Global GacA-steered control of cyanide and exoprotease production in Pseudomonas fluorescens involves specific ribosome binding sites.

The conserved two-component regulatory system GacS/GacA determines the expression of extracellular products and virulence factors in a variety of Gram-negative bacteria. In the biocontrol strain CHA0 of Pseudomonas fluorescens, the response regulator GacA is essential for the synthesis of extracellular protease (AprA) and secondary metabolites including hydrogen cyanide. GacA was found to exert its control on the hydrogen cyanide biosynthetic genes (hcnABC) and on the aprA gene indirectly via a posttranscriptional mechanism. Expression of a translational hcnA'-'lacZ fusion was GacA-dependent whereas a transcriptional hcnA-lacZ fusion was not. A distinct recognition site overlapping with the ribosome binding site appears to be primordial for GacA-steered regulation. GacA-dependence could be conferred to the Escherichia coli lacZ mRNA by a 3-bp substitution in the ribosome binding site. The gene coding for the global translational repressor RsmA of P. fluorescens was cloned. RsmA overexpression mimicked partial loss of GacA function and involved the same recognition site, suggesting that RsmA is a downstream regulatory element of the GacA control cascade. Mutational inactivation of the chromosomal rsmA gene partially suppressed a gacS defect. Thus, a central, GacA-dependent switch from primary to secondary metabolism may operate at the level of translation.

Informed Control Over Inputs and Extent of Industrial Processing, June 2005

Stylized facts regarding the industrial process include emphases on obtaining information about and control over the quality of raw materials. We provide a model that establishes conditions under which informed control involves ensuring uniformity in inputs and increased uniformity encourages more extensive processing. We show when the Boltzmann-Shannon entropy statistic is an appropriate measure of uniformity.

Distinct mechanisms control human naive and antigen-experienced CD8+ T lymphocyte proliferation.

Human Ag-specific CD8(+) T lymphocytes are heterogeneous and include functionally distinct populations. In this study, we report that at least two distinct mechanisms control the expansion of circulating naive, memory, and effector CD8(+) T lymphocytes when exposed to mitogen or Ag stimulation. The first one leads to apoptosis and occurs shortly after in vitro stimulation. Susceptibility to cell death is prominent among primed T cell subsets, and it is inversely correlated with the size of the ex vivo Bcl-2(high) population within these subsets. Importantly, the Bcl-2(high) phenotype is associated to the proportion of responsive CD8(+) T cells, independently of their differentiation stage. The second one depends on the expression of newly synthesized cyclin-dependent kinase inhibitor p16(INK4a) that occurs in a significant fraction of T cells that had been actively cycling, leading to their cell cycle arrest upon stimulation. Strikingly, accumulation of p16(INK4a) protein preferentially occurs in naive as opposed to primed derived T lymphocytes and is not related to apoptosis. Significant levels of p16 are readily detectable in a small number of ex vivo CD8(+) T cells. Our observations reveal that activation-induced p16 expression represents an alternative process to apoptosis, limiting the proliferation potential of activated naive derived T lymphocytes.

Learning and adaptation in physical heterogeneous teams of robots

In this paper we present a novel approach to assigning roles to robots in a team of physical heterogeneous robots. Its members compete for these roles and get rewards for them. The rewards are used to determine each agent’s preferences and which agents are better adapted to the environment. These aspects are included in the decision making process. Agent interactions are modelled using the concept of an ecosystem in which each robot is a species, resulting in emergent behaviour of the whole set of agents. One of the most important features of this approach is its high adaptability. Unlike some other learning techniques, this approach does not need to start a whole exploitation process when the environment changes. All this is exemplified by means of experiments run on a simulator. In addition, the algorithm developed was applied as applied to several teams of robots in order to analyse the impact of heterogeneity in these systems

A circuit-based gatekeeper for adult neural stem cell proliferation: Parvalbumin-expressing interneurons of the dentate gyrus control the activation and proliferation of quiescent adult neural stem cells.

Newborn neurons are generated in the adult hippocampus from a pool of self-renewing stem cells located in the subgranular zone (SGZ) of the dentate gyrus. Their activation, proliferation, and maturation depend on a host of environmental and cellular factors but, until recently, the contribution of local neuronal circuitry to this process was relatively unknown. In their recent publication, Song and colleagues have uncovered a novel circuit-based mechanism by which release of the neurotransmitter, γ-aminobutyric acid (GABA), from parvalbumin-expressing (PV) interneurons, can hold radial glia-like (RGL) stem cells of the adult SGZ in a quiescent state. This tonic GABAergic signal, dependent upon the activation of γ(2) subunit-containing GABA(A) receptors of RGL stem cells, can thus prevent their proliferation and subsequent maturation or return them to quiescence if previously activated. PV interneurons are thus capable of suppressing neurogenesis during periods of high network activity and facilitating neurogenesis when network activity is low.

Two novel MvaT-like global regulators control exoproduct formation and biocontrol activity in root-associated Pseudomonas fluorescens CHA0.

Pseudomonas fluorescens CHA0 protects various crop plants against root diseases caused by pathogenic fungi. Among a range of exoproducts excreted by strain CHA0, the antifungal compounds 2,4-diacetylphloroglucinol (DAPG) and pyoluteorin (PLT) are particularly relevant to the strain's biocontrol potential. Here, we report on the characterization of MvaT and MvaV as novel regulators of biocontrol activity in strain CHA0. We establish the two proteins as further members of an emerging family of MvaT-like regulators in pseudomonads that are structurally and functionally related to the DNA-binding protein H-NS. In mvaT and mvaV in frame-deletion mutants of strain CHA0, PLT production was enhanced about four- and 1.5-fold, respectively, whereas DAPG production remained at wild-type levels. Remarkably, PLT production was increased up to 20-fold in an mvaT mvaV double mutant. DAPG biosynthesis was almost completely repressed in this mutant. The effects on antibiotic production could be confirmed by following expression of gfp-based reporter fusions to the corresponding biosynthetic genes. MvaT and MvaV also influenced levels of other exoproducts, motility, and physicochemical cell-surface properties to various extents. Compared with the wild type, mvaT and mvaV mutants had an about 20% reduced capacity (in terms of plant fresh weight) to protect cucumber from a root rot caused by Pythium ultimum. Biocontrol activity was nearly completely abolished in the double mutant Our findings indicate that MvaT and MvaV act together as further global regulatory elements in the complex network controlling expression of biocontrol traits in plant-beneficial pseudomonads.

Improvement of rehabilitation possibilities with the MotionMaker (TM)

"MotionMaker (TM)" is a stationary programmable test and training system for the lower limbs developed at the 'Ecole Polytechnique Federale de Lausanne' with the 'Fondation Suisse pour les Cybertheses'.. The system is composed of two robotic orthoses comprising motors and sensors, and a control unit managing the trans-cutaneous electrical muscle stimulation with real-time regulation. The control of the Functional Electrical Stimulation (FES) induced muscle force necessary to mimic natural exercise is ensured by the control unit which receives a continuous input from the position and force sensors mounted on the robot. First results with control subjects showed the feasibility of creating movements by such closed-loop controlled FES induced muscle contractions. To make exercising with the MotionMaker (TM) safe for clinical trials with Spinal Cord Injured (SCI) volunteers, several original safety features have been introduced. The MotionMaker (TM) is able to identify and manage the occurrence of spasms. Fatigue can also be detected and overfatigue during exercise prevented.

Different transcriptional control of metabolism and extracellular matrix in visceral and subcutaneous fat of obese and rimonabant treated mice.

BACKGROUND: The visceral (VAT) and subcutaneous (SCAT) adipose tissues play different roles in physiology and obesity. The molecular mechanisms underlying their expansion in obesity and following body weight reduction are poorly defined. METHODOLOGY: C57Bl/6 mice fed a high fat diet (HFD) for 6 months developed low, medium, or high body weight as compared to normal chow fed mice. Mice from each groups were then treated with the cannabinoid receptor 1 antagonist rimonabant or vehicle for 24 days to normalize their body weight. Transcriptomic data for visceral and subcutaneous adipose tissues from each group of mice were obtained and analyzed to identify: i) genes regulated by HFD irrespective of body weight, ii) genes whose expression correlated with body weight, iii) the biological processes activated in each tissue using gene set enrichment analysis (GSEA), iv) the transcriptional programs affected by rimonabant. PRINCIPAL FINDINGS: In VAT, "metabolic" genes encoding enzymes for lipid and steroid biosynthesis and glucose catabolism were down-regulated irrespective of body weight whereas "structure" genes controlling cell architecture and tissue remodeling had expression levels correlated with body weight. In SCAT, the identified "metabolic" and "structure" genes were mostly different from those identified in VAT and were regulated irrespective of body weight. GSEA indicated active adipogenesis in both tissues but a more prominent involvement of tissue stroma in VAT than in SCAT. Rimonabant treatment normalized most gene expression but further reduced oxidative phosphorylation gene expression in SCAT but not in VAT. CONCLUSION: VAT and SCAT show strikingly different gene expression programs in response to high fat diet and rimonabant treatment. Our results may lead to identification of therapeutic targets acting on specific fat depots to control obesity.

Entomopathogenic nematodes for the control of phorid and sciarid flies in mushroom crops

The objective of this work was to evaluate the efficacy of two nematodes, Steinernema feltiae and S. carpocapsae, to control mushroom flies and to evaluate the effect of these treatments on Agaricus bisporus production. Two mushroom cultivation trials were carried out in controlled conditions, in substrate previously infested with the diptera Megaselia halterata and Lycoriella auripila, with two treatments: 106infective juveniles (IJ) per square meter of S. feltiae and 0.5x106IJ m-2S. feltiae + 0.5x106IJ m-2S. carpocapsae. Another experiment was carried out using the same treatments to evaluate the possible nematode effect on mushroom yield. The number of adults emerging from the substrate was evaluated for each fly species. No decrease in the population of M. halterata was detected with nematode application, whereas the number of L. auripila was reduced in both treatments, particularly in the individual treatment with S. feltiae. The application of entomopathogenic nematodes has no adverse effect on mushroom production.

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Assessing chronic disease management in European health systems : concepts and approaches

This book comprises two volumes and builds on the findings of the DISMEVAL project (Developing and validating DISease Management EVALuation methods for European health care systems), funded under the European Union's (EU) Seventh Framework Programme (FP7) (Agreement no. 223277). DISMEVAL was a three-year European collaborative project conducted between 2009 and 2011. It contributed to developing new research methods and generating the evidence base to inform decision-making in the field of chronic disease management evaluation (www.dismeval.eu). In this book, we report on the findings of the project's first phase, capturing the diverse range of contexts in which new approaches to chronic care are being implemented and evaluating the outcomes of these initiatives using an explicit comparative approach and a unified assessment framework. In this first volume, we describe the range of approaches to chronic care adopted in 12 European countries. By reflecting on the facilitators and barriers to implementation, we aim to provide policy-makers and practitioners with a portfolio of options to advance chronic care approaches in a given policy context.

Robottihitsauksen tehokas käyttöönotto

Työn tavoitteena oli selvittää uuden robottihitsaussolun käyttöönotto siten, että se tapahtuu mahdollisimman tehokkaasti ja taloudellisesti. Uudella robotilla on tarkoitus hitsata nykyisin käsinhitsattavia kauhakuormaajien takarunkoja sekä alihankintana tilattavia kauhoja. Tuotannon kotiuttamisella alihankinnasta ja hitsauksen robotisoinnilla pyritään nostamaan omaa tuotantovolyymiä ja pienentämään valmistuskustannuksia. Työn teoriaosuudessa selvitettiin tyypilliset robotiikkaan liittyvät asiat, kuten robotit, niiden ohjaus ja ohjelmointi sekä perusteet hitsauksen robotisoinnista. Lisäksi käsiteltiin hitsattavan tuotteen suunnittelu- ja valmistusnäkökohtia ja hitsauksen kustannuslaskennan perusteet. Työn käytännön osuudessa tehtiin kartoitus kahden valitun takarunkomallin soveltuvuudesta robottihitsaukseen ja muutosehdotuksia, joilla voidaan parantaa runkojen robottihitsattavuutta. Lisäksi käytiin läpi hitsauksen nykytilanne osavalmistuksesta aina hitsauksen jälkeiseen viimeistelyyn. Hitsauksen kustannusten selvittämistä varten tehtiin taulukkolaskentaohjelma, jolla tehtiin esimerkkinä kuvitteellinen kustannussäätölaskelma. Tuottavuusmittari laadittiin niin, että sillä voidaan mitata sekä robotin että kokohitsaustapahtuman tehokkuutta pitkällä ja lyhyellä aikavälillä. Näiden lisäksi laadittiin sisäinen ohje robottihitsattavien kappaleiden silloitukseen sekä suunnittelijoille ohjeistus huomioitavista asioista suunniteltaessa kappaletta robottihitsaukseen.

Interfacing Health Care Information Systems Design and Implementation

Terveydenhuollossa käytetään nykyisin informaatioteknologian (IT) mahdollisuuksia parantamaan hoidon laatua, vähentämään hoitoon liittyviä kuluja sekä yksinkertaistamaan ja selkeyttämään laakareiden työnkulkua. Tietojärjestelmät, jotka edustavat jokaisen IT-ratkaisun ydintä, täytyy kehittää täyttämään lukuisia vaatimuksia, ja yksi niistä on kyky integroitua saumattomasti toisten tietojärjestelmien kanssa. Järjestelmäintegraatio on kuitenkin yhä haastava tehtävä, vaikka sita varten on kehitetty useita standardeja. Tässä työssä kuvataan vastakehitetyn lääketieteellisen tietojärjestelmän liittymäratkaisu. Työssä pohditaan vaatimuksia, jotka tällaiselle sovellukselle asetetaan, ja myös tapa, jolla vaatimukset toteutuvat on esitetty. Liittymaratkaisu on jaettu kahteen osaan, tietojärjestelmaliittymään ja "liittymakoneeseen" (interfacing engine). Edellinen on käsittää perustoiminnallisuuden, jota tarvitaan vastaanottamaan ja lähettämään tietoa toisiin järjestelmiin, kun taas jälkimmäinen tarjoaa tuen tuotantoympäristössa käytettäville standardeille. Molempien osien suunnitelu on esitelty perusteellisesti tässä työssä. Ongelma ratkaistiin modulaarisen ja geneerisen suunnittelun avulla. Tämä lähestymistapa osoitetaan työssä kestäväksi ja joustavaksi ratkaisuksi, jota voidaan käyttää tarkastelemaan laajaa valikoimaa liittymäratkaisulle asetettuja vaatimuksia. Lisaksi osoitetaan kuinka tehty ratkaisu voidaan joustavuutensa ansiosta helposti mukauttaa vaatimuksiin, joita ei ole etukäteen tunnistettu, ja siten saavutetaan perusta myös tulevaisuuden tarpeille