Ottimizzazione del consumo dei grassi durante esercizio fisico: studio di un test per il target mirato di allenamento individuale

Il primo studio ha verificato l'affidabilità del software Polimedicus e gli effetti indotti d'allenamento arobico all’intensità del FatMax. 16 soggetti sovrappeso, di circa 40-55anni, sono stati arruolati e sottoposti a un test incrementale fino a raggiungere un RER di 0,95, e da quel momento il carico è stato aumentato di 1 km/ h ogni minuto fino a esaurimento. Successivamente, è stato verificato se i valori estrapolati dal programma erano quelli che si possono verificare durante a un test a carico costante di 1ora. I soggetti dopo 8 settimane di allenamento hanno fatto un altro test incrementale. Il dati hanno mostrato che Polimedicus non è molto affidabile, soprattutto l'HR. Nel secondo studio è stato sviluppato un nuovo programma, Inca, ed i risultati sono stati confrontati con i dati ottenuti dal primo studio con Polimedicus. I risultati finali hanno mostrato che Inca è più affidabile. Nel terzo studio, abbiamo voluto verificare l'esattezza del calcolo del FatMax con Inca e il test FATmaxwork. 25 soggetti in sovrappeso, tra 40-55 anni, sono stati arruolati e sottoposti al FATmaxwork test. Successivamente, è stato verificato se i valori estrapolati da INCA erano quelli che possono verificarsi durante un carico di prova costante di un'ora. L'analisi ha mostrato una precisione del calcolo della FatMax durante il carico di lavoro. Conclusione: E’ emersa una certa difficoltà nel determinare questo parametro, sia per la variabilità inter-individuale che intra-individuale. In futuro bisognerà migliorare INCA per ottenere protocolli di allenamento ancora più validi.

Lotta alla criminalita' e salvaguardia dei diritti e delle liberta' fondamentali nell'U.E.

La ricerca è dedicata a verificare se e come, a livello dell’Unione europea, la lotta alla criminalità (ed in particolare quella organizzata) venga condotta nel rispetto di diritti e libertà fondamentali, e se la cooperazione tra Stati membri su questo fronte possa giungere a promuovere standard omogenei ed elevati di tutela degli stessi. Gli ambiti di cooperazione interessati sono principalmente quello giudiziario in materia penale e quello di polizia, e la ritrosia degli Stati a cedere all’Unione competenze in materia si è accompagnata ad un ritardo ancora maggiore dell’emersione, nell’ambito degli stessi, della dimensione dei diritti. Ciò ha reso molto difficile lo sviluppo completo ed equilibrato di uno “spazio di libertà, sicurezza e giustizia” (art. 67 TFUE). L’assetto istituzionale introdotto dal Trattato di Lisbona e l’attribuzione di valore giuridico vincolante alla Carta hanno però posto le basi per il superamento della condizione precedente, anche grazie al fatto che, negli ambiti richiamati, la salvaguardia dei diritti è divenuta competenza ed obiettivo esplicito dell’Unione. Centrale è per la ricerca la cooperazione giudiziaria in materia penale, che ha visto la ricca produzione normativa di stampo repressivo recentemente bilanciata da interventi del legislatore europeo a finalità garantista e promozionale. L’analisi degli strumenti nella prospettiva indicata all’inizio dell’esposizione è quindi oggetto della prima parte dell’elaborato. La seconda parte affronta invece la cooperazione di polizia e quello degli interventi volti alla confisca dei beni e ad impedire il riciclaggio, misure – queste ultime - di particolare rilievo soprattutto per il contrasto al crimine organizzato. Sottesi all’azione dell’Unione in queste materie sono, in modo preponderante, due diritti: quello alla salvaguardia dei dati personali e quello al rispetto della proprietà privata. Questi, anche in ragione delle peculiarità che li caratterizzano e della loro natura di diritti non assoluti, sono analizzati con particolare attenzione.

