Restoring Global Gene Regulation through Experimental Evolution Uncovers a NAP (Nucleoid-Associated Protein)-Like Behavior of Crp/Cap

Here we report that mutations in the topA gene compensate for loss of cAMP, showing that the interplay between Crp and the supercoiling status of promoters is key to global stress response. Furthermore, we observed an effect of apoCrp on gene expression in the absence of its effector cAMP. This provides support for the proposed NAP-like role for Crp, suggesting that it represents an intermediate point in the evolution of a ligand-controlled TF from a NAP.

Sequential Multiple Assignment Randomized Trial (SMART) to identify optimal sequences of telemedicine interventions for improving initiation of insulin therapy: A simulation study

Background To examine the value of a Sequential Multiple Assignment Randomized Trial (SMART) design compared to a conventional randomized control trial (RCT) for telemedicine strategies to support titration of insulin therapy for Type 2 Diabetes Mellitus (T2DM) patients new to insulin. Methods Microsimulation models were created in R using a synthetic sample based on primary data from 63 subjects enrolled in a pilot study of a smartphone application (App), Diabetes Pal compared to a nurse-based telemedicine strategy (Nurse). For comparability, the SMART and an RCT design were constructed to allow comparison of four (embedded) adaptive interventions (AIs). Results In the base case scenario, the SMART has similar overall mean expected HbA1c and cost per subject compared with RCT, for sample size of n = 100 over 10,000 simulations. SMART has lower (better) standard deviations of the mean expected HbA1c per AI, and higher efficiency of choosing the correct AI across various sample sizes. The differences between SMART and RCT become apparent as sample size decreases. For both trial designs, the threshold value at which a subject was deemed to have been responsive at an intermediate point in the trial had an optimal choice (i.e., the sensitivity curve had a U-shape). SMART design dominates the RCT, in the overall mean HbA1c (lower value) when the threshold value is close to optimal. Conclusions SMART is suited to evaluating the efficacy of different sequences of treatment options, in addition to the advantage of providing information on optimal treatment sequences.

Village Kisiskhevi - the Best Resource for the Development of Cultural Tourism

Kakheti region is rich in abundance and diversity of tourist resources. The study and popularization of the tourism resources of each municipality is important for the cultural and economic development of both the region and each village. The article presents the multifaceted tourist opportunities in the territory of one of the ancient villages, Kisiskhevi, as a basis for tourism development. The unique cultural and religious objects in and around the village are analyzed, which make it possible to plan various tourist routes. Especially noteworthy is the "Ghvtismshoblis chalis" complex. The area "Nakaravnali" was an intermediate point on the road that passed through this valley. On the medieval roads, every thirty kilometers, there was a stop for a caravan or caravanserai, where the caravan rested. The diverse cultural heritage of the village of Kisiskhevi provides an opportunity to plan tourist tours of different types, complexity and themes (cultural, cognitive, religious, extreme, etc). The involvement in the routes of the ancient churches and monasteries will have a positive impact on the promotion of tourist resources.

Methodology for Optimal Placement of Containers in Trains in Case of Cargo Operations Along the Route

A new approach to organisation of container block trains is considered based on the principles of passenger traffic. The technology assumes container train’s traffic subject to the timetable with sale of cargo space in the train. The train is made up at the departure station and follows the established route with stops at intermediate container terminals or stations, where a container for which this station is designated as destination is removed and a new container is placed on the vacated place to be delivered to subsequent points of the route.The objective of this study is to develop a methodology for optimal placement of containers in a block train intended for en route cargo handling operations. The technique involves an iterative search for such an order of placement of packages so that containers assigned to each intermediate point are as close to each other as possible. The technique is an authors’ algorithm based on combinatorial optimisation methods.The implementation of the proposed algorithm makes it possible to reduce the excessive mileage of handlers and loaders at intermediate points and, consequently, to increase speed of cargo operations when rearranging containers, as well as to reduce operating costs of using the loading facilities of the container terminal.The proposed mathematical algorithm as compared to exhaustive search allows significantly reducing the number of iterations in search for a solution and can be implemented as software.

Sensitivity of the “intermediate point” in the mean value theorem: an approach via the Legendre-Fenchel transformation

We study the sensitivity, essentially the differentiability, of the so-called “intermediate point” c in the classical mean value theorem $ \frac{f(a)-f(b)}{b-a}={f}^{\prime}(c)$we provide the expression of its gradient ∇c(d,d), thus giving the asymptotic behavior of c(a, b) when both a and b tend to the same point d. Under appropriate mild conditions on f, this result is “universal” in the sense that it does not depend on the point d or the function f. The key tool to get at this result turns out to be the Legendre-Fenchel transformation for convex functions.

