834 resultados para limitations of therapy


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Injectable drug nanocarriers have greatly benefited in their clinical development from the addition of a superficial hydrophilic corona to improve their cargo pharmacokinetics. The most studied and used polymer for this purpose is poly(ethylene glycol), PEG. However, in spite of its wide use for over two decades now, there is no general consensus on the optimum PEG chain coverage-density and size required to escape from the mononuclear phagocyte system and to extend the circulation time. Moreover, cellular uptake and active targeting may have conflicting requirements in terms of surface properties of the nanocarriers which complicates even more the optimization process. These persistent issues can be largely attributed to the lack of straightforward characterization techniques to assess the coverage-density, the conformation or the thickness of a PEG layer grafted or adsorbed on a particulate drug carrier and is certainly one of the main reasons why so few clinical applications involving PEG coated particle-based drug delivery systems are under clinical trial so far. The objective of this review is to provide the reader with a brief description of the most relevant techniques used to assess qualitatively or quantitatively PEG chain coverage-density, conformation and layer thickness on polymeric nanoparticles. Emphasis has been made on polymeric particle (solid core) either made of copolymers containing PEG chains or modified after particle formation. Advantages and limitations of each technique are presented as well as methods to calculate PEG coverage-density and to investigate PEG chains conformation on the NP surface.

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En génétique dite « classique », l’examen d’un phénotype conduit à l’étude des gènes impliqués dans son obtention. La génétique inverse est une méthode expérimentale très puissante dans laquelle, au contraire, le matériel génétique est modifié et utilisé pour reconstruire un organisme complet, afin de déterminer le résultat de ces modifications. Cette approche est spécialement bien adaptée à l'étude des virus, compte tenu de la relative simplicité et de la petite taille de leurs génomes; l’obstacle principal demeure de récupérer des virus infectieux à partir de génomes viraux clonés. Au cours des années, cet exploit a été accompli pour des représentants de presque toutes les familles de virus de mammifères. Jusqu’à récemment, les Reoviridae, virus à génome d'ARN bicaténaire segmenté, faisaient toutefois exception. Dans cette revue, les progrès réalisés vers la mise au point de la génétique inverse pour l'étude du réovirus seront discutés. La génétique inverse pourrait avoir un impact majeur dans l'optimisation de nouvelles souches de réovirus pour leur utilisation en thérapie comme agents oncolytiques et pour le développement de vaccins dans le cas des rotavirus et des orbivirus. Les travaux actuels font toutefois ressortir les limites de l'approche, la nécessité d’une analyse prudente des résultats obtenus, ainsi que le besoin de développer des systèmes plus efficaces et polyvalents.

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Sonar signal processing comprises of a large number of signal processing algorithms for implementing functions such as Target Detection, Localisation, Classification, Tracking and Parameter estimation. Current implementations of these functions rely on conventional techniques largely based on Fourier Techniques, primarily meant for stationary signals. Interestingly enough, the signals received by the sonar sensors are often non-stationary and hence processing methods capable of handling the non-stationarity will definitely fare better than Fourier transform based methods.Time-frequency methods(TFMs) are known as one of the best DSP tools for nonstationary signal processing, with which one can analyze signals in time and frequency domains simultaneously. But, other than STFT, TFMs have been largely limited to academic research because of the complexity of the algorithms and the limitations of computing power. With the availability of fast processors, many applications of TFMs have been reported in the fields of speech and image processing and biomedical applications, but not many in sonar processing. A structured effort, to fill these lacunae by exploring the potential of TFMs in sonar applications, is the net outcome of this thesis. To this end, four TFMs have been explored in detail viz. Wavelet Transform, Fractional Fourier Transfonn, Wigner Ville Distribution and Ambiguity Function and their potential in implementing five major sonar functions has been demonstrated with very promising results. What has been conclusively brought out in this thesis, is that there is no "one best TFM" for all applications, but there is "one best TFM" for each application. Accordingly, the TFM has to be adapted and tailored in many ways in order to develop specific algorithms for each of the applications.

