Dynamic Winkler Modulus for Axially Loaded End-Bearing Piles

The problem of dynamic pile-soil interaction and its modeling through the concept of a Dynamic Winkler Foundation are revisited. It is shown that depth-dependent Winkler springs and dashpots, obtained by dividing the complex-valued soil shear tractions and the corresponding displacements along the pile, may faithfully describe pile-soil interaction, contrary to common perception that the Winkler model is always approximate. A theoretical wave model is then derived for analyzing the response of axially loaded endbearing piles embedded in a homogeneous viscoelastic soil medium. Closed-form solutions are obtained for: (i) the displacement field in the soil and along the pile; (ii) the impedance coefficients (stiffness and damping) at the pile head; (iii) the depth-dependent Winkler moduli along the pile; (iv) the average, depth-independent, Winkler moduli to match the impedance coefficient at the pile head. Results are presented in terms of dimensionless graphs and charts that highlight the salient features of the problem. The predictions of the model compare favorably with established solutions from the literature, while new results are presented

Exploiting Amoeboid and Non-Vertebrate Animal Model Systems to Study the Virulence of Human Pathogenic Fungi

Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host–fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis

Seismic Risk of Inter-urban Transportation Networks

AbstractThe paper presents a holistic approach for assessing and managing the seismic risk and potential loss in inter-urban highway networks in earthquake-prone areas. The vulnerability of all elements of the intercity transportation system (i.e., roads, bridges, abutments, retaining walls, and tunnels) is assessed considering the interdependency among the structural, transportational and geotechnical components of the network under different seismic scenarios. Both the direct earthquake-induced damage, as well as the indirect socio-economic loss attributed to reduced network functionality are taken into account in an explicit and transparent formulation that is then displayed in space through an ad-hoc developed GIS-based software. The methodology and the decision-making tools developed are adequately modular, for them to be utilized after appropriate adaptation by local authorities in identifying, prior to a major earthquake event, those vulnerable components of their network whose failure may have a disproportional socio-economic impact. In this way, a rational and effective emergency plan can be deployed to minimize potential human, social and financial loss after a future earthquake. The outline of a foreseen application is also presented for the case of the road network of the Region of Western Macedonia in Greece. Through this pilot application, the methodology is to be optimized in real conditions before being cast in the form of a fully parameterised seismic risk tool, to be used in other earthquake prone areas as well

Varying Vaccination Rates Among Patients Seeking Care for Acute Respiratory Illness:A Systematic Review and Meta-analysis

Background: Complications following influenza infection are a major cause of morbidity and mortality, and the Centers for Disease Control Advisory Committee on Immunization Practices recommends universal annual vaccination. However, vaccination rates have remained significantly lower than the Department of Health and Human Services goal. The aim of this work was to assess the vaccination rate among patients who present to health care providers with influenza-like illness and identify groups with lower vaccination rates. Methods: We performed a systematic search of the PubMed and EMBASE databases with a time frame of January 1, 2010, to March 1, 2019 and focused on the vaccination rate among patients seeking care for acute respiratory illness in the United States. A random effects meta-analysis was performed to estimate the pooled seasonal influenza vaccination rate, and we used a time trend analysis to identify differences in annual vaccination over time. Results: The overall pooled influenza vaccination rate was 48.61% (whites: 50.87%; blacks: 36.05%; Hispanics: 41.45%). There was no significant difference among gender groups (men: 46.43%; women: 50.11%). Interestingly, the vaccination rate varied by age group and was significantly higher among adults aged >65 (78.04%) and significantly lower among children 9-17 years old (36.45%). Finally, we found a significant upward time trend in the overall influenza vaccination rate among whites (coef. = .0107; P = .027). Conclusions: In conclusion, because of the significantly lower influenza vaccination rates in black and Hispanic communities, societal initiatives and community outreach programs should focus on these populations and on children and adolescents aged 9-17 years

Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay

There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (∼1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as “probe compounds” and may have antifungal activity against other fungi

Whole Animal Automated Platform for Drug Discovery against Multi-Drug Resistant Staphylococcus aureus

Staphylococcus aureus, the leading cause of hospital-acquired infections in the United States, is also pathogenic to the model nematode Caenorhabditis elegans. The C. elegans-S. aureus infection model was previously carried out on solid agar plates where the bacteriovorous C. elegans feeds on a lawn of S. aureus. However, agar-based assays are not amenable to large scale screens for antibacterial compounds. We have developed a high throughput liquid screening assay that uses robotic instrumentation to dispense a precise amount of methicillin resistant S. aureus (MRSA) and worms in 384-well assay plates, followed by automated microscopy and image analysis. In validation of the liquid assay, an MRSA cell wall defective mutant, MW2ΔtarO, which is attenuated for killing in the agar-based assay, was found to be less virulent in the liquid assay. This robust assay with a Z’-factor consistently greater than 0.5 was utilized to screen the Biomol 4 compound library consisting of 640 small molecules with well characterized bioactivities. As proof of principle, 27 of the 30 clinically used antibiotics present in the library conferred increased C. elegans survival and were identified as hits in the screen. Surprisingly, the antihelminthic drug closantel was also identified as a hit in the screen. In further studies, we confirmed the anti-staphylococcal activity of closantel against vancomycin-resistant S. aureus isolates and other Gram-positive bacteria. The liquid C. elegans – S. aureus assay described here allows screening for anti-staphylococcal compounds that are not toxic to the host