Identification of novel therapeutics for complex diseases from genome-wide association data

Human genome sequencing has enabled the association of phenotypes with genetic loci, but our ability to effectively translate this data to the clinic has not kept pace. Over the past 60 years, pharmaceutical companies have successfully demonstrated the safety and efficacy of over 1,200 novel therapeutic drugs via costly clinical studies. While this process must continue, better use can be made of the existing valuable data. In silico tools such as candidate gene prediction systems allow rapid identification of disease genes by identifying the most probable candidate genes linked to genetic markers of the disease or phenotype under investigation. Integration of drug-target data with candidate gene prediction systems can identify novel phenotypes which may benefit from current therapeutics. Such a drug repositioning tool can save valuable time and money spent on preclinical studies and phase I clinical trials.

Understanding context in knowledge translation: a concept analysis study protocol.

AIM: To conduct a concept analysis of clinical practice contexts (work environments) that facilitate or militate against the uptake of research evidence by healthcare professionals in clinical practice. This will involve developing a clear definition of context by describing its features, domains and defining characteristics. BACKGROUND: The context where clinical care is delivered influences that care. While research shows that context is important to knowledge translation (implementation), we lack conceptual clarity on what is context, which contextual factors probably modify the effect of knowledge translation interventions (and hence should be considered when designing interventions) and which contextual factors themselves could be targeted as part of a knowledge translation intervention (context modification). DESIGN: Concept analysis. METHODS: The Walker and Avant concept analysis method, comprised of eight systematic steps, will be used: (1) concept selection; (2) determination of aims; (3) identification of uses of context; (4) determination of defining attributes of context; (5) identification/construction of a model case of context; (6) identification/construction of additional cases of context; (7) identification/construction of antecedents and consequences of context; and (8) definition of empirical referents of context. This study is funded by the Canadian Institutes of Health Research (January 2014). DISCUSSION: This study will result in a much needed framework of context for knowledge translation, which identifies specific elements that, if assessed and used to tailor knowledge translation activities, will result in increased research use by nurses and other healthcare professionals in clinical practice, ultimately leading to better patient care.

The impact of socially responsible human resource management on employees' organizational citizenship behaviour: the mediating role of organizational identification

Based on insights from social exchange and social identity theories, this paper examines the influence of three dimensions of socially responsible human resource management (SR-HRM), namely legal compliance HRM, employee-oriented HRM and general CSR facilitation HRM, on employees' organizational citizenship behaviour (OCB). Structural equation modelling of dyadic data collected from Chinese employees and their direct supervisors in three phases revealed that whilst organizational identification fully mediated the relationship between employee-oriented HRM and employee OCB, general CSR facilitation HRM had a direct effect on employee OCB. In contrast, legal compliance HRM neither influenced employee OCB directly, nor indirectly through organizational identification. The findings highlight the important but complex role played by SR-HRM in eliciting positive employee work outcomes, and contribute to our knowledge of the mechanisms underlying this relationship.

KBRE: a framework for knowledge-based requirements engineering

Detecting inconsistencies is a critical part of requirements engineering (RE) and has been a topic of interest for several decades. Domain knowledge and semantics of requirements not only play important roles in elaborating requirements but are also a crucial way to detect conflicts among them. In this paper, we present a novel knowledge-based RE framework (KBRE) in which domain knowledge and semantics of requirements are central to elaboration, structuring, and management of captured requirements. Moreover, we also show how they facilitate the identification of requirements inconsistencies and other-related problems. In our KBRE model, description logic (DL) is used as the fundamental logical system for requirements analysis and reasoning. In addition, the application of DL in the form of Manchester OWL Syntax brings simplicity to the formalization of requirements while preserving sufficient expressive power. A tool has been developed and applied to an industrial use case to validate our approach.

