Indispensability arguments in favour of reductive explanations

Instances of explanatory reduction are often advocated on metaphysical grounds; given that the only real things in the world are subatomic particles and their interaction, we have to try to explain everything in terms of the laws of physics. In this paper, we show that explanatory reduction cannot be defended on metaphysical grounds. Nevertheless, indispensability arguments for reductive explanations can be developed, taking into account actual scientific practice and the role of epistemic interests. Reductive explanations might be indispensable to address some epistemic interest answering a specific explanation-seeking question in the most accurate, adequate and efficient way. Just like explanatory pluralists often advocate the indispensability of higher levels of explanation pointing at the pragmatic value of the explanatory information obtained on these higher levels, we argue that explanatory reduction – traditionally understood as the contender of pluralism – can be defended in a similar way. The pragmatic value reductionist, lower level explanations might have in the biomedical sciences and the social sciences is illustrated by some case studies

Synthesis of thiaheterocyclic benzohydroxamic acids and evaluation of their HDAC6 inhibitory activity

The hydroxamic acid functionality is an important group in different chemistry disciplines, such as coordination chemistry and medicinal chemistry, due to its excellent metal-chelating properties. In this PhD thesis, the interest in the hydroxamic acid moiety is specifically related to effective and selective histone deacetylase 6 (HDAC6) inhibition. HDAC6 is a member of the broader histone deacetylases enzyme family, which regulate the folding of DNA around histones and thus indirectly influence transcription. A major drawback associated with non-selective HDAC inhibitors concerns their toxic side effects. As HDAC6 recently emerged as a relevant drug target, the aim of this PhD thesis is to move away from classical pan-HDAC inhibitors and thus to synthesize new HDAC6 inhibitors with potential applications in medicine. In particular, three novel classes of thiaheterocyclic benzohydroxamic acids were developed as potent HDAC6 inhibitors displaying excellent selectivity on both an enzymatic and a cellular level. The most promising inhibitors identified in this work can be considered as valuable lead structures for elaborate follow-up studies

Causal pluralism and scientific knowledge: an underexposed problem

Causal pluralism is currently a hot topic in philosophy. However, the consequences of this view on causation for scientific knowledge and scientific methodology is heavily underexposed in the present debate. My aim in this paper is to argue that an epistemological-methodological point of view should be valued as a line of approach on its own and to demonstrate how epistemological- methodological causal pluralism differs in its scope from conceptual and metaphysical causal pluralism. Further, I defend epistemological- methodological causal pluralism and try to illustrate that scientific practice needs diverse causal concepts in diverse domains, and even diverse causal concepts within singular domains

