Molecular recognition of an RNA trafficking element by heterogeneous nuclear ribonucleoprotein A2

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a multitasking protein involved in RNA packaging, alternative splicing of pre-mRNA. telomere maintenance, cytoplasmic RNA trafficking, and translation. It binds short segments of single-stranded nucleic acids, including the A2RE11 RNA element that is necessary and sufficient for cytoplasmic transport of a subset of rnRNAs in oligodendrocytes and neurons. We have explored the structures of hnRNP A2, its RNA recognition motifs (RRMs) and Gly-rich module, and the RRM complexes with A2RE11. Circular dichroism spectroscopy showed that the secondary structure of the first 189 residues of hnRNP A2 parallels that of the tandem beta alpha beta beta alpha beta RRMs of its paralogue, hnRNP A1, previously deduced from X-ray diffraction studies. The unusual GRD was shown to have substantial beta-sheet and beta-turn structure. Sedimentation equilibrium and circular dichroism results were consistent with the tandem RRM region being monomeric and supported earlier evidence for the binding of two A2RE11 oligoribonucleotides to this domain, in contrast to the protein dimer formed by the complex of hnRNP A1 with the telomeric ssDNA repeat. A three-dimensional structure for the N-terminal, two-RRM-containing segment of hnRNP A2 was derived by homology modeling. This structure was used to derive a model for the complex with A2RE11 using the previously described interaction of pairs of stacked nucleotides with aromatic residues on the RRM beta-sheet platforms, conserved in other RRM-RNA complexes, together with biochemical data and molecular dynamics-based observations of inter-RRM mobility.

Solvent extraction of phosphoric acid

This work investigated the purification of phosphoric acid using a suitable organic solvent, followed by re-extraction of the acid from the solvent using water. The work consisted of practical batch and continuous studies and the economics and design of a full scale plant, based on the experimental data. A comprehensive literature survey on the purification of wet process phosphoric acid by organic solvents is presented and the literature describing the design and operation of mixer-settlers has also been reviewed. In batch studies, the equilibrium and distribution curves for the systems water-phosphoric acid-solvent for Benzaldehyde, Cyclohexanol and Methylisobutylketone (MIBK) were determined together with hydrodynamic characteristics for both pure and impure systems. The settling time increased with acid concentration, but power input had no effect. Drop size was found to reduce with acid concentration and power input. For the continuous studies a novel horizontal mixer~settler cascade was designed, constructed and operated using pure and impure acid with MIBK as the solvent. The cascade incorporates three air turbine agitated, cylindrical 900 ml mixers, and three cylindrical 200 ml settlers with air-lift solvent interstage transfer. Mean drop size in the fully baffled mixer was correlated. Drop size distributions were log-normal and size decreased with acid concentration and power input and increased with dispersed phase hold-up. Phase inversion studies showed that the width of the ambivalent region depended upon rotor speed, hold-up and acid concentration. Settler characteristics were investigated by measuring wedge length. Distribution coefficients of impurities and acid were also investigated. The following optimum extraction conditions were found: initial acid concentration 63%, phase ratio of solvent to acid 1:1 (v/v), impeller speed recommended 900 r.p.m. In the washing step the maximum phase ratio of solvent to water was 8:1 (v/v). Work on phosphoric acid concentration involved constructing distillation equipment consisting of a 10& spherical still. A 100 T/d scale detailed process design including capital cost, operating cost and profitability was also completed. A profit model for phosphoric acid extraction was developed and maximised. Recommendations are made for both the application of the results to a practical design and for extensions of the study.

A Kuhnian crisis in neo-Darwinism

Policy issues which receive large inputs of scientific and technical information are frequently marred by acrimonious controversies between contributing experts. There are few if any examples of a public policy decision being based on a firm consensus of scientific and technical experts. Such a consensus is taken for granted by the `Rational' model of decision making and its derivatives. Comparing the dynamics of conflict in policy-relevant issues with those of conflict in `pure' science, one is struck by their great similarity. In both cases we witness examples of rhetorical statements about incompetence, conflicting interpretations of data, and interdisciplinary communication problems. Noting this similarity, this thesis attempts to answer the question, `Is there a similarity of cause: do the same causes lie at the roots of conflict in policy-relevant and policy-irrelevant science?' In answering this question this thesis examines recent controversies in a generally policy-irrelevant science - evolutionary biology. Three episodes of conflict are studied: the `Neutral Allele Theory', `Punctuated Equilibrium', and `Structuralist versus Functionalist approaches to evolution'. These controversies are analysed in terms of both Kuhn's account of scientific `crises' and Collingridge and Reeve's (1986) `Overcritical Model'. Comparing its findings with those of Collingridge and Reeve, this thesis concludes that, (a) there is a Kuhnian crisis in contemporary evolution theory and, (b) that common causes do lie at the roots of conflict in policy-relevant and policy-irrelevant science. Science has an inherent tendency to degenerate into acrimonious conflict but at the same time has mechanisms which eventually resolve such conflicts. Unfortunately, when science is incorporated into the policy arena these mechanisms are prevented from operating. This thesis reinforces Collingridge and Reeve's conclusion that science is of little use to policy.

Evolutionary market agents for resource allocation in decentralised systems

We introduce self-interested evolutionary market agents, which act on behalf of service providers in a large decentralised system, to adaptively price their resources over time. Our agents competitively co-evolve in the live market, driving it towards the Bertrand equilibrium, the non-cooperative Nash equilibrium, at which all sellers charge their reserve price and share the market equally. We demonstrate that this outcome results in even load-balancing between the service providers. Our contribution in this paper is twofold; the use of on-line competitive co-evolution of self-interested service providers to drive a decentralised market towards equilibrium, and a demonstration that load-balancing behaviour emerges under the assumptions we describe. Unlike previous studies on this topic, all our agents are entirely self-interested; no cooperation is assumed. This makes our problem a non-trivial and more realistic one.

Using overlay test to evaluate fracture properties of field-aged asphalt concrete

Field material testing provides firsthand information on pavement conditions which are most helpful in evaluating performance and identifying preventive maintenance or overlay strategies. High variability of field asphalt concrete due to construction raises the demand for accuracy of the test. Accordingly, the objective of this study is to propose a reliable and repeatable methodology to evaluate the fracture properties of field-aged asphalt concrete using the overlay test (OT). The OT is selected because of its efficiency and feasibility for asphalt field cores with diverse dimensions. The fracture properties refer to the Paris’ law parameters based on the pseudo J-integral (A and n) because of the sound physical significance of the pseudo J-integral with respect to characterizing the cracking process. In order to determine A and n, a two-step OT protocol is designed to characterize the undamaged and damaged behaviors of asphalt field cores. To ensure the accuracy of determined undamaged and fracture properties, a new analysis method is then developed for data processing, which combines the finite element simulations and mechanical analysis of viscoelastic force equilibrium and evolution of pseudo displacement work in the OT specimen. Finally, theoretical equations are derived to calculate A and n directly from the OT test data. The accuracy of the determined fracture properties is verified. The proposed methodology is applied to a total of 27 asphalt field cores obtained from a field project in Texas, including the control Hot Mix Asphalt (HMA) and two types of warm mix asphalt (WMA). The results demonstrate a high linear correlation between n and −log A for all the tested field cores. Investigations of the effect of field aging on the fracture properties confirm that n is a good indicator to quantify the cracking resistance of asphalt concrete. It is also indicated that summer climatic condition clearly accelerates the rate of aging. The impact of the WMA technologies on fracture properties of asphalt concrete is visualized by comparing the n-values. It shows that the Evotherm WMA technology slightly improves the cracking resistance, while the foaming WMA technology provides the comparable fracture properties with the HMA. After 15 months aging in the field, the cracking resistance does not exhibit significant difference between HMA and WMAs, which is confirmed by the observations of field distresses.

A Bertrand-Edgeworth-oligopóliumok (Bertrand-Edgeworth oligopolies – a survey of the literature)

Az irodalomban az olyan oligopolmodellek, amelyekben mind az ár, mind a mennyiség döntési változó, Bertrand-Edgeworth-oligopóliumok néven ismertek. E tanulmányban a Bertrand-Edgeworth-oligopóliumokkal kapcsolatos érdekesebb eredményeket tekintjük át. Tárgyaljuk a Bertrand-Edgeworth-típusú oligopolmodellek specifikációját, a Nash-egyensúly létezését, a Nash-egyensúly meghatározását és a Bertrand-Edgeworth-oligopóliumok alkalmazásait. / === / Oligopoly models in which both price and quantity are decisive variables are known in the literature as Bertrand-Edgeworth oligopolies, the most interesting results with which are surveyed in this paper. The author assumes the existence of the Nash equilibrium, as the specification of Bertrand-Edgeworth-type oligopoly models, the determination of the Nash equilibrium, and the application of Bertrand-Edgeworth oligopolies.

A magyar gazdaságpolitika dilemmái = Dilemmas of the Hungarian economic policy

A cikk a magyar gazdaságpolitika dilemmáit helyezi szélesebb közgazdasági perspektívába, a stabilizációs programcsomag intézkedéseiből kiindulva. Elemzi azokat az összefüggéseket, amelyek a posztszocialista átmenet három súlyosan nyomasztó feladata: a külső egyensúly és belső pénzügyi egyensúly javítása, valamint a tartós növekedés feltételeinek megteremtése között állnak fenn. A jelen pillanatban a külső egyensúly jól érzékelhető javítása a legsürgősebb; a rövid távú intézkedéseknek elsősorban ennek a feladatnak a szolgálatában kell állniuk. Sajnálatos, hogy az azonnali intézkedések csomagja mindeddig nem ágyazódott be egy meggyőző közép­ és hosszú távú reformtervbe. A cikk végül a gazdasági stabilizáció politikai feltételeit elemzi, és a társadalmi összefogás és önmérséklet jelentőségét hangsúlyozza. / === / The article examines the dilemmas of the Hungarian economic policy, placing it into a wider economic perspective and setting out from the measures prescribed stabilization program. The author analyses the interrelations among the three gravely distressing tasks of the post­socialist transition: improvement of the external balances and domestic financial equilibrium, and creation of the conditions of sustainable growth. For the moment, a well perceptible improvement of the external equilibrium is the most urgent task; the short­term measures have to serve first of all this purpose. Unfortunately, the package of short­term measures has not yet been embedded into a convincing medium and long­term reform program. Finally, the article analyses the political conditions of economic stabilization and emphasesizes the importance of joining the social forces and of self restraint.

Munkavásárlás vagy dolgozóbérlés? Elmélkedés a munkaviszony közgazdasági értelmezéséről. = Purchase of work or renting of workers?

Munkaszolgáltatások adásvételeként értelmezendő-e a munkaviszony vagy dolgozók bérléseként? A közgazdaság-tudomány álláspontja következetlen: jellemzően dolgozóbérlésnek deklarálja, ugyanakkor ideálisan munkaszolgáltatások adásvételeként gondolja el. Az írás érvelése szerint e következetlenség vélhető oka az abból fakadó szaktudományi dilemma, hogy a tömeges dolgozóbérlés színtereként értelmezett munkaerőpiac versenyzői egyensúlya elvi lehetetlenség. _______ Should the employment relationship be interpreted as a form of purchase of labour services or as one of renting workers? Economics typically portrays it as the latter, but idealizes it as the former. This apparent inconsistency can presumably be attributed to the dilemma arising from the theoretical incompatibility of the core economic concept of competitive equilibrium and the reality of mass renting of people in the labour market.

Localized surface plasmon resonance biosensors for real-time biomolecular binding study

Surface Plasmon Resonance (SPR) and localized surface plasmon resonance (LSPR) biosensors have brought a revolutionary change to in vitro study of biological and biochemical processes due to its ability to measure extremely small changes in surface refractive index (RI), binding equilibrium and kinetics. Strategies based on LSPR have been employed to enhance the sensitivity for a variety of applications, such as diagnosis of diseases, environmental analysis, food safety, and chemical threat detection. In LSPR spectroscopy, absorption and scattering of light are greatly enhanced at frequencies that excite the LSPR, resulting in a characteristic extinction spectrum that depends on the RI of the surrounding medium. Compositional and conformational change within the surrounding medium near the sensing surface could therefore be detected as shifts in the extinction spectrum. This dissertation specifically focuses on the development and evaluation of highly sensitive LSPR biosensors for in situ study of biomolecular binding process by incorporating nanotechnology. Compared to traditional methods for biomolecular binding studies, LSPR-based biosensors offer real-time, label free detection. First, we modified the gold sensing surface of LSPR-based biosensors using nanomaterials such as gold nanoparticles (AuNPs) and polymer to enhance surface absorption and sensitivity. The performance of this type of biosensors was evaluated on the application of small heavy metal molecule binding affinity study. This biosensor exhibited ∼7 fold sensitivity enhancement and binding kinetics measurement capability comparing to traditional biosensors. Second, a miniaturized cell culture system was integrated into the LSPR-based biosensor system for the purpose of real-time biomarker signaling pathway studies and drug efficacy studies with living cells. To the best of our knowledge, this is the first LSPR-based sensing platform with the capability of living cell studies. We demonstrated the living cell measurement ability by studying the VEGF signaling pathway in living SKOV-3 cells. Results have shown that the VEGF secretion level from SKOV-3 cells is 0.0137 ± 0.0012 pg per cell. Moreover, we have demonstrated bevacizumab drug regulation to the VEGF signaling pathway using this biosensor. This sensing platform could potentially help studying biomolecular binding kinetics which elucidates the underlying mechanisms of biotransportation and drug delivery.

