BDI agents for Real Time Strategy games

While the use of distributed intelligence has been incrementally spreading in the design of a great number of intelligent systems, the field of Artificial Intelligence in Real Time Strategy games has remained mostly a centralized environment. Despite turn-based games have attained AIs of world-class level, the fast paced nature of RTS games has proven to be a significant obstacle to the quality of its AIs. Chapter 1 introduces RTS games describing their characteristics, mechanics and elements. Chapter 2 introduces Multi-Agent Systems and the use of the Beliefs-Desires-Intentions abstraction, analysing the possibilities given by self-computing properties. In Chapter 3 the current state of AI development in RTS games is analyzed highlighting the struggles of the gaming industry to produce valuable. The focus on improving multiplayer experience has impacted gravely on the quality of the AIs thus leaving them with serious flaws that impair their ability to challenge and entertain players. Chapter 4 explores different aspects of AI development for RTS, evaluating the potential strengths and weaknesses of an agent-based approach and analysing which aspects can benefit the most against centralized AIs. Chapter 5 describes a generic agent-based framework for RTS games where every game entity becomes an agent, each of which having its own knowledge and set of goals. Different aspects of the game, like economy, exploration and warfare are also analysed, and some agent-based solutions are outlined. The possible exploitation of self-computing properties to efficiently organize the agents activity is then inspected. Chapter 6 presents the design and implementation of an AI for an existing Open Source game in beta development stage: 0 a.d., an historical RTS game on ancient warfare which features a modern graphical engine and evolved mechanics. The entities in the conceptual framework are implemented in a new agent-based platform seamlessly nested inside the existing game engine, called ABot, widely described in Chapters 7, 8 and 9. Chapter 10 and 11 include the design and realization of a new agent based language useful for defining behavioural modules for the agents in ABot, paving the way for a wider spectrum of contributors. Chapter 12 concludes the work analysing the outcome of tests meant to evaluate strategies, realism and pure performance, finally drawing conclusions and future works in Chapter 13.

Synthetical engineering of supramolecular properties of large polycyclic aromatic hydrocarbons

An important property for devices is the charge-carrier mobility values for discotic organic materials like hexa-peri-hexabenzocoronenes. A close relation exists between the degree of their columnar self-arrangement of the molecules and their mobilities. Within this first step an induction of a higher order via hydrogen-bonding was considered, which mainly pointed towards the improvement of the intracolumnar stacking of the materials. For the analytics a broad range of methods was used including differential scanning calorimetry (DSC), wide-angle X-ray diffractometry (WAXS), solid-state NMR spectroscopy and scanning tunneling microscopy (STM). Indeed, a specific influence of the hydrogen-bonds could be identified, although in several cases by the cost of a severe reduction of solubility and processability. This effect was dampened by the addition of a long alkyl chain next to the hydrogen-bond exerting functional group, which resulted in an improved columnar arrangement by retention of processability. In contrast to the before mentioned example of inducing a higher intracolumnar order by hydrogen-bonding, the focus was also be set upon larger aromatic systems. The charge-carrier mobility is also in close relation to the size of the aromatic core and larger π-areas are expected to lead to improved mobilities. For photovoltaic applications a high extinction coefficient over a broad range of the spectrum is favorable, which can also be achieved by enlarging the aromatic core component. In addition the stronger π-interactions between the aromatic core components should yield an improved columnar stability and order. However the strengthening of the π-interactions between the aromatic core components led to a reduction of the solubility and the processability due to the stronger aggregation of the molecules. This required the introduction of efficiently solubilizing features in terms of long alkyl chains in the corona of the aromatic entity, in combination of a distortion of the aromatic core moiety by bulky tert-butyl groups. By this approach not only the processing and cleaning of the materials with standard laboratory techniques became possible, but moreover the first structure-rich UV/vis and a resolved 1H-NMR spectra for an aromatic system two times larger than hexa-peri-hexabenzocoronene were recorded. The bulk properties in an extruded fiber as well as on the surface showed a columnar self-assembly including a phase in which a homeotropic alignment on a substrate was observed, which turns the material into an interesting candidate for future applications in electronic devices.

Il "Progetto Bagnacavallo": prevalenza dell'ipertransaminasemia e NAFLD nella popolazione generale

Nel corso degli ultimi due decenni in particolare si è andata evidenziando a livello epatologico una entità definita oggi Non-alcoholic Fatty Liver Disease (NAFLD) che si è andata ad affiancare alle cause in precedenza conosciute, fino a risultare, attraverso il succedersi di riscontri scientifici, la causa prevalente di epatopatia, in particolare nei paesi occidentali e industrializzati. Negli stessi anni un'altra problematica clinica complessa che va sotto il nome di Sindrome Metabolica si è andata via via delineando attraverso le sue molteplici correlazioni con quelle che sono le cause di morbidità e mortalità prevalenti nella nostra realtà, dal diabete alla patologia cardiovascolare e non ultima alla NAFLD stessa. Scopo dello Studio in oggetto a questa tesi era proprio di rivalutare nel territorio italiano la prevalenza di epatopatia in particolare correlabile alla NAFLD e la sua associazione con la Sindrome Metabolica.

Trattamenti termici: valutazione delle degradazioni termossidative di oli da frittura e determinazione di composti aromatici in matrici alimentari complesse

Lo studio condotto durante il Dottorato di Ricerca è stato focalizzato sulla valutazione e sul monitoraggio delle diverse degradazioni termossidative in oli da frittura. Per raggiungere tale obiettivo si è ritenuto opportuno procedere mediante uno screening dei principali oli presenti sul mercato italiano e successiva messa a punto di due miscele di oli vegetali che sono state sottoposte a due piani sperimentali di frittura controllata e standardizzata in laboratorio, seguiti da due piani di frittura eseguiti in due differenti situazioni reali quali mensa e ristorante. Ognuna delle due miscele è stata messa a confronto con due oli di riferimento. A tal fine è stata identificato il profilo in acidi grassi, la stabilità ossidativa ed idrolitica, il punto di fumo, i composti polari, il contenuto in tocoferoli totali, ed i composti volatili sia sugli oli crudi che sottoposti ai diversi processi di frittura. Lo studio condotto ha permesso di identificare una delle miscele ideate come valida alternativa all’impiego dell’olio di palma ampiamente utilizzato nelle fritture degli alimenti, oltre a fornire delle indicazioni più precise sulla tipologia e sull’entità delle modificazioni che avvengono in frittura, a seconda delle condizioni impiegate.

Risposta Immunitaria Epatite B specifica in pazienti affetti da Epatocarcinoma

Hepatitis B x protein (HBx) is a non structural, multifunctional protein of hepatitis B virus (HBV) that modulates a variety of host processes.Due to its transcriptional activity,able to alter the expression of growth-control genes,it has been implicated in hepatocarcinogenesis.Increased expression of HBx has been reported on the liver tissue samples of hepatocellular carcinoma (HCC),and a specific anti-HBx immune response can be detected in the peripheral blood of patients with chronic HBV.However,its role and entity has not been yet clarified.Thus,we performed a cross-sectional analysis of anti-HBx specific T cell response in HBV-infected patients in different stage of disease.A total of 70 HBV-infected subjects were evaluated:15 affected by chronic hepatitis (CH-median age 45 yrs),14 by cirrhosis (median age 55 yrs),11 with dysplastic nodules (median age 64 yrs),15 with HCC (median age 60 yrs),15 with IC(median age 53 yrs).All patients were infected by virus genotype D with different levels of HBV viremia and most of them (91%) were HBeAb positive.The HBx-specific T cell response was evaluated by anti-Interferon (IFN)-gamma Elispot assay after in vitro stimulation of peripheral blood mononuclear cells,using 20 overlapping synthetic peptides covering all HBx protein sequence.HBx-specific IFN-gamma-secreting T cells were found in 6 out of 15 patients with chronic hepatitis (40%), 3 out of 14 cirrhosis (21%), in 5 out of 11 cirrhosis with macronodules (54%), and in 10 out of 15 HCC patients (67%). The number of responding patients resulted significantly higher in HCC than IC (p=0.02) and cirrhosis (p=0.02). Central specific region of the protein x was preferentially recognize,between 86-88 peptides. HBx response does not correlate with clinical feature disease(AFP,MELD).The HBx specific T-cell response seems to increase accordingly to progression of the disease, being increased in subjects with dysplastic or neoplastic lesions and can represent an additional tool to monitor the patients at high risk to develop HCC

Un applicativo Web con tecnologia single-page AJAX, servizi REST e grafica X3D, per la configurazione di modelli CAD tridimensionali

In questa tesi è stato realizzato un sistema web-based, per la configurazione di modelli meccanici tridimensionali. L’intero software è basato su architettura multi-tier. Il back-end espone servizi RESTful che permettono l’interrogazione di una base di dati contenente l’anagrafica dei modelli e l’interazione con il CAD 3D SolidWorks. Il front-end è rappresentato da due pagine HTML ideate come SPA (Single Page Application), una per l’amministratore e l’altra per l’utente finale; esse sono responsabili delle chiamate asincrone verso i servizi, dell’aggiornamento automatico dell’interfaccia e dell’interazione con immagini tridimensionali.

DNA block copolymers - synthesis, morphologies and applications

The last decades have witnessed significant and rapid progress in polymer chemistry and molecular biology. The invention of PCR and advances in automated solid phase synthesis of DNA have made this biological entity broadly available to all researchers across biological and chemical sciences. Thanks to the development of a variety of polymerization techniques, macromolecules can be synthesized with predetermined molecular weights and excellent structural control. In recent years these two exciting areas of research converged to generate a new type of nucleic acid hybrid material, consisting of oligodeoxynucleotides and organic polymers. By conjugating these two classes of materials, DNA block copolymers are generated exhibiting engineered material properties that cannot be realized with polymers or nucleic acids alone. Different synthetic strategies based on grafting onto routes in solution or on solid support were developed which afforded DNA block copolymers with hydrophilic, hydrophobic and thermoresponsive organic polymers in good yields. Beside the preparation of DNA block copolymers with a relative short DNA-segment, it was also demonstrated how these bioorganic polymers can be synthesized exhibiting large DNA blocks (>1000 bases) applying the polymerase chain reaction. Amphiphilic DNA block copolymers, which were synthesized fully automated in a DNA synthesizer, self-assemble into well-defined nanoparticles. Hybridization of spherical micelles with long DNA templates that encode several times the sequence of the micelle corona induced a transformation into rod-like micelles. The Watson-Crick motif aligned the hydrophobic polymer segments along the DNA double helix, which resulted in selective dimer formation. Even the length of the resulting nanostructures could be precisely adjusted by the number of nucleotides of the templates. In addition to changing the structural properties of DNA-b-PPO micelles, these materials were applied as 3D nanoscopic scaffolds for organic reactions. The DNA strands of the corona were organized by hydrophobic interactions of the organic polymer segments in such a fashion that several DNA-templated organic reactions proceeded in a sequence specific manner; either at the surface of the micelles or at the interface between the biological and the organic polymer blocks. The yields of reactions employing the micellar template were equivalent or better than existing template architectures. Aside from its physical properties and the morphologies achieved, an important requirement for a new biomaterial is its biocompatibility and interaction with living systems, i.e. human cells. The toxicity of the nanoparticles was analyzed by a cell proliferation assay. Motivated by the non-toxic nature of the amphiphilic DNA block copolymers, these nanoobjects were employed as drug delivery vehicles to target the anticancer drug to a tumor tissue. The micelles obtained from DNA block copolymers were easily functionalized with targeting units by hybridization. This facile route allowed studying the effect of the amount of targeting units on the targeting efficacy. By varying the site of functionalization, i.e. 5’ or 3’, the outcome of having the targeting unit at the periphery of the micelle or in the core of the micelle was studied. Additionally, these micelles were loaded with an anticancer drug, doxorubicin, and then applied to tumor cells. The viability of the cells was calculated in the presence and absence of targeting unit. It was demonstrated that the tumor cells bearing folate receptors showed a high mortality when the targeting unit was attached to the nanocarrier.

Spinal cord injury: assessment of autonomic state-dependent control of cardiovascular system and body core temperature

Spinal cord injury (SCI) results not only in paralysis; but it is also associated with a range of autonomic dysregulation that can interfere with cardiovascular, bladder, bowel, temperature, and sexual function. The entity of the autonomic dysfunction is related to the level and severity of injury to descending autonomic (sympathetic) pathways. For many years there was limited awareness of these issues and the attention given to them by the scientific and medical community was scarce. Yet, even if a new system to document the impact of SCI on autonomic function has recently been proposed, the current standard of assessment of SCI (American Spinal Injury Association (ASIA) examination) evaluates motor and sensory pathways, but not severity of injury to autonomic pathways. Beside the severe impact on quality of life, autonomic dysfunction in persons with SCI is associated with increased risk of cardiovascular disease and mortality. Therefore, obtaining information regarding autonomic function in persons with SCI is pivotal and clinical examinations and laboratory evaluations to detect the presence of autonomic dysfunction and quantitate its severity are mandatory. Furthermore, previous studies demonstrated that there is an intimate relationship between the autonomic nervous system and sleep from anatomical, physiological, and neurochemical points of view. Although, even if previous epidemiological studies demonstrated that sleep problems are common in spinal cord injury (SCI), so far only limited polysomnographic (PSG) data are available. Finally, until now, circadian and state dependent autonomic regulation of blood pressure (BP), heart rate (HR) and body core temperature (BcT) were never assessed in SCI patients. Aim of the current study was to establish the association between the autonomic control of the cardiovascular function and thermoregulation, sleep parameters and increased cardiovascular risk in SCI patients.

Ein neues Lumineszenzverfahren zur quantitativen und räumlichen Darstellung von Produkten des Glukosestoffwechsels in Tumoren

