Stochastic simulations of the tetracycline operon

<p>Abstract</p> <p>Background</p> <p>The tetracycline operon is a self-regulated system. It is found naturally in bacteria where it confers resistance to antibiotic tetracycline. Because of the performance of the molecular elements of the tetracycline operon, these elements are widely used as parts of synthetic gene networks where the protein production can be efficiently turned on and off in response to the presence or the absence of tetracycline. In this paper, we investigate the dynamics of the tetracycline operon. To this end, we develop a mathematical model guided by experimental findings. Our model consists of biochemical reactions that capture the biomolecular interactions of this intriguing system. Having in mind that small biological systems are subjects to stochasticity, we use a stochastic algorithm to simulate the tetracycline operon behavior. A sensitivity analysis of two critical parameters embodied this system is also performed providing a useful understanding of the function of this system.</p> <p>Results</p> <p>Simulations generate a timeline of biomolecular events that confer resistance to bacteria against tetracycline. We monitor the amounts of intracellular TetR2 and TetA proteins, the two important regulatory and resistance molecules, as a function of intrecellular tetracycline. We find that lack of one of the promoters of the tetracycline operon has no influence on the total behavior of this system inferring that this promoter is not essential for <it>Escherichia coli</it>. Sensitivity analysis with respect to the binding strength of tetracycline to repressor and of repressor to operators suggests that these two parameters play a predominant role in the behavior of the system. The results of the simulations agree well with experimental observations such as tight repression, fast gene expression, induction with tetracycline, and small intracellular TetR2 amounts.</p> <p>Conclusions</p> <p>Computer simulations of the tetracycline operon afford augmented insight into the interplay between its molecular components. They provide useful explanations of how the components and their interactions have evolved to best serve bacteria carrying this operon. Therefore, simulations may assist in designing novel gene network architectures consisting of tetracycline operon components.</p

MatVPC: A User-Friendly MATLAB-Based Tool for the Simulation and Evaluation of Systems Pharmacology Models

International audienceQuantitative systems pharmacology (QSP) models are progressively entering the arena of contemporary pharmacology. The efficient implementation and evaluation of complex QSP models necessitates the development of flexible computational tools that are built into QSP mainstream software. To this end, we present MatVPC, a versatile MATLAB-based tool that accommodates QSP models of any complexity level. MatVPC executes Monte Carlo simulations as well as automatic construction of visual predictive checks (VPCs) and quantified VPCs (QVPCs). VPC is a model diagnostic tool that facilitates the evaluation of both the structural and the stochastic part of a model. It is constructed by superimposing the observations over the model simulations while accounting for both the interindivid-ual variability as well as the residual variability. 1 Once underutilized, 2 the VPC now is recognized as one of the most valuable model diagnostics in pharmacological model evaluation. 3–5 Its superiority over comparable diagnostic tools has been established 6 and reflected by the fact that regulatory agencies recommend it as one of the central model diagnostics.

How to Build Kinetic Models of BioBricks

This BioBricks Foundation Request for Comments (BBF RFC) provides instructions on how to automatically generate a model of any BioBrick sequence. These models can be used in computer simulations of the dynamic behavior of all molecular components of the BioBrick

Polarised Multiangular Reflectance Measurements Using the Finnish Geodetic Institute Field Goniospectrometer

The design, operation, and properties of the Finnish Geodetic Institute Field Goniospectrometer (FIGIFIGO) are presented. FIGIFIGO is a portable instrument for the measurement of surface Bidirectional Reflectance Factor (BRF) for samples with diameters of 10 – 50 cm. A set of polarising optics enable the measurement of linearly polarised BRF over the full solar spectrum (350 – 2,500 nm). FIGIFIGO is designed mainly for field operation using sunlight, but operation in a laboratory environment is also possible. The acquired BRF have an accuracy of 1 – 5% depending on wavelength, sample properties, and measurement conditions. The angles are registered at accuracies better than 2°. During 2004 – 2008, FIGIFIGO has been used in the measurement of over 150 samples, all around northern Europe. The samples concentrate mostly on boreal forest understorey, snow, urban surfaces, and reflectance calibration surfaces

