300 resultados para Drug Discovery


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Background: There is a growing trend for individuals to seek health information from online sources. Alcohol and other drug (AOD) use is a significant health problem worldwide, but access and use of AOD websites is poorly understood. ----- ----- Objective: To investigate content and functionality preferences for AOD and other health websites. Methods: An anonymous online survey examined general Internet and AOD-specific usage and search behaviors, valued features of AOD and health-related websites (general and interactive website features), indicators of website trustworthiness, valued AOD website tools or functions, and treatment modality preferences. ----- ----- Results: Surveys were obtained from 1214 drug (n = 766) and alcohol website users (n = 448) (mean age 26.2 years, range 16-70). There were no significant differences between alcohol and drug groups on demographic variables, Internet usage, indicators of website trustworthiness, or on preferences for AOD website functionality. A robust website design/navigation, open access, and validated content provision were highly valued by both groups. While attractiveness and pictures or graphics were also valued, high-cost features (videos, animations, games) were minority preferences. Almost half of respondents in both groups were unable to readily access the information they sought. Alcohol website users placed greater importance on several AOD website tools and functions than did those accessing other drug websites: online screening tools (χ²2 = 15.8, P < .001, n = 985); prevention programs (χ²2 = 27.5, P < .001, n = 981); tracking functions (χ²2 = 11.5, P = .003, n = 983); self help treatment programs (χ²2 = 8.3, P = .02, n = 984); downloadable fact sheets for friends (χ²2 = 11.6, P = .003, n = 981); or family (χ²2 = 12.7, P = .002, n = 983). The most preferred online treatment option for both the user groups was an Internet site with email therapist support. Explorations of demographic differences were also performed. While gender did not affect survey responses, younger respondents were more likely to value interactive and social networking features, whereas downloading of credible information was most highly valued by older respondents. ----- ----- Conclusions: Significant deficiencies in the provision of accessible information on AOD websites were identified, an important problem since information seeking was the most common reason for accessing these websites, and, therefore, may be a key avenue for engaging website users in behaviour change. The few differences between AOD website users suggested that both types of websites may have similar features, although alcohol website users may more readily be engaged in screening, prevention and self-help programs, tracking change, and may value fact sheets more highly. While the sociodemographic differences require replication and clarification, these differences support the notion that the design and features of AOD websites should target specific audiences to have maximal impact.

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Poly(lactide-co-glycolide) (PLGA) beads have been widely studied as a potential drug/protein carrier. The main shortcomings of PLGA beads are that they lack bioactivity and controllable drug-delivery ability, and their acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Akermanite (AK) (Ca(2) MgSi(2) O(7) ) is a novel bioactive ceramic which has shown excellent bioactivity and degradation in vivo. This study aimed to incorporate AK to PLGA beads to improve the physiochemical, drug-delivery, and biological properties of PLGA beads. The microstructure of beads was characterized by SEM. The effect of AK incorporating into PLGA beads on the mechanical strength, apatite-formation ability, the loading and release of BSA, and the proliferation, and differentiation of bone marrow stromal cells (BMSCs) was investigated. The results showed that the incorporation of AK into PLGA beads altered the anisotropic microporous structure into homogenous one and improved their compressive strength and apatite-formation ability in simulated body fluids (SBF). AK neutralized the acidic products from PLGA beads, leading to stable pH value of 7.4 in biological environment. AK led to a sustainable and controllable release of bovine serum albumin (BSA) in PLGA beads. The incorporation of AK into PLGA beads enhanced the proliferation and alkaline phosphatase activity of BMSCs. This study implies that the incorporation of AK into PLGA beads is a promising method to enhance their physiochemical and biological property. AK/PLGA composite beads are a potential bioactive drug-delivery system for bone tissue repair.

