. These results support previous studies suggesting a role for MUC1 in colorectal cancer development possibly through its effects on cell adhesion

Increasing delirium skills at the front door : results from a repeated survey on delirium knowledge and attitudes

© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: [email protected] reviewedPostprin

Induction of methionine-sulfoxide reductases protects neurons from amyloid β-protein insults in vitro and in vivo

Amyloid β-protein (Aβ) self-assembly into toxic oligomers and fibrillar polymers is believed to cause Alzheimer’s disease (AD). In the AD brain, a high percentage of Aβ contains Met-sulfoxide at position 35, though the role this modification plays in AD is not clear. Oxidation of Met35 to sulfoxide has been reported to decrease Aβ assembly and neurotoxicity, whereas surprisingly, Met35 oxidation to sulfone yields similar toxicity to unoxidized Aβ. We hypothesized that the lower toxicity of Aβ-sulfoxide might result not only from structural alteration of the C-terminal region, but also from activation of methionine-sulfoxide reductase (Msr), an important component of the cellular antioxidant system. Supporting this hypothesis, we found that the low toxicity of Aβ-sulfoxide correlated with induction of Msr activity. In agreement with these observations, in MsrA−/− mice the difference in toxicity between native Aβ and Aβ-sulfoxide was essentially eliminated. Subsequently, we found that treatment with N-acetyl-Met-sulfoxide could induce Msr activity and protect neuronal cells from Aβ toxicity. In addition, we measured Msr activity in a double-transgenic mouse model of AD and found that it was increased significantly relative to non-transgenic mice. Immunization with a novel methionine sulfoxide-rich antigen for six months led to antibody production, decreased Msr activity, and lowered hippocampal plaque burden. The data suggest an important neuroprotective role for the Msr system in the AD brain, which may lead to development of new therapeutic approaches for AD

How the other half lives: CRISPR-Cas's influence on bacteriophages

CRISPR-Cas is a genetic adaptive immune system unique to prokaryotic cells used to combat phage and plasmid threats. The host cell adapts by incorporating DNA sequences from invading phages or plasmids into its CRISPR locus as spacers. These spacers are expressed as mobile surveillance RNAs that direct CRISPR-associated (Cas) proteins to protect against subsequent attack by the same phages or plasmids. The threat from mobile genetic elements inevitably shapes the CRISPR loci of archaea and bacteria, and simultaneously the CRISPR-Cas immune system drives evolution of these invaders. Here we highlight our recent work, as well as that of others, that seeks to understand phage mechanisms of CRISPR-Cas evasion and conditions for population coexistence of phages with CRISPR-protected prokaryotes.Comment: 24 pages, 8 figure

Data protection risk modeling into business process analysis

We present a novel way to link business process model with data protection risk management. We use established body of knowledge regarding risk manager concepts and business process towards data protections. We try to contribute to the problems that today organizations should find a suitable data protection model that could be used in as a risk framework. The purpose of this document is to define a model to describe data protection in the context of risk. Our approach including the identification of the main concepts of data protection according to the scope of the with EU directive data protection regulation. We outline data protection model as a continuous way of protection valued organization information regarding personal identifiable information. Data protection encompass the preservation of personal data information from unauthorized access, use, modification, recording or destruction. Since this kind of service is offered in a continuous way, it is important to stablish a way to measure the effectiveness of awareness of data subject discloses regrading personal identifiable information.info:eu-repo/semantics/publishedVersio

SuperMeshing: a new deep learning architecture for increasing the mesh density of physical fields in metal forming numerical simulation

In stress field analysis, the finite element method is a crucial approach, in which the mesh-density has a significant impact on the results. High mesh density usually contributes authentic to simulation results but costs more computing resources. To eliminate this drawback, we propose a data-driven mesh-density boost model named SuperMeshingNet that uses low mesh-density as inputs, to acquire high-density stress field instantaneously, shortening computing time and cost automatically. Moreover, the Res-UNet architecture and attention mechanism are utilized, enhancing the performance of SuperMeshingNet. Compared with the baseline that applied the linear interpolation method, SuperMeshingNet achieves a prominent reduction in the mean squared error (MSE) and mean absolute error (MAE) on the test data. The well-trained model can successfully show more excellent performance than the baseline models on the multiple scaled mesh-density, including 2X, 4X, and 8X. Enhanced by SuperMeshingNet with broaden scaling of mesh density and high precision output, FEA can be accelerated with seldom computational time and cost