Eine neue auf einer Pyruvat abhängigen Biolumineszenzreaktion basierende Methode zur quantitativen Bestimmung und räumlichen Darstellung von Pyruvat in Gefrierschnitten von Gewebeproben wurde entwickelt. Dabei wurden biochemische Reaktionen so verknüpft, dass sichtbares Licht proportional zum eingesetzten Pyruvatgehalt entstand. Eine hoch signifikante positive Korrelation beider Parameter ermöglichte eine Kalibrierung mit definierten Pyruvatgehalten und damit die Quantifizierung in unbekannten Proben. Die Nachweisgrenze lag bei 0,04 pmol Pyruvat mit einer Auflösung von 0,02 µmol/g. Das Biolumineszenzverfahren wurde mit Hilfe anderer Methoden validiert, wobei eine Wiederfindung mit einer konzentrationsabhängigen Abweichung von ≤ 15 % erzielt wurde. Ein wesentlicher Vorteil der neuen Methode gegenüber bisherigen Verfahren zum Pyruvatnachweis liegt in der Messwerterfassung definierter histologischer Gewebsareale. Dies wird durch computergesteuerte Überlagerung von Metabolitverteilungen mit Schnittbildern aus Strukturfärbungen und interaktiver, „optischer Mikrodissektion“ der Gewebeschnitte möglich. Ein weiterer Nutzen der Methode ist deren optionale Kombination mit der Biolumineszenztechnik für andere Stoffwechselprodukte. So ermöglicht eine exakte Superposition zweier Metabolitbilder von unmittelbar aufeinander folgenden Gewebeschnitten eine korrelative Kolokalisationsanalyse beider Metabolite. Das Ergebnis lässt sich zum einen in Form von „Pixel-zu-Pixel“-Korrelationen dokumentieren, zum anderen kann für jeden Bildpunkt ein Laktat/Pyruvat-Verhältnis als Maß für den Redoxzustand des Gewebes berechnet und dargestellt werden. Hieraus ergeben sich z.B. räumliche L/P-Verteilungen (L/P-Karten). Ein solches „Redoximaging“ durch Kartierung des L/P-Quotienten ist bislang mit keinem anderen Verfahren möglich. Während die Entwicklung des Pyruvatnachweises eine Kernaufgabe der vorliegenden Arbeit darstellte, bestand ein weiterer wesentlicher Teil in der praktischen Anwendung der neuen Methode im Bereich der experimentellen Tumorforschung. So ergaben Messungen an acht verschiedenen Linien von humanen HNSCC-Xenotransplantaten (n = 70 Tumoren) einen mittleren Pyruvatgehalt von 1,24 ± 0,20 µmol/g. In sechs Humanbiopsien derselben Tumorentität wurde ein durchschnittlicher Pyruvatgehalt von 0,41 ± 0,09 µmol/g gemessen. Bei den Xenotransplantaten konnte eine signifikante positive Korrelation zwischen der Summe aus Laktat und Pyruvat bzw. dem L/P Verhältnis und der Strahlensensibilität gefunden werden, wobei das L/P-Verhältnis ebenso wie die Summe aus Laktat und Pyruvat maßgeblich von Laktat bestimmt wurden. Der Zusammenhang der Metabolite mit der Strahlensensibilität lässt sich durch deren antioxidative Eigenschaften erklären. Da der Redoxzustand der Zelle kritisch bezüglich der Effizienz von ROS induzierenden Therapieansätzen, wie z.B. Bestrahlung oder bestimmter Chemotherapeutika sein kann, könnte die Bestimmung des L/P Verhältnisses als prognostischer Faktor prädiktive Aussagen über die Sensibilität gegenüber solchen Behandlungen erlauben.

Le Coliti Microscopiche nei soggetti con diarrea non ematica: uno studio prospettico

Introduzione: le Coliti Microscopiche, altrimenti note come Colite Collagena e Colite Linfocitica, sono disordini infiammatori cronici del colon che causano diarrea e colpiscono più frequentemente donne in età avanzata e soggetti in terapia farmacologica. Negli ultimi anni la loro incidenza sembra aumentata in diversi paesi occidentali ma la prevalenza in Italia è ancora incerta. Scopo: il presente studio prospettico e multicentrico è stato disegnato per valutare la prevalenza delle CM in pazienti sottoposti a colonscopia per diarrea cronica non ematica. Pazienti e metodi: dal Maggio 2010 al Settembre 2010 sono stati arruolati consecutivamente tutti i soggetti adulti afferenti in due strutture dell’area metropolitana milanese per eseguire una pancolonscopia. Nei soggetti con diarrea cronica non ematica sono state eseguite biopsie multiple nel colon ascendente, sigma e retto nonché in presenza di lesioni macroscopiche. Risultati: delle 8008 colonscopie esaminate 265 sono state eseguite per diarrea cronica; tra queste, 8 presentavano informazioni incomplete, 52 riscontri endoscopici consistenti con altri disordini intestinali (i.e. IBD, tumori, diverticoliti). 205 colonscopie sono risultate sostanzialmente negative, 175 dotate di adeguato campionamento microscopico (M:F=70:105; età mediana 61 anni). L’analisi istologica ha permesso di documentare 38 nuovi casi di CM (M:F=14:24; età mediana 67.5 anni): 27 CC (M:F=10:17; età mediana 69 anni) e 11 CL (M:F=4:7; età mediana 66 anni). In altri 25 casi sono state osservate alterazioni microscopiche prive dei sufficienti requisiti per la diagnosi di CM. Conclusioni: nel presente studio l’analisi microscopica del colon ha identificato la presenza di CM nel 21,7% dei soggetti con diarrea cronica non ematica ed indagine pancolonscopica negativa. Lo studio microscopico del colon è pertanto un passo diagnostico fondamentale per il corretto inquadramento diagnostico delle diarree croniche, specialmente dopo i 60 anni di età. Ampi studi prospettici e multicentrici dovranno chiarire ruolo e peso dei fattori di rischio associati a questi disordini.