Wahlbeteiligung bei Europawahlen : eine empirische Studie zu Deutschland und Polen

In der Arbeit wird die Wahlbeteiligung bei Europawahlen analysiert. Es geht um die Beantwortung der Frage, ob die individuelle Wahlteilnahme in alten und neuen EU-Mitgliedsstaaten bzw. alten und jungen Demokratien auf die gleichen Erklärungsgrößen zurückgeht oder ob möglicherweise Unterschiede zwischen beiden Ländergruppen bestehen. rnAls Bezugspunkt dient die Europawahl, die im Juni 2009 stattfand: Bei dieser Wahl fällt nicht nur die generell niedrige Beteiligung auf, sondern auch erhebliche Niveauunterschiede zwischen den einzelnen Mitgliedsstaaten. Um diesen Befund erklären zu können, wird zunächst ein theoretisches Erklärungsmodell entwickelt, das sich auf die folgenden fünf Dimensionen bezieht: politisches System der EU, europäische politische Gemeinschaft, Wählermobilisierung während des Europawahlkampfes, Gewohnheitswahl und Einschätzung der staatlichen sowie der eigenen wirtschaftlichen Lage. Als Erklärungsgröße werden in den fünf Bereichen jeweils unterschiedlich stark ausgeprägte Defizite in den beiden Ländergruppen angenommen. rnExemplarisch werden Deutschland und Polen untersucht. Die empirischen Analysen basieren auf dem umfangreichen Datensatz der European Election Study 2009 (ESS), hier werden die Daten der Voter Study verwendet. Nicht alle Hypothesen lassen sich im Rahmen der Arbeit bestätigten, nur ein Teil der unabhängigen Variablen hat auch im multivariaten Modell noch einen Einfluss auf die Europawahlbeteiligung. rnFür Deutschland zeigen die Ergebnisse, dass Wahlnorm und Wählermobilisierung einen größeren Effekt auf die Stimmabgabe ausüben als die Nutzenseite (Effektivität) der Wahlen. Im zweiten Modell, das für die polnischen Befragten berechnet wurde, erweisen sich nur zwei der unabhängigen Variablen als signifikant, d.h. nur die Einschätzung der Effektivität der Wahl und die internalisierte Wahlnorm haben einen Einfluss auf die Wahlteilnahme. Von der Effektivitätseinstufung geht eine größere Erklärungskraft aus als von der Wahlnorm; in diesem Modell überwiegt folglich die Nutzenseite der Europawahl. Es kann gezeigt werden, dass die unterschiedlichen Beteiligungsraten in den beiden Staaten durch unterschiedlich stark ausgeprägte Defizite in den Bereichen des politischen Systems und der Wahlnorm zustande kommen. Die Defizite sind in Polen stärker ausgeprägt und können so die niedrigere Wahlbeteiligung erklären. Darüber hinaus kann resümiert werden, dass die Nutzenseite der Europawahl in Polen einen stärkeren Einfluss auf die Beteiligung ausübt als in Deutschland.

L’Orientalismo tra vocazione imperialista, suggestioni esotiche e omoerotiche. Le rappresentazioni storiche del passaggio tra l’epoca omayyade e abbaside.

