Hsp110 chaperones control client fate determination in the hsp70-Hsp90 chaperone system.

Heat shock protein 70 (Hsp70) plays a central role in protein homeostasis and quality control in conjunction with other chaperone machines, including Hsp90. The Hsp110 chaperone Sse1 promotes Hsp90 activity in yeast, and functions as a nucleotide exchange factor (NEF) for cytosolic Hsp70, but the precise roles Sse1 plays in client maturation through the Hsp70-Hsp90 chaperone system are not fully understood. We find that upon pharmacological inhibition of Hsp90, a model protein kinase, Ste11DeltaN, is rapidly degraded, whereas heterologously expressed glucocorticoid receptor (GR) remains stable. Hsp70 binding and nucleotide exchange by Sse1 was required for GR maturation and signaling through endogenous Ste11, as well as to promote Ste11DeltaN degradation. Overexpression of another functional NEF partially compensated for loss of Sse1, whereas the paralog Sse2 fully restored GR maturation and Ste11DeltaN degradation. Sse1 was required for ubiquitinylation of Ste11DeltaN upon Hsp90 inhibition, providing a mechanistic explanation for its role in substrate degradation. Sse1/2 copurified with Hsp70 and other proteins comprising the "early-stage" Hsp90 complex, and was absent from "late-stage" Hsp90 complexes characterized by the presence of Sba1/p23. These findings support a model in which Hsp110 chaperones contribute significantly to the decision made by Hsp70 to fold or degrade a client protein.

Genes to blood pressure: The effects of variation in genes of the renin-angiotensin system on the hormonal and renal control of blood pressure

Objective. Essential hypertension affects 25% of the US adult population and is a leading contributor to morbidity and mortality. Because BP is a multifactorial phenotype that resists simple genetic analysis, intermediate phenotypes within the complex network of BP regulatory systems may be more accessible to genetic dissection. The Renin-Angiotensin System (RAS) is known to influence intermediate and long-term blood pressure regulation through alterations in vascular tone and renal sodium and fluid resorption. This dissertation examines associations between renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1) gene variation and interindividual differences in plasma hormone levels, renal hemodynamics, and BP homeostasis.^ Methods. A total of 150 unrelated men and 150 unrelated women, between 20.0 and 49.9 years of age and free of acute or chronic illness except for a history of hypertension (11 men and 7 women, all off medications), were studied after one week on a controlled sodium diet. RAS plasma hormone levels, renal hemodynamics and BP were determined prior to and during angiotensin II (Ang II) infusion. Individuals were genotyped by PCR for a variable number tandem repeat (VNTR) polymorphism in REN, and for the following restriction fragment length polymorphisms (RFLP): AGT M235T, ACE I/D, and AT1 A1166C. Associations between clinical measurements and allelic variation were examined using multiple linear regression statistical models.^ Results. Women homozygous for the AT1 1166C allele demonstrated higher intracellular levels of sodium (p = 0.044). Men homozygous for the AGT T235 allele demonstrated a blunted decrement in renal plasma flow in response to Ang II infusion (p = 0.0002). There were no significant associations between RAS gene variation and interindividual variation in RAS plasma hormone levels or BP.^ Conclusions. Rather than identifying new BP controlling genes or alleles, the study paradigm employed in this thesis (i.e., measured genes, controlled environments and interventions) may provide mechanistic insight into how candidate genes affect BP homeostasis. ^

Periacetabular osteotomy through the pararectus approach: technical feasibility and control of fragment mobility by a validated surgical navigation system in a cadaver experiment

PURPOSE The pararectus approach has been validated for managing acetabular fractures. We hypothesised it might be an alternative approach for performing periacetabular osteotomy (PAO). METHODS Using four cadaver specimens, we randomly performed PAO through either the pararectus or a modified Smith-Petersen (SP) approach. We assessed technical feasibility and safety. Furthermore, we controlled fragment mobility using a surgical navigation system and compared mobility between approaches. The navigation system's accuracy was tested by cross-examination with validated preoperative planning software. RESULTS The pararectus approach is technically feasible, allowing for adequate exposure, safe osteotomies and excellent control of structures at risk. Fragment mobility is equal to that achieved through the SP approach. Validation of these measurements yielded a mean difference of less <1 mm without statistical significance. CONCLUSION Experimental data suggests the pararectus approach might be an alternative approach for performing PAO. Clinical validation is necessary to confirm these promising preliminary results.

Food safety control system of Chinese eel exports and its challenges

This paper analyzes factors associated with the rejection of products at ports of importer countries and remedial actions taken by producers in China. As an example, it uses one of the most competitive agro-food products of China: live and processed eels. This paper provides an overview of eel production and trade trends in China. In addition, it identifies the causes of port rejection of Chinese eel products as veterinary drug residues by examining the detailed case studies of export firms and the countermeasures taken by the government and firms.

Formal verification of safety protocol in train control system

In order to satisfy the safety-critical requirements, the train control system (TCS) often employs a layered safety communication protocol to provide reliable services. However, both description and verification of the safety protocols may be formidable due to the system complexity. In this paper, interface automata (IA) are used to describe the safety service interface behaviors of safety communication protocol. A formal verification method is proposed to describe the safety communication protocols using IA and translate IA model into PROMELA model so that the protocols can be verified by the model checker SPIN. A case study of using this method to describe and verify a safety communication protocol is included. The verification results illustrate that the proposed method is effective to describe the safety protocols and verify deadlocks, livelocks and several mandatory consistency properties. A prototype of safety protocols is also developed based on the presented formally verifying method.

Artificial cognitive control system based on the shared circuits model of sociocognitive capacities. A first approach

sharedcircuitmodels is presented in this work. The sharedcircuitsmodelapproach of sociocognitivecapacities recently proposed by Hurley in The sharedcircuitsmodel (SCM): how control, mirroring, and simulation can enable imitation, deliberation, and mindreading. Behavioral and Brain Sciences 31(1) (2008) 1–22 is enriched and improved in this work. A five-layer computational architecture for designing artificialcognitivecontrolsystems is proposed on the basis of a modified sharedcircuitsmodel for emulating sociocognitive experiences such as imitation, deliberation, and mindreading. In order to show the enormous potential of this approach, a simplified implementation is applied to a case study. An artificialcognitivecontrolsystem is applied for controlling force in a manufacturing process that demonstrates the suitability of the suggested approach

Adaptive control system based on lineal control theory for the path-following problem of a car-like mobile robot

The objective of this paper is to design a path following control system for a car-like mobile robot using classical linear control techniques, so that it adapts on-line to varying conditions during the trajectory following task. The main advantages of the proposed control structure is that well known linear control theory can be applied in calculating the PID controllers to full control requirements, while at the same time it is exible to be applied in non-linear changing conditions of the path following task. For this purpose the Frenet frame kinematic model of the robot is linearised at a varying working point that is calculated as a function of the actual velocity, the path curvature and kinematic parameters of the robot, yielding a transfer function that varies during the trajectory. The proposed controller is formed by a combination of an adaptive PID and a feed-forward controller, which varies accordingly with the working conditions and compensates the non-linearity of the system. The good features and exibility of the proposed control structure have been demonstrated through realistic simulations that include both kinematics and dynamics of the car-like robot.

ClimApp: A Novel Approach of an Intelligent HVAC Control System

This paper describes a novel deployment of an intelligent user-centered HVAC (Heating, Ventilating and Air Conditioner) control system. The main objective of this system is to optimize user comfort and to reduce energy consumption in office buildings. Existing commercial HVAC control systems work in a fixed and predetermined way. The novelty of the proposed system is that it adapts dynamically to the user and to the building environment. For this purpose the system architecture has been designed under the paradigm of Ambient Intelligence. A prototype of the system proposed has been tested in a real-world environment.

Variable impedance LED matrix control system for lamps in PV applications

The interest in LED lighting has been growing recently due to the high efficacy, lifelime and ruggedness that this technology offers. However the key element to guarantee those parameters with these new electronic devices is to keep under control the working temperature of the semiconductor crystal. This paper propases a LED lamp design that fulfils the requ irements of a PV lighting systems, whose main quality criteria is reliability. It uses directly as a power supply a non·stabilized constant voltage source, as batteries. An electronic control architecture is used to regulate the current applied to the LEO matri)( according to their temperature and the voltage output value of the batteries with two pulse modulation signals (PWM) signals. The first one connects and disconnects the LEOs to the power supply and the second one connects and disconnects several emitters to the electric circuit changing its overall impedance. A prototype of the LEO lamp has been implemented and tested at different temperaturas and battery voltages.

Dynamic control of a reconfigurable stair-climbing mobility system

Electric-powered wheelchairs improve the mobility of people with physical disabilities, but the problem to deal with certain architectural barriers has not been resolved satisfactorily. In order to solve this problem, a stair-climbing mobility system (SCMS) was developed. This paper presents a practical dynamic control system that allows the SCMS to exhibit a successful climbing process when faced with typical architectural barriers such as curbs, ramps, or staircases. The implemented control system depicts high simplicity, computational efficiency, and the possibility of an easy implementation in a microprocessor-/microcontroller-based system. Finally, experiments are included to support theoretical results.

Responses to increasing exercise upon reaching the anaerobic threshold, and their control by the central nervous system

Sistema nervioso y ejercicio

3-Phase Rectifier System with very demanding dynamic load: Architecture analysis and control strategy

A distributed power architecture for aerospace application with very restrictive specifications is analyzed. Parameters as volume, weight and losses are analyzed for the considered power architectures. In order to protect the 3 phase generator against high load steps, an intermediate bus (based in a high capacitance) to provide energy to the loads during the high load steps is included. Prototypes of the selected architecture for the rectifier and EMI filter are built and the energy control is validated.

On-line learning of a fuzzy controller for a precise vehicle cruise control system

Usually, vehicle applications require the use of artificial intelligent techniques to implement control methods, due to noise provided by sensors or the impossibility of full knowledge about dynamics of the vehicle (engine state, wheel pressure or occupiers weight). This work presents a method to on-line evolve a fuzzy controller for commanding vehicles? pedals at low speeds; in this scenario, the slightest alteration in the vehicle or road conditions can vary controller?s behavior in a non predictable way. The proposal adapts singletons positions in real time, and trapezoids used to codify the input variables are modified according with historical data. Experimentation in both simulated and real vehicles are provided to show how fast and precise the method is, even compared with a human driver or using different vehicles.