Stemming the Global Trade in Falsified and Substandard Medicines

Drug safety and quality is an essential assumption of clinical medicine, but there is growing concern that this assumption is not always correct. Poor manufacturing and deliberate fraud occasionally compromises the drug supply in the United States, and the problem is far more common and serious in low- and middle-income countries with weak drug regulatory systems. An Institute of Medicine consensus committee report identified the causes and possible solutions to the problem of falsified and substandard drugs around the world. The vocabulary people use to discuss the problem is itself a concern. The word counterfeit is often used innocuously to describe any drug that is not what it seems, but some NGOs and emerging manufacturing nations object to this term. These groups see hostility to generic pharmaceuticals in a discussion of counterfeit medicines. These groups see hostility to generic pharmaceuticals in a discussion of counterfeit medicines. Precisely speaking, a counterfeit drug infringes on a registered trademark, and trademark infringement in not necessarily a problem of public health consequence. Instead of talking broadly about counterfeit drugs, the WHO and other stakeholders should consider two main categories of drug quality problems. Falsified medicines misrepresent the product’s identity or source or both. Substandard drugs fail to meet the national specifications given in an accepted pharmacopeia or the manufacturer’s dossier. In practice, there is often considerable overlap between categories. There is considerable uncertainty about the size of the falsified and substandard drug market. Improved pharmacovigilance, especially in developing countries, give a better picture of the scope of the problem. In the United States, tighter regulatory controls on the wholesale market and a mandatory drug tracking system would improve drug safety. In developing countries, development finance organizations should invest in small- and medium-sized pharmaceutical manufacturers, and governments should use tools such as franchising, accreditation, low-interest loans, and task shifting to encourage private sector investment in drug retail. Finally, the WHO should work with stakeholders such as the UNODC and the WCO to develop an international code of practice on falsified and substandard drugs

New Constraints on Neutralino Dark Matter in the Supersymmetric Standard Model

We investigate the prospects for neutralino dark matter within the Supersymmetric Standard Model (SSM) including the constraints from universal soft supersymmetry breaking and radiative breaking of the electroweak symmetry. The latter is enforced by using the one-loop Higgs effective potential which automatically gives the one-loop corrected Higgs boson masses. We perform an exhaustive search of the allowed five-dimensional parameter space and find that the neutralino relic abundance $\Omega_\chi h^2_0$ depends most strongly on the ratio $\xi_0\equiv m_0/m_{1/2}$. For $\xi_0\gg1$ the relic abundance is almost always much too large, whereas for $\xi_0\ll1$ the opposite occurs. For $\xi_0\sim1$ there are wide ranges of the remaining parameters for which $\Omega_\chi\sim1$. We also determine that m_{\tilde q}\gsim250\GeV and m_{\tilde l}\gsim100\GeV are necessary in order to possibly achieve $\Omega_\chi\sim1$. These lower bounds are much weaker than the corresponding ones derived previously when radiative breaking was {\it not} enforced.Comment: 12 pages plus 6 figures (not included), CERN-TH.6584/92, CTP-TAMU-56/92, UAHEP921

Hindered Rotation in Methyl Alcohol with Note on Ethyl Alcohol

The potential barrier to the internal rotation in methyl alcohol is recalculated from the entropy with the aid of new molecular dimensions generously provided by Burkhard and Dennison. The barrier calculation is examined for temperature dependence and checked for reliability by recalculation with the Clapeyron equation substituted for parts of the data. The result is 1600±700 cal./mole, which includes the new spectroscopic barrier of Burkhard and Dennison at 326 cm−1. Within the range covered by the result, a residual entropy up to 0.50 cal./mole deg. is possible, and the retention of 0.46 e.u. by the crystal is consistent with a reasonable simple assumption about the distribution of hydrogen bonds.It is suggested, by analogy, that the barrier to the hydroxyl group rotation in ethyl alcohol should be about 1000 cal./mole.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71293/2/JCPSA6-18-3-361-1.pd

