Oligon-coated contact lens case study: The efficacy of oligodynamic iontophoresis as a contact lens disinfection system as determined by FDA stand-alone protocol

Prototype contact lens cases have been prepared which are coated with an Oligon antimicrobial silicone formulation. The Oligon silicone coating incorporates a conductive additive, silver and platinum powder to set up an electrochemical system, that when contacted by chloride ions found in physiological saline, releases silver ions into the surrounding aqueous medium. Silver ions have been reported in the literature to be a potent antimicrobial agent, showing effectiveness against both gram-positive and gram-negative bacteria as well as yeasts and molds. This study was designed to study the effectiveness of Oligon coated contact lens cases against FDA (Food and Drug Administration) approved Stand Alone protocol for disinfecting contact lenses for the following organisms: Psuedomonas aeruginosa, Serratia marcenscens, Staphylococcus aureus, Candida albicans, and Fusarium solani. The results of the study conclude that the Oligon cases do not meet the 8 hour FDA stand alone criteria for any of the organisms tested, but with modification, may be an exciting new frontier for the future of contact lens disinfection

Addendum: "The Dynamics of M15: Observations of the Velocity Dispersion Profile and Fokker-Planck Models" (ApJ, 481, 267 [1997])

It has recently come to our attention that there are axis scale errors in three of the figures of Dull et al. (1997, hereafter D97). D97 presented Fokker-Planck models for the collapsed-core globular cluster M15 that include a dense, centrally concentrated population of neutron stars and massive white dwarfs, but do not include a central black hole. In this Addendum, we present corrected versions of Figures 9, 10, and 12, and an expanded version of Figure 6. This latter figure, which shows the full run of the velocity dispersion profile, indicates that the D97 model predictions are in good agreement with the moderately rising HST-STIS velocity dispersion profile for M15 reported by Gerssen et al. (2002, astro-ph/0209315). Thus, a central black hole is not required to fit the new STIS velocity measurements, provided that there is a sufficient population of neutron stars and massive white dwarfs. This conclusion is consistent with the findings of Gerssen et al. (2002, astro-ph/0210158), based on a reapplication of their Jeans equation analysis using the corrected mass-to-light profile (Figure 12) for the D97 models.Comment: 4 pages, 4 figures, submitted to Ap

Identification of Four Potential Epigenetic Modulators from the NCI Structural Diversity Library Using a Cell-Based Assay

Epigenetic pathways help control the expression of genes. In cancer and other diseases, aberrant silencing or overexpression of genes, such as those that control cell growth, can greatly contribute to pathogenesis. Access to these genes by the transcriptional machinery is largely mediated by chemical modifications of DNA or histones, which are controlled by epigenetic enzymes, making these enzymes attractive targets for drug discovery. Here we describe the characterization of a locus derepression assay, a fluorescence-based mammalian cellular system which was used to screen the NCI structural diversity library for novel epigenetic modulators using an automated imaging platform. Four structurally unique compounds were uncovered that, when further investigated, showed distinct activities. These compounds block the viability of lung cancer and melanoma cells, prevent cell cycle progression, and/or inhibit histone deacetylase activity, altering levels of cellular histone acetylation

Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase

BACKGROUND Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies where we demonstrated amide-type local anaesthetics block TNFα-induced Src activation in malignant cells, we hypothesized that local anaesthetics might also inhibit the activation and/or phosphorylation of Akt, FAK and caveolin-1, thus attenuating MMP release and invasion of malignant cells. METHODS NCI-H838 lung adenocarcinoma cells were incubated with ropivacaine or lidocaine (1 nM-100 µM) in absence/presence of TNFα (20 ng ml(-1)) for 20 min or 4 h, respectively. Activation/phosphorylation of Akt, FAK and caveolin-1 were evaluated by Western blot, and MMP-9 secretion was determined by enzyme-linked immunosorbent assay. Tumour cell migration (electrical wound-healing assay) and invasion were also assessed. RESULTS Ropivacaine (1 nM-100 μM) and lidocaine (1-100 µM) significantly reduced TNFα-induced activation/phosphorylation of Akt, FAK and caveolin-1 in NCI-H838 cells. MMP-9 secretion triggered by TNFα was significantly attenuated by both lidocaine and ropivacaine (half-maximal inhibitory concentration [IC50]=3.29×10(-6) M for lidocaine; IC50=1.52×10(-10) M for ropivacaine). The TNFα-induced increase in invasion was completely blocked by both lidocaine (10 µM) and ropivacaine (1 µM). CONCLUSIONS At clinically relevant concentrations both ropivacaine and lidocaine blocked tumour cell invasion and MMP-9 secretion by attenuating Src-dependent inflammatory signalling events. Although determined entirely in vitro, these findings provide significant insight into the potential mechanism by which local anaesthetics might diminish metastasi

