HWMA/RCRA Closure Plan for the Fluorinel Dissolution Process Makeup and Cooling and Heating Systems Voluntary Consent Order SITE-TANK-005 Action Plan Tank Systems INTEC-066, INTEC-067, INTEC-068, and INTEC-072

This Hazardous Waste Management Act/Resource Conservation and Recovery Act closure plan for the fluorinel dissolution process makeup and cooling and heating systems located in the Fluorinel Dissolution Process and Fuel Storage Facility (CPP-666), Idaho Nuclear Technology and Engineering Center, Idaho National Laboratory Site, was developed to meet milestones established under the Voluntary Consent Order. The systems to be closed include waste piping associated with the fluorinel dissolution process makeup systems. This closure plan presents the closure performance standards and methods of achieving those standards

Poisson-Boltzmann analysis of the lambda repressor-operator interaction

A theoretical study of the ion atmosphere contribution to the binding free energy of the lambda repressor-operator complex is presented. The finite-difference form of the Poisson-Boltzmann equation was solved to calculate the electrostatic interaction energy of the amino-terminal domain of the lambda repressor with a 9 or 45 base pair oligonucleotide. Calculations were performed at various distances between repressor and operator as well as at different salt concentrations to determine ion atmosphere contributions to the total electrostatic interaction. Details in the distribution of charges on DNA and protein atoms had a strong influence on the calculated total interaction energies. In contrast, the calculated salt contributions are relatively insensitive to changes in the details of the charge distribution. The results indicate that the ion atmosphere contribution favors association at all protein-DNA distances studied. The theoretical number of ions released upon repressor-operator binding appears to be in reasonable agreement with experimental data

K022: Effect of combination therapy (ANG II antagonist, valsartan and a calcium channel blocker) in a hypertensive model of diabetic nephropathy

Recently, it has been suggested that in the context of diabetes and hypertension, more aggressive blood pressure targets should be considered. To achieve these levels of blood pressure control, it is likely that combination therapy will need to be used. The present study has explored the role of the addition of either a dihydropyridine or a non-dihydropyridine calcium channel blocker (CCB) to Ang II antagonist based treatment in an experimental model of hypertension and diabetes. The doses chosen for the combination therapy groups were lower than those used with monotherapy in order to achieve similar antihypertensive efficacy. Diabetic (streptozotocin induced) SHR were randomised to no treatment, valsartan (30 mg/kg/day), the non-dihydropyridine CCB verapamil (20 mg/kg/day), the dihydropyridine CCB amlodipine (6 mg/kg/day), a combination of valsartan and amlodipine (20 mg + 4 mg/kg/day respectively) or valsartan and verapamil (20 mg + 15 mg/kg/day respectively). Serial measurements of systolic blood pressure (BP) and albumin excretion rate (AER) were performed monthly (data are shown at week 16 for AER and mean of wk 20-28 for BP). This model was associated with hypertension (control, 217 ± 8, diabetic, 200 ± 5 mmHg) which was reduced by most treatments to a similar degree (valsartan 165 ± 3, amlodipine 164 ± 2, verapamil 182 ± 4, valsartan + amlodipine 151 ± 3 and valsartan + verapamil 169 ± 5 mmHg). Diabetes was associated with a progressive increase in AER (control 1.5 vs diabetic 17 mg/24 hr). Valsartan retarded the increase in AER (11 mg/24 hr). Similar efficacy was observed in the valsartan + amlodipine combination (9 mg/24 hr) but not with amlodipine alone (16 mg/24 hr) despite similar effects on blood pressure. No advantage of verapamil versus amlodipine either as monotherapy or in combination with valsartan was observed. The present study indicates that the combination of an Ang II antagonist and a dihydropyridine CCB is an effective regimen at reducing blood pressure and albuminuria in the context of diabetes and hypertensio

Targeting lentiviral vectors to antigen-specific immunoglobulins

Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell Populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient rnethod to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and hi vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral Surface. This engineered vector could specifically bind to cells expressing Surface immunoglobulin recognizing CD20 (αCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing αCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin-specific cells to deliver a therapeutic effect. Such targeting lentivectors also Could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology

Ultrasonographic assessment of splenic volume at presentation and after anti-malarial therapy in children with malarial anaemia

Background: Splenic enlargement is a component of the host response to malaria and may also influence the genesis and progression of malarial anaemia. Few cross-sectional and no longitudinal studies have assessed the relationship between splenic volume measured ultrasonographically and haemoglobin concentrations in children with malaria. Methods: Fifteen Papua New Guinean children with severe malarial anaemia (SMA; haemoglobin <50 g/L) and ten with moderate malarial anaemia (MMA; 51-99 g/L) were recruited. The SMA patients were given intramuscular artemether followed by oral artemisinin combination therapy (ACT), and were transfused one unit of packed cells 0.3-4.0 days post-admission. The MMA patients were treated with ACT. Splenic enlargement (Hackett's grade, subcostal distance and ultrasonographically determined volume) and haemoglobin concentrations were measured on days 0, 1, 2, 3, 7, 14, 28, and 42. Results: Associations between Hackett's grade, subcostal distance and splenic volume were modest (r(s) = 0.90). Mean splenic volume had fallen by approximately 50 % at day 14 in children with MMA ( P = 0.30). There was no change in haemoglobin in the MMA group during follow-up but a rise in the SMA group to day 7 ( P <= 0.05 vs days 0, 1, 2, and 3) which paralleled the packed cell volume transfused. Conclusions: Clinical assessment of splenomegaly is imprecise compared with ultrasonography. Serial splenic volumes and haemoglobin concentrations suggest that the spleen does not influence post-treatment haemoglobin, including after transfusion

A Diverse Array of Fluvial Depositional Systems in Arabia Terra: Evidence for mid‐Noachian to Early Hesperian Rivers on Mars

Branching to sinuous ridges systems, 100s of kilometers in length and comprising layered strata, are present across much of Arabia Terra, Mars. These ridges are interpreted as depositional fluvial channels, now preserved as inverted topography. Here we use high resolution image and topographic datasets to investigate the morphology of these depositional systems and show key examples of their relationships to associated fluvial landforms. The inverted channel systems likely comprise indurated conglomerate, sandstone, and mudstone bodies, which form a multi‐storey channel stratigraphy. The channel systems intersect local basins and indurated sedimentary mounds, that we interpret as paleolake deposits. Some inverted channels are located within erosional valley networks, which have regional and local catchments. Inverted channels are typically found in downslope sections of valley networks, sometimes at the margins of basins, and numerous different transition morphologies are observed. These relationships indicate a complex history of erosion and deposition, possibly controlled by changes in water or sediment flux, or base level variation. Other inverted channel systems have no clear preserved catchment; likely lost due to regional resurfacing of upland areas. Sediment may have been transported through Arabia Terra towards the dichotomy and stored in local and regional‐scale basins. Regional stratigraphic relations suggest these systems were active between the mid‐Noachian and early Hesperian. The morphology of these systems is supportive of an early Mars climate which was characterized by prolonged precipitation and runoff

Prevalence, Characteristics, and Prognostic Significance of HFE Gene Mutations in Type 2 Diabetes: The Fremantle Diabetes Study

OBJECTIVE—To examine the relationship between iron status, hereditary hemochromatosis (HFE) gene mutations, and clinical features and outcomes of type 2 diabetes in a well-characterized representative sample of community-based patients