Morpho-functionality of the toothed whale external ear canal

Tesi en modalitat de cotutela: Universitat Politècnica de Catalunya i Universita degli studi di PadovaWhile marine, anthropogenic noise pollution is a scientific and societal matter of concern, there is limited knowledge on how sea animals, particularly cetaceans, perceive their environment through sounds. Toothed whales, like all cetaceans, show a series of astonishing morphological and physiological evolutionary adaptations, of which one of the most striking can be found in the complex configuration of the hearing apparatus. The external ear canal, although no longer considered a direct actor in the sound reception process, also shows surprising adaptation with many active structures and a complex peripheral innervation, although basic knowledge on its morphology is inconclusive at the moment. This study aimed at providing fundamental knowledge on the morphology of the external ear canal in various toothed whales, associated to its sensory capabilities with in-depth morphological descriptions of its shape and course, lumen and content, epithelium, glands, lymphoid tissue, vascularization, innervation, muscular tissue, cartilage, fat and connective tissue. Furthermore, specific attention was given to the identification and morphological characterization of the sensory formations associated with the external ear canal, and the comparison with the terrestrial cetartiodactyl external ear canal, to gain perspective of a comprehensive understanding of the cetacean sensory abilities. Post-mortem samples were gathered during necropsies of wild toothed whales, in an international collaborative effort. The tissues were inspected macroscopically and subjected to microscopic studies including immunohistochemical analyses using antibodies specific for nervous tissue, various histochemical techniques, ultrastructural investigation using transmission electron microscopy, and 3D reconstruction from histological slides of the ear canal and associated tissues. The winding structure of the external ear canal revealed a complex organ that comprises a physiological function reflected in its delicate anatomical structures, all of which are discussed in detail. Remarkably, the innervation showed an extensive intramural nervous plexus with the predominant presence of simple lamellar corpuscles, similar to Pacinian corpuscles although without an outer core or capsule. There were differences in conformation along the canal, from a network that fully encompasses the ear canal to a nervous tissue ridge that bulges into the lumen. The work elaborates on hypotheses related to the external ear canal’s function and the somatosensory system in toothed whales, taking into account the importance of the perspective of sensory modalities in the marine environment. The results indicate it plays an important physiological function, which impairment may have direct effects on their sensory capabilities and compromise essential physiological processes. It also puts into question to what extent there might be an adverse effect from various sources of anthropogenic noise, as it can cause physical changes in the sensory tissues in cetaceans and other marine fauna.Morfo-funcionalitat del canal auditiu extern en odontocets. Si bé la contaminació acústica marina antropogènica és un assumpte que preocupa la comunitat científica i la societat en general, el coneixement sobre com els animals marins, en particular els cetacis, perceben el seu entorn a través dels sons és limitat. Els odontocets, com tots els cetacis, presenten una sèrie de sorprenents adaptacions evolutives morfològiques i fisiològiques. Entre elles, una de les més notables es troba en la complexa configuració de l'aparell auditiu. El canal auditiu extern, tot i que no es considera que tingui un paper directe en el procés de recepció de el so, també mostra una sorprenent adaptació al medi marí, mostrant moltes estructures actives i una complexa innervació perifèrica. Malgrat això, els coneixements bàsics sobre la seva morfologia no són concloents de moment. Aquest estudi tenia com a objectiu la descripció fonamental de la morfologia del conducte auditiu extern en diversos odontocets, associant-la a les seves capacitats sensorials a través de descripcions morfològiques en profunditat de la seva forma i curs, lumen i contingut, epiteli, glàndules, teixit limfoide, vascularització, innervació, teixit muscular, cartílag, teixit adipós i connectiu. A més, es va parar especial atenció a la identificació i caracterització morfològica de les formacions sensorials associades al canal auditiu extern, i es va fer una comparació amb el conducte auditiu extern de cetartiodáctilos terrestres, per tal d'assolir una comprensió integral de les capacitats sensorials dels cetacis. Es van recol·lectar mostres post-mortem durant necròpsies d¿odontocets salvatges, en un esforç de col·laboració internacional. Els teixits es van inspeccionar macroscòpicament i es van sotmetre a estudis microscòpics, incloent anàlisis immunohistoquímics amb anticossos específics per teixit nerviós, diverses tècniques histoquímiques, investigació ultraestructural mitjançant microscòpia electrònica de transmissió i reconstrucció 3D a partir de talls histològics de canal auditiu i teixits associats. L'estructura sinuosa de canal auditiu extern va revelar un òrgan complex, la funció fisiològica del qual es reflecteix en les seves delicades estructures anatòmiques, que presenten una morfologia que es discuteix en detall. Sorprenentment, la innervació va mostrar un extens plexe nerviós intramural amb la presència predominant de corpuscles lamelares simples, similars als corpuscles de Pacini, encara que sense capa externa o càpsula. Es van observar diferències en la conformació dels corpuscles al llarg del canal auditiu, des d'una xarxa que abasta completament el conducte fins a una cresta de teixit nerviós que sobresurt en el lumen. El treball desenvolupa hipòtesis relacionades amb la funció del conducte auditiu extern i el sistema somatosensorial en odontocets, tenint en compte la importància de la perspectiva de les modalitats sensorials en el medi marí. Els resultats indiquen que el canal exerceix una funció fisiològica important, el deteriorament del qual pot tenir efectes directes sobre les seves capacitats sensorials i comprometre processos fisiològics essencials. També qüestiona fins a quin punt les diverses fonts de soroll antropogènic poden tenir un efecte advers, ja que poden provocar canvis físics en els teixits sensorials en cetacis i altra fauna marinaStudio morfo-funzionale del canale uditivo esterno negli odontoceti. Nonostante