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Multidrug resistance in Cancer: Pharmacological Strategies from Basic Research to Clinical Issues

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196159 Year: Pages: 99 DOI: 10.3389/978-2-88919-615-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology --- Science (General) --- Therapeutics
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More than 40 years ago, the observation that doxorubicin-resistant tumor cells were cross-resistant to several structurally different anticancer agents was the first step in the discovery of P-glycoprotein (P-gp). P-gp belongs to the superfamily of ATP-binding cassette (ABC) transporters;its overexpression has become a therapeutic target for overcoming multidrug resistance in tumors. However, P-gp is also expressed in cells of normal tissues where it plays a physiological role, by protecting them from the toxic effects of xenobiotics. Also, ABCB1 gene polymorphisms may influence the response to anticancer drugs substrate of P-gp. Several strategies to overcome P-gp tumor drug resistance have been suggested. P-gp 'circumvention’ is the most explored and is based on the coadministration of anticancer agents and pump inhibitors (P-gp modulators). Despite the positive findings obtained in preclinical studies, results of clinical trials are not yet successful and clinical research is still ongoing. Other investigational approaches have been studied (e.g. P-gp targeting antibodies, use of antisense strategies or transcriptional regulators targeting ABCB1 gene expression) but their use is still circumscribed to the preclinical setting. A further approach is represented by the encapsulation of P-gp substrate anticancer drugs into liposomes or nanoparticles. This strategy has shown higher efficacy in tumor previously treated with the free drug. The reasons explaining the increased efficacy of liposomal/nanoparticle-based drugs in Pgp-overexpressing tumors include the coating with specific surfactants, the composition changes in the plasma membrane microdomains where P-gp is embedded, the direct impairment of P-gp catalytic mechanisms exerted by specific component of the liposomal shell, but are not yet fully understood. A second strategy to overcome P-gp tumor drug resistance is represented by exploiting the P-gp presence. Actually, P-gp-overexpressing cells show increased sensitivity (collateral sensitivity) to some drugs (e.g. verapamil, narcotic analgesics) and to some investigational compounds (e.g. NSC73306). P-gp-overexpressing cell are hypersensitive to reactive oxygen species, to agents perturbing the energetic metabolic pathways, changing the membrane compositions, reducing the efflux of endogenous toxic catabolites. However, the mechanisms explaining collateral sensitivity have not been fully elucidated. Another approach to exploit P-gp is represented by ABCB1 gene transfer to transform bone marrow progenitor cells into a drug resistant state which may allow conventional or higher doses of anticancer drug substrates of P-gp to be administered safely after transplantation. More recently the development and introduction in the clinics of anticancer drugs which are not substrates of P-gp (e.g. new microtubule modulators, topoisomerase inhibitors) has provided a new and promising strategy to overcome P-gp tumor drug resistance (P-gp 'evasion'). This ‘research topic’ issue aims at exploding the above mentioned matters, in particular by: -retracing the history of the first researches on P-gp - describing the physiological role of P-gp - describing the molecular basis, structural features and mechanism of action of P-gp - describing diagnostic laboratory methods useful to determine the expression of P-gp and its transporter function - describing strategies to overcome tumor drug resistance due to P-gp and other ABC transporters - indicating novel approaches to overcome P-gp multidrug resistance, ranging from basic research studies to pre-clinical/clinical studies.

The multiple roles of antibiotics and antibiotic resistance in nature

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195251 Year: Pages: 134 DOI: 10.3389/978-2-88919-525-1 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
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Antibiotics and antibiotic resistance have most commonly been viewed in the context of human use and effects. However, both have co-existed in nature for millennia. Recently the roles of antibiotics and antibiotic resistance genes have started to be discussed in terms of functions other than bacterial inhibition and protection. This special topic will focus on both the traditional role of antibiotics as warfare mechanisms and their alternative roles and uses within nature such as antibiotics as signals or communication mechanisms, antibiotic selection at low concentrations, the non-specific role of resistance mechanisms in nature: e.g. efflux pumps, evolution of antibiotic resistance and the role of persisters in natural antibiotic resistance.

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Microbiology --- mobile elements --- Plasmids --- Soil --- Water --- human --- environment --- Standards --- risk

Multiregionalism and Multilateralism : Asian-European Relations in a Global Context

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Book Series: ICAS Publications Series / Edited Volumes ISBN: 9789053569290 Year: Pages: 192 DOI: 10.5117/9789053569290 Language: English
Publisher: Amsterdam University Press
Subject: Social Sciences --- Political Science
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The Asia-Europe Meeting (ASEM, est. 1996) is an interregional forum which consists of the members of the European Union and the Association of Southeast Asian Nations and China, Japan and South Korea. The main components of the ASEM process include political dialogue, economy, education and culture. Multiregionalism and Multilateralism focuses on the institutionalsiation of intra-regional and inter-regional cooperation in the international system with emphasis on the changing relationship between the EU, China and India. The role of ASEM in this relationship is growing more important because of the growth of multilateralism as cornerstone of the international system.