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The thesis has covered various aspects of modeling and analysis of finite mean time series with symmetric stable distributed innovations. Time series analysis based on Box and Jenkins methods are the most popular approaches where the models are linear and errors are Gaussian. We highlighted the limitations of classical time series analysis tools and explored some generalized tools and organized the approach parallel to the classical set up. In the present thesis we mainly studied the estimation and prediction of signal plus noise model. Here we assumed the signal and noise follow some models with symmetric stable innovations.We start the thesis with some motivating examples and application areas of alpha stable time series models. Classical time series analysis and corresponding theories based on finite variance models are extensively discussed in second chapter. We also surveyed the existing theories and methods correspond to infinite variance models in the same chapter. We present a linear filtering method for computing the filter weights assigned to the observation for estimating unobserved signal under general noisy environment in third chapter. Here we consider both the signal and the noise as stationary processes with infinite variance innovations. We derived semi infinite, double infinite and asymmetric signal extraction filters based on minimum dispersion criteria. Finite length filters based on Kalman-Levy filters are developed and identified the pattern of the filter weights. Simulation studies show that the proposed methods are competent enough in signal extraction for processes with infinite variance.Parameter estimation of autoregressive signals observed in a symmetric stable noise environment is discussed in fourth chapter. Here we used higher order Yule-Walker type estimation using auto-covariation function and exemplify the methods by simulation and application to Sea surface temperature data. We increased the number of Yule-Walker equations and proposed a ordinary least square estimate to the autoregressive parameters. Singularity problem of the auto-covariation matrix is addressed and derived a modified version of the Generalized Yule-Walker method using singular value decomposition.In fifth chapter of the thesis we introduced partial covariation function as a tool for stable time series analysis where covariance or partial covariance is ill defined. Asymptotic results of the partial auto-covariation is studied and its application in model identification of stable auto-regressive models are discussed. We generalize the Durbin-Levinson algorithm to include infinite variance models in terms of partial auto-covariation function and introduce a new information criteria for consistent order estimation of stable autoregressive model.In chapter six we explore the application of the techniques discussed in the previous chapter in signal processing. Frequency estimation of sinusoidal signal observed in symmetric stable noisy environment is discussed in this context. Here we introduced a parametric spectrum analysis and frequency estimate using power transfer function. Estimate of the power transfer function is obtained using the modified generalized Yule-Walker approach. Another important problem in statistical signal processing is to identify the number of sinusoidal components in an observed signal. We used a modified version of the proposed information criteria for this purpose.

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The general objective of the study is to examine in depth the organisation and management practices of newspaper industry in Kerala with particular reference to the marketing aspects, with a View to suggesting measures for improving the economics and the managerial efficiency of the industry. The detailed investigation into the management aspects of the industry is done with particular reference to the two most popular Malayalam dailies in Kerala, namely, the Malayala Manorama and the Mathrubhumi. The purposeful selection of these two papers for the study is amply justified as these two dailies together account for about 80 percent of the total circulation of the newspapers in Kerala. Technically speaking, both these papers are owned by organisations registered as public limited companies and are, to a large extent professionally managed. The Malayala Manorama, though a public limited company in principle, functions, however, more or less as a private company or a family concern. These two papers therefore provide a scope for studying the management of newspaper industry practically under two different organisational set up, namely private limited company and public limited company The study has been divided into eight chapters. Chapter-I spells out an introduction about the newspaper industry and its unique features.Chapter-II, deals with a review of literature, objective, scope, methodology and limitations of the study. Chapter-III deals with origin, growth and status of newspaper industry. Chapter—IV examines the cost, revenue and profitability of the Malayala Manorama and Mathrubhumi. Chapter-V deals with the Organisation and Management. Chapter-VI examines the Marketing Management of Newspapers. Chapter-VII deals with the Marketing Strategy and Performance of Malayala Manorama and Mathrubhumi: An Assessment. Chapter-VIII presents the main findings of the study.

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The co-operative credit structure in a state set up consists of 3 tiers — Primary Societies at the base, District Co-operative Banks at the middle and State Cooperative Bank at the top. But, some societies at the primary level are governed by, in addition to Co-operative Societies Act, the Banking Regulation Act. Thus they are under dual control. In addition, they are working under the direct purview of Reserve Bank of India. The scope of this study is restricted to such Primary Societies, District Co-operative Banks and State Co-operative Bank. For the evaluation of the working of Co-operative Banks, the board of directors and staff were interviewed with the help of pre-constructed and pre-tested interview schedules. However, the share holders and customers were not interviewed mainly because almost all respondents were reluctant to provide copies of an exhaustive list of share holders and non-share holder customers, for the purpose of maintaining secrecy. This being an individual work, it was found physically and financially very difficult to extend the study so as to cover the share holders and non-share holder customers. Limitations of time were also responsible for restricting this study. The period of study was restricted to 1980-'81 to 1983-'84 as the data relating to earlier periods were firstly not available from all banks and secondly the prior data was considered out of date for the purpose of the study.

