New biocide active substances:needs and challenges in the EU as viewed by industry

Emerging regulatory initiatives in the EU are driving towards more environmentally safe chemicals, used as such or in a wide range of products and applications. The aim of the regulations is also to foster and support the emergence of new or safer alternatives and to drive innovations thereof. Biocides are chemicals, which are used in a vast and steadily growing number of applications in order to preserve product safety and quality, however, the number of the Active Substances (AS) used in biocides is decreasing in the EU concurrent with the implementation of the Biocidal Product Directive (BPD). Accordingly, the present study attempts to elucidate views of representatives of the biocide industry in order to identify some of the present drivers and challenges of new AS development in the different biocide application areas, with emphasis on the economic feasibility of safer biocide development in the future. Notably, the costs of vertebrate testing are a major factor in development of new AS. Therefore, an evaluation of the costs of such tests and their total proportion of total AS development costs is also discussed. Industry expectations for the implementation of the BPD and impacts thereof are presented.<br

Feasibility of Active Ingredient (AI) development for new biocides in the EU

Biocides usage covers a vast industrial area and the history of biocide and other antimicrobial agent usage in various forms and applications dates back centuries. While the emerging EU regulations (BPD, REACH and others) strive to increase the safety and the eco-efficiency of chemical products and production processes, such changes may also create voids in the availability of current biocides due to outphasing. The present study evaluated the need for new Active Ingredient (AI) development. The feasibility of such development was explored, and the data of economic feasibility analysis shows that, contrary to general expectations, AI development can become profitable within certain economic boundaries

Breakdown of long-range temporal correlations in theta oscillations in patients with major depressive disorder

Neuroimaging has revealed robust large-scale patterns of high neuronal activity in the human brain in the classical eyes-closed wakeful rest condition, pointing to the presence of a baseline of sustained endogenous processing in the absence of stimulus-driven neuronal activity. This baseline state has been shown to differ in major depressive disorder. More recently, several studies have documented that despite having a complex temporal structure, baseline oscillatory activity is characterized by persistent autocorrelations for tens of seconds that are highly replicable within and across subjects. The functional significance of these long-range temporal correlations has remained unknown. We recorded neuromagnetic activity in patients with a major depressive disorder and in healthy control subjects during eyes-closed wakeful rest and quantified the long-range temporal correlations in the amplitude fluctuations of different frequency bands. We found that temporal correlations in the theta-frequency band (3-7 Hz) were almost absent in the 5-100 s time range in the patients but prominent in the control subjects. The magnitude of temporal correlations over the left temporocentral region predicted the severity of depression in the patients. These data indicate that long-range temporal correlations in theta oscillations are a salient characteristic of the healthy human brain and may have diagnostic potential in psychiatric disorders. We propose a link between the abnormal temporal structure of theta oscillations in the depressive patients and the systems-level impairments of limbic-cortical networks that have been identified in recent anatomical and functional studies of patients with major depressive disorder. Copyright © 2005 Society for Neuroscience

The modern way of performing construction management responsibilities

Digital technologies are becoming increasingly wide-spread both in our personal and in our professional lives. This change has been evident also in the construction industry, although the industry has been identified as one of the least digitalised industry sectors. This research investigates how various digital technologies have become and are becoming part of construction management responsibilities. Construction management responsibilities have been identified through a document analysis as eight responsibility groups including management of time, cost, quality, health and safety, environmental factors, resources, and contracts, and development of human resources and processes. Construction management related digital technologies on the other hand have been identified through a document analysis and a systematic literature review and categorised under communication and other enabling technologies, technologies combining hardware and software in intelligent systems, and data technologies. The way how the construction management responsibilities and the digital technologies interlink forms a description of the modern way of performing construction management responsibilities. Some of the technologies are in everyday use across construction management professionals, however, many are at their pilot stage offering a perspective not just to the present but to the near future for the whole discipline.publishedVersionPeer reviewe

Symbolic Partial-Order Execution for Testing Multi-Threaded Programs

We describe a technique for systematic testing of multi-threaded programs. We combine Quasi-Optimal Partial-Order Reduction, a state-of-the-art technique that tackles path explosion due to interleaving non-determinism, with symbolic execution to handle data non-determinism. Our technique iteratively and exhaustively finds all executions of the program. It represents program executions using partial orders and finds the next execution using an underlying unfolding semantics. We avoid the exploration of redundant program traces using cutoff events. We implemented our technique as an extension of KLEE and evaluated it on a set of large multi-threaded C programs. Our experiments found several previously undiscovered bugs and undefined behaviors in memcached and GNU sort, showing that the new method is capable of finding bugs in industrial-size benchmarks.Comment: Extended version of a paper presented at CAV'2

