Study of the Ethiopian live cattle and beef value chain

Rats achieve remarkable texture discriminations by sweeping their facialwhiskers along surfaces. This work explores how neurons at two levels of the sensory pathway, trigeminal ganglion and barrel cortex, carry information about such stimuli. We identified two biologically plausible coding mechanisms, spike counts and patterns, and used “mutual information” to quantify how reliably neurons in anesthetized rats reported texture when “decoded” according to these candidate mechanisms. For discriminations between surfaces of different coarseness, spike counts could be decoded reliably and rapidly (within 30 ms after stimulus onset in cortex). Information increased as responseswere considered as spike patterns with progressively finer temporal precision. At highest temporal resolution (spike sequences across six bins of 4ms), the quantity of “information” in patterns rose 150% for ganglion neurons and 110% for cortical neurons above that in spike counts. In some cases, patterns permitted discriminations not supported by spike counts alone

APX001 Is Effective in the Treatment of Murine Invasive Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis (IPA) due to Aspergillus fumigatus is a serious fungal infection in the immunosuppressed patient population. Despite the introduction of new antifungal agents, mortality rates remain high, and new treatments are needed. The novel antifungal APX001A targets the conserved Gwt1 enzyme required for the localization of glycosylphosphatidylinositol-anchored mannoproteins in fungi. We evaluated the in vitro activity of APX001A against A. fumigatus and the in vivo activity of its prodrug APX001 in an immunosuppressed mouse model of IPA. APX001A inhibited the growth of A. fumigatus with a minimum effective concentration of 0.03 μg/ml. The use of 50 mg/kg 1-aminobenzotriazole (ABT), a suicide inhibitor of cytochrome P450 enzymes, enhanced APX001A exposures (area under the time-concentration curve [AUC]) 16- to 18-fold and enhanced serum half-life from ∼1 to 9 h, more closely mimicking human pharmacokinetics. We evaluated the efficacy of APX001 (with ABT) in treating murine IPA compared to posaconazole treatment. Treatment of mice with 78 mg/kg once daily (QD), 78 mg/kg twice daily, or 104 mg/kg QD APX001 significantly enhanced the median survival time and prolonged day 21 postinfection overall survival compared to the placebo. Furthermore, administration of APX001 resulted in a significant reduction in lung fungal burden (4.2 to 7.6 log10 conidial equivalents/g of tissue) versus the untreated control and resolved the infection, as judged by histopathological examination. The observed survival and tissue clearance were comparable to a clinically relevant posaconazole dose. These results warrant the continued development of APX001 as a broad-spectrum, first-in-class treatment of invasive fungal infections

Knowledge of hepatitis C screening and management by internal medicine residents: trends over 2 years

Over 2 million people in the United States are infected with hepatitis C, and there has been an explosion in knowledge regarding this disease in the last decade. Internal medicine residents must be able to identify patients at risk for hepatitis C and institute appropriate diagnostic testing and referral of these patients. Methods : A survey regarding hepatitis C risk factors and the management of hepatitis C patients was administered on three occasions over 15 months (time 0, 1 month, and 15 months) to members of a large university-based internal medicine residency. Results : During the study period 59 residents completed all three surveys. Less than half of the residents (39%) ask patients about hepatitis C risk factors. Only 58% reported that they would refer a hepatitis C antibody positive patient with elevated liver enzymes to a subspecialist on the initial survey. The residents who did not refer patients cited low response rates, high side-effect profiles, and the high cost of therapy as reasons for not referring the patient. There was significant improvement (58% vs 78%, p < 0.01 ) in the rate of patient referral during the 15-month study period but no substantial improvement in the other knowledge deficits. Conclusions : The knowledge base of the internal medicine residents about hepatitis C screening and management is suboptimal. New, more effective hepatitis C education programs for internal medicine residents should be initiated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75407/1/j.1572-0241.2002.05708.x.pd

Fosmanogepix (APX001) Is Effective in the Treatment of Immunocompromised Mice Infected with Invasive Pulmonary Scedosporiosis or Disseminated Fusariosis.

There are limited treatment options for immunosuppressed patients with lethal invasive fungal infections due to Fusarium and Scedosporium Manogepix (MGX; APX001A) is a novel antifungal that targets the conserved Gwt1 enzyme required for localization of glycosylphosphatidylinositol-anchored mannoproteins in fungi. We evaluated the in vitro activity of MGX and the efficacy of the prodrug fosmanogepix (APX001) in immunosuppressed murine models of hematogenously disseminated fusariosis and pulmonary scedosporiosis. The MGX minimum effective concentration (MEC) for Scedosporium isolates was 0.03 μg/ml and ranged from 0.015 to 0.03 μg/ml for Fusarium isolates. In the scedosporiosis model, treatment of mice with 78 mg/kg and 104 mg/kg of body weight fosmanogepix, along with 1-aminobenzotriazole (ABT) to enhance the serum half-life of MGX, significantly increased median survival time versus placebo from 7 days to 13 and 11 days, respectively. Furthermore, administration of 104 mg/kg fosmanogepix resulted in an ∼2-log10 reduction in lung, kidney, or brain conidial equivalents/gram tissue (CE). Similarly, in the fusariosis model, 78 mg/kg and 104 mg/kg fosmanogepix plus ABT enhanced median survival time from 7 days to 12 and 10 days, respectively. A 2- to 3-log10 reduction in kidney and brain CE was observed. In both models, reduction in tissue fungal burden was corroborated with histopathological data, with target organs showing reduced or no abscesses in fosmanogepix-treated mice. Survival and tissue clearance were comparable to a clinically relevant high dose of liposomal amphotericin B (10 to 15 mg/kg). Our data support the continued development of fosmanogepix as a first-in-class treatment for infections caused by these rare molds