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The present study is entitled The Aesthetics of Paul Verlaine and Changampuzha Krishnapillai - a comparative perspective. The purpose of the study is to compare the poetic genius of the French poet Paul Verlaine (1844-1896) and that of the Malayalam poet Changampuzha Krishnapillai (1911-1948), within a descriptive framework. The investigation will hopefully answer the questions- Has Changampuzha been indeed influenced by Verlaine, if so, to what extent? Can the aesthetic appreciation be justified in both poets as illustrated in their works? The comparative methodology of juxtaposing the selected oeuvres of the poets is largely adopted in the study. Since the span of analysis is across national and linguistic borders, the distinguishing as well as exclusive traits of the individual poets will be of much importance in formulating the comparative assumption in this work. The vastly differing geographical, linguistic and cultural milieus of these two poets,-one a national French poet and the other, a regional Indian poet writing in Malayalam prima facie,endow the theme of the dissertation with an innate hue of diversity. Such an ambitious task would naturally entail a renewed research into the dedication of the poets to their muses and their ultimate contributions to poetics. The analysis, while attempting to illuminate from a fresh angle, the amply researched oeuvre of Verlaine and the lesser studied one of Changampuzha, cannot but be aware of the limitations of the task at hand. The present study is the first of its kind on the specific theme of analysis, and is hoped that it would be of relevance since no work has so far been known to have been undertaken on the topic. At a time when the birth centenary celebrations of Changampuzha have just concluded, this study is hoped to assume significance as it would help in isolating the originality of the poet's works, extricating the garb of the French influence. Ultimately, this study aims at creating a wider appreciation of the impact that the French writers have had on Malayalam writers, thus shedding new light on the benign foreign influences that served to enhance the beauty of our cultural heritage

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Internationalization of higher education has become one of the most important policies for institutions of higher education worldwide. Though universities are international by nature, the need for intensified quality activities of international nature has promoted internationalization to be under spotlight of researchers, administrators and policy makers and to be an area for research. Each institution follows its certain way to govern its international affairs. Most Universities, especially in the 'Developed World' started to plan it strategically. This study explores the meanings and importance of internationalization especially that it means different things to different people. It also studies the rationales behind internationalizing higher education. It focuses on the four main prevailing rationales; political, cultural/social, economic/financial, and academic on both national and institutional levels. With the increasing need to strategically plan, the study explores internationalization strategies in terms of how to develop them, what are their approaches and types, and their components and dimensions. Damascus University has witnessed an overwhelming development of its international relations and activities. Therefore, it started to face a problem of how to deal with this increasing load especially that its International Office is the only unit that deals with the international issues. In order to study the internationalization phenomenon at Damascus University, the 2WH approach, which asks the what, why, and how questions, is used and in order to define the International Office's role in the internationalization process of the University, it studies it and the international offices of Kassel University, and Humboldt University in Germany, The University of Jordan, and Al Baath University in Syria using the 'SOCIAL' approach that studies and analyses the situation, organization, challenges, involvement, ambitions, and limitations of these offices. The internationalization process at the above-mentioned Universities is studied and compared in terms of its meaning, rationales for both the institution and its academic staff, challenges and strategic planning. Then a comparison is made among the international offices of the Universities to identify their approaches, what led to their success and what led to their failure in their practices. The aim is to provide Damascus University and its International Office with some good practices and, depending on the experiences of the professionals of the case-studies, a suggested guidance to the work of this Office and the University in general is given. The study uses the interviews with the different officials and stakeholders of the case-studies as the main method of collecting the information in addition to site visits, studying their official documents and their websites. The study belongs to qualitative research that has an action dimension in it since the recommendations will be applied in the International Office. The study concludes with few learned lessons for Damascus University and its International Office depending on the comparison that was done according to a set of dimensions. Finally a reflection on the relationship between internationalization of higher education and politics, the impact of politics on Middle Eastern Universities, and institutional internationalization strategies are presented.

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The structural, electronic and magnetic properties of one-dimensional 3d transition-metal (TM) monoatomic chains having linear, zigzag and ladder geometries are investigated in the frame-work of first-principles density-functional theory. The stability of long-range magnetic order along the nanowires is determined by computing the corresponding frozen-magnon dispersion relations as a function of the 'spin-wave' vector q. First, we show that the ground-state magnetic orders of V, Mn and Fe linear chains at the equilibrium interatomic distances are non-collinear (NC) spin-density waves (SDWs) with characteristic equilibrium wave vectors q that depend on the composition and interatomic distance. The electronic and magnetic properties of these novel spin-spiral structures are discussed from a local perspective by analyzing the spin-polarized electronic densities of states, the local magnetic moments and the spin-density distributions for representative values q. Second, we investigate the stability of NC spin arrangements in Fe zigzag chains and ladders. We find that the non-collinear SDWs are remarkably stable in the biatomic chains (square ladder), whereas ferromagnetic order (q =0) dominates in zigzag chains (triangular ladders). The different magnetic structures are interpreted in terms of the corresponding effective exchange interactions J(ij) between the local magnetic moments μ(i) and μ(j) at atoms i and j. The effective couplings are derived by fitting a classical Heisenberg model to the ab initio magnon dispersion relations. In addition they are analyzed in the framework of general magnetic phase diagrams having arbitrary first, second, and third nearest-neighbor (NN) interactions J(ij). The effect of external electric fields (EFs) on the stability of NC magnetic order has been quantified for representative monoatomic free-standing and deposited chains. We find that an external EF, which is applied perpendicular to the chains, favors non-collinear order in V chains, whereas it stabilizes the ferromagnetic (FM) order in Fe chains. Moreover, our calculations reveal a change in the magnetic order of V chains deposited on the Cu(110) surface in the presence of external EFs. In this case the NC spiral order, which was unstable in the absence of EF, becomes the most favorable one when perpendicular fields of the order of 0.1 V/Å are applied. As a final application of the theory we study the magnetic interactions within monoatomic TM chains deposited on graphene sheets. One observes that even weak chain substrate hybridizations can modify the magnetic order. Mn and Fe chains show incommensurable NC spin configurations. Remarkably, V chains show a transition from a spiral magnetic order in the freestanding geometry to FM order when they are deposited on a graphene sheet. Some TM-terminated zigzag graphene-nanoribbons, for example V and Fe terminated nanoribbons, also show NC spin configurations. Finally, the magnetic anisotropy energies (MAEs) of TM chains on graphene are investigated. It is shown that Co and Fe chains exhibit significant MAEs and orbital magnetic moments with in-plane easy magnetization axis. The remarkable changes in the magnetic properties of chains on graphene are correlated to charge transfers from the TMs to NN carbon atoms. Goals and limitations of this study and the resulting perspectives of future investigations are discussed.

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Catadioptric sensors are combinations of mirrors and lenses made in order to obtain a wide field of view. In this paper we propose a new sensor that has omnidirectional viewing ability and it also provides depth information about the nearby surrounding. The sensor is based on a conventional camera coupled with a laser emitter and two hyperbolic mirrors. Mathematical formulation and precise specifications of the intrinsic and extrinsic parameters of the sensor are discussed. Our approach overcomes limitations of the existing omni-directional sensors and eventually leads to reduced costs of production

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Introducción: los tumores neuroendocrinos gastroenteropancreáticos se diagnostican en estadio avanzado en 60 - 80% de los pacientes y las opciones terapéuticas son limitadas. Se realizó una revisión sobre el beneficio clínico del tratamiento con [177Lu - DOTA - Tyr3] - Octreotate en pacientes con enfermedad metastásica o inoperable. Objetivos: evaluar la eficacia, impacto en calidad de vida y toxicidad de la terapia con 177Lu DOTATE en pacientes con tumores neuroendocrinos gastroenteropancreáticos avanzados. Materiales y Métodos: se condujo una revisión sistemática de la literatura mediante la búsqueda de estudios clínicos prospectivos y retrospectivos en bases electrónicas (MEDLINE, EMBASE, LILACS, SCIELO, OVID y la Biblioteca Cochrane) de cualquier idioma, año y estado de publicación. Se incluyeron 5 estudios, por la heterogeneidad existente entre los estudios no se realizó un metaanálisis. Resultados: la respuesta tumoral global fue del 45 - 57%, la enfermedad permaneció estable en 27% - 38% y progresó en 6% - 21% de casos en las series incluidas. El tiempo libre de progresión osciló entre 31 - 40 meses y la sobrevida global de 31– 51 meses. Se observó toxicidad hematológica grado 3-4 hasta en 9.5% de pacientes. Hubo mejoría significativa en la calidad de vida de pacientes tratados con 177LuDOTATATE. Conclusiones: la terapia con 177Lu- DOTATATE ofrece un beneficio clínico a los pacientes con tumores neuroendocrinos bien diferenciados avanzados por su impacto positivo en calidad de vida, control de síntomas, ralentiza la progresión tumoral y su toxicidad es baja.