K-Center: an approach on the multi-source identification of information diffusion

The global diffusion of epidemics, computer viruses, and rumors causes great damage to our society. It is critical to identify the diffusion sources and timely quarantine them. However, most methods proposed so far are unsuitable for diffusion with multiple sources because of the high computational cost and the complex spatiotemporal diffusion processes. In this paper, based on the knowledge of infected nodes and their connections, we propose a novel method to identify multiple diffusion sources, which can address three main issues in this area: 1) how many sources are there? 2) where did the diffusion emerge? and 3) when did the diffusion break out? We first derive an optimization formulation for multi-source identification problem. This is based on altering the original network into a new network concerning two key elements: 1) propagation probability and 2) the number of hops between nodes. Experiments demonstrate that the altered network can accurately reflect the complex diffusion processes with multiple sources. Second, we derive a fast method to optimize the formulation. It has been proved that the proposed method is convergent and the computational complexity is O(mn log α) , where α = α (m,n) is the slowly growing inverse-Ackermann function, n is the number of infected nodes, and m is the number of edges connecting them. Finally, we introduce an efficient algorithm to estimate the spreading time and the number of diffusion sources. To evaluate the proposed method, we compare the proposed method with many competing methods in various real-world network topologies. Our method shows significant advantages in the estimation of multiple sources and the prediction of spreading time.

Structural integrity identification based on smart materials and neural networks

This paper presents a non-model based technique to detect, locate, and characterize structural damage by combining the impedance-based structural health monitoring technique with an artificial neural network. The impedance-based structural health monitoring technique, which utilizes the electromechanical coupling property of piezoelectric materials, has shown engineering feasibility in a variety of practical field applications. Relying on high frequency structural excitations (typically>30 kHz), this technique is very sensitive to minor structural changes in the near field of the piezoelectric sensors. In order to quantitatively assess the state of structures, two sets of artificial neural networks, which utilize measured electrical impedance signals for input patterns, were developed. By employing high frequency ranges and by incorporating neural network features, this technique is able to detect the damage in its early stage and to estimate the nature of damage without prior knowledge of the model of structures. The paper concludes with an experimental example, an investigation on a massive quarter scale model of a steel bridge section, in order to verify the performance of this proposed methodology.

Identification of Mechanical Systems through Kautz Filter

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Injuries and envenoming by aquatic animals in fishermen of Coxim and Corumbá municipalities, state of Mato Grosso do Sul, Brazil: identification of the causative agents, clinical aspects and first aid measures

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Identification, characterization and expression analysis of hepcidin gene in sheep

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Organization of Repeated DNA Elements in the Genome of the Cichlid Fish Cichla kelberi and Its Contributions to the Knowledge of Fish Genomes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An integrated approach to identification and conservation of medicinal plants in the tropical forest - A Brazilian experience

An integrated and interdisciplinary research programme with native medicinal plants from tropical forests has been performed in order to obtain new forest products for sustainable use in regional markets vis-à-vis ecosystem conservation. For the success of this programme ethnopharmacological studies are very important with respect to (i) identification of useful plants including medicinal and aromatic species; (ii) recuperation and preservation of traditional knowledge about native plants; and (iii) identification of potential plants with economic value. The plants are selected with a view to evaluate efficacy and safety (pharmacological and toxicological studies), and phytochemical profile and quality control (phytochemical and chromatographic characterization). These studies are very important to add value to plant products and also to mitigate unscrupulous exploitation of medicinal plants by local communities, since multiple use of plants represents an excellent strategy for sustaining the tropical ecosystem through ex situ and in situ conservation. Thus, conservation of tropical resources is possible in conjunction with improvements in the quality of life of the traditional communities and production of new products with therapeutic, cosmetic and 'cosmeceutic' value. © NIAB 2005.

Optimization of algorithm to identification of duplicate tuples through similarity phonetic based on multithreading

Aiming to ensure greater reliability and consistency of data stored in the database, the data cleaning stage is set early in the process of Knowledge Discovery in Databases (KDD) and is responsible for eliminating problems and adjust the data for the later stages, especially for the stage of data mining. Such problems occur in the instance level and schema, namely, missing values, null values, duplicate tuples, values outside the domain, among others. Several algorithms were developed to perform the cleaning step in databases, some of them were developed specifically to work with the phonetics of words, since a word can be written in different ways. Within this perspective, this work presents as original contribution an optimization of algorithm for the detection of duplicate tuples in databases through phonetic based on multithreading without the need for trained data, as well as an independent environment of language to be supported for this. © 2011 IEEE.

Identification of sperm head subpopulations with defined pleiomorphic characteristics in ejaculates of captive Goeldi's monkeys (Callimico goeldii)

The aim of this study was to evaluate the incidence of pleiomorphisms and its influence on the distribution of sperm morphometric subpopulations in ejaculates from the vulnerable Goeldi's monkey (Callimico goeldii) by using a combination of computerized analysis system and Principal Component Analysis (PCA) methods Each sperm head was measured for four primary spermatozoal head dimensional parameters (area [A (μm2)], perimeter [P (μm)], length [L (μm)] and width [W (μm)]) and three head shape derived parameters (ellipticity [(L/W)], elongation [(L-W)/(L+W)] and rugosity [(4πA/P2)]) Six separate subpopulations (SPs) were identified: SP1, constituted by very large, narrow and very elliptical spermatozoa (A=16.85±1.56μm2, W=2.75±0.42μm and ellipticity=2.16±0.24); SP2, characterized by average sized, short, wide and round spermatozoa (A=15.00±1.92μm2, L=5.06±0.49μm, W=3.51±0.31μm and ellipticity=1.44±0.15); SP3, represented by small, wide and slightly round spermatozoa (A=14.95±1.75μm2, W=3.47±0.29μm and ellipticity=1.48±0.14); SP4 included very small, short and very round spermatozoa (A=14.15±2.38μm2, L=4.90±0.57μm and elongation=0.18±0.05); SP5 consisted of average sized and slightly elliptical spermatozoa (A=15.14±1.72μm2 and ellipticity=1.49±0.14); and SP6 included large and round spermatozoa (A=16.30±1.62μm2 and elongation=0.19±0.04) There were differences in the sperm subpopulation distribution (P<0.001) among the five donors analyzed In conclusion, the results of the current study confirmed that the use of computer sperm analysis methods combined with PCA cluster analyses are useful methods to identify, classify, and characterize different sperm head morphometric subpopulations in neotropical primates Broadening our knowledge of C goeldii sperm morphometric abnormalities as well as developing reliable techniques for sperm evaluation may be essential for ex situ conservation of this threatened species © 2012 Elsevier B.V.

Identification of blood meal sources of Lutzomyia longipalpis using polymerase chain reaction-restriction fragment length polymorphism analysis of the cytochrome B gene

An analysis of the dietary content of haematophagous insects can provide important information about the transmission networks of certain zoonoses. The present study evaluated the potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome B (cytb)gene to differentiate between vertebrate species that were identified as possible sources of sandfly meals. The complete cytb gene sequences of 11 vertebrate species available in the National Center for Biotechnology Information database were digested with Aci I, Alu I, Hae III and Rsa I restriction enzymes in silico using Restriction Mapper software. The cytb gene fragment (358 bp) was amplified from tissue samples of vertebrate species and the dietary contents of sandflies and digested with restriction enzymes. Vertebrate species presented a restriction fragment profile that differed from that of other species, with the exception of Canis familiaris and Cerdocyon thous. The 358 bp fragment was identified in 76 sandflies. Of these, 10 were evaluated using the restriction enzymes and the food sources were predicted for four: Homo sapiens (1), Bos taurus (1) and Equus caballus (2). Thus, the PCR-RFLP technique could be a potential method for identifying the food sources of arthropods. However, some points must be clarified regarding the applicability of the method, such as the extent of DNA degradation through intestinal digestion, the potential for multiple sources of blood meals and the need for greater knowledge regarding intraspecific variations in mtDNA.

Identification of blood meal sources of Lutzomyia longipalpis using polymerase chain reaction-restriction fragment length polymorphism analysis of the cytochrome B gene

An analysis of the dietary content of haematophagous insects can provide important information about the transmission networks of certain zoonoses. The present study evaluated the potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome B (cytb) gene to differentiate between vertebrate species that were identified as possible sources of sandfly meals. The complete cytb gene sequences of 11 vertebrate species available in the National Center for Biotechnology Information database were digested with Aci I, Alu I, Hae III and Rsa I restriction enzymes in silico using Restriction Mapper software. The cytb gene fragment (358 bp) was amplified from tissue samples of vertebrate species and the dietary contents of sandflies and digested with restriction enzymes. Vertebrate species presented a restriction fragment profile that differed from that of other species, with the exception of Canis familiaris and Cerdocyon thous. The 358 bp fragment was identified in 76 sandflies. Of these, 10 were evaluated using the restriction enzymes and the food sources were predicted for four: Homo sapiens (1), Bos taurus (1) and Equus caballus (2). Thus, the PCR-RFLP technique could be a potential method for identifying the food sources of arthropods. However, some points must be clarified regarding the applicability of the method, such as the extent of DNA degradation through intestinal digestion, the potential for multiple sources of blood meals and the need for greater knowledge regarding intraspecific variations in mtDNA.