Three-Dimensional patchy lattice model for empty fluids

The phase diagram of a simple model with two patches of type A and ten patches of type B (2A10B) on the face centred cubic lattice has been calculated by simulations and theory. Assuming that there is no interaction between the B patches the behavior of the system can be described in terms of the ratio of the AB and AA interactions, r. Our results show that, similarly to what happens for related off-lattice and two-dimensional lattice models, the liquid-vapor phase equilibria exhibit reentrant behavior for some values of the interaction parameters. However, for the model studied here the liquid-vapor phase equilibria occur for values of r lower than 1/3, a threshold value which was previously thought to be universal for 2AnB models. In addition, the theory predicts that below r = 1/3 (and above a new condensation threshold which is < 1/3) the reentrant liquid-vapor equilibria are so extreme that it exhibits a closed loop with a lower critical point, a very unusual behavior in single-component systems. An order-disorder transition is also observed at higher densities than the liquid-vapor equilibria, which shows that the liquid-vapor reentrancy occurs in an equilibrium region of the phase diagram. These findings may have implications in the understanding of the condensation of dipolar hard spheres given the analogy between that system and the 2AnB models considered here.

Opening Pousada da Serra da Estrela in Covilhã: A two-way impact analysis - Interacting with public agents

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Asynchronous growth and competition in a two-sex age-structured population model

Asynchronous exponential growth has been extensively studied in population dynamics. In this paper we find out the asymptotic behaviour in a non-linear age-dependent model which takes into account sexual reproduction interactions. The main feature of our model is that the non-linear process converges to a linear one as the solution becomes large, so that the population undergoes asynchronous growth. The steady states analysis and the corresponding stability analysis are completely made and are summarized in a bifurcation diagram according to the parameter R0. Furthermore the effect of intraspecific competition is taken into account, leading to complex dynamics around steady states.

Work and health : remodelling perspectives of working life research, as proposed by Järvholm et al. (2009)

Järvholm and Co-workers (2009) proposed a conceptual model for research on working life. Models are powerful communication and decision tools. This model is strongly unidirectional and does not cover the mentioned interactions in the arguments.With help of a genealogy of work and of health it is shown that work and health are interactive and have to be analysed on the background of society.Key words: research model, work, health, occupational health, society, interaction, discussion paperRemodellierung der von Järvholm et al. (2009) vorgeschlagenen Forschungsperspektiven in Arbeit und GesundheitJärvholm und Kollegen stellten 2009 ein konzeptionelles Modell für die Forschung im Bereich Arbeit und Gesundheit vor. Modelle stellen kraftvolle Kommunikations- und Entscheidungsinstrumente dar. Die Einflussfaktoren im Modell verlaufen jedoch nur in einer Richtung und bilden die interaktiven Argumente im Text nicht ab. Mit Hilfe einer Genealogie der Begriffe Arbeit und Gesundheit wird aufgezeigt, dass Arbeit und Gesundheit sich gegenseitig beeinflussen und nur vor dem Hintergrund der jeweiligen gesellschaftlichen Kontextfaktoren zu analysieren sind.Introduction : After an interesting introduction about the objectives of research on working life, Järvholm and Co-workers (2009) manage to define a conceptual model for working life research out of a small survey of Occupational Safety and Health (OSH) definitions. The strong point of their model is the entity 'working life' including personal development, as well as career paths and aging. Yet, the model Järvholm et al. (2009) propose is strangely unidirectional; the arrows point from the population to working life, from there to health and to disease, as well as to productivity and economic resources. The diagram only shows one feed-back loop: between economic resources and health. We all know that having a chronic disease condition influences work and working capacity. Economic resources have a strong influence on work, too. Having personal economic resources will influence the kind of work someone accepts and facilitate access to continuous professional education. A third observation is that society is not present in the model, although this is less the case in the arguments. In fact, there is an incomprehensible gap between the arguments brought forth by Järvholm and co-workers and their reductionist model.Switzerland has a very low coverage of occupational health specialists. Switzerland is a long way from fulfilling the WHO's recommendations on workers' access to OSH services as described in its Global plan of action. The Institute for Work and Health (IST) in Lausanne is the only organisation which covers the major domains of OSH research that are occupational medicine, occupational hygiene, ergonomic and psychosocial research. As the country's sole occupational health institution we are forced to reflect the objectives of working life research so as not to waste the scare resources available.I will set out below a much shortened genealogy of work and of health, with the aim of extending Järvholm et al's (2009) analyses on the perspectives of working life research in two directions. Firstly towards the interactive nature of work and health and the integration of society, and secondly towards the question of what working life means or where working life could be situated.Work, as we know it today - paid work regulated by a contract as the basis for sustaining life and as a base for social rights - was born in modern era. Therefore I will start my genealogy in the pre-modern era, focus on the important changes that occurred during industrial revolution and the modern era and end in 2010 taking into account the enormous transformations of the past 20-30 years. I will put aside some 810 years of advances in science and technology that have expanded the world's limits and human understanding, and restrict my genealogy to work and to health/body implicating also the societal realm. [Author]

The fou2 gain-of-function allele and the wild-type allele of Two Pore Channel 1 contribute to different extents or by different mechanisms to defense gene expression in Arabidopsis.

The fatty acid oxygenation up-regulated 2 (fou2) mutant in Arabidopsis thaliana creates a gain-of-function allele in a non-selective cation channel encoded by the Two Pore Channel 1 (TPC1) gene. This mutant genetically implicates cation fluxes in the control of the positive feedback loop whereby jasmonic acid (JA) stimulates its own synthesis. In this study we observed extensive transcriptome reprogramming in healthy fou2 leaves closely resembling that induced by treatment with methyl jasmonate, biotic stresses and the potassium starvation response. Proteomic analysis of fou2 leaves identified increased levels of seven biotic stress- and JA-inducible proteins. In agreement with these analyses, epistasis studies performed by crossing fou2 with aos indicated that elevated levels of JA in fou2 are the major determinant of the mutant phenotype. In addition, generation of fou2 aba1-5, fou2 etr1-1 and fou2 npr1-1 double mutants showed that the fou2 phenotype was only weakly affected by ABA levels and unaffected by mutations in NPR1 and ETR1. The results now suggest possible mechanisms whereby fou2 could induce JA synthesis/signaling early in the wound response. In contrast to fou2, transcriptome analysis of a loss-of-function allele of TPC1, tpc1-2, revealed no differential expression of JA biosynthesis genes in resting leaves. However, the analysis disclosed reduced mRNA levels of the pathogenesis-related genes PDF1.2a and THI2.1 in healthy and diseased tpc1-2 leaves. The results suggest that wild-type TPC1 contributes to their expression by mechanisms somewhat different from those affecting their expression in fou2.

Access of extracellular cations to their binding sites in Na,K-ATPase: role of the second extracellular loop of the alpha subunit.

Na,K-ATPase, the main active transport system for monovalent cations in animal cells, is responsible for maintaining Na(+) and K(+) gradients across the plasma membrane. During its transport cycle it binds three cytoplasmic Na(+) ions and releases them on the extracellular side of the membrane, and then binds two extracellular K(+) ions and releases them into the cytoplasm. The fourth, fifth, and sixth transmembrane helices of the alpha subunit of Na,K-ATPase are known to be involved in Na(+) and K(+) binding sites, but the gating mechanisms that control the access of these ions to their binding sites are not yet fully understood. We have focused on the second extracellular loop linking transmembrane segments 3 and 4 and attempted to determine its role in gating. We replaced 13 residues of this loop in the rat alpha1 subunit, from E314 to G326, by cysteine, and then studied the function of these mutants using electrophysiological techniques. We analyzed the results using a structural model obtained by homology with SERCA, and ab initio calculations for the second extracellular loop. Four mutants were markedly modified by the sulfhydryl reagent MTSET, and we investigated them in detail. The substituted cysteines were more readily accessible to MTSET in the E1 conformation for the Y315C, W317C, and I322C mutants. Mutations or derivatization of the substituted cysteines in the second extracellular loop resulted in major increases in the apparent affinity for extracellular K(+), and this was associated with a reduction in the maximum activity. The changes produced by the E314C mutation were reversed by MTSET treatment. In the W317C and I322C mutants, MTSET also induced a moderate shift of the E1/E2 equilibrium towards the E1(Na) conformation under Na/Na exchange conditions. These findings indicate that the second extracellular loop must be functionally linked to the gating mechanism that controls the access of K(+) to its binding site.

Understanding the two-component sensing System of virulent bacteria

Report for the scientific sojourn carried out at the l’ Institute for Computational Molecular Science of the Temple University, United States, from 2010 to 2012. Two-component systems (TCS) are used by pathogenic bacteria to sense the environment within a host and activate mechanisms related to virulence and antimicrobial resistance. A prototypical example is the PhoQ/PhoP system, which is the major regulator of virulence in Salmonella. Hence, PhoQ is an attractive target for the design of new antibiotics against foodborne diseases. Inhibition of the PhoQ-mediated bacterial virulence does not result in growth inhibition, presenting less selective pressure for the generation of antibiotic resistance. Moreover, PhoQ is a histidine kinase (HK) and it is absent in animals. Nevertheless, the design of satisfactory HK inhibitors has been proven to be a challenge. To compete with the intracellular ATP concentrations, the affinity of a HK inhibidor must be in the micromolar-nanomolar range, whereas the current lead compounds have at best millimolar affinities. Moreover, the drug selectivity depends on the conformation of a highly variable loop, referred to as the “ATP-lid, which is difficult to study by X-Ray crystallography due to its flexibility. I have investigated the binding of different HK inhibitors to PhoQ. In particular, all-atom molecular dynamics simulations have been combined with enhanced sampling techniques in order to provide structural and dynamic information of the conformation of the ATP-lid. Transient interactions between these drugs and the ATP-lid have been identified and the free energy of the different binding modes has been estimated. The results obtained pinpoint the importance of protein flexibility in the HK-inhibitor binding, and constitute a first step in developing more potent and selective drugs. The computational resources of the hosting institution as well as the experience of the members of the group in drug binding and free energy methods have been crucial to carry out this work.

TCR-alpha CDR3 loop audition regulates positive selection.

How positive selection molds the T cell repertoire has been difficult to examine. In this study, we use TCR-beta-transgenic mice in which MHC shapes TCR-alpha use. Differential AV segment use is directly related to the constraints placed on the composition of the CDR3 loops. Where these constraints are low, efficient selection of alphabeta pairs follows. This mode of selection preferentially uses favored AV-AJ rearrangements and promotes diversity. Increased constraint on the alpha CDR3 loops leads to inefficient selection associated with uncommon recombination events and limited diversity. Further, the two modes of selection favor alternate sets of AJ segments. We discuss the relevance of these findings to the imprint of self-MHC restriction and peripheral T cell activation.

Focal dystonia and the Sensory-Motor Integrative Loop for Enacting (SMILE).

Performing accurate movements requires preparation, execution, and monitoring mechanisms. The first two are coded by the motor system, the latter by the sensory system. To provide an adaptive neural basis to overt behaviors, motor and sensory information has to be properly integrated in a reciprocal feedback loop. Abnormalities in this sensory-motor loop are involved in movement disorders such as focal dystonia, a hyperkinetic alteration affecting only a specific body part and characterized by sensory and motor deficits in the absence of basic motor impairments. Despite the fundamental impact of sensory-motor integration mechanisms on daily life, the general principles of healthy and pathological anatomic-functional organization of sensory-motor integration remain to be clarified. Based on the available data from experimental psychology, neurophysiology, and neuroimaging, we propose a bio-computational model of sensory-motor integration: the Sensory-Motor Integrative Loop for Enacting (SMILE). Aiming at direct therapeutic implementations and with the final target of implementing novel intervention protocols for motor rehabilitation, our main goal is to provide the information necessary for further validating the SMILE model. By translating neuroscientific hypotheses into empirical investigations and clinically relevant questions, the prediction based on the SMILE model can be further extended to other pathological conditions characterized by impaired sensory-motor integration.

New insights on the crystalline forms in binary systems of n-alkanes: Characterization of the solid ordered phases in the phase diagram tricosane + pentacosane

X-ray diffraction analyses of the pure components n-tricosane and n-pentacosane and of their binary mixed samples have enabled us to characterize the crystalline phases observed at low temperature. On the contrary to what was announced in literature on the structural behavior of mixed samples in odd-odd binary systems with D n = 2, the three domains are not all orthorhombic. This work has enabled us to show that two of the domains are, in fact, monoclinic, (Aa, Z = 4) and the other one is orthorhombic (Pca21, Z = 4). The conclusions drawn in this work can be easily transposed to other binary systems of n-alkanes.

Regulatory roles of the GacS/GacA two-component system in plant-associated and other gram-negative bacteria.

The sensor kinase GacS and the response regulator GacA are members of a two-component system that is present in a wide variety of gram-negative bacteria and has been studied mainly in enteric bacteria and fluorescent pseudomonads. The GacS/GacA system controls the production of secondary metabolites and extracellular enzymes involved in pathogenicity to plants and animals, biocontrol of soilborne plant diseases, ecological fitness, or tolerance to stress. A current model proposes that GacS senses a still-unknown signal and activates, via a phosphorelay mechanism, the GacA transcription regulator, which in turn triggers the expression of target genes. The GacS protein belongs to the unorthodox sensor kinases, characterized by an autophosphorylation, a receiver, and an output domain. The periplasmic loop domain of GacS is poorly conserved in diverse bacteria. Thus, a common signal interacting with this domain would be unexpected. Based on a comparison with the transcriptional regulator NarL, a secondary structure can be predicted for the GacA sensor kinases. Certain genes whose expression is regulated by the GacS/GacA system are regulated in parallel by the small RNA binding protein RsmA (CsrA) at a posttranscriptional level. It is suggested that the GacS/GacA system operates a switch between primary and secondary metabolism, with a major involvement of posttranscriptional control mechanisms.

Pairing in a two-component ultracold Fermi gas: Phases with broken-space symmetries

We explore the phase diagram of a two-component ultracold atomic Fermi gas interacting with zero-range forces in the limit of weak coupling. We focus on the dependence of the pairing gap and the free energy on the variations in the number densities of the two species while the total density of the system is held fixed. As the density asymmetry is increased, the system exhibits a transition from a homogenous Bardeen-Cooper-Schrieffer (BCS) phase to phases with spontaneously broken global space symmetries. One such realization is the deformed Fermi surface superfluidity (DFS) which exploits the possibility of deforming the Fermi surfaces of the species into ellipsoidal form at zero total momentum of Cooper pairs. The critical asymmetries at which the transition from DFS to the unpaired state occurs are larger than those for the BCS phase. In this precritical region the DFS phase lowers the pairing energy of the asymmetric BCS state. We compare quantitatively the DFS phase to another realization of superconducting phases with broken translational symmetry: the single-plane-wave Larkin-Ovchinnikov-Fulde-Ferrell phase, which is characterized by a nonvanishing center-of-mass momentum of the Cooper pairs. The possibility of the detection of the DFS phase in the time-of-flight experiments is discussed and quantified for the case of 6Li atoms trapped in two different hyperfine states.

Loop bifurcation and magnetization rotation in exchange-biased Ni/FeF2

Exchange-biased Ni/FeF2 films have been investigated using vector coil vibrating-sample magnetometry as a function of the cooling field strength HFC . In films with epitaxial FeF2 , a loop bifurcation develops with increasing HFC as it divides into two sub-loops shifted oppositely from zero field by the same amount. The positively biased sub-loop grows in size with HFC until only a single positively shifted loop is found. Throughout this process, the negative and positive (sub)loop shifts maintain the same discrete value. This is in sharp contrast to films with twinned FeF2 where the exchange field gradually changes with increasing HFC . The transverse magnetization shows clear correlations with the longitudinal subloops. Interestingly, over 85% of the Ni reverses its magnetization by rotation, either in one step or through two successive rotations. These results are due to the single-crystal nature of the antiferromagnetic FeF2 , which breaks down into two opposite regions of large domains.

Potts fully frustrated model: Thermodynamics, percolation and dynamics in two dimensions

We consider a Potts model diluted by fully frustrated Ising spins. The model corresponds to a fully frustrated Potts model with variables having an integer absolute value and a sign. This model presents precursor phenomena of a glass transition in the high-temperature region. We show that the onset of these phenomena can be related to a thermodynamic transition. Furthermore, this transition can be mapped onto a percolation transition. We numerically study the phase diagram in two dimensions (2D) for this model with frustration and without disorder and we compare it to the phase diagram of (i) the model with frustration and disorder and (ii) the ferromagnetic model. Introducing a parameter that connects the three models, we generalize the exact expression of the ferromagnetic Potts transition temperature in 2D to the other cases. Finally, we estimate the dynamic critical exponents related to the Potts order parameter and to the energy.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.