Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites - In vivo assessment using phospho-specific antibodies

Recent studies have provided evidence that breast cancer susceptibility gene products (Brca1 and Brca2) suppress cancer, at least in part, by participating in DNA damage signaling and DNA repair. Brca1 is hyperphosphorylated in response to DNA damage and co-localizes with Rad51, a protein involved in homologous-recombination, and Nbs1.Mre11.Rad50, a complex required for both homologous-recombination and nonhomologous end joining repair of damaged DNA. Here, we report that there is a qualitative difference in the phosphorylation states of Brca1 between ionizing radiation (IR) and UV radiation. Brca1 is phosphorylated at Ser-1423 and Ser-1524 after IR and W; however, Ser-1387 is specifically phosphorylated after IR, and Ser-1457 is predominantly phosphorylated after W. These results suggest that different types of DNA-damaging agents might signal to Brca1 in different ways. We also provide evidence that the rapid phosphorylation of Brca1 at Ser-1423 and Ser-1524 after IR (but not after W) is largely ataxia telangiectasia mutated (ATM) kinase-dependent. The overexpression of catalytically inactive ATM and Rad3 related (ATR) kinase inhibited the UV-induced phosphorylation of Brca1 at these sites, indicating that ATR controls Brca1 phosphorylation in vivo after the exposure of cells to UV light. Moreover, ATR associates with Brca1; ATR and Brca1 foci co-localize both in cells synchronized in S phase and after exposure of cells to DNA-damaging agents. ATR can itself phosphorylate the region of Brca1 phosphorylated by ATM (Ser-Gln cluster in the C terminus of Brca1, amino acids 1241-1530), However, there are additional uncharacterized ATR phosphorylation site(s) between residues 521 and 757 of Brca1, Taken together, our results support a model in which ATM and ATR act in parallel but somewhat overlapping pathways of DNA damage signaling but respond primarily to different types of DNA lesion.

In vitro evidence for a bacterial pathogenesis of equine laminitis

Utilizing an in vitro laminitis explant model, we have investigated how bacterial broth cultures and purified bacterial proteases activate matrix metalloproteinases (MMPs) and alter structural integrity of cultured equine lamellar hoof explants. Four Gram-positive Streptococcus spp. and three Gram-negative bacteria all induced a dose-dependent activation of MMP-2 and MMP-9 and caused lamellar explants to separate. MMP activation was deemed to have occurred if a specific MMP inhibitor, batimastat, blocked MMP activity and prevented lamellar separation. Thermolysin and streptococcal pyrogenic exotoxin B (SpeB) both separated explants dose-dependently but only thermolysin was inhibitable by batimastat or induced MMP activation equivalent to that seen with bacterial broths. Additionally, thermolysin and broth MMP activation appeared to be cell dependent as MMP activation did not occur in isolation. These results suggest the rapid increase in streptococcal species in the caecum and colon observed in parallel with carbohydrate induced equine laminitis may directly cause laminitis via production of exotoxin(s) capable of activating resident MMPs within the lamellar structure. Once activated, these MMPs can degrade key components of the basement membrane (BM) hemidesmosome complex, ultimately separating the BM from the epidermal basal cells resulting in the characteristic laminitis histopathology of hoof lamellae. While many different causative agents have been evaluated in the past, the results of this study provide a unifying aetiological mechanism for the development of carbohydrate induced equine laminitis. (C) 2001 Elsevier Science B.V. All rights reserved.

Integrating environmental and economic life cycle analysis in product development: a material selection case study