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It is in the interest of most states to eliminate double taxation (i.e. the payment of the same tax in two jurisdictions) of transnational commercial enterprises. Because such disputes involve, on the one hand, the state imposition of taxes, a right universally asserted by all states, and private entities on the other, taxation disputes between such parties are not, on their face, easily susceptible to arbitration. This article analyzes two dispute settlement procedures-the OECD First Model Tax Convention and a similar EU Convention-with the exclusive focus on disputes relating to the imposition of double taxation. It will look at the ways in which state roles may vary under these procedures from assisting in the negotiation process to taking a part similar to, but with important differences from, diplomatic protection on behalf of an affected enterprise. The article will examine the situations under which the settlement procedure is required and/or available, how the procedures are triggered, the obligations and parts played by the parties, the means by which the disputes are resolved (from negotiations to tribunals) and the limitations of the procedures. Are they “taxpayer friendly”? As a result the reader may draw comparisons between the two procedures. Finally, the article will look at the proposed OECD Arbitration Clause which is intended to be incorporated into Article 25 of the OECD Model Tax Convention as well as how these mechanisms relate and/or conflict with bilateral tax treaties and the GATS.

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The goal of this research was to identify predic- tive psychosocial factors of the subjective quality of life in a group of 60 people, with ages between 19 and 57, from both sexes, included in the program of demobilization and social inclusion of the Pro- grama de la Alta Consejería para la Reintegración Social y Económica de Personas y Grupos Alzados en Armas en Colombia. this research was a predic- tive correlational descriptive study. the Question- naire of optimism/Pessimism was used to assess the optimist or pessimist trend, and, for assess the quality of life, these strategies were combined: a home visit to value the objective quality of life, the Analogous scale of subjective Quality of Life to value satisfaction and well-being, and a general format to collect socio-demographic and juridical information. Results show that some variables as perceived health, optimism, educational level, re- ligious believes, objective quality of life, type of demobilization and years spent in the armed group operating outside the law, are associated to better levels of perceived quality of life. The findings and limitations of the study are discussed.  

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At the end of the last century, a model to explain clinical observations related to the mandibular growth was developed. According to it, the lateral pterigoid muscle (LPM) was one of the main modulators of the differentiation of mesenquimal cells inside the condyle to condroblasts or osteoblasts, and therefore of the growth of the mandibular condilar cartilage (CCM). The main components of the model were the humoral and the mechanical. Nowadays, the humoral would include growth factors such as IGF-I, FGF-2 and VEGF, which seem to be involved in mandibular growth. Since skeletal muscle can secrete these growth factors, there is a possibility that LPM modulates the growth of CCM by a paracrine or endocrine mechanism. The mechanical component derived from the observations that both the blood flow inside the temporomandibular joint (ATM) and the action of the retrodiscal pad on the growth of the CCM, depend, in part, on the contractile activity of the LPM. Despite the fact that there are some results suggesting  hat LPM is activated under conditions of mandibular protrusion, there is no full agreement on whether this can stimulate the growth of CCM. In this review, the contributions and limitations of the works related to mandibular growth are discussed and a model which integrates the available information to explain the role of the LPM in the growth of the CCM is proposed.

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The growth and expansion of cities during the last century can’t be seen without taking into account the important role they have assumed in the transport infrastructure. In Bogota have passed trough streetcar, buses and automóviles was deciding for the city, because all this periods marked a drastic change in growth morphology. This article studies the planning of Mass Transit System –MTS– Transmilenio and its interaction with the urban structure, in light of the current city planning framework. It also specifies the behavior of land use in the construction of the system first phase. One of the most important findings of this study is that there is no articulation between land and transport use system, despite the decisions taken in the ordering model. Similarly, local and intermediate planning exhibits Peak articulation.The existing infrastructure of the MTS reiterates the tendency to concentrate the accessibility in one place: the center has the largest accessibility whereas periphery fails to overcome its limitations of accessibility. While the city continued with this trend the existence of a coordinated planning system for Bogota and the ability to meet expectations of planning model is questionable, however it is something that depends not only on MTS.