PartsList: a web-based system for dynamically ranking protein folds based on disparate attributes, including whole-genome expression and interaction information

As the number of protein folds is quite limited, a mode of analysis that will be increasingly common in the future, especially with the advent of structural genomics, is to survey and re-survey the finite parts list of folds from an expanding number of perspectives. We have developed a new resource, called PartsList, that lets one dynamically perform these comparative fold surveys. It is available on the web at http://bioinfo.mbb.yale.edu/partslist and http://www.partslist.org. The system is based on the existing fold classifications and functions as a form of companion annotation for them, providing ‘global views’ of many already completed fold surveys. The central idea in the system is that of comparison through ranking; PartsList will rank the approximately 420 folds based on more than 180 attributes. These include: (i) occurrence in a number of completely sequenced genomes (e.g. it will show the most common folds in the worm versus yeast); (ii) occurrence in the structure databank (e.g. most common folds in the PDB); (iii) both absolute and relative gene expression information (e.g. most changing folds in expression over the cell cycle); (iv) protein–protein interactions, based on experimental data in yeast and comprehensive PDB surveys (e.g. most interacting fold); (v) sensitivity to inserted transposons; (vi) the number of functions associated with the fold (e.g. most multi-functional folds); (vii) amino acid composition (e.g. most Cys-rich folds); (viii) protein motions (e.g. most mobile folds); and (ix) the level of similarity based on a comprehensive set of structural alignments (e.g. most structurally variable folds). The integration of whole-genome expression and protein–protein interaction data with structural information is a particularly novel feature of our system. We provide three ways of visualizing the rankings: a profiler emphasizing the progression of high and low ranks across many pre-selected attributes, a dynamic comparer for custom comparisons and a numerical rankings correlator. These allow one to directly compare very different attributes of a fold (e.g. expression level, genome occurrence and maximum motion) in the uniform numerical format of ranks. This uniform framework, in turn, highlights the way that the frequency of many of the attributes falls off with approximate power-law behavior (i.e. according to V–b, for attribute value V and constant exponent b), with a few folds having large values and most having small values.

Provirus integration into a gene encoding a ubiquitin-conjugating enzyme results in a placental defect and embryonic lethality.

Ubiquitin-conjugating enzymes (E2 or Ubc) constitute a family of conserved proteins that play a key role in ubiquitin-dependent degradation of proteins in eukaryotes. We describe here a transgenic mouse strain where retrovirus integration into an Ubc gene, designated UbcM4, results in a recessive-lethal mutation. UbcM4 is the mouse homologue of the previously described human UbcH7 that is involved in the in vitro ubiquitination of several proteins including the tumor suppressor protein p53. The provirus is located in the first intron of the gene. When both alleles are mutated the level of steady-state mRNA is reduced by about 70%. About a third of homozygous mutant embryos die around day 11.5 of gestation. Embryos that survive that stage are growth retarded and die perinatally. The lethal phenotype is most likely caused by impairment of placenta development as this is the only organ that consistently showed pathological defects. The placental labyrinth is drastically reduced in size and vascularization is disturbed. The UbcM4 mouse mutant represents the first example in mammals of a mutation in a gene involved in ubiquitin conjugation. Its recessive-lethal phenotype demonstrates that the ubiquitin system plays an essential role during mouse development.

Site-specific integration by adeno-associated virus.

Adeno-associated virus (AAV) has attracted considerable interest as a potential vector for gene delivery. Wild-type virus is notable for the lack of association with any human disease and the ability to stably integrate its genome in a site-specific manner in a locus on human chromosome 19 (AAVS1). Use of a functional model system for AAV DNA integration into AAVS1 has allowed us to conclude that the recombination event is directed by cellular DNA sequences. Recombinant junctions isolated from our integration assay were analyzed and showed characteristics similar to those found in latently infected cell lines. The minimal DNA signals within AAVS1 required for targeted integration were identified and shown to contain functional motifs of the viral origin of replication. A replication mediated model of AAV DNA integration is proposed.

Homeologous recombination and mismatch repair during transformation in Streptococcus pneumoniae: saturation of the Hex mismatch repair system.

