The essential role of toll like receptor-4 in the control of Aggregatibacter actinomycetemcomitans infection in mice

Objective: Aggregatibacter actinomycetemcomitans is an oral Gram-negative bacterium that contributes to periodontitis progression. Isolated antigens from A. actinomycetemcomitans could be activating innate immune cells through Toll-like receptors (TLRs). In this study, we evaluated the role of TLR4 in the control of A. actinomycetemcomitans infection. Material and Methods: We examined the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR4(-/-) mice. The production of cytokines was evaluated by ELISA. The bacterial load was determined by counting the number of colony-forming units per gram of tissue. Results: The results showed that TLR4-deficient mice developed less severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly lower bone loss and inflammatory cell migration to periodontal tissues. However, the absence of TLR4 facilitated the A. actinomycetemcomitans dissemination. Myeloperoxidase activity was diminished in the periodontal tissue of TLR4(-/-) mice. We observed a significant reduction in the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta in the periodontal tissue of TLR4(-/-) mice. Conclusion: The results of this study highlighted the role of TLR4 in controlling A. actinomycetemcomitans infection.

Postural control of the trunk in response to lateral support surface translations during trunk movement and loading

The postural response to translation of the support surface may be influenced by the performance of an ongoing voluntary task. This study was designed to test this proposal by applying lateral perturbations while subjects handled a load in the frontal plane. Measurements were made of medio-lateral displacement of the centre of pressure, angular displacement of the trunk and thigh in the frontal plane and intra-abdominal pressure. Subjects were translated randomly to the left and right in a variety of conditions that involved standing either quietly or with a 5 kg load in their left hand, which they were required either to hold statically or to lift or lower. The results indicate that when the perturbation occurred towards the loaded left side the subjects were able to return their centre of pressure, trunk and thigh rapidly and accurately to the initial position. However, when the perturbation occurred towards the right (away from the load) this correction was delayed and associated with multiple changes in direction of movement, suggesting decreased efficiency of the postural response. This reduced efficiency can be explained by a conflict between the motor commands for the ongoing voluntary task and the postural response, and/or by the mechanical effect of the asymmetrical addition of load to the trunk.

Control of nitrate recirculation flow in predenitrification systems

The control of the nitrate recirculation flow in a predenitrification system is addressed. An elementary mass balance analysis on the utilisation efficiency of the influent biodegradable COD (bCOD) for nitrate removal indicates that the control problem can be broken down into two parts: maintaining the anoxic zone anoxic (i.e. nitrate is present throughout the anoxic zone) and maximising the usage of influent soluble bCOD for denitrification. Simulation studies using the Simulation Benchmark developed in the European COST program show that both objectives can be achieved by maintaining the nitrate concentration at the outlet of the anoxic zone at around 2 mgN/L. This setpoint appears to be robust towards variations in the influent characteristics and sludge kinetics.

A role for pectin in the control of cell expansion

Uptake of nutrients and water depends on the growth of roots through elongation of individual cells near the. root tip. Many of the numerous components of Type I primary cell walls, those of dicotyledons and monocotyledons other than grasses (Poaceae), have been determined, and many hypotheses have been proposed for the control of cell expansion. This important aspect of plant growth still needs elucidation, however. A model is proposed in which pectin, which occurs as a calcium (Ca) pectate gel between the load-bearing cellulose microfibrils and xyloglucan (XG) chains, controls the rate at which cells expand. It is considered that the increasing tension generated by the expanding cell is transmitted to interlocked XG chains and cellulose microfibrils. The resulting deformation of the embedded Ca pectate gel elicits the excretion of protons from the cytoplasm, possibly via compounds such as cell wall-associated kinases, that weakens the Ca pectate gel, permitting slippage of XG molecules through the action of expansin. Further slippage is prevented by deformation of the pectic gel, proton diffusion, and the transfer of residual tension to adjacent XG chains. Evidence for this model is based on the effects of pH, Ca, and aluminum (Al) on root elongation and on the reactions of these cations with Ca pectate. This model allows for genetic selection of plants and adaptation of individual plants to root environmental conditions.

