Gradual Decline in Malaria-Specific Memory T Cell Responses Leads to Failure to Maintain Long-Term Protective Immunity to Plasmodium chabaudi AS Despite Persistence of B Cell Memory and Circulating Antibody

The mechanisms responsible for the generation and maintenance of immunological memory to Plasmodium are poorly understood and the reasons why protective immunity in humans is so difficult to achieve and rapidly lost remain a matter for debate. A possible explanation for the difficulty in building up an efficient immune response against this parasite is the massive T cell apoptosis resulting from exposure to high-dose parasite Ag. To determine the immunological mechanisms required for long-term protection against P. chabaudi malaria and the consequences of high and low acute phase parasite loads for acquisition of protective immunity, we performed a detailed analysis of T and B cell compartments over a period of 200 days following untreated and drug-treated infections in female C57BL/6 mice. By comparing several immunological parameters with the capacity to control a secondary parasite challenge, we concluded that loss of full protective immunity is not determined by acute phase parasite load nor by serum levels of specific IgG2a and IgG1. Abs, but appears to be a consequence of the progressive decline in memory T cell response to parasites, which occurs similarly in untreated and drug-treated mice with time after infection. Furthermore, by analyzing adoptive transfer experiments, we confirmed the major role of CD4(+) T cells for guaranteeing long-term full protection against P. chabaudi malaria. The Journal of Immunology, 2008, 181: 8344-8355.

iNOS-derived Nitric Oxide Modulates Infection-stimulated Bone Loss

Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) plays an important role in host defense, as well as in inflammation-induced tissue lesions. Here we evaluated the role of NO in bone loss in bacterial infection-induced apical periodontitis by using iNOS-deficient mice (iNOS(-/-)). The iNOS(-/-) mice developed greater inflammatory cell recruitment and osteolytic lesions than WT mice. Moreover, tartrate-resistant acid-phosphatase-positive (TRAP(+)) osteoclasts were significantly more numerous in iNOS-/- mice. Furthermore, the increased bone resorption in iNOS(-/-) mice also correlated with the increased expression of receptor activator NF-kappaB (RANK), stromal-cell-derived factor-1 alpha (SDF-1 alpha/CXCL12), and reduced expression of osteoprotegerin (OPG). These results show that NO deficiency was associated with an imbalance of bone-resorption-modulating factors, leading to severe infection-stimulated bone loss.

CCR5 Mediates Pro-osteoclastic and Osteoclastogenic Leukocyte Chemoattraction

Periodontal disease (PD) progression involves the selective leukocyte infiltration into periodontium, supposedly mediated by the chemokine/chemokine receptor system. In this study, we investigated the role of chemokine receptor CCR5 in the immunoregulation of experimental PD in C57BL/6 (WT) and CCR5KO mice. Aggregatibacter actinomycetem comitans infection triggered the chemoattraction of distinct CCR5+ leukocyte subpopulations (determined by flow cytometry): CCR5+F4/80+ leukocytes, which co-express CD14, CCR2, TNF-alpha, and IL-1 beta, indicative of activated macrophages; and CCR5+CD4+ cells, which co-express CXCR3, IFN-gamma, and RANKL, indicative of Th1 lymphocytes, therefore comprising pro-osteoclastic and osteoclastogenic cell subsets, respectively. CCR5KO mice presented a lower PD severity (lower inflammation and alveolar bone loss) when compared with the WT strain, since the migration of F4/80+, TNF-alpha+, CD4+, and RANKL+ cells specifically decreased due to the lack of CCR5. Also, ELISA analysis demonstrated that the production of TNF-alpha, IL-1 beta, IL-6, IFN-gamma, and RANKL in periodontal tissues was significantly decreased in the CCR5KO strain. The periodontal bacterial load and antimicrobial patterns were unaltered in CCR5KO mice. Our results demonstrate that the chemokine receptor is involved in the migration of distinct leukocyte subpopulations throughout experimental PD, being a potential target for therapeutic intervention in PD.

Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection

Background. Periodontal diseases (PDs) are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. Recently, viruses have been implicated in the pathogenesis of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present with abnormal oral health and a marked increased prevalence of periodontal disease. Methods. In this study, we investigated the patterns of periodontopathogen infection and local inflammatory immune markers in HTLV-1-seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared with HTLV-1 -seronegative individuals with chronic periodontitis (CP group) and periodontally healthy, HTLV-1 -seronegative individuals (control group). Results. Patients in the CP/HTLV-1 group had significantly higher values of bleeding on probing, mean probing depth, and attachment loss than patients in the CP group. The expression of tumor necrosis factor a and interleukin (IL) 4 was found to be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended toward a higher expression in the CP/HTLV-1 group. A significant increase was seen in the levels of IL-1 beta and interferon gamma in the CP/HTLV-1 group compared with the CP group, whereas expression of the regulatory T cell marker FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1 group. Interestingly, similar frequency and/or load of periodontopathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically associated with PDs were found in the CP/HTLV and CP groups. Conclusions. HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.

Emergence and loss of assortative mating in sympatric speciation

We have studied an agent model which presents the emergence of sexual barriers through the onset of assortative mating, a condition that might lead to sympatric speciation. In the model, individuals are characterized by two traits, each determined by a single locus A or B. Heterozygotes on A are penalized by introducing an adaptive difference from homozygotes. Two niches are available. Each A homozygote is adapted to one of the niches. The second trait, called the marker trait has no bearing on the fitness. The model includes mating preferences, which are inherited from the mother and subject to random variations. A parameter controlling recombination probabilities of the two loci is also introduced. We study the phase diagram by means of simulations, in the space of parameters (adaptive difference, carrying capacity, recombination probability). Three phases are found, characterized by (i) assortative mating, (ii) extinction of one of the A alleles and (iii) Hardy-Weinberg like equilibrium. We also make perturbations of these phases to see how robust they are. Assortative mating can be gained or lost with changes that present hysteresis loops, showing the resulting equilibrium to have partial memory of the initial state and that the process of going from a polymorphic panmictic phase to a phase where assortative mating acts as sexual barrier can be described as a first-order transition. (C) 2009 Published by Elsevier Ltd.

Tempol ameliorates murine viral encephalomyelitis by preserving the blood-brain barrier, reducing viral load, and lessening inflammation

Multiple sclerosis (MS) is a progressive inflammatory and/or demyelinating disease of the human central nervous system (CNS). Most of the knowledge about the pathogenesis of MS has been derived from murine models, such as experimental autoimmune encephalomyelitis and vital encephalomyelitis. Here, we infected female C57BL/6 mice with a neurotropic strain of the mouse hepatitis virus (MHV-59A) to evaluate whether treatment with the multifunctional antioxidant tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) affects the ensuing encephalomyelitis. In untreated animals, neurological symptoms developed quickly: 90% of infected mice died 10 days after virus inoculation and the few survivors presented neurological deficits. Treatment with tempol (24 mg/kg, ip, two doses on the first day and daily doses for 7 days plus 2 mM tempol in the drinking water ad libitum) profoundly altered the disease outcome: neurological symptoms were attenuated, mouse survival increased up to 70%, and half of the survivors behaved as normal mice. Not Surprisingly, tempol substantially preserved the integrity of the CNS, including the blood-brain barrier. Furthermore, treatment with tempol decreased CNS vital titers, macrophage and T lymphocyte infiltration, and levels of markers of inflammation, such as expression of inducible nitric oxide synthase, transcription of tumor necrosis factor-alpha and interferon-gamma, and protein nitration. The results indicate that tempol ameliorates murine viral encephalomyelitis by altering the redox status of the infectious environment that contributes to an attenuated CNS inflammatory response. overall, our study supports the development of therapeutic strategies based on nitroxides to manage neuroinflammatory diseases, including MS. (C) 2009 Elsevier Inc. All rights reserved.

