Control of alternative pre-mRNA splicing by distributed pentameric repeats

Multiple copies of the hexamer TGCATG have been shown to regulate fibronectin pre-mRNA alternative splicing. GCATG repeats also are clustered near the regulated calcitonin-specific 3′ splice site in the rat calcitonin/CGRP gene. Specific mutagenesis of these repeats in calcitonin/CGRP pre-mRNA resulted in the loss of calcitonin-specific splicing, suggesting that the native repeats act to enhance alternative exon inclusion. Mutation of subsets of these elements implies that alternative splicing requires a minimum of two repeats, and that the combination of one intronic and one exonic repeat is necessary for optimal cell-specific splicing. However, multimerized intronic repeats inhibited calcitonin-specific splicing in both the wild-type context and in a transcript lacking endogenous repeats. These results suggest that both the number and distribution of repeats may be important features for the regulation of tissue-specific alternative splicing. Further, RNA containing a single repeat bound cell-specific protein complexes, but tissue-specific differences in protein binding were not detected by using multimerized repeats. Together, these data support a novel model for alternative splicing regulation that requires the cell-specific recognition of multiple, distributed sequence elements.

Multi-agent system for control of robots inspired on the distributed activity and hormonal regulation of humans

Robotics is an emerging field with great activity. Robotics is a field that presents several problems because it depends on a large number of disciplines, technologies, devices and tasks. Its expansion from perfectly controlled industrial environments toward open and dynamic environment presents a many new challenges. New uses are, for example, household robots or professional robots. To facilitate the low cost, rapid development of robotic systems, reusability of code, its medium and long term maintainability and robustness are required novel approaches to provide generic models and software systems who develop paradigms capable of solving these problems. For this purpose, in this paper we propose a model based on multi-agent systems inspired by the human nervous system able to transfer the control characteristics of the biological system and able to take advantage of the best properties of distributed software systems. Specifically, we model the decentralized activity and hormonal variation.

Advances in distributed parameter approach to the dynamics and control of activated sludge processes for wastewater treatment

This paper presents a review of modelling and control of biological nutrient removal (BNR)-activated sludge processes for wastewater treatment using distributed parameter models described by partial differential equations (PDE). Numerical methods for solution to the BNR-activated sludge process dynamics are reviewed and these include method of lines, global orthogonal collocation and orthogonal collocation on finite elements. Fundamental techniques and conceptual advances of the distributed parameter approach to the dynamics and control of activated sludge processes are briefly described. A critical analysis on the advantages of the distributed parameter approach over the conventional modelling strategy in this paper shows that the activated sludge process is more adequately described by the former and the method is recommended for application to the wastewater industry (c) 2006 Elsevier Ltd. All rights reserved.

Distributed control of computer communication systems

Flow control in Computer Communication systems is generally a multi-layered structure, consisting of several mechanisms operating independently at different levels. Evaluation of the performance of networks in which different flow control mechanisms act simultaneously is an important area of research, and is examined in depth in this thesis. This thesis presents the modelling of a finite resource computer communication network equipped with three levels of flow control, based on closed queueing network theory. The flow control mechanisms considered are: end-to-end control of virtual circuits, network access control of external messages at the entry nodes and the hop level control between nodes. The model is solved by a heuristic technique, based on an equivalent reduced network and the heuristic extensions to the mean value analysis algorithm. The method has significant computational advantages, and overcomes the limitations of the exact methods. It can be used to solve large network models with finite buffers and many virtual circuits. The model and its heuristic solution are validated by simulation. The interaction between the three levels of flow control are investigated. A queueing model is developed for the admission delay on virtual circuits with end-to-end control, in which messages arrive from independent Poisson sources. The selection of optimum window limit is considered. Several advanced network access schemes are postulated to improve the network performance as well as that of selected traffic streams, and numerical results are presented. A model for the dynamic control of input traffic is developed. Based on Markov decision theory, an optimal control policy is formulated. Numerical results are given and throughput-delay performance is shown to be better with dynamic control than with static control.

The choice of the model in inventory control and the cost of sophistication

This thesis is concerned with the inventory control of items that can be considered independent of one another. The decisions when to order and in what quantity, are the controllable or independent variables in cost expressions which are minimised. The four systems considered are referred to as (Q, R), (nQ,R,T), (M,T) and (M,R,T). Wiith ((Q,R) a fixed quantity Q is ordered each time the order cover (i.e. stock in hand plus on order ) equals or falls below R, the re-order level. With the other three systems reviews are made only at intervals of T. With (nQ,R,T) an order for nQ is placed if on review the inventory cover is less than or equal to R, where n, which is an integer, is chosen at the time so that the new order cover just exceeds R. In (M, T) each order increases the order cover to M. Fnally in (M, R, T) when on review, order cover does not exceed R, enough is ordered to increase it to M. The (Q, R) system is examined at several levels of complexity, so that the theoretical savings in inventory costs obtained with more exact models could be compared with the increases in computational costs. Since the exact model was preferable for the (Q,R) system only exact models were derived for theoretical systems for the other three. Several methods of optimization were tried, but most were found inappropriate for the exact models because of non-convergence. However one method did work for each of the exact models. Demand is considered continuous, and with one exception, the distribution assumed is the normal distribution truncated so that demand is never less than zero. Shortages are assumed to result in backorders, not lost sales. However, the shortage cost is a function of three items, one of which, the backorder cost, may be either a linear, quadratic or an exponential function of the length of time of a backorder, with or without period of grace. Lead times are assumed constant or gamma distributed. Lastly, the actual supply quantity is allowed to be distributed. All the sets of equations were programmed for a KDF 9 computer and the computed performances of the four inventory control procedures are compared under each assurnption.

Development of Database for Distributed Information Measurement and Control System

The purpose of this work is the development of database of the distributed information measurement and control system that implements methods of optical spectroscopy for plasma physics research and atomic collisions and provides remote access to information and hardware resources within the Intranet/Internet networks. The database is based on database management system Oracle9i. Client software was realized in Java language. The software was developed using Model View Controller architecture, which separates application data from graphical presentation components and input processing logic. The following graphical presentations were implemented: measurement of radiation spectra of beam and plasma objects, excitation function for non-elastic collisions of heavy particles and analysis of data acquired in preceding experiments. The graphical clients have the following functionality of the interaction with the database: browsing information on experiments of a certain type, searching for data with various criteria, and inserting the information about preceding experiments.

Engineering access control for distributed enterprise applications

Access control (AC) is a necessary defense against a large variety of security attacks on the resources of distributed enterprise applications. However, to be effective, AC in some application domains has to be fine-grain, support the use of application-specific factors in authorization decisions, as well as consistently and reliably enforce organization-wide authorization policies across enterprise applications. Because the existing middleware technologies do not provide a complete solution, application developers resort to embedding AC functionality in application systems. This coupling of AC functionality with application logic causes significant problems including tremendously difficult, costly and error prone development, integration, and overall ownership of application software. The way AC for application systems is engineered needs to be changed. ^ In this dissertation, we propose an architectural approach for engineering AC mechanisms to address the above problems. First, we develop a framework for implementing the role-based access control (RBAC) model using AC mechanisms provided by CORBA Security. For those application domains where the granularity of CORBA controls and the expressiveness of RBAC model suffice, our framework addresses the stated problem. ^ In the second and main part of our approach, we propose an architecture for an authorization service, RAD, to address the problem of controlling access to distributed application resources, when the granularity and support for complex policies by middleware AC mechanisms are inadequate. Applying this architecture, we developed a CORBA-based application authorization service (CAAS). Using CAAS, we studied the main properties of the architecture and showed how they can be substantiated by employing CORBA and Java technologies. Our approach enables a wide-ranging solution for controlling the resources of distributed enterprise applications. ^

Engineering access control for distributed enterprise applications

Access control (AC) is a necessary defense against a large variety of security attacks on the resources of distributed enterprise applications. However, to be effective, AC in some application domains has to be fine-grain, support the use of application-specific factors in authorization decisions, as well as consistently and reliably enforce organization-wide authorization policies across enterprise applications. Because the existing middleware technologies do not provide a complete solution, application developers resort to embedding AC functionality in application systems. This coupling of AC functionality with application logic causes significant problems including tremendously difficult, costly and error prone development, integration, and overall ownership of application software. The way AC for application systems is engineered needs to be changed. In this dissertation, we propose an architectural approach for engineering AC mechanisms to address the above problems. First, we develop a framework for implementing the role-based access control (RBAC) model using AC mechanisms provided by CORBA Security. For those application domains where the granularity of CORBA controls and the expressiveness of RBAC model suffice, our framework addresses the stated problem. In the second and main part of our approach, we propose an architecture for an authorization service, RAD, to address the problem of controlling access to distributed application resources, when the granularity and support for complex policies by middleware AC mechanisms are inadequate. Applying this architecture, we developed a CORBA-based application authorization service (CAAS). Using CAAS, we studied the main properties of the architecture and showed how they can be substantiated by employing CORBA and Java technologies. Our approach enables a wide-ranging solution for controlling the resources of distributed enterprise applications.

Changes In Motor Behavior During Pregnancy In Rats: The Basis For A Possible Animal Model Of Restless Legs Syndrome.

Pregnant women have a 2-3 fold higher probability of developing restless legs syndrome (RLS - sleep-related movement disorders) than general population. This study aims to evaluate the behavior and locomotion of rats during pregnancy in order to verify if part of these animals exhibit some RLS-like features. We used 14 female 80-day-old Wistar rats that weighed between 200 and 250 g. The rats were distributed into control (CTRL) and pregnant (PN) groups. After a baseline evaluation of their behavior and locomotor activity in an open-field environment, the PN group was inducted into pregnancy, and their behavior and locomotor activity were evaluated on days 3, 10 and 19 of pregnancy and in the post-lactation period in parallel with the CTRL group. The serum iron and transferrin levels in the CTRL and PN groups were analyzed in blood collected after euthanasia by decapitation. There were no significant differences in the total ambulation, grooming events, fecal boli or urine pools between the CTRL and PN groups. However, the PN group exhibited fewer rearing events, increased grooming time and reduced immobilization time than the CTRL group (ANOVA, p<0.05). These results suggest that pregnant rats show behavioral and locomotor alterations similar to those observed in animal models of RLS, demonstrating to be a possible animal model of this sleep disorder.

Tumor slices as a model to evaluate doxorubicin in vitro treatment and expression of trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 in canine mammary gland cancer

Background: In women with breast cancer submitted to neoadjuvant chemotherapy based in doxorubicin, tumor expression of groups of three genes (PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2) have classified them as responsive or resistant. We have investigated whether expression of these trios of genes could predict mammary carcinoma response in dogs and whether tumor slices, which maintain epithelial-mesenchymal interactions, could be used to evaluate drug response in vitro. Methods: Tumors from 38 dogs were sliced and cultured with or without doxorubicin 1 mu M for 24 h. Tumor cells were counted by two observers to establish a percentage variation in cell number, between slices. Based on these results, a reduction in cell number between treated and control samples >= 21.7%, arbitrarily classified samples, as drug responsive. Tumor expression of PRSS11, MTSS1, CLPTM1 and SMYD2, was evaluated by real time PCR. Relative expression results were then transformed to their natural logarithm values, which were spatially disposed according to the expression of trios of genes, comprising PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. Fisher linear discrimination test was used to generate a separation plane between responsive and non-responsive tumors. Results: Culture of tumor slices for 24 h was feasible. Nine samples were considered responsive and 29 non-responsive to doxorubicin, considering the pre-established cut-off value of cell number reduction = 21.7%, between doxorubicin treated and control samples. Relative gene expression was evaluated and tumor samples were then spatially distributed according to the expression of the trios of genes: PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. A separation plane was generated. However, no clear separation between responsive and non-responsive samples could be observed. Conclusion: Three-dimensional distribution of samples according to the expression of the trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 could not predict doxorubicin in vitro responsiveness. Short term culture of mammary gland cancer slices may be an interesting model to evaluate chemotherapy activity.

