HIV-1 RNA Levels and Antiretroviral Drug Resistance in Blood and Non-Blood Compartments from HIV-1–Infected Men and Women enrolled in AIDS Clinical Trials Group Study A5077

Background: Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study. Methods: Blood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher’s and McNemar’s exact tests to compare VL between sexes and among compartments. Results: Samples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% ‘untreated’ (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001). A higher proportion of men had genital shedding versus women (78% versus 41%), and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women) paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77%) and genital-secretions (68%). Resistance discordance was observed between compartments in 14% of subjects. Conclusions: HIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites. Mechanisms of potential sex-dependent tissue compartmentalization should be further characterized to aid in optimizing treatment and prevention of HIV transmission. Trial Registration ClinicalTrials.gov NCT0000748

Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: implications for future treatment options

Article approval pendingDrug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy

Minorías sexuales: Sobre el paradigma de la Tolerancia y el paradigma de la Ciudadanía Plena

We propose two paradigms for analyzing the rights of sexual minorities within a juridical-political-social framework. The first paradigm arises from the idea of Tolerance; whereas the second stems from the notion of Full Citizenship. The features of both paradigms have been gleaned from bills, laws and judicial cases concerning the Right to Association and the Right to Same-Sex Marriage. The article reviews the legal discourse and political implications of the aforementioned legal sources as well as some socio-historical issues concerning the struggle for equal rights of sexual minorities in Argentina.Proponemos dos formas paradigmáticas de concebir los derechos de las minorías sexuales en un marco jurídico-político y social general. El primer paradigma es una mirada a través del prisma de la “Tolerancia”, el segundo desde la perspectiva de la “Ciudadanía Plena”. Hemos deducido las características de ambos paradigmas a partir de proyectos de leyes, leyes y casos jurisprudenciales referentes al “Derecho de Asociación” y al “Derecho al Matrimonio entre Personas del Mismo Sexo”. Revisamos el discurso jurídico y las implicancias políticas de las sentencias, y algunos aspectos histórico-sociales de las luchas por las reivindicaciones de las minorías sexuales en Argentina

Base normativa y anecdotario legislativo del Sistema Métrico Legal Argentino (SIMELA)

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Geometric Configurations, Regular Subalgebras of E10 and M-Theory Cosmology

We re-examine previously found cosmological solutions to eleven-dimensional supergravity in the light of the E_{10}-approach to M-theory. We focus on the solutions with non zero electric field determined by geometric configurations (n_m, g_3), n\leq 10. We show that these solutions are associated with rank $g$ regular subalgebras of E_{10}, the Dynkin diagrams of which are the (line) incidence diagrams of the geometric configurations. Our analysis provides as a byproduct an interesting class of rank-10 Coxeter subgroups of the Weyl group of E_{10}.Comment: 48 pages, 27 figures, 5 tables, references added, typos correcte

Comparing Cognitive Theories of Learning Transfer to Advance Cybersecurity Instruction, Assessment, and Testing

The cybersecurity threat landscape evolves quickly, continually, and consequentially. This means that the transfer of cybersecurity learning is crucial. We compared how different recognized “cognitive” transfer theories might help explain and synergize three aspects of cybersecurity education. These include teaching and training in diverse settings, assessing learning formatively & summatively, and testing & measuring achievement, proficiency, & readiness. We excluded newer sociocultural theories and their implications for inclusion as we explore those theories elsewhere. We first summarized the history of cybersecurity education and proficiency standards considering transfer theories. We then explored each theory and reviewed the most relevant cybersecurity education research; in some cases, we broadened our search to computing education. We concluded that (a) archaic differential transfer theories are still influential but have negative implications to be avoided, (b) constructionist theories are popular in K-12 settings but raise issues for assessment and transfer, (c) many embrace a general cognitive science perspective that can resolve tensions between modern cognitive-associationist and cognitive-constructivist theories that are popular with innovators, and (d) new perceptual and coordinative theories have potential worth exploring. These insights should support “generative” cybersecurity learning that transfers readily and widely to future classes, tests, and workplaces. These insights should be beneficial when designing and using cyber “ranges” and other hyper-realistic simulations, where transfer assumptions inform costly design decisions and undergird the validity of performance as evidence of proficiency