Supervisory control of a variable speed wind turbine with doubly fed induction generator

This paper is on an onshore variable speed wind turbine with doubly fed induction generator and under supervisory control. The control architecture is equipped with an event-based supervisor for the supervision level and fuzzy proportional integral or discrete adaptive linear quadratic as proposed controllers for the execution level. The supervisory control assesses the operational state of the variable speed wind turbine and sends the state to the execution level. Controllers operation are in the full load region to extract energy at full power from the wind while ensuring safety conditions required to inject the energy into the electric grid. A comparison between the simulations of the proposed controllers with the inclusion of the supervisory control on the variable speed wind turbine benchmark model is presented to assess advantages of these controls. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

FPGA field oriented control of an axial flux motor-in-wheel

This paper presents the design and the prototype implementation of a three-phase power inverter developed to drive a motor-in-wheel. The control system is implemented in a FPGA (Field Programmable Gate Array) device. The paper describes the Field Oriented Control (FOC) algorithm and the Space Vector Modulation (SVM) technique that were implemented. The control platform uses a Spartan-3E FPGA board, programmed with Verilog language. Simulation and experimental results are presented to validate the developed system operation under different load conditions. Finally are presented conclusions based on the experimental results.

Field oriented control of an axial flux permanent magnet synchronous motor for traction solutions

Electric Vehicles (EVs) are increasingly used nowadays, and different powertrain solutions can be adopted. This paper describes the control system of an axial flux Permanent Magnet Synchronous Motor (PMSM) for EVs powertrain. It is described the implemented Field Oriented Control (FOC) algorithm and the Space Vector Modulation (SVM) technique. Also, the mathematical model of the PMSM is presented. Both, simulation and experimental, results with different types of mechanical load are presented. The experimental results were obtained using a laboratory test bench. The obtained results are discussed.

Prevalence and control of Babesiosis in the Americas

This review presents up-to-date information on the distribution and control measures of babesiosis in Latin America. Bovine babesiosis caused by Babesia bovis and B. bigemia will be emphasized. The disease is endemic is most countries and poses a serious economic burdenon livestock production in the region (U.S.$1365 million/year, FAO, 1989). Of the estimated 250 million cattle in Central and South America, approximately 175 million (70%) are in tick-infested regions. Humid, tropical and subtropical areas favor development of the main vector, the one-host tick Boophilus microplus. In many regions bovine babesiosis is enzootically stable as consequence of a balanced host-parasite relationship. However, Latin America offers a wide range of epidemiologica conditions that are influenced by variations from tropical to cool climates and by susceptible purebred cattle that are regularly imported to upgrade local stocks. The control measures employed in most countries for babesiosis esentially rely on chemotherapy, use of acaricides for B. microplus, and to a lesser degree, on immunization methods. In general, these measures are expensive, time consuming, and in many cases, provide limited success. Finally, the zoonotic potential ob babesiosis will be addressd, with special emphasis on the situation in the United States. Even though bovine babesiosis has long been eradicated from the U.S.A., human babesiosis in endemic in the northeastern region of the country.

Experiences with the control of schistosomiasis mansoni in two foci in Central Africa

Experiences with population-based chemotherapy and other methods for the control of schistosomiasis mansoni in two subsaharan foci are described. In the forest area of Maniema (Zaire), intense transmission of Schistosoma mansoni, high prevalences and intensities of infection, and important morbidity have been documental. Taking into account the limited financial means and the poor logistic conditions, the control strategy has been based mainly on targeted chemotherapy of heavily infected people (>600 epg). After ten years of intervention, prevalences and intensities have hardly been affected, but the initial severe hepatosplenic morbidity has almost disappeared. In Burundi, a national research and control programme has been initiated in 1982. Prevalences, intensities and morbidity were moderate, transmission was focal and erratic in time and space. A more structural control strategy was developed, based on screening and selective therapy, health education, sanitation and domestic water supply. Prevalences and intensities have been considerably reduced, though the results show focal and unpredicatable variations. Transmission and reinfection were not signifcantly affected by chemotherapy alone, and eventual outcome of repeated selective treatment appears to be limited by the sensitivity of the screening method. Intestinal morbidity was strongly reduced by community-based selective treatment, but hepatosplenic enlargement was hardly affected; this is possibly due to the confounding impact of increasing malaria morbidity. The experiences show the importance of local structures and conditions for the development of an adapted control strategy. It is further concluded that population-based chemotherapy is a highly valid tool for the rapid control of morbidity, but should in most operational conditions not be considered as a tool for transmission control. Integration of planning, execution and surveillance in regular health services...

Evolutionary Control of Infectious Disease: Prospects for Vectorborne and Waterborne Pathogens

Evolutionary theory may contribute to practical solutions for control of disease by identifying interventions that may cause pathogens to evolve to reduced virulence. Theory predicts, for example, that pathogens transmitted by water or arthropod vectors should evolve to relatively high levels of virulence because such pathogens can gain the evolutionary benefits of relatively high levels of host exploitation while paying little price from host illness. The entrance of Vibrio cholerae into South America in 1991 has generated a natural experiment that allows testing of this idea by determining whether geographic and temporal variations in toxigenicity correspond to variation in the potential for waterborne transmission. Preliminary studies show such correspondences: toxigenicity is negatively associated with access to uncontaminated water in Brazil; and in Chile, where the potential for waterborne transmission is particularly low, toxigenicity of strains declined between 1991 and 1998. In theory vector-proofing of houses should be similarly associated with benignity of vectorborne pathogens, such as the agents of dengue, malaria, and Chagas' disease. These preliminary studies draw attention to the need for definitive prospective experiments to determine whether interventions such as provisioning of uncontaminated water and vector-proofing of houses cause evolutionary reductions in virulence

Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication.

HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-gamma and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCV-derived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-gamma and single IFN-gamma-producing CD4+ and dual IL-2/IFN-gamma and single IFN-gamma-producing CD8+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV co-infected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-gamma-producing CD8+ T cells. In addition, HCV-specific proliferation of CD4+ and CD8+ T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, "only effector" T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation.

Control of pancreatic β-cell mass and function by gluco-incretin hormones : identification of novel regulatory mechanisms for the treatment of diabetes

