A Proposal for a Multi-Drive Heterogeneous Modular Pipe- Inspection Micro-Robot

This paper presents the architecture used to develop a micro-robot for narrow pipes inspection. Both the electromechanical design and the control scheme will be described. In pipe environments it is very useful to have a method to retrieve information of the state of the inside part of the pipes in order to detect damages, breaks and holes. Due to the di_erent types of pipes that exists, a modular approach with di_erent types of modules has been chosen in order to be able to adapt to the shape of the pipe and to chose the most appropriate gait. The micro-robot has been designed for narrow pipes, a _eld in which there are not many prototypes. The robot incorporates a camera module for visual inspection and several drive modules for locomotion and turn (helicoidal, inchworm, two degrees of freedom rotation). The control scheme is based on semi-distributed behavior control and is also described. A simulation environment is also presented for prototypes testing

Enhancement of the stability of genetic switches by overlapping upstream regulatory domains

We study genetic switches formed from pairs of mutually repressing operons. The switch stability is characterised by a well defined lifetime which grows sub-exponentially with the number of copies of the most-expressed transcription factor, in the regime accessible by our numerical simulations. The stability can be markedly enhanced by a suitable choice of overlap between the upstream regulatory domains. Our results suggest that robustness against biochemical noise can provide a selection pressure that drives operons, that regulate each other, together in the course of evolution.Comment: 4 pages, 5 figures, RevTeX

Novel cruzain inhibitors for the treatment of Chagas' disease.

The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas' disease, affects millions of individuals and continues to be an important global health concern. The poor efficacy and unfavorable side effects of current treatments necessitate novel therapeutics. Cruzain, the major cysteine protease of T. cruzi, is one potential novel target. Recent advances in a class of vinyl sulfone inhibitors are encouraging; however, as most potential therapeutics fail in clinical trials and both disease progression and resistance call for combination therapy with several drugs, the identification of additional classes of inhibitory molecules is essential. Using an exhaustive virtual-screening and experimental validation approach, we identify several additional small-molecule cruzain inhibitors. Further optimization of these chemical scaffolds could lead to the development of novel drugs useful in the treatment of Chagas' disease

Analytical study of an exclusive genetic switch

The nonequilibrium stationary state of an exclusive genetic switch is considered. The model comprises two competing species and a single binding site which, when bound to by a protein of one species, causes the other species to be repressed. The model may be thought of as a minimal model of the power struggle between two competing parties. Exact solutions are given for the limits of vanishing binding/unbinding rates and infinite binding/unbinding rates. A mean field theory is introduced which is exact in the limit of vanishing binding/unbinding rates. The mean field theory and numerical simulations reveal that generically bistability occurs and the system is in a symmetry broken state. An exact perturbative solution which in principle allows the nonequilibrium stationary state to be computed is also developed and computed to first and second order.Comment: 28 pages, 6 figure

Universally Sloppy Parameter Sensitivities in Systems Biology

Quantitative computational models play an increasingly important role in modern biology. Such models typically involve many free parameters, and assigning their values is often a substantial obstacle to model development. Directly measuring \emph{in vivo} biochemical parameters is difficult, and collectively fitting them to other data often yields large parameter uncertainties. Nevertheless, in earlier work we showed in a growth-factor-signaling model that collective fitting could yield well-constrained predictions, even when it left individual parameters very poorly constrained. We also showed that the model had a `sloppy' spectrum of parameter sensitivities, with eigenvalues roughly evenly distributed over many decades. Here we use a collection of models from the literature to test whether such sloppy spectra are common in systems biology. Strikingly, we find that every model we examine has a sloppy spectrum of sensitivities. We also test several consequences of this sloppiness for building predictive models. In particular, sloppiness suggests that collective fits to even large amounts of ideal time-series data will often leave many parameters poorly constrained. Tests over our model collection are consistent with this suggestion. This difficulty with collective fits may seem to argue for direct parameter measurements, but sloppiness also implies that such measurements must be formidably precise and complete to usefully constrain many model predictions. We confirm this implication in our signaling model. Our results suggest that sloppy sensitivity spectra are universal in systems biology models. The prevalence of sloppiness highlights the power of collective fits and suggests that modelers should focus on predictions rather than on parameters.Comment: Submitted to PLoS Computational Biology. Supplementary Information available in "Other Formats" bundle. Discussion slightly revised to add historical contex

Maximizing Maximal Angles for Plane Straight-Line Graphs

Let $G=(S, E)$ be a plane straight-line graph on a finite point set $S\subset\R^2$ in general position. The incident angles of a vertex $p \in S$ of $G$ are the angles between any two edges of $G$ that appear consecutively in the circular order of the edges incident to $p$. A plane straight-line graph is called $\phi$-open if each vertex has an incident angle of size at least $\phi$. In this paper we study the following type of question: What is the maximum angle $\phi$ such that for any finite set $S\subset\R^2$ of points in general position we can find a graph from a certain class of graphs on $S$ that is $\phi$-open? In particular, we consider the classes of triangulations, spanning trees, and paths on $S$ and give tight bounds in most cases.Comment: 15 pages, 14 figures. Apart of minor corrections, some proofs that were omitted in the previous version are now include

Advancing the remote sensing of precipitation

Satellite-based global precipitation data has addressed the limitations of rain gauges and weather radar systems in forecasting applications and for weather and climate studies. Inspite of this ability, a number of issues that require the development of advanced concepts to address key challenges in satellite-based observations of precipitation were identified during the Advanced Concepts Workshop on Remote Sensing of Precipitation at Multiple Scales at the University of California. These include quantification of uncertainties of individual sensors and their propagation into multisensor products warrants a great deal of research. The development of metrics for validation and uncertainty analysis are of great importance. Bias removal, particularly probability distribution function (PDF)-based adjustment, deserves more in-depth research. Development of a near-real-time probabilistic uncertainty model for satellitebased precipitation estimates is highly desirable

Fluctuations in Gene Regulatory Networks as Gaussian Colored Noise

The study of fluctuations in gene regulatory networks is extended to the case of Gaussian colored noise. Firstly, the solution of the corresponding Langevin equation with colored noise is expressed in terms of an Ito integral. Then, two important lemmas concerning the variance of an Ito integral and the covariance of two Ito integrals are shown. Based on the lemmas, we give the general formulae for the variances and covariance of molecular concentrations for a regulatory network near a stable equilibrium explicitly. Two examples, the gene auto-regulatory network and the toggle switch, are presented in details. In general, it is found that the finite correlation time of noise reduces the fluctuations and enhances the correlation between the fluctuations of the molecular components.Comment: 10 pages, 4 figure

Vibrational Enhancement of the Effective Donor - Acceptor Coupling

The paper deals with a simple three sites model for charge transfer phenomena in an one-dimensional donor (D) - bridge (B) - acceptor (A) system coupled with vibrational dynamics of the B site. It is found that in a certain range of parameters the vibrational coupling leads to an enhancement of the effective donor - acceptor electronic coupling as a result of the formation of the polaron on the B site. This enhancement of the charge transfer efficiency is maximum at the resonance, where the effective energy of the fluctuating B site coincides with the donor (acceptor) energy.Comment: 5 pages, 3 figure

Simple Wriggling is Hard unless You Are a Fat Hippo

We prove that it is NP-hard to decide whether two points in a polygonal domain with holes can be connected by a wire. This implies that finding any approximation to the shortest path for a long snake amidst polygonal obstacles is NP-hard. On the positive side, we show that snake's problem is "length-tractable": if the snake is "fat", i.e., its length/width ratio is small, the shortest path can be computed in polynomial time.Comment: A shorter version is to be presented at FUN 201