Purpose Achieving sustainability by rethinking products, services and strategies is an enormous challenge currently laid upon the economic sector, in which materials selection plays a critical role. In this context, the present work describes an environmental and economic life cycle analysis of a structural product, comparing two possible material alternatives. The product chosen is a storage tank, presently manufactured in stainless steel (SST) or in a glass fibre reinforced polymer composite (CST). The overall goal of the study is to identify environmental and economic strong and weak points related to the life cycle of the two material alternatives. The consequential win-win or trade-off situations will be identified via a Life Cycle Assessment/Life Cycle Costing (LCA/LCC) integrated model. Methods The LCA/LCC integrated model used consists in applying the LCA methodology to the product system, incorporating, in parallel, its results into the LCC study, namely those of the Life Cycle Inventory (LCI) and the Life Cycle Impact Assessment (LCIA). Results In both the SST and CST systems the most significant life cycle phase is the raw materials production, in which the most significant environmental burdens correspond to the Fossil fuels and Respiratory inorganics categories. The LCA/LCC integrated analysis shows that the CST has globally a preferable environmental and economic profile, as its impacts are lower than those of the SST in all life cycle stages. Both the internal and external costs are lower, the former resulting mainly from the composite material being significantly less expensive than stainless steel. This therefore represents a full win-win situation. As a consequence, the study clearly indicates that using a thermoset composite material to manufacture storage tanks is environmentally and economically desirable. However, it was also evident that the environmental performance of the CST could be improved by altering its End-of-Life stage. Conclusions The results of the present work provide enlightening insights into the synergies between the environmental and the economic performance of a structural product made with alternative materials. Further, they provide conclusive evidence to support the integration of environmental and economic life cycle analysis in the product development processes of a manufacturing company, or in some cases even in its procurement practices.

The role of Lifelong Learning in the creation of a knowledge-based society for Europe: european policies

Link do editor: http://www.igi-global.com/chapter/role-lifelong-learning-creation-european/13314

The Role of lifelong learning in creation of a european knowledge-based society

The dominant discourse in education and training policies, at the turn of the millennium, was on lifelong learning (LLL) in the context of a knowledge-based society. As Green points (2002, pp. 611-612) several factors contribute to this global trend: The demographic change: In most advanced countries, the average age of the population is increasing, as people live longer; The effects of globalisation: Including both economic restructuring and cultural change which have impacts on the world of education; Global economic restructuring: Which causes, for example, a more intense demand for a higher order of skills; the intensified economic competition, forcing a wave of restructuring and creating enormous pressure to train and retrain the workforce In parallel, the “significance of the international division of labour cannot be underestimated for higher education”, as pointed out by Jarvis (1999, p. 250). This author goes on to argue that globalisation has exacerbated differentiation in the labour market, with the First World converting faster to a knowledge economy and a service society, while a great deal of the actual manufacturing is done elsewhere.

Towards the wide implementation of standards IEC 61968/70 (CIM) and IEC 61850 in the distribution system (CIGRÉ C6-105_2010)

Currently, power systems (PS) already accommodate a substantial penetration of distributed generation (DG) and operate in competitive environments. In the future, as the result of the liberalisation and political regulations, PS will have to deal with large-scale integration of DG and other distributed energy resources (DER), such as storage and provide market agents to ensure a flexible and secure operation. This cannot be done with the traditional PS operational tools used today like the quite restricted information systems Supervisory Control and Data Acquisition (SCADA) [1]. The trend to use the local generation in the active operation of the power system requires new solutions for data management system. The relevant standards have been developed separately in the last few years so there is a need to unify them in order to receive a common and interoperable solution. For the distribution operation the CIM models described in the IEC 61968/70 are especially relevant. In Europe dispersed and renewable energy resources (D&RER) are mostly operated without remote control mechanisms and feed the maximal amount of available power into the grid. To improve the network operation performance the idea of virtual power plants (VPP) will become a reality. In the future power generation of D&RER will be scheduled with a high accuracy. In order to realize VPP decentralized energy management, communication facilities are needed that have standardized interfaces and protocols. IEC 61850 is suitable to serve as a general standard for all communication tasks in power systems [2]. The paper deals with international activities and experiences in the implementation of a new data management and communication concept in the distribution system. The difficulties in the coordination of the inconsistent developed in parallel communication and data management standards - are first addressed in the paper. The upcoming unification work taking into account the growing role of D&RER in the PS is shown. It is possible to overcome the lag in current practical experiences using new tools for creating and maintenance the CIM data and simulation of the IEC 61850 protocol – the prototype of which is presented in the paper –. The origin and the accuracy of the data requirements depend on the data use (e.g. operation or planning) so some remarks concerning the definition of the digital interface incorporated in the merging unit idea from the power utility point of view are presented in the paper too. To summarize some required future work has been identified.

Beliefs and attitudes about endemic dental fluorosis among adolescents in rural Brazil

OBJECTIVE: To understand beliefs and attitudes about fluorosis among young people living in a rural area. METHODOLOGICAL PROCEDURES: Qualitative study consisting of semi-structured interviews with 23 adolescents with dental fluorosis, 14 teachers and three health authorities in the city of São Francisco, Southeastern Brazil, in 2002. Content analysis and social representation theory were applied. ANALYSIS OF RESULTS: The organoleptic characteristics of carbonates that affect groundwater (salty flavor, whitish coloration, and turbidity) associated with negative aspects of household use of this water are considered a cause of mottled enamel. Even after contact with researchers who investigated this phenomenon and helped find a solution for this condition, the local population is still unwilling to accept fluoride as the cause of the problem and does not fully agree to use water from other sources because they are afraid of the quality of water. CONCLUSIONS: Misperceptions of the causes of dental fluorosis and water treatment costs compromise the implementation of uncontaminated surface water supplies. Health education strategies are required in parallel with solutions for securing water supply in drought-ravaged areas.

Collision-free prioritized medium access control in wireless networks with hidden nodes

We propose a collision-free medium access control (MAC) protocol, which implements static-priority scheduling and works in the presence of hidden nodes. The MAC protocol allows multiple masters and is fully distributed; it is an adaptation to a wireless channel of the dominance protocol used in the CAN bus. But unlike that protocol, our protocol does not require a node having the ability to sense the channel while transmitting to the channel. Our protocol is collision-free even in the presence of hidden nodes and it achieves this without synchronized clocks or out-of-band busy tones. In addition, the protocol is designed to ensure that many non-interfering nodes can transmit in parallel and it functions for both broadcast and unicast transmissions.

A shared-disk parallel cluster file system

Dissertação apresentada para obtenção do Grau de Doutor em Informática Pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Temporal trends in the prevalence of asthma and rhinoconjunctivitis in adolescents

ABSTRACT OBJECTIVE To analyze the temporal trend of asthma and rhinoconjunctivitis prevalences as well as their symptoms in adolescents. METHODS Two cross-sectional studies were conducted using the same methodology and questionnaire as was used for adolescents aged 12 to 14 years in the Brazilian city of Florianopolis, SC, Southern Brazil. Based on the international protocol of the International Study of Asthma and Allergies in Childhood (ISAAC) study, adolescents were evaluated in 2001 and 3,150 in 2012. The schools included in this study were the same as in the 2001 study. These schools were randomly selected after stratification by network (public and private) and geographic location. The total average percentage variation was estimated for the prevalence of asthma and rhinoconjunctivitis and their symptoms. RESULTS The prevalence of reported asthma was 10.9% in 2001 and 14.8% in 2012, with an average variation of 2.8% in the period. The highest average variation in the period was observed among female adolescents (4.1%). In parallel a significant increase occurred in reported physician-diagnosed asthma, 7.3% in 2001 and 11,1% in 2012, with an annual variation of 4.5%. The largest increases in reported physician-diagnosed asthma were seen in female (5.9%) and male (4.5%) public school pupils. In addition, a significant increase in reported rhinoconjunctivitis occurred, with the average variation in the period being 5.2%. Reports of severe asthma symptoms remained unchanged during the period, while the annual variation for reported current wheezing (-1.3%) and wheezing during exercise (-1.2%) decreased. CONCLUSIONS The results showed a significant increase in the annual average variation for asthma and rhinoconjunctivitis prevalence during the 2001 to 2012 period.

