Assessing the resilience and interdependence of civil infrastructure systems in order to provide a resilient community for resident has become a prevalent topic among policy-makers, authorities, and ...scholars around the world. Despite significant advances in this field, there is still a lack of research regarding comprehension of the actual behavior of civil infrastructures in response to hazards and disasters due to their complexity and hidden interconnectivity.
This study utilizes disruption data and a network analysis framework to describe resilience dimensions in two infrastructures and further validate the previously presented model. Following the evaluation of infrastructures and the previous model, interdependency between two lifelines will be discussed. Service disruption data is a valuable resource to confirm various theoretical methods. A case study of lifelines in Bhaktapur, Nepal is presented to show applicability of the network analysis model and service disruption data in evaluating the interdependencies between these two lifelines. The resilient characteristics of water infrastructure and the interdependence to power infrastructure are explained.
The contribution of this article is threefold: (i) validation of a novel network approach using disruption information, (ii) analysis of recoverability, sensitivity, and types of disruption patterns, and (iii) comparison of behavior and interdependencies between the infrastructures.
Understanding nanoparticle uptake by biological cells is fundamentally important to wide-ranging fields from nanotoxicology to drug delivery. It is now accepted that the arrival of nanoparticles at ...the cell is an extremely complicated process, shaped by many factors including unique nanoparticle physico-chemical characteristics, protein-particle interactions and subsequent agglomeration, diffusion and sedimentation. Sequentially, the nanoparticle internalisation process itself is also complex, and controlled by multiple aspects of a cell's state. Despite this multitude of factors, here we demonstrate that the statistical distribution of the nanoparticle dose per endosome is independent of the initial administered dose and exposure duration. Rather, it is the number of nanoparticle containing endosomes that are dependent on these initial dosing conditions. These observations explain the heterogeneity of nanoparticle delivery at the cellular level and allow the derivation of simple, yet powerful probabilistic distributions that accurately predict the nanoparticle dose delivered to individual cells across a population.
All herpesviruses have mechanisms for passing through cell junctions, which exclude neutralizing antibodies and offer a clear path to neighboring, uninfected cells. In the case of herpes simplex ...virus type 1 (HSV-1), direct cell-to-cell transmission takes place between epithelial cells and sensory neurons, where latency is established. The spreading mechanism is poorly understood, but mutations in four different HSV-1 genes can dysregulate it, causing neighboring cells to fuse to produce syncytia. Because the host proteins involved are largely unknown (other than the virus entry receptor), we were intrigued by an earlier discovery that cells infected with wild-type HSV-1 will form syncytia when treated with salubrinal. A biotinylated derivative of this drug was used to pull down cellular complexes, which were analyzed by mass spectrometry. One candidate was a protein tyrosine phosphatase (PTP1B), and although it ultimately proved not to be the target of salubrinal, it was found to be critical for the mechanism of cell-to-cell spread. In particular, a highly specific inhibitor of PTP1B (CAS 765317-72-4) blocked salubrinal-induced fusion, and by itself resulted in a dramatic reduction in the ability of HSV-1 to spread in the presence of neutralizing antibodies. The importance of this phosphatase was confirmed in the absence of drugs by using PTP1B-/- cells. Importantly, replication assays showed that virus titers were unaffected when PTP1B was inhibited or absent. Only cell-to-cell spread was altered. We also examined the effects of salubrinal and the PTP1B inhibitor on the four Syn mutants of HSV-1, and strikingly different responses were found. That is, both drugs individually enhanced fusion for some mutants and reduced fusion for others. PTP1B is the first host factor identified to be specifically required for cell-to-cell spread, and it may be a therapeutic target for preventing HSV-1 reactivation disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Evidence is increasingly pointing towards the importance of early life strategies to prevent childhood overweight and obesity. This systematic review synthesizes qualitative research ...concerning parental perceptions regarding behaviours for preventing overweight and obesity in young children. During May and June 2008, a range of electronic databases were searched and together with lateral searching techniques 21 studies were identified for review. Data extraction and synthesis using thematic content analysis revealed six organizing and 32 finer level themes. These related to child factors, family dynamics, parenting, knowledge and beliefs, extra‐familial influences and resources and environment. Themes were mapped to a socioecological model which illustrated how factors at individual, interpersonal, community, organizational and societal levels interact in complex ways to impact on parental perceptions about healthy behaviours for preventing child overweight. Although parents suggested several ideas to promote healthy child weight‐related behaviours, many of their views concerned perceived barriers, some of which may be amenable to practical intervention. Furthermore, intergenerational influences on parental health beliefs and knowledge suggest that health promotion strategies may be more effective if directed at the wider family, rather than parents alone. Significantly, many parents believed strategies to promote healthy weight should start early in a child's life.
Glycoprotein E (gE) of HSV plays a key role in cell-to-cell spread and virus-induced cell fusion. Here, we report that this function of gE requires the cooperation of tegument proteins UL11, UL16, ...and UL21. We found that the four proteins come together with very high efficiency to form a complex in transfected cells and in a manner that is regulated and coordinated. In particular, the inefficient interaction of UL16 with each membrane protein (UL11 and gE) observed in pairwise transfections became efficient when other binding partners were present. The significance of these interactions was revealed in studies of viral mutants, which showed that each of these tegument proteins is critical for processing, transport and biological activity of gE. These findings provide insights into the mechanisms of how gE executes its function and also have implications in understanding HSV assembly and budding.
Background
A clinical diagnosis (CDx) of pancreatitis includes evaluation of clinical signs, abdominal ultrasound (AUS), and pancreatic lipase. However, practitioners are using AUS to diagnose ...pancreatitis and are using AUS severity to guide decisions. The validity of this is unknown.
Objectives
To determine whether (1) there is a correlation between AUS, specific canine pancreatic lipase (Spec cPL) assay, and CDx; (2) individual AUS abnormalities correlate more closely with CDx than others; (3) AUS severity mirrors clinical severity indices; (4) changes in AUS can be used as a marker for changes in Spec cPL or CDx; and (5) the sensitivity and specificity of AUS for pancreatitis.
Animals
One hundred fifty‐seven dogs.
Methods
In this retrospective case study, inclusion criteria were signs of gastrointestinal, pancreatic disease, or both, in addition to having a Spec cPL and AUS performed within 30 hours. Information extracted from the records included bloodwork, Spec cPL, AUS images/clips, and severity of ultrasonographic findings.
Results
AUS was weakly correlated with Spec cPL (rs = .0178, P = .03) and moderately correlated with CDx (rs = .379, P = <.001). Pancreatic size (rs = .285, P = <.001), echogenicity (rs = .365, P = <.001), and mesenteric echogenicity (rs = .343, P = <.001) were correlated with CDx. Change in AUS was not correlated with Spec cPL or CDx changes. When pancreatic enlargement, echogenicity, or altered mesenteric echogenicity were required for a diagnosis, the sensitivity and specificity were 89% (95% confidence interval CI 71.8, 97.7) and 43% (95% CI 34.0, 51.6). When all 3 criteria were required, the sensitivity and specificity were 43% (95% CI 24.5, 62.8) and 92% (95% CI 85.3, 95.7).
Conclusions
AUS should not be used in isolation to diagnose pancreatitis and is a poor indicator of severity.
Background
Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune‐mediated hemolytic anemia (na‐IMHA) is weak.
Hypothesis/Objectives
Investigate the efficacy of ...various drugs in na‐IMHA.
Animals
Two hundred forty‐two dogs.
Methods
Multi‐institutional retrospective study (2015‐2020). Immunosuppressive effectiveness was determined by time to packed cell volume (PCV) stabilization and duration of hospitalization through analysis by mixed model linear regression. Occurrence of disease relapse, death, and antithrombotic effectiveness, were analyzed using mixed model logistic regression.
Results
Use of corticosteroids vs a multi‐agent protocol had no effect on time to PCV stabilization (P = .55), duration of hospitalization (P = .13), or case fatality (P = .06). A higher rate of relapse (P = .04; odds ratio: 3.97; 95% confidence interval CI: 1.06‐14.8) was detected in dogs receiving corticosteroids (11.3%) during follow‐up (median: 28.5 days, range: 0‐1631 days) compared to multiple agents (3.1%) during follow up (median: 47.0 days, range: 0‐1992 days). When comparing drug protocols, there was no effect on time to PCV stabilization (P = .31), relapse (P = .44), or case fatality (P = .08). Duration of hospitalization was longer, by 1.8 days (95% CI: 0.39‐3.28 days), for the corticosteroid with mycophenolate mofetil group (P = .01) compared to corticosteroids alone. Use of clopidogrel vs multiple agents had no effect on development of thromboses (P ≥ .36).
Conclusions and Clinical Importance
Addition of a second immunosuppressive agent did not alter immediate outcome measures but might be associated with a reduction in relapse. Use of multiple antithrombotic agents did not reduce incidence of thrombosis.
The objective of this article was to provide the nonmodeler reader of Poultry Science, an overview of the system dynamics modeling method (SDM) through development of a broiler house disease ...management simulator (BHDMS). System dynamics modeling uses feedback theory and computer-aided simulation to help elucidate relationships between factors in complex systems, which may be circular or interrupted with long delays. Materials used to build the simulator include data from literature and industry indices. The methods used were the steps in SDM, namely: 1) Identify the problem and boundaries; 2) develop a dynamic hypothesis explaining cause of the problem; 3) build the causal loop diagram (CLD); 4) develop the stock and flow model; 5) conduct model simulations; and 6) model validation. Results presented here are the CLD and stock and flow model of the simulator, results of scenario simulations, and model validity tests. The simulator consists of the main model, the disease submodel, and the antimicrobial use submodel. The main model represents a cycle of production in the broiler house of a specified length of time, which repeats after a specified down time. The disease submodel shows population dynamics in the broiler house in terms of changes over time in number of susceptible, infected, recovered, and dead birds. Production parameters that could be modified in the model include delivery size, grow-out period, down time, and efficacy of antimicrobials. Disease mortality levels, above the set threshold, trigger antimicrobial use in the model. The model showed the effect of antimicrobial use intervention on the population dynamics, namely, on the proportion of the susceptible, infected, recovered, and dead birds in the population. Thus, the BHDMS was able to simulate the effect of the intervention on population dynamics and would facilitate evaluating management interventions such as antimicrobial use.
The initial goal of this study was to reexamine the requirement of UL21 for herpes simplex virus 1 (HSV-1) replication. Previous studies suggested that UL21 is dispensable for replication in cell ...cultures, but a recent report on HSV-2 challenges those findings. As was done for the HSV-2 study, a UL21-null virus was made and propagated on complementing cells to discourage selection of compensating mutations. This HSV-1 mutant was able to replicate in noncomplementing cells, even at a low multiplicity of infection (MOI), though a reduction in titer was observed. Also, increased proportions of empty capsids were observed in the cytoplasm, suggesting a role for UL21 in preventing their exit from the nucleus. Surprisingly, passage of the null mutant resulted in rapid outgrowth of syncytial (Syn) variants. This was unexpected because UL21 has been shown to be required for the Syn phenotype. However, earlier experiments made use of only the A855V syncytial mutant of glycoprotein B (gB), and the Syn phenotype can also be produced by substitutions in glycoprotein K (gK), UL20, and UL24. Sequencing of the syncytial variants revealed mutations in the gK locus, but UL21 was shown to be dispensable for UL20
and UL24
To test whether UL21 is needed only for the A855V mutant, additional gB
derivatives were examined in the context of the null virus, and all produced lytic rather than syncytial sites of infection. Thus, UL21 is required only for the gB
phenotype. This is the first example of a differential requirement for a viral protein across the four
loci.
UL21 is conserved among alphaherpesviruses, but its role is poorly understood. This study shows that HSV-1 can replicate without UL21, although the virus titers are greatly reduced. The null virus had greater proportions of empty (DNA-less) capsids in the cytoplasm of infected cells, suggesting that UL21 may play a role in retaining them in the nucleus. This is consistent with reports showing UL21 to be capsid associated and localized to the nuclei of infected cells. UL21 also appears to be needed for viral membrane activities. It was found to be required for virus-mediated cell fusion, but only for mutants that harbor syncytial mutations in gB (not variants of gK, UL20, or UL24). The machinery needed for syncytial formation is similar to that needed for direct spread of the virus through cell junctions, and these studies show that UL21 is required for cell-to-cell spread even in the absence of syncytial mutations.
A virulent clonal population of Aeromonas hydrophila (VAh) is recognized as the etiological agent in outbreaks of motile aeromonas septicemia (MAS) in catfish aquaculture in the southeastern United ...States since 2009. Genomic subtraction revealed three outer membrane proteins present in VAh strain ML09-119 but not in low virulence reference A. hydrophila strains: major outer membrane protein OmpA1, TonB-dependent receptor (Tdr), and transferrin-binding protein A (TbpA). Here, the genes encoding ompA1, tdr, and tbpA were cloned from A. hydrophila ML09-119 and expressed in Escherichia coli. The purified recombinant OmpA1, Tdr, and TbpA proteins had estimated molecular weights of 37.26, 78.55, and 41.67 kDa, respectively. Catfish fingerlings vaccinated with OmpA1, Tdr, and TbpA emulsified with non-mineral oil adjuvant were protected against subsequent VAh strain ML09-119 infection with 98.59%, 95.59%, and 47.89% relative percent survival (RPS), respectively. Furthermore, the mean liver, spleen, and anterior kidney bacterial concentrations were significantly lower in catfish vaccinated with the OmpA1 and Tdr than the sham-vaccinated control group. ELISA demonstrated that catfish immunized with OmpA1, Tdr, and TbpA produce significant antibody response by 21 days post-immunization. Therefore, OmpA1 and Tdr proteins could be used as potential candidates for vaccine development against virulent A. hydrophila infection. However, TbpA protein failed to provide strong protection.
•Since 2009, virulent Aeromonas hydrophila (VAh) has been causing an epizootic in catfish aquaculture in the U.S.•Outer membrane proteins OmpA1, Tdr, and TbpA unique to VAh were expressed and tested as vaccine antigens in catfish.•OmpA1 and Tdr provided significant protection in catfish experimentally infected with VAh.
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