Optimal Trajectory Planning Analysis of Robot Manipulator Using PSO

For large- and small-scale industry, the major issue considered as to obtain the orientation and desire position of robot manipulators. The analysis of robotic manipulation requires two kinds of kinematic analysis namely inverse and forward kinematic analysis. This article aims to frame the inverse kinematic model of 5 DOF and 6 DOF robot manipulator. Planning of a movement flow has been designed followed by the evaluation of all the Denavit –Hartenberg (DH) parameter for the estimation of the desired orientation and position of the end effector. For the inverse Kinematics solution, conventional technique like DH notation, iteration and transformation were being utilized. The trajectory inverse kinematics minimization has been the main objective in this study and it has been achieved by Particle Swarm Optimization PSO. A quintic 5th order polynomial with joint space trajectory has been implemented in this study to find the paths for velocity and acceleration evaluation. Cartesian Trajectory is applied to the shortest path and get the transformation matrix for each intermediate point. Finally, the obstacle avoidance has been exhibited by PSO. The distance velocity, acceleration and angular displacement have been evaluated to analyse the shortest path and obstacle path avoidance.

Design of a Tandem Compressor for the Electrically-Driven Turbocharger of a Hybrid City Car

Within a broader national project aimed at the hybridization of a standard city car (the 998 cc Mitsubishi-derived gasoline engine of the Smart W451), our team tackled the problem of improving the supercharger performance and response. The originally conceived design innovation was that of eliminating the mechanical connection between the compressor and the turbine. In the course of the study, it turned out that it is also possible to modify both components to extract extra power from the engine and to use it to recharge the battery pack. This required a redesign of both compressor and turbine. First, the initial configuration was analyzed on the basis of the design data provided by the manufacturer. Then, a preliminary performance assessment of the turbocharged engine allowed us to identify three “typical” operating points that could be used to properly redesign the turbomachinery. It was decided to maintain the radial configuration for both turbine and compressor, but to redesign the latter by adding an inducer. For the turbine, only minor modifications to the nozzle guide vanes (NGV) and rotor blades shape were deemed necessary, while a more substantial modification was in order for the compressor. Fully 3-D computational fluid dynamics simulations of the rotating machines were performed to assess their performance at three operating points: the kick-in point of the original turbo (2000 rpm), the maximum power regime (5500 rpm), and an intermediate point (3500 rpm) close to the minimum specific fuel consumption for the original engine. The results presented in this paper demonstrate that the efficiency of the compressor is noticeably improved for steady operation at all three operating points, and that its choking characteristics have been improved, while its surge line has not been appreciably affected. The net energy recovery was also calculated and demonstrated interesting returns in terms of storable energy in the battery pack.

Sequential Multiple Assignment Randomized Trial (SMART) To Identify Optimal Sequences Of Telemedicine Interventions For Improving Initiation of Insulin Therapy: A Simulation Study

Background: To examine the value of a Sequential Multiple Assignment Randomized Trial (SMART) design compared to a conventional randomized control trial (RCT) for telemedicine strategies to support titration of insulin therapy for Type 2 Diabetes Mellitus (T2DM) patients new to insulin. Methods: Microsimulation models were created in R using a synthetic sample based on primary data from 63 subjects enrolled in a pilot study of a smartphone application (App), Diabetes Pal compared to a nurse-based telemedicine strategy (Nurse). For comparability, the SMART and an RCT design were constructed to allow comparison of four (embedded) adaptive interventions (AIs). Results: In the base case scenario, the SMART has similar overall mean expected HbA1c and cost per subject compared with RCT, for sample size of n = 100 over 10000 simulations. SMART has lower (better) standard deviations of the mean expected HbA1c per AI, and higher efficiency of choosing the correct AI across various sample sizes. The differences between SMART and RCT become apparent as sample size decreases. For both trial designs, the threshold value at which a subject was deemed to have been responsive at an intermediate point in the trial had an optimal choice (i.e., the sensitivity curve had a U-shape). SMART design dominates the RCT, in the overall mean HbA1c (lower value) when the threshold value is close to optimal. Conclusions: SMART is suited to evaluating the efficacy of different sequences of treatment options, in addition to the advantage of providing information on optimal treatment sequences.

Interpolation with Specified Error of a Point Series Belonging to a Monotone Curve

The paper addresses the problem of modeling a smooth contour interpolating a point series belonging to a curve containing no special points, which represents the original curve with specified accuracy. The contour is formed within the area of possible location of the parts of the interpolated curve along which the curvature values are monotonously increased or decreased. The absolute interpolation error of the point series is estimated by the width of the area of possible location of the curve. As a result of assigning each intermediate point, the location of two new sections of the curve that lie within the area of the corresponding output section is obtained. When the interpolation error becomes less than the given value, the area of location of the curve is considered to be formed, and the resulting point series is interpolated by a contour that lies within the area. The possibility to shape the contours with arcs of circles specified by characteristics is investigated.