A general framework for multi-compartmental analysis of drug chemotherapy dynamics in human immunodeficiency virus type-1 infected individuals

An optimal control strategy for the highly active antiretroviral therapy associated to the acquired immunodeficiency syndrome should be designed regarding a comprehensive analysis of the drug chemotherapy behavior in the host tissues, from major viral replication sites to viral sanctuary compartments. Such approach is critical in order to efficiently explore synergistic, competitive and prohibitive relationships among drugs and, hence, therapy costs and side-effect minimization. In this paper, a novel mathematical model for HIV-1 drug chemotherapy dynamics in distinct host anatomic compartments is proposed and theoretically evaluated on fifteen conventional anti-retroviral drugs. Rather than interdependence between drug type and its concentration profile in a host tissue, simulated results suggest that such profile is importantly correlated with the host tissue under consideration. Furthermore, the drug accumulative dynamics are drastically affected by low patient compliance with pharmacotherapy, even when a single dose lacks. (C) 2012 Elsevier Inc. All rights reserved.

Connections between the Sznajd model with general confidence rules and graph theory

The Sznajd model is a sociophysics model that is used to model opinion propagation and consensus formation in societies. Its main feature is that its rules favor bigger groups of agreeing people. In a previous work, we generalized the bounded confidence rule in order to model biases and prejudices in discrete opinion models. In that work, we applied this modification to the Sznajd model and presented some preliminary results. The present work extends what we did in that paper. We present results linking many of the properties of the mean-field fixed points, with only a few qualitative aspects of the confidence rule (the biases and prejudices modeled), finding an interesting connection with graph theory problems. More precisely, we link the existence of fixed points with the notion of strongly connected graphs and the stability of fixed points with the problem of finding the maximal independent sets of a graph. We state these results and present comparisons between the mean field and simulations in Barabasi-Albert networks, followed by the main mathematical ideas and appendices with the rigorous proofs of our claims and some graph theory concepts, together with examples. We also show that there is no qualitative difference in the mean-field results if we require that a group of size q > 2, instead of a pair, of agreeing agents be formed before they attempt to convince other sites (for the mean field, this would coincide with the q-voter model).

Equation of Motion Governing the Dynamics of Vertically Collapsing Buildings

The present paper aims at contributing to a discussion, opened by several authors, on the proper equation of motion that governs the vertical collapse of buildings. The most striking and tragic example is that of the World Trade Center Twin Towers, in New York City, about 10 years ago. This is a very complex problem and, besides dynamics, the analysis involves several areas of knowledge in mechanics, such as structural engineering, materials sciences, and thermodynamics, among others. Therefore, the goal of this work is far from claiming to deal with the problem in its completeness, leaving aside discussions about the modeling of the resistive load to collapse, for example. However, the following analysis, restricted to the study of motion, shows that the problem in question holds great similarity to the classic falling-chain problem, very much addressed in a number of different versions as the pioneering one, by von Buquoy or the one by Cayley. Following previous works, a simple single-degree-of-freedom model was readdressed and conceptually discussed. The form of Lagrange's equation, which leads to a proper equation of motion for the collapsing building, is a general and extended dissipative form, which is proper for systems with mass varying explicitly with position. The additional dissipative generalized force term, which was present in the extended form of the Lagrange equation, was shown to be derivable from a Rayleigh-like energy function. DOI: 10.1061/(ASCE)EM.1943-7889.0000453. (C) 2012 American Society of Civil Engineers.

Bamboo overabundance alters forest structure and dynamics in the Atlantic Forest hotspot

With fast growth rates and clonal reproduction, bamboos can rapidly invade forest areas, drastically changing their original structure. In the Brazilian Atlantic Forest, where recent mapping efforts have shown that woody bamboos dominate large areas, the present study assessed the differences in soil and vegetation between plots dominated (>90% of bamboo coverage) and not dominated (<10% of coverage) by the native Guadua tagoara. Surface soil was physically and chemically analyzed, and trees at three size classes (seedling, sapling, and adult) were counted, identified and measured. New inventories were conducted to assess recruitment, mortality, and damage rates. Bamboo plots had more fertile soils (higher bases saturation and lower potential acidity) due to the preferential occurrence of G. tagoara on more clayey soils. Bamboo-dominated plots had lower density of adult trees (diameter >5 cm) and lower species density. In addition, overall tree diameter distribution was very different between environments, with bamboo plots having greater concentration of small-sized trees. Such differences are probably related to the general tendency of higher mortality, recruitment, and damage rates in bamboo plots. Greater physical (wind and bamboo-induced damages) and physiological stress (heat and light) in bamboo plots are probable causes of bamboo-dominated plots being more dynamic. Finally, we discuss the differences between Atlantic and Amazonian Guadua-dominated forests, causes, and possible consequences of bamboo overabundance to the Atlantic Forest conservation. (C) 2012 Elsevier Ltd. All rights reserved.

