WELFARE EFFECTS OF AGRICULTURAL TRADING BLOCS: THE SIMULATION OF A NORTH AMERICAN CUSTOMS UNION

Agricultural trade liberalization among the three North American Free Trade Agreement (NAFTA) signatories is modeled using a political preference function. The model distinguishes among Canada, Mexico, the United States, and a politically passive rest of the world. Through the use of intracountry compensation, the analysis shows that, from an agricultural perspective, economic integration is in the best interest of the group as a whole, although not in the best interest of individual countries. More specifically, of the agricultural production sectors, Canadian dairy, Mexican corn, and U.S. beef producers suffer the greatest losses from the formation of North American customs union.International Relations/Trade,

Barbaetis: A New Genus of Eastern Nearctic Mayflies (Ephemeroptera: Baetidae)

The new genus Barbaetis Waltz and McCafferty, and new species Barbaetis benfieldi Kennedy are described from larvae collected from the New River, Virginia. Barbaetis is easily told from Baetis by the presence of procoxal osmobranchia. Cladistics of B. benfieldi, related Pseudocloeon species, and the lutheri and pavidus complexes of Baetis are presented and indicate the need for further taxonomic revision. The habitat of B. benfieldi is described in terms of several ecological parameters. The new species demonstrates a univoltine life history with postembryonic development restricted to a short springtime period

Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites <i>Trypanosoma brucei rhodesiense</i> or <i>Trypanosoma brucei gambiense</i>, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in the severity of the neuroinflammatory response was detected when the inhibitor was administered in animals exhibiting the more severe, late central nervous system stage, of the infection. <i>In vitro</i> assays showed that Ro-61-8048 had no direct effect on trypanosome proliferation suggesting that the anti-inflammatory action is due to a direct effect of the inhibitor on the host cells and not a secondary response to parasite destruction. These findings demonstrate that kynurenine pathway catabolites are involved in the generation of the more severe inflammatory reaction associated with the late central nervous system stages of the disease and suggest that Ro-61-8048 or a similar drug may prove to be beneficial in preventing or ameliorating the PTRE when administered as an adjunct to conventional trypanocidal chemotherap

Hydrophobic Ligand Binding by Zn-α_2-glycoprotein, a Soluble Fat-depleting Factor Related to Major Histocompatibility Complex Proteins

Zn-alpha2-glycoprotein (ZAG) is a member of the major histocompatibility complex (MHC) class I family of proteins and is identical in amino acid sequence to a tumor-derived lipid-mobilizing factor associated with cachexia in cancer patients. ZAG is present in plasma and other body fluids, and its natural function, like leptin's, probably lies in lipid store homeostasis. X-ray crystallography has revealed an open groove between the helices of ZAG's alpha1 and alpha2 domains, containing an unidentified small ligand in a position similar to that of peptides in MHC proteins (Sanchez, L. M., Chirino, A. J., and Bjorkman, P. J. (1999) Science 283, 1914-1919). Here we show, using serum-derived and bacterial recombinant protein, that ZAG binds the fluorophore-tagged fatty acid 11-(dansylamino)undecanoic acid (DAUDA) and, by competition, natural fatty acids such as arachidonic, linolenic, eicosapentaenoic, and docosahexaenoic acids. Other MHC class I-related proteins (FcRn, HFE, HLA-Cw*0702) showed no such evidence of binding. Fluorescence and isothermal calorimetry analysis showed that ZAG binds DAUDA with Kd in the micromolar range, and differential scanning calorimetry showed that ligand binding increases the thermal stability of the protein. Addition of fatty acids to ZAG alters its intrinsic (tryptophan) fluorescence emission spectrum, providing a strong indication that ligand binds in the expected position close to a cluster of exposed tryptophan side chains in the groove. This study therefore shows that ZAG binds small hydrophobic ligands, that the natural ligand may be a polyunsaturated fatty acid, and provides a fluorescence-based method for investigating ZAG-ligand interactions

Fast field-cycling NMR of cartilage : a way toward molecular imaging

Peer reviewedPublisher PD

The Length of an SLE - Monte Carlo Studies

The scaling limits of a variety of critical two-dimensional lattice models are equal to the Schramm-Loewner evolution (SLE) for a suitable value of the parameter kappa. These lattice models have a natural parametrization of their random curves given by the length of the curve. This parametrization (with suitable scaling) should provide a natural parametrization for the curves in the scaling limit. We conjecture that this parametrization is also given by a type of fractal variation along the curve, and present Monte Carlo simulations to support this conjecture. Then we show by simulations that if this fractal variation is used to parametrize the SLE, then the parametrized curves have the same distribution as the curves in the scaling limit of the lattice models with their natural parametrization.Comment: 18 pages, 10 figures. Version 2 replaced the use of "nu" for the "growth exponent" by 1/d_H, where d_H is the Hausdorff dimension. Various minor errors were also correcte

Stability, reliability and cross-mode correlations of tests in a recommended 8-minute performance assessment battery

A need exists for an automated performance test system to study drugs, agents, treatments, and stresses of interest to the aviation, space, and environmental medical community. The purpose of this present study is to evaluate tests for inclusion in the NASA-sponsored Automated Performance Test System (APTS). Twenty-one subjects were tested over 10 replications with tests previously identified as good candidates for repeated-measure research. The tests were concurrently administered in paper-and-pencil and microcomputer modes. Performance scores for the two modes were compared. Data from trials 1 to 10 were examined for indications of test stability and reliability. Nine of the ten APT system tests achieved stability. Reliabilities were generally high. Cross-correlation of microbased tests with traditional paper-and-pencil versions revealed similarity of content within tests in the different modes, and implied at least three cognition and two motor factors. This protable, inexpensive, rugged, computerized battery of tests is recommended for use in repeated-measures studies of environmental and drug effects on performance. Identification of other tests compatible with microcomputer testing and potentially capable of tapping previously unidentified factors is recommended. Documentation of APTS sensitivity to environmental agents is available for more than a dozen facilities and is reported briefly. Continuation of such validation remains critical in establishing the efficacy of APTS tests