'Multiregionalism' en 'multilateralism' worden in de vakliteratuur gebruikt voor twee fenomenen die iedereen uit de praktijk kent. Bij multilateralisme gaat het om het oplossen van wereldwijde problemen door samenwerking tussen vele landen, zoals bijvoorbeeld in de Verenigde Naties. Bij multiregionalisme gaat het om blokken van samenwerkende landen die daardoor sterker staan, zoals bijvoorbeeld bij de EU. De nationale staat brokkelt onder de toenemende invloed van deze twee krachten steeds verder af terwijl de rol van NGO's als Green Peace of Human Rights Watch steeds groter worden. Ook in de verhoudingen tussen Azië en Europa spelen die krachten een steeds grotere rol. Multiregionalism and Multilateralism. Asian-European Relations in a Global Context geeft daarvan aansprekende voorbeelden.

Multisensory and sensorimotor interactions in speech perception

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195480 Year: Pages: 263 DOI: 10.3389/978-2-88919-548-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Psychology
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Speech is multisensory since it is perceived through several senses. Audition is the most important one as speech is mostly heard. The role of vision has long been acknowledged since many articulatory gestures can be seen on the talker's face. Sometimes speech can even be felt by touching the face. The best-known multisensory illusion is the McGurk effect, where incongruent visual articulation changes the auditory percept. The interest in the McGurk effect arises from a major general question in multisensory research: How is information from different senses combined? Despite decades of research, a conclusive explanation for the illusion remains elusive. This is a good demonstration of the challenges in the study of multisensory integration. Speech is special in many ways. It is the main means of human communication, and a manifestation of a unique language system. It is a signal with which all humans have a lot of experience. We are exposed to it from birth, and learn it through development in face-to-face contact with others. It is a signal that we can both perceive and produce. The role of the motor system in speech perception has been debated for a long time. Despite very active current research, it is still unclear to which extent, and in which role, the motor system is involved in speech perception. Recent evidence shows that brain areas involved in speech production are activated during listening to speech and watching a talker's articulatory gestures. Speaking involves coordination of articulatory movements and monitoring their auditory and somatosensory consequences. How do auditory, visual, somatosensory, and motor brain areas interact during speech perception? How do these sensorimotor interactions contribute to speech perception? It is surprising that despite a vast amount of research, the secrets of speech perception have not yet been solved. The multisensory and sensorimotor approaches provide new opportunities in solving them. Contributions to the research topic are encouraged for a wide spectrum of research on speech perception in multisensory and sensorimotor contexts, including novel experimental findings ranging from psychophysics to brain imaging, theories and models, reviews and opinions.

Multisensory Integration in Action Control

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193127 Year: Pages: 142 DOI: 10.3389/978-2-88919-312-7 Language: English
Publisher: Frontiers Media SA
Subject: Psychology --- Science (General)
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The integration of multisensory information is an essential mechanism in perception and in controlling actions. Research in multisensory integration is concerned with how the information from the different sensory modalities, such as the senses of vision, hearing, smell, taste, touch, and proprioception, are integrated to a coherent representation of objects. Multisensory integration is central for action control. For instance, when you grasp for a rubber duck, you can see its size and hear the sound it produces. Moreover, identical physical properties of an object can be provided by different senses. You can both see and feel the size of the rubber duck. Even when you grasp for the rubber duck with a tool (e.g. with tongs), the information from the hand, from the effect points of the tool and from the eyes are integrated in a manner to act successfully. Over the recent decade a surge of interest in multisensory integration and action control has been witnessed, especially in connection with the idea that multiple sensory sources are integrated in an optimized way. For this perspective to mature, it will be helpful to delve deeper into the information processing mechanisms and their neural correlates, asking about the range and constraints of this mechanisms, about its localization and involved networks.

Multisensory Integration: Brain, Body and the World

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197927 Year: Pages: 186 DOI: 10.3389/978-2-88919-792-7 Language: English
Publisher: Frontiers Media SA
Subject: Psychology --- Science (General)
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Behaviour, language, and reasoning are expressions of neural functions par excellence, as the brain must draw on sensory modalities to gather information on the rest of the body and on the outer world. Cortical areas processing the identity and location of sensory inputs were once thought to be organised hierarchically, with some branches dedicated to basic features and other branches dedicated to complex features. Yet current studies have uncovered synergistic effects at early sensory cortices as well as at higher-level association areas. A less hierarchical functional architecture of the brain has emerged such that, irrespective of sensory modality, inputs would be allocated to the best suited cortical substrate. It is our hope that the articles included in this special issue will offer novel insights into recent developments relating to multisensory integration and brain functioning.

