A Global Health Partnership's Use of Time-Limited Support to Catalyze Health Practice Change: The Case of GAVI's Injection Safety Support

This paper presents the findings of a study to assess the effectiveness and sustainability of a GAVI (Global Alliance of Vaccines and Immunization) sponsored, time-limited Injection Safety (INS) support. The support came in two forms: 1) in-kind, in the form of AD syringes and safety boxes, and 2) in cash, for those countries that already had a secure, multi-year source of AD syringes and safety boxes, but proposed to use INS support to strengthen their injection safety activities. In total, GAVI gave INS support for a three-year period to 58 countries: 46 with commodities and 12 with cash support. To identify variables that might be associated with financial sustainability, frequencies and cross-tabulations were run against various programmatic and socio-economic variables in the 58 countries. All but two of the 46 commodity-recipient countries were able to replace and sustain the use of AD syringes and safety boxes after the end of their GAVI INS support despite the fact that standard disposable syringes are less costly than ADs (10–15 percent differential). In addition, all 12 cash-recipient countries continued to use AD syringes and safety boxes in their immunization programs in the years following GAVI INS assistance. At the same time, countries were often not prepared for the increased waste management requirements associated with the use of the syringes, suggesting the importance of anticipating challenges with the introduction of new technologies. The sustained use of AD syringes in countries receiving injection safety support from GAVI, in a majority of cases through government financing, following the completion of three years of time-limited support, represents an early indication of how GHPs can contribute to improved health outcomes in immunization safety in the world's poorest countries in a sustainable way

Real-time single-molecule observation of rolling-circle DNA replication

We present a simple technique for visualizing replication of individual DNA molecules in real time. By attaching a rolling-circle substrate to a TIRF microscope-mounted flow chamber, we are able to monitor the progression of single-DNA synthesis events and accurately measure rates and processivities of single T7 and Escherichia coli replisomes as they replicate DNA. This method allows for rapid and precise characterization of the kinetics of DNA synthesis and the effects of replication inhibitors

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Solar Energetic Particle Spectrum on 13 December 2006 Determined by IceTop

On 13 December 2006 the IceTop air shower array at the South Pole detected a major solar particle event. By numerically simulating the response of the IceTop tanks, which are thick Cherenkov detectors with multiple thresholds deployed at high altitude with no geomagnetic cut-off, we determined the particle energy spectrum in the energy range 0.6 to 7.6 GeV. This is the first such spectral measurement using a single instrument with a well defined viewing direction. We compare the IceTop spectrum and its time evolution with previously published results and outline plans for improved resolution of future solar particle spectra.Comment: To appear in Astrophysical Journal Letters, 6 pages, 4 figure

In vitro nuclear interactome of the HIV-1 Tat protein

<p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

Evolution of pygmy angelfishes: Recent divergences, introgression, and the usefulness of color in taxonomy

The pygmy angelfishes (genus Centropyge, family Pomacanthidae) are brightly colored species that occupy reef habitats in every tropical ocean. Some species are rarely observed because they occur below conventional scuba depths. Their striking coloration can command thousands of U.S. dollars in the aquarium trade, and closely related species are often distinguished only by coloration. These factors have impeded phylogenetic resolution, and every phylogeographic survey to date has reported discordance between coloration, taxonomy, and genetic partitions. Here we report a phylogenetic survey of 29 of the 34 recognized species (N= 94 plus 23 outgroups), based on two mtDNA and three nuclear loci, totaling 2272. bp. The resulting ML and Baysian trees are highly concordant and indicate that the genus Centropyge is paraphyletic, consistent with a previous analysis of the family Pomacanthidae. Two recognized genera (Apolemichthys and Genicanthus) nest within Centropyge, and two subgenera (Xiphypops and Paracentropyge) comprise monophyletic lineages that should be elevated to genus level. Based on an age estimate of 38. Ma for the family Pomacanthidae, Centropyge diverged from the closest extant genus Pygoplites about 33. Ma, three deep lineages within Centropyge diverged about 18-28. Ma, and four species complexes diverged 3-12. Ma. However, in 11 of 13 cases, putative species in these complexes are indistinguishable based on morphology and genetics, being defined solely by coloration. These cases indicate either emerging species or excessive taxonomic splitting based on brightly colored variants. © 2014 Elsevier Inc

Kinetic Model under Light-Limited Condition for Photoinitiated Thiol–Ene Coupling Reactions

© 2018 American Chemical Society. Thiol-ene click chemistry has become a powerful paradigm in synthesis, materials science, and surface modification in the past decade. In the photoinitiated thiol-ene reaction, an induction period is often observed before the major change in its kinetic curve, for which a possible mechanism is proposed in this report. Briefly, light soaking generates radicals following the zeroth-order reaction kinetics. The radical is the reactant that initializes the chain reaction of thiol-ene coupling, which is a first-order reaction. Combining both and under the light-limited conditions, a surprising kinetics represented by a Gaussian-like model evolves that is different from the exponential model used to describe the first-order reaction of the final product. The experimental data are fitted well with the new model, and the reaction kinetic constants can be pulled out from the fitting