The ability of the Hex generalized mismatch repair system to prevent recombination between partially divergent (also called homeologous) sequences during transformation in Streptococcus pneumoniae was investigated. By using as donor in transformation cloned fragments 1.7-17.5% divergent in DNA sequence from the recipient, it was observed that the Hex system prevents chromosomal integration of the least and the most divergent fragments but frequently fails to do so for other fragments. In the latter case, the Hex system becomes saturated (inhibited) due to an excess of mismatches: it is unable to repair a single mismatch located elsewhere on the chromosome. Further investigation with chromosomal donor DNA, carrying only one genetically marked divergent region, revealed that a single divergent fragment can lead to saturation of the Hex system. Increase in cellular concentration of either HexA, the MutS homologue that binds mismatches, or HexB, the MutL homologue for which the essential role in repair as yet remains obscure, was shown to restore repair ability in previously saturating conditions. Investigation of heterospecific transformation by chromosomal DNA from two related streptococcal species, Streptococcus oralis and Streptococcus mitis, also revealed complete saturation of the Hex system. Therefore the Hex system is not a barrier to interspecies recombination in S. pneumoniae. These results are discussed in light of those described for the Mut system of Escherichia coli.

Architecture of a multi-modal dialogue system oriented to multilingual question-answering

In this paper, a proposal of a multi-modal dialogue system oriented to multilingual question-answering is presented. This system includes the following ways of access: voice, text, avatar, gestures and signs language. The proposal is oriented to the question-answering task as a user interaction mechanism. The proposal here presented is in the first stages of its development phase and the architecture is presented for the first time on the base of the experiences in question-answering and dialogues previously developed. The main objective of this research work is the development of a solid platform that will permit the modular integration of the proposed architecture.

Decomposition of human behavior using model of competencies: application to robotic control system

For many years, humans and machines have shared the same physical space. To facilitate their interaction with humans, their social integration and for more rational behavior has been sought that the robots demonstrate human-like behavior. For this it is necessary to understand how human behavior is generated, discuss what tasks are performed and how relate to themselves, for subsequent implementation in robots. In this paper, we propose a model of competencies based on human neuroregulator system for analysis and decomposition of behavior into functional modules. Using this model allow separate and locate the tasks to be implemented in a robot that displays human-like behavior. As an example, we show the application of model to the autonomous movement behavior on unfamiliar environments and its implementation in various simulated and real robots with different physical configurations and physical devices of different nature. The main result of this work has been to build a model of competencies that is being used to build robotic systems capable of displaying behaviors similar to humans and consider the specific characteristics of robots.

Data normalization and integration in robotic systems using web services technologies

The robotics is one of the most active areas. We also need to join a large number of disciplines to create robots. With these premises, one problem is the management of information from multiple heterogeneous sources. Each component, hardware or software, produces data with different nature: temporal frequencies, processing needs, size, type, etc. Nowadays, technologies and software engineering paradigms such as service-oriented architectures are applied to solve this problem in other areas. This paper proposes the use of these technologies to implement a robotic control system based on services. This type of system will allow integration and collaborative work of different elements that make up a robotic system.

Model of Competencies for Decomposition of Human Behavior: Application to Control System of Robots

Humans and machines have shared the same physical space for many years. To share the same space, we want the robots to behave like human beings. This will facilitate their social integration, their interaction with humans and create an intelligent behavior. To achieve this goal, we need to understand how human behavior is generated, analyze tasks running our nerves and how they relate to them. Then and only then can we implement these mechanisms in robotic beings. In this study, we propose a model of competencies based on human neuroregulator system for analysis and decomposition of behavior into functional modules. Using this model allow separate and locate the tasks to be implemented in a robot that displays human-like behavior. As an example, we show the application of model to the autonomous movement behavior on unfamiliar environments and its implementation in various simulated and real robots with different physical configurations and physical devices of different nature. The main result of this study has been to build a model of competencies that is being used to build robotic systems capable of displaying behaviors similar to humans and consider the specific characteristics of robots.

Integration of different models in the design of chemical processes: Application to the design of a power plant

With advances in the synthesis and design of chemical processes there is an increasing need for more complex mathematical models with which to screen the alternatives that constitute accurate and reliable process models. Despite the wide availability of sophisticated tools for simulation, optimization and synthesis of chemical processes, the user is frequently interested in using the ‘best available model’. However, in practice, these models are usually little more than a black box with a rigid input–output structure. In this paper we propose to tackle all these models using generalized disjunctive programming to capture the numerical characteristics of each model (in equation form, modular, noisy, etc.) and to deal with each of them according to their individual characteristics. The result is a hybrid modular–equation based approach that allows synthesizing complex processes using different models in a robust and reliable way. The capabilities of the proposed approach are discussed with a case study: the design of a utility system power plant that has been decomposed into its constitutive elements, each treated differently numerically. And finally, numerical results and conclusions are presented.