When is a GIST not a GIST? A case report of synchronous metastatic gastrointestinal stromal tumor and fibromatosis

<p>Abstract</p> <p>Background</p> <p>A number of non-malignant diseases that share similar morphological features as gastrointestinal stromal tumor (GIST) have been reported. Co-existence of GIST with these other diseases is rarely recognized or reported.</p> <p>Case presentation</p> <p>We report a case of a 62 year-old man with long-term stable control of metastatic GIST with systemic therapy, presented with an apparent intra-abdominal progression but not supported by imaging with positron emission tomography. Subsequent resection of the intra-abdominal tumor identified a non-malignant fibroid.</p> <p>Conclusion</p> <p>Differentiating localized progression of GIST from other diseases has important prognostic and therapeutic implications. The potential for co-existence of non-malignant soft tissue neoplasm should always be considered.</p

Inferences of Mantle Viscosity Based on Ice Age Data Sets: The Bias in Radial Viscosity Profiles Due to the Neglect of Laterally Heterogeneous Viscosity Structure

Inferences of mantle viscosity using glacial isostatic adjustment (GIA) data are hampered by data sensitivity to the space‐time geometry of ice cover. A subset of GIA data is relatively insensitive to this ice history: the Fennoscandian relaxation spectrum (FRS), postglacial decay times in Canada and Scandinavia, and the rate of change of the degree‐2 zonal harmonic of the geopotential ( urn:x-wiley:21699313:media:jgrb53014:jgrb53014-math-0001). These geographically limited data have been inverted to constrain the radial (one‐dimensional [1D]) mantle viscosity profile. We explore potential biases in these 1D inversions introduced by neglecting a three‐dimensional (3D) viscosity structure. We perform 1D Bayesian inversions of synthetic GIA data generated from Earth models with realistic 3D variations in mantle viscosity and lithospheric thickness and compare results to the 1D viscosity profile associated with the 3D model used to generate the synthetics. Differences between these two 1D profiles reflect GIA data resolution and biasing introduced by neglecting, in the inversions, a 3D viscosity structure. We focus on the second issue, demonstrating that the largest bias occurs within the upper mantle (in particular, the transition zone). This remains consistent when varying inversion parameters (e.g., prior/starting models) and the 1D/3D viscosity fields adopted in generating the synthetics. Inversions of individual data sets show 3D biasing increases for data exhibiting shallower (thus more localized) sensitivity to viscosity. Of the data considered herein, inversions of the FRS are subject to the largest bias followed by decay time data. The bias is minimal for urn:x-wiley:21699313:media:jgrb53014:jgrb53014-math-0002, as its deeper sensitivity is accompanied by broader averaging of structure in radial and lateral directions

Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome : a systematic review and meta-analysis

Aims/hypothesis FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. Methods A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. Results A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10−11) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10−10). This translated into an approximately 3.3 kg/m2 increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. Conclusions/interpretation The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS

Damage Analysis of Reinforced Concrete Structures with Substandard Detailing

The goal of this study is to investigate seismic behaviour of existing R/C buildings designed and constructed in accordance with standards that do not meet current seismic code requirements. In these structures, not only flexure, but also shear and bond-slip deformation mechanisms need to be considered, both separately and in combination. To serve this goal, a finite element model is developed for inelastic seismic analysis of complete planar R/C frames. The proposed finite element is able to capture gradual spread of inelastic flexural and shear deformations as well as their interaction in the end regions of R/C members. Additionally, it is capable of predicting shear failures caused by degradation of shear strength in the plastic hinges of R/C elements, as well as pullout failures caused by inadequate anchorage of the reinforcement in the joint regions. The finite element is fully implemented in the general inelastic finite element code IDARC2D and it is verified against experimental results involving individual column and plane frame specimens with nonductile detailing. It is shown that, in all cases, satisfactory correlation is established between the model predictions and the experimental evidence. Finally, parametric studies are conducted to illustrate the significance of each deformation mechanism on the seismic response of the specimens under investigation. It is concluded, that all deformation mechanisms, as well as their interaction, should be taken into consideration in order to predict reliably seismic damage of R/C structures with substandard detailing