The Mouse Genome Database (MGD): integration nexus for the laboratory mouse

The Mouse Genome Database (MGD) is the community database resource for the laboratory mouse, a key model organism for interpreting the human genome and for understanding human biology and disease (http://www.informatics.jax.org). MGD provides standard nomenclature and consensus map positions for mouse genes and genetic markers; it provides a curated set of mammalian homology records, user-defined chromosomal maps, experimental data sets and the definitive mouse ‘gene to sequence’ reference set for the research community. The integration and standardization of these data sets facilitates the transition between mouse DNA sequence, gene and phenotype annotations. A recent focus on allele and phenotype representations enhances the ability of MGD to organize and present data for exploring the relationship between genotype and phenotype. This link between the genome and the biology of the mouse is especially important as phenotype information grows from large mutagenesis projects and genotype information grows from large-scale sequencing projects.

Architecture and mechanism of the light-harvesting apparatus of purple bacteria

Photosynthetic organisms fuel their metabolism with light energy and have developed for this purpose an efficient apparatus for harvesting sunlight. The atomic structure of the apparatus, as it evolved in purple bacteria, has been constructed through a combination of x-ray crystallography, electron microscopy, and modeling. The detailed structure and overall architecture reveals a hierarchical aggregate of pigments that utilizes, as shown through femtosecond spectroscopy and quantum physics, elegant and efficient mechanisms for primary light absorption and transfer of electronic excitation toward the photosynthetic reaction center.

Pantropic retroviral vectors integrate and express in cells of the malaria mosquito, Anopheles gambiae.

The lack of efficient mechanisms for stable genetic transformation of medically important insects, such as anopheline mosquitoes, is the single most important impediment to progress in identifying novel control strategies. Currently available techniques for foreign gene expression in insect cells in culture lack the benefit of stable inheritance conferred by integration. To overcome this problem, a new class of pantropic retroviral vectors has been developed in which the amphotropic envelope is completely replaced by the G glycoprotein of vesicular stomatitis virus. The broadened host cell range of these particles allowed successful entry, integration, and expression of heterologous genes in cultured cells of Anopheles gambiae, the principle mosquito vector responsible for the transmission of over 100 million cases of malaria each year. Mosquito cells in culture infected with a pantropic vector expressing hygromycin phosphotransferase from the Drosophila hsp70 promoter were resistant to the antibiotic hygromycin B. Integrated provirus was detected in infected mosquito cell clones grown in selective media. Thus, pantropic retroviral vectors hold promise as a transformation system for mosquitoes in vivo.

Arabidopsis mutants deficient in T-DNA integration.

Arabidopsis thaliana mutants originally isolated as hypersensitive to irradiation were screened for the ability to be transformed by Agrobacterium transferred DNA (T-DNA). One of four UV-hypersensitive mutants and one of two gamma-hypersensitive mutants tested showed a significant reduction in the frequency of stable transformants compared with radioresistant controls. In a transient assay for T-DNA transfer independent of genomic integration, both mutant lines took up and expressed T-DNA as efficiently as parental lines. These lines are therefore deficient specifically in stable T-DNA integration and thus provide direct evidence for the role of a plant function in that process. As radiation hypersensitivity suggests a deficiency in repair of DNA damage, that plant function may be one that is also involved in DNA repair, possibly, from other evidence, in repair of double-strand DNA breaks.

Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31.

MAP30 (Momordica anti-HIV protein of 30 kDa) and GAP31 (Gelonium anti-HIV protein of 31 kDa) are anti-HIV plant proteins that we have identified, purified, and cloned from the medicinal plants Momordica charantia and Gelonium multiflorum. These antiviral agents are capable of inhibiting infection of HIV type 1 (HIV-1) in T lymphocytes and monocytes as well as replication of the virus in already-infected cells. They are not toxic to normal uninfected cells because they are unable to enter healthy cells. MAP30 and GAP31 also possess an N-glycosidase activity on 28S ribosomal RNA and a topological activity on plasmid and viral DNAs including HIV-1 long terminal repeats (LTRs). LTRs are essential sites for integration of viral DNA into the host genome by viral integrase. We therefore investigated the effect of MAP30 and GAP31 on HIV-1 integrase. We report that both of these antiviral agents exhibit dose-dependent inhibition of HIV-1 integrase. Inhibition was observed in all of the three specific reactions catalyzed by the integrase, namely, 3' processing (specific cleavage of the dinucleotide GT from the viral substrate), strand transfer (integration), and "disintegration" (the reversal of strand transfer). Inhibition was studied by using oligonucleotide substrates with sequences corresponding to the U3 and U5 regions of HIV LTR. In the presence of 20 ng of viral substrate, 50 ng of target substrate, and 4 microM integrase, total inhibition was achieved at equimolar concentrations of the integrase and the antiviral proteins, with EC50 values of about 1 microM. Integration of viral DNA into the host chromosome is a vital step in the replicative cycle of retroviruses, including the AIDS virus. The inhibition of HIV-1 integrase by MAP30 and GAP31 suggests that impediment of viral DNA integration may play a key role in the anti-HIV activity of these plant proteins.

An Empirical Comparison of Reuse in Embedded and Nonembedded Systems

High-quality software, delivered on time and budget, constitutes a critical part of most products and services in modern society. Our government has invested billions of dollars to develop software assets, often to redevelop the same capability many times. Recognizing the waste involved in redeveloping these assets, in 1992 the Department of Defense issued the Software Reuse Initiative. The vision of the Software Reuse Initiative was "To drive the DoD software community from its current "re-invent the software" cycle to a process-driven, domain-specific, architecture-centric, library-based way of constructing software.'' Twenty years after issuing this initiative, there is evidence of this vision beginning to be realized in nonembedded systems. However, virtually every large embedded system undertaken has incurred large cost and schedule overruns. Investigations into the root cause of these overruns implicates reuse. Why are we seeing improvements in the outcomes of these large scale nonembedded systems and worse outcomes in embedded systems? This question is the foundation for this research. The experiences of the Aerospace industry have led to a number of questions about reuse and how the industry is employing reuse in embedded systems. For example, does reuse in embedded systems yield the same outcomes as in nonembedded systems? Are the outcomes positive? If the outcomes are different, it may indicate that embedded systems should not use data from nonembedded systems for estimation. Are embedded systems using the same development approaches as nonembedded systems? Does the development approach make a difference? If embedded systems develop software differently from nonembedded systems, it may mean that the same processes do not apply to both types of systems. What about the reuse of different artifacts? Perhaps there are certain artifacts that, when reused, contribute more or are more difficult to use in embedded systems. Finally, what are the success factors and obstacles to reuse? Are they the same in embedded systems as in nonembedded systems? The research in this dissertation is comprised of a series of empirical studies using professionals in the aerospace and defense industry as its subjects. The main focus has been to investigate the reuse practices of embedded systems professionals and nonembedded systems professionals and compare the methods and artifacts used against the outcomes. The research has followed a combined qualitative and quantitative design approach. The qualitative data were collected by surveying software and systems engineers, interviewing senior developers, and reading numerous documents and other studies. Quantitative data were derived from converting survey and interview respondents' answers into coding that could be counted and measured. From the search of existing empirical literature, we learned that reuse in embedded systems are in fact significantly different from nonembedded systems, particularly in effort in model based development approach and quality where the development approach was not specified. The questionnaire showed differences in the development approach used in embedded projects from nonembedded projects, in particular, embedded systems were significantly more likely to use a heritage/legacy development approach. There was also a difference in the artifacts used, with embedded systems more likely to reuse hardware, test products, and test clusters. Nearly all the projects reported using code, but the questionnaire showed that the reuse of code brought mixed results. One of the differences expressed by the respondents to the questionnaire was the difficulty in reuse of code for embedded systems when the platform changed. The semistructured interviews were performed to tell us why the phenomena in the review of literature and the questionnaire were observed. We asked respected industry professionals, such as senior fellows, fellows and distinguished members of technical staff, about their experiences with reuse. We learned that many embedded systems used heritage/legacy development approaches because their systems had been around for many years, before models and modeling tools became available. We learned that reuse of code is beneficial primarily when the code does not require modification, but, especially in embedded systems, once it has to be changed, reuse of code yields few benefits. Finally, while platform independence is a goal for many in nonembedded systems, it is certainly not a goal for the embedded systems professionals and in many cases it is a detriment. However, both embedded and nonembedded systems professionals endorsed the idea of platform standardization. Finally, we conclude that while reuse in embedded systems and nonembedded systems is different today, they are converging. As heritage embedded systems are phased out, models become more robust and platforms are standardized, reuse in embedded systems will become more like nonembedded systems.

EnvironmentalWaveletTool: Continuous and discrete wavelet analysis and filtering for environmental time series

A MATLAB-based computer code has been developed for the simultaneous wavelet analysis and filtering of several environmental time series, particularly focused on the analyses of cave monitoring data. The continuous wavelet transform, the discrete wavelet transform and the discrete wavelet packet transform have been implemented to provide a fast and precise time–period examination of the time series at different period bands. Moreover, statistic methods to examine the relation between two signals have been included. Finally, the entropy of curves and splines based methods have also been developed for segmenting and modeling the analyzed time series. All these methods together provide a user-friendly and fast program for the environmental signal analysis, with useful, practical and understandable results.

MINLP Optimization Algorithm for the Synthesis of Heat and Work Exchange Networks

This paper introduces a new optimization model for the simultaneous synthesis of heat and work exchange networks. The work integration is performed in the work exchange network (WEN), while the heat integration is carried out in the heat exchanger network (HEN). In the WEN synthesis, streams at high-pressure (HP) and low-pressure (LP) are subjected to pressure manipulation stages, via turbines and compressors running on common shafts and stand-alone equipment. The model allows the use of several units of single-shaft-turbine-compressor (SSTC), as well as helper motors and generators to respond to any shortage and/or excess of energy, respectively, in the SSTC axes. The heat integration of the streams occurs in the HEN between each WEN stage. Thus, as the inlet and outlet streams temperatures in the HEN are dependent of the WEN design, they must be considered as optimization variables. The proposed multi-stage superstructure is formulated in mixed-integer nonlinear programming (MINLP), in order to minimize the total annualized cost composed by capital and operational expenses. A case study is conducted to verify the accuracy of the proposed approach. The results indicate that the heat integration between the WEN stages is essential to enhance the work integration, and to reduce the total cost of process due the need of a smaller amount of hot and cold utilities.

Procedure for calculating the chloride diffusion coefficient and surface concentration from a profile having a maximum beyond the concrete surface

Chlorides induce local corrosion in the steel reinforcements when reaching the bar surface. The measurement of the rate of ingress of these ions, is made by mathematically fitting the so called “error function equation” into the chloride concentration profile, obtaining so the diffusion coefficient and the chloride concentration at the concrete surface. However, the chloride profiles do not always follow Fick’s law by having the maximum concentration at the concrete surface, but often the profile shows a maximum concentration more in the interior, which indicates a different composition and performance of the most external concrete layer with respect to the internal zones. The paper presents a procedure prepared during the time of the RILEM TC 178-TMC: “Testing and modeling chloride penetration in concrete”, which suggests neglecting the external layer where the chloride concentration increases and using the maximum as an “apparent” surface concentration, called C max and to fit the error function equation into the decreasing concentration profile towards the interior. The prediction of evolution should be made also from the maximum.

Twenty-year advanced DInSAR analysis of severe land subsidence: The Alto Guadalentín Basin (Spain) case study

A twenty-year period of severe land subsidence evolution in the Alto Guadalentín Basin (southeast Spain) is monitored using multi-sensor SAR images, processed by advanced differential interferometric synthetic aperture radar (DInSAR) techniques. The SAR images used in this study consist of four datasets acquired by ERS-1/2, ENVISAT, ALOS and COSMO-SkyMed satellites between 1992 and 2012. The integration of ground surface displacement maps retrieved for different time periods allows us to quantify up to 2.50 m of cumulated displacements that occurred between 1992 and 2012 in the Alto Guadalentín Basin. DInSAR results were locally compared with global positioning system (GPS) data available for two continuous stations located in the study area, demonstrating the high consistency of local vertical motion measurements between the two different surveying techniques. An average absolute error of 4.6 ± 4 mm for the ALOS data and of 4.8 ± 3.5 mm for the COSMO-SkyMed data confirmed the reliability of the analysis. The spatial analysis of DInSAR ground surface displacement reveals a direct correlation with the thickness of the compressible alluvial deposits. Detected ground subsidence in the past 20 years is most likely a consequence of a 100–200 m groundwater level drop that has persisted since the 1970s due to the overexploitation of the Alto Guadalentín aquifer system. The negative gradient of the pore pressure is responsible for the extremely slow consolidation of a very thick (> 100 m) layer of fine-grained silt and clay layers with low vertical hydraulic permeability (approximately 50 mm/h) wherein the maximum settlement has still not been reached.

Associative Behaviours and Political Participation of EU migrants

Civic culture is structured on a network of interpersonal associations with different degrees of formalization. According to theories on civic and political action, certain agents, such as associations, play a key role in setting targets, socializing or coordinating sociopolitical actions, among other functions. Associations strengthen the political and civic system of societies. Likewise, they are a vehicle for individuals’ integration, which is particularly important in the case of immigrants. For these, associations are both a vehicle for integration and an instrument for political participation. This article explores the use and purpose of associations according to immigrants from Romania, Poland, the United Kingdom and Germany living in Spain.