Nickel catalysts supported on ZrO2, Y2O3-stabilized ZrO2 and CaO-stabilized ZrO2 for the steam reforming of ethanol: Effect of the support and nickel load

Catalysts with various nickel loads were prepared on supports of ZrO2, ZrO2-Y2O3 and ZrO2-CaO, characterized by XRD and TPR and tested for activity in ethanol steam reforming. XRD of the supports identified the monoclinic crystalline phase in the ZrO2 and cubic phases in the ZrO2-Y2O3 and ZrO2-CaO supports. In the catalysts, the nickel impregnated on the supports was identified as the NiO phase. In the TPR analysis, peaks were observed showing the NiO phase having different interactions with the supports. In the catalytic tests, practically all the catalysts achieved 100% ethanol conversion, H-2 yield was near 70% and the gaseous concentrations of the other co-products varied in accordance with the equilibrium among them, affected principally by the supports. It was observed that when the ZrO2 was modified with Y2O3 and CaO, there were big changes in the CO and CO2 concentrations, which were attributed to the rise in the number of oxygen vacancies, permitting high-oxygen mobility and affecting the gaseous equilibrium. The liquid products analysis showed a low selectivity to liquid co-products during the reforming reactions. (c) 2007 Published by Elsevier B.V.

Load balancing solution and evaluation of F5 content switch equipment

The Thesis focused on hardware based Load balancing solution of web traffic through a load balancer F5 content switch. In this project, the implemented scenario for distributing HTTPtraffic load is based on different CPU usages (processing speed) of multiple member servers.Two widely used load balancing algorithms Round Robin (RR) and Ratio model (weighted Round Robin) are implemented through F5 load balancer. For evaluating the performance of F5 content switch, some experimental tests has been taken on implemented scenarios using RR and Ratio model load balancing algorithms. The performance is examined in terms of throughput (bits/sec) and Response time of member servers in a load balancing pool. From these experiments we have observed that Ratio Model load balancing algorithm is most suitable in the environment of load balancing servers with different CPU usages as it allows assigning the weight according to CPU usage both in static and dynamic load balancing of servers.

A Unified Load Generator for Geographically Distributed Generation ofNetwork Traffic

During the last decade, the Internet usage has been growing at an enormous rate which has beenaccompanied by the developments of network applications (e.g., video conference, audio/videostreaming, E-learning, E-Commerce and real-time applications) and allows several types ofinformation including data, voice, picture and media streaming. While end-users are demandingvery high quality of service (QoS) from their service providers, network undergoes a complex trafficwhich leads the transmission bottlenecks. Considerable effort has been made to study thecharacteristics and the behavior of the Internet. Simulation modeling of computer networkcongestion is a profitable and effective technique which fulfills the requirements to evaluate theperformance and QoS of networks. To simulate a single congested link, simulation is run with asingle load generator while for a larger simulation with complex traffic, where the nodes are spreadacross different geographical locations generating distributed artificial loads is indispensable. Onesolution is to elaborate a load generation system based on master/slave architecture.

Load and Season Adapted Solar Collectors

In Sweden solar irradiation and space heating loads are unevenly distributed over the year. Domestic hot water loads may be nearly constant. Test results on solar collector performance are often reported as yearly output of a certain collector at fixed temperatures, e g 25, 50 and 75 C. These data are not suitable for dimensioning of solar systems, because the actual performance of the collector depends heavily on solar fraction and load distribution over the year.At higher latitudes it is difficult to attain high solar fractions for buildings, due to overheating in summer and small marginal output for added collector area. Solar collectors with internal reflectors offer possibilities to evade overheating problems and deliver more energy at seasons when the load is higher. There are methods for estimating the yearly angular irradiation distribution, but there is a lack of methods for describing the load and the storage in such a way as to enable optical design of season and load adapted collectors.This report describes two methods for estimation of solar system performance with relevance for season and load adaption. Results regarding attainable solar fractions as a function of collector features, load profiles, load levels and storage characteristics are reported. The first method uses monthly collector output data at fixed temperatures from the simulation program MINSUN for estimating solar fractions for different load profiles and load levels. The load level is defined as estimated yearly collector output at constant collector temperature divided be yearly load. This table may examplify the results:CollectorLoadLoadSolar Improvementtypeprofile levelfractionover flat plateFlat plateDHW 75 %59 %Load adaptedDHW 75 %66 %12 %Flat plateSpace heating 50 %22 %Load adaptedSpace heating 50 %28 %29 %The second method utilises simulations with one-hour timesteps for collectors connected to a simplified storage and a variable load. Collector output, optical and thermal losses, heat overproduction, load level and storage temperature are presented as functions of solar incidence angles. These data are suitable for optical design of load adapted solar collectors. Results for a Stockholm location indicate that a solar combisystem with a solar fraction around 30 % should have collectors that reduce heat production at solar heights above 30 degrees and have optimum efficiency for solar heights between 8 and 30 degrees.

Load Adapted Solar Thermal Combisystems - Optical Analysis and Systems Optimization

In a northern European climate a typical solar combisystem for a single family house normally saves between 10 and 30 % of the auxiliary energy needed for space heating and domestic water heating. It is considered uneconomical to dimension systems for higher energy savings. Overheating problems may also occur. One way of avoiding these problems is to use a collector that is designed so that it has a low optical efficiency in summer, when the solar elevation is high and the load is small, and a high optical efficiency in early spring and late fall when the solar elevation is low and the load is large.The study investigates the possibilities to design the system and, in particular, the collector optics, in order to match the system performance with the yearly variations of the heating load and the solar irradiation. It seems possible to design practically viable load adapted collectors, and to use them for whole roofs ( 40 m2) without causing more overheating stress on the system than with a standard 10 m2 system. The load adapted collectors collect roughly as much energy per unit area as flat plate collectors, but they may be produced at a lower cost due to lower material costs. There is an additional potential for a cost reduction since it is possible to design the load adapted collector for low stagnation temperatures making it possible to use less expensive materials. One and the same collector design is suitable for a wide range of system sizes and roof inclinations. The report contains descriptions of optimized collector designs, properties of realistic collectors, and results of calculations of system output, stagnation performance and cost performance. Appropriate computer tools for optical analysis, optimization of collectors in systems and a very fast simulation model have been developed.

Solvärmesystem för hög täckningsgrad - Load adapted concentrating collectors for high solar fractions

Dagens kombisolvärmesystem för enfamiljshus har i storleksordningen 10 m2 solfångare och kan täcka i runda tal 10 ? 30 % av det årliga värmebehovet. Ökar man solfångarytan för att öka solvärmetäckningsgraden uppstår det vanligtvis en överproduktion av värme sommartid viket kan orsaka problem i form av termisk utmattning av material, att material förstörs eller att säkerhetsventiler utlöses med driftsstopp som följd. Vidare förkortas glykolens livslängd radikalt och detta kan ge följdskador såsom korrosion, beläggningar i rören och t o m igensättning av systemet. Ett sätt att undvika problemen med överhettning i solvärmesystem med hög täckningsgrad är att använda lastanpassade solfångare. Med detta menas solfångare som har en verkningsgrad som är beroende av solhöjden och varierar över året. Verkningsgraden är hög när värmelasten är hög (vanligtvis sen höst, vinter och tidig vår) medan verkningsgraden är låg då värmelasten är låg (vanligtvis sen vår, sommar och tidig höst). I denna rapport visas att det är möjligt att bygga lastanpassade solfångarsystem med hög täckningsgrad för enfamiljshus med solfångarytor som täcker hela villatak (>= 40 m2), utan att den termiska påfrestningen på systemet blir större än för vanliga solvärmesystem med 10 m2 plana solfångare. Detta kan göras med samma systemkomponenter som finns i system med plana solfångare. De lastanpassade solfångarna levererar ungefär samma energimängd per m2 som plana solfångare, men de bör kunna bli billigare, på grund av lägre materialkostnad. Det finns även en potential att konstruera lastanpassade solvärmesystem med begränsad stagnationstemperatur, vilket kan möjliggöra användandet av billigare material. En och samma solfångartyp är lämplig för såväl stora som små system och för olika takvinklar. I rapporten redovisas optimerade solfångargeometrier för lastanpassade solvärmesystem, geometrier och optiska egenskaper för praktiskt möjliga solfångare samt beräkningar av förväntat årsutbyte, stagnationstemperaturer, stagnationstider och kostnader. Testresultat för två prototyper av lastanpassade solfångare presenteras. Optimeringsalgoritmer för design av optiken för lastanpassade solfångare i system samt ett ray-tracingverktyg och snabba men ändå tillräckligt noggranna simuleringsverktyg har utvecklats.