The multiple convolution integral approach to uncertainty analysis in fate and transport models used in risk assessment

Probabilistic risk estimates are typically not obtained for time-dependent releases of radioactive contaminants to the geosphere when a series of sequentially coupled transport models are required for determining results. This is due, in part, to the geophysical complexity of the site, numerical complexity of the fate and transport models, and a lack of a practical tool for linking the transport components in a fashion that facilitates uncertainty analysis. Using the theory of convolution integration, sequentially coupled submodels can be replaced with an independent system of impulse responses for each submodel. Uncertainties are then propagated independently through each of the submodels to significantly reduce the complexity of the calculations and computational time. The impulse responses of the submodels are then convolved to obtain a final result that is equivalent to the sequentially coupled estimates for each source distribution of interest. In this research a multiple convolution integral (MCI) approach is developed and the decoupling of fate and transport processes into an independent system is described. A conceptual model, extracted from the Inactive Tanks project at the Oak Ridge National Laboratory (ORNL), is used to demonstrate the approach. Potential releases of 90Sr from a disposal facility, WC-1 at ORNL, through the vadose zone are modeled and then transported through the groundwater to a downgradient point at Fifth Creek. An analytical surface water model is used to transport the contaminants to a down stream potential receptor point at White Oak Creek. The probability density functions (PDFs) of the computed concentrations, and thus risks, using the MCI approach are found to be in agreement with those obtained by the traditional approach with processor time savings of, at least, a factor of two. In this application, uncertainties in the final risk estimates resulting from the ingestion of surface water show that the range of variations of the right tail of the PDFs are over several order of magnitude. Also, sensitivity analysis shows that uncertainty in the final risk is mainly attributed to uncertainties inherent in the parameter values of the transport model and exposure duration. These results demonstrate that while the variation in the tail of time- dependent risk PDF(the region of interest to regulatory decisions) are large, the resulting confidence level that human health has been protected is only slightly increased (e.g. about 4% between the 95 and 99 fractiles). In terms of remediation cost, this slight increase yields huge costs, and might reflect poor management decisions. The MCI approach is proven here to be a vital tool for a successful and viable application of uncertainty analysis in fate and transport processes. Ultimately, the MCI approach made uncertainty analysis a highly automated process and restored it as beneficial tool for investigators and decision makers while maintaining an effective balance between cost and level of accuracy of the model predictions

Cloning, Expression and Interaction Studies of the Potential RubisCO Activase CbbQ

Carboxysomes are polyhedral microcompartments found in all cyanobacteria and in many chemoautotrophs. Within their shell they contain the enzyme ribulose-1, 5-bisphosphate carboxylase/oxygenase (RubisCO), which fixes CO2. Downstream of the carboxysome operon there is another gene cluster containing several genes that may enhance carboxysome function. Two of these genes, cbbQ and cbbO, encode potential RubisCO activases. Using recombinant CbbQ and CbbO protein, and RubisCO isolated from carboxysomes the interaction between these proteins was studied. The CbbO and CbbQ proteins were both His tagged, allowing them to be purified with Ni2+-NTA column chromatography. Each of these tagged proteins was incubated with RubisCO on a Ni2+-NTA column to determine if both proteins could be co-eluted. These studies suggest that recombinant CbbO and CbbQ do not interact individually with RubisCO. Since His-tagged CbbO and untagged CbbQ, when co-expressed in E. coli, form a complex, ongoing studies are focused on determining if both potential activases are needed to interact with RubisCO when co-expressed

Deletion of Putative msa Operon Gene Fragment and Its Phenotypic Characterization in Community Acquired-Methicillin Resistant \u3ci\u3eStaphylococcus aureus\u3c/i\u3e USA300 Strain LAC

Staphylococcus aureus is an important human pathogen that causes a wide variety of diseases. Many S. aureus strains have emerged which are resistant to the penicillin class of antibiotics. Of primary importance is methicillin-resistant S. aureus (MRSA), which has cause frequent hospitalizations due to infections. In the past, MRSA was typically confined to hospital settings, but recently, community-associated MRSA (CA-MRSA) have been reported. CA-MRSA poses a major public health threat because of increased virulence and success in infecting otherwise healthy individuals. Previously we discovered a gene, msa, which plays a critical role in biofilm formation and regulation of the disease process. Recent studies indicate that msa is part of a three open reading frame operon and that the upstream neighboring genes may play a role in the regulation of the msa operon. In this study, we investigated the possibility that genes 1294-1298 regulate virulence factors of S. aureus. We constructed a 1294-1298 mutant in CA-MRSA USA300 strain LAC using the allelic replacement vector pKOR1 and found that it produced a weaker biofilm in addition to increased autolysis, protease production, pigmentation production, hemolysin production and lipase production-all indicators that genes 1294-1298 play a role in the virulence of S. aureus. We hope to explore the possibility of exploring the regulatory network of the msa operon and its neighboring genes and exploit them as a target for therapy for recalcitrant staph infections

