Systematic derivation of Generalized Langevin Equations for coarse-graining and bridge-scaling procedures

Scientific Conference (2020, July)

In many branches of physics, one must often deal with processes involving a huge number of degrees of freedom. Instead of describing the dynamics of each individual of them, one rather wants to ... [more ▼]

In many branches of physics, one must often deal with processes involving a huge number of degrees of freedom. Instead of describing the dynamics of each individual of them, one rather wants to characterize the process of interest via a small set of observ- ables that capture its main features of the process. Even if the microscopic dynamics can be resolved using Newton’s equations of motion, it quickly becomes a computation- ally very expensive calculation to make. It is however much more convenient to come up with a self-consistent equation of motion for the ’global’ observable of interest itself in order to reduce the complexity of the problem. The development of the Mori-Zwanzig formalism in the 1960’s allowed to systematically derive such equations for arbitrary observables in stationary processes. This framework, derived from first principles by means of projection operator techniques, proves the structure of what is now known as the Generalized Langevin Equation, i.e. a stochastic equation of motion which a priori exhibits memory effects in the form on non-localities in time. We propose to extend the formalism and its corollaries to a broad class of out-of- equilibrium processes. We show that the structure of the Generalized Langevin Equa- tion is overall robust but must be adapted to account for the non-stationary dynamics [1,2]. The function that controls memory effects the stochastic term are related through a relation that can be associated to fluctuation-dissipation theorems. This formalism is very convenient to study two-time auto-correlation functions for which we can write a self-consistent differential equation as well. We finally show a new method to evaluate the memory function from numerical or experimental data [3]. [less ▲]

Systematic examination of polymorphism in amyloid fibrils by molecular-dynamics simulation.

in Biophysical Journal (2011), 100(9), 2234-2242

Systematic genomic analysis reveals the complementary aerobic and anaerobic respiration capacities of the human gut microbiota

in Frontiers in Microbiology (2014)

Because of the specific anatomical and physiological properties of the human intestine, a specific oxygen gradient builds up within this organ that influences the intestinal microbiota. The intestinal ... [more ▼]

Because of the specific anatomical and physiological properties of the human intestine, a specific oxygen gradient builds up within this organ that influences the intestinal microbiota. The intestinal microbiome has been intensively studied in recent years, and certain respiratory substrates used by gut inhabiting microbes have been shown to play a crucial role in human health. Unfortunately, a systematic analysis has not been previously performed to determine the respiratory capabilities of human gut microbes (HGM). Here, we analyzed the distribution of aerobic and anaerobic respiratory reductases in 254 HGM genomes. In addition to the annotation of known enzymes, we also predicted a novel microaerobic reductase and novel thiosulfate reductase. Based on this comprehensive assessment of respiratory reductases in the HGM, we proposed a number of exchange pathways among different bacteria involved in the reduction of various nitrogen oxides. The results significantly expanded our knowledge of HGM metabolism and interactions in bacterial communities. [less ▲]

Systematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity.

in Genome research (2015), 25(5), 701-13

Assemblies of huntingtin (HTT) fragments with expanded polyglutamine (polyQ) tracts are a pathological hallmark of Huntington's disease (HD). The molecular mechanisms by which these structures are formed ... [more ▼]

Assemblies of huntingtin (HTT) fragments with expanded polyglutamine (polyQ) tracts are a pathological hallmark of Huntington's disease (HD). The molecular mechanisms by which these structures are formed and cause neuronal dysfunction and toxicity are poorly understood. Here, we utilized available gene expression data sets of selected brain regions of HD patients and controls for systematic interaction network filtering in order to predict disease-relevant, brain region-specific HTT interaction partners. Starting from a large protein-protein interaction (PPI) data set, a step-by-step computational filtering strategy facilitated the generation of a focused PPI network that directly or indirectly connects 13 proteins potentially dysregulated in HD with the disease protein HTT. This network enabled the discovery of the neuron-specific protein CRMP1 that targets aggregation-prone, N-terminal HTT fragments and suppresses their spontaneous self-assembly into proteotoxic structures in various models of HD. Experimental validation indicates that our network filtering procedure provides a simple but powerful strategy to identify disease-relevant proteins that influence misfolding and aggregation of polyQ disease proteins. [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 Model-Driven Security

in The 20th Asia-Pacific Software Engineering Conference Proceedings (2013, December)

To face continuously growing security threats and requirements, sound methodologies for constructing secure systems are required. In this context, Model-Driven Security (MDS) has emerged since more than a ... [more ▼]

To face continuously growing security threats and requirements, sound methodologies for constructing secure systems are required. In this context, Model-Driven Security (MDS) has emerged since more than a decade ago as a specialized Model-Driven Engineering approach for supporting the development of secure systems. MDS aims at improving the productivity of the development process and quality of the resulting secure systems, with models as the main artifact. This paper presents how we systematically examined existing published work in MDS and its results. The systematic review process, which is based on a formally designed review protocol, allowed us to identify, classify, and evaluate different MDS approaches. To be more specific, from thousands of relevant papers found, a final set of the most relevant MDS publications has been identified, strictly selected, and reviewed. We present a taxonomy for MDS, which is used to synthesize data in order to classify and evaluate the selected MDS approaches. The results draw a wide picture of existing MDS research showing the current status of the key aspects in MDS as well as the identified most relevant MDS approaches.We discuss the main limitations of the existing MDS approaches and suggest some potential research directions based on these insights. [less ▲]

A systematic review on heart rate variability in Bulimia Nervosa

in Neuroscience and Biobehavioral Reviews (2016), 63

Eating disorders are associated with alterations of the autonomic nervous system (ANS). Heart rate variability (HRV) provides a readily available index of ANS function. While ANS dysfunction indexed by ... [more ▼]

Eating disorders are associated with alterations of the autonomic nervous system (ANS). Heart rate variability (HRV) provides a readily available index of ANS function. While ANS dysfunction indexed by HRV in Anorexia Nervosa has been addressed in previous reviews, here we aimed to review the current evidence on HRV in Bulimia Nervosa (BN). A systematic literature search in Web of Science, PsycInfo, Scopus, and PubMed identified 17 studies reporting HRV in patients with BN. Studies described (i) differences in resting state HRV in patients with BN compared to controls, (ii) alterations in the stress response in BN indexed by HRV, and (iii) treatment effects on HRV in patients with BN. Despite a number of conflicting results, we conclude that BN is characterized by increased resting state vagally-mediated HRV and an impaired stress-response. Intervention-studies suggest that altered ANS-activity in BN is at least partially reversible. Future studies on the complex relation between BN and HRV should investigate the effect of comorbid disorders, subtypes of BN, and mechanisms affecting treatment outcome. [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 ▲]