l'inquinamento acustico marino sia una questione che induce una crescente preoccupazione scientifica e sociale, la conoscenza su come gli animali marini, in particolare i cetacei, percepiscono il loro ambiente attraverso i suoni è ancora limitata. Gli odontoceti in particolare mostrano una serie di notevoli adattamenti evolutivi morfologici e fisiologici, di cui uno dei più eclatanti si trova nella complessa configurazione dell'apparato uditivo. Il condotto uditivo esterno, sebbene non sia più considerato una parte direttamente interessata nel processo di ricezione del suono, mostra un sorprendente adattamento con molte strutture attive e una complessa innervazione periferica. Tuttavia, le conoscenze basilari sulla sua morfologia e funzione sono incomplete al momento. Questo studio mira ad approfondire la morfologia del condotto uditivo esterno in vari odontoceti, con descrizioni morfologiche fornendo dettagli sulla sua forma e decorso, lume e contenuto, epitelio, ghiandole, tessuto linfoide, vascolarizzazione, innervazione, tessuto muscolare, cartilagine, tessuto adiposo e connettivo. Inoltre, una particolare attenzione è stata data all'identificazione e caratterizzazione morfologica delle formazioni sensoriali associate al condotto uditivo esterno, e al confronto con la medesima struttura in altri ceto-artiodattili terrestri, per ottenere una prospettiva di comprensione complessiva delle capacità sensoriali dei cetacei. I campioni sono stati raccolti durante necroscopie di odontoceti spiaggiati, in uno sforzo di collaborazione internazionale. I tessuti sono stati valutati macroscopicamente e quindi sottoposti a studi microscopici, comprendenti analisi immunoistochimiche utilizzando anticorpi specifici per il tessuto nervoso, insieme a varie tecniche istochimiche e indagini ultrastrutturali mediante microscopia elettronica a trasmissione. Ciò ha inoltre portato alla ricostruzione 3D partendo da vetrini istologici del condotto uditivo e dei tessuti associati. Il condotto uditivo esterno si è rivelato un organo complesso che comprende una funzione fisiologica riflessa nella sua delicata struttura anatomica. L'innervazione mostrava un esteso plesso nervoso intramurale con la presenza predominante di semplici corpuscoli lamellari, simili ai corpuscoli del Pacini, sebbene senza strato esterno o capsula. Lungo il decorso del condotto si sono notate alcune differenze nella sua architettura e distribuzione, da una rete che racchiude completamente il condotto uditivo a una papilla di tessuto nervoso che si gonfia nel lume. Grazie a questo studio si è potuto, al termine del lavoro, elaborare ipotesi relative alla funzione del condotto uditivo esterno e del sistema somatosensoriale nelle balene dentate, tenendo conto dell'importanza della prospettiva delle modalità sensoriali nell'ambiente marino. I risultati indicano che svolge una rilevante funzione fisiologica, la cui compromissione può avere effetti diretti sulla capacità sensoriali dei odontoceti e possibilmente compromettere i processi fisiologici essenziali. Questo studio sottolinea come potrebbe esserci effetti da varie fonti di rumore antropico, che possono causare cambiamenti fisici nei tessuti sensoriali dei cetacei e di altra fauna marinaMorfo-funcionalidad del canal auditivo externo en odontocetos. Si bien la contaminación acústica marina antropogénica es un asunto que preocupa a la comunidad científica y a la sociedad en general, existe un conocimiento limitado sobre cómo los animales marinos, en particular los cetáceos, perciben su entorno a través de los sonidos. Los odontocetos, como todos los cetáceos, presentan una serie de asombrosas adaptaciones evolutivas morfológicas y fisiológicas. Entre ellas, una de las más notables se encuentra en la compleja configuración del aparato auditivo. El canal auditivo externo, aunque no se considera que tenga un rol directo en el proceso de recepción del sonido, también muestra una sorprendente adaptación al medio marino, mostrando muchas estructuras activas y una compleja inervación periférica. No obstante, los conocimientos básicos sobre su morfología no son concluyentes por el momento. Este estudio tuvo como objetivo la descripción fundamental de la morfología del conducto auditivo externo en diversos odontocetos, asociándola a sus capacidades sensoriales a través de descripciones morfológicas en profundidad de su forma y curso, lumen y contenido, epitelio, glándulas, tejido linfoide, vascularización, inervación, tejido muscular, cartílago, tejido adiposo y conectivo. Además, se prestó especial atención a la identificación y caracterización morfológica de las formaciones sensoriales asociadas al canal auditivo externo, y se hace una comparación con el conducto auditivo externo de cetartiodáctilos terrestres, con el fin de alcanzar una comprensión integral de las capacidades sensoriales de los cetáceos. Se recolectaron muestras post-mortem durante necropsias de odontocetos salvajes, en un esfuerzo de colaboración internacional. Los tejidos se inspeccionaron macroscópicamente y se sometieron a estudios microscópicos, incluyendo análisis inmunohistoquímicos con anticuerpos específicos para tejido nervioso, diversas técnicas histoquímicas, investigación ultraestructural mediante microscopía electrónica de transmisión y reconstrucción 3D a partir de cortes histológicos del canal auditivo y tejidos asociados. La estructura sinuosa del canal auditivo externo reveló un órgano complejo cuya función fisiológica se refleja en sus delicadas estructuras anatómicas, la morfología de las cuales se discuten en detalle. Sorprendentemente, la inervación mostró un extenso plexo nervioso intramural con la presencia predominante de corpúsculos lamelares simples, similares a los corpúsculos de Pacini, aunque sin capa externa o cápsula. Se observaron diferencias en la conformación de los corpúsculos a lo largo del canal auditivo, desde una red que abarca completamente el conducto hasta una cresta de tejido nervioso que sobresale en el lumen. El trabajo desarrolla hipótesis relacionadas con la función del conducto auditivo externo y el sistema somatosensorial en odontocetos, teniendo en cuenta la importancia de la perspectiva de las modalidades sensoriales en el medio marino. Los resultados indican que el canal desempeña una función fisiológica importante, cuyo deterioro puede tener efectos directos sobre sus capacidades sensoriales y comprometer procesos fisiológicos esenciales. También cuestiona hasta qué punto las diversas fuentes de ruido antropogénico pueden tener un efecto adverso, ya que pueden provocar cambios físicos en los tejidos sensoriales en cetáceos y otra fauna marinaPostprint (published version