Analisi molecolare delle fasi evolutive della micosi fungoide

Lo scopo del progetto triennale del dottorato di ricerca è lo studio delle alterazioni genetiche in un gruppo di pazienti affetti da micosi fungoide ed un gruppo di pazienti affetti da sindrome di Sezary. Dalle biopsie cutanee è stato estratto il DNA e analizzato, comparandolo con DNA sano di riferimento, utilizzando la tecnica array-CGH, allo scopo di identificare la presenza di geni potenzialmente implicati nel processo di oncogenesi. Questa analisi è stata eseguita, per ogni paziente, su biopsie effettuate ad una fase iniziale di malattia e ad una fase di progressione della stessa. Sugli stessi pazienti è stata inoltre eseguita un’analisi miRNA. Si ipotizza che il profilo d’espressione dei miRNA possa infatti dare informazioni utili per predire lo stato di malattia, il decorso clinico, la progressione tumorale e la riposta terapeutica. Questo lavoro è stato poi eseguito su biopsie effettuate in pazienti affetti da sindrome di Sezary che, quando non insorge primitivamente come tale, si può considerare una fase evolutiva della micosi fungoide. La valutazione delle alterazioni genetiche, ed in particolare la correlazione esistente tra duplicazione e delezione genetica e sovra/sottoespressione genetica, è stata possibile attraverso l’interpretazione e la comparazione dei dati ottenuti attraverso le tecniche array-CGH e miRNA. Sono stati comparati i risultati ottenuti per valutare quali fossero le alterazioni cromosomiche riscontrate nei diversi stadi di malattia. L’applicazione dell’array-CGH e della metodica di analisi mi-RNA si sono rivelate molto utili per l’identificazione delle diverse aberrazioni cromosomiche presenti nel genoma dei pazienti affetti da micosi fungoide e sindrome di Sezary, per valutare la prognosi del paziente e per cercare di migliorare o trovare nuove linee terapeutiche per il trattamento delle due patologie. Lo studio di questi profili può rappresentare quindi uno strumento di grande importanza nella classificazione e nella diagnosi dei tumori.

Design and implementation of a testbed for data distribution management

Data Distribution Management (DDM) is a core part of High Level Architecture standard, as its goal is to optimize the resources used by simulation environments to exchange data. It has to filter and match the set of information generated during a simulation, so that each federate, that is a simulation entity, only receives the information it needs. It is important that this is done quickly and to the best in order to get better performances and avoiding the transmission of irrelevant data, otherwise network resources may saturate quickly. The main topic of this thesis is the implementation of a super partes DDM testbed. It evaluates the goodness of DDM approaches, of all kinds. In fact it supports both region and grid based approaches, and it may support other different methods still unknown too. It uses three factors to rank them: execution time, memory and distance from the optimal solution. A prearranged set of instances is already available, but we also allow the creation of instances with user-provided parameters. This is how this thesis is structured. We start introducing what DDM and HLA are and what do they do in details. Then in the first chapter we describe the state of the art, providing an overview of the most well known resolution approaches and the pseudocode of the most interesting ones. The third chapter describes how the testbed we implemented is structured. In the fourth chapter we expose and compare the results we got from the execution of four approaches we have implemented. The result of the work described in this thesis can be downloaded on sourceforge using the following link: https://sourceforge.net/projects/ddmtestbed/. It is licensed under the GNU General Public License version 3.0 (GPLv3).

