Epistasis may play an important role in evolution and speciation. Under multiplicative interactions between different loci, an analytical model is proposed to estimate genetic parameters at the individual locus level that contribute to interspecific differences in outcrossing species. The multiplicative epistasis model, inferred from a number of animal and plant experiments, suggests that genotypes at a pair of loci have genotypic values equal to the product of genotypic values at the two different loci. By considering the genetic property of outcrossing species (i.e., high polymorphisms) in the multilevel family structure analysis for an intra- and interspecific factorial mating design, a method is developed to provide estimates for allele frequencies and additive and dominant effects at individual loci in each of the two parental populations, the genotypic values of newly formed heterozygotes through species combination each with one allele from a parental population and the second from the other parental population, and the numbers of genetic factors that lead to species differentiation. Use of clones offers a tremendous power to test the adequacy of the model. However, the utilization of the model with species that cannot be cloned is also discussed. An example with interspecific hybrids of two forest tree species is used to demonstrate the model.

Carbon nanotubes have attracted great interest in multidisciplinary study since their discovery. Herein, radionuclide 243Am(III) sorption to uncapped multiwall carbon nanotubes (MWCNTs) was carried out at 20+/-2 degrees C in 0.01 and 0.1 M NaClO4 solutions. Effects of 243Am(III) solution concentration, ionic strength, and pH on 243Am(III) sorption to MWCNTs were also investigated. The sorption is strongly dependent on pH values and weakly dependent on the ionic strength in the experimental conditions. The results show that MWCNTs can adsorb 243Am(III) with extraordinarily high efficiency by forming very stable complexes. Chemisorption or chemicomplexation is the main mechanism of 243Am(III) sorption on the surface of MWCNTs. MWCNTs can be a promising candidate for the preconcentration and solidification of 243Am(III) or its analogue lanthanides and actinides from large volumes of aqueous solution, as required for remediation purposes, and perhaps also as a sorbent for the removal of heavy metal ions from the industry wastewater.

No abstract

The enantioselective synthesis of spirocycles has long been pursued by organic chemists. Despite their unique 3D properties and presence in several natural products, the difficulty in their enantioselective synthesis makes them underrepresented in pharmaceutical libraries. Since the first pioneering reports of the enantioselective construction of spirosilanes by Tamao et al., significant effort has been devoted towards the development of new promising asymmetric methodologies. Remarkably, with the advent of organocatalysis, particularly over six years, the reported methodologies for the synthesis of spirocycles have increased exponentially. The aim of this review is to summarize the latest trends and developments in the enantioselective synthesis of spirocompounds during these last six years.

Investigation of HIV viral dynamics is important for understanding the HIV pathogenesis and for development of treatment strategies. Perelson et al. demonstrated that simple viral dynamic models fit to data on viral load as measured by plasma HIV-RNA could produce estimates of rates of clearance of virus and of infected CD4+ T-lymphocytes. In this paper we extend the work of Perelson et al. by proposing models with less restrictive assumptions about drug activity. Our models take into account the fact that infectious and non-infectious virions are produced by infected T-cells both before and after the treatment. We also show that direct measurement of infectious virus load provides sufficient information for estimation of antiretroviral drug efficacy parameter. For characterizing viral dynamics of populations and estimation of dynamic parameters, we propose a hierarchical non-linear model. Compared to other methods such as the non-linear least square method used by Perelson et al., we show that the proposed approach has the following advantages: (i) it is more appropriate for modelling within-patient and between-patient variation and to characterize the population dynamics; (ii) it is flexible enough to deal with both rich and sparse individual data; (iii) it has more power to detect model misspecification; (iv) it allows incorporation of covariates for viral dynamic parameters; (v) it makes more efficient use of between-subject information to get better parameter estimates. We give two simulation examples to illustrate the proposed approach and its advantages. Finally, we discuss practical issues regarding the clinical trial design for viral dynamic studies.

No abstract

This paper describes the development and testing of VirtualDose--a software for reporting organ doses for adult and pediatric patients who undergo x-ray computed tomography (CT) examinations. The software is based on a comprehensive database of organ doses derived from Monte Carlo (MC) simulations involving a library of 25 anatomically realistic phantoms that represent patients of different ages, body sizes, body masses, and pregnant stages. Models of GE Lightspeed Pro 16 and Siemens SOMATOM Sensation 16 scanners were carefully validated for use in MC dose calculations. The software framework is designed with the 'software as a service (SaaS)' delivery concept under which multiple clients can access the web-based interface simultaneously from any computer without having to install software locally. The RESTful web service API also allows a third-party picture archiving and communication system software package to seamlessly integrate with VirtualDose's functions. Software testing showed that VirtualDose was compatible with numerous operating systems including Windows, Linux, Apple OS X, and mobile and portable devices. The organ doses from VirtualDose were compared against those reported by CT-Expo and ImPACT-two dosimetry tools that were based on the stylized pediatric and adult patient models that were known to be anatomically simple. The organ doses reported by VirtualDose differed from those reported by CT-Expo and ImPACT by as much as 300% in some of the patient models. These results confirm the conclusion from past studies that differences in anatomical realism offered by stylized and voxel phantoms have caused significant discrepancies in CT dose estimations.

A virologic marker, the number of HIV RNA copies or viral load, is currently used to evaluate anti-HIV therapies in AIDS clinical trials. This marker can be used to assess the antiviral potency of therapies, but is easily affected by noncompliance, drug resistance, toxicities, and other factors during the long-term treatment evaluation process. Recently it has been suggested to use viral dynamics to assess the potency of antiviral drugs and therapies, since viral decay rates in viral dynamic models have been shown to be related to the antiviral drug potency directly, and they need a shorter evaluation time. In this paper we first review the two statistical approaches for characterizing HIV dynamics and estimating viral decay rates: the individual nonlinear least squares regression (INLS) method and the population nonlinear mixed-effect model (PMEM) approach. To compare the viral decay rates between two treatment arms, parametric and nonparametric tests, based on the estimates of viral decay rates (the derived variables) from both the INLS and PMEM methods, are proposed and studied. We show, using the concept of exchangeability, that the test based on the empirical Bayes' estimates from the PMEM is valid, powerful and robust. This proposed method is very useful in most practical cases where the INLS-based tests and the general likelihood ratio test may not apply. We validate and compare various tests for finite samples using Monte Carlo simulations. Finally, we apply the proposed tests to an AIDS clinical trial to compare the antiviral potency between a 3-drug combination regimen and a 4-drug combination regimen. The proposed tests provide some significant evidence that the 4-drug regimen is more potent than the 3-drug regimen, while the naive methods fail to give a significant result.*To whom correspondence should be addressed.