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Strain amplitude response and the microstructure of PA/clay nanocomposites
Polyamide 6/clay nanocomposites (PAn, where n is the mass fraction of clay) with various clay loading were prepared by melt compounding in a twin screw extruder. Exfoliation of clay in a PA matrix was confirmed by X-ray diffraction. Strain amplitude response of PAn in both melt and solution states has been investigated. In the melt state, critical strain amplitude of PAn is sensitive to strain amplitude response and decrease logarithmically with increasing clay loading. The elastic moduli (GâČ) of PAn are reversible under frequency loop sweeps. Comparisons of strain amplitude response in both melt and solution states have been conducted. Two different responses have been observed: strain thinning in the melt state and weak strain overshoot in the solution state. FTIR studies show that amide II band of PAn shifts toward high wavenumbers, but amide I band and NâH stretching vibration are independent of clay loading. We suggest that two types of strain amplitude response of PAn can be explained: strain thinning which is dominant in PAn caused by physical adsorption and entanglement of PA chains on nanoclays and weak strain overshoot caused by weak bonds between PA chains and nanoclays
Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection
Murine norovirus (MNV) is widely used as a model for studying norovirus biology. While MNV isolates vary in their pathogenesis, infection of immunocompetent mice mostly results in persistent infection. The ability of a virus to establish a persistent infection is dependent on its ability to subvert or avoid the host immune response. Previously, we described the identification and characterization of virulence factor 1 (VF1) in MNV, and demonstrated its role as an innate immune antagonist. Here, we explore the role of VF1 during persistent MNV infection in an immunocompetent host. Using reverse genetics, we generated MNV-3 viruses carrying a single or a triple termination codon inserted in the VF1 ORF. VF1-deleted MNV-3 replicated to comparable levels to the wildtype virus in tissue culture. Comparative studies between MNV-3 and an acute MNV-1 strain show that MNV-3 VF1 exerts the same functions as MNV-1 VF1, but with reduced potency. C57BL/6âmice infected with VF1-deleted MNV-3 showed significantly reduced replication kinetics during the acute phase of the infection, but viral loads rapidly reached the levels seen in mice infected with wildtype virus after phenotypic restoration of VF1 expression. Infection with an MNV-3 mutant that had three termination codons inserted into VF1, in which reversion was suppressed, resulted in consistently lower replication throughout a 3âmonth persistent infection in mice, suggesting a role for VF1 in viral fitness in vivo. Our results indicate that VF1 expressed by a persistent strain of MNV also functions to antagonize the innate response to infection. We found that VF1 is not essential for viral persistence, but instead contributes to viral fitness in mice. These data fit with the hypothesis that noroviruses utilize multiple mechanisms to avoid and/or control the host response to infection and that VF1 is just one component of this
Physical and psychological symptoms of quality of life in the CHART randomized trial in head and neck cancer: short-term and long-term patient reported symptoms
The randomized multicentre trial of continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in patients with advanced head and neck cancer showed no good evidence of a difference in any of the major clinical outcomes of survival, freedom from metastases, loco-regional control and disease-free survival. Therefore an assessment of the effect of treatment on physical and psychological symptoms is vital to balance the costs and benefits of the two treatments. A total of 615 patients were asked to complete a Rotterdam Symptom Checklist and the Hospital Anxiety and Depression Scale, which cover a variety of physical and psychological symptoms, at a total of ten time points. The data consisted of short-term data (the initial 3 months) and long-term data (1 and 2 years). The short-term data was split into an exploratory data set and a confirmatory data set, and analysed using subject-specific and group-based methods. Differences were only claimed if hypotheses generated in the exploratory data set were confirmed in the confirmatory data set. The long-term data was not split into two data sets and was analysed using a group-based approach. There was evidence of significantly worse symptoms of pain at day 21 in those treated with CHART and significantly worse symptoms of cough and hoarseness at 6 weeks in those treated conventionally. There was also evidence to suggest a higher degree of decreased sexual interest at 1 year and sore muscles at 2 years in those treated with conventional radiotherapy. There is no clear indication that one regimen is superior to the other in terms of âquality of lifeâ, generally the initially more severe reaction in the CHART group being offset by the longer duration of symptoms in the conventionally treated group. © 1999 Cancer Research Campaig