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The enforcement of Intellectual Property rights poses one of the greatest current threats to the privacy of individuals online. Recent trends have shown that the balance between privacy and intellectual property enforcement has been shifted in favour of intellectual property owners. This article discusses the ways in which the scope of preliminary discovery and Anton Piller orders have been overly expanded in actions where large amounts of electronic information is available, especially against online intermediaries (service providers and content hosts). The victim in these cases is usually the end user whose privacy has been infringed without a right of reply and sometimes without notice. This article proposes some ways in which the delicate balance can be restored, and considers some safeguards for user privacy. These safeguards include restructuring the threshold tests for discovery, limiting the scope of information disclosed, distinguishing identity discovery from information discovery, and distinguishing information preservation from preliminary discovery.

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Recent research has begun to address and even compare nascent entrepreneurship and nascent corporate entrepreneurship. An opportunity based view holds great potential to integrate both streams of research, but also presents challenges in how we define corporate entrepreneurship. We extend (corporate) entrepreneurship literature to the opportunity identification phase by providing a framework to classify different types of corporate entrepreneurship. Through analysis of a large dataset on nascent (corporate) entrepreneurship (PSEDII) we show that these corporate entrepreneurs differ largely from each other in terms of human capital. Prior studies have indicated that independent and corporate entrepreneurs pursue different types of opportunities and utilize different strategies. Our findings from the opportunity identification phase challenge those differences and seem to indicate a difference between the opportunities corporate entrepreneurs identify versus the opportunities they exploit.

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In today’s electronic world vast amounts of knowledge is stored within many datasets and databases. Often the default format of this data means that the knowledge within is not immediately accessible, but rather has to be mined and extracted. This requires automated tools and they need to be effective and efficient. Association rule mining is one approach to obtaining knowledge stored with datasets / databases which includes frequent patterns and association rules between the items / attributes of a dataset with varying levels of strength. However, this is also association rule mining’s downside; the number of rules that can be found is usually very big. In order to effectively use the association rules (and the knowledge within) the number of rules needs to be kept manageable, thus it is necessary to have a method to reduce the number of association rules. However, we do not want to lose knowledge through this process. Thus the idea of non-redundant association rule mining was born. A second issue with association rule mining is determining which ones are interesting. The standard approach has been to use support and confidence. But they have their limitations. Approaches which use information about the dataset’s structure to measure association rules are limited, but could yield useful association rules if tapped. Finally, while it is important to be able to get interesting association rules from a dataset in a manageable size, it is equally as important to be able to apply them in a practical way, where the knowledge they contain can be taken advantage of. Association rules show items / attributes that appear together frequently. Recommendation systems also look at patterns and items / attributes that occur together frequently in order to make a recommendation to a person. It should therefore be possible to bring the two together. In this thesis we look at these three issues and propose approaches to help. For discovering non-redundant rules we propose enhanced approaches to rule mining in multi-level datasets that will allow hierarchically redundant association rules to be identified and removed, without information loss. When it comes to discovering interesting association rules based on the dataset’s structure we propose three measures for use in multi-level datasets. Lastly, we propose and demonstrate an approach that allows for association rules to be practically and effectively used in a recommender system, while at the same time improving the recommender system’s performance. This especially becomes evident when looking at the user cold-start problem for a recommender system. In fact our proposal helps to solve this serious problem facing recommender systems.

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Many data mining techniques have been proposed for mining useful patterns in text documents. However, how to effectively use and update discovered patterns is still an open research issue, especially in the domain of text mining. Since most existing text mining methods adopted term-based approaches, they all suffer from the problems of polysemy and synonymy. Over the years, people have often held the hypothesis that pattern (or phrase) based approaches should perform better than the term-based ones, but many experiments did not support this hypothesis. This paper presents an innovative technique, effective pattern discovery which includes the processes of pattern deploying and pattern evolving, to improve the effectiveness of using and updating discovered patterns for finding relevant and interesting information. Substantial experiments on RCV1 data collection and TREC topics demonstrate that the proposed solution achieves encouraging performance.

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This study examined the effect that temporal order within the entrepreneurial discovery-exploitation process has on the outcomes of venture creation. Consistent with sequential theories of discovery-exploitation, the general flow of venture creation was found to be directed from discovery toward exploitation in a random sample of nascent ventures. However, venture creation attempts which specifically follow this sequence derive poor outcomes. Moreover, simultaneous discovery-exploitation was the most prevalent temporal order observed, and venture attempts that proceed in this manner more likely become operational. These findings suggest that venture creation is a multi-scale phenomenon that is at once directional in time, and simultaneously driven by symbiotically coupled discovery and exploitation.

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It is a big challenge to guarantee the quality of discovered relevance features in text documents for describing user preferences because of the large number of terms, patterns, and noise. Most existing popular text mining and classification methods have adopted term-based approaches. However, they have all suffered from the problems of polysemy and synonymy. Over the years, people have often held the hypothesis that pattern-based methods should perform better than term-based ones in describing user preferences, but many experiments do not support this hypothesis. The innovative technique presented in paper makes a breakthrough for this difficulty. This technique discovers both positive and negative patterns in text documents as higher level features in order to accurately weight low-level features (terms) based on their specificity and their distributions in the higher level features. Substantial experiments using this technique on Reuters Corpus Volume 1 and TREC topics show that the proposed approach significantly outperforms both the state-of-the-art term-based methods underpinned by Okapi BM25, Rocchio or Support Vector Machine and pattern based methods on precision, recall and F measures.

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An existing model for solvent penetration and drug release from a spherically-shaped polymeric drug delivery device is revisited. The model has two moving boundaries, one that describes the interface between the glassy and rubbery states of polymer, and another that defines the interface between the polymer ball and the pool of solvent. The model is extended so that the nonlinear diffusion coefficient of drug explicitly depends on the concentration of solvent, and the resulting equations are solved numerically using a front-fixing transformation together with a finite difference spatial discretisation and the method of lines. We present evidence that our scheme is much more accurate than a previous scheme. Asymptotic results in the small-time limit are presented, which show how the use of a kinetic law as a boundary condition on the innermost moving boundary dictates qualitative behaviour, the scalings being very different to the similar moving boundary problem that arises from modelling the melting of an ice ball. The implication is that the model considered here exhibits what is referred to as ``non-Fickian'' or Case II diffusion which, together with the initially constant rate of drug release, has certain appeal from a pharmaceutical perspective.

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The use of mesoporous bioactive glasses (MBG) for drug delivery and bone tissue regeneration has grown significantly over the past 5 years. In this review, we highlight the recent advances made in the preparation of MBG particles, spheres, fibers and scaffolds. The advantages of MBG for drug delivery and bone scaffold applications are related to this material’s well-ordered mesopore channel structure, superior bioactivity, and the application for the delivery of both hydrophilic and hydrophobic drugs. A brief forward-looking perspective on the potential clinical applications of MBG in regenerative medicine is also discussed.

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Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

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A model for drug diffusion from a spherical polymeric drug delivery device is considered. The model contains two key features. The first is that solvent diffuses into the polymer, which then transitions from a glassy to a rubbery state. The interface between the two states of polymer is modelled as a moving boundary, whose speed is governed by a kinetic law; the same moving boundary problem arises in the one-phase limit of a Stefan problem with kinetic undercooling. The second feature is that drug diffuses only through the rubbery region, with a nonlinear diffusion coefficient that depends on the concentration of solvent. We analyse the model using both formal asymptotics and numerical computation, the latter by applying a front-fixing scheme with a finite volume method. Previous results are extended and comparisons are made with linear models that work well under certain parameter regimes. Finally, a model for a multi-layered drug delivery device is suggested, which allows for more flexible control of drug release.

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We consider the problem of choosing, sequentially, a map which assigns elements of a set A to a few elements of a set B. On each round, the algorithm suffers some cost associated with the chosen assignment, and the goal is to minimize the cumulative loss of these choices relative to the best map on the entire sequence. Even though the offline problem of finding the best map is provably hard, we show that there is an equivalent online approximation algorithm, Randomized Map Prediction (RMP), that is efficient and performs nearly as well. While drawing upon results from the "Online Prediction with Expert Advice" setting, we show how RMP can be utilized as an online approach to several standard batch problems. We apply RMP to online clustering as well as online feature selection and, surprisingly, RMP often outperforms the standard batch algorithms on these problems.