Spitzer observations of the asteroid-comet transition object and potential spacecraft target 107P (4015) Wilson-Harrington

Context. Near-Earth asteroid-comet transition object 107P/ (4015) Wilson-Harrington is a possible target of the joint European Space Agency (ESA) and Japanese Aerospace Exploration Agency (JAXA) Marco Polo sample return mission. Physical studies of this object are relevant to this mission, and also to understanding its asteroidal or cometary nature. Aims. Our aim is to obtain significant new constraints on the surface thermal properties of this object. Methods. We present mid-infrared photometry in two filters (16 and 22 microns) obtained with NASA's Spitzer Space Telescope on February 12, 2007, and results from the application of the Near Earth Asteroid Thermal Model (NEATM).We obtained high S/N in two mid-IR bands allowing accurate measurements of its thermal emission. Results. We obtain a well constrained beaming parameter (eta = 1.39 +/- 0.26) and obtain a diameter and geometric albedo of D = 3.46 +/- 0.32 km, and pV = 0.059 +/- 0.011. We also obtain similar results when we apply this best-fitting thermal model to single-band mid-IR photometry reported by Campins et al. (1995), Kraemer et al. (2005) and Reach et al. (2007). Conclusions. The albedo of 4015 Wilson-Harrington is low, consistent with those of comet nuclei and primitive C-, P-, D-type asteorids. We establish a rough lower limit for the thermal inertia of W-H of 60 Jm^-2s^(-0.5)K^-1 when it is at r=1AU, which is slightly over the limit of 30 Jm^-2s^(-0.5)K-1 derived by Groussin et al. (2009) for the thermal inertia of the nucleus of comet 22P/Kopff.Comment: 4 pages, 1 figure and 3 tables. Paper accepted for publicatio

Preliminary Feeding Assessments for Asiatic Garden Beetle, Maladera formosae (Coleoptera: Scarabaeidae), Grubs and Adults

The Asiatic garden beetle, Maladera formosae (Brenske) (syn. M. castanea [Arrow]), is an annual white grub species that was unintentionally introduced from east Asia to North America in 1921 in New Jersey, and has since spread to at least 25 states and two Canadian provinces. Grub populations in the Great Lakes region have recently emerged as significant early-season pests of field crops, particularly field corn, grown in sandy soils. Asiatic garden beetle has also recently become established in other regions including Alabama. Prior research on this species was conducted mainly in the 1930s in horticultural and turfgrass systems of New York and New Jersey. In this study, we document Asiatic garden beetle preference and performance on previously un-investigated food resources, in populations from Ohio and Alabama. The objectives of these experiments were to a) understand if grubs show preference to potential diet choices present in a typical Ohio corn-soybean rotation, and gained mass when provided a single diet, and b) to conduct a preliminary assessment on the development, survival, and fecundity of field-collected beetles on different diets present in suburban Alabama. In general, grubs were more likely to be found at corn and marestail and they significantly increased in body mass when subjected to those diets. However, they were also able to survive and gain mass when provided soybean, crop residues or bare soil. Adults consumed more rose flower petals than floral tissue of white clover and Queen Anne’s lace. In no-choice trials, only females that were fed a diet of rose petals laid eggs, and diet consumption rates were similar among males and females. These findings provide insight into the feeding behaviors of Asiatic garden beetle grubs and adults collected from novel environments

Accurate Neutralino Relic Density Computations in Supergravity Models

We investigate the question of the proper thermal averaging of neutralino annihilation amplitudes which possess poles and thresholds, as they impact on the calculated neutralino relic density and therefore on the cosmological viability of supersymmetric models. We focus on two typical resonances, namely the $Z$ boson and the lightest Higgs boson ($h$). In the context of supergravity models with radiative electroweak symmetry breaking, an exploration of the whole parameter space of the model is possible and the overall relevance of these sophisticated analyses can be ascertained. As an example we chose the minimal $SU(5)$ supergravity model since the presence of such poles is essential to obtain a cosmologically acceptable model. We find that the proper thermal averaging is important for individual points in parameter space and that the fraction of cosmologically acceptable points is increased somewhat by the accurate procedure. However, qualitatively the new set of points is very similar to that obtained previously using the usual series approximations to the thermal average. We conclude that all phenomenological analyses based on the previously determined cosmologically allowed set remain valid.Comment: 15 pages, 9 figures (available upon request as uuencoded file or separate ps files), tex (harvmac) CTP-TAMU-14/9