Fluctuations of elastic interfaces in fluids: Theory and simulation

We study the dynamics of elastic interfaces-membranes-immersed in thermally excited fluids. The work contains three components: the development of a numerical method, a purely theoretical approach, and numerical simulation. In developing a numerical method, we first discuss the dynamical coupling between the interface and the surrounding fluids. An argument is then presented that generalizes the single-relaxation time lattice-Boltzmann method for the simulation of hydrodynamic interfaces to include the elastic properties of the boundary. The implementation of the new method is outlined and it is tested by simulating the static behavior of spherical bubbles and the dynamics of bending waves. By means of the fluctuation-dissipation theorem we recover analytically the equilibrium frequency power spectrum of thermally fluctuating membranes and the correlation function of the excitations. Also, the non-equilibrium scaling properties of the membrane roughening are deduced, leading us to formulate a scaling law describing the interface growth, W^2(L,T)=L^3 g[t/L^(5/2)], where W, L and T are the width of the interface, the linear size of the system and the temperature respectively, and g is a scaling function. Finally, the phenomenology of thermally fluctuating membranes is simulated and the frequency power spectrum is recovered, confirming the decay of the correlation function of the fluctuations. As a further numerical study of fluctuating elastic interfaces, the non-equilibrium regime is reproduced by initializing the system as an interface immersed in thermally pre-excited fluids.Comment: 15 pages, 11 figure

Optimization of Material and Energy Integration in Eco-Industrial Networks

This work develops a generalized modeling framework using several techniques for assessing the feasibility of an eco-industrial network or ‘eco-park’ in order to demonstrate the environmental and economic benefits of industrial facilities with cooperative goals to conserve energy and materials. The work takes advantage of three distinct types of modeling techniques (linear programming, mixed-integer linear programming and mixed-integer non-linear programming) to incorporate increasingly complex circumstances for designing eco-industrial networks. The purpose of this research is to provide policy-makers and facility designers with an approach to optimize construction of facilities based upon economic and environmental incentives. This framework allows for optimizing the material and energy efficiency of a network of facilities to reduce emissions, waste, and input of materials and energy while maintaining production levels. Major contributions from this thesis are to examine the potential for alternative-fuel vehicles within the concept of a hydrogen economy and exploration of eco-industrial networks, utilizing the tools of life cycle analysis and system optimization. Life-cycle assessment is utilized as a tool for decision-making throughout this thesis and is an invaluable asset in making environmentally-conscious decisions. This type of assessment evaluates the emissions of a product from virgin material extraction through to final disposition in the aquatic, terrestrial or atmospheric domain. The use of life-cycle assessment techniques shows clear impacts on society over the entire lifecycle of the products and processes considered herein. Development of a dual-objective function to account for economics and environmental performance of industrial facilities is developed and utilized to aid in the decision process for policy-makers and facility designers. The concept of eco-industrial networks is further extended by including additional components, such as transportation modes, within the model. To this end, preliminary work examines the practical possibility of shifting automobile propulsion technologies to alternative fuels with emphasis on the criteria air contaminants considered herein of greenhouse gases, volatile organic compounds, and oxides of sulphur and nitrogen. The scenarios presented are based on a model of the electricity system in the province of Ontario, Canada and energy pathway analysis to assess the supportable market penetration of, and emissions from, alternative vehicle technologies. The recommendation of this work is that a transition to electric vehicles in the near-term followed by a transition to hydrogen fuel cell vehicles will yield the largest reduction in criteria air contaminants in both the urban centre of Toronto, Ontario and in the province as a whole. The consideration of transportation and transitional technologies feeds directly into the concept of eco-industrial parks and the benefit to society of their implementation. The reduction in transportation distance between relatable chemical manufacturers has been hailed as a major benefit of implementing eco-industrial park topology. This work develops a generalized modeling framework for eco-industrial parks based on a dual objective of societal and industrial requirements. The nodes considered in this work include: energy generation via hydrocarbon gasification or reforming, carbon capture, carbon sequestration, pressure-swing adsorption in addition to the manufacture of ammonia and urea within the context of refueling a fleet of 1000 hydrogen vehicles. Life-cycle assessment is applied to form the societal benefits of operating facilities within an eco-industrial framework and the long-term economics of the processes are considered to form the economic portion of the objective. Modeling is carried out in three distinct types: linear programming, mixed-integer linear programming and mixed-integer non-linear programming. Each of these types represents a different modeling framework developed to assess various complexities in the eco-industrial network and yet they share common goals, themes and analysis methods. Using each of these approaches, a case study eco-industrial park is analyzed using the three types of modeling methodologies mentioned. The simpler LP model is unable to account for some of the complexities inherent in an eco-park network and thus the results from this model are subsequently viewed as an upper boundary on the benefits of eco-industrial integration for the case study mentioned. The subsequent efforts of mixed-integer linear and non-linear programming serve to refine the model and provide more realistic investigation of the benefits of such a network. In order to achieve a reduction in emissions of harmful substances to the air, water and land to meet national targets, analysis of the interactions between humans and the environment must be explored to unlock new avenues of production and consumption to reduce the impact that society is having on the environment. This work is completed within the larger context of the potential hydrogen economy with the supposition that such a scenario will be enabled by increasingly effective technology. The transition of our current infrastructure to the hydrogen economy shows benefits to air quality from reduced emissions of vehicles and also from a reduced industrial contribution.4 month

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo