Systematic approaches to mouse mutagenesis.

in Current Opinion in Genetics & Development (2001), 11(3), 268-73

A major challenge in post-genomics is the systematic determination of mammalian gene function. A variety of mouse mutagenesis technologies, both gene- and phenotype-driven, are being used to underpin ... [more ▼]

A major challenge in post-genomics is the systematic determination of mammalian gene function. A variety of mouse mutagenesis technologies, both gene- and phenotype-driven, are being used to underpin systematic and comprehensive approaches to mammalian gene function studies. Recently, a number of centres have completed large-scale ENU mutagenesis programmes that employ a phenotype-driven approach to the generation of mouse mutants. The use of ENU mutagenesis represents a powerful and efficient approach to mammalian gene-function studies, but many parallel developments are needed in downstream technologies to properly harness the new enlarged mouse-mutant resources that are being created. [less ▲]

Systematic assessment of local & global signal control policies: A methodological perspective

in Proceedings of 2015 International Conference on Models and Technologies for Intelligent Transportation Systems, MT-ITS 2015 (2015)

Traffic control performance on networks depends on the flow response to the policy adopted, which in turn contributes to determine the optimal signal settings. This paper focuses on the relationship ... [more ▼]

Traffic control performance on networks depends on the flow response to the policy adopted, which in turn contributes to determine the optimal signal settings. This paper focuses on the relationship between local and network wide traffic control policies within the combined traffic control and assignment problem. Through a full exploration of the solution space, an in depth cross comparison is performed between the well-known local policies P0 and Equisaturation, versus the global policies Maximum Throughput and Minimum Delay, to verify how the two local policies approximate the optimal settings for signalized intersections. Realistic traffic dynamics, such as congestion, multiple controllers and spillback are considered, to empirically determine the conditions under which the local policies are able to approximate global performances. After presenting the different local and global control policies, experiments are performed on simple toy networks. The complexity of the underlying network and, therefore, of the problems' boundary conditions is then increased, allowing us to showcase how the different metrics perform in different situations. Finally, conclusions on the results are drawn. © 2015 BME. [less ▲]

Systematic Construction of Linear Transform based Full Diversity, Rate One Space-Time-Frequency Codes

in IEEE Transactions on Signal Processing (2009), 57(6), 2285-2298

In this paper, we generalize the existing rate-one space frequency (SF) and space-time frequency (STF) code constructions. The objective of this exercise is to provide a systematic design of full ... [more ▼]

In this paper, we generalize the existing rate-one space frequency (SF) and space-time frequency (STF) code constructions. The objective of this exercise is to provide a systematic design of full-diversity STF codes with high coding gain. Under this generalization, STF codes are formulated as linear transformations of data. Conditions on these linear transforms are then derived so that the resulting STF codes achieve full diversity and high coding gain with a moderate decoding complexity. Many of these conditions involve channel parameters like delay profile (DP) and temporal correlation. When these quantities are not available at the transmitter, design of codes that exploit full diversity on channels with arbitrary DP and temporal correlation is considered. Complete characterization of a class of such robust codes is provided and their bit error rate (BER) performance is evaluated. On the other hand, when channel DP and temporal correlation are available at the transmitter, linear transforms are optimized to maximize the coding gain of full-diversity STF codes. BER performance of such optimized codes is shown to be better than those of existing codes. [less ▲]

Systematic Design of 18S rRNA Gene Primers for Determining Eukaryotic Diversity in Microbial Consortia

in PLoS ONE (2014)

High-throughput sequencing of ribosomal RNA gene (rDNA) amplicons has opened up the door to large-scale comparative studies of microbial community structures. The short reads currently produced by ... [more ▼]

High-throughput sequencing of ribosomal RNA gene (rDNA) amplicons has opened up the door to large-scale comparative studies of microbial community structures. The short reads currently produced by massively parallel sequencing technologies make the choice of sequencing region crucial for accurate phylogenetic assignments. While for 16S rDNA, relevant regions have been well described, no truly systematic design of 18S rDNA primers aimed at resolving eukaryotic diversity has yet been reported. Here we used 31,862 18S rDNA sequences to design a set of broad-taxonomic range degenerate PCR primers. We simulated the phylogenetic information that each candidate primer pair would retrieve using paired- or single-end reads of various lengths, representing different sequencing technologies. Primer pairs targeting the V4 region performed best, allowing discrimination with paired-end reads as short as 150 bp (with 75% accuracy at genus level). The conditions for PCR amplification were optimised for one of these primer pairs and this was used to amplify 18S rDNA sequences from isolates as well as from a range of environmental samples which were then Illumina sequenced and analysed, revealing good concordance between expected and observed results. In summary, the reported primer sets will allow minimally biased assessment of eukaryotic diversity in different microbial ecosystems. [less ▲]

Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes

in Frontiers in Genetics (2015), 6

The human gut microbiota supplies its host with essential nutrients, including B-vitamins. Using the PubSEED platform, we systematically assessed the genomes of 256 common human gut bacteria for the ... [more ▼]

The human gut microbiota supplies its host with essential nutrients, including B-vitamins. Using the PubSEED platform, we systematically assessed the genomes of 256 common human gut bacteria for the presence of biosynthesis pathways for eight B-vitamins: biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin. On the basis of the presence and absence of genome annotations, we predicted that each of the eight vitamins was produced by 40–65% of the 256 human gut microbes. The distribution of synthesis pathways was diverse; some genomes had all eight biosynthesis pathways, whereas others contained no de novo synthesis pathways. We compared our predictions to experimental data from 16 organisms and found 88% of our predictions to be in agreement with published data. In addition, we identified several pairs of organisms whose vitamin synthesis pathway pattern complemented those of other organisms. This analysis suggests that human gut bacteria actively exchange B-vitamins among each other, thereby enabling the survival of organisms that do not synthesize any of these essential cofactors. This result indicates the co-evolution of the gut microbes in the human gut environment. Our work presents the first comprehensive assessment of the B-vitamin synthesis capabilities of the human gut microbiota. We propose that in addition to diet, the gut microbiota is an important source of B-vitamins, and that changes in the gut microbiota composition can severely affect our dietary B-vitamin requirements. [less ▲]

Systematic molecular measurements reveal key microbial populations driving community-wide phenotype

Poster (2013)

Natural microbial communities are heterogeneous and dynamic. Therefore, a major consideration for multiple omic data studies is the sample-to-sample heterogeneity, which can lead to inconsistent results ... [more ▼]

Natural microbial communities are heterogeneous and dynamic. Therefore, a major consideration for multiple omic data studies is the sample-to-sample heterogeneity, which can lead to inconsistent results if the different biomolecular fractions are obtained from distinct sub-samples. Conversely, systematic omic measurements, i.e. the standardised, reproducible and simultaneous measurement of multiple features from a single undivided sample, result in fully integrable datasets. Objective In order to prove the feasibility and benefits of such systematic measurements in the study of the respective contributions of different populations to the community-wide phenotype, we purified and analysed all biomolecular fractions, i.e. DNA, RNA, proteins and metabolites, obtained from a unique undivided sample of lipid accumulating microbial community (LAMC) from wastewater treatment plant and integrate the resulting datasets. Methods One time point of particular interest was first selected out of 4 LAMC samples for its high diversity and strong lipid accumulation phenotype. Then, the systematic measurement strategy was applied to the selected undivided LAMC sample and the purified biomolecules were analysed by high-throughput techniques. DNA and RNA sequencing reads were assembled at the population-level using different binning strategies. A database, containing predicted proteins, was constructed to identify the detected peptides. Finally, all biomolecular information was mapped onto the assembled composite genomes to identify the precise roles of the different populations in the community-wide lipid accumulation phenotype. Results Metabolomics and 16S diversity analyses were used to select the sample of highest interest for detailed analysis. The systematic measurements of the selected sample followed by data integration have allowed us to probe the functional relevance of the population-level composite genomes, leading to the identification of the LAMC key players. Conclusion As community phenotype is not the sum of the different partner phenotypes, understanding a microbial community system requires more than the study of isolated organisms. Even if both approaches are complementary, top-down systematic approached only provides a holistic perspective of micro-ecological processes. [less ▲]

Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework

in Gut Microbes (2015), 6(2), 120-130

The gut microbiota is well known to affect host metabolic phenotypes. The systemic effects of the gut microbiota on host metabolism are generally evaluated via the comparison of germfree and conventional ... [more ▼]

The gut microbiota is well known to affect host metabolic phenotypes. The systemic effects of the gut microbiota on host metabolism are generally evaluated via the comparison of germfree and conventional mice, which is impossible to perform for humans. Hence, it remains difficult to determine the impact of the gut microbiota on human metabolic phenotypes. We demonstrate that a constraint-based modeling framework that simulates “germfree” and “exgermfree” human individuals can partially fill this gap and allow for in silico predictions of systemic human-microbial cometabolism. To this end, we constructed the first constraint-based host-microbial community model, comprising the most comprehensive model of human metabolism and 11 manually curated, validated metabolic models of commensals, probiotics, pathogens, and opportunistic pathogens. We used this host-microbiota model to predict potential metabolic host-microbe interactions under 4 in silico dietary regimes. Our model predicts that gut microbes secrete numerous health-relevant metabolites into the lumen, thereby modulating the molecular composition of the body fluid metabolome. Our key results include the following: 1. Replacing a commensal community with pathogens caused a loss of important host metabolic functions. 2. The gut microbiota can produce important precursors of host hormone synthesis and thus serves as an endocrine organ. 3. The synthesis of important neurotransmitters is elevated in the presence of the gut microbiota. 4. Gut microbes contribute essential precursors for glutathione, taurine, and leukotrienes. This computational modeling framework provides novel insight into complex metabolic host-microbiota interactions and can serve as a powerful tool with which to generate novel, non-obvious hypotheses regarding host-microbe co-metabolism. [less ▲]

A Systematic Review and Meta-analysis of Interventions for Sexual Health Promotion Involving Serious Digital Games.

in Games for health journal (2015), 4(2), 78-90

OBJECTIVE: Serious games may be effective in promoting sexual health behavior. Their confidential nature may encourage users to discuss sensitive sexuality topics. Furthermore, they can tailor messages to ... [more ▼]

OBJECTIVE: Serious games may be effective in promoting sexual health behavior. Their confidential nature may encourage users to discuss sensitive sexuality topics. Furthermore, they can tailor messages to the individual's needs and may be intrinsically motivating. This meta-analysis investigates the effectiveness of interventions for sexual health promotion that use serious games. MATERIALS AND METHODS: A database search was conducted in PubMed, Web of Science, CINAHL, and PsycINFO for publications before the end of July 2013. Serious digital games studies measuring effects on behavior or its determinants, using a control condition, allowing the calculation of an effect size (Hedges' g, random-effects model) were included. RESULTS: Seven game studies for sexual health promotion were included. These showed positive effects on determinants (g=0.242; 95 percent confidence interval, 0.129, 0.356), albeit of small effect size. The effects on behavior, measured in only two studies, were not significant (g=0.456; 95 percent confidence interval, -0.649, 1.561). Most games did not use many game features that are considered to be immersive or enhancing flow. Instead, there was a strong reliance on pure gamification features, such as rewards and feedback. CONCLUSIONS: The effectiveness of the next generation of games may be enhanced by building on the behavioral change and educational gaming literatures (e.g., using role-play and simulation game formats, individual tailoring, offering adaptation in the difficulty of the challenge, and amount and timing of the feedback). There is a need for studies with rigorous evaluations of game effectiveness, longer-term follow-up, and using measures of behavior rather than merely their determinants. [less ▲]

A systematic review of self-care assistive technologies for aging population

in Boll, Thomas; Ferring, Dieter; Valsiner, Jaan (Eds.) Cultures of care in aging (2018)

A gradual decline in functional and mental capacity as well as a growing risk of care dependency constitute major concerns of life in old age. These should become larger and more urgent in future, because ... [more ▼]

A gradual decline in functional and mental capacity as well as a growing risk of care dependency constitute major concerns of life in old age. These should become larger and more urgent in future, because the number of people 80+ is projected to more than double from 2010 to 2050 at least in EU and OECD countries. On the other side, there is a strong desire of older people, their relatives and policy makers to maintain the autonomy in old age as long as possible. In reaction to this, there have been strong social policy recommendations to develop and promote the use of assistive technologies (ATs). Whereas systematic reviews already exist for several other kinds of ATs, reviews about self-care ATs are still missing. Based on systematic literature searches in PsycINFO, MEDLINE, and Google Scholar databases 203 papers were identified of which 12 were included according to our selection criteria. The methodological quality of all the reviewed studies is evaluated. We reviewed findings on indicators of independent living as efficiency criteria as well as evidence about facilitators and barriers of using these technologies. Self-care ATs turned out to be efficient with respect to reduced care hours and increased independence level. The actual use of these ATs was associated with personal, contextual, and device factors. Lack of randomized control trial studies and a need for further research about ATs in several domains of self-care activities is revealed. Based on the findings of the current review, we generate recommendations for future research. [less ▲]

A systematic review on the engineering of software for ubiquitous systems

in Journal of Systems and Software (2016), 118

Context: Software engineering for ubiquitous systems has experienced an important and rapid growth, however the vast research corpus makes it difficult to obtain valuable information from it. Objective ... [more ▼]

Context: Software engineering for ubiquitous systems has experienced an important and rapid growth, however the vast research corpus makes it difficult to obtain valuable information from it. Objective: To identify, evaluate, and synthesize research about the most relevant approaches addressing the different phases of the software development life cycle for ubiquitous systems. Method: We conducted a systematic literature review of papers presenting and evaluating approaches for the different phases of the software development life cycle for ubiquitous systems. Approaches were classified according to the phase of the development cycle they addressed, identifying their main concerns and limitations. Results: We identified 128 papers reporting 132 approaches addressing issues related to different phases of the software development cycle for ubiquitous systems. Most approaches have been aimed at addressing the implementation, evolution/maintenance, and feedback phases, while others phases such as testing need more attention from researchers. Conclusion: We recommend to follow existing guidelines when conducting case studies to make the studies more reproducible and closer to real life cases. While some phases of the development cycle have been extensively explored, there is still room for research in other phases, toward a more agile and integrated cycle, from requirements to testing and feedback. [less ▲]