Summary : Control of pancreatic ß-cell mass and function by gluco-incretin hormones: Identification of novel regulatory mechanisms for the treatment of diabetes The ß-cells of islets of Langerhans secrete insulin to reduce hyperglycemia. The number of pancreatic islet ß-cells and their capacity to secrete insulin is modulated in normal physiological conditions to respond to the metabolic demand of the organism. A failure of the endocrine pancreas to maintain an adequate insulin secretory capacity due to a reduced ß-cell number and function underlies the pathogenesis of both type 1 and type 2 diabetes. The molecular mechanisms controlling the glucose competence of mature ß-cells, i.e., the magnitude of their insulin secretion response to glucose, ß-cell replication, their differentiation from precursor cells and protection against apoptosis are poorly understood. To investigate these mechanisms, we studied the effects on ß-cells of the gluco-incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) which are secreted by intestinal endocrine cells after food intake. Besides acutely potentiating glucose-stimulated insulin secretion, these hormones induce ß-cell differentiation from precursor cells, stimulate mature ß-cell replication, and protect them against apoptosis. Therefore, understanding the molecular basis for gluco-incretin action may lead to the uncovering of novel ß-cell regulatory events with potential application for the treatment or prevention of diabetes. Islets from mice with inactivation of both GIP and GLP-1 receptor genes (dK0) present a defect in glucose-induced insulin secretion and are more sensitive than control islets to cytokine-induced apoptosis. To search for regulatory genes, that may control both glucose competence and protection against apoptosis, we performed comparative transcriptomic analysis of islets from control and dK0 mice. We found a strong down-regulation of the IGF1 Rexpression in dK0 islets. We demonstrated in both a mouse insulin-secreting cell line and primary islets, that GLP-1 stimulated IGF-1R expression and signaling. Importantly, GLP-1induced IGF-1R-dependent Akt phosphorylation required active secretion, indicating the presence of an autocrine activation mechanism. We further showed that activation of IGF-1R signaling was dependent on the secretion of IGF-2 and IGF-2 expression was regulated by nutrients. Finally, we demonstrated that the IGF-Z/IGF-1R autocrine loop was required for GLP-1 i) to protect ß-cells against cytokine-induced apoptosis, ii) to enhance their glucose competence and iii) to increase ß-cell proliferation. Résumé : Contrôle de la masse des cellules ß pancréatiques et de leur fonction par les hormones glucoincrétines: Identification de nouveaux mécanismes régulateurs pour le traitement du diabète Les cellules ß des îlots de Langerhans sécrètent l'insuline pour diminuer l'hyperglycémie. Le nombre de cellules ß et leur capacité à sécréter l'insuline sont modulés dans les conditions physiologiques normales pour répondre à la demande métabolique de l'organisme. Un échec du pancréas endocrine à maintenir sa capacité sécrétoire d'insuline dû à une diminution du nombre et de la fonction des cellules ß conduit au diabète de type 1 et de type 2. Les mécanismes moléculaires contrôlant la compétence au glucose des cellules ß matures, tels que, l'augmentation de la sécrétion d'insuline en réponse au glucose, la réplication des cellules ß, leur différentiation à partir de cellules précurseurs et la protection contre l'apoptose sont encore peu connus. Afin d'examiner ces mécanismes, nous avons étudié les effets sur les cellules ß des hormones gluco-incrétines, glucose-dépendent insulinotropic polypeptide (G1P) et glucagon-like peptide-1 (GLP-1) qui sont sécrétées par les cellules endocrines de l'intestin après la prise alimentaire. En plus de potentialiser la sécrétion d'insuline induite par le glucose, ces hormones induisent la différentiation de cellules ß à partir de cellules précurseurs, stimulent leur prolifération et les protègent contre l'apoptose. Par conséquent, comprendre les mécanismes d'action des gluco-incrétines permettrait de découvrir de nouveaux processus régulant les cellules ß avec d'éventuelles applications dans le traitement ou la prévention du diabète. Les îlots de souris ayant une double inactivation des gènes pour les récepteurs du GIP et du GLP-1 (dK0) présentent un défaut de sécrétion d'insuline stimulée par le glucose et une sensibilité accrue à l'apoptose induite par les cytokines. Afin de déterminer les gènes régulés, qui pourraient contrôler à la fois la compétence au glucose et la protection contre l'apoptose, nous avons effectué une analyse comparative transcriptomique sur des îlots de souris contrôles et dKO. Nous avons constaté une forte diminution de l'expression d'IGF-1R dans les îlots dKO. Nous avons démontré, à la fois dans une lignée cellulaire murine sécrétant l'insuline et dans îlots primaires, que le GLP-1 stimulait l'expression d'IGF-1R et sa voie de signalisation. Par ailleurs, la phosphorylation d'Akt dépendante d'IGF1-R induite parle GLP-1 nécessite une sécrétion active, indiquant la présence d'un mécanisme d'activation autocrine. Nous avons ensuite montré que l'activation de la voie de signalisation d'IGF-1R était dépendante de la sécrétion d'IGF-2, dont l'expression est régulée par les nutriments. Finalement, nous avons démontré que la boucle autocrine IGF-2/IGF-1R est nécessaire pour le GLP-1 i) pour protéger les cellules ß contre l'apoptose induite par les cytokines, ii) pour améliorer la compétence au glucose et iii) pour augmenter la prolifération des cellules ß. Résumé tout public : Contrôle de la masse des cellules ß pancréatiques et de leur fonction par les hormones gluco-incrétines: Identification de nouveaux mécanismes régulateurs pour le traitement du diabète Chez les mammifères, la concentration de glucose sanguine (glycémie) est régulée et maintenue à une valeur relativement constante d'environ 5 mM. Cette régulation est principalement contrôlée par 2 hormones produites par les îlots pancréatiques de Langerhans: l'insuline sécrétée par les cellules ß et le glucagon sécrété par les cellules a. A la suite d'un repas, l'augmentation de la glycémie entraîne la sécrétion d'insuline ce qui permet le stockage du glucose dans le foie, les muscles et le tissu adipeux afin de diminuer le taux de glucose circulant. Lors d'un jeûne, la diminution de la glycémie permet la sécrétion de glucagon favorisant alors la production de glucose par le foie, normalisant ainsi la glycémie. Le nombre de cellules ß et leur capacité sécrétoire s'adaptent aux variations de la demande métabolique pour assurer une normoglycémie. Une destruction complète ou partielle des cellules ß conduit respectivement au diabète de type 1 et de type 2. Bien que l'augmentation de la glycémie soit le facteur stimulant de la sécrétion d'insuline, des hormones gluco-incrétines, principalement le GLP-1 (glucagon-like peptide-1) et le GIP (glucose-dependent insulinotropic polypeptide) sont libérées par l'intestin en réponse aux nutriments (glucose, acides gras) et agissent au niveau des cellules ß, potentialisant la sécrétion d'insuline induite par le glucose, stimulant leur prolifération, induisant la différentiation de cellules précurseurs en cellules ß matures et les protègent contre la mort cellulaire (apoptose). Afin d'étudier plus en détail ces mécanismes, nous avons généré des souris déficientes pour les récepteurs du GIP et du GLP-l. Les îlots pancréatiques de ces souris présentent un défaut de sécrétion d'insuline stimulée par le glucose et une sensibilité accrue à l'apoptose par rapport aux îlots de souris contrôles. Nous avons donc cherché les gènes régulés pas ces hormones contrôlant la sécrétion d'insuline et la protection contre l'apoptose. Nous avons constaté une forte diminution de l'expression du récepteur à l'IGF-1 (IGF-1R) dans les îlots de souris déficientes pour les récepteurs des gluco-incrétines. Nous avons démontré dans un model de cellules ß en culture et d'îlots que le GLP-1 augmentait l'expression d'IGF-1R et la sécrétion de son ligand (IGF-2) permettant l'activation de la voie de signalisation. Finalement, nous avons montré que l'activation de la boucle IGF-2/IGF-1R induite par le GLP-1 était nécessaire pour la protection contre l'apoptose, l'augmentation de la sécrétion et la prolifération des cellules ß.

