eCAD System Design - Applications in Architecture

The rapid advances in learning technologies, computer modeling, multimedia and spatial sciences, as well as the availability of many powerful graphics PCs and workstations, make 3-D modeling-based methods for personalized e-learning with eCAD (modeling) functionality feasible. Personalized eCAD learning is a new term in engineering, environment and architecture education, related to the development of learning educational units (3-D learning objects) with re-usable digital architecture functionality, and introduced to literature for the first time within this paper. In particular, for university education courses in eCAD, digital architecture, design computing and CAAD (reagarding spatial information systems, architectures, monuments, cultural heritage sites, etc.), such a e-learning methodolgy must be able to derive spatial, pictorial, geometric, spatial, topological, learning and semantic information from the target object (a 3-D model) or scene (a 3-D landscape environment) or procedure (a 3-D simulation approach to a phenomenon), in such a way that it can be directly used for e-learning purposes regarding the spatial topology, the history, the architecture, the structure and the temporal (time-based) 3-D geometry of the projected object, scene or procedure. This paper is about the system design of such a e-learning method. For this purpose, the requirements, objectives and pedagogical extensions are presented and discussed. Finaly, a practical project is used to demonstrate the functionality and the performance of the proposed methodology in architectur

Mesenchymal/Stromal Gene Expression Signature Relates to Basal-Like Breast Cancers, Identifies Bone Metastasis and Predicts Resistance to Therapies

BACKGROUND: Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm. METHODOLOGY/PRINCIPAL FINDINGS: By integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathways of previously described carcinoma-derived mesenchymal tumor cells (A17) with that of both carcinomas and other mesenchymal phenotypes, such as mesenchymal stem cells (MSCs), breast stroma, and various types of sarcomas. We identified three mesenchymal/stromal-signatures which A17 cells shares with MSCs and breast stroma. By using a recently developed computational approach with publicly available microarray data, we show that these signatures: 1) significantly relates to basal-like breast cancer subtypes; 2) significantly relates to bone metastasis; 3) are up-regulated after hormonal treatment; 4) predict resistance to neoadjuvant therapies. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that mesenchymalization is an intrinsic property of the most aggressive tumors and it relates to therapy resistance as well as bone metastasis

Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation

Objective: To examine the performance of screening for early-, preterm- and term-preeclampsia (PE) at 11 13 weeks’ gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PLGF) and serum pregnancy associated plasma protein A (PAPP A). Methods The data for this study were derived from three previously reported prospective non intervention screening studies at 11+0 – 13+6 weeks’ gestation in a combined total of 61,174 singleton pregnancies, including 1,770 (2.9%) that developed PE. Bayes theorem was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiple of the median (MoM) values to derive the p patient specific risks of delivery with PE at <37 weeks’ gestation. The performance of such screening was estimated. Results In pregnancies that develop ed PE , compared to those without PE, the MoM values of UtA-PI and MAP were increased and PAPP A and PLGF were decreased and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PLGF predicted 90% of early PE, 75% of preterm PE and 4 1 % of term PE, at screen positive rate of 10%; inclusion of PAPP A did not improve the performance of screening The performance of screening depended on the racial origin of the women; in screening by a combination of maternal factors, MAP, UtA-PI and PLGF and use of the risk cut off of 1 in 10 0 for PE at <37 weeks in Caucasian women, the screen positive rate was 10% and detection rates for early --, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut off in women of Afro Caribbean racial origin, the screen positive rate was 34% and detection rates for early --, preterm and term PE were 100%, 92% and 75%, respectively. Conclusion Screening by maternal factors and biomarkers at 11-13 weeks’ gestation can identify a high proportion of pregnancies that develop early- and preterm-PE

The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols

The Combination of RAD001 and NVP-BEZ235 Exerts Synergistic Anticancer Activity against Non-Small Cell Lung Cancer In Vitro and In Vivo

The phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit PI3K, mTOR or both are currently under development. The mTOR allosteric inhibitor, RAD001, and the PI3K/mTOR dual kinase inhibitor, BEZ235, are examples of these agents. We were interested in developing strategies to enhance mTOR-targeted caner therapy. In this study, we found that BEZ235 alone effectively inhibited the growth of rapamycin-resistant cancer cells. Interestingly, the combination of sub-optimal concentrations of RAD001 and BEZ235 exerted synergistic inhibition of the growth of human lung cancer cells along with induction of apoptosis and G1 arrest. Furthermore, the combination was also more effective than either agent alone in inhibiting the growth of lung cancer xenografts in mice. The combination showed enhanced effects on inhibiting mTOR signaling and reducing the expression of c-Myc and cyclin D1. Taken together, our results suggest that the combination of RAD001 and BEZ235 is a novel strategy for cancer therapy

Intradialytic versus home based exercise training in hemodialysis patients: a randomised controlled trial

Background: Exercise training in hemodialysis patients improves fitness, physical function, quality of life and markers of cardiovascular disease such as arterial stiffness. The majority of trials investigating this area have used supervised exercise training during dialysis (intradialytic), which may not be feasible for some renal units. The aim of this trial is to compare the effects of supervised intradialytic with unsupervised home-based exercise training on physical function and arterial stiffness

Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells

Introduction: We assessed expression of p85 and p110a PI3K subunits in non-small cell lung cancer (NSCLC) specimens and the association with mTOR expression, and studied effects of targeting the PI3K/AKT/mTOR pathway in NSCLC cell lines. Methods: Using Automated Quantitative Analysis we quantified expression of PI3K subunits in two cohorts of 190 and 168 NSCLC specimens and correlated it with mTOR expression. We studied effects of two PI3K inhibitors, LY294002 and NVP-BKM120, alone and in combination with rapamycin in 6 NSCLC cell lines. We assessed activity of a dual PI3K/mTOR inhibitor

Identification of Shell Colour Pigments in Marine Snails Clanculus pharaonius and C. margaritarius (Trochoidea; Gastropoda)

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ The attached file is the published version of the article

Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications

Minichromosome maintenance proteins (MCM) have recently emerged as novel proliferation markers with prognostic implications in several tumour types. This is the first study investigating MCM-2 and MCM-5 immunohistochemical expression in a series of ovarian adenocarcinomas and low malignant potential (LMP) tumours aiming to determine possible associations with clinicopathological parameters, the conventional proliferation index Ki-67, cell cycle regulators (p53, p27Kip1, p21WAF1 and pRb) and patients' outcome. Immunohistochemistry was applied in a series of 43 cases of ovarian LMP tumours and 85 cases of adenocarcinomas. Survival analysis was restricted to adenocarcinomas. The median MCM-2 and MCM-5 labelling indices (LIs) were significantly higher in adenocarcinomas compared to LMP tumours (P<0.0001 for both associations). In adenocarcinomas, the levels of MCM-2 and MCM-5 increased significantly with advancing tumour stage (P=0.0052 and P=0.0180, respectively), whereas both MCM-2 and MCM-5 increased significantly with increasing tumour grade (P=0.0002 and P=0.0006, respectively) and the presence of bulky residual disease (P<0.0001 in both relationships). A strong positive correlation was established between MCM-2 or MCM-5 expression level and Ki-67 LI (P<0.0001) as well as p53 protein (P=0.0038 and P=0.0500, respectively). Moreover, MCM-2 LI was inversely correlated with p27Kip−1 LI (P=0.0068). Finally, both MCM-2 and MCM-5 were associated significantly with adverse patients' outcome in both univariate (⩾20 vs >20%, P=0.0011 and ⩾25 vs <25%, P=0.0100, respectively) and multivariate (P=0.0001 and 0.0090, respectively) analysis. An adequately powered independent group of 45 patients was used in order to validate our results in univariate survival analysis. In this group, MCM-2 and MCM-5 expression retained their prognostic significance (P<0.0001 in both relationships). In conclusion, MCM-2 and MCM-5 proteins appear to be promising as prognostic markers in patients with ovarian adenocarcinomas