Towards the reconstruction of integrated genome-scale models of metabolism and gene expression

The reconstruction of integrated genome-scale models of metabolism and gene expression has been a challenge for a while now. In fact, various methods that allow integrating reconstructions of Transcriptional Regulatory Networks, gene expression data or both into Genome-Scale Metabolic Models have been proposed. Several of these methods are surveyed in this article, which allowed identifying their strengths and weaknesses concerning the reconstruction of integrated models for multiple prokaryotic organisms. Additionally, the main resources of regulatory information were also surveyed, as the existence of novel sources of regulatory information and gene expression data may contribute for the improvement of methodologies referred herein.This study was supported by the Portuguese Foundation for Science andTechnology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit andBioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European RegionalDevelopment Fund under the scope of Norte2020-Programa Operacional Regional do Norte. Fernando Cruz holds a doctoral fellowship (SFRH/BD/139198/2018) funded by the FCT. The authors thank project SHIKIFACTORY100 - Modular cell factories for the production of 100 compounds from the shikimate pathway (814408) funded by the European Commission.info:eu-repo/semantics/publishedVersio

Fault-tolerant Cooperative Tasking for Multi-agent Systems

A natural way for cooperative tasking in multi-agent systems is through a top-down design by decomposing a global task into sub-tasks for each individual agent such that the accomplishments of these sub-tasks will guarantee the achievement of the global task. In our previous works [1], [2] we presented necessary and sufficient conditions on the decomposability of a global task automaton between cooperative agents. As a follow-up work, this paper deals with the robustness issues of the proposed top-down design approach with respect to event failures in the multi-agent systems. The main concern under event failure is whether a previously decomposable task can still be achieved collectively by the agents, and if not, we would like to investigate that under what conditions the global task could be robustly accomplished. This is actually the fault-tolerance issue of the top-down design, and the results provide designers with hints on which events are fragile with respect to failures, and whether redundancies are needed. The main objective of this paper is to identify necessary and sufficient conditions on failed events under which a decomposable global task can still be achieved successfully. For such a purpose, a notion called passivity is introduced to characterize the type of event failures. The passivity is found to reflect the redundancy of communication links over shared events, based on which necessary and sufficient conditions for the reliability of cooperative tasking under event failures are derived, followed by illustrative examples and remarks for the derived conditions.Comment: Preprint, Submitted for publicatio

Treatment of chronic back pain by sensory discrimination training. A Phase I RCT of a novel device (FairMed) vs. TENS

Background: The causes of chronic low back pain (CLBP) remain obscure and effective treatment of symptoms remains elusive. A mechanism of relieving chronic pain based on the consequences of conflicting unpleasant sensory inputs to the central nervous system has been hypothesised. As a result a device was generated to deliver sensory discrimination training (FairMed), and this randomised controlled trial compared therapeutic effects with a comparable treatment modality, TENS. Methods: 60 patients with CLBP were recruited from physiotherapy referrals to a single-blinded, randomised controlled, non-inferiority trial. They were randomised to receive either FairMed or TENS and asked to use the allocated device for 30 minutes, twice a day, for 3 weeks. The primary outcome variable measured at 0 and 3 weeks was pain intensity measured using a visual analogue scale averaged over 7 days. Secondary outcome measures were Oswestry Disability Index, 3 timed physical tests, 4 questionnaires assessing different aspects of emotional coping and a global measure of patient rating of change. Data were analysed for the difference in change of scores between groups using one-way ANOVA. Results: Baseline characteristics of the two groups were comparable. The primary outcome, change in pain intensity (VAS) at 3 weeks showed a mean difference between groups of -0.1, (non significant p = 0.82). The mean difference in change in ODI scores was 0.4; (non significant p = 0.85). Differences in change of physical functioning showed that no significant difference in change of scores for any of these test (p = 0.58 – 0.90). Changes in scores of aspects of emotional coping also demonstrated no significant difference in change scores between the groups (p = 0.14 – 0.94). Conclusion: FairMed was not inferior to TENS treatment. The findings have implications for further research on current chronic pain theories and treatments. Further work to explore these mechanisms is important to expand our understanding of chronic pain and the role of neuro-modulation

Functional Characterization of the Frost Gene in Drosophila melanogaster: Importance for Recovery from Chill Coma

BACKGROUND: Almost all animals, including insects, need to adapt to temperature fluctuations. The molecular basis of thermal adaptation is not well understood, although a number of candidate genes have been proposed. However, a functional link between candidate genes and thermal tolerance has rarely been established. The gene Frost (Fst) was first discovered when Drosophila flies were exposed to cold stress, but the biological function(s) of Fst has so far not been characterized. Because Fst is up-regulated after a cold stress, we tested whether it was essential for chill-coma recovery. METHODOLOGY/PRINCIPAL FINDINGS: A marked increase in Fst expression was detected (by RT-PCR) during recovery from cold stress, peaking at 42-fold after 2 h. The GAL4/UAS system was used to knock down expression of Fst and recovery ability was assessed in transgenic adults following 12 h of chill coma at 0 degrees C. The ability to recover from cold stress (short-, medium- and long-term) was significantly altered in the transgenic adults that had Fst silenced. These findings show that Fst plays an essential role in the recovery from chill coma in both males and females. CONCLUSIONS/SIGNIFICANCE: The Frost gene is essential for cold tolerance in Drosophila melanogaster and may play an important role in thermal adaptation

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

<p>Abstract</p> <p>Background</p> <p>Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis.</p> <p>Methods</p> <p>Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots.</p> <p>Results</p> <p>A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein).</p> <p>Conclusions</p> <p>A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.</p

Characterizing Community-Based Mental Health Services for Children with Autism Spectrum Disorders and Disruptive Behavior Problems

This study describes the characteristics of children with autism spectrum disorders (ASD) with disruptive behavior problems served in community-based mental health clinics, characterizes psychotherapy process and outcome, and examines differences between children with ASD and a non-ASD comparison group. Results indicate that children with ASD served in this setting are high functioning and diagnostically complex. Certain research-based behavioral and cognitive behavioral psychotherapeutic strategies were observed frequently, while parent training strategies and active teaching strategies were observed less frequently. The intensity or thoroughness with which strategies were pursued was relatively low. Outcome analyses indicate improvement in child symptoms and family functioning. Treatment delivery and outcome were similar for children with and without ASD. These findings represent the first detailed observational data characterizing community-based mental health services for children with ASD

Child and Family Therapy Process: Concordance of Therapist and Observational Perspectives

The objective of this study is to examine the characteristics of outpatient mental health services delivered in community-based outpatient clinics, comparing information obtained from two different sources, therapists serving children and families, and observational coders viewing tapes of the same treatment sessions. Videotaped therapy sessions were rated by therapists and independent coders regarding goals and strategies pursued during each session. Sixty-three sessions were taped of outpatient care provided to 18 children and their caregivers by 11 therapists. Children were 4–13 years old and families were receiving services at least in part due to reported child behavior problems, confirmed by ratings from the Child Behavior Checklist and Conners Parent Rating Scale—Revised. Analyses assessed the frequency, type, and intensity of goals and strategies pursued in therapy sessions from both therapist and observational coders’ perspectives. Reliability of observer ratings and correspondence between therapist and observer reports were also examined. The reliability of observational coding of goals and strategies was moderate to good, with 76% of 39 codes having ICCs of .5 or greater. Therapists reported pursuing 2.5 times more goals and strategies per session, on average, than identified by observational coders. Correspondence between therapists and coders about the occurrence of specific goals and strategies in treatment sessions was low, with 20.5% of codes having a Kappa of .4 or higher. Substantial differences exist in what therapists and independent coders report as occurring in outpatient treatment sessions. Both perspectives suggest major differences between the content of services provided in community-based outpatient clinics and the structure of evidence-based programs, which emphasize intense pursuit of a small number of goals and strategies in each treatment session. Implications of the findings for quality improvement efforts in community-based mental health care settings are discussed

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques