Description: A passive, 20-element, short-period (1 Hz) and broadband seismic array was deployed over the Chicxulub impact structure for c. 100 days in early 1996. The principal objective was to study the shear-wave anisotropy associated with the structure; in particular, to determine the presence (or absence= of radial symmetry which will allow comment on the time variance of that anisotropy. A total of 15 teleseismic, 75 regional, and 100 local events were recorded. Preliminary results from studies of the surface-wave dispersion of the local events, and a receiver function analysis of a single teleseismic event are reported here. Thirty local events have been located, a number of which originated from quarries within the array. Analysis of seismograms from three of these events demonstrates a bimodal distribution; those whose ray-paths cross the outer part of the impact structure show a strong inverse produced by the sedimentary depositional environment, with deeper water sedimentation in the outer part of the post-impact crater basin and shallower water sedimentation over the upraised peak-ring block at the centre. Receiver functions derived for an event originating in Peru are dominated by an efficient mode conversion, simply modelled as a P-S multiple from the base Tertiary boundary. This shows a strong correlation with distance from the centre of the impact structure and implies it has an S-wave radial symmetry. The multiple also has a variable delay probably related to the depth of the conversion boundary. Unfortunately, the Moho conversion occurs at almost exactly the same time as this surface layer sediment multiple, restricting any modelling of Moho topography and its influence on the receiver functions.

Description: We have synthesized a novel derivative of indomethacin, phospho-tyrosol-indomethacin (PTI; MPI-621), and evaluated its anticancer efficacy in vitro and in vivo . PTI inhibited the growth of human colon, breast and lung cancer cell lines 6–30-fold more potently than indomethacin. In vivo , in contrast to indomethacin that was unable to inhibit colon cancer xenograft growth, PTI inhibited the growth of colon (69% at 10mg/kg/day, P 〈 0.01) and lung (91% at 15mg/kg/day, P 〈 0.01) subcutaneous cancer xenografts in immunodeficient mice, suppressing cell proliferation by 33% and inducing apoptosis by 75% ( P 〈 0.05, for both). Regarding its pharmacokinetics in mice, after a single intraperitoneal injection of PTI, its plasma levels reached the maximum concentration ( C max = 46 μM) at 2h ( T max ) and became undetectable at 4h. Indomethacin is the major metabolite of PTI, with plasma C max = 378 μM and T max = 2.5h; it became undetectable 24h postadministration. The cellular uptake of PTI (50–200 μM) at 6h was about 200-fold greater than that of indomethacin. Regarding its safety, PTI had no significant genotoxicity, showed less gastrointestinal toxicity than indomethacin and presented no cardiac toxicity. Mechanistically, PTI suppressed prostaglandin E 2 production in A549 human lung cancer cells and strongly inhibited nuclear factor-B activation in A549 xenografts. These findings indicate that PTI merits further evaluation as an anticancer agent.

Description: The enigma of the Bahamas is that this highly productive carbonate system has existed for at least 100 m.y., building a vast edifice of carbonates, thousands of meters thick, in an essentially nutrient-poor environment. Based on measurements of the insoluble material, the Fe and Mn in the carbonate fraction, and the 15 N of the sedimentary organic matter, we suggest a paradigm shift in order to explain the formation of the Bahamas and possibly other similar platforms. We propose that the Great Bahama Bank is currently, and may in the past have been, fertilized by atmospheric dust, promoting the fixation of atmospheric N 2 by cyanobacteria. These cyanobacteria provided a source of nitrogen to the rest of the community in this nutrient-poor environment. The fixation of N has imparted a characteristic 15 N signal and has been responsible, through the drawdown of CO 2 , for initiating the precipitation of carbonate in the shallow waters. This phenomenon might be responsible for the formation of vast amounts of sediments in the oceans, not only within recent times, but throughout geological history, particularly in the early history of the Earth prior to the existence of calcium carbonate–secreting organisms.

Description: Kingella kingae is a human pathogen that causes pediatric osteoarticular infections and infective endocarditis in children and adults. The bacterium is usually susceptible to β-lactam antibiotics, although β-lactam resistance has been reported in rare isolates. This study was conducted to identify β-lactam-resistant strains and to characterize the resistance mechanism. Screening of a set of 90 K. kingae clinical isolates obtained from different geographic locations revealed high-level resistance to penicillins among 25% of the strains isolated from Minnesota and Iceland. These strains produced TEM-1 β-lactamase and were shown to contain additional ≥50-kb plasmids. Ion Torrent sequencing of extrachromosomal DNA from a β-lactamase-producing strain confirmed the plasmid location of the bla TEM gene. An identical plasmid pattern was demonstrated by multiplex PCR in all β-lactamase producers. The porin gene's fragments were analyzed to investigate the relatedness of bacterial strains. Phylogenetic analysis revealed 27 single-nucleotide polymorphisms (SNPs) in the por gene fragment, resulting in two major clusters with 11 allele types forming bacterial-strain subclusters. β-Lactamase producers were grouped together based on por genotyping. Our results suggest that the β-lactamase-producing strains likely originate from a single plasmid-bearing K. kingae isolate that traveled from Europe to the United States, or vice versa. This study highlights the prevalence of penicillin resistance among K. kingae strains in some regions and emphasizes the importance of surveillance for antibiotic resistance of the pathogen.

Description: It can be more challenging to efficiently model the covariance matrices for multivariate longitudinal data than for the univariate case, due to the correlations arising between multiple responses. The positive-definiteness constraint and the high dimensionality are further obstacles in covariance modelling. In this paper, we develop a data-based method by which the parameters in the covariance matrices are replaced by unconstrained and interpretable parameters with reduced dimensions. The maximum likelihood estimators for the mean and covariance parameters are shown to be consistent and asymptotically normally distributed. Simulations and real data analysis show that the new approach performs very well even when modelling bivariate nonstationary dependence structures.

Description: Langmuir DOI: 10.1021/acs.langmuir.6b02641

Description: Langmuir DOI: 10.1021/acs.langmuir.6b00061

Description: Given that glioblastoma multiforme (GBM) is associated with poor prognosis, new agents are urgently needed. We developed phospho-glycerol-ibuprofen-amide (PGIA), a novel ibuprofen derivative, and evaluated its safety and efficacy in preclinical models of GBM, and its mechanism of action using human GBM cells and animal tumor models. Furthermore, we explored whether formulating PGIA in polymeric nanoparticles could enhance its levels in the brain. PGIA was 3.7- to 5.1-fold more potent than ibuprofen in suppressing the growth of human GBM cell lines. PGIA 0.75 x IC 50 inhibited cell proliferation by 91 and 87% in human LN-229 and U87-MG GBM cells, respectively, and induced strong G 1 /S arrest. In vivo , compared with control, PGIA reduced U118-MG and U87-MG xenograft growth by 77 and 56%, respectively ( P 〈 0.05), and was 〉2-fold more efficacious than ibuprofen. Normal human astrocytes were resistant to PGIA, indicating selectivity. Mechanistically, PGIA reduced cyclin D1 levels in a time- and concentration-dependent manner in GBM cells and in xenografts. PGIA induced cyclin D1 degradation via the proteasome pathway and induced dephosphorylation of GSK3β, which was required for cyclin D1 turnover. Furthermore, cyclin D1 overexpression rescued GBM cells from the cell growth inhibition by PGIA. Moreover, the formulation of PGIA in poly-( l )-lactic acid poly(ethylene glycol) polymeric nanoparticles improved its pharmacokinetics in mice, delivering PGIA to the brain. PGIA displays strong efficacy against GBM, crosses the blood-brain barrier when properly formulated, reaching the target tissue, and establishes cyclin D1 as an important molecular target. Thus, PGIA merits further evaluation as a potential therapeutic option for GBM.

Description: Objective Prostate-specific antigen (PSA) screening is controversial. A community jury allows presentation of complex information and may clarify how participants view screening after being well-informed. We examined whether participating in a community jury had an effect on men's knowledge about and their intention to participate in PSA screening. Design Random allocation to either a 2-day community jury or a control group, with preassessment, postassessment and 3-month follow-up assessment. Setting Participants from the Gold Coast (Australia) recruited via radio, newspaper and community meetings. Participants Twenty-six men aged 50–70 years with no previous diagnosis of prostate cancer. Intervention The control group (n=14) received factsheets on PSA screening. Community jury participants (n=12) received the same factsheets and further information about screening for prostate cancer. In addition, three experts presented information on PSA screening: a neutral scientific advisor provided background information, one expert emphasised the potential benefits of screening and another expert emphasised the potential harms. Participants discussed information, asked questions to the experts and deliberated on personal and policy decisions. Main outcome and measures Our primary outcome was change in individual intention to have a PSA screening test. We also assessed knowledge about screening for prostate cancer. Results Analyses were conducted using intention-to-treat. Immediately after the jury, the community jury group had less intention-to-screen for prostate cancer than men in the control group (effect size=–0.6 SD, p=0.05). This was sustained at 3-month follow-up. Community jury men also correctly identified PSA test accuracy and considered themselves more informed (effect size=1.2 SD, p〈0.001). Conclusions Evidence-informed deliberation of the harms and benefits of PSA screening effects men's individual choice to be screened for prostate cancer. Community juries may be a valid method for eliciting target group input to policy decisions. Trial registration number Australian and New Zealand Clinical Trials Registry (ACTRN12612001079831).

Description: Organic Letters DOI: 10.1021/acs.orglett.5b02680