Innovative Strategies for the Synthesis of Biologically Active Small Molecules

The post genomic era, set the challenge to develop drugs that target an ever-growing list of proteins associated with diseases. However, an increase in the number of drugs approved every year is nowadays still not observed. To overcome this gap, innovative approaches should be applied in drug discovery for target validation, and at the same time organic synthetic chemistry has to find new fruitful strategies to obtain biologically active small molecules not only as therapeutic agents, but also as diagnostic tools to identify possible cellular targets. In this context, in view of the multifactorial mechanistic nature of cancer, new chimeric molecules, which can be either antitumor lead candidates, or valuable chemical tools to study molecular pathways in cancer cells, were developed using a multitarget-directed drug design strategy. According to this approach, the desired hybrid compounds were obtained by combining in a single chemical entity SAHA analogues, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives able to block cell cycle, to induce apoptosis and cell differentiation and with Sorafenib derivative, a multikinase inhibitor. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on leukemia Bcr-Abl-expressing K562 cell lines, as well as their HDACs inhibition. Preliminary results confirmed that one of the hybrid compounds has the desired chimeric profile. A distinct project was developed in the laboratory of Dr Spring, regarding the synthesis of a diversity-oriented synthesis (DOS) library of macrocyclic peptidomimetics. From a biological point of view, this class of molecules is extremely interesting but underrepresented in drug discovery due to the poor synthetic accessibility. Therefore it represents a valid challenge for DOS to take on. A build/couple/pair (B/C/P) approach provided, in an efficient manner and in few steps, the structural diversity and complexity required for such compounds.

Topological aspects of the human protein interaction network

It is currently widely accepted that the understanding of complex cell functions depends on an integrated network theoretical approach and not on an isolated view of the different molecular agents. Aim of this thesis was the examination of topological properties that mirror known biological aspects by depicting the human protein network with methods from graph- and network theory. The presented network is a partial human interactome of 9222 proteins and 36324 interactions, consisting of single interactions reliably extracted from peer-reviewed scientific publications. In general, one can focus on intra- or intermodular characteristics, where a functional module is defined as "a discrete entity whose function is separable from those of other modules". It is found that the presented human network is also scale-free and hierarchically organised, as shown for yeast networks before. The interactome also exhibits proteins with high betweenness and low connectivity which are biologically analyzed and interpreted here as shuttling proteins between organelles (e.g. ER to Golgi, internal ER protein translocation, peroxisomal import, nuclear pores import/export) for the first time. As an optimisation for finding proteins that connect modules, a new method is developed here based on proteins located between highly clustered regions, rather than regarding highly connected regions. As a proof of principle, the Mediator complex is found in first place, the prime example for a connector complex. Focusing on intramodular aspects, the measurement of k-clique communities discriminates overlapping modules very well. Twenty of the largest identified modules are analysed in detail and annotated to known biological structures (e.g. proteasome, the NFκB-, TGF-β complex). Additionally, two large and highly interconnected modules for signal transducer and transcription factor proteins are revealed, separated by known shuttling proteins. These proteins yield also the highest number of redundant shortcuts (by calculating the skeleton), exhibit the highest numbers of interactions and might constitute highly interconnected but spatially separated rich-clubs either for signal transduction or for transcription factors. This design principle allows manifold regulatory events for signal transduction and enables a high diversity of transcription events in the nucleus by a limited set of proteins. Altogether, biological aspects are mirrored by pure topological features, leading to a new view and to new methods that assist the annotation of proteins to biological functions, structures and subcellular localisations. As the human protein network is one of the most complex networks at all, these results will be fruitful for other fields of network theory and will help understanding complex network functions in general.