Role of fibroblast growth factor receptors (FGFR) and FGFR like-1 (FGFRL1) in mesenchymal stromal cell differentiation to osteoblasts and adipocytes

Fibroblast growth factors (FGF) and their receptors (FGFRs) regulate many developmental processes including differentiation of mesenchymal stromal cells (MSC). We developed two MSC lines capable of differentiating to osteoblasts and adipocytes and studied the role of FGFRs in this process. We identified FGFR2 and fibroblast growth factor receptor like-1 (FGFRL1) as possible actors in MSC differentiation with gene microarray and qRT-PCR. FGFR2 and FGFRL1 mRNA expression strongly increased during MSC differentiation to osteoblasts. FGF2 treatment, resulting in downregulation of FGFR2, or silencing FGFR2 expression with siRNAs inhibited osteoblast differentiation. During adipocyte differentiation expression of FGFR1 and FGFRL1 increased and was down-regulated by FGF2. FGFR1 knockdown inhibited adipocyte differentiation. Silencing FGFR2 and FGFR1 in MSCs was associated with decreased FGFRL1 expression in osteoblasts and adipocytes, respectively. Our results suggest that FGFR1 and FGFR2 regulate FGFRL1 expression. FGFRL1 may mediate or modulate FGFR regulation of MSC differentiation together with FGFR2 in osteoblastic and FGFR1 in adipocytic lineage.</div

Managing Inventory on Blood Supply Chain

There is unbalance the amount of blood demand and the availability of blood for each component at Blood Transfusion Unit in Indonesia. As the result, this component run into inventory shortage so management need to maintain the strategy of blood supply chain for the patients. Purpose of this is to manage inventory on the blood component of Packed Red Cells which it to be the highest blood component requirement for patient in this case study. Managing inventory is done through several stages including forecasting method, safety stock, and re-order point. Finding of this study was obtained that exponential smoothing (α = 0.95) to be the best forecasting method. Then, to manage inventory, this agency need to prepared 34 blood bags for safety stock and 76 blood bags for re-order point. This results able to give recommendation to the Blood Transfusion Unit at Indonesia regarding with the number of blood component provided and how much re-order to be made at the time of reaching the lead time. Further study is suggested to conduct simulation method in order to evaluate policy in managing blood inventory and prepare scenario for optimizing inventory level. Keywords Blood ·Blood transfusion unit, Production Re-order point, Inventory · Safety stock, Supply cha

Adapting Component-based Systems at Runtime via Policies with Temporal Patterns

International audienceDynamic reconfiguration allows adding or removing components of component-based systems without incurring any system downtime. To satisfy specific requirements, adaptation policies provide the means to dynamically reconfigure the systems in relation to (events in) their environment. This paper extends event-based adaptation policies by integrating temporal requirements into them. The challenge is to reconfigure component-based systems at runtime while considering both their functional and non-functional requirements. We illustrate our theoretical contributions with an example of an autonomous vehicle location system. An implementation using the Fractal component model constitutes a practical contribution. It enables dynamic reconfigurations guided by either enforcement or reflection adaptation policies

Dovitinib dilactic acid reduces tumor growth and tumor-induced bone changes in an experimental breast cancer bone growth model

Advanced breast cancer has a high incidence of bone metastases. In bone, breast cancer cells induce osteolytic or mixed bone lesions by inducing an imbalance in bone formation and resorption. Activated fibroblast growth factor receptors (FGFRs) are important in regulation of tumor growth and bone remodeling. In this study we used FGFR1 and FGFR2 gene amplifications containing human MFM223 breast cancer cells in an experimental xenograft model of breast cancer bone growth using intratibial inoculation technique. This model mimics bone metastases in breast cancer patients. The effects of an FGFR inhibitor, dovitinib dilactic acid (TKI258) on tumor growth and tumor-induced bone changes were evaluated. Cancer-induced bone lesions were smaller in dovitinib-treated mice as evaluated by X-ray imaging. Peripheral quantitative computed tomography imaging showed higher total and cortical bone mineral content and cortical bone mineral density in dovitinib-treated mice, suggesting better preserved bone mass. CatWalk gait analysis indicated that dovitinib-treated mice experienced less cancer-induced bone pain in the tumor-bearing leg. A trend towards decreased tumor growth and metabolic activity was observed in dovitinib-treated mice quantified by positron emission tomography imaging with 2-[ 18 F]fluoro-2-deoxy-D-glucose at the endpoint. We conclude that dovitinib treatment decreased tumor burden, cancer-induced changes in bone, and bone pain. The results suggest that targeting FGFRs could be beneficial in breast cancer patients with bone metastases.</p