Lo studio si tratta di mettere in evidenza il cambiamento che ha subito il termine Oriente nel secolo XX in alcuni testi della letteratura italiana contemporanea. L’opera di Edward Said, L’Orientalismo è un testo di riferimento per i nostri studi. Nel quale abbiamo focalizzato l’attenzione su alcuni aspetti salienti: il concetto di orientalismo; l’interesse nei confronti dell’Oriente sul piano politico, scientifico, letterario; l’impossibilità di separare lo studioso dalle circostanze biografiche e sociali. Siamo riusciti, quindi, a stabilire che il cambiamento dell’immagine orientale dipende da tre fattori: lo scrittore (emittente), il soggetto (la fonte) ed il lettore (destinatario), dai quali si origina l’oggetto (il testo). Basandoci su questi tre elementi abbiamo cercato di inquadrare l’interesse letterario per l’Oriente vista da una triplice prospettiva: imperialismo, fascino ed erotismo. Per studiare le prime due prospettive, abbiamo scelto due opere. La prima presenta l’immagine dell’imperialismo, si tratta di Sanya, La moglie egiziana e il Romanzo dell’Oriente Moderno (1927) di Bruno Corra. La seconda prospettiva dove troviamo l’immagine dell’Oriente fascinoso è nello scritto di Annie Vivanti, La terra di Cleopatra (1925). Il punto centrale della tesi si tratta di studiare Annie Messina (1910-1996), è una scrittrice che ha uno stile peculiare ed un approccio tutto suo al tema dell’Oriente. I testi studiati sono : "Il mirto e la rosa" (1982), "Il banchetto dell'emiro" (1997) e "La principessa e il wâlî" (1996), tutti pubblicati dalla casa editrice Sellerio.L’unico pubblicato da Mondadori è "La palma di Rusafa" (1989). L’ultima parte del lavoro abbiamo esposto un profilo storico e socio-religioso della letteratura erotica araba. In cui abbiamo rintracciato le origini dell’immagine erotico dell’Oriente e il tema dell’omosessualità, mettendo a confronto il testo omosessuale di Messina con la letteratura italiana contemporanea.

High precision radial velocities with giano spectra

Radial velocities measured from near-infrared (NIR) spectra are a potential tool to search for extrasolar planets around cool stars. High resolution infrared spectrographs now available reach the high precision of visible instruments, with a constant improvement over time. GIANO is an infrared echelle spectrograph and it is a powerful tool to provide high resolution spectra for accurate radial velocity measurements of exo-planets and for chemical and dynamical studies of stellar or extragalactic objects. No other IR instruments have the GIANO's capability to cover the entire NIR wavelength range. In this work we develop an ensemble of IDL procedures to measure high precision radial velocities on a few GIANO spectra acquired during the commissioning run, using the telluric lines as wevelength reference. In Section 1.1 various exoplanet search methods are described. They exploit different properties of the planetary system. In Section 1.2 we describe the exoplanet population discovered trough the different methods. In Section 1.3 we explain motivations for NIR radial velocities and the challenges related the main issue that has limited the pursuit of high-precision NIR radial velocity, that is, the lack of a suitable calibration method. We briefly describe calibration methods in the visible and the solutions for IR calibration, for instance, the use of telluric lines. The latter has advantages and problems, described in detail. In this work we use telluric lines as wavelength reference. In Section 1.4 the Cross Correlation Function (CCF) method is described. This method is widely used to measure the radial velocities.In Section 1.5 we describe GIANO and its main science targets. In Chapter 2 observational data obtained with GIANO spectrograph are presented and the choice criteria are reported. In Chapter 3 we describe the detail of the analysis and examine in depth the flow chart reported in Section 3.1. In Chapter 4 we give the radial velocities measured with our IDL procedure for all available targets. We obtain an rms scatter in radial velocities of about 7 m/s. Finally, we conclude that GIANO can be used to measure radial velocities of late type stars with an accuracy close to or better than 10 m/s, using telluric lines as wevelength reference. In 2014 September GIANO is being operative at TNG for Science Verification and more observational data will allow to further refine this analysis.