Predictors of recurrence, early treatment failure and death from Staphylococcus aureus bacteraemia: observational analyses within the ARREST trial
Adjunctive rifampicin did not reduce failure/recurrence/death as a composite endpoint in the ARREST trial of Staphylococcus aureus bacteraemia, but did reduce recurrences. We investigated clinically-defined 14-day treatment failure, and recurrence and S. aureus-attributed/unattributed mortality by 12-weeks to further define their predictor
Algebraic generation of minimum size orthogonal fractional factorial designs: an approach based on integer linear programming
Generation of orthogonal fractional factorial designs (OFFDs) is an important and extensively studied subject in applied statistics. In this paper we show how searching for an OFFD that satisfies a set of constraints, expressed in terms of orthogonality between simple and interaction effects, is, in many applications, equivalent to solving an integer linear programming problem.We use a recent methodology, based on polynomial counting functions and strata, that represents OFFDs as the positive integer solutions of a system of linear equations. We use this system to set up an optimization problem where the cost function to be minimized is the size of the OFFD and the constraints are represented by the system itself. Finally we search for a solution using standard integer programming techniques. Some applications are also presented in the computational results section. It is worth noting that the methodology does not put any restriction either on the number of levels of each factor or on the orthogonality constraints and so it can be applied to a very wide range of designs, including mixed orthogonal array
The Intensive Care Unit as a Research Laboratory: Developing Strategies to Prevent Antimicrobial Resistance
Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study
Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (pâ<â0.001) in the fit group (mean 1.21â±â3.42) compared to the unfit group (mean -0.74â±â2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth
Redox linked flavin sites in extracellular decaheme proteins involved in microbe-mineral electron transfer
Extracellular microbe-mineral electron transfer is a major driving force for the oxidation of organic carbon in many subsurface environments. Extracellular multi-heme cytochromes of the Shewenella genus play a major role in this process but the mechanism of electron exchange at the interface between cytochrome and acceptor is widely debated. The 1.8 Ă
x-ray crystal structure of the decaheme MtrC revealed a highly conserved CX8C disulfide that, when substituted for AX8A, severely compromised the ability of S. oneidensis to grow under aerobic conditions. Reductive cleavage of the disulfide in the presence of flavin mononucleotide (FMN) resulted in the reversible formation of a stable flavocytochrome. Similar results were also observed with other decaheme cytochromes, OmcA, MtrF and UndA. The data suggest that these decaheme cytochromes can transition between highly reactive flavocytochromes or less reactive cytochromes, and that this transition is controlled by a redox active disulfide that responds to the presence of oxygen
Induction of humoral immune response to multiple recombinant Rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission
BACKGROUND: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiological agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect feeding success and possibly reduce tick-borne transmission of T. parva. Here we report the evaluation of a multivalent vaccine cocktail of tick antigens for their ability to reduce R. appendiculatus feeding success and possibly reduce tick-transmission of T. parva in a natural host-tick-parasite challenge model.
METHODS: Cattle were inoculated with a multivalent antigen cocktail containing recombinant tick protective antigen subolesin as well as two additional R. appendiculatus saliva antigens: the cement protein TRP64, and three different histamine binding proteins. The cocktail also contained the T. parva sporozoite antigen p67C. The effect of vaccination on the feeding success of nymphal and adult R. appendiculatus ticks was evaluated together with the effect on transmission of T. parva using a tick challenge model.
RESULTS: To our knowledge, this is the first evaluation of the anti-tick effects of these antigens in the natural host-tick-parasite combination. In spite of evidence of strong immune responses to all of the antigens in the cocktail, vaccination with this combination of tick and parasite antigens did not appear to effect tick feeding success or reduce transmission of T. parva.
CONCLUSION: The results of this study highlight the importance of early evaluation of anti-tick vaccine candidates in biologically relevant challenge systems using the natural tick-host-parasite combination
Systematic review of antiepileptic drugsâ safety and effectiveness in feline epilepsy
Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDsâ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total
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