Today we live in a society that is becoming increasingly modern and the development of various technologies is therefore quicken to advance. Some exemples are the possibility to perform Internet banking and submit declaration. These are sensistive and personal issues; by new techniques it has become possible. The next step of such technology progression may be the potential to vote electronically. This in turn leads to the main purpose of this essay, which is to investigate the possibility of an electronic voting procedure, and if it is in accordance with the regulation about the free, confidential and direct elections as provided in the constitution. Existing legislation contains detailed procedures on how the voting will occur and how the free, confidential and direct elections should be maintained. The most challenging problem is subsequently how the confidential elections can be guaranteed. In order to answer the purpose and investigation of existing law and the various proposals on electronic voting different sources of the law is used in a hierarchical order. Secondly the experience of electronic elections in Norway and Finland is analysed, and lastly the recommendation of a common standard for e-voting by the Council of Europe is being analysed. With this premise, it is appropriate to discuss how future regulatory context should be developed.In the current situation electronic elections, internet voting and e-voting in the voting room, is not sufficient and legally secure, as there are too broad queries and demand about how the free and confidential elections should be maintained. Nonetheless, there is a possibility that e-voting in a voting room may be established in the future. It is still unclear whether solidarity, integrity and incorruptibility may become legal values as the secure system we use today.


The synthesis of non-isocyanate polyurethanes (NIPUs) has recently gained great attention. In this respect, a bifunctional catalyst and an abundant metal catalyst system were investigated for the conversion of polyfunctional epoxides to gain general access to the corresponding cyclic carbonates as monomers for NIPU synthesis. A Ca-based catalytic system and a bifunctional ammonium salt were established for the synthesis of these monomers. In total, 14 terminal polyfunctional epoxides were converted to the corresponding carbonates in yields up to 99% and high purities. With regard to the one-pot synthesis of NIPUs directly from epoxides and CO2, the influence of the catalyst systems was evaluated. In general, both catalytic systems allowed the synthesis of NIPUs in a sequential one-pot procedure yielding polymers with a molecular mass of up to 19 kg·mol–1.


We present ab-initio investigation of oxygen adsorption up to two monolayer coverage on the stoichiometric TiAl(100) surface to illustrate the initial oxidation stage. The formation of band gap near the Fermi level demonstrates the transformation from metal to oxide surface with increasing oxygen coverage. The oxidation of Ti rather than Al is observed from our electronic structure calculations. The energy barriers of oxygen diffusion between different sites on surface as well as in subsurface and bulk region are derived. It is shown that the diffusion of oxygen is much easier on the surface than that into the subsurface region.


Tantalum doped rutile nanorods were hydrothermally grown on FTO substrates using a new seeding approach. This approach allows the incorporation of high concentrations of up to 4.8 at% tantalum as active doping and results in a significant enhancement of the photoelectrochemical water splitting rate (1.8 mA cm-2 at a potential of +1.5 V vs. RHE) which corresponds to ∼1% photocurrent conversion efficiency under AM 1.5, 100 mW cm-2 simulated sunlight irradiation.


Compressive spectral clustering (CSC) efficiently leverages graph filter and random sampling techniques to speed up clustering process. However, we find that CSC algorithm suffers from two main problems: i) The direct use of the dichotomy and eigencount techniques for estimating laplacian matrix's k-th eigenvalue is expensive. ii) The computation of polynomial approximation repeats in each iteration for every cluster in the interpolation process, which occupies most of the computation time of CSC. To address these problems, we propose a new approach called FCSC for fast compressive spectral clustering. FCSC addresses the first problem by assuming that the eigenvalues approximately satisfy local uniform distribution, and addresses the second problem by recalculating the pairwise similarity between nodes with low-dimensional representation to reconstruct denoised laplacian matrix. The time complexity of reconstruction is linear with the number of non-zeros in laplacian matrix. As experimentally demonstrated on artificial and real-world datasets, our approach significantly reduces the computation time while preserving high clustering accuracy comparable to previous designs, verifying the effectiveness of FCSC.


Preface.List of Common Symbols and Notations.1 Derivatives Pricing, Hedging and Risk Management: The State of the Art.1.1 Introduction.1.2 Derivative pricing basics: the binomial model.1.2.1 Replicating portfolios.1.2.2 No-arbitrage and the risk-neutral probability measure.1.2.3 No-arbitrage and the objective probability measure.1.2.4 Discounting under different probability measures.1.2.5 Multiple states of the world.1.3 The Black-Scholes model.1.3.1 Ito's lemma.1.3.2 Girsanov theorem.1.3.3 The martingale property.1.3.4 Digital options.1.4 Interest rate derivatives.1.4.1 Affine factor models.1.4.2 Forward martingale measure.1.4.3 LIBOR market model.1.5 Smile and term structure effects of volatility.1.5.1 Stochastic volatility models.1.5.2 Local volatility models.1.5.3 Implied probability.1.6 Incomplete markets.1.6.1 Back to utility theory.1.6.2 Super-hedging strategies.1.7 Credit risk.1.7.1 Structural models.1.7.2 Reduced form models.1.7.3 Implied default probabilities.1.7.4 Counterparty risk.1.8 Copula methods in finance: a primer.1.8.1 Joint probabilities, marginal probabilities and copula functions.1.8.2 Copula functions duality.1.8.3 Examples of copula functions.1.8.4 Copula functions and market comovements.1.8.5 Tail dependence.1.8.6 Equity-linked products.1.8.7 Credit-linked products.2 Bivariate Copula Functions.2.1 Definition and properties.2.2 Frechet bounds and concordance order.2.3 Sklar's theorem and the probabilistic interpretation of copulas.2.3.1 Sklar's theorem.2.3.2 The subcopula in Sklar's theorem.2.3.3 Modeling consequences.2.3.4 Sklar's theorem in financial applications: toward a non-Black-Scholes world.2.4 Copulas as dependence functions: basic facts.2.4.1 Independence.2.4.2 Comonotonicity.2.4.3 Monotone transforms and copula invariance.2.4.4 An application: VaR trade-off.2.5 Survival copula and joint survival function.2.5.1 An application: default probability with exogenous shocks.2.6 Density and canonical representation.2.7 Bounds for the distribution functions of sum of r.v.s.2.7.1 An application: VaR bounds.2.8 Appendix.3 Market Comovements and Copula Families.3.1 Measures of association.3.1.1 Concordance.3.1.2 Kendall's tau.3.1.3 Spearman's rhoS.3.1.4 Linear correlation.3.1.5 Tail dependence.3.1.6 Positive quadrant dependency.3.2 Parametric families of bivariate copula.3.2.1 The bivariate Gaussian copula.3.2.2 The bivariate Student's t copula.3.2.3 The Fr-echet family.3.2.4 Archimedean copulas.3.2.5 The Marshall-Olkin copula.4 Multivariate Copulas.4.1 Definition and basic properties.4.2 Frechet bounds and concordance order: the multidimensional case.4.3 Sklar's theorem and the basic probabilistic interpretation: the multidimensional case.4.3.1 Modeling consequences.4.4 Survival copula and joint survival function.4.5 Density and canonical representation of a multidimensional copula.4.6 Bounds for distribution functions of sums of n random variables.4.7 Multivariate dependence.4.8 Parametric families of n-dimensional copulas.4.8.1 The multivariate Gaussian copula.4.8.2 The multivariate Student's t copula.4.8.3 The multivariate dispersion copula.4.8.4 Archimedean copulas.5 Estimation and Calibration from Market Data.5.1 Statistical inference for copulas.5.2 Exact maximum likelihood method.5.2.1 Examples.5.3 IFM method.5.3.1 Application: estimation of the parametric copula for market data.5.4 CML method.5.4.1 Application: estimation of the correlation matrix for a Gaussian copula.5.5 Non-parametric estimation.5.5.1 The empirical copula.5.5.2 Kernel copula.5.6 Calibration method by using sample dependence measures.5.7 Application.5.8 Evaluation criteria for copulas.5.9 Conditional copula.5.9.1 Application to an equity portfolio.6 Simulation of Market Scenarios.6.1 Monte Carlo application with copulas.6.2 Simulation methods for elliptical copulas.6.3 Conditional sampling.6.3.1 Clayton n-copula.6.3.2 Gumbel n-copula.6.3.3 Frank n-copula.6.4 Marshall and Olkin's method.6.5 Examples of simulations.7 Credit Risk Applications.7.1 Credit derivatives.7.2 Overview of some credit derivatives products.7.2.1 Credit default swap.7.2.2 Basket default swap.7.2.3 Other credit derivatives products.7.2.4 Collateralized debt obligation (CDO).7.3 Copula approach.7.3.1 Review of single survival time modeling and calibration.7.3.2 Multiple survival times: modeling.7.3.3 Multiple defaults: calibration.7.3.4 Loss distribution and the pricing of CDOs.7.3.5 Loss distribution and the pricing of homogeneous basket default swaps.7.4 Application: pricing and risk monitoring a CDO.7.4.1 Dow Jones EuroStoxx50 CDO.7.4.2 Application: basket default swap.7.4.3 Empirical application for the EuroStoxx50 CDO.7.4.4 EuroStoxx50 pricing and risk monitoring.7.4.5 Pricing and risk monitoring of the basket default swaps.7.5 Technical appendix.7.5.1 Derivation of a multivariate Clayton copula density.7.5.2 Derivation of a 4-variate Frank copula density.7.5.3 Correlated default times.7.5.4 Variance-covariance robust estimation.7.5.5 Interest rates and foreign exchange rates in the analysis.8 Option Pricing with Copulas.8.1 Introduction.8.2 Pricing bivariate options in complete markets.8.2.1 Copula pricing kernels.8.2.2 Alternative pricing techniques.8.3 Pricing bivariate options in incomplete markets.8.3.1 Frcicing: super-replication in two dimensions.8.3.2 Copula pricing kernel.8.4 Pricing vulnerable options.8.4.1 Vulnerable digital options.8.4.2 Pricing vulnerable call options.8.4.3 Pricing vulnerable put options.8.4.4 Pricing vulnerable options in practice.8.5 Pricing rainbow two-color options.8.5.1 Call option on the minimum of two assets.8.5.2 Call option on the maximum of two assets.8.5.3 Put option on the maximum of two assets.8.5.4 Put option on the minimum of two assets.8.5.5 Option to exchange.8.5.6 Pricing and hedging rainbows with smiles: Everest notes.8.6 Pricing barrier options.8.6.1 Pricing call barrier options with copulas: the general framework.8.6.2 Pricing put barrier option: the general framework.8.6.3 Specifying the trigger event.8.6.4 Calibrating the dependence structure.8.6.5 The reflection copula.8.7 Pricing multivariate options: Monte Carlo methods.8.7.1 Application: basket option.Bibliography.Index.


The title of liberty fashioned by Moroni represented a rallying point for those who would defend the most cherished aspects of Nephite culture: families, religion, peace, and freedom. A key facet of the title of liberty incident is its deep-rooted martial setting, suggesting that the title of liberty functioned as a war banner. Numerous aspects of the title of liberty episode related to warfare and battle standards fit comfortably in an ancient Mesoamerican context. Additionally, various linguistic and poetic features in the details surrounding the title of liberty in Alma 46 closely correlate to Mesoamerican traditions, indicative of a common cultural origin.


Currently, the use of services that can be marketed online is almost a mandatory strategy that companies must incorporate to generate customer loyalty with the institution. The research deals with the study of the behavior of the members of the Savings and Credit Cooperatives regarding the integration of electronic financial services. Cooperatives are autonomous societies that help their members face their economic, social and cultural needs. Specifically, savings and credit cooperatives have the function of delivering financial intermediation for the benefit of their customers (Mella & Bravo, 2014). The investigation is exploratory scope and descriptive type whose approach is mixed. There were applied techniques such as: (a) the observation to the cooperatives to evaluate the technological progress of the financial services that currently have; (b) interviews with managers of certain entities of the sector; (c) a focus group to certain actors involved; and (d) a questionnaire of closed questions to members of different savings and credit unions in the city of Guayaquil. Among the most important results, the following stand out: (a) 43% use the smartphone to access the internet; and (b) 82% have ever used an electronic financial platform.


)Internal evaluation with expert help was conducted in four Icelandic preschools. The main factors regarding childcare and preschool services were assessed. A participatory approach to the evaluation, in particular democratic evaluation, was adopted. The directors of these four schools were interviewed, and they helped with the selection of participants for group interviews and focus groups. Group interviews were conducted with children aged four to five years and focus groups were held with the representatives of both the children's parents and preschool personnel. This is a case of internal evaluation, carried out with the participation of the preschools' main stakeholders, i.e. personnel, parents and children, but with the support of an external agent. The approach to the evaluation was deliberative democratic evaluation, which consists of three layers: a) inclusion, looking after the interests of all stakeholder groups and including them in the discussions; b) dialogue, having a dialogue in the beginning of the evaluation process, where the interests of all stakeholders are considered in the planning stage; and c) deliberation, where results are discussed by groups of stakeholders in order to determine the best ways of using those results as a basis for a development plan. The benefits and limitations of a deliberative democratic evaluation of preschool operations were considered. The limitations of a deliberative democratic approach mainly comprise how time consuming it is, as well as participants' fear of interest conflicts. The primary benefit of a democratic evaluation consists in the dialogue between stakeholders on the value of evaluation and the criteria to be used in the process. The mosaic approach emphasizes the active participation of children in the evaluation work, listening to their views and conducting a constant dialogue with them on what goes on in their school. The views of the children provide an insight into the way in which they experience the school and give indications as to what could be done to promote learning and meet their needs. However, in spite of the obvious advantages of seeking children's views, this is very seldom done when preschool work is evaluated. The method used for presenting their views in this study was having focus group conversations with three to four children at a time and having them draw their own pictures during conversations. Their views were then presented to focus groups of parents and personnel, along with the pictures that the children allowed the evaluator to use, and thoroughly discussed. Some surprising elements came up in these conversations. The children were, for example, not concerned with the length of time that they spent at preschool, as long as they were enjoying themselves, which was news to many parents and staff members. In spite of the staff trying to make sure that they had a democratic choice in what they were playing with at each time, they did not perceive that they had much choice. This was news to many of the parents and personnel as well, and engendered dialogue among those groups. Vacation times and length of time spent at school were delicate issues between parents and personnel. However, these issues were presented here and discussed, which is necessary if meaningful evaluation work is to be conducted. This, however, demands a level of trust which may have to be developed, as one group has the most power in these conversations, i.e. personnel. Other stakeholder groups need to be able to have their say as well, even on delicate matters. Thus it is possible to create a situation where operations are not only in the interest of a single stakeholder, i.e. personnel, but also take into account the views of others, i.e. children and parents.


3D-QSAR of 34 N-(3-phenyipropyl) piperazine type of σ1 receptor ligands was performed with comparative molecular fields analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). 3D-QSAR models with different conformations were established. The frontier orbits of the above ligands were investigated with B3LYP/6-31G(d) using Gaussian 03 software. The in vitro K(subscript i) values of two newly designed compounds showed good agreements with predictions. These data indicate that established models show strong predictability. This will be useful in further investigation of a receptor ligand interactions and in designing new piperazine ligands with high affinity for a receptors.


Nowadays, there is an effective equality of opportunity in the society, to be able to make up the disable people through Collaboration Agreements between Associations and Companies, but they are limited because of the lack of continuity in time. This is the story of Yeya, an intellectual disabled people, who is included in a Collaboration Agreement. She has been working for three years, but her contract is going to finish in a few weeks time in spite of her social and working integration. She could break the bubble that protects her and claimed her human quality because of her urge to improve to be able to show what she can bring to society. She is afraid of what the future will provide her and to lose all she has reached: her independence and her social integration


Abstract The Google search engine is a major presence in the online world. It has become a household word and has changed the way people do research and conduct business. The American Dialect Society, a scholarly association dedicated to the study of the English language in North America, chose "google" as the "most useful" word of 2002.1 The Oxford American Dictionary included "google" as a verb in its latest edition. Google accounted for almost half of the 5.1 billion search engine inquiries performed in the United States in December 2005.2


We present a framework aimed at estimating the potential damage to an offshore wind farm from hurricanes. Our approach is related to assessing risks that are assumed to be fundamentally related to the estimation of wind speed exceedance probabilities at selected hub heights of wind turbines in the farm and of associated wind turbine loads. As part of this preliminary framework for risk assessment, synthetic storm tracks are first simulated over the ocean using available historical tropical storm data; then, a hurricane intensity evolution model based on thermodynamic and atmospheric environmental variables is developed for each of the tracks as they get to regions within the proximity of the chosen wind farm site. Based on this intensity model, a turbulent wind field can be simulated at locations of interest along the hurricane track. The simulated turbulent wind field may then be used to estimate wind speed exceedance probability distributions and, when combined with correlated waves, it can also be used in analysis of the response of individual turbines in a wind farm. The framework for the overall risk assessment is presented; the individual components that comprise such an assessment are described briefly in illustrative applications.© 2012 ASME


I F a student of 100years ago were to return to his medical school today he would find developments in medical science and in the methods for the diagnosis and treatment of disease quite beyond his comprehension. However, if he accompanied his fellow students to their various classes he might not feel quite so lost as he observed how they received their education. Much teaching is still in the form of lectures and students laboriously take notes. The blackboard was in use early in the 19th century but today's teachers, no longer required to illustrate their scientific papers by their own drawings, would not display the artistic talent of their predecessors in its employment. Even the projector would be no novelty to our returning visitor. Projection of lantern slides by means of the magic lantern was invented about 1660 (Thomas, 1970)and Benjamin Martin in 1740 suggested that it might be used for displaying 'The transparent parts of Animal and Vegetable substances as wings of flies, membranes ....', A magic lantern in Harvard University's collection of scientific instruments which is dated about 1780was presumably used in education. Around 1850 magic lanterns and slides were commonly advertised for use as teaching aids. Photography was firmly established a hundred years ago. Transparencies had been made on glass since the introduction of the wet collodion process by F. S. Archer in 1851, but modern photography with short exposures really dates from the introduction of the dry plate in 1878. In his tour around the classes in the medical school, our Victorian student would sometimes notice teaching techniques new to him, but in general he would conclude that progress in educational methods had lagged far behind the advancement of knowledge in medical science. On enquiry he would learn that colour photography, tape-recording and television were all well known 20 years ago but perhaps he would not be surprised that they were not more widely used, realising that teachers have always been conservative by nature (Audio-visual Aids in Higher ScientificEducation, 1965). After all, Socrates had resisted the use of written words suggesting that they would produce forgetfulness and neglect of the memory. And so today, some dons regard the use of audio-visual aids, teaching machines and the computer with great suspicion, though they do not now object to the automated printing press and the university library. Assessing the present situation we might say that though there has been no shotgun wedding between technology and education we are at present witnessing a courtship between the two, a period of excitement and adventure.


A detailed analysis of 32 of the 38 halo white dwarf candidates identified by Oppenheimer et al. is presented, based on model atmosphere fits to observed energy distributions built from optical BVRI and infrared JHK CCD photometry. Effective temperatures and atmospheric compositions are determined for all objects, as well as masses and cooling ages when trigonometric parallax measurements are available. This sample is combined with that of other halo white dwarf candidates and disk white dwarfs to study the nature of these objects in terms of reduced proper motion diagrams, tangential velocities, and stellar ages. We reaffirm the conclusions of an earlier analysis based on photographic magnitudes of the same sample that total stellar ages must be derived in order to associate a white dwarf with the old halo population, and that this can only be accomplished through precise mass and distance determinations.


This study provides a first consistent answer to the important question of whether decarbonizing institutional portfolios affects the stock prices of carbon-intensive companies and if it contributes to the reduction of carbon emissions. With a new method to identify decarbonization trades in a comprehensive dataset of equity mutual fund holdings and firm-level carbon emissions, and controlling for endogeneity, we find that portfolio divestment of carbon-intensive holdings pressures stock prices downwards over several periods. Furthermore, we find first evidence of divestment-affected firms reducing their carbon emissions as compared to non-divested firms. This confirms the divestment movement's hope that a critical mass of investors will be able to positively influence firms' carbon-emitting behavior.


It has been repeatedly shown (Wolff, Rubin & Chaikoff, 1950; Goldberg & Chaikoff, 1951; Goldberg, Wolff & Greep, 1955, 1957; Castor & Beierwaltes, 1956) that the administration of 2,4-dinitrophenol to mammals is accompanied by a sharp decrease of the plasma PBI without an increase of TSH secretion by the pituitary. (The following abbreviations are used: 2,4-dinitrophenol (DNP); thyroid-stimulating hormone (TSH); proteinbound iodine (PBI); trichloracetic acid precipitable (TCAp); thyroxinebinding globulin (TBG).) These findings are usually considered to be due to 'disruption' of the classical thyroid-pituitary feed-back mechanism. Goldberg et al. (1957) showed that the pituitaries of DNP-treated animals had not lost the ability of reacting to other stimuli, and concluded from their results that the data 'were not consistent with the simple classical feed-back theory of thyroid-pituitary interrelationships. It is likely that the pituitary cells secreting TSH are influenced not only by the actual circulating level of thyroid hormone(s) but by one or more of its peripheral actions'. Data obtained while studying the influence of DNP on the peripheral metabolism of L-thyroxine in thyroidectomized, L-thyroxine-maintained rats (Escobar de] Rey & Morreale de Escobar, 1958 a, b) led us to suggest that the sharply lowered plasma PBI of treated animals might not necessarily mean that a similar decrease had occurred in the concentration of thyroid hormone in the peripheral tissues: we had observed and have later confirmed in more extensive experiments in vivo and in vitro (Morreale de Escobar & Escobar del Rey, 1961) that DNIP alters the normal partition of the thyroid hormone between plasma or protein-free incubation media and cells in favour of the latter. It has been the working hypothesis for this work that, in non-thyroidectomized rats receiving DNP, the tissue concentration of thyroid hormone(s)


The article is devoted to the development of theoretical, methodological and methodical approaches to modeling of interaction processes of legal and shadow components of the economy. In this paper, the mathematical model of legal and shadow economies interaction, taking into account the economic structure of society, is built.


transformation of muscle cells was less frequent, cell infiltrates were less intense, and contained fibroblasts earlier in compared to the control group; Trichinella larvae in the treated animals encapsulated slower and their capsule was thinner than in the control group. In mice treated at the stage of progressing muscular invasion (16 - 28 days p. i.) parasitological studies performed in the 58 th day post invasion demonstrated lower intensity of invasion compared to the control group; pathomorphological examination documented destruction of encapsulated Trichinella larvae, presence of rich cellular infiltrates of focal fibrosis around the larvae.


THIS ARTICLE deals with the flux resetting characteristics of several magnetic materials commonly employed in magnetic amplifiers. In this study the flux was forced to change under the influence of a constant external magnetizing force. The operation of a core employed in self-saturating magnetic amplifier circuits with high-impedance control windings approximates these conditions during the nonconducting half-cycle of supply voltage. The data collected therefore are readily applicable to studying this type of magnetic amplifier.


In practice we often observe some kind of 'self-acceleration' when degradation causes the local temperature to increase, and in turn the temperature accelerates degradation. In this paper an extended model for failure kinetics is proposed to describe the phenomenon mentioned above. It is a common belief that a non-linear relation between logarithmic lifetime and inverse temperature reveals a change of failure mechanisms. The results of the paper tell us that non-linearity may be produced by a single failure process with more complex failure kinetics than the simple reaction of the first order.


At the dawn of the twenty-first century, leading businesses are focusing on innovation as the means for achieving their strategic objectives and obtaining competitive advantages. Strategic management's priorities are shifting from focusing on the product delivery system and selling products to leading change through creativity and discovering new opportunities in the business environment. Conventional new-product development (NPD) approaches are evolving into powerful, comprehensive management processes and techniques that integrate opportunity, innovation, and the development process into highly capable and responsive constructs. For example, General Electric's (GE's) Chief Executive Officer (CEO) Jeffrey Immelt wants GE to focus more on innovation, and to become the leader in introducing new products and services. The conceptual level involves the exploration of new-product ideas, the maturation of new-product concepts, the selection of appropriate opportunities for further development, and the determination of the overall game plan for the NPD program. The conceptual level as defined in Chapter 2 includes the activities and decisions necessary for laying the foundation for the successful design and development, and commercialization of a new product. The road has many pitfalls, problems, and challenges as organizations have to respond to the ever-changing landscape of demanding customers and concerned stakeholders. The NPD process has to be systematic, yet flexible enough to accommodate shifting requirements over time. The conceptual level aims at managing Idea Generation, Concept Development and Selection, and Program Definition phases in an integrated fashion that is both comprehensive and expeditious.


Multidrug resistance in tumor cells may be caused by reduced drug accumulation resulting from expression of one or more proteins belonging to the ATP-binding cassette (ABC) transporter superfamily. In addition to their drug efflux properties, certain ABC proteins such as MRP1 (ABCC1) mediate the ATP-dependent transport of a broad array of organic anions. The intrinsically photoreactive glutathione conjugated cysteinyl leukotriene C4 (LTC4) is a high affinity physiological substrate of MRP1 and is widely regarded as a model compound for evaluating the substrate binding and transport properties of wild-type and mutant forms of the transporter. In the present study, we have optimized high level expression of recombinant human MRP1 in P. pastoris and developed a two step purification scheme that results in purification of the transporter to >90% homogeneity. Peptide mapping by MALDI-TOF mass spectrometry of the peptides generated by in-gel protease digestions of purified underglycosylated MRP1 identified 96.7% of the MRP1 sequence with >98% coverage of its 17 transmembrane helices. Subsequent comparisons with mass spectra of MRP1 photolabeled with LTC4 identified six candidate LTC4-modified peptide fragments which are consistent with the conclusion that the intracellular juxtamembrane positions of transmembrane helices 6, 7, 10, 17, and a COOH-proximal portion of the cytoplasmic loop that links the first and second membrane spanning domains are part of the LTC4 binding site of the transporter. Our studies confirm the usefulness of mass spectrometry for analysis of mammalian polytopic membrane proteins and for identification of substrate binding sites of human MRP1. This article has not been copyedited and formatted. The final version may differ from this version. Molecular Pharmacology Fast Forward. Published on August 16, 2005 as DOI: 10.1124/mol.105.016576 at A PE T Jornals on A ril 5, 2021 m oharm .aspeurnals.org D ow nladed from "MOL 16576" Page 4 of 37 Resistance to anti-cancer agents remains a major cause of chemotherapeutic failure in patients with malignant diseases. One widely accepted mechanism of resistance is the active extrusion of drugs out of cells by membrane transport proteins, resulting in cellular drug levels below the threshold needed for cytotoxicity (Haimeur et al., 2004b). Numerous clinical and in vitro studies have established that multidrug resistance may be caused by enhanced expression of one or more proteins belonging to the ABC transporter superfamily that use the energy provided by ATP binding and hydrolysis at their NBDs to power the transport of substrates across biological membranes. MRP1 (ABCC1) belongs to the 'C' branch of ABC transporters and was originally identified based on its elevated expression in a multidrug resistant lung cancer cell line (Cole et al., 1992). In tumor cells, MRP1 confers resistance to a broad range of antineoplastic drugs while in normal tissues, MRP1 serves a protective role against these and other cytotoxic agents (Haimeur et al., 2004b; Leslie et al., 2005). A typical mammalian ABC protein has a 4-domain structure with two MSDs and two NBDs. However, MRP1 contains a third MSD at its NH2terminus that is linked to the 4-domain core by a cytoplasmic loop, CL3 (also referred to as L0), of approximately 125 amino acids. Thus the 1531 amino acid MRP1 contains 17 TM helices distributed among three MSDs configured MSD-CL3-MSD-NBD1-MSD-NBD2 (Haimeur et al., 2004b). In addition to anticancer drugs, many of the chemicals transported by MRP1 are organic anions that include GSH, glucuronate, and sulfate conjugates that are not transported by the well known but distantly related drug transporter P-glycoprotein (ABCB1) (Haimeur et al., 2004b; Leslie et al., 2005). Most studies to date suggest that the first contacts of the hydrophilic amphipathic substrates of MRP1 are amino acids located in the inner leaflet of the membrane or in close proximity to the cytosolic-membrane interface of the transporter's two core MSDs. The best characterized organic anion substrate of MRP1 in vitro is the cysteinyl leukotriene This article has not been copyedited and formatted. The final version may differ from this version. Molecular Pharmacology Fast Forward. Published on August 16, 2005 as DOI: 10.1124/mol.105.016576 at A PE T Jornals on A ril 5, 2021 m oharm .aspeurnals.org D ow nladed from "MOL 16576" Page 5 of 37 LTC4 that is formed by conjugation of LTA4 with GSH during inflammatory and immunological responses (Leier et al., 1994; Loe et al., 1996; Muller et al., 1994; Mao et al., 2000). Analyses of Mrp1 knock-out mice have confirmed that LTC4 is an endogenous substrate of MRP1 in vivo (Wijnholds et al., 1997). LTC4 has a high affinity (Km ~100 nM) for MRP1 and is also intrinsically photoreactive (Leier et al., 1994; Loe et al., 1996). Consequently, LTC4 has been widely used as a model substrate to evaluate the substrate binding and transport properties of MRP1 (Qian et al., 2001; Lee and Altenberg, 2003b, b; Yang et al., 2003; Bakos et al., 1998; Cai et al., 2001; Haimeur et al., 2002). In previous studies, we showed that both the second and third MSDs of MRP1 can be photolabeled by [H]LTC4 with significantly more of the radioactivity associated with the NH2proximal half of the transporter (Qian et al., 2001). We also determined that a significant portion of CL3 is a prerequisite for efficient LTC4 binding to the NH2-terminal half of the protein, although neither this region nor the first MSD are themselves radiolabeled by the tritiated cysteinyl leukotriene. In addition, site-directed mutagenesis studies have identified a number of mutation-sensitive amino acids with respect to transport and/or binding of LTC4. Thus, nonconservative (and in some cases, conservative) substitutions of certain residues located in or proximal to the cytosolic interface of TM6 (Lys, Asp), TM8 (Asp), TM11 (Asn, Arg, Phe, Pro), TM16 (Arg), and TM17 (Arg) eliminate or substantially decrease LTC4 binding to the transporter (Haimeur et al., 2002, 2004a; Campbell et al., 2004; Koike et al., 2004; Situ et al., 2004; Zhang et al., 2004). However, it is not known whether these amino acids are in direct contact with LTC4 or whether they have a critical role in maintaining the architecture of the LTC4 binding site on the protein, or both. Progress in elucidating the substrate binding sites and transport mechanism of MRP1 and other mammalian ABC proteins has been hampered by the lack of high-resolution crystal structures. Mass spectrometry is a complementary approach to identifying substrate or This article has not been copyedited and formatted. The final version may differ from this version. Molecular Pharmacology Fast Forward. Published on August 16, 2005 as DOI: 10.1124/mol.105.016576 at A PE T Jornals on A ril 5, 2021 m oharm .aspeurnals.org D ow nladed from "MOL 16576" Page 6 of 37 inhibitor binding sites on proteins that has been used with increasing success in recent years. However, their hydrophobicity and propensity to aggregate has limited the analysis of integral membrane proteins by this method. On the other hand, the feasibility of detailed mass spectrometric analysis has been enhanced by recent improvements in large-scale production of mammalian membrane proteins, as well as advances in solubilization, purification, and proteolytic digestion methods (Eichacker et al., 2004; Washburn et al., 2001; Quach et al., 2003). Nevertheless, complete sequence coverage of large polytopic mammalian proteins like MRP1 by mass spectrometry remains rare. In the current study, we have explored the feasibility of using mass spectrometry to better define how MRP1 interacts with LTC4. This article has not been copyedited and formatted. The final version may differ from this version. Molecular Pharmacology Fast Forward. Published on August 16, 2005 as DOI: 10.1124/mol.105.016576 at A PE T Jornals on A ril 5, 2021 m oharm .aspeurnals.org D ow nladed from "MOL 16576" Page 7 of 37 Materials and Methods Chemicals and Reagents. The P. pastoris strain KM71 transformed with plasmid pHILMRP1-cHA-His6 was a generous gift of Drs. Philippe Gros and Jie Cai (McGill University, Montreal, PQ) (Cai et al., 2001). Leupeptin and aprotinin were from Roche Applied Science (Indianapolis, IN). PMSF and pepstatin A were from ICN (Aurora, OH) and LPG was from Avanti Polar Lipids (Alabaster, AL). DDM, chymotrypsin (protein and peptide sequencing grade), protease V8 (protein and peptide sequencing grade), and 4-HCCA were from SigmaAldrich (St. Louis, MO). Trypsin Gold (mass spectrometry grade) was from Promega Corp (Madison, WI). BD Talon superflow Co-IMAC resins were from BD Biosciences Clontech (Palo Alto, CA). Pre-swollen microgranular anion exchange DE52 diethylaminoethyl cellulose was from Whatman International Ltd (Maidstone, UK). [14,15,19,20-H]LTC4 (115.3 Ci mmol ) was from Amersham Biosciences (Piscataway, NJ). LTC4 was from CalBiochem (San Diego, CA). Other chemicals were HPLC or analytical grade unless specified otherwise. Large-scale Expression of MRP1 in P. pastoris. Large-scale expression of MRP1 in P. pastoris was carried out in baffled flasks at 28-30 °C essentially as described by the manufacturer (Invitrogen, Carlsbad, CA). Briefly, a single colony was inoculated in 50 ml of MGY (1.34% yeast nitrogen base with ammonium sulfate, 1% glycerol, 4×10% biotin) in a 250 ml flask and incubated at 28-30 °C and 250-275 rpm overnight. Ten ml of cultured cells were transferred into 1.0 l of MGY and further incubated to an OD600 2.0-6.0. Cells were collected by centrifugation and resuspended in the same volume of MM (1.34% yeast nitrogen base with ammonium sulfate, 0.5% methanol, 4×10% biotin) to induce MRP1 expression. Cell growth was then continued for a further 3 days and methanol was added to a final concentration of 0.5% every 24 h to maintain induction. Finally, cells were collected by centrifugation and washed three times with


Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. The purpose of this article is to discuss the concept of Quality by Design and describe how it can help to ensure pharmaceutical quality. QbD has to assist both industry and FDA to move towards a more scientific, risk based, holistic and proactive approach to pharmaceutical development. QbD uses a systematic approach to ensure quality by developing a thorough understanding of the compatibility of a finished product to all of the components and processes involved in manufacturing that product. Instead of relying on finished product testing alone, QbD provides insights upstream throughout the development process. Under this concept of QbD throughout designing and development of a product, it is essential to define desire product performance profile i.e. Quality Target Product Profile (QTPP) and identify Critical Quality Attributes (CQA). On the basis of this we can design the product formulation and process to meet the product attributes. This leads to recognise the impact of raw materials [Critical Material Attributes (CMA)], Critical Process Parameters (CPP) on the CQAs and identification and control sources of variability. Implementation of QbD is enabling transformation of the chemistry, manufacturing, and controls (CMC) review of Abbreviated New Drug Applications (ANDAs) into a modern, science and risk based pharmaceutical quality assessment.


I came to be interested inJules Regnault by a circuitous route. About eight years ago, I was simultaneously revising a book on the attitudes of French peasants toward medical care and helping a Cambodian student improve her English. Sometimes, my student would describe what her mother did for her when she was sick back home near Battambang before the arrival of the Khmer Rouge. Some of the remedies she described a camphor-based medicine, for example sounded similar to what the nineteenth-century French peasants I was studying at the time used. Other procedures-employing a coin to scrape bad elements off the skin of the arm-sounded completely different. I wondered about the French presence in Indochina after the 1860s and what kinds of medical transmissions might have taken place. Did French doctors affect Indochinese thinking about health and the body? How did French physicians deal with the medical beliefs of the people they found in Indochina? As I read the rapidly growing literature on tropical medicine and articles and field documents written by French physicians who served in Indochina between the early 1860s and the First World War, I realized the difficulties of analyzing popular reactions to the French medi-


Near-infrared (NIR) spectroscopy was used to measure the moisture content (MC) of in-shell Virginia and Valencia type peanuts. NIR spectral data from 400 to 2500 nm were collected on calibration samples from Virginia type peanuts ranging in moisture from 6% to 22%. Calibration models to estimate MC were developed using raw and derivative data, and an appropriate model was selected based on parameters such as standard error of calibration and prediction. The ability to predict MC in different types of in-shell peanuts with a single calibration model would save time and labor, otherwise needed for multiple calibrations, and could be useful in developing a commercial instrument.


We discuss a fully automatic technique for extracting roads in urban environments. The method has its bases in a vegetation mask derived from multispectral IKONOS data and in texture derived from pan- chromatic IKONOS data. These two techniques together are used to distinguish road pixels. We then move from individual pixels to an object- based representation that allows reasoning on a higher level. Recogni- tion of individual segments and intersections and the relationships among them are used to determine underlying road structure and to then logically hypothesize the existence of additional road network compo- nents. We show results on an image of San Diego, California. The object-based processing component may be adapted to utilize other ba- sis techniques as well, and could be used to build a road network in any


A pseudoaneurysm is a collection of blood leaking from a damaged arterial wall. Development of the false aneurysm is due to either initial injury of the vessel or is a complication of internal fixation of the femoral fracture. Femoral artery pseudoaneurysms (FAPs) may close spontaneously if the tear is small enough to allow for clotting and sealing. On the other hand, rupture of the aneurysm can trigger thrombosis, distal embolization and compression of adjacent structures. We present a case of left superficial femoral arterial pseudoaneurysm in a 36-year-old male with fracture of left femoral shaft. A 36-year-old male with history of road traffic accident presented to our institute with pain and swelling in left thigh. Patient was investigated and diagnosed with fracture left femoral shaft with a pseudoaneurysm of the left superficial femoral artery (SFA). Stenting was done for SFA followed by open reduction and internal fixation of the femoral shaft fracture. Such cases require multidisciplinary approach and a proper planning with involvement of different medical specialities to achieve optimal results and to minimise any intraoperative and post operative complications.


A serologic survey was carried out and blood samples were taken from 124 unvaccinated, clinically healthy dogs of different ages (from 6 to 156 months). Serum samples were tested by using hemagglutination inhibition (HI) test having titers of HI antibodies to CPV-2 varying from 0 to 1:2048.Out of 124 dogs tested, 96 (77.42%) had HI titers of 1:16 or greater (a criteria that established the positivity) and 28 of them had HI titers less than 1:16 that meant a negative result. The seroprevalence in communities of Kamenica, Rahovec, Peja, Prishtina and Prizren was 78.0%, 76.5%, 64.2%, 75.0% and 100%, respectively. It showed a high prevalence of CPV-2 antibodies in each community involved in the study as well as that at the nation level 96 (77.42%). Such a finding indicates that the prevalence of anti-CPV-2 antibodies is high, and as a consequence, the CPV-2 itself is widespread all-over the country. In addition to the serological studies, clinical and pathological findings were taken into account as well. The more frequent clinical symptoms noticed were depression, anorexia, watery and/or bloody diarrhea, vomiting, tachycardia and severe dehydration. In spite of the supportive therapy, a diet consisting of 50% yoghurt of homemade cow milk mixed with 50% water was introduced. Of 6 puppies that received the yoghurt, 5 survived (83.3%) and only one died (16.6%). A necropsy was carried out in 14 puppies died from hemorrhagic enteritis. All 12 puppies belonged to the shelter of stray dogs of Rahovec from the communities of Gjakova, Rahovec, Kamenica and Peja. Based on a rapid test for CPV-2 antigen detection, 12 puppies tested positive for CPV-2, one was identified with clostridia infection and one resulted negative for CPV-2. The most lesion-pronounced organs affected by CPV-2 were the small intestine.


In mass production, the RF performance of wireless devices must be tested online. The directional capability of the antenna can be used to reduce the mutual interference between the testing systems. This paper designed a planar antenna for the above application. The planar horn-shaped structure is applied on the antenna to realize directional radiation and a ridge type slow-wave structure is introduced to reduce the antenna size. Simulation and measuring results meet well. The antenna has the advantages of good directivity, easy fabrication and low cost. So it has the potential to be applied to wireless device online test.


The present paper reveals the results of disinfectant action of detergent-disinfectant means as MUK-D on different surfaces, processed with pork and beef fat beforehand. The results showed that already 3% concentration preparation disinfected test-objects of wood, metal, tile, rubber, concrete and brick from E.coli, St.aureus, Mycobacterium phlei and Bacillus subtilis at maximum 2 hours exposure and lower according to materials and microorganisms specie.


This paper presents a novel framework for snow cover mapping with multi-basis Poincare sphere parameters obtained from full-polarimetric SAR images in conjunction with an Auto-Encoder neural network. The neural network comprises of two stages where an unsupervised stochastic sampling Auto-Encoder (AE) learns a summarized representation of multi-basis polarimetric SAR data, and a supervised Feed Forward (FF) network performs classification. The proposed algorithm is demonstrated for snow-cover mapping using the Radarsat-2 (FQ-28) C-band full-polarimetric SAR datasets acquired over the Manali-Dhundi region of Himachal Pradesh, India. The results are visualized along with the NDSI-based snow cover map derived from the LANDSAT-8 imagery for the region.


The invention relate to medicine. The method for creating spatial disorientation in an individual comprises stimulating the visual and auditory analyzers synchronously and in harmony with one another. The remaining sense organs are not stimulated in a manner equal to the visual and auditory analyzers, nor synchronously, and are mismatched with one another, which results in the mismatching of the cortical and subcortical functional systems of the brain that respond to perception of space and, as a consequence, causes spatial disorientation. In the device for carrying out the method, the base is in the form of a rectangular plate and is provided with telescopic supports which are mounted vertically at the corners of the plate and have extensible rods. The supporting element comprises a rectangular platform, an electric drive, a driving roller and a displacement mechanism. The device is also provided with an inflatable pneumatic foot rest which is arranged on the platform, a compressor and a biaxial horizon sensor which is mounted on the platform, and is also electrically connected to a power supply unit, a commutator and computer. The computer is electrically connected by an input to the biaxial horizon sensor and by an output to the commutator, the outputs of which are electrically connected to electric drives of a longitudinal and transverse carrier, respectively.


The CREATOUR project – an incubator and a multidisciplinary collaborative research initiative – was created in order to develop a network of creative tourism initiatives in four Portuguese regions. This study's main purpose was to analyse the dynamics observed in the first stage of implementing this network and to understand the relationships and connections established between creative tourism actors operating at a regional and national level. The research also included examining the main goals and challenges these actors face when developing creative tourism activities in small cities and rural areas of Portugal. Stakeholder and social network analyses were used to process the data collected from each of the 20 pilots involved in this stage of the CREATOUR project. The results highlight relationships between various creative tourism pilot programmes and other regional and/or external actors and include an analysis of stakeholders' expectations regarding the network's future development.


It was found by experiment that axial and cubic pointsymmetries of rare earths in CaF2 may be changed into the other by annealing processes. The experiments were performed on CaF2 crystals containing 0.01 to 0.001% gadolinium, by heating them in a furnace to 1200 °C, holding at this temperature for 18 hr, and then cooling. Slow cooling (100 ° /hr) was found to result in gadolinium having axial symmetry; whereas quenching from 1200 °C to room temperature in 1 to 2 hr gave cubic symmetry. Heating at 1200°C for a short period or at low temperatures gives incomplete conversion of cubic into axial symmetry. It is concluded that excess F - ions are not tightly bound to the cube nearest the impurity at high temperatures and, under quenching conditions, have no time to diffuse to the energetically stable sites near the impurity.


An adaptation of Michel Faber's 2000 novel about alien invasion that updates the scifi horror tradition of the 1970s in an art-cinema mode, Under the Skin (Glazer, 2013) offers a stellar example of the 'monstrous' as both figure and form. Generally speaking, the interstitiality of the 'monstrous' demands strategies grounded in the disconnection between categories (image and sound, diegetic and nondiegetic), some of which have become horror movie cliches. Under the Skin is no exception. Its aesthetics of instability, correlated to a 'monstrous' figure that casts a defamiliarizing gaze on our world before attempting to 'become human', produces a complex subtext on contemporary alienation and identity politics, that puts the viewer in a position where he or she must both take moral responsibility for the categories he or she constructs (such as the 'monstrous'), and experience the mysterious physicality at the core of life itself.


Since its introduction in 1997, the Vitek 2 system (bioMerieux, Marcy-l'Etoile, France) has established itself as a stable and accurate automated system for rapid bacterial identification. Bacterial suspensions and test cards containing a panel of substrates are both placed into the instrument,


The objective of this study is to define the factors that hinder an effective online education through the opinions of the instructors regarding the transition process to emergency remote education due to the COVID-19 global pandemic as well as to determine the measures that are possible to be taken for the enhancement of the qualities in the field of education. As a qualitative research method, a phenomenological pattern is applied to the study for a detailed version of the teachers' experiences throughout the study. While composing the study group, the criterion sampling method is applied accordingly. The study group of this work is composed of 13 instructors who are determined from 7 universities which are actively functioning within TRNC. A semi-structured interview form with four questions, observation, and document analysis are used to collect data in order to increase the credibility of this study and to provide a thorough review of the issue. The outcome of this work indicates that problems occurred due to technical substructure inadequacies, thus the instructors encountered problems with the lessons that required application. It is found that the instructors need training for technology utilisation in teaching. It is considered that this work is to contribute to higher education institutions for the measurements to be taken for the betterment of the emergency remote teaching process and to enhance the quality of the teaching.


s for 2014th Annual Poster Presentation 624 the cultured cells were transferred to the normal medium, KIF11 was recruited to the membrane with other tight junction molecules. Cyst formation of MDCK cells was observed in matrigel within a week. Under 3D culture condition, KIF11 was exactly located at the apical lumen of MDCK cells. Conclusion: KIF11 is tightly associated with tight junction of renal epithelial cells in vivo and in vitro. Calcium switch experiment indicates that KIF11 is involved in the tight junction formation. Three-Dimensional Architecture of Podocytes Revealed by Block-Face Scanning Electron Microscopy Koichiro Ichimura , Masato Koike , Tatsuo Sakai 1 1 Department of Anatomy and Life Structure, 2 Department of Cell Biology and Neuroscience Block-face imaging is a scanning electron microscopic technique which enables easier acquisition of serial ultrastructural images directly from the surface of resin-embedded biological samples with a similar quality to transmission electron micrographs. In the present study, we analyzed the three-dimensional architecture of podocytes using serial block-face imaging. It was previously believed that podocytes are divided into three kinds of subcellular compartment: cell body, primary process, and foot process, which are simply aligned in this order. When the reconstructed podocytes were viewed from their basal side, the foot processes were branched from a ridge-like prominence, which was formed on the basal surface of the primary process and was similar to the usual foot processes in structure. Moreover, from the cell body, the foot processes were also emerged via the ridge-like prominence, as found in the primary process. The ridge-like prominence anchored the cell body and primary process to the glomerular basement membrane, and connected the foot processes to the cell body and primary process. In conclusion, serial block-face imaging is a powerful tool for clear understanding the three-dimensional architecture of podocytes through its ability to reveal novel structures which were difficult to determine by conventional transmission and scanning electron


In Good Morning Chick, a little chick pops o ut of its shell, ready to explore its new surroundings. With Mama by its side, the chick explores the barnyard. '


Benthic invertebrate communities of the upper Clark Fork River were sampled yearly from 1972 to 1984. Invertebrates were collected in fall using a modified Hess sampler at seven stations on the upper Clark Fork River, Mill and Willow Creek and Silver Bow Creek. The upstream control station on Mill and Willow Creek (CFRO) exhibited a balanced, diverse invertebrate community throughout the study. However, during the early part of the study no invertebrates were collected at the other headwater station on Silver Bow Creek (SBC5). Following improved mine wastewater treatment upstream of SBC5 in 1972, insects were eventually collected in 1975 and benthic densities and number of taxa have generally increased through 1984. Nonetheless, over the last 4 years, the densities (3708/m2) and number of taxa (26) in SBC5 have been considerably lower than those at CFRO (12 356/m2 and 57, respectively), The stations below the outflow of the Warm Springs Ponds have exhibited a noticeable response to the outflow of plankton from the ponds with benthic densities exceedil1g 60000/m2. These communities are composed primarily of filter feeding insects, both hydropsychid caddis flies and black flies. At the downstream stations, densities and number of taxa approach those originally observed at CFRO. However, the species composition at these lower stations 18 more typical of a large, low-gradient river rather than the headwater stream community found upstream.


Manufacturing method of an image display apparatus of the present invention, the horizontal a step of adhering to the substrate surface of the image display panel having a scratch that display defects the adhesive optical film, the adhesive optical film, the panel substrate portrait attached to the adhesive area of 10mm, and the creep amount of displacement (mm) after 1 hour at 23 ℃ in a case where loads in 500g X, Y the thickness (mm) of the pressure-sensitive adhesive layer of the pressure-sensitive adhesive type optical film and the image display panel, when the long side of the scratches (mm) / 2 of the panel surface of the substrate to a Z, the formula: is used by selecting according to the image display panel so as to satisfy Y × (0.97X + 0.45)> 0.19Z-0.006. According to the present invention, by filling the scratch by which the panel displays the defect on the substrate of the image display panel in the adhesive layer of the adhesive optical film, it is possible to eliminate the display defects due to scratches on the panel surface of the substrate. Adhesive optical film, an image display panel, the image display device


Our Vocabulary of ultimate purpose and order Apocalypse (Greek for "revelation of divine mysteries") means disaster, cosmic catastrophe, the end of the world; in scripture it is a vision of the future shape of eschatological events. The rich Jewish tradition of apocalyptic1 visions was inherited by Christ and his disciples,2 especially the second-generation figure of John of Patmos,author of the book of Revelation (also called Apocalypse) (ca.95 C.E.) The Jewish and Christian traditions, both profoundly influenced by Zoroastrianism, reverberate in the Qur'an's eschatological accounts 3 and,especially, the apocalyptic Hadith. Apocalypticism is the belief that the end is imminent.When an apocalyptic sense of imminence spreads,eschatological groups typically emerge under charismatic leaders. Every age produces a variety of apocalyptic movements appropriate to its circumstances, and their actions may focus on private salvation, sometimes through a combination of quietism and a withdrawal from the world, or on reform, or radical segregation of the righteous from the sinful majority, or on militant activism bent on restructuring society in order to hasten the final event. Islamic history is filled with apocalyptic movements, of differing nature, which fall within any of these categories. Millennialism, or millenarianism, is the belief in the kingdom of holiness, peace, justice, and plenty that the Messiah will establish on earth b efore the last judgment. Although the term millennium implies a thousand year kingdom, its duration—which is predicted in the Islamic sources in a variety of time frames—is of secondary importance; what matters is that, initiated by signs portending the cataclysmic end of ordinary time, and after a preliminary period of purging and transformation, human society reaches its final state on earth when all conflicts are resolved and all injustices removed. In the Islamic Hadith, two messianic figures, Jesus and the Mahdi, are portrayed as end-time rulers whose reigns signify that last period of justice and plenty. While apocalypticism is about disruption, upheaval, devastation, and endings, millennialism is about new beginnings, restoration, and regeneration. But the millennium itself is only a transitional, liminal "band of time," before in a final cataclysm the earth is devastated and the process of creation reversed. Apocalyptic millenarianism is defined as a form of activism that directs groups of believers who see themselves at the threshold of the awaited millennium (in the eschatological sense) toward radical political action, including anti-establishment attempts at restructuring society. It is a reaction to a collective sense of extremity, dislocation, and the feeling of living in truly terrible times. Natural disasters, political persecution, economic deprivation, even change itself—in the form of a negative discrepancy between expectation and reality—have triggered it, while atomic and ecological eschatology have recently added a new dimension. In the Islamic context, the Israeli-Palestinian conflict has joined the list of major grievances that, especially as formulated in popular sermons, pulp fiction narratives, on Websites and the like, can set the tone for an apocalyptic millenarian mind-frame in their mass audiences and readers.


Nasopharyngeal carcinoma is endemic in Southern China and the majority of patients present with local symptoms due to the tumor.


Purpose This study aims to report the incidence, severity and extent of pulmonary thromboembolic disease (PTD) in patients with confirmed COVID-19 who have undergone CT pulmonary angiography (CTPA) in a tertiary centre. Materials and Methods This is a retrospective analysis of all patients undergoing CTPA between 23rd March 2020 and 19th April 2020 in a tertiary centre. The presence of PTD, location and involved pulmonary lobes were documented. The pattern and extent of pulmonary parenchymal abnormalities including the presence of fibrosis, lymph node enlargement and pleural effusion were evaluated by two experienced observers independently and consensus was achieved for the most disparate results. Inter-observer agreement was assessed using Kappa statistics. Student t-test, Chi square and Mann-Whitney U tests were used to compare imaging features between PTD and non-PTD sub-groups. Results During the study period, 2157 patients were confirmed with COVID-19, 297/2157 (13.8%) had CT imaging, 100/2157 (4.6%) were CTPA studies, 93 studies were analysed, excluding sub-optimal studies. Overall incidence of PTD was 41/93 (44%) with a third of patients showing segmental and subsegmental PTD (n=28/93, 30%,). D-dimer was elevated in 90/93 (96.8%) of cases. High Wells score did not differentiate between PE and non-PE groups (p=0.801). The inter-observer agreement was fair (Kappa=0.659) for parenchymal pattern and excellent (Kappa = 0.816) for severity. Lymph node enlargement was found in 34/93 of cases (36.6%) with 29/34 (85.3%) showing no additional source of infection. Fibrosis was seen in 16/93 (17.2%) of cases, mainly demonstrating fibrotic organising pneumonia. Conclusion There is a high incidence of PTD in COVID -19 patients undergoing CTPA, complicated by lack of a valid risk stratification tool. Our data indicates a much higher suspicion of PTD is needed in severe COVID-19 patients. The concomitant presence of fibrotic features on CT indicates the need for follow-up for evaluation of chronic pulmonary complications.


This work constitutes a detailed study of the symmetries of the time-dependent Schrodinger equation in two spatial dimensions with an added inverse square potential of the form $(({a / {x_1^2 }}) + ({\beta / {x_2^2 }}))$. An intimate connection between these symmetries and the coordinate systems in which the equation separates is established. It is shown that there is a 1–1 correspondence between orbits of commuting pairs of symmetry operators—one taken from the Lie algebra of the symmetry group G and the other a second order symmetry operator—and G—inequivalent separable coordinate systems for the equation. The spectral analysis for all the basis functions corresponding to the different separable coordinate systems is computed. Then, making use of the symmetry group G, many addition and expansion theorems for the basis functions are derived. In this way, we find many special function identities involving Jacobi and Gegenbauer polynomials, Laguerre and Hermite polynomials, Whittaker functions, Bessel func...


During the Cassini mission (2004-2017) the Radio and Plasma Wave Science (RPWS) experiment has recorded the lightning radio emissions from multiple thunderstorms in Saturn's atmosphere. Most of the storms were located in the storm alley at a planetocentric latitude of 35°South, and there was one extra-large storm at 35°North called "Great White Spot" (GWS), which emitted millions of SEDs. This is short for "Saturn Electrostatic Discharges", a widely-used synonym for the radio emission from Saturn lightning. Most lightning storms have also been observed by the Cassini cameras or by ground-based amateur astronomers as bright white spots with diameters around 2000 km ("smaller" storms in the storm alley) or as large as 10,000 km (GWS at 35°North).

In this presentation we focus on a cyclone at 50°North planetocentric latitude, which was observed by the Cassini cameras from 2007 until the end of 2013. Its average diameter was around 3000 km, and it also exhibited some weak SED activity. The first SED outbreak was in December 2010, at the same time when the GWS was raging further south. Due to the differences in longitude and SED rate of the 50°N cyclone compared to the GWS, it is partly possible to separate the SEDs emitted from the cyclone to those emitted from the GWS. The SED rate of the cyclone is rather low, typically a few SEDs per minute, whereas the GWS showed SED rates up to 10 SEDs per second. The SED activity of the 50°North cyclone was very intermittent, it usually lasted for a few weeks before disappearing again for several months. After the first outbreak in December 2010, there was some more activity in early 2011, autumn 2011, December 2011, spring 2012, July 2012, summer 2013, and finally autumn 2013. By comparing SED data from RPWS with images from the Cassini camera we will show that almost all SEDs taking place after the GWS had their origin in the 50°N cyclone, since the SED sub-spacecraft longitude range is consistent with the longitude of the cyclone. The last SED activity from this cyclone took place in November 2013, and it was also the last SED activity recorded by RPWS during the whole Cassini mission. No more SEDs were found from November 2013 until Cassini burned up in Saturn's upper atmosphere in September 2017.


Spinel concentration in MS-7 glass (0% others) with its limited components shows to be dependent on several variable properties during heat treatments, primarily the limited number of nucleation sites and the growth rate of spinel. Equilibrium seems to be unaffected by this phenomenon, but the kinetics of spinel crystallization show a dependence. An empirical relationship between the number density (ns) of spinel in glass and the rate constant (k) in the Avrami equation was established showing that the kinetics of crystallization are temperature (T) and ns dependent.


Soley (1) argues that our study (2) does not prove that "transgenerational [epigenetic] inheritance serv[es] an adaptive role in evolution" in honey bees. This view misrepresents our intent. Our main findings are that in honey bees 1) DNA methylation profiles are much more similar between fathers and daughters than between unrelated males and females of different generations and 2) DNAmethylation profiles are conserved across somatic and germline tissues (2). We are agnostic as to whether DNA methylation marks are caused by environmental or genetic factors. Rather, we stress that DNA methylation patterns are conserved across generations. Soley misrepresents our main findings by stating that "only a fraction of the methylated regions was considered to have been thus transferred to the following generation" (1), referring to "the proportion of methylated CpGs that were inherited specifically from fathers to daughters [being] between 18 and 29%." These figures are correct, yet they only refer to a small portion of the methylome that has informative polymorphisms for which it is possible to ascertain parental origin. In fact, 85 ± 3% of DNA methylation sites have an identical status across generations (2). Soley argues that sequence polymorphism is probably the key determinant of the DNA methylation state in honey bees (1). We concur, as already highlighted in some of our previous papers (3, 4). Soley further questions the absence of epigenetic reprogramming in honey-bee embryos (1). We agree that our findings leave open the possibility that DNA methylation marks are erased and reapplied in a genotype-specific manner each generation. Yet, recent studies have clearly shown that there is no remodeling of DNA methylation during development in honey bees (5, 6). We thus think that epigenetic reprogramming is highly unlikely in honey bees, and probably in many other nonmammalian organisms (7). Finally, we welcome Soley's points on future directions needed to fully ascertain the presence of transgenerational epigenetic inheritance in bees (1), as we state in our own conclusions: "Whether [transgenerational epigenetic inheritance] processes are adaptive or able to influence macroevolution remains unclear.. . . It is thus more than ever necessary to uncover the molecular consequences of DNA methylation if we are to understand its evolutionary implications" (2).


The check-list of mosses of the Lappland State Nature Reserve includes 253 species. 69 ones were found on this territory for the first time. 15 moss species are protected in the Murmansk region


This paper describes the development of an Integrated Structural Design System for Reinforced Concrete Buildings
(INDECON) that incorporates design systems for the design of reinforced concrete buildings. This paper begins with formal
design models for the integrated system and explores implementation methodologies of the integrated system using the design
models. The design models include the Design Object Mode(DOM) and the Design Activity Model(DAM), which describe design
data and design tasks, respectively, during the structural design process of reinforced concrete buildings. The design models
cover the structural design process from the preliminary design phase to the detailed design phase for a limited scope of
reinforced concrete buildings. The design models could automate, by organizing the topology of structural components in
three-dimensional space, several design tasks such as arranging beams and slabs, assuming structural component section
dimensions, grouping structural components, and generating design loads. Then the design models are transformed and specified
in detail for each part of the integrated system, which involves a central database and three design modules: a preliminary
design module(PDM), a structural design module(SDM), and a detailed design module(DDM). The integrated system can be
used for the design of regular shape reinforced concrete buildings, but the methodologies used for developing the integrated
system can be applied to more comprehensive integrated systems for various kinds of reinforced concrete buildings.


In reviewing the literature dealing with the bacteriology of rheumatoid arthritis, 1 one is impressed by the diversity of the results obtained. While the relation of focal infection to rheumatoid arthritis is generally recognized, there is doubt in the minds of many as to whether the joint manifestations are actually metastatic infections or whether they are merely an expression of some toxic or allergic influence. In respect to the bacteriologic agent responsible for the disease, the majority of investigators look on the streptococcus as the exciting cause, but there is considerable disagreement as to which type is responsible. Some workers consider rheumatoid arthritis a Streptococcus hemolyticus infection while others look on the indifferent or green producing streptococcus as the causative agent. Still other investigators believe that the staphylococcus, the diphtheroid bacillus or other micro-organisms as well as the streptococcus can produce deforming arthritis. Although a number of workers have found


Different devices are used to connect the micro-grid with the main network. As of their performance difference, the effect on main-network may not be the same, so it is necessary to carry out relevant research. Firstly, based on the structure of PET, one of the advanced access device, a steady-state analysis model is constructed in ETAP. Secondly, according to the composition of the discussed micro-grid, its operational analysis is done when the supply and demand vary. Finally, the variation of power loss, voltage deviation, harmonic components in the main grid, which reflect the influence of micro-grid with PET are shown. Meanwhile, the corresponding control strategy of PET is also given.


Among a number of English translations of Lisao, Yang Xianyi and Gladys Yang's version and Xu Yuanchong's version are often regarded as the most representative ones. The article, based on the self-built parallel corpus of Lisao and the corpora of English British Romantic Poems, explores the stylistic features of Lisao's English translations of the Yangs and Xu Yuanchong through analysis of the collected data. The findings have shown that the Yang's version is more variable in the use of words, more complex in sentence structures and more difficult in readability than Xu's. The former has the tendency of explicitation while the latter simplification; In addition, the Yang's version is faithful and close to the original structure, and Xu's is simple and smooth in diction and sentence structure. The stylistic differences of the two translations by the Yangs and Xu can be attributed to the translators' different views on translation their purposes and the strategies they chose.


The differential cross sections for the excitation of helium atoms to the n=2 level are calculated in the high-energy region by applying the Coulomb-projected Born approximation as proposed by Geltman (1971). Good agreement in the angular distribution is obtained with recently published data.


Inflammatory bowel disease (IBD) patients are an emerging category of patients at risk of HCMV infection, because they are often immunosuppressed and because HCMV has preferential tropism for sites of inflammation. However, the role of the virus in this population of patients is still unclear. Current and most widely theories suggest that HCMV could be responsible for flares and/or make the patient develop resistance to medical treatment; besides, some data suggest that HCMV infection could be responsible for a more aggressive course of the disease. We still do not know if the flare of HCMV is related to a loss of competence of the immune system in IBD patients due to immunosuppressive medications or to the reactivation of the disease itself.
Aims of the study were:
1) assessment of low-grade HCMV infection (microinfection) on colonic biopsies from a cohort of IBD patients and evaluation of the correlation with inflammation and the therapeutical regimen.
2) assessment of HCMV specific T-cell response in IBD patients in peripheral blood and evaluation of its possible correlation with disease activity and type of treatment.
The first part of the study has been conducted on a retrospective cohort of consecutive non-selected IBD patients and controls (patients who performed colonoscopy for colorectal cancer screening or because of gastrointestinal symptoms, without any pathological finding at endoscopy and at histological examination). Intestinal biopsies were evaluated through a highly sensitive immunohistochemistry (IHC) protocol for HCMV immediate early (IE) and pp65 antigens. In addition real time PCR for HCMV IE-DNA and micro-RNA UL112 (the latest being involved in immune-evasion strategies) was performed.
The HCMV-specific T cell response was evaluated in a prospective cohort of consecutive, non-selected IBD patients (in a cross-sectional and longitudinal study). For each patient the HCMV serology status was evaluated and in IgG-positive patients the HCMV-specific T-cell response was assessed in monocytes from peripheral blood (PBMCs), using an IFN-γ EliSpot assay. Patients were stratified according to the disease clinical activity indexes validated for Crohn'€™s disease (CD) and for ulcerative colitis (UC) and according to the therapeutic regimen. Levels of HCMV-specific immune response were considered normal if the EliSpot assay displayed at least 20 spot forming colonies (SFCs)/200000 PBMCs.
The retrospective part of the study was conducted on 32 IBD patients (11 CD and 21 UC) and 8 controls; a total of 116 biopsies (collected during 55 different colonoscopies) were analyzed using IHC for HCMV antigens. 84 biopsies (72%) were collected on inflamed mucosa, while the remaining from uninflamed mucosa of IBD patients or from healthy mucosa from controls. IE-IHC was positive in 43% of the biopsies; none of them were from uninflamed mucosa; pp65-IHC was positive in 45% of biopsies, only one coming from a control patient. Intestinal inflammation was associated to an increased percentage of HCMV-IHC positivity; no difference was observed between biopsies collected from uninflamed mucosa of IBD patients and from control subjects. Immunosuppressive therapy (both monotherapy and combination therapy) was not associated with an increased risk of HCMV antigens positivity at IHC. However, non-immunosuppressed IBD patients were more frequently HCMV positive than controls. The study of HCMV IE-DNA expression was performed on 40 intestinal biopsies, with no evidence of HCMV in 65% of cases. In the positive cases the levels of expression were significantly inferior to the reference standard, with non difference between biopsies collected from inflamed and non-inflamed areas. A pilot study of the expression of HCMV UL112 microRNA has been performed on 24 biopsies; this microRNA was expressed in all the biopsies studied, however levels of expression were significantly inferior to the reference standard.
In the prospective study 167 patients were enrolled and 125 (75%) were HCMV IgG-positive. 13% patients had low levels of HCMV-T cell specific response with a median value of 6 SFCs/200000 PBMCs (range 0-19). Twelve out of these 17 patients were on immunosoppressive therapy at the time of inclusion in the study. In 10 patients the disease was at least mildly active. The 29% of patients had moderate response (median 60.5 SFCs/200000 PBMCs (range 24-99); the majority of patients displayed a high HCMV specific immune response (median 199.5 SFC/200000 PBMCs (range 100-1000)). CD and UC patients displayed similar levels of specific response. Medical therapy did not influence the levels of immunity (in terms of number and types of immunosuppressors used). In particular, 19 patients tested before and after the beginning of anti-TNF therapy did not display a significant change in the specific levels of immunity.
In conclusion, it seems plausible that latent virus could reactivate in inflammatory conditions, regardless the therapeutic regimen of the patient. On the other hand, the virus activates immune-evasion strategies in order to restore the latency status and ensure its own persistence in the host.


The comprehension of learning sciences (IPA) connected type in senior high school (SLTP) 21 Surabayapurposes to describing as follows: (1) The activities of teacher and students, (2) The abilities of teacher onlearning management, (3) Students Respons to learning proses, (4) Evaluation student Result after attendinglearning Process (KBM) IPA type connected. Data observation had been done during 5-19 May 2001. Theresearch result showed teather activities in KBM increasing significantly, Student respons to KBM wasinterested in continuing the lessons. The proportion of answer-question is right encrising from 0.23 to 0.92.The conclusion of research is connected type.


Hand burns are extremely common. Morbidity from such burns can be significant and overall quality of life post injury relies heavily on appropriate hand function. It is important to identify and treat burns of the hands in order to minimize morbidity. Appropriate assessment of burn wound depth and hand function is critical with particular attention to prevention of vascular compromise via procedures for decompression of pressure.


Over the last few years severe insect damage has been caused to several species of Gasteria and Haworthia plants (Asphodelaceae) in greenhouses at the Kirstenbosch National Botanical Garden, Cape Town, Western Cape, resulting in the death of the plants (Fig. 1). Examination of the plants showed that the damage was caused by lepidopterous larvae. The larvae destroy the roots of the plants by tunnelling into them, hollowing them out and eventually rendering the plants without roots (Fig. 2). Then they tunnel into the base of the plant and, if it still survives as the hardy succulents can do, into the leaves. The plants eventually disintegrate. The larvae were reared to the adult stage and the moth was identified as Opogona scaphopis Meyrick (Lepidoptera: Tineidae: Hieroxestinae). The phytophagous behaviour of this species is unusual for members of the Tineidae, the family to which the clothes moths belong, as they mostly feed on decaying animal or vegetable matter or fungi (Henning 1985; Davis & Peña 1990). However, two other Opogona species also feed on living plants. Opogona omoscopa (Meyrick), which is present in South Africa (with specimens from Cape Town in the Iziko South African Museum, Cape Town), feeds on decaying vegetation, but also on gladioli corms and pineapple roots (Sterling et al. 2009). Opogona sacchari (Bojer), known as the banana moth, can cause damage to a wide range of plants by burrowing into the plant tissue, including sugar cane, maize, banana (particularly the inflorescences) (Davis & Peña 1990) and pineapple (Vorsino et al. 2005). The latter has also been recorded from South Africa (Davis & Peña 1990), but (like O. scaphopis) is not listed by Prinsloo & Uys (2015) as an insect of cultivated plants. Earlier references to O. scaphopis are Meyrick (1909), who described the species from specimens reared from Aloe, and Taylor (1957) who mentions roots of Haworthia sp. as a host for O. scaphopis. The mature larva of O. scaphopis is 8–10 mm long, dirty grey to brown in colour, with a prominent dark brown head. The alimentary canal usually shows black through the semi-transparent integument (Fig. 3). The pupal case is formed from silk and covered with small sand particles (Fig. 4). It was found in the detritus remains of damaged plants and on dry leaves. The folded wings of the small adult moth (Fig. 5) have a pale yellow-green or mustard colour (clear pale ochreous-yellow, according to Meyrick 1909). At the back they show a dark, semi-triangular patch stretching to the middle of the body. In this study the adults appeared during the period April to June. Opogona scaphopis has previously only been collected in the eastern and northern parts of South Africa. The type specimen in the Iziko South African Museum was collected in Port Elizabeth and Taylor (1975) lists Port Elizabeth as a locality for this species. The Ditsong National Museum of Natural History, Pretoria, has specimens from Grahamstown and Pretoria. The species was probably brought to the Western Cape with Gasteria and Haworthia specimens collected in the Eastern Cape for the Kirstenbosch Botanical Garden (E. van Jaarsveld, pers. comm.) where it is presently confined to the greenhouse where the plants are kept. In view of the serious damage caused by the insect, attempts will be made to eradicate it with repeated applications of the insecticide cypermethrin. Suggested common names for this insect: Gasteria borer, Gasteria boorder (Afrikaans).


PURPOSE: A method for effectively searching a homepage through the recalculation of the URL(Uniform Resource Locator) included relation based similarity is provided to easily know whether a searched web document is the homepage or not without visiting the URL of the searched web document. CONSTITUTION: A text is extracted from the searched web document according to a query from a user(S400). An index file for performing the web searching is generated by indexing the extracted text(S406). The web document and a searching result ranking the web document by considering the weight of a searching query are output. The similarity for the ranked searching result web documents is recalculated by using the URL included relation of the searched web document. The web document corresponding to the homepage is displayed with a high priority by rearranging the rank of the web document through the recalculated similarity.


The present invention relates to a stereovision eye test device. The stereovision eye test device includes: a three-dimensional display unit which displays a three-dimensional image; a reference two-dimensional display unit which displays a reference two-dimensional image; an ocular unit which is placed to face the reference two-dimensional display unit for viewing of the three-dimensional image and the reference two-dimensional image; a reflection mirror which is installed closely to but separably from the three-dimensional display unit while being placed to face the three-dimensional display unit; and a half mirror which is placed between the three-dimensional display unit and the reflection mirror and is placed in the intersecting area between the progress path of the reference two-dimensional image and the progress path of the three-dimensional image. The reference two-dimensional image displayed from the reference two-dimensional display unit penetrates through the half mirror and goes towards the ocular unit. The three-dimensional image from the three-dimensional display unit penetrates through the half mirror, is reflected by the reflection mirror, then is reflected by the half mirror, and goes towards the ocular unit. By doing so, when examining stereovision capability of each individual, it is possible to accurately measure stereovision capability of each individual.


Significance Growing partisan polarization and democratic "backsliding" in various parts of the world have raised concerns about the attachment of ordinary Americans to democratic institutions and procedures. I find that substantial numbers of Republicans endorse statements contemplating violations of key democratic norms, including respect for the law and for the outcomes of elections and eschewing the use of force in pursuit of political ends. The strongest predictor by far of these antidemocratic attitudes is ethnic antagonism—especially concerns about the political power and claims on government resources of immigrants, African-Americans, and Latinos. The strong tendency of ethnocentric Republicans to countenance violence and lawlessness, even prospectively and hypothetically, underlines the significance of ethnic conflict in contemporary US politics. Most Republicans in a January 2020 survey agreed that "the traditional American way of life is disappearing so fast that we may have to use force to save it." More than 40% agreed that "a time will come when patriotic Americans have to take the law into their own hands." (In both cases, most of the rest said they were unsure; only one in four or five disagreed.) I use 127 survey items to measure six potential bases of these and other antidemocratic sentiments: partisan affect, enthusiasm for President Trump, political cynicism, economic conservatism, cultural conservatism, and ethnic antagonism. The strongest predictor by far, for the Republican rank-and-file as a whole and for a variety of subgroups defined by education, locale, sex, and political attitudes, is ethnic antagonism—especially concerns about the political power and claims on government resources of immigrants, African-Americans, and Latinos. The corrosive impact of ethnic antagonism on Republicans' commitment to democracy underlines the significance of ethnic conflict in contemporary US politics.


Post-traumatic stress disorder (PTSD) is an anxiety disorder that may develop after exposure to a life-threatening traumatic experience and according to the DSM-IV diagnostic criteria, involves characteristic features such as persistent experiencing of trauma, avoidance, numbing, and hyperarousal (DSM-IV, 1994). Although many individuals with PTSD recover during the first couple of years following traumatic exposure, up to 30–40% remain chronically symptomatic (Kessler et al., 1995). Furthermore, individuals with chronic PTSD were shown to maintain conditioned fear responses to traumatic stimuli even 40–50 years after the trauma (Orr et al., 1993). The largest body of treatment literature exists for antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). Extensive clinical experience with these agents and their efficacy for disorders that are commonly comorbid with PTSD means that their use will likely continue until better treatment options are found (Davidson, 2000; Ravindran & Stein, 2009) even though their efficacy and that of other pharmacological treatments is generally limited. The high prevalence, chronicity, and resistance to treatment underscore the importance of the development of effective therapeutic strategies for PTSD. The endocannabinoid (eCB) system has arisen as part of the complex circuitry that regulates anxiety and as a crucial mediator of emotional learning (Marsicano et al., 2002; Viveros et al., 2005; Laviolette & Grace, 2006a,2006b; Gorzalka et al., 2008; Ganon-Elazar & Akirav, 2009; Lutz, 2009; Hill & Gorzalka, 2009; Parolaro et al., 2010). The idea that the eCB system is involved in the control of anxiety-like behaviour is rooted in the fact that Cannabis sativa is used recreationally, mainly for its euphoric effects. However, this picture is confounded by the fact that cannabis abusers sometimes experience dysphoric reactions, with feelings of anxiety and panic. Additionally, it has been suggested that a temporary form of drug‐induced psychosis can occur in some cannabis users. This 'marijuana psychosis' is usually due to exposure to large doses of the drug (Iversen, 2003) and has similar symptoms to paranoid schizophrenia. This has led some to propose a 'cannabinoid hypothesis of schizophrenia', suggesting that the symptoms of schizophrenic illness might be caused by an abnormal over‐activity of endogenous cannabinoid mechanisms in the brain (Emrich et al., 1997). An interesting question in cannabis research is whether cannabis use can precipitate long‐term psychiatric illness. There are several reports suggesting that the development of cannabis dependence in young people is associated with increased rates of psychiatric symptoms, including psychosis, depression and anxiety (Andreasson et al., 1987; Mathers &


Grass pollen extract adsorbed on to a suspension of L‐tyrosine has been tested over 2 years as a treatment for hay fever. Eight‐ or nine‐dose courses terminating at doses of between 1000 and 10,000 Noon units were equally effective when compared either with a placebo or with a pyridine‐extracted alum precipitate.


Alcuronium pharmacokinetics and pharmacodynamics were studied in ten patients, aged between two and six years and weighing between 10 and 20 kg, who were undergoing elective surgery. Eight patients received a single dose of alcuronium quaternary base, 0.25 mg·kg−1; two patients required an additional dose after a similar initial dose. Alcuronium concentrations were determined using a specific liquid chromatographic procedure. In all patients, alcuronium plasma concentrations decline in a bi‐exponential fashion with time. Several significant differences were noted when the pharmacokinetic parameters in children were compared with those obtained previously in adults. Young children had shorter mean distribution (5 vs 14 min, P < 0.001) and elimination phase half‐lives (131 vs 199 min, P < 0.05) and a faster clearance from the body when corrected for differences in body weight (2.7 vs 1.4 ml·min−1·kg−1, P < 0.005). Alcuronium volumes of distribution were smaller in children compared with adults in absolute (uncorrected) terms, but no differences were observed when these were expressed relative to body weight. Maximum paralysis achieved in children was similar to that in adults, but was observed to occur more rapidly (4 vs 10 min, P < 0.005). Alcuronium plasma concentrations, at peak paralysis, were not different to those in adults (1.8 vs 1.4 μg·ml−1). Young children eliminate alcuronium more efficiently, but exhibit the same sensitivity to alcuronium during onset of paralysis as adults.


Education in Indonesia must be transformed based on the 21st century era, which resulted in religious, character, intelligent students, and based on the Law on the National Education System in 2003, and Government Regulation of the Republic of Indonesia Number 57 of 2021 concerning National Education Standards. This study aimed to develop a learning model of Angkola Batak culture-based Experience, South Tapanuli, North Sumatra, through teaching practices in micro-teaching courses. This research used the Research and Development research method by applying the Plomp development model. Random sampling used as a sampling technique consisted of 90 students from the Teacher Education of Islamic Elementary School, Institut Agama Islam Negeri Padangsidimpuan in the sixth semester. Data collected used observation and questionnaires assisted by google form. Data analysis used STATCAL software. The results showed discrepancies were found between the program and expectations as well as reality, while students had not fully understood designing lesson plans based on the applicable curriculum, synchronized the design of lesson plans and the practice, and students were not allowed to teach in schools in order to be able to practice theory and practical teaching applications. At the same time, the program study vision is to prepare Islamic Elementary School teachers with Islamic, innovative, competitive, and professional personalities associated with South Tapanuli culture, like the Angkola Batak. So, it is necessary to develop programs to improve students' skills in applying the learning in the 21st century.


Rural leisure industry is an integral part of the happiness-oriented industries in counties, and is also the important content to increase the people's welfare, build the beautiful country, and realize economic, political, cultural, social, and ecological progress. Based on the interpretation of happiness-oriented rural leisure industries, combined with the system of happiness-oriented rural leisure industries and the characteristics of local resources, from the perspectives of the dominant industry construction and leisure benefits, this paper takes Pinghe county in Zhangzhou as an example, and proposes the development models and construction means of happiness-oriented rural leisure industries, to develop the county economy, and improve the sense of happiness of local residents and tourists.


Inverse Reinforcement Learning (IRL) deals with the problem of recovering the reward function optimized by an expert given a set of demonstrations of the expert's policy. Most IRL algorithms need to repeatedly compute the optimal policy for different reward functions. This paper proposes a new IRL approach that allows to recover the reward function without the need of solving any "direct" RL problem. The idea is to find the reward function that minimizes the gradient of a parameterized representation of the expert's policy. In particular, when the reward function can be represented as a linear combination of some basis functions, we will show that the aforementioned optimization problem can be efficiently solved. We present a preliminary empirical evaluation of the proposed approach on a multidimensional version of the Linear-Quadratic Regulator (LQR) both in the case where the parameters of the expert's policy are known and in the (more realistic) case where the parameters of the expert's policy need to be inferred from the expert's demonstrations.