Correlation of the Sulphur River Formation

The geologic relations here exhibited and the radiocarbon dates obtained suggest a correlation of the Sulphur River Formation with the Prairie Formation, of the Red River terrace sequence, and with the Holloway Prairie Formation of the Gulf Coastal Plain. Radiocarbon dates of 8,000 and 12,000 B.P. have been measured on materials presumably taken from the latter (Bray and Nelson, 1956; Stevens et al., 1956)

FARM COSTS AND EXPORTS

International Relations/Trade,

Coulomb Drag between One-Dimensional Wigner Crystal Rings

We consider the Coulomb drag between two metal rings in which the long range Coulomb interaction leads to the formation of a Wigner crystal. The first ring is threaded by an Ahranov Bohm flux creating a persistent current J_0. The second ring is brought in close proximity to the second and due to the Coulomb interaction between the two rings a drag current J_D is produced in the second. We investigate this system at zero temperature for perfect rings as well as the effects of impurities. We show that the Wigner crystal state can in principle lead to a higher ratio of drag current to drive current J_D/J_0 than in weakly interacting electron systems.Comment: 12 pages, 10 figure

The effects of the filter-feeding clam Mercenaria mercenaria on carbon cycling in experimental marine mesocosms

The metabolism and the fate of 14C labelled carbon was examined in 4 outdoor mesocosm (13 m3) tanks containing both benthic and pelagic compartments. Mesocosms with (16/m2) and without the clam, Mercenaria mercenaria were compared. System production, net and gross sedimentation of particulate carbon and benthic remineralization of dissolved inorganic nitrogen were all greater in mesocosms with clams. A filtration rate model, dependent on clam size and temperature, explained between 74–114% of the increased gross sedimentation in clam tanks relative to controls.The higher production in the clam tanks was at least in part due to a greater flux of dissolved inorganic nitrogen from the benthos. Despite this greater production in the clam tanks, water column biomass remained similar to controls. Calculations based on the filtration rate model indicated that clams could have consumed between 30% and 46% of the excess biomass produced during the day. Loss of particles due to processes in the water column appeared to consume most of this excess biomass. Although clams enhanced production and sedimentation, they did not limit phytoplankton biomass in the water column through filtration

Conceptual models of the climate : 2002 program of study, Bounds on turbulent transport

The subject of "Bounds of Turbulent Transport" was introduced in a series of ten lectures. The six lecturers constitute almost all the contributors to this subject. The subject was introduced and foundations laid by five lectures by F. H. Busse. In the middle of the first week, L. Howard reviewed his historical first approach to this subject and described more recent advances. Additional lectures by P. Constantine, R. Kerswell, C. Caulfield and C. Doering provided modern advances. We trust that the lecture notes will constitute a timely review of this promising subject.Funding was provided by the Office of Naval Research under contract number N00014-97-1-0934 and The National Science Foundation under contract number OCE 98-10647

A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age, based on data from the Spanish FLIP study

Background: The aim of this study, conducted in Europe, was to develop a validated risk factor based model to predict RSV-related hospitalisation in premature infants born 33-35 weeks' gestational age (GA). Methods: The predictive model was developed using risk factors captured in the Spanish FLIP dataset, a case-control study of 183 premature infants born between 33-35 weeks' GA who were hospitalised with RSV, and 371 age-matched controls. The model was validated internally by 100-fold bootstrapping. Discriminant function analysis was used to analyse combinations of risk factors to predict RSV hospitalisation. Successive models were chosen that had the highest probability for discriminating between hospitalised and non-hospitalised infants. Receiver operating characteristic (ROC) curves were plotted. Results: An initial 15 variable model was produced with a discriminant function of 72% and an area under the ROC curve of 0.795. A step-wise reduction exercise, alongside recalculations of some variables, produced a final model consisting of 7 variables: birth +/- 10 weeks of start of season, birth weight, breast feeding for = 2 years, family members with atopy, family members with wheeze, and gender. The discrimination of this model was 71% and the area under the ROC curve was 0.791. At the 0.75 sensitivity intercept, the false positive fraction was 0.33. The 100-fold bootstrapping resulted in a mean discriminant function of 72% (standard deviation: 2.18) and a median area under the ROC curve of 0.785 (range: 0.768-0.790), indicating a good internal validation. The calculated NNT for intervention to treat all at risk patients with a 75% level of protection was 11.7 (95% confidence interval: 9.5-13.6). Conclusion: A robust model based on seven risk factors was developed, which is able to predict which premature infants born between 33-35 weeks' GA are at highest risk of hospitalisation from RSV. The model could be used to optimise prophylaxis with palivizumab across Europe

Functionality of aryl hydrocarbon receptors (AhR1 and AhR2) of white sturgeon (Acipenser transmontanus) and implications for the risk assessment of dioxin-like compounds

ABSTRACT: Worldwide, populations of sturgeons are endangered, and it is hypothesized that anthropogenic chemicals, including dioxin-like compounds (DLCs), might be contributing to the observed declines in populations. DLCs elicit their toxic action through activation of the aryl hydrocarbon receptor (AhR), which is believed to regulate most, if not all, adverse effects associated with exposure to these chemicals. Currently, risk assessment of DLCs in fishes uses toxic equivalency factors (TEFs) developed for the World Health Organization (WHO) that are based on studies of embryo-lethality with salmonids. However, there is a lack of knowledge of the sensitivity of sturgeons to DLCs, and it is uncertain whether TEFs developed by the WHO are protective of these fishes. Sturgeons are evolutionarily distinct from salmonids, and the AhRs of sturgeons differ from those of salmonids. Therefore, this study investigated the sensitivity of white sturgeon (Acipenser transmontanus) to DLCs in vitro via the use of luciferase reporter gene assays using COS-7 cells transfected with AhR1 or AhR2 of white sturgeon. Specifically, activation and relative potencies (RePs) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran, 2,3,7,8-tetrachloro-dibenzofuran, 3,3′,4,4′,5-pentachlorobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, and 2,3,3′,4,4′-pentachlorobiphenyl were determined for each AhR. It was demonstrated that white sturgeon expresses AhR1s and AhR2s that are both activated by DLCs with EC 50 values for 2,3,7,8-TCDD that are lower than those of any other AhR of vertebrates tested to date. Both AhRs of white sturgeon had RePs for polychlorinated dibenzofurans more similar to TEFs for birds, while RePs for polychlorinated biphenyls were most similar to TEFs for fishes. Measured concentrations of select DLCs in tissues of white sturgeon from British Columbia, Canada, were used to calculate toxic equivalents (TEQs) by use of TEFs for fishes used by the WHO and TCDD equivalents (TCDD-EQs) via the use of RePs for AhR2 of white sturgeon as determined by transfected COS-7 cells. TCDD-EQs calculated for endangered populations of white sturgeon were approximately 10-fold greater than TEQs and were within ranges known to cause adverse effects in other fishes, including other species of sturgeons. Therefore, TEFs used by the WHO might not adequately protect white sturgeon, illuminating the need for additional investigation into the sensitivity of these fish to DLCs

Modified Cav1.4 Expression in the Cacna1fnob2 Mouse Due to Alternative Splicing of an ETn Inserted in Exon 2

The Cacna1fnob2 mouse is reported to be a naturally occurring null mutation for the Cav1.4 calcium channel gene and the phenotype of this mouse is not identical to that of the targeted gene knockout model. We found two mRNA species in the Cacna1fnob2 mouse: approximately 90% of the mRNA represents a transcript with an in-frame stop codon within exon 2 of CACNA1F, while approximately 10% of the mRNA represents a transcript in which alternative splicing within the ETn element has removed the stop codon. This latter mRNA codes for full length Cav1.4 protein, detectable by Western blot analysis that is predicted to differ from wild type Cav1.4 protein in a region of approximately 22 amino acids in the N-terminal portion of the protein. Electrophysiological analysis with either mouse Cav1.4wt or Cav1.4nob2 cDNA revealed that the alternatively spliced protein does not differ from wild type with respect to activation and inactivation characteristics; however, while the wild type N-terminus interacted with filamin proteins in a biochemical pull-down experiment, the alternatively spliced N-terminus did not. The Cacna1fnob2 mouse electroretinogram displayed reduced b-wave and oscillatory potential amplitudes, and the retina was morphologically disorganized, with substantial reduction in thickness of the outer plexiform layer and sprouting of bipolar cell dendrites ectopically into the outer nuclear layer. Nevertheless, the spatial contrast sensitivity (optokinetic response) of Cacna1fnob2 mice was generally similar to that of wild type mice. These results suggest the Cacna1fnob2 mouse is not a CACNA1F knockout model. Rather, alternative splicing within the ETn element can lead to full-length Cav1.4 protein, albeit at reduced levels, and the functional Cav1.4 mutant may be incapable of interacting with cytoskeletal filamin proteins. These changes, do not alter the ability of the Cacna1fnob2 mouse to detect and follow moving sine-wave gratings compared to their wild type counterparts

Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy

Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid βâ glucosidase), with consequent cellular accumulation of glucosylceramide (GLâ 1). The disease is managed by intravenous administrations of recombinant glucocerebrosidase (imiglucerase), although symptomatic patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy (ERT) is not an option may also be treated by substrate reduction therapy (SRT) with miglustat. To determine whether the sequential use of both ERT and SRT may provide additional benefits, we compared the relative pharmacodynamic efficacies of separate and sequential therapies in a murine model of Gaucher disease (D409V/null). As expected, ERT with recombinant glucocerebrosidase was effective in reducing the burden of GLâ 1 storage in the liver, spleen, and lung of 3â monthâ old Gaucher mice. SRT using a novel inhibitor of glucosylceramide synthase (Genzâ 112638) was also effective, albeit to a lesser degree than ERT. Animals administered recombinant glucocerebrosidase and then Genzâ 112638 showed the lowest levels of GLâ 1 in all the visceral organs and a reduced number of Gaucher cells in the liver. This was likely because the additional deployment of SRT following enzyme therapy slowed the rate of reaccumulation of GLâ 1 in the affected organs. Hence, in patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genzâ 112638 could potentially be used as a convenient maintenance therapy. In patients naïve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147062/1/jimd0281.pd

Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2×10−201), ABCG2 (p = 3.1×10−26), SLC17A1 (p = 3.0×10−14), SLC22A11 (p = 6.7×10−14), SLC22A12 (p = 2.0×10−9), SLC16A9 (p = 1.1×10−8), GCKR (p = 1.4×10−9), LRRC16A (p = 8.5×10−9), and near PDZK1 (p = 2.7×10−9). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0×10−26) and propionyl-L-carnitine (p = 5.0×10−8) concentrations, which in turn were associated with serum UA levels (p = 1.4×10−57 and p = 8.1×10−54, respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels