Dendritic Plasmonics for Mid-Infrared Spectroscopy

Metallic nanostructures that exhibit tailored optical resonances spanning from the near to mid-infrared spectral range are of particular interest for spectroscopic and optical measurements in these spectral domains that can benefit from localized surface-enhancement effects. Plasmon resonances shifted in the near or mid-infrared range could be used to further enhance the excitation and/or the emission of an optical process. Surface-enhanced infrared absorption (SEIRA) is one of such processes and can particularly benefit from plasmon-enhanced local fields yielding an increase in sensitivity towards the detection of an analyte. Herein, we have fabricated a series of gold dendritic nanostructures, prepared by electron-beam lithography, that exhibit plasmon resonances spanning the near and mid-infrared spectral regions. We explore the influence of the number of branches of the dendritic structures, as well as the length of each generation together with the overall effect of the shape and symmetry on the resulting optica

Incidence of Influenza in Healthy Adults and Healthcare Workers: A Systematic Review and Meta-Analysis

BACKGROUND: Working in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs). METHODS AND FINDINGS: We searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction. From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs. CONCLUSIONS: Compared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza

Mitigating effects of vaccination on influenza outbreaks given constraints in stockpile size and daily administration capacity

<p>Abstract</p> <p>Background</p> <p>Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination <it>proportional </it>to the population at each point in time.</p> <p>Methods</p> <p>We present a SIR-like model that explicitly takes into account vaccine supply and the <it>number </it>of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the <it>non-proportional </it>model of vaccination and compare it to the proportional scheme typically found in the literature.</p> <p>Results</p> <p>The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity.</p> <p>Conclusions</p> <p>The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing nations with a wide variety of financial and medical resources. Finally, the model can be used by government and medical officials to create customized pandemic preparedness plans based on the supply and administration constraints of specific communities.</p

p65 Negatively Regulates Transcription of the Cyclin E Gene*

NF-κB family members play a pivotal role in many cellular and organismal functions, including the cell cycle. As an activator of cyclin D1 and p21Waf1 genes, NF-κB has been regarded as a critical modulator of cell cycle. To study the involvement of NF-κB in G1/S phase regulation, the levels of selected transcriptional regulators were monitored following overexpression of NF-κB or its physiological induction by tumor necrosis factor-α. Cyclin E gene was identified as a major transcriptional target of NF-κB. Recruitment of NF-κB to the cyclin E promoter was correlated with the transrepression of cyclin E gene. Ligation-mediated PCR and micrococcal nuclease-Southern assays suggested the nucleosomal nature of this region while chromatin immunoprecipitation analysis confirmed the exchange of cofactors following tumor necrosis factor-α treatment or release from serum starvation. There was a progressive reduction in cyclin E transcription along with the accumulation of catalytically inactive cyclin E-cdk2 complexes and arrest of cells in G1/S-phase. Thus, our study clearly establishes NF-κB as a negative regulator of cell cycle through transcriptional repression of cyclin E

Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production

<div><p>Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.</p></div