Vaccinia Virus Protein C6 Inhibits Type I IFN Signalling in the Nucleus and Binds to the Transactivation Domain of STAT2.

The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells. Ectopic expression of C6 inhibits the induction of interferon stimulated genes (ISGs) in response to IFNα treatment at both the mRNA and protein level. C6 inhibits the IFNα-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway at a late stage, downstream of STAT1 and STAT2 phosphorylation, nuclear translocation and binding of the interferon stimulated gene factor 3 (ISGF3) complex to the interferon stimulated response element (ISRE). Mechanistically, C6 associates with the transactivation domain of STAT2 and this might explain how C6 inhibits the type I IFN signalling very late in the pathway. During virus infection C6 reduces ISRE-dependent gene expression despite the presence of the viral protein phosphatase VH1 that dephosphorylates STAT1 and STAT2. The ability of a cytoplasmic replicating virus to dampen the immune response within the nucleus, and the ability of viral immunomodulators such as C6 to inhibit multiple stages of the innate immune response by distinct mechanisms, emphasizes the intricacies of host-pathogen interactions and viral immune evasion.Wellcome-Trust, Lister Institute of Preventive Medicine U

Atmospheric effects of the emerging mainland Chinese transportation system at and beyond the regional scale

Local surface travel needs in the People's Republic of China (mainland China) have traditionally been met largely by nonpolluting bicycles. A major automobile manufacturing/importing effort has begun in the country over the last decade, and planning documents indicate that the Chinese may strive to acquire more than 100 million vehicles early in the next century. By analogy with large automotive fleets already existing in the western world, both regional and global scale pollution effects are to be expected from the increase. The present work adopts the latest projections of Chinese automobile manufacture and performs some quantitative assessments of the extent of pollution generation. Focus for the investigation is placed upon the oxidant ozone. Emissions of the precursor species nitrogen oxides and volatile organics are constructed based on data for the current automotive sector in the eastern portion of the United States. Ozone production is first estimated from measured values for continental/oceanic scale yields relative to precursor oxidation. The estimates are then corroborated through idealized two dimensional modeling of the photochemistry taking place in springtime air flow off the Asian land mass and toward the Pacific Ocean. The projected fleet sizes could increase coastal and remote oceanic ozone concentrations by tens of parts per billion (ppb) in the lower troposphere. Influences on the tropospheric aerosol system and on the major greenhouse gas carbon dioxide are treated peripherally. Nitrogen oxides created during the vehicular internal combustion process will contribute to nitrate pollution levels measured in the open Pacific. The potential for soot and fugitive dust increases should be considered as the automotive infrastructure develops. Since the emerging Chinese automotive transportation system will represent a substantial addition to the global fleet and all the carbon in gasoline is eventually oxidized completely, a significant rise in global carbon dioxide inputs will ensue as well. Some policy issues are treated preliminary. The assumption is made that alterations to regional oxidant/aerosol systems and to terrestrial climate are conceivable. The likelihood that the Chinese can achieve the latest vehicle fleet goals is discussed, from the points of view of new production, positive pollution feedbacks from a growing automobile industry, and known petroleum reserves. Vehicular fuel and maintenance options lying before the Chinese are outlines and compared. To provide some perspective on the magnitude of the environmental changes associated with an Asian automotive buildup, recent estimates of the effects of future air traffic over the Pacific Rim are described

Designed Dynamic Reference with Model Predictive Control for Bidirectional EV Chargers

© 2013 IEEE. This paper presents a finite control set model predictive control (MPC) using a designed dynamic reference for bidirectional electric vehicle (EV) chargers. In the conventional MPC scheme, a PI controller is involved to generate an active power reference from the DC voltage reference. It is hard to find one fixed set of coefficients for all working conditions. In this paper, a designed dynamic reference based MPC strategy is proposed to replace the PI control loop. In the proposed method, a DC voltage dynamic reference is developed to formulate the inherent relationship between the DC voltage reference and the active power reference. Multi-objective control can be achieved in the proposed scheme, including controlling of the DC voltage, battery charging/discharging current, active power and reactive power, independently. Bidirectional power flow is operated effectively between the EV- and the grid-side. Experimental results are obtained from a laboratory three-phase two-stage bidirectional EV charger controlled by dSPACE DS1104. The results show that fast dynamic and good steady state performance of tracking the above objectives can be achieved with the proposed method. Compared with the system performance obtained by the conventional MPC method, the proposed method generates less active power ripples and produces a better grid current performance

Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence

P. gingivalis LPS enhances human β-defensins expression in gingival epithelia

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Expression of human β-defensins-1 and -2 in periodontal health and disease

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Loss to follow-up in a community clinic in South Africa – roles of gender, pregnancy and CD4 count

Background. Faith-based organisations have expanded antiretroviral therapy (ART) in community clinics across South Africa. Loss to follow-up (LTFU), however, limits the potential individual and population treatment benefits and optimal care. Objective. To identify patient characteristics associated with LTFU 6 months after starting ART in a large community clinic. Methods. Patients initiating ART between April 2004 and October 2006 in one South African Catholic Bishops’ Conference HIV treatment clinic who had at least one follow-up visit were included and routinely monitored every 6 months after ART initiation. Standardised instruments were used to collect data. Rates of LTFU over time were estimated by the Kaplan-Meier method. The Cox proportional hazard regression examined the impact of age, baseline CD4 count, baseline HIV RNA, gender and pregnancy status on LTFU. Results. Data from 925 patients (age >14 years, median age 36 years, 70% female, of whom 16% were pregnant) were included: 51 (6%) were lost to follow-up 6 months after ART initiation. Younger age (≤30 years) (hazard ratio (HR) 2.14, 95% confidence interval (CI) 1.05 - 4.38) and pregnancy for women (HR 3.75, 95% CI 1.53 - 9.16) were significantly associated with higher LTFU rates. When stratified by baseline CD4 count, gender and pregnancy status, pregnant women with lower baseline CD4 counts (≤200 cells/ μl) had 6.06 times the hazard (95% CI 2.20 - 16.71) of LTFU at 6 months compared with men. Conclusions. HIV-infected pregnant women initiating ART were significantly more likely to be lost to follow-up in a community clinic in South Africa. Urgent interventions to successfully retain pregnant women in care are needed

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Subgraph Mining for Anomalous Pattern Discovery in Event Logs

Conformance checking allows organizations to verify whether their IT system complies with the prescribed behavior by comparing process executions recorded by the IT system against a process model (representing the normative behavior). However, most of the existing techniques are only able to identify low-level deviations, which provide a scarce support to investigate what actually happened when a process execution deviates from the specification. In this work, we introduce an approach to extract recurrent deviations from historical logging data and generate anomalous patterns representing high-level deviations. These patterns provide analysts with a valuable aid for investigating nonconforming behaviors; moreover, they can be exploited to detect high-level deviations during conformance checking. To identify anomalous behaviors from historical logging data, we apply frequent subgraph mining techniques together with an ad-hoc conformance checking technique. Anomalous patterns are then derived by applying frequent items algorithms to determine highly-correlated deviations, among which ordering relations are inferred. The approach has been validated by means of a set of experiments

Quantum simulation of the wavefunction to probe frustrated Heisenberg spin systems

Quantum simulators are controllable quantum systems that can reproduce the dynamics of the system of interest, which are unfeasible for classical computers. Recent developments in quantum technology enable the precise control of individual quantum particles as required for studying complex quantum systems. Particularly, quantum simulators capable of simulating frustrated Heisenberg spin systems provide platforms for understanding exotic matter such as high-temperature superconductors. Here we report the analog quantum simulation of the ground-state wavefunction to probe arbitrary Heisenberg-type interactions among four spin-1/2 particles . Depending on the interaction strength, frustration within the system emerges such that the ground state evolves from a localized to a resonating valence-bond state. This spin-1/2 tetramer is created using the polarization states of four photons. The single-particle addressability and tunable measurement-induced interactions provide us insights into entanglement dynamics among individual particles. We directly extract ground-state energies and pair-wise quantum correlations to observe the monogamy of entanglement