Data analytics in the cloud with flexible mapreduced workflows

Data analytic applications are characterized by large data sets that are subject to a series of processing phases. Some of these phases are executed sequentially but others can be executed concurrently or in parallel on clusters, grids or clouds. The MapReduce programming model has been applied to process large data sets in cluster and cloud environments. For developing an application using MapReduce there is a need to install/configure/access specific frameworks such as Apache Hadoop or Elastic MapReduce in Amazon Cloud. It would be desirable to provide more flexibility in adjusting such configurations according to the application characteristics. Furthermore the composition of the multiple phases of a data analytic application requires the specification of all the phases and their orchestration. The original MapReduce model and environment lacks flexible support for such configuration and composition. Recognizing that scientific workflows have been successfully applied to modeling complex applications, this paper describes our experiments on implementing MapReduce as subworkflows in the AWARD framework (Autonomic Workflow Activities Reconfigurable and Dynamic). A text mining data analytic application is modeled as a complex workflow with multiple phases, where individual workflow nodes support MapReduce computations. As in typical MapReduce environments, the end user only needs to define the application algorithms for input data processing and for the map and reduce functions. In the paper we present experimental results when using the AWARD framework to execute MapReduce workflows deployed over multiple Amazon EC2 (Elastic Compute Cloud) instances.

Study on the growth promoting capacity of calf and fetal bovine serum for animal cells "in vitro" II: electrophoretic study and survey on the antiproteolytic activity of pools of calf and fetal bovine serum

Calf serum and fetal bovine serum present great variability as to its growth promoting efficiency (GPE). As supplement of culture media to cultivate cells of animal origin they stimulate the "in vitro" multiplication and maintain cell viability. When fourteen lots of calf sera of variable GPE had the total protein contents as well as the percentages of serum fractions determined, no significant differences that could possibly explain the variability of the GPE were observed. Evaluation of the antiproteolytic activity of nineteen lots of calf serum and eighteen serum lots of younger calves showed that the former exhibited lower antiproteolytic titers (1:40 to 1:80) than the latter (1:80 to 1:160). Twelve lots of fetal bovine serum studied in parallel, showed the highest concentration of antiproteolytic factors, with titers equal to 1:320. Sera of bovine origin, but not fetal sera, are usually heat-inactivated, what was demonstrated to be responsible for the decrease of the antiproteolytic activity of 75% of the lots tested. This could explain the inability of certain heat-inactivated sera in promoting multiplication of some cells "in vitro", as verified with primary monkey kidney cells. The results obtained in this study indicated the convenience of submiting each lot of serum to be introduced in cell culture to previous determination of its characteristics, such as growth promoting efficiency, antiproteolytic activity and also toxicity, absence of extraneous agents, etc., in order to minimize the possibility of using serum lots of questionable quality, thus preventing not only the loss of cell lines, but also undesirable and sometimes expensive delays.

Autonomic Activities in the Execution of Scientific Workflows: Evaluation of the AWARD Framework

Workflows have been successfully applied to express the decomposition of complex scientific applications. However the existing tools still lack adequate support to important aspects namely, decoupling the enactment engine from tasks specification, decentralizing the control of workflow activities allowing their tasks to run in distributed infrastructures, and supporting dynamic workflow reconfigurations. We present the AWARD (Autonomic Workflow Activities Reconfigurable and Dynamic) model of computation, based on Process Networks, where the workflow activities (AWA) are autonomic processes with independent control that can run in parallel on distributed infrastructures. Each AWA executes a task developed as a Java class with a generic interface allowing end-users to code their applications without low-level details. The data-driven coordination of AWA interactions is based on a shared tuple space that also enables dynamic workflow reconfiguration. For evaluation we describe experimental results of AWARD workflow executions in several application scenarios, mapped to the Amazon (Elastic Computing EC2) Cloud.

A quest for the right word enhancing reflexivity and technology in terminology training

INTED2010, the 4th International Technology, Education and Development Conference was held in Valencia (Spain), on March 8, 9 and 10, 2010.

New analytical methodologies for doping control – detection of anabolic androgenic steroids in human urine

Dissertation submitted to Faculdade de Ciências e Tecnologia - Universidade Nova de Lisboa in fulfilment of the requirements for the degree of Doctor of Philosophy (Biochemistry - Biotechnology)