Demography in eusocial Hymenoptera

In my doctoral thesis I investigated the evolution of demographic traits within eusocial Hymenoptera. In the social bees, wasps and ants, eusociality has a unique effect on life span evolution as female larvae with the same genetic background can develop through phenotypic plasticity to a queen or a worker with vastly diverging life-history traits. Ant queens belong to the longest-lived insect species, while workers in most species live only a fraction of the queen’s life span. The average colony size of a species is positively correlated with social complexity, division of labor and diverging morphological female phenotypes all of which also affect life span. Therefore the demographic traits of interest in this thesis were life span and colony size. To understand the evolution of worker life span I applied a trade-off model that includes both hierarchical levels important in eusocial systems, namely the colony- and the individual-level. I showed that the evolution of worker life span may be an adaptive trait on the colony level to optimize resource allocation and therefore fitness in response to different levels of extrinsic mortality. A shorter worker life span as a result of reduced resource investments under high levels of extrinsic mortality increases colony fitness. In a further study I showed that Lasius niger colonies produce different aging phenotypes throughout colony development. Smaller colonies which apply a different foraging strategy than larger colonies produced smaller workers, which in turn have a longer life span as compared to larger workers produced in larger colonies. With the switch to cooperative foraging in growing colonies individual workers become less important for the colony caused by their increasing redundancy. Alternatively a trade of between growth and life span may lead to the results found in this study. A further comparative analysis to study the effect of colony size on life span showed a correlation between queen and worker life span when colony size is taken into account. While neither worker nor queen life span was associated with colony size, the differences between queen and worker life span increase with larger average colony sizes across all eusocial Hymenoptera. As colony size affects both queen and worker life span, I aimed to understand which factors lead to the small colony sizes displayed by some ant species. I therefore analyzed per-capita productivity at different colony sizes of eight cavity dwelling ant species. Most colonies of the study species grew larger than optimal productivity predicted. Larger colony size was shown to increase colony homeostasis, the predictability of future productivity and in turn the survival probability of the colony. I also showed that species that deploy an individual foraging mode may circumvent the density dependent decline in foraging success by splitting the colony to several nest sites.

Development of a highly potent bispecific antibody format targeting the novel tumor-specific antigen CLDN18.2

Due to multiple immune evasion mechanisms of cancer cells, novel therapy approaches are required to overcome the limitations of existing immunotherapies. Bispecific antibodies are potent anti-cancer drugs, which redirect effector T cells for specific tumor cell lysis, thus enabling the patient’s immune system to fight cancer cells. The antibody format used in this proof of concept study–bispecific ideal monoclonal antibodies termed BiMAB–is a tailor-made recombinant protein, which consists of two fused scFv antibodies recognizing different antigens. Both are arranged in tandem on a single peptide chain and the individual variable binding domains are separated by special non-immunogenic linkers. The format is comprised of a scFv targeting CLDN18.2–a gastric cancer tumor associated antigen (TAA) –while the second specificity binds the CD3 epsilon (CD3ε) subunit of the T cell receptor (TCR) on T cells. For the first time, we compared in our IMAB362-based BiMAB setting, four different anti-CD3-scFvs, respectively derived from the mAbs TR66, CLB-T3, as well as the humanized and the murine variant of UCHT1. In addition, we investigated the impact of an N- versus a C-terminal location of the IMAB362-derived scFv and the anti-CD3-scFvs. Thus, nine CLDN18.2 specific BiMAB proteins were generated, of which all showed a remarkably high cytotoxicity towards CLDN18.2-positive tumor cells. Because of its promising effectiveness, 1BiMAB emerged as the BiMAB prototype. The selectivity of 1BiMAB for its TAA and CD3ε, with affinities in the nanomolar range, has been confirmed by in vitro assays. Its dual binding depends on the design of an N-terminally positioned IMAB362 scFv and the consecutive C-terminally positioned TR66 scFv. 1BiMAB provoked a concentration and target cell dependent T cell activation, proliferation, and upregulation of the cytolytic protein Granzyme B, as well as the consequent elimination of target cells. Our results demonstrate that 1BiMAB is able to activate T cells independent of elements that are usually involved in the T cell recognition program, like antigen presentation, MHC restriction, and co-stimulatory effector molecules. In the first in vivo studies using a subcutaneous xenogeneic tumor mouse model in immune incompetent NSG mice, we could prove a significant therapeutic effect of 1BiMAB with partial or complete tumor elimination. The initial in vitro RIBOMAB experiments correspondingly showed encouraging results. The electroporation of 1BiMAB IVT-RNA into target or effector cells was feasible, while the functionality of translated 1BiMAB was proven by induced T cell activation and target cell lysis. Accordingly, we could show that the in vitro RIBOMAB approach was applicable for all nine BiMABs, which proves the RIBOMAB concept. Thus, the CLDN18.2-BiMAB strategy offers great potential for the treatment of cancer. In the future, administered either as protein or as IVT-RNA, the BiMAB format will contribute towards finding solutions to raise and sustain tumor-specific cellular responses elicited by engaged and activated endogenous T cells. This will potentially enable us to overcome immune evasion mechanisms of tumor cells, consequently supporting current solid gastric cancer therapies.