Basal Insulin Regimens for Adults with Type 1 Diabetes Mellitus : A Cost-Utility Analysis

Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.OBJECTIVES: To assess the cost-effectiveness of basal insulin regimens for adults with type 1 diabetes mellitus in England. METHODS: A cost-utility analysis was conducted in accordance with the National Institute for Health and Care Excellence reference case. The UK National Health Service and personal and social services perspective was used and a 3.5% discount rate was applied for both costs and outcomes. Relative effectiveness estimates were based on a systematic review of published trials and a Bayesian network meta-analysis. The IMS CORE Diabetes Model was used, in which net monetary benefit (NMB) was calculated using a threshold of £20,000 per quality-adjusted life-year (QALY) gained. A wide range of sensitivity analyses were conducted. RESULTS: Insulin detemir (twice daily) [iDet (bid)] had the highest mean QALY gain (11.09 QALYs) and NMB (£181,456) per patient over the model time horizon. Compared with the lowest cost strategy (insulin neutral protamine Hagedorn once daily), it had an incremental cost-effectiveness ratio of £7844/QALY gained. Insulin glargine (od) [iGlarg (od)] and iDet (od) were ranked as second and third, with NMBs of £180,893 and £180,423, respectively. iDet (bid) remained the most cost-effective treatment in all the sensitivity analyses performed except when high doses were assumed (>30% increment compared with other regimens), where iGlarg (od) ranked first. CONCLUSIONS: iDet (bid) is the most cost-effective regimen, providing the highest QALY gain and NMB. iGlarg (od) and iDet (od) are possible options for those for whom the iDet (bid) regimen is not acceptable or does not achieve required glycemic control.Peer reviewe

Optimization of an off-grid PV/biogas hybrid energy system for electrification: A case study in a rural area in Egypt

The increasing demand for energy in remote or rural areas, coupled with the environmental benefits and cost-effectiveness of renewable energy sources, has led to a growing interest in off-grid energy systems. This paper proposes an optimized off-grid energy system to supply energy demand for a village and a desalination reverse osmosis water plant (RO) in Shalateen, Egypt, using a combination of photovoltaic (PV) and biomass technologies. To achieve minimizing Loss of Power Supply Probability (LPSP) and Total Net Present Cost (TNPC), two decision variables are optimized using the Harmony Search algorithm implemented in MATLAB. The reliability of a designed system is met by considering the LPSP concept. The proposed system utilizes PV system as the primary energy source to power the electrical loads, with a biomass plant serving as a backup to increase system reliability and cost-effectiveness. The Demand Side Management (DSM) strategy is applied to further enhance the system\u27s cost-effectiveness. Five scenarios are studied to investigate their impact on the optimal design, the obtained results indicate that using PV/biomass generation system with DSM and LPSP is more promising

Curie Points and Direct Current Electrical Conductivity for Inverse Li-Spinel Ferrite Replaced by Zn2+ Ion

The conventional ceramic double sintering method was used to prepare a series of mixed Li-Zn spinel ferrites (SFs) Direct electric (DC) electrical conductivity (σ) and inductance (L) were studied for the prepared series of samples from room temperature to well beyond the Curie point (TC). σ was measured as a function of temperature, the relation between lnσ with 1/T indicated that σ was increased with increasing of the temperature, which proves that the prepared samples have a semiconductor behavior. The maximum value of the σ was reported for the sample of x = 0.8. The σ results were interpreted in terms of hopping model. The relation between lnσT and 1/T showed a change in the slope which is attributed to the change of samples from ferrimagnetic to paramagnetic at TC. The values of L increased exponentially from room temperature up to TC, and then they decreased sharply. The calculated activation energy Ea in the ferromagnetic region was less than that in paramagnetic region. The calculated activation energy (Ea) decreased with increasing of Zn content. The values of the TC for the prepared samples were determined from σ and L measurements, which decreased with increasing of Zn content.The conventional ceramic double sintering method was used to prepare a series of mixed Li-Zn spinel ferrites (SFs) Direct electric (DC) electrical conductivity (σ) and inductance (L) were studied for the prepared series of samples from room temperature to well beyond the Curie point (TC). σ was measured as a function of temperature, the relation between lnσ with 1/T indicated that σ was increased with increasing of the temperature, which proves that the prepared samples have a semiconductor behavior. The maximum value of the σ was reported for the sample of x = 0.8. The σ results were interpreted in terms of hopping model. The relation between lnσT and 1/T showed a change in the slope which is attributed to the change of samples from ferrimagnetic to paramagnetic at TC. The values of L increased exponentially from room temperature up to TC, and then they decreased sharply. The calculated activation energy Ea in the ferromagnetic region was less than that in paramagnetic region. The calculated activation energy (Ea) decreased with increasing of Zn content. The values of the TC for the prepared samples were determined from σ and L measurements, which decreased with increasing of Zn content