BDKRB2+9/-9 Polymorphism Is Associated with Higher Risk for Diabetes Mellitus in the Brazilian General Population

Some mechanisms have been proposed to explain the role of bradykinin on glucose homeostasis and some studies reported that the BDKRB2 +9/-9 polymorphism was associated to the transcriptional activity of the receptor. In this scenario, the main aim of this study was to evaluate the association of the BDKRB2 +9/-9 polymorphism with diabetes mellitus risk in the Brazilian general population. This study included 1,032 subjects of the general urban population. Anthropometrical, blood pressure, biochemical, and genotype analyses for the BDKRB2 +9/-9 bp insertion/deletion polymorphism were performed. Individuals carrying +9/+9 or +9/-9 genotypes had higher glucose values (84.5 mg/dL versus 80.6 mg/dL, resp.) and higher frequency of diabetes mellitus (7.6% versus 3.6%, resp.) compared to individuals carrying -9/-9, adjusting for age and gender. In addition, higher diabetes mellitus risk was associated to presence of the +9/+9 or +9/-9 genotypes (OR = 1.91; 95% CI = 1.09-4.19; P = 0.03). Our data suggest that the BDKRB2 +9/-9 polymorphism may act as a genetic modulator of glucose homeostasis. It was previously associated to insulin sensitivity, glucose uptake, and insulin secretion, and, in this study, data suggest that the polymorphism may increase susceptibility to chronic metabolic conditions such as diabetes in the Brazilian population.

Cylindrospermopsis raciborskii exudate-Cu complexes: impact on copper dynamics and bioavailability in an aquatic food chain

The increasing contamination of aquatic environments motivates studies on the interactions among natural dissolved organic matter, metals, and the biota. This investigation focused on the organic exudates of the toxic cyanobacteria Cylindrospermopsis raciborskii as a Cu carrier through a three-level aquatic trophic chain (bacteria, protozoa, and copepod). The effects of bacteria activity and growth on the metal-organic complexes were evaluated through changes in free Cu2+ ions, total dissolved, and total particulate Cu. To be sure that the added copper would be complexed to the exudates, its complexing properties were previously determined. The cyanobacteria exudate-Cu complexes were furnished to bacteria that were further used as a food source to the protozoan Paramercium caudatum. This was then furnished as food to the copepod Mesocyclops sp. The results showed that, in general, the cyanobacterial exudates decreased Cu bioavailability and toxicity to the first trophic level (bacteria), but because the heterotrophic bacteria accumulated Cu, they were responsible for the transference for the otherwise low availability metal form. Both the bacteria and protozoan organisms accumulated Cu, but no metal accumulation was detected in the copepods.

A General Latent Class Model for Performance Evaluation of Diagnostic Tests in the Absence of a Gold Standard: An Application to Chagas Disease

We propose a new general Bayesian latent class model for evaluation of the performance of multiple diagnostic tests in situations in which no gold standard test exists based on a computationally intensive approach. The modeling represents an interesting and suitable alternative to models with complex structures that involve the general case of several conditionally independent diagnostic tests, covariates, and strata with different disease prevalences. The technique of stratifying the population according to different disease prevalence rates does not add further marked complexity to the modeling, but it makes the model more flexible and interpretable. To illustrate the general model proposed, we evaluate the performance of six diagnostic screening tests for Chagas disease considering some epidemiological variables. Serology at the time of donation (negative, positive, inconclusive) was considered as a factor of stratification in the model. The general model with stratification of the population performed better in comparison with its concurrents without stratification. The group formed by the testing laboratory Biomanguinhos FIOCRUZ-kit (c-ELISA and rec-ELISA) is the best option in the confirmation process by presenting false-negative rate of 0.0002% from the serial scheme. We are 100% sure that the donor is healthy when these two tests have negative results and he is chagasic when they have positive results.