Synthetic Data and Data Formats for the GPM GMI Radiometer

No abstract availabl

Pb0.4Bi1.6Sr2Ca1Cu2O8+xPb_{0.4}Bi_{1.6}Sr_{2}Ca_{1}Cu_{2}O_{8+x} and Oxygen Stoichiometry: Structure, Resistivity, Fermi Surface Topology and Normal State Properties

$Pb_{0.4}Bi_{1.6}Sr_2CaCu_2O_{8+x}$ ($Bi(Pb)-$2212) single crystal samples were studied using transmission electron microscopy (TEM), $ab-$plane ($\rho_{ab}$) and $c-$axis ($\rho_c$) resistivity, and high resolution angle-resolved ultraviolet photoemission spectroscopy (ARUPS). TEM reveals that the modulation in the $b-$axis for $Pb(0.4)-$doped $Bi(Pb)-$2212 is dominantly of $Pb-$type that is not sensitive to the oxygen content of the system, and the system clearly shows a structure of orthorhombic symmetry. Oxygen annealed samples exhibit a much lower $c-$axis resistivity and a resistivity minimum at $80-130$K. He-annealed samples exhibit a much higher $c-$axis resistivity and $d\rho_c/dT<0$ behavior below 300K. The Fermi surface (FS) of oxygen annealed $Bi(Pb)-$2212 mapped out by ARUPS has a pocket in the FS around the $\bar{M}$ point and exhibits orthorhombic symmetry. There are flat, parallel sections of the FS, about 60\% of the maximum possible along $k_x = k_y$, and about 30\% along $k_x = - k_y$. The wavevectors connecting the flat sections are about $0.72(\pi, \pi)$ along $k_x = k_y$, and about $0.80(\pi, \pi)$ along $k_x = - k_y$, rather than $(\pi,\pi)$. The symmetry of the near-Fermi-energy dispersing states in the normal state changes between oxygen-annealed and He-annealed samples.Comment: APS_REVTEX 3.0, 49 pages, including 11 figures, available upon request. Submitted to Phys. Rev. B

Base excision repair apurinic/apyrimidinic endonucleases in apicomplexan parasite Toxoplasma gondii

DNA repair is essential for cell viability and proliferation. In addition to reactive oxygen produced as a byproduct of their own metabolism, intracellular parasites also have to manage oxidative stress generated as a defense mechanism by the host. The spontaneous loss of DNA bases due to hydrolysis and oxidative DNA damage in intracellular parasites is great, but little is known about the type of DNA repair machineries that exist in these early-branching eukaryotes. However, it is clear, processes similar to DNA base excision repair (BER) must exist to rectify spontaneous and host-mediated damage in Toxoplasma gondii. Here we report that T. gondii, an opportunistic protozoan pathogen, possesses two apurinic/apyrimidinic (AP) endonucleases that function in DNA BER. We characterize the enzymatic activities of Toxoplasma exonuclease III (ExoIII, or Ape1) and endonuclease IV (EndoIV, or Apn1), designated TgAPE and TgAPN, respectively. Over-expression of TgAPN in Toxoplasma conferred protection from DNA damage, and viable knockouts of TgAPN were not obtainable. We generated an inducible TgAPN knockdown mutant using a ligand-controlled destabilization domain to establish that TgAPN is critical for Toxoplasma to recover from DNA damage. The importance of TgAPN and the fact that humans lack any observable APN family activity highlights TgAPN as a promising candidate for drug development to treat toxoplasmosis