Independent Evaluation of Phase 1 of the Affordable Medicines Facility - malaria (AMFm), Multi-Country Independent Evaluation Final Report

The success of malaria control efforts depends on a high level of coverage in the use of effective antimalarials such as artemisinin-based combination therapies (ACTs). Although these anti-malarials have been procured in large amounts by countries, evidence suggests that ACT use still remains far below target levels. In response to this issue, the Affordable Medicines Facility – malaria (AMFm) hosted by the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) was set up. AMFm comprises three key elements: (i) price reductions through negotiations with ACT manufacturers; (ii) a buyer subsidy through a ‘co-payment’ for ACTs at the top of the global supply chain; and (iii) supporting interventions to promote appropriate use of ACTs. Examples of these supporting interventions include training providers and outreach to communities to promote ACT use. All ACTs subsidized through AMFm bear a green leaf logo on their packaging. The four main objectives of AMFm are to: (i) increase ACT affordability; (ii) increase ACT availability; (iii) increase ACT use, including among vulnerable groups; and (iv) “crowd out” oral artemisinin monotherapies, chloroquine and sulfadoxine-pyrimethamine (SP) by increasing the market share for ACTs

Spatially-resolved electronic and vibronic properties of single diamondoid molecules

Diamondoids are a unique form of carbon nanostructure best described as hydrogen-terminated diamond molecules. Their diamond-cage structures and tetrahedral sp3 hybrid bonding create new possibilities for tuning electronic band gaps, optical properties, thermal transport, and mechanical strength at the nanoscale. The recently-discovered higher diamondoids (each containing more than three diamond cells) have thus generated much excitement in regards to their potential versatility as nanoscale devices. Despite this excitement, however, very little is known about the properties of isolated diamondoids on metal surfaces, a very relevant system for molecular electronics. Here we report the first molecular scale study of individual tetramantane diamondoids on Au(111) using scanning tunneling microscopy and spectroscopy. We find that both the diamondoid electronic structure and electron-vibrational coupling exhibit unique spatial distributions characterized by pronounced line nodes across the molecular surfaces. Ab-initio pseudopotential density functional calculations reveal that the observed dominant electronic and vibronic properties of diamondoids are determined by surface hydrogen terminations, a feature having important implications for designing diamondoid-based molecular devices.Comment: 16 pages, 4 figures. to appear in Nature Material

The heavy top quark in the two Higgs doublet model

Constraints on the two Higgs doublet model are presented, assuming a top mass of 174 $\pm$ 17 GeV. We concentrate primarily on the ``type II'' model, where up--type quarks receive their mass from one Higgs doublet, and down--type quarks receive their mass from the second doublet. High energy constraints derived from the $W$ mass, the full width of the $Z$ and the $b \bar b$ partial width of the $Z$ are combined with low energy constraints from $\Gamma(b\to s \gamma)$, $\Gamma(b \to c \tau \bar\nu_\tau)$ and $B^0$-$\bar B^0$ mixing to determine the experimentally favored configurations of the model. This combination of observables rules out small charged Higgs masses and small values of $\tan\beta$, and provides some information about the neutral Higgs masses and the mixing angle $\alpha$. In particular, constraints derived from the $\rho$ parameter rule out configurations where the charged Higgs is much heavier or much lighter than the neutral Higgses. We discuss a scenario where $\Gamma(Z\to b \bar b)$ is enhanced relative to the standard model result, which unfortunately is on the verge of being ruled out by the combination of $\Gamma(b\to s \gamma)$ and $\rho$ parameter constraints. Implications for various extensions of the standard model are briefly discussed.Comment: 26 page

Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes

We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re

The Buffer Gas Beam: An Intense, Cold, and Slow Source for Atoms and Molecules

Beams of atoms and molecules are stalwart tools for spectroscopy and studies of collisional processes. The supersonic expansion technique can create cold beams of many species of atoms and molecules. However, the resulting beam is typically moving at a speed of 300-600 m/s in the lab frame, and for a large class of species has insufficient flux (i.e. brightness) for important applications. In contrast, buffer gas beams can be a superior method in many cases, producing cold and relatively slow molecules in the lab frame with high brightness and great versatility. There are basic differences between supersonic and buffer gas cooled beams regarding particular technological advantages and constraints. At present, it is clear that not all of the possible variations on the buffer gas method have been studied. In this review, we will present a survey of the current state of the art in buffer gas beams, and explore some of the possible future directions that these new methods might take

Immunoelectron Microscopic Evidence for Tetherin/BST2 as the Physical Bridge between HIV-1 Virions and the Plasma Membrane