Einsatz eines Aerosolmassenspektrometers während der CYPHEX-Kampagne und zur Methodenentwicklung einer Echtzeitquantifizierung gasförmiger Amine

Atmosphärische Aerosole haben einen starken Einfluss auf das Klima, der bisher nur grundlegend verstanden ist und weiterer Forschung bedarf. Das atmosphärische Verhalten der Aerosolpartikel hängt maßgeblich von ihrer Größe und chemischen Zusammensetzung ab. Durch Reflexion, Absorption und Streuung des Sonnenlichtes verändern sie den Strahlungshaushalt der Erde direkt und durch ihre Einflussnahme auf die Wolkenbildung indirekt. Besonders gealterte, stark oxidierte organische Aerosole mit großem Sauerstoff-zu-Kohlenstoff-Verhältnis wirken als effektive Wolkenkondensationskeime. Neben primären Aerosolpartikeln, die direkt partikelförmig in die Atmosphäre gelangen, spielen sekundäre Aerosolpartikel eine große Rolle, die aus Vorläufergasen in der Atmosphäre entstehen. Aktuelle Forschungsergebnisse legen nahe, dass kurzkettige aliphatische Amine bei Nukleationsprozessen beteiligt sind und somit die Partikelneubildung vielerorts mitsteuern. Um die Rolle von Aminen in der Atmosphäre besser erforschen und industrielle Emissionen kontrollieren zu können, bedarf es einer zuverlässigen Methode zur Echtzeitquantifizierung gasförmiger Amine mit hoher Zeitauflösung und niedriger Nachweisgrenze.rnDas hochauflösende Flugzeit-Aerosolmassenspektrometer (HR-ToF-AMS) bietet die Möglichkeit, atmosphärische Partikel in Echtzeit zu analysieren. Dabei werden Größe, Menge und grundlegende chemische Zusammensetzung erfasst. Anorganische Aerosolbestandteile können eindeutig zugeordnet werden. Es ist jedoch kaum möglich, einzelne organische Verbindungen in den komplizierten Massenspektren atmosphärischer Aerosole zu identifizieren und quantifizieren.rnIn dieser Arbeit wird atmosphärisches Aerosol untersucht, das im Westen Zyperns während der CYPHEX-Kampagne mit einem HR-ToF-AMS gemessen wurde. An diesem Standort ist vor allem stark gealtertes Aerosol vorzufinden, das aus Zentral- und Westeuropa stammt. Lokale Einflüsse spielen fast keine Rolle. Es wurde eine durchschnittliche Massenkonzentration von 10,98 μg/m3 gefunden, zusammengesetzt aus 57 % Sulfat, 30 % organischen Bestandteilen, 12 % Ammonium, < 1 % Nitrat und < 1 % Chlorid, bezogen auf das Gewicht. Der Median des vakuum-aerodynamischen Durchmessers betrug 446,25 nm. Es wurde sehr acides Aerosol gefunden, dessen anorganische Bestandteile weitgehend der Zusammensetzung von Ammoniumhydrogensulfat entsprachen. Tag-Nacht-Schwankungen in der Zusammensetzung wurden beobachtet. Die Sulfatkonzentration und die Acidität zeigten tagsüber Maxima und nachts Minima. Konzentrationsschwankungen an Nitrat und Chlorid zeigten einen weniger ausgeprägten Rhythmus, Maxima fallen aber immer mit Minima der Sulfatkonzentration, Aerosolacidität und Umgebungstemperatur zusammen. Organische Aerosolbestandteile entsprachen stark gealtertem, schwerflüchtigem oxidiertem organischem Aerosol. Es wurde eine interne Mischung der Partikel beobachtet, die ebenfalls meist bei alten Aerosolen auftritt.rnUm mit dem HR-ToF-AMS auch einzelne organische Verbindungen identifizieren und quantifizieren zu können, wurde eine Methode entwickelt, mit der man Amine der Gasphase selektiv in künstlich erzeugte Phosphorsäurepartikel aufnimmt und so für die HR-ToF-AMS-Messung zugänglich macht. Dadurch kombiniert man die Vorteile der Online-Messung des HR-ToF-AMS mit den Vorteilen klassischer Offline-Probenahmen. So können in Echtzeit sehr einfache Massenspektren gemessen werden, in denen störende Komponenten abgetrennt sind, während die Analyten eindeutig identifiziert werden können. Systeme dieser Art wurden GTRAP-AMS (Gaseous compound TRapping in Artificially-generated Particles – Aerosol Mass Spectrometry) genannt. Kalibrierungen für (Mono)Methylamin, Dimethylamin, Trimethylamin, Diethylamin und Triethylamin ergaben Nachweisgrenzen im ppt-Bereich bei einer Zeitauflösung von 3 min. Kammerexperimente zur Aminemission von Pflanzen zeigten eine gute Übereinstimmung des neu entwickelten Systems mit einer Gasdiffusionsabscheider-Offline-Probenahme und anschließender ionenchromatographischer Analyse. Beide Methoden zeigten Reaktionen der Pflanzen auf eine Veränderung der Lichtverhältnisse, während erhöhte Ozonkonzentrationen die Aminemission nicht veränderten. Die GTRAP-AMS-Methode eignet sich bereits für die Messung von Umgebungsluftkonzentrationen an einigen Orten, für die meisten Orte reicht die Nachweisgrenze allerdings noch nicht aus. Die Technik könnte bereits zur Echtzeitkontrolle industrieller Abgasemissionen eingesetzt werden.

Comprehensive assessment of gesture production: a new test of upper limb apraxia (TULIA)

BACKGROUND: Only few standardized apraxia scales are available and they do not cover all domains and semantic features of gesture production. Therefore, the objective of the present study was to evaluate the reliability and validity of a newly developed test of upper limb apraxia (TULIA), which is comprehensive and still short to administer. METHODS: The TULIA consists of 48 items including imitation and pantomime domain of non-symbolic (meaningless), intransitive (communicative) and transitive (tool related) gestures corresponding to 6 subtests. A 6-point scoring method (0-5) was used (score range 0-240). Performance was assessed by blinded raters based on videos in 133 stroke patients, 84 with left hemisphere damage (LHD) and 49 with right hemisphere damage (RHD), as well as 50 healthy subjects (HS). RESULTS: The clinimetric findings demonstrated mostly good to excellent internal consistency, inter- and intra-rater (test-retest) reliability, both at the level of the six subtests and at individual item level. Criterion validity was evaluated by confirming hypotheses based on the literature. Construct validity was demonstrated by a high correlation (r = 0.82) with the De Renzi-test. CONCLUSION: These results show that the TULIA is both a reliable and valid test to systematically assess gesture production. The test can be easily applied and is therefore useful for both research purposes and clinical practice.

Osteochondritis dissecans of the femoral head

Seven patients with symptomatic osteochondritic lesions of the femoral head are presented. All were male with a mean age of 26 years (16 - 33 years). Two distinct morphologic appearances of the hip joint could be identified. Five patients presented with a coxa valga deformity, four of whom had signs of epiphyseal dysplasia. There were 2 patients whose hips appeared normal apart from the osteochondrontic lesions. In both cases an additional acetabular rim lesion due to a reproducible femoro-acetabular impingement was diagnosed at arthrotomy. This may have acted as the underlying cause of osteochondritis dissecans in these cases. All 7 patients underwent surgical treatment. An intertrochanteric osteotomy (I.O.) alone was performed in 2 patients. Follow-up of these patients at 6.5 and 8.5 years after surgery revealed that the osteochondritic lesions had not healed and one individual remained symptomatic. In the remaining 5 patients, treatment consisted of femoral head dislocation and screw fixation of the osteochondritic lesion. This was combined with an I.O. in two of these patients for coxa valga and osteoplasty of a broad femoral neck in 2 other patients. All lesions had healed at an average follow-up of 4.3 years (2 - 8.5 years). Three patients were asymptomatic and 2 patients had minor residual pain. No progressive osteoarthritic changes or signs of avascular necrosis of the femoral head were observed.

Multimodal therapy of functional gastrointestinal disorders

A multimodal approach is state-of-the art for effective treatment of functional gastrointestinal disorders (FGD) like irritable bowel syndrome and functional dyspepsia. Based on the now established view that the pathogenesis of FGD is multicausal, evidence-based therapeutic options comprise education about the nature of the disorder, dietary modifications, relaxation techniques, behavioral changes, and pharmacological treatments. These therapies are variously combined depending on the severity of the FGD and the individual needs of the patient. Our overview portrays the options for the therapy of FGD and proposes that these are best provided by an interdisciplinary team of primary care physicians, gastroenterologists, and psychosomatic medicine specialists.

Natural products as leads for anticancer drug discovery: discovery of new chemotypes of microtubule stabilizers through reengineering of the epothilone scaffold

Epothilones are bacterial macrolides with potent microtubule-stabilizing and antiproliferative activity, which have served as successful lead structures for the discovery of several clinical candidates for cancer treatment. Overall, seven epothilone-type agents have been advanced to clinical evaluation in humans so far and one of these has been approved by the FDA in 2007 for clinical use in breast cancer patients. Notwithstanding these impressive numbers, however, the structural diversity represented by the collection of epothilone analogs that have been (or still are) investigated clinically is rather limited and their individual structures show little divergence from the original natural product leads. In contrast, we have elaborated a series of epothilone-derived macro-lactones, whose overall structural features significantly deviate from those of the natural epothilone scaffold and thus define new structural families of microtubule-stabilizing agents. Key elements of our hypermodification strategy are the change of the natural epoxide geometry from cis to trans, the incorporation of conformationally constrained side chains, the removal of the C(3)-hydroxyl group, and the replacement of C(12) with nitrogen. The latter modification leads to aza-macrolides that may be described as 'non-natural natural products'.

An Exploratory Study about Microblogging Acceptance at Work

Microblogging is the new Web 2.0 hype in the media. Techies, politicians, family members and many more use Twitter to keep in touch with their interest groups, their voters or their friends and relatives. We wanted to know whether Twitter can also keep us aware about our team colleagues, how this improves teamwork and finally why Twitter is accepted and used in teams. Based on an action research study about Twitter usage in a team of seven researchers and the findings of prior literature, we attempt to extend the unified theory of technology acceptance (Venkatesh 2003) and adapt it to the specific context of microblogging in teams. Extending the performance expectancy construct, we propose two groups of factors inherent to social software that should be integrated into the UTAUT: the task characteristics of other users and the individual motivations for using social software

Chapter IV: Treatment of critical limb ischaemia

Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural.

Playground Series

Playground is intended to open a window into a world, however familiar it may first appear, that resonates with one of our universal compassions and the icons of contemporary life: the act and ritual of taking photographs. This project aims to magnify the extraordinary in the ordinary, revealing facial expressions, gestures or body language of the subjects behind their own visual recording device. It is about the drama of people in their private moments, when their face or body language reveals the most hidden parts of their inner world in public places. The interplay between private and public, individual and social are the main inhabitants of this photographic project.