Spatial data infrastructures in Malta : state of play 2010

This report aims at summarizing the state of play of SDI in Malta, and at reflecting the degree to which the SDI situation in Malta is similar to the ideas set out in the INSPIRE position papers and the more recent INSPIRE scoping documents. Since documents, project references could hardly be found, the report is based mainly on the study of the few web sites readily accessible in English (some sites with technical specifications or illustrations also in Maltese). The report has been completed by integration and consolidation of comments received early 2003 from representatives of the National Statistics Office and the Malta Environment and Planning Authority (MEPA). Early 2004, more comments were received and taken into account, coming from Malta Environment and Planning Authority and from a private GI-company (Datatrak IT services). The comments were provided in written form (e-mail). The update of 2005 was based on input from Ms. Carol Valentino from MEPA. The update for 2006 was based on various sources, focusing on the legal and organisational elements of the SDI. For the update of 2007, no information regarding data sharing, data sets or services was received. Some information on licence fees could be found through other channels. For the 2009 update, no information regarding the survey questionnaire was received and the main source of information was extracted from the 2009 ICT components for a Shared Environmental Information System State of Play report. In this version obsolete information was removed, while a conclusion paragraph regarding the status of each indicator was added for each component.peer-reviewe

A Compact Laboratory Spectro-Goniometer (CLabSpeG) to Assess the BRDF of Materials. Presentation, Calibration and Implementation on Fagus sylvatica L. Leaves

The design and calibration of a new hyperspectral Compact Laboratory Spectro-Goniometer (CLabSpeG) is presented. CLabSpeG effectively measures the bidirectionalreflectance Factor (BRF) of a sample, using a halogen light source and an AnalyticalSpectral Devices (ASD) spectroradiometer. The apparatus collects 4356 reflectance datareadings covering the spectrum from 350 nm to 2500 nm by independent positioning of thesensor, sample holder, and light source. It has an azimuth and zenith resolution of 30 and15 degrees, respectively. CLabSpeG is used to collect BRF data and extract BidirectionalReflectance Distribution Function (BRDF) data of non-isotropic vegetation elements suchas bark, soil, and leaves. Accurate calibration has ensured robust geometric accuracy of theapparatus, correction for the conicality of the light source, while sufficient radiometricstability and repeatability between measurements are obtained. The bidirectionalreflectance data collection is automated and remotely controlled and takes approximatelytwo and half hours for a BRF measurement cycle over a full hemisphere with 125 cmradius and 2.4 minutes for a single BRF acquisition. A specific protocol for vegetative leafcollection and measurement was established in order to investigate the possibility to extractBRDF values from Fagus sylvatica L. leaves under laboratory conditions. Drying leafeffects induce a reflectance change during the BRF measurements due to the laboratorySensors 2007, 7 1847 illumination source. Therefore, the full hemisphere could not be covered with one leaf. Instead 12 BRF measurements per leaf were acquired covering all azimuth positions for a single light source zenith position. Data are collected in radiance format and reflectance is calculated by dividing the leaf cycle measurement with a radiance cycle of a Spectralon reference panel, multiplied by a Spectralon reflectance correction factor and a factor to correct for the conical effect of the light source. BRF results of measured leaves are presented

Describing biophysical and optical characteristics of forests through computer modelling and visualisation

status: publishe

An analysis of contracting officer technical representative training requirements

The activities within the Navy Field Contracting System (NFCS) which exercise regional contract management responsibilities are writing and administering an increasing number of services type contracts. These contracts require active participation in the contract administration function by the activities for which the contracts are written. The persons assigned the duty of representing the contracting officer and performing the technical liaison functions are usually called Contracting Officer Technical Representatives (COTRs). Since the environment COTRs must work in is often new and requires different knowledge and skills, the content and quality of training of these individuals is of significant importance. This research identifies the knowledge and skill requirements for COTRS, examines the assets currently in use to satisfy COTR training needs, and proposes a new approach to the structure and administration of COTR training. A modular structure using several presentation media is emphasized, and video sessions are featured. Examinations are also given.http://archive.org/details/analysisofcontra00coleCommander, United States NavyLieutenant, United States NavyApproved for public release; distribution is unlimited

Spatial Data Infrastructures in Poland: State of Play 2010

nrpages: 40status: publishe