AC Conductivity and Dielectric Properties of Cu–Zn ferrites

In this work, we have studied the effects of the 2 Zn ions on the electric and the dielectric properties of the Cu spinel ferrite. The mixed Cu-Zn spinel ferrite, of chemical formula 1 s s 2 4 Cu Zn Fe O , where s stepped by 0.2 according to ( 0.0 s 1.0), were prepared from purity metal oxides using the standard ceramic preparation. The AC conductivity was determined for the ferrite samples in the applied frequency range (10 10 )Hz 4 6 . In this range of frequency, the AC conductivity increases rapidly as a function of the applied frequency. The dielectric properties for the ferrite samples were also determined at room temperature. The general trend for all samples was found to decrease continuously with increasing of the applied frequency. The measurements of the electric and the dielectric properties show that, the behavior of the ferrite samples is similar to that of the semiconductor materials. The results of the electric and dielectric properties are inadequate to previous studies for various ferrite compounds. The electric conductivity for the samples was explained using the electron hopping model.In this work, we have studied the effects of the 2 Zn ions on the electric and the dielectric properties of the Cu spinel ferrite. The mixed Cu-Zn spinel ferrite, of chemical formula 1 s s 2 4 Cu Zn Fe O , where s stepped by 0.2 according to ( 0.0 s 1.0), were prepared from purity metal oxides using the standard ceramic preparation. The AC conductivity was determined for the ferrite samples in the applied frequency range (10 10 )Hz 4 6 . In this range of frequency, the AC conductivity increases rapidly as a function of the applied frequency. The dielectric properties for the ferrite samples were also determined at room temperature. The general trend for all samples was found to decrease continuously with increasing of the applied frequency. The measurements of the electric and the dielectric properties show that, the behavior of the ferrite samples is similar to that of the semiconductor materials. The results of the electric and dielectric properties are inadequate to previous studies for various ferrite compounds. The electric conductivity for the samples was explained using the electron hopping model

Improved bioavailability of timolol maleate via transdermal transfersomal gel: Statistical optimization, characterization, and pharmacokinetic assessment

AbstractTimolol maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from extensive first pass effect, resulting in a reduction of oral bioavailability (F%) to 50% and a short elimination half-life of 4h; parameters necessitating its frequent administration. The current study was therefore, designed to formulate and optimize the transfersomal TiM gel for transdermal delivery. TiM loaded transfersomal gel was optimized using two 23 full factorial designs; where the effects of egg phosphatidyl choline (PC): surfactant (SAA) molar ratio, solvent volumetric ratio, and the drug amount were evaluated. The formulation variables; including particle size, drug entrapment efficiency (%EE), and release rate were characterized. The optimized transfersomal gel was prepared with 4.65:1 PC:SAA molar ratio, 3:1 solvent volumetric ratio, and 13mg drug amount with particle size of 2.722μm, %EE of 39.96%, and a release rate of 134.49μg/cm2/h. The permeation rate of the optimized formulation through the rat skin was excellent (151.53μg/cm2/h) and showed four times increase in relative bioavailability with prolonged plasma profile up to 72h compared with oral aqueous solution. In conclusion, a potential transfersomal transdermal system was successfully developed and the factorial design was found to be a smart tool, when optimized

The Effect of Al3+ Ions Concentration on DC Conductivity and Curie Temperature of Ni - Spinel Ferrite

A series of Al substituted Ni spinel ferrites with the empirical formula , where x = 0.0, 0.1, 0.2, 0.3, 0.4 and 0.5, were prepared by conventional ceramic double sintering method. DC electric properties and initial permeability ( ) were carried out for the prepared series of samples from room temperature to well beyond the Curie point temperature ( ). The thermal behavior of the DC electric conductivity for the prepared samples indicated that they act as semiconducting materials. On the other hand, DC electric conductivity is greatly affected when the  ions are increased. The DC electrical conductivity results were interpreted in terms of electron hopping model. The calculated activation energy in the ferrimagnetic region was less than that in paramagnetic region. The initial permeability showed constant values from room temperature to , then it decreased sharply. The Curie temperature was determined from DC electrical properties and initial permeability. was found to decrease with increasing of  ions