Tetherin/BST2 was identified in 2008 as the cellular factor responsible for restricting HIV-1 replication at a very late stage in the lifecycle. Tetherin acts to retain virion particles on the plasma membrane after budding has been completed. Infected cells that express large amounts of tetherin display large strings of HIV virions that remain attached to the plasma membrane. Vpu is an HIV-1 accessory protein that specifically counteracts the restriction to virus release contributed by tetherin. Tetherin is an unusual Type II transmembrane protein that contains a GPI anchor at its C-terminus and is found in lipid rafts. The leading model for the mechanism of action of tetherin is that it functions as a direct physical tether bridging virions and the plasma membrane. However, evidence that tetherin functions as a physical tether has thus far been indirect. Here we demonstrate by biochemical and immunoelectron microscopic methods that endogenous tetherin is present on the viral particle and forms a bridge between virion particles and the plasma membrane. Endogenous tetherin was found on HIV particles that were released by partial proteolytic digestion. Immunoelectron microscopy performed on HIV-infected T cells demonstrated that tetherin forms an apparent physical link between virions and connects patches of virions to the plasma membrane. Linear filamentous strands that were highly enriched in tetherin bridged the space between some virions. We conclude that tetherin is the physical tether linking HIV-1 virions and the plasma membrane. The presence of filaments with which multiple molecules of tetherin interact in connecting virion particles is strongly suggested by the morphologic evidence

Competing electric and magnetic excitations in backward electron scattering from heavy deformed nuclei

Important $E2$ contributions to the $(e,e^{\prime})$ cross sections of low-lying orbital $M1$ excitations are found in heavy deformed nuclei, arising from the small energy separation between the two excitations with $I^{\pi}K = 2^+1$ and 1$^+1$, respectively. They are studied microscopically in QRPA using DWBA. The accompanying $E2$ response is negligible at small momentum transfer $q$ but contributes substantially to the cross sections measured at $\theta = 165 ^{\circ}$ for $0.6 < q_{\rm eff} < 0.9$ fm$^{-1}$ ($40 \le E_i \le 70$ MeV) and leads to a very good agreement with experiment. The electric response is of longitudinal $C2$ type for $\theta \le 175 ^{\circ}$ but becomes almost purely transverse $E2$ for larger backward angles. The transverse $E2$ response remains comparable with the $M1$ response for $q_{\rm eff} > 1.2$ fm$^{-1}$ ($E_i > 100$ MeV) and even dominant for $E_i > 200$ MeV. This happens even at large backward angles $\theta > 175 ^{\circ}$, where the $M1$ dominance is limited to the lower $q$ region.Comment: RevTeX, 19 pages, 8 figures included Accepted for publication in Phys Rev

Osteoarthritic changes in vervet monkey knees correlate with meniscus degradation and increased matrix metalloproteinase and cytokine secretion

Meniscus injury increases osteoarthritis risk but its pathobiology in osteoarthritis is unclear. We hypothesized that older adult vervet monkeys would exhibit knee osteoarthritic changes and the degenerative menisci from these animals would secrete matrix metalloproteinases (MMPs) and pro-inflammatory cytokines that contribute to the development of osteoarthritis

Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1maturation inhibitor bevirimat

Background: The maturation inhibitor bevirimat (BVM) potently inhibits human immunodeficiency virus type 1 (HIV-1) replication by blocking capsid-spacer peptide 1 (CA-SP1) cleavage. Recent clinical trials demonstrated that a significant proportion of HIV-1-infected patients do not respond to BVM. A patient’s failure to respond correlated with baseline polymorphisms at SP1 residues 6-8. Results: In this study, we demonstrate that varying levels of BVM resistance are associated with point mutations at these residues. BVM susceptibility was maintained by SP1-Q6A, -Q6H and -T8A mutations. However, an SP1-V7A mutation conferred high-level BVM resistance and SP1-V7M and T8Δ mutations conferred intermediate levels of BVM resistance. Conclusions: Future exploitation of the CA-SP1 cleavage site as an antiretroviral drug target will need to overcome the baseline variability in the SP1 region of Gag.Publisher PDFPeer reviewe

Constraints on the Mass and Mixing of the 4th Generation Quark From Direct CP Violationϵ′/ϵ\epsilon^{\prime}/\epsilon and Rare K Decays

We investigate the $\epsilon^{\prime} /\epsilon$ for $K\to \pi\pi$ in a sequential fourth generation model. By giving the basic formulae for $\epsilon^{\prime}/\epsilon$ in this model, we analyze the numerical results which are dependent of $m_{t^{\prime}}$ and imaginary part of the fourth CKM factor, ${Im}V^{*}_{t^{'}s}V_{t^{'}d}$ (or $V^{*}_{t^{'}s}V_{t^{'}d}$ and the fourth generation CKM matrix phase $\theta$). We find that, unlike the SM, when taking the central values of all parameters for $\epsilon^{\prime}/\epsilon$, the values of $\epsilon^{\prime}/ \epsilon$ can easily fit to the current experimental data for all values of hadronic matrix elements estimated from various approaches. Also, we show that the experimental values of $\epsilon^{\prime}/\epsilon$ and rare K decays can provide a strong constraint on both mass and mixing of the fourth generation quark. When taking the values of hadronic matrix elements from the lattice or 1/N expansion calculations, a large region of the up-type quark mass $m_{t^{\prime}}$ is excluded.Comment: 18 pages, 4 eps figure