Microscopically-based energy density functionals for nuclei using the density matrix expansion: Implementation and pre-optimization

In a recent series of papers, Gebremariam, Bogner, and Duguet derived a microscopically based nuclear energy density functional by applying the Density Matrix Expansion (DME) to the Hartree-Fock energy obtained from chiral effective field theory (EFT) two- and three-nucleon interactions. Due to the structure of the chiral interactions, each coupling in the DME functional is given as the sum of a coupling constant arising from zero-range contact interactions and a coupling function of the density arising from the finite-range pion exchanges. Since the contact contributions have essentially the same structure as those entering empirical Skyrme functionals, a microscopically guided Skyrme phenomenology has been suggested in which the contact terms in the DME functional are released for optimization to finite-density observables to capture short-range correlation energy contributions from beyond Hartree-Fock. The present paper is the first attempt to assess the ability of the newly suggested DME functional, which has a much richer set of density dependencies than traditional Skyrme functionals, to generate sensible and stable results for nuclear applications. The results of the first proof-of-principle calculations are given, and numerous practical issues related to the implementation of the new functional in existing Skyrme codes are discussed. Using a restricted singular value decomposition (SVD) optimization procedure, it is found that the new DME functional gives numerically stable results and exhibits a small but systematic reduction of our test $\chi^2$ function compared to standard Skyrme functionals, thus justifying its suitability for future global optimizations and large-scale calculations.Comment: 17 pages, 6 figure

Fob1 and Fob2 Proteins Are Virulence Determinants of Rhizopus oryzae via Facilitating Iron Uptake from Ferrioxamine.

Dialysis patients with chronic renal failure receiving deferoxamine for treating iron overload are uniquely predisposed for mucormycosis, which is most often caused by Rhizopus oryzae. Although the deferoxamine siderophore is not secreted by Mucorales, previous studies established that Rhizopus species utilize iron from ferrioxamine (iron-rich form of deferoxamine). Here we determined that the CBS domain proteins of Fob1 and Fob2 act as receptors on the cell surface of R. oryzae during iron uptake from ferrioxamine. Fob1 and Fob2 cell surface expression was induced in the presence of ferrioxamine and bound radiolabeled ferrioxamine. A R. oryzae strain with targeted reduced Fob1/Fob2 expression was impaired for iron uptake, germinating, and growing on medium with ferrioxamine as the sole source of iron. This strain also exhibited reduced virulence in a deferoxamine-treated, but not the diabetic ketoacidotic (DKA), mouse model of mucormycosis. The mechanism by which R. oryzae obtains iron from ferrioxamine involves the reductase/permease uptake system since the growth on ferrioxamine supplemented medium is associated with elevated reductase activity and the use of the ferrous chelator bathophenanthroline disulfonate abrogates iron uptake and growth on medium supplemented with ferrioxamine as a sole source of iron. Finally, R. oryzae mutants with reduced copies of the high affinity iron permease (FTR1) or with decreased FTR1 expression had an impaired iron uptake from ferrioxamine in vitro and reduced virulence in the deferoxamine-treated mouse model of mucormycosis. These two receptors appear to be conserved in Mucorales, and can be the subject of future novel therapy to maintain the use of deferoxamine for treating iron-overload

Fluctuations, line tensions, and correlation times of nanoscale islands on surfaces

We analyze in detail the fluctuations and correlations of the (spatial) Fourier modes of nano-scale single-layer islands on (111) fcc crystal surfaces. We analytically show that the Fourier modes of the fluctuations couple due to the anisotropy of the crystal, changing the power spectrum of the fluctuations, and that the actual eigenmodes of the fluctuations are the appropriate linear combinations of the Fourier modes. Using kinetic Monte Carlo simulations with bond-counting parameters that best match realistic energy barriers for hopping rates, we deduce absolute line tensions as a function of azimuthal orientation from the analyses of the fluctuation of each individual mode. The autocorrelation functions of these modes give the scaling of the correlation times with wavelength, providing us with the rate-limiting kinetics driving the fluctuations, here step-edge diffusion. The results for the energetic parameters are in reasonable agreement with available experimental data for Pb(111) surfaces, and we compare the correlation times of island-edge fluctuations to relaxation times of quenched Pb crystallites.Comment: 11 pages, 8 figures; to appear in PRB 70, xxx (15 Dec 2004), changes in MC and its implication