Report on the Aachen OCL meeting

As a continuation of the OCL workshop during the MODELS 2013 conference in October 2013, a number of OCL experts decided to meet in November 2013 in Aachen for two days to discuss possible short term improvements of OCL for an upcoming OMG meeting and to envision possible future long-term developments of the language. This paper is a sort of "minutes of the meeting" and intended to quickly inform the OCL community about the discussion topics

Software for full-color 3D reconstruction of the biological tissues internal structure

A software for processing sets of full-color images of biological tissue histological sections is developed. We used histological sections obtained by the method of high-precision layer-by-layer grinding of frozen biological tissues. The software allows restoring the image of the tissue for an arbitrary cross-section of the tissue sample. Thus, our method is designed to create a full-color 3D reconstruction of the biological tissue structure. The resolution of 3D reconstruction is determined by the quality of the initial histological sections. The newly developed technology available to us provides a resolution of up to 5 - 10 {\mu}m in three dimensions.Comment: 11 pages, 8 figure

Pharmacological And Genetic Reversal Of Age-Dependent Cognitive Deficits Attributable To Decreased Presenilin Function

Alzheimer\u27s disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced

Plk1 Phosphorylation of Orc2 and Hbo1 Contributes to Gemcitabine Resistance in Pancreatic Cancer

Although gemcitabine is the standard chemotherapeutic drug for treatment of pancreatic cancer, almost all patients eventually develop resistance to this agent. Previous studies identified Polo-like kinase 1 (Plk1) as the mediator of gemcitabine resistance, but the molecular mechanism remains unknown. In this study, we show that Plk1 phosphorylation of Orc2 and Hbo1 mediates the resistance to gemcitabine. We show that the level of Plk1 expression positively correlates with gemcitabine resistance, both in pancreatic cancer cells and xenograft tumors. Overexpression of Plk1 increases gemcitabine resistance, while inhibition of Plk1 sensitizes pancreatic cancer cells to gemcitabine treatment. To validate our findings, we show that inhibition of Plk1 sensitizes tumors to gemcitabine treatment in a mouse xenograft study. Mechanistically, we find that Plk1 phosphorylation of Orc2 maintains DNA replication on gemcitabine treatment. Furthermore, Plk1 phosphorylation of Hbo1 transcriptionally increases cFos expression and consequently elevates its target multidrug resistance 1 (MDR1), which was previously reported to confer chemotherapeutic drug resistance. Knockdown of cFos or MDR1 sensitizes gemcitabine-resistant cells to gemcitabine treatment. Finally, pancreatic cancer cells expressing Plk1-unphosphorylatable mutants of Orc2 or Hbo1 are more sensitive to gemcitabine than cells expressing wild-type Orc2 or Hbo1. In short, our study provides a mechanism for Plk1-mediated gemcitabine resistance, suggesting that Plk1 is a promising target for treatment of gemcitabine-resistant pancreatic cancer

An Innovative System for Monitoring Radon and Indoor Air Quality

Nowadays, a global trend towards increasing the performance of a building is the reduction in energy consumption. In this respect, for existing residential buildings the most common techniques are the application of a thermal insulation layer to the exterior wall of the building and / or window replacements. Unfortunately, their application without proper education of those involved may have a negative effect on the indoor air quality. The use of a continuous monitoring device can give the owner the ability to understand the impact of his behaviour on indoor air quality and, as such, to adjust his routine in order to maintain the indoor air quality at the desired level. This paper introduces a prototype, called ICA system, for continuous, real-time indoor air quality monitoring. The ICA system presents sensors for monitoring the concentration of radon, CO2, CO, VOCs, as well as meteorological parameters, such as temperature, pressure, and relative humidity. Experiments were performed both in laboratory and in situ conditions for testing and validating the proposed system.This work was supported by the project ID P_37_229, Contract No. 22/01.09.2016, with the title “Smart Systems for Public Safety through Control and Mitigation of Residential Radon linked with Energy Efficiency Optimization of Buildings in Romanian Major Urban Agglomerations SMART-RAD-EN” of the POC Programme

Drug discovery in advanced prostate cancer: translating biology into therapy.

Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs