Boolean Models of Bistable Biological Systems

This paper presents an algorithm for approximating certain types of dynamical systems given by a system of ordinary delay differential equations by a Boolean network model. Often Boolean models are much simpler to understand than complex differential equations models. The motivation for this work comes from mathematical systems biology. While Boolean mechanisms do not provide information about exact concentration rates or time scales, they are often sufficient to capture steady states and other key dynamics. Due to their intuitive nature, such models are very appealing to researchers in the life sciences. This paper is focused on dynamical systems that exhibit bistability and are desc ribedby delay equations. It is shown that if a certain motif including a feedback loop is present in the wiring diagram of the system, the Boolean model captures the bistability of molecular switches. The method is appl ied to two examples from biology, the lac operon and the phage lambda lysis/lysogeny switch

Real-time observations of single bacteriophage λ DNA ejections in vitro

The physical, chemical, and structural features of bacteriophage genome release have been the subject of much recent attention. Many theoretical and experimental studies have centered on the internal forces driving the ejection process. Recently, Mangenot et al. [Mangenot S, Hochrein M, Rädler J, Letellier L (2005) Curr Biol 15:430–435.] reported fluorescence microscopy of phage T5 ejections, which proceeded stepwise between DNA nicks, reaching a translocation speed of 75 kbp/s or higher. It is still unknown how high the speed actually is. This paper reports real-time measurements of ejection from phage {lambda}, revealing how the speed depends on key physical parameters such as genome length and ionic state of the buffer. Except for a pause before DNA is finally released, the entire 48.5-kbp genome is translocated in {approx}1.5 s without interruption, reaching a speed of 60 kbp/s. The process gives insights particularly into the effects of two parameters: a shorter genome length results in lower speed but a shorter total time, and the presence of divalent magnesium ions (replacing sodium) reduces the pressure, increasing ejection time to 8–11 s. Pressure caused by DNA–DNA interactions within the head affects the initiation of ejection, but the close packing is also the dominant source of friction: more tightly packed phages initiate ejection earlier, but with a lower initial speed. The details of ejection revealed in this study are probably generic features of DNA translocation in bacteriophages and have implications for the dynamics of DNA in other biological systems

The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p

Rab guanosine triphosphatases regulate intracellular membrane traffic by binding specific effector proteins. The yeast Rab Sec4p plays multiple roles in the polarized transport of post-Golgi vesicles to, and their subsequent fusion with, the plasma membrane, suggesting the involvement of several effectors. Yet, only one Sec4p effector has been documented to date: the exocyst protein Sec15p. The exocyst is an octameric protein complex required for tethering secretory vesicles, which is a prerequisite for membrane fusion. In this study, we describe the identification of a second Sec4p effector, Sro7p, which is a member of the lethal giant larvae tumor suppressor family. Sec4-GTP binds to Sro7p in cell extracts as well as to purified Sro7p, and the two proteins can be coimmunoprecipitated. Furthermore, we demonstrate the formation of a ternary complex of Sec4-GTP, Sro7p, and the t-SNARE Sec9p. Genetic data support our conclusion that Sro7p functions downstream of Sec4p and further imply that Sro7p and the exocyst share partially overlapping functions, possibly in SNARE regulation

LR characterization of chirotopes of finite planar families of pairwise disjoint convex bodies

We extend the classical LR characterization of chirotopes of finite planar families of points to chirotopes of finite planar families of pairwise disjoint convex bodies: a map \c{hi} on the set of 3-subsets of a finite set I is a chirotope of finite planar families of pairwise disjoint convex bodies if and only if for every 3-, 4-, and 5-subset J of I the restriction of \c{hi} to the set of 3-subsets of J is a chirotope of finite planar families of pairwise disjoint convex bodies. Our main tool is the polarity map, i.e., the map that assigns to a convex body the set of lines missing its interior, from which we derive the key notion of arrangements of double pseudolines, introduced for the first time in this paper.Comment: 100 pages, 73 figures; accepted manuscript versio

On the principal bifurcation branch of a third order nonlinear long-wave equation

We study the principal bifurcation curve of a third order equation which describes the nonlinear evolution of several systems with a long--wavelength instability. We show that the main bifurcation branch can be derived from a variational principle. This allows to obtain a close estimate of the complete branch. In particular, when the bifurcation is subcritical, the large amplitude stable branch can be found in a simple manner.Comment: 11 pages, 3 figure

Diffuse-interface model for rapid phase transformations in nonequilibrium systems

A thermodynamic approach to rapid phase transformations within a diffuse interface in a binary system is developed. Assuming an extended set of independent thermodynamic variables formed by the union of the classic set of slow variables and the space of fast variables, we introduce finiteness of the heat and solute diffusive propagation at the finite speed of the interface advancing. To describe the transformation within the diffuse interface, we use the phase-field model which allows us to follow the steep but smooth change of phases within the width of diffuse interface. The governing equations of the phase-field model are derived for the hyperbolic model, model with memory, and for a model of nonlinear evolution of transformation within the diffuse-interface. The consistency of the model is proved by the condition of positive entropy production and by the outcomes of the fluctuation-dissipation theorem. A comparison with the existing sharp-interface and diffuse-interface versions of the model is given.Comment: 15 pages, regular article submitted to Physical Review

Applying a User-centred Approach to Interactive Visualization Design

Analysing users in their context of work and finding out how and why they use different information resources is essential to provide interactive visualisation systems that match their goals and needs. Designers should actively involve the intended users throughout the whole process. This chapter presents a user-centered approach for the design of interactive visualisation systems. We describe three phases of the iterative visualisation design process: the early envisioning phase, the global specification hase, and the detailed specification phase. The whole design cycle is repeated until some criterion of success is reached. We discuss different techniques for the analysis of users, their tasks and domain. Subsequently, the design of prototypes and evaluation methods in visualisation practice are presented. Finally, we discuss the practical challenges in design and evaluation of collaborative visualisation environments. Our own case studies and those of others are used throughout the whole chapter to illustrate various approaches

Progress on the development of the Stellar X-ray Polarimeter on board of the Spectrum-X-Gamma Satellite

We present the status of the Stellar X-ray Polarimeter at November’94 devoted to measure linear polarisation from cosmic X-ray sources between 2 keV and 15 keV which will be flown on the Spectrum-X-Gamma Satellite. In particular, we focus on the performances of the engineering model after the calibrations at Lawrence Livermore Laboratories and on the improvements which have been introduced on the four flight model imaging proportional counters which are key parts of the experiment

Distribution and Regulation of the Mobile Genetic Element-Encoded Phenol-Soluble Modulin PSM-mec in Methicillin-Resistant Staphylococcus aureus

The phenol-soluble modulin PSM-mec is the only known staphylococcal toxin that is encoded on a mobile antibiotic resistance determinant, namely the staphylococcal cassette chromosome (SCC) element mec encoding resistance to methicillin. Here we show that the psm-mec gene is found frequently among methicillin-resistant Staphylococcus aureus (MRSA) strains of SCCmec types II, III, and VIII, and is a conserved part of the class A mec gene complex. Controlled expression of AgrA versus RNAIII in agr mutants of all 3 psm-mec-positive SCCmec types demonstrated that expression of psm-mec, which is highly variable, is controlled by AgrA in an RNAIII-independent manner. Furthermore, psm-mec isogenic deletion mutants showed only minor changes in PSMα peptide production and unchanged (or, as previously described, diminished) virulence compared to the corresponding wild-type strains in a mouse model of skin infection. This indicates that the recently reported regulatory impact of the psm-mec locus on MRSA virulence, which is opposite to that of the PSM-mec peptide and likely mediated by a regulatory RNA, is minor when analyzed in the original strain background. Our study gives new insight in the distribution, regulation, and role in virulence of the PSM-mec peptide and the psm-mec gene locus

An Application of the Concept of the Therapeutic Alliance To Sadomasochistic Pathology

This paper traces the history of the therapeutic alliance concept, examining how it has been used and misused, at times elevated to a central position and at others rejected altogether. The loss of this concept created a vacuum in classical psychoanalysis that has been filled by rival theories. The continuing usefulness of looking at the treatment process through the lens of the therapeutic alliance, particularly in relation to the manifold difficulties of working with sadomasochistic pathology, is suggested. To this end, revisions of the theory of the therapeutic alliance are suggested to address some of the difficulties that have arisen in conceptualizing this aspect of the therapeutic relationship, and to provide an integrated dynamic model for working with patients at each phase of treatment. This revised model acknowledges the complexity of the domain and encompasses the multiple tasks, functions, partners, and treatment phases involved. The utility of the revised theory is illustrated in application to understanding the sadomasochistic, omnipotent resistances of a female patient through the phases of her analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66889/2/10.1177_00030651980460031301.pd