Dynamics of spatial heterogeneity in a landfill with interacting phase densities:a stochastic analysis

A landfill represents a complex and dynamically evolving structure that can be stochastically perturbed by exogenous factors. Both thermodynamic (equilibrium) and time varying (non-steady state) properties of a landfill are affected by spatially heterogenous and nonlinear subprocesses that combine with constraining initial and boundary conditions arising from the associated surroundings. While multiple approaches have been made to model landfill statistics by incorporating spatially dependent parameters on the one hand (data based approach) and continuum dynamical mass-balance equations on the other (equation based modelling), practically no attempt has been made to amalgamate these two approaches while also incorporating inherent stochastically induced fluctuations affecting the process overall. In this article, we will implement a minimalist scheme of modelling the time evolution of a realistic three dimensional landfill through a reaction-diffusion based approach, focusing on the coupled interactions of four key variables - solid mass density, hydrolysed mass density, acetogenic mass density and methanogenic mass density, that themselves are stochastically affected by fluctuations, coupled with diffusive relaxation of the individual densities, in ambient surroundings. Our results indicate that close to the linearly stable limit, the large time steady state properties, arising out of a series of complex coupled interactions between the stochastically driven variables, are scarcely affected by the biochemical growth-decay statistics. Our results clearly show that an equilibrium landfill structure is primarily determined by the solid and hydrolysed mass densities only rendering the other variables as statistically "irrelevant" in this (large time) asymptotic limit. The other major implication of incorporation of stochasticity in the landfill evolution dynamics is in the hugely reduced production times of the plants that are now approximately 20-30 years instead of the previous deterministic model predictions of 50 years and above. The predictions from this stochastic model are in conformity with available experimental observations.

Results of Closed-Flow Column Experiments (zip-archive 2.3 MB)

The identification of transport parameters by inverse modeling often suffers from equifinality or parameter correlation when models are fitted to observations of the solute breakthrough in column outflow experiments. This parameters uncertainty can be approached by the application of multiple experimental designs such as column experiments in open-flow mode and the recently proposed closed-flow mode. Latter are characterized by the recirculation of the column effluent into the solution supply vessel that feeds the inflow. Depending on the experimental conditions, the solute concentration in the solution supply vessel and the effluent follows a damped sinusoidal oscillation. As a result, the closed-flow experiment provides additional observables in the breakthrough curve. The evaluation of these emergent features allows intrinsic control over boundary conditions and impacts the uncertainty of parameters in inverse modeling. We present a comprehensive sensitivity analysis to illustrate the potential application of closed-flow experiments. We show that the sensitivity with respect to the apparent dispersion can be controlled by the experimenter leading to a decrease in parameter uncertainty as compared to classical experiments by an order of magnitude for optimal settings. With these finding we are also able to reduce the equifinality found for situations, where rate-limited interactions impede a proper determination of the apparent dispersion and rate coefficients. Furthermore, we show the expected breakthrough curve for equilibrium and kinetic sorption, the latter showing strong similarities to the behavior found for completely mixed batch reactor experiments. This renders the closed-flow mode a useful complementary approach to classical column experiments.