The information systems integration for a better caring and chronic patients´ empowerment

The technology innovation (TI) in the health system has been confirmed as the best format to share information and to facilitate the communication between all the actors involved in the chronic patients´ care.

Benefits of management systems integration: a literature review

The purpose of this paper is to identify the benefits of integrated management systems by comparing them with the benefits obtained through the individual implementation of ISO 9001 and ISO 14001 standards. The methodology used is a literature review based on an electronic search in the Web of Science, ScienceDirect, Scopus and Emerald databases. Findings show that although some benefits are common regardless the system management type, the benefits obtained with integration are greater than considering management systems separately because of the wider scope considered in integration. This is one of the first papers, to the best of our knowledge, to compare benefits from the two management systems standards when implemented separately and when integrated. In addition, some ideas are proposed for consideration in future research on the internalization of management systems and selection effect.

Health-Sector Responses to Intimate Partner Violence Fitting the Response Into the Biomedical Health System or Adapting the System to Meet the Response?

This study aims to analyze how middle-level health systems’ managers understand the integration of a health care response to intimate partner violence (IPV) within the Spanish health system. Data were obtained through 26 individual interviews with professionals in charge of coordinating the health care response to IPV within the 17 regional health systems in Spain. The transcripts were analyzed following grounded theory in accordance with the constructivist approach described by Charmaz. Three categories emerged, showing the efforts and challenges to integrate a health care response to IPV within the Spanish health system: “IPV is a complex issue that generates activism and/or resistance,” “The mandate to integrate a health sector response to IPV: a priority not always prioritized,” and “The Spanish health system: respectful with professionals’ autonomy and firmly biomedical.” The core category, “Developing diverse responses to IPV integration,” crosscut the three categories and encompassed the range of different responses that emerge when a strong mandate to integrate a health care response to IPV is enacted. Such responses ranged from refraining to deal with the issue to offering a women-centered response. Attempting to integrate a response to nonbiomedical health problems as IPV into health systems that remain strongly biomedicalized is challenging and strongly dependent both on the motivation of professionals and on organizational factors. Implementing and sustaining changes in the structure and culture of the health care system are needed if a health care response to IPV that fulfills the World Health Organization guidelines is to be ensured.

Redrawing Identity Boundaries through Integration Policies: Strategies of Inclusion/Exclusion of Immigrants in Québec and South Tyrol. EDAP Paper 01/2013

Following the research agenda introduced by Will Kymlicka, this qualitative study offers an interpretation of how the sub-national elites of Québec and South Tyrol police the integration of immigrants. For these national minority groups, which are constantly undergoing a process of redefinition of their collective identities by differentiating themselves from the Others who do not belong to the in-group, immigrants have progressively become the most significant Others as they are not part of the original system of compromises. This article questions how sub-national elites are handling this relatively new kind of ethnocultural diversity brought about by large-scale permanent immigration on two levels: first, the political narrative of the ruling sub-national parties, their electoral appeals, manifestos and speeches; second, the policy arrangements for the integration of immigrants in education, language and social policy. The initial approach of the article is pessimistic, as it assumes that sub-national elites will marginalize immigrants to please core nationalist supporters. In fact, the hypotheses to be tested are whether the national minority groups of Québec and South Tyrol engage in a process of reconstruction of their ethnic identity bounded by opposition to real or imagined Others – the newcomers; and whether they adopt practical measures that force newcomers to be assimilated into the group or to be marginalized. The comparison between Québec and South Tyrol provides a basic understanding of the impact of immigration in two sub-national polities that are very different, but still adopt similar political narratives and policy strategies with regard to the integration of newcomers.

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.

Aging and the governance of the healthcare system in Japan. Bruegel Working Paper 2014/14, December 2014

Japan is the most rapidly aging country in the world. This is evidence that the social security system, which consists of the pension system, healthcare system and other programmes, has been working well. The population is shrinking because of a falling birth rate. It is expected that the population will fall from 128 million in 2010 to 87 million in 2060. During this period, the ratio of people aged 65 or over will rise from 23 percent to 39.9 percent. Japan’s age dependency ratio was 62 in 2013, the highest among advanced nations. It is expected to rise sharply to 94 in 2050 (see Figure 1 on page 4). A total reform of the Japanese social security system, therefore, is inevitable. From the point of view of fiscal reconstruction, reform of the healthcare system is the most important issue. The biggest problem in the healthcare system is that both the funding system and the care-delivery system are extremely fragmented. The government is planning its reform of the healthcare system based on the principle of integration. Other advanced economies could learn from the Japanese experience.