Macro-Fiber Composite Actuators for Flow Control of a Variable Camber Airfoil

This research employs solid-state actuators for delay of flow separation seen in airfoils at low Reynolds numbers. The flow control technique investigated here is aimed for a variable camber airfoil that employs two active surfaces and a single four-bar (box) mechanism as the internal structure. To reduce separation, periodic excitation to the flow around the leading edge of the airfoil is induced by a total of nine piezocomposite actuated clamped-free unimorph benders distributed in the spanwise direction. An electromechanical model is employed to design an actuator capable of high deformations at the desired frequency for lift improvement at post-stall angles. The optimum spanwise distribution of excitation for increasing lift coefficient is identified experimentally in the wind tunnel. A 3D (non-uniform) excitation distribution achieved higher lift enhancement in the post-stall region with lower power consumption when compared to the 2D (uniform) excitation distribution. A lift coefficient increase of 18.4% is achieved with the identified non-uniform excitation mode at the bender resonance frequency of 125 Hz, the flow velocity of 5 m/s and at the reduced frequency of 3.78. The maximum lift (Clmax) is increased 5.2% from the baseline. The total power consumption of the flow control technique is 639 mW(RMS).

A landscape-scale test of the predictive ability of a spatially explicit model for population viability analysis

1. Although population viability analysis (PVA) is widely employed, forecasts from PVA models are rarely tested. This study in a fragmented forest in southern Australia contrasted field data on patch occupancy and abundance for the arboreal marsupial greater glider Petauroides volans with predictions from a generic spatially explicit PVA model. This work represents one of the first landscape-scale tests of its type. 2. Initially we contrasted field data from a set of eucalypt forest patches totalling 437 ha with a naive null model in which forecasts of patch occupancy were made, assuming no fragmentation effects and based simply on remnant area and measured densities derived from nearby unfragmented forest. The naive null model predicted an average total of approximately 170 greater gliders, considerably greater than the true count (n = 81). 3. Congruence was examined between field data and predictions from PVA under several metapopulation modelling scenarios. The metapopulation models performed better than the naive null model. Logistic regression showed highly significant positive relationships between predicted and actual patch occupancy for the four scenarios (P = 0.001-0.006). When the model-derived probability of patch occupancy was high (0.50-0.75, 0.75-1.00), there was greater congruence between actual patch occupancy and the predicted probability of occupancy. 4. For many patches, probability distribution functions indicated that model predictions for animal abundance in a given patch were not outside those expected by chance. However, for some patches the model either substantially over-predicted or under-predicted actual abundance. Some important processes, such as inter-patch dispersal, that influence the distribution and abundance of the greater glider may not have been adequately modelled. 5. Additional landscape-scale tests of PVA models, on a wider range of species, are required to assess further predictions made using these tools. This will help determine those taxa for which predictions are and are not accurate and give insights for improving models for applied conservation management.

Histopathology, humoral and cellular immune response in the murine model of Leishmania (Viannia) shawi

Leishmania (Viannia) shawl was recently characterized and few studies concerning modifications in cellular and humoral immune responses in experimental leishmaniasis have been conducted. In this work, immunopathological changes induced by L. shawl in chronically infected BALB/c mice were investigated. Infected BALB/c mice developed increased lesion size associated with strong inflammatory infiltrate diffusely distributed in the dermis, with highly infected macrophages. The humoral immune response was predominantly directed toward the IgG1 isotype. The functional activity of CD4(+) and CD8(+) T cells showed significantly increased TNF-alpha mRNA levels associated with reduced IFN-gamma expression by CD4(+) T cells and the double negative (dn) CD4CD8 cell subset. High IL-4 levels expressed by CD8(+) T cells and dnCD4CD8 and TGF-beta by CD4(+) and CD8(+) T cells were detected, while IL-10 was highly expressed by all three cell subpopulations. Taken together, these results show an evident imbalance between TNF-alpha and IFN-gamma that is unfavorable to amastigote replication control. Furthermore, L. shawi seems to regulate different cell populations to express deactivating cytokines to avoid its own destruction. This study indicates BALB/c mice as a potentially good experimental model for further studies on American cutaneous leishmaniosis caused by L. shawi. (C) 2010 Elsevier Ireland Ltd. All rights reserved.