Crenças e atitudes dos profissionais da educação face à sexualidade dos alunos com incapacidade intelectual num agrupamento de escolas da Maia

A sexualidade é um dos aspetos essenciais para o equilíbrio psicossomático e o desenvolvimento integral do ser humano. No caso da sexualidade das pessoas com incapacidade intelectual, o preconceito, mitos, tabus e a discriminação colaboram para uma perspetiva de que a pessoa com incapacidade não tem direito a exercer a sua sexualidade. Neste contexto, esta investigação tem como objetivo descrever e compreender Crenças e Atitudes dos profissionais da educação face à sexualidade dos alunos com incapacidade intelectual num agrupamento de escolas da rede pública. Nesta pesquisa, de tipo descritivo, os dados foram recolhidos através de um questionário em formato digital com perguntas abertas e fechadas e analisados de forma qualitativa e quantitativa. Participaram neste estudo 106 docentes e 50 assistentes operacionais em funções num agrupamento de escolas da Maia. Globalmente, os resultados obtidos mostram que existe concordância elevada nos dois grupos de estudo relativamente ao facto de a sexualidade integrar as várias dimensões (Afetividade, Comunicação, Prazer e Reprodução), da necessidade de obterem informação no âmbito da Educação Sexual e concordância moderada no facto de ser difícil falar sobre o tema da sexualidade com os alunos com Incapacidade Intelectual. Tanto os docentes do sexo masculino, como os assistentes operacionais do mesmo género revelam níveis médios de atitudes positivas superiores relativamente aos pares do sexo feminino.

Relevance or irrelevance of capital structure?

In this paper we examine the effects of asymmetric information on the nature of financial equilibrium and on the capital structure of firms. In the first model presented, the financial contracts on offer involve pooling equilibrium with no adverse selection. However, in the special case analyzed, where contracts are of mixed form, there may be a separating equilibrium and also equilibrium may not exist. Interesting result is that the separating equilibrium found is not economically efficient since aggregate investments falls short of first-best level. More importantly, capital structure does matter. The relative magnitude of outside equity makes a real difference to the quantity of aggregate investment in equilibrium.

A emergência das minorias étnicas no Brasil : agendamento das políticas públicas para comunidades quilombolas

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciência Política, Programa de Pós-Graduação em Ciência Política, 2014.

Localized Surface Plasmon Resonance Biosensors for Real-Time Biomolecular Binding Study

Surface Plasmon Resonance (SPR) and localized surface plasmon resonance (LSPR) biosensors have brought a revolutionary change to in vitro study of biological and biochemical processes due to its ability to measure extremely small changes in surface refractive index (RI), binding equilibrium and kinetics. Strategies based on LSPR have been employed to enhance the sensitivity for a variety of applications, such as diagnosis of diseases, environmental analysis, food safety, and chemical threat detection. In LSPR spectroscopy, absorption and scattering of light are greatly enhanced at frequencies that excite the LSPR, resulting in a characteristic extinction spectrum that depends on the RI of the surrounding medium. Compositional and conformational change within the surrounding medium near the sensing surface could therefore be detected as shifts in the extinction spectrum. This dissertation specifically focuses on the development and evaluation of highly sensitive LSPR biosensors for in situ study of biomolecular binding process by incorporating nanotechnology. Compared to traditional methods for biomolecular binding studies, LSPR-based biosensors offer real-time, label free detection. First, we modified the gold sensing surface of LSPR-based biosensors using nanomaterials such as gold nanoparticles (AuNPs) and polymer to enhance surface absorption and sensitivity. The performance of this type of biosensors was evaluated on the application of small heavy metal molecule binding affinity study. This biosensor exhibited ~7 fold sensitivity enhancement and binding kinetics measurement capability comparing to traditional biosensors. Second, a miniaturized cell culture system was integrated into the LSPR-based biosensor system for the purpose of real-time biomarker signaling pathway studies and drug efficacy studies with living cells. To the best of our knowledge, this is the first LSPR-based sensing platform with the capability of living cell studies. We demonstrated the living cell measurement ability by studying the VEGF signaling pathway in living SKOV-3 cells. Results have shown that the VEGF secretion level from SKOV-3 cells is 0.0137 ± 0.0012 pg per cell. Moreover, we have demonstrated bevacizumab drug regulation to the VEGF signaling pathway using this biosensor. This sensing platform could potentially help studying biomolecular binding kinetics which elucidates the underlying mechanisms of biotransportation and drug delivery.