Phylodynamics and Dispersal of HRSV Entails Its Permanence in the General Population in between Yearly Outbreaks in Children

Background: Human respiratory syncytial virus (HRSV) is one of the major etiologic agents of respiratory tract infections among children worldwide. Methodology/Principal Findings: Here through a comprehensive analysis of the two major HRSV groups A and B (n = 1983) which comprise of several genotypes, we present a complex pattern of population dynamics of HRSV over a time period of 50 years (1956-2006). Circulation pattern of HRSV revealed a series of expansions and fluctuations of co-circulating lineages with a predominance of HRSVA. Positively selected amino acid substitutions of the G glycoprotein occurred upon population growth of GB3 with a 60-nucleotide insertion (GB3 Insert), while other genotypes acquired substitutions upon both population growth and decrease, thus possibly reflecting a role for immune selected epitopes in linkage to the traced substitution sites that may have important relevance for vaccine design. Analysis evidenced the co-circulation and predominance of distinct HRSV genotypes in Brazil and suggested a year-round presence of the virus. In Brazil, GA2 and GA5 were the main culprits of HRSV outbreaks until recently, when the GB3 Insert became highly prevalent. Using Bayesian methods, we determined the dispersal patterns of genotypes through several inferred migratory routes. Conclusions/Significance: Genotypes spread across continents and between neighboring areas. Crucially, genotypes also remained at any given region for extended periods, independent of seasonal outbreaks possibly maintained by re-infecting the general population.

Exact dynamics of single-qubit-gate fidelities under the measurement-based quantum computation scheme

Measurement-based quantum computation is an efficient model to perform universal computation. Nevertheless, theoretical questions have been raised, mainly with respect to realistic noise conditions. In order to shed some light on this issue, we evaluate the exact dynamics of some single-qubit-gate fidelities using the measurement-based quantum computation scheme when the qubits which are used as a resource interact with a common dephasing environment. We report a necessary condition for the fidelity dynamics of a general pure N-qubit state, interacting with this type of error channel, to present an oscillatory behavior, and we show that for the initial canonical cluster state, the fidelity oscillates as a function of time. This state fidelity oscillatory behavior brings significant variations to the values of the computational results of a generic gate acting on that state depending on the instants we choose to apply our set of projective measurements. As we shall see, considering some specific gates that are frequently found in the literature, the fast application of the set of projective measurements does not necessarily imply high gate fidelity, and likewise the slow application thereof does not necessarily imply low gate fidelity. Our condition for the occurrence of the fidelity oscillatory behavior shows that the oscillation presented by the cluster state is due exclusively to its initial geometry. Other states that can be used as resources for measurement-based quantum computation can present the same initial geometrical condition. Therefore, it is very important for the present scheme to know when the fidelity of a particular resource state will oscillate in time and, if this is the case, what are the best times to perform the measurements.

Cwc24p Is a General Saccharomyces cerevisiae Splicing Factor Required for the Stable U2 snRNP Binding to Primary Transcripts

Splicing of primary transcripts is an essential process for the control of gene expression. Specific conserved sequences in premature transcripts are important to recruit the spliceosome machinery. The Saccharomyces cerevisiae catalytic spliceosome is composed of about 60 proteins and 5 snRNAs (U1, U2, U4/U6 and U5). Among these proteins, there are core components and regulatory factors, which might stabilize or facilitate splicing of specific substrates. Assembly of a catalytic complex depends on the dynamics of interactions between these proteins and RNAs. Cwc24p is an essential S. cerevisiae protein, originally identified as a component of the NTC complex, and later shown to affect splicing in vivo. In this work, we show that Cwc24p also affects splicing in vitro. We show that Cwc24p is important for the U2 snRNP binding to primary transcripts, co-migrates with spliceosomes, and that it interacts with Brr2p. Additionally, we show that Cwc24p is important for the stable binding of Prp19p to the spliceosome. We propose a model in which Cwc24p is required for stabilizing the U2 association with primary transcripts, and therefore, especially important for splicing of RNAs containing non- consensus branchpoint sequences.

Molting dynamics and juvenile hormone titer profiles in the nymphal stages of a lower termite, Cryptotermes secundus (Kalotermitidae) - signatures of developmental plasticity