Beyond the Darkness: Research on Participation in Online Media and Discourse

This commentary reflects on the notion of ‘dark participation’ which is central in this thematic issue. It asks whether there are patches of light and whether our research is becoming too obsessed with the darkness

The news coverage of the 2004 European Parliamentary Election Campaign in 25 countries

This article analyzes the news coverage of the 2004 European Parliamentary\ud (EP) elections in all 25 member states of the European Union (EU). It\ud provides a unique pan-European overview of the campaign coverage based\ud on an analysis of three national newspapers and two television newscasts in\ud the two weeks leading up to the elections. On average, the elections were\ud more visible in the new 10 member states than in the 15 old EU member\ud states. The political personalities and institutional actors featured in news\ud stories about the elections were generally national political actors and not EU\ud actors. When it was evaluative, the news in the old EU-15 was generally\ud negative towards the EU, while in the new countries a mixed pattern was\ud found. The findings of the study are discussed in the light of the literature on\ud the EU’s legitimacy and communication deficit

The EU as a public sphere

This Living Review takes stock of our current theoretical and empirical knowledge with respect to a European public sphere. It first provides a discussion of the notion of a public sphere and the virtual incompatibility between the notion of a public sphere in the nation state and the current state of European integration. It is then argued why a notion of a (Europeanized national) public space for debate between citizens and with power-holders is important for the legitimacy and accountability of the EU. A three-fold typology is proposed that organizes previous research on the European public sphere: the Utopian, the Elitist and the Realist perspective. The diverging conclusions stemming from extant research are reviewed in the light of the methodological pluralism in the studies. It is demonstrated that most signs of Europeanization of national public spheres stem from studies focusing on the quality broadsheet press, whereas studies focusing on the popular press, television and new media provide little evidence (yet) of a Europeanization trend. The review looks ahead in both theoretical and methodological terms and also assesses the consequences of the (absence of) a European public sphere and current policy initiatives in this area