Un approccio innovativo alla pianificazione della mobilità ciclabile

L’approccio innovativo di questa tesi alla pianificazione ciclabile consiste nell’integrare le linee guida per la redazione di un biciplan con aspetti, metodologie e strumenti nuovi, per rendere più efficace la programmazione di interventi. I limiti del biciplan risiedono nella fase di pianificazione e di monitoraggio, quindi, nel 1° capitolo, vengono esaminate le differenze esistenti tra la normativa americana (AASHTO) e quella italiana (D.P.R. 557/99). Nel 2° capitolo vengono analizzati gli indicatori usati nella fase di monitoraggio e la loro evoluzione fino alla definizione degli attuali indici per la determinazione del LOS delle infrastrutture ciclabili: BLOS e BCI. L’analisi è integrata con le nuove applicazioni di questi indici e con lo studio del LOS de HCM 2010. BCI e BISI sono stati applicati alla rete di Bologna per risolvere problemi di pianificazione e per capire se esistessero problemi di trasferibilità. Gli indici analizzati prendono in considerazione solo il lato offerta del sistema di trasporto ciclabile; manca un giudizio sui flussi, per verificare l’efficacia delle policy. Perciò il 3° capitolo è dedicato alla metodologia sul monitoraggio dei flussi, mediante l’utilizzo di comuni traffic counter per le rilevazioni dei flussi veicolari. Dal monitoraggio è possibile ricavare informazioni sul numero di passaggi, periodi di punta, esistenza di percorsi preferiti, influenza delle condizioni climatiche, utili ai progettisti; si possono creare serie storiche di dati per controllare l’evoluzione della mobilità ciclabile e determinare l’esistenza di criticità dell’infrastruttura. L’efficacia della pianificazione ciclabile è legata al grado di soddisfazione dell’utente e all’appetibilità delle infrastrutture, perciò il progettista deve conoscere degli elementi che influenzano le scelte del ciclista. Nel 4° capitolo sono analizzate le tecniche e gli studi sulle scelte dell’itinerario dei ciclisti, e lo studio pilota fatto a Bologna per definire le variabili che influenzano le scelte dei ciclisti e il loro peso.

Integrative Musterbildung kranialer Strukturen

Form und Gestalt kraniofazialer Strukturen sind primär beeinflusst durch die inhärente Integration der unterschiedlichsten Funktionssysteme und externer selektiver Einflüsse. Die Variabilität der Schädel-Morphe ist ein Indikator für solche Einflussfaktoren und damit ein idealer Gegenstand für vergleichende Analysen morphogenetischer Formbildung. Zur Ermittlung morphologisch-adaptiver Trends und Muster wurden sowohl Hypothesen zur morphologischen Differenziertheit als auch zu Korrelationen zwischen modularen Schädelkompartimenten (fazial, neurokranial, basikranial) untersucht. Zusätzlich wurden aus Schichtröntgenaufnahmen (CT) virtuelle Modelle rekonstruiert, welche die Interpretation der statistischen Befunde unterstützen sollten. Zur Berechnung der Gestaltunterschiede wurden mittels eines mechanischen Gelenkarm-Messgerätes (MicroScribe-G2) max. 85 ektokraniale Messpunkte (Landmarks) bzw. dreidimensionale Koordinaten an ca. 520 Schädeln von fünf rezenten Gattungen der Überfamilie Hominoidea (Hylobates, Pongo, Gorilla, Pan und Homo) akquiriert. Aus dem Datensatz wurden geometrische Störfaktoren (Größe, Translation, Rotation) mathematisch eliminiert und die verbleibenden Residuale bzw. ‚Gestalt-Variablen‘ diversen multivariat-statistischen Verfahren unterzogen (Faktoren, Cluster-, Regressions- und Korrelationsanalysen sowie statistische Tests). Die angewandten Methoden erhalten die geometrische Information der Untersuchungsobjekte über alle Analyseschritte hinweg und werden unter der Bezeichnung „Geometric Morphometrics (GMM)“ als aktueller Ansatz der Morphometrie zusammengefasst. Für die unterschiedlichen Fragestellungen wurden spezifische Datensätze generiert. Es konnten diverse morphologische Trends und adaptive Muster mit Hilfe der Synthese statistischer Methoden und computer-basierter Rekonstruktionen aus den generierten Datensätzen ermittelt werden. Außerdem war es möglich, präzise zu rekonstruieren, welche kranialen Strukturen innerhalb der Stichprobe miteinander wechselwirken, einzigartige Variabilitäten repräsentieren oder eher homogen gestaltet sind. Die vorliegenden Befunde lassen erkennen, dass Fazial- und Neurokranium am stärksten miteinander korrelieren, während das Basikranium geringe Abhängigkeiten in Bezug auf Gesichts- oder Hirnschädelveränderungen zeigte. Das Basikranium erweist sich zudem bei den nicht-menschlichen Hominoidea und über alle Analysen hinweg als konservative und evolutiv-persistente Struktur mit dem geringsten Veränderungs-Potential. Juvenile Individuen zeigen eine hohe Affinität zueinander und zu Formen mit einem kleinem Gesichts- und großem Hirnschädel. Während das Kranium des rezenten Menschen primär von Enkephalisation und fazialer Retraktion (Orthognathisierung) dominiert ist und somit eine einzigartige Gestalt aufweist, zeigt sich der Kauapparat als maßgeblich formbildendes Kompartiment bei den nicht-menschlichen Formen. Die Verbindung von GMM mit den interaktiven Möglichkeiten computergenerierter Modelle erwies sich als valides Werkzeug zur Erfassung der aufgeworfenen Fragestellungen. Die Interpretation der Befunde ist durch massive Interkorrelationen der untersuchten Strukturen und der statistisch-mathematischen Prozeduren als hoch komplex zu kennzeichnen. Die Studie präsentiert einen innovativen Ansatz der modernen Morphometrie, welcher für zukünftige Untersuchungen im Bereich der kraniofazialen Gestaltanalyse ausgebaut werden könnte. Dabei verspricht die Verknüpfung mit ‚klassischen’ und modernen Zugängen (z. B. Molekularbiologie) gesteigerte Erkenntnismöglichkeiten für künftige morphometrische Fragestellungen.

Early Warning For Large Earthquakes: Observations, Models and Real-Time Data Analysis

This thesis is a collection of works focused on the topic of Earthquake Early Warning, with a special attention to large magnitude events. The topic is addressed from different points of view and the structure of the thesis reflects the variety of