The "European model" of international law and its significance for Asia. Some critical reflections. EU Centre in Singapore Working Paper No. 7, June 2012

There is a certain arrogance in the affirmation that a “European model” of regional integration and of compliance with international law should be adopted anywhere in the world, and in Asia in particular. This article argues on the contrary that Asia and Europe are in fundamentally different situations vis-à-vis international law. Based on an analysis of recent events and latest legal developments in Europe, it puts the “European model” of regional integration and the European selective compliance with international law in perspective with regard to the Asian context. Without denying that “civilizations” should learn from one another and that the European experience may be relevant to some extent in Asia, this article concludes that the tools developed in Europe should be used differently in Asia.

Regional health governance: a comparative perspective on EU and ASEAN. EU Centre in Singapore Policy Brief No. 4, June 2012

Globalisation has led to new health challenges for the 21st Century. These challenges have transnational implications and involve a large range of actors and stakeholders. National governments no longer hold the sole responsibility for the health of their people. These changes in health trends have led to the rise of Global Health Governance as a theoretical notion for health policy-making. The Southeast Asian region is particularly prone to public health threats and it is for this reason that this brief looks at the potential of the Association of Southeast Asian Nations (ASEAN) as a regional organisation to take a lead in health cooperation. Through a comparative study between the regional mechanisms for health cooperation of the European Union (EU) and ASEAN, we look at how ASEAN could maximise its potential as a global health actor. Regional institutions and a network of civil society organisations are crucial in relaying global initiatives for health, and ensuring their effective implementation at the national level. While the EU benefits from higher degrees of integration and involvement in the sector of health policy making, ASEAN’s role as a regional body for health governance will depend both on greater horizontal and vertical regional integration through enhanced regional mechanisms and a wider matrix of cooperation.

Towards a new design of South American integration? Jean Monnet/Robert Schuman Paper Series, Special Issue January 2013

The design of South American integration is becoming different. This has been quite common in the trajectory of over six decades of initiatives aimed at generating institutional frameworks to facilitate regional integration. However, even when it has become apparent that the previous design is undergoing a new process of change, it would be difficult to predict for how long the one that is beginning to take shape will remain in effect. The experience of recent decades suggests great caution in forecasts that are optimistic about any eventual longevity. Several factors are contributing to this redesign. Some are external to the region while others are endogenous. The combination of these factors will influence the future design of South American integration. If past lessons are correctly capitalized and certain advantage is derived from the leeway provided by a decentralized international system with multiple options, we can anticipate that what will predominate in the region will be multidimensional integration agreements (with political and economic objectives at the same time) and with cross-memberships and commitments. If this were the case, the actual impact on regional governance, social and productive integration and the competitive insertion at a global scale will depend largely on the following factors: the quality and sustainability of the strategy for development and global and regional insertion of each country; the combination of a reasonable degree of flexibility and predictability in the commitments made and their corresponding ground rule, and the density of the network of cross-interests that can be achieved as a result of the respective regional integration agreements, reflected in multiple transnational social and production networks.

The Theory of Interhybridity: Socio-political Dimensions and Migration Experiences of Post-communist Western Balkan States

The Western Balkans integration within the EU has started a legal process which is the rejection of former communist legal/political approaches and the transformation of former communist institutions. Indeed, the EU agenda has brought vertical/horizontal integration and Europeanization of national institutions (i.e. shifting power to the EU institutions and international authorities). At this point, it is very crucial to emphasize the fact that the Western Balkans as a whole region has currently an image that includes characteristics of both the Soviet socialism and the European democracy. The EU foreign policies and enlargement strategy for Western Balkans have significant effects on four core factors (i.e. Schengen visa regulations, remittances, asylum and migration as an aggregate process). The convergence/divergence of EU member states’ priorities for migration policies regulate and even shape directly the migration dynamics in migrant sender countries. From this standpoint, the research explores how main migration factors are influenced by political and judicial factors such as; rule of law and democracy score, the economic liberation score, political and human rights, civil society score and citizenship rights in Western Balkan countries. The proposal of interhybridity explores how the hybridization of state and non-state actors within home and host countries can solve labor migration-related problems. The economical and sociopolitical labor-migration model of Basu (2009) is overlapping with the multidimensional empirical framework of interhybridity. Indisputably, hybrid model (i.e. collaboration state and non-state actors) has a catalyst role in terms of balancing social problems and civil society needs. Paradigmatically, it is better to perceive the hybrid model as a combination of communicative and strategic action that means the reciprocal recognition within the model is precondition for significant functionality. This will shape social and industrial relations with moral meanings of communication.