Influence of anatomical variations on lumbar foraminal stenosis pathogenesis.

INTRODUCTION: Symptomatic foraminal stenosis has been observed in patients with degenerative disc disease, scoliosis, asymmetrical disc degeneration and spondylolisthesis. Nevertheless not all patients with the above pathologies will develop symptomatic foraminal stenosis. We hypothesised that symptomatic patients have anatomical predisposition to foraminal stenosis, namely a larger pedicle height (PH) to vertebral body height (VH) ratio, leaving less room below the pedicle for the exiting nerve root compared to asymptomatic patients. PATIENT SAMPLE: 66 Patients were divided in two groups. The surgical group consisted of 37 patients (average age of 61 years) who presented with severe radicular symptoms resisting to conservative measures and requiring decompression and transforaminal lumbar interbody fusion (TLIF). The control group consisted of 29 patients (average age of 51 years) presenting with low back pain (LBP) but with no radicular symptoms and who were treated conservatively. METHODS: We measured VH at the level of the posterior wall as well as PH on parasagittal images (CT or MRI) on all lumbar levels (L1 to L5). Statistical analysis was performed using Student's t test. RESULTS: No difference in PH was found between the two groups for L1 to L4 levels. By contrast, there was a highly statistically significant difference in VH between the two groups from L1 to L4 level. In the surgical group, the VH was smaller (p < 0.001). CONCLUSIONS: Symptomatic patients with foraminal stenosis have smaller VH leading to lesser space beneath the pedicle and putting the exiting nerve root at risk in cases of spondylolisthesis or disc degeneration.

The achievable region approach to the optimal control of stochastic systems

The achievable region approach seeks solutions to stochastic optimisation problems by: (i) characterising the space of all possible performances(the achievable region) of the system of interest, and (ii) optimisingthe overall system-wide performance objective over this space. This isradically different from conventional formulations based on dynamicprogramming. The approach is explained with reference to a simpletwo-class queueing system. Powerful new methodologies due to the authorsand co-workers are deployed to analyse a general multiclass queueingsystem with parallel servers and then to develop an approach to optimalload distribution across a network of interconnected stations. Finally,the approach is used for the first time to analyse a class of intensitycontrol problems.

Neural control of vascular reactions: impact of emotion and attention.

This study investigated the neural regions involved in blood pressure reactions to negative stimuli and their possible modulation by attention. Twenty-four healthy human subjects (11 females; age = 24.75 ± 2.49 years) participated in an affective perceptual load task that manipulated attention to negative/neutral distractor pictures. fMRI data were collected simultaneously with continuous recording of peripheral arterial blood pressure. A parametric modulation analysis examined the impact of attention and emotion on the relation between neural activation and blood pressure reactivity during the task. When attention was available for processing the distractor pictures, negative pictures resulted in behavioral interference, neural activation in brain regions previously related to emotion, a transient decrease of blood pressure, and a positive correlation between blood pressure response and activation in a network including prefrontal and parietal regions, the amygdala, caudate, and mid-brain. These effects were modulated by attention; behavioral and neural responses to highly negative distractor pictures (compared with neutral pictures) were smaller or diminished, as was the negative blood pressure response when the central task involved high perceptual load. Furthermore, comparing high and low load revealed enhanced activation in frontoparietal regions implicated in attention control. Our results fit theories emphasizing the role of attention in the control of behavioral and neural reactions to irrelevant emotional distracting information. Our findings furthermore extend the function of attention to the control of autonomous reactions associated with negative emotions by showing altered blood pressure reactions to emotional stimuli, the latter being of potential clinical relevance.