Evidence for antibody as a protective correlate for COVID-19 vaccines

A correlate of protection (CoP) is urgently needed to expedite development of additional COVID-19 vaccines to meet unprecedented global demand. To assess whether antibody titers may reasonably predict efficacy and serve as the basis of a CoP, we evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccines for which sufficient data have been generated. Once calibrated to titers of human convalescent sera reported in each study, a robust correlation was seen between neutralizing titer and efficacy (ρ = 0.79) and binding antibody titer and efficacy (ρ = 0.93), despite geographically diverse study populations subject to different forces of infection and circulating variants, and use of different endpoints, assays, convalescent sera panels and manufacturing platforms. Together with evidence from natural history studies and animal models, these results support the use of post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccines

External Mass Accumulation onto Core Potentials: Implications for Star Clusters, Galaxies and Galaxy Clusters

Accretion studies have been focused on the flow around bodies with point mass gravitational potentials, but few general results are available for non-point mass distributions. Here, we study the accretion flow onto non-divergent, core potentials moving through a background medium. We use Plummer and Hernquist potentials as examples to study gas accretion onto star clusters, dwarf and large galaxy halos and galaxy clusters in a variety of astrophysical environments. The general conditions required for a core potential to collectively accrete large quantities of gas from the external medium are derived using both simulations and analytic results. The consequences of large mass accumulation in galaxy nuclei, dwarf galaxies and star clusters are twofold. First, if the gas cools effectively star formation can be triggered, generating new stellar members in the system. Second, if the collective potential of the system is able to alter the ambient gas properties before the gas is accreted onto the individual core members, the augmented mass supply rates could significantly alter the state of the various accreting stellar populations and result in an enhanced central black hole accretion luminosity.Comment: 24 pages, 15 figures, accepted to Ap

Towards a population-based threshold of protection for COVID-19 vaccines

Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with efficacies for protection against infection with wild-type, alpha and delta variant SARS-CoV-2 virus. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies for WT virus was 154 BAU/ml (95 %CI 42–559), and for studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA regimens) was 60 BAU/ml (95 %CI 35–102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious

An overview of the Michigan Positron Microscope Program

An overview of the Michigan Positron Microscope Program is presented with particular emphasis on the second generation microscope that is presently near completion. The design and intended applications of this microscope will be summarized.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87602/2/391_1.pd

Measuring gravitational waves from binary black hole coalescences: I. Signal to noise for inspiral, merger, and ringdown

We estimate the expected signal-to-noise ratios (SNRs) from the three phases (inspiral,merger,ringdown) of coalescing binary black holes (BBHs) for initial and advanced ground-based interferometers (LIGO/VIRGO) and for space-based interferometers (LISA). LIGO/VIRGO can do moderate SNR (a few tens), moderate accuracy studies of BBH coalescences in the mass range of a few to about 2000 solar masses; LISA can do high SNR (of order 10^4) high accuracy studies in the mass range of about 10^5 to 10^8 solar masses. BBHs might well be the first sources detected by LIGO/VIRGO: they are visible to much larger distances (up to 500 Mpc by initial interferometers) than coalescing neutron star binaries (heretofore regarded as the "bread and butter" workhorse source for LIGO/VIRGO, visible to about 30 Mpc by initial interferometers). Low-mass BBHs (up to 50 solar masses for initial LIGO interferometers; 100 for advanced; 10^6 for LISA) are best searched for via their well-understood inspiral waves; higher mass BBHs must be searched for via their poorly understood merger waves and/or their well-understood ringdown waves. A matched filtering search for massive BBHs based on ringdown waves should be capable of finding BBHs in the mass range of about 100 to 700 solar masses out to 200 Mpc (initial LIGO interferometers), and 200 to 3000 solar masses out to about z=1 (advanced interferometers). The required number of templates is of order 6000 or less. Searches based on merger waves could increase the number of detected massive BBHs by a factor of order 10 or more over those found from inspiral and ringdown waves, without detailed knowledge of the waveform shapes, using a "noise monitoring" search algorithm. A full set of merger templates from numerical relativity could further increase the number of detected BBHs by an additional factor of up to 4.Comment: 40 pages, Revtex, psfig.tex, seven figures, submitted to Phys Rev