Termites are social cockroaches and this sociality is founded on a high plasticity during development. Three molting types (progressive, stationary and regressive molts) are fundamental to achieve plasticity during alate/sexual development, and they make termites a major challenge to any model on endocrine regulation in insect development. As the endocrine signatures underpinning this plasticity are barely understood, we studied the developmental dynamics and their underlying juvenile hormone OH) titers in a wood-dwelling termite. Cryptotermes secundus, which is characterized by an ancestral life style of living in dead wood and individuals being totipotent in development. The following general pattern elements could be identified during winged sexual development (i) regressive molts were accompanied by longer intermolt periods than other molting types, (ii) JH titers decreased gradually during the developmental transition from larva (immatures without wing buds), to nymph (immatures with wing buds), to winged adult, (iii) in all nymphal stages, the JH titer rose before the next molt and dropped thereafter within the first week, (iv) considerable variation in JH titers occurred in the midphase of the molting cycle of the 2nd and 3rd nymphal instar, inferring that this variation may reflect the underlying endocrine signature of each of the three molting types, (v) the 4th nymphal instar, the shortest of all, seems to be a switch point in development, as nymphs in this stage mainly developed progressively. When comparing these patterns with endocrine signatures seen in cockroaches, the developmental program of Cryprotermes can be interpreted as a co-option and repetitive use of hormonal dynamics of the post dorsal-closure phase of cockroach embryonic development. (C) 2012 Elsevier Ltd. All tights reserved.

Records of sedimentary dynamics in the continental shelf and upper slope between Aveiro-Espinho (N Portugal)

The sedimentary unconsolidated cover of the Aveiro-Espinho continental shelf and upper slope (NW Portugal) records a complex interplay of processes including wave energy and currents, fluvial input, sediment transport alongshore and cross-shelf, geological and oceanographic processes and sediment sources and sinks. In order to study this record, a set of surface sediment samples was studied. Sediment grain size and composition, as well as the mineralogical composition (by XRD) of the fine (<63 mu m) and clay (<2 mu m) fractions and benthic microfaunal (foraminifera) data were analysed. Cluster analysis applied to the sedimentological data (grain size, sediment composition and mineralogy) allowed the establishment of three main zones corresponding to the: inner-, mid- and outer-shelf/upper slope. On the inner-shelf, the sedimentary coverture is composed of siliciclastic fine to very fine sand, essentially comprising modern (immature) terrigenous particles. The sediment grain size, as well as mineralogical and microfaunal composition, denote the high energetic conditions of this sector in which the alongshore transport of sand is predominantly southward and occurs mostly during the spring-summer oceanographic regime, when the main river providing sediments to this area, the River Douro, undergoes periods of drought. This effect may emphasize the erosive character of this coastal sector at present, since the Ria de Aveiro provides the shelf with few sediments. On the mid-shelf, an alongshore siliciclastic band of coarse sand and gravel can be found between the 40 m and 60 m isobaths. This gravelly deposit includes relic sediments deposited during lower sea-level stands. This structure stays on the surface due to the high bottom energy, which promotes the remobilization of the fine-grained sediments, and/or events of sediments bypassing. Benthic foraminifera density and "Benthic Foraminifera High Productivity" (BFHP) proxy values are in general low, which is consistent with the overall small supply of organic matter to the oceanic bottom in the inner- and mid-shelf. However, the Ria de Aveiro outflow, which delivers organic matter to the shelf, leaves its imprint mainly on the mid-shelf, identifiable by the increase in foraminifera density and BFHP values in front of the lagoon mouth. The higher values of BFHP along the 100 m isobath trace the present position of an oceanic thermal front whose situation may have changed in the last 3/5 ka BP. This zone marks a clear difference in the density, diversity and composition of benthic foraminifera assemblages. Here, in addition, sediment composition changes significantly, giving rise to carbonate-rich fine to medium sand in the deeper sector. The low bottom energy and the small sedimentation rate of the outer-shelf contributed to the preservation of a discontinuous carbonate-rich gravel band, between the 100 m and 140 m isobaths, also related to paleo-littorals, following the transgression that has occurred since the Last Glacial Maximum. The winter oceanographic regime favours the transport of fine grained sediments to the outer-shelf and upper slope. The inner- and mid-shelf, however, have low amounts of this kind of sediment and the Cretacic carbonated complexes Pontal da Galega and Pontal da Cartola, rocky outcrops located at the mid- and outer-shelf, act as morphological barriers to the cross-shelf transport of sediments. Thus a reduced sedimentation rate occurs in these deeper sectors, as indicated by the lower abundance of detrital minerals, which is compensated for the high sedimentary content of biogenic carbonates. The relatively high BFHP and Shannon Index values indicate water column stratification, high supply of organic matter and environmental stability, which provide favourable conditions for a diversified benthic fauna to flourish. These conditions also encourage authigenic chemical changes, favourable to glauconite formation, as well as illite and kaolinite degradation. Benthic foraminifera and clay mineral assemblages also reveal the effect of the internal waves pushing upward, and downslope losses of the sediments on the outer-shelf and upper slope.