176 research outputs found
Branched versus linear alkane adsorption in carbonaceous slit pores
The presence of carbonaceous deposits on the internal surfaces of a spark ignition engine has been linked in the literature to impaired vehicle performance, as manifested by increased knocking, higher fuel consumption, higher emissions and other adverse effects. One of the proposed mechanisms, in which the deposits affect the processes in the engine, is the adsorption and desorption of fuel components in the pores within the deposit. In this article we investigate this mechanism in more detail by considering single component adsorption of normal and branched alkanes in selected model slit pores representing the structure of the deposits. We further extend these studies to the binary mixture of normal heptane and isooctane, corresponding to a primary reference fuel blend. In particular, we show that in larger pores adsorption selectivity towards isooctane is about 1.2 on average throughout the pressure range. However, in the smaller 10 Å pore selectivity towards isooctane can be in excess of three as a result of packing effects. These results are then placed in the context of engine performance issues
Patterns and correlates of tobacco control behavior among american association of pediatric dentistry members: a cross-sectional national study
<p>Abstract</p> <p>Background</p> <p>To determine the tobacco-related knowledge, attitudes, and practice behaviors among US pediatric dentists.</p> <p>Methods</p> <p>A survey was conducted in 1998 among a national, random sample of 1500 American Academy of Pediatric Dentistry members. Chi-square tests and logistic regression with odds ratios (ORs) and 95% confidence intervals assessed factors related to pediatric dentists' tobacco control behaviors.</p> <p>Results</p> <p>Response was 65% for the survey. Only 12% of respondents had prior tobacco prevention/cessation training. Of those untrained, 70% were willing to be trained. Less than two-thirds correctly answered any of four tobacco-related knowledge items. Over one-half agreed pediatric dentists should engage in tobacco control behaviors, but identified patient resistance as a barrier. About 24% of respondents reported always/often asking their adolescent patients about tobacco use; 73% reported always/often advising known tobacco users to quit; and 37% of respondents always/often assisting with stopping tobacco use. Feeling prepared to perform tobacco control behaviors (ORs = 1.9–2.8), a more positive attitude score (4 points) from 11 tobacco-related items (ORs = 1.5–1.8), and a higher statewide tobacco use prevalence significantly predicted performance of tobacco control behaviors.</p> <p>Conclusion</p> <p>Findings suggest thatraining programs on tobacco use and dependence treatment in the pediatric dental setting may be needed to promote tobacco control behaviors for adolescent patients.</p
YwdL in Bacillus cereus: Its Role in Germination and Exosporium Structure
In members of the Bacillus cereus group the outermost layer of the spore is the exosporium, which interacts with hosts and the environment. Efforts have been made to identify proteins of the exosporium but only a few have so far been characterised and their role in determining spore architecture and spore function is still poorly understood. We have characterised the exosporium protein, YwdL. ΔywdL spores have a more fragile exosporium, subject to damage on repeated freeze-thawing, although there is no evidence of altered resistance properties, and coats appear intact. Immunogold labelling and Western blotting with anti-YwdL antibodies identified YwdL to be located exclusively on the inner surface of the exosporium of B. cereus and B. thuringiensis. We conclude that YwdL is important for formation of a robust exosporium but is not required to maintain the crystalline assembly within the basal layer or for attachment of the hairy nap structure. ΔywdL spores are unable to germinate in response to CaDPA, and have altered germination properties, a phenotype that confirms the expected defect in localization of the cortex lytic enzyme CwlJ in the coat
Animal products, calcium and protein and prostate cancer risk in the Netherlands Cohort Study
Prostate cancer risk in relation to consumption of animal products, and intake of calcium and protein was investigated in the Netherlands Cohort Study. At baseline in 1986, 58,279 men aged 55-69 years completed a self-administered 150-item food frequency questionnaire and a questionnaire on other risk factors for cancer. After 6.3 years of follow-up, 642 prostate cancer cases were available for analysis. In multivariate case-cohort analyses adjusted for age, family history of prostate cancer and socioeconomic status, no associations were found for consumption of fresh meat, fish, cheese and eggs. Positive trends in risk were found for consumption of cured meat and milk products (P-values 0.04 and 0.02 respectively). For calcium and protein intake, no associations were observed. The hypothesis that dietary factors might be more strongly related to advanced prostate rumours could not be confirmed in our study. We conclude that, in this study, animal products are not strongly related to prostate cancer risk
Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease
COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments were progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease
Novel Plasmids and Resistance Phenotypes in Yersinia pestis: Unique Plasmid Inventory of Strain Java 9 Mediates High Levels of Arsenic Resistance
Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not restricted to the three classical virulence plasmids. The Java 9 strain of Y. pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it retains virulence in mouse and non-human primate animal models. While comparing diverse Y. pestis strains using subtractive hybridization, we identified sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying the transposon Tn2502, which is known to encode arsenic resistance. Here we demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic resistance was self-transmissible from Java 9 to other Y. pestis strains via conjugation. Genomic analysis of the atypical plasmid inventory of Java 9 identified pCD and pPCP plasmids of atypical size and two previously uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9 are found on all four indigenous plasmids, including the two novel cryptic plasmids. This unique mobilome introduces more than 105 genes into the species gene pool. The majority of these are encoded by the two entirely novel self-transmissible plasmids, which show partial homology and synteny to other enterics. In contrast to the reductive evolution in Y. pestis, this study underlines the major impact of a dynamic mobilome and lateral acquisition in the genome evolution of the plague bacterium
Quasispecies Theory and the Behavior of RNA Viruses
A large number of medically important viruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. This diversity allows a viral population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy
A Multi-Step Process of Viral Adaptation to a Mutagenic Nucleoside Analogue by Modulation of Transition Types Leads to Extinction-Escape
Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-β-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is mediated by amino acid substitutions in the viral polymerase that either increase the general template copying fidelity of the enzyme or decrease the incorporation of ribavirin into RNA. Here we describe experiments that show that replication of the important picornavirus pathogen foot-and-mouth disease virus (FMDV) in the presence of increasing concentrations of ribavirin results in the sequential incorporation of three amino acid substitutions (M296I, P44S and P169S) in the viral polymerase (3D). The main biological effect of these substitutions is to attenuate the consequences of the mutagenic activity of ribavirin —by avoiding the biased repertoire of transition mutations produced by this purine analogue—and to maintain the replicative fitness of the virus which is able to escape extinction by ribavirin. This is achieved through alteration of the pairing behavior of ribavirin-triphosphate (RTP), as evidenced by in vitro polymerization assays with purified mutant 3Ds. Comparison of the three-dimensional structure of wild type and mutant polymerases suggests that the amino acid substitutions alter the position of the template RNA in the entry channel of the enzyme, thereby affecting nucleotide recognition. The results provide evidence of a new mechanism of resistance to a mutagenic nucleoside analogue which allows the virus to maintain a balance among mutation types introduced into progeny genomes during replication under strong mutagenic pressure
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