Multisensory Perception And Action: Psychophysics, Neural Mechanisms, And Applications

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193813 Year: Pages: 174 DOI: 10.3389/978-2-88919-381-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
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Our senses are not separated. Information received from one sensory modality may be linked with, or distorted by information provided from another modality, such as in the ventriloquism illusion and experiences of crossmodal correspondence. Scientific interest in how we integrate multisensory information and how we interact with a multisensory world has increased dramatically over the last two decades, as evidenced by an exponential growth of relevant studies using behavioral and/or neuro-scientific approaches to investigate multisensory integration and the underlying brain mechanisms. This work has revealed that the brain integrates information across senses in a statistically optimal manner; also, some key multisensory brain areas, such as the superior colliculus, have been identified. However, many questions remain unresolved. For example, at what age do we develop optimal multisensory integration? How does the brain 'know' which stimuli to combine, and which to segregate? What are the principles that govern crossmodal interactions? Does multisensory integration rely solely on the variability of sensory information? Do primary sensory cortices also contribute to multisensory integration? How does multisensory integration influence our sensorimotor interactions? To take stock of the most recent developments, this Research Topic aims to provide a broad scope of research on multisensory perception and action from different perspectives/approaches and disciplines, including behavioral and neuro-sciences, computational/mathematical modeling, and engineering science. Specifically, the Research Topic will focus on the following topics: 1. Functional and behavioral mechanisms of multisensory perception 2. Neural mechanisms of multisensory coding 3. Multisensory perception and sensorimotor interaction 4. Multisensory applications

Mundo do crime: a ordem pelo avesso

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ISBN: 9788599662267 Year: Pages: 166 DOI: http://dx.doi.org/10.7476/9788599662267 Language: PT
Publisher: SciELO Books - Centro Edelstein
Subject: Social and Public Welfare
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O crime e a prisão constituem os objetos de estudo deste livro. Procura-se percebê-los a partir da ótica do próprio criminoso enquanto preso, ponto de vista nem sempre reconhecido como legítimo. As várias discussões sobre o tema têm sistematicamente colocado em uma nova roupagem velhas concepções sobre os criminosos e a prisão, concepções estas que em geral reproduzem versões difundidas pelo sistema judiciário. É para pensar esta temática através de outra perspectiva, que este trabalho procura se desenvolver. Discute-se aqui, não só a versão do criminoso sobre o mundo do crime e suas formas de manifestação na prisão, como também as formas pelas quais sua consciência capta a situação num contexto mais amplo, em que a origem social tem um peso fundamental na sua identificação enquanto delinqüente.

Keywords

Centro Edelstein

Municipalités et pouvoirs locaux au Liban

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ISBN: 9782905465207 9782351594537 Year: Language: fr
Publisher: Presses de l’Ifpo
License: OpenEdition licence for Books

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Huit ans après la fin de la guerre du Liban, les élections municipales de 1998, les premières depuis 1963, sont perçues comme un enjeu de représentation par l'ensemble des forces sociales et politiques au sens où elles consacrent dans le court terme l'émergence d'un nouveau personnel politique dans les instances locales. Elles sont vues aussi comme un moyen de redonner aux municipalités un rôle au niveau du développement local, dans le cadre plus général de la reconstruction des structures ét...

Der Munizipalsozialismus in Europa /Le socialisme municipal en Europe

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Book Series: Pariser Historische Studien ISSN: 2190-1325 ISBN: 9783486832945 Year: Volume: 57 Pages: 155 DOI: 10.1524/9783486832945 Language: German, French
Publisher: De Gruyter
Subject: History
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Im ausgehenden 19. Jahrhundert standen alle Städte vor dem Problem, eine rasch wachsende Bevölkerung mit öffentlichen Dienstleistungen zu versorgen. Diese Aufgabe ging weit über den bisherigen Tätigkeitsbereich der Gemeinden hinaus. In unterschiedlichem Ausmaß und Breite boten die Städte Leistungen an, die bislang als gänzlich private Angelegenheit gegolten hatten. Während einerseits "Munizipalsozialismus" eine Politik bezeichnete, die am Anfang des modernen Wohlfahrtsstaates steht, galt er andererseits als Staatsintervention, welche die Grundlagen der liberal-kapitalistischen Gesellschaft bedrohte. Die aktuellen Debatten über Deregulierung und die bereits verwirklichten Schritte in diese Richtung lassen es sinnvoll erscheinen, einen Blick darauf zu werfen, was denn "Munizipalsozialismus" in Europas zwischen 1880 und 1939 tatsächlich bedeutete. Die Beiträge über Frankreich, Spanien, Deutschland, England und die Schweiz zeigen die ganze Spannweite kommunaler Interventionspolitik auf, die sich je nach den politischen Rahmenbedingungen von purem Fiskalismus bis zu Maßnahmen erstreckte, die eindeutig sozialistischer Theorie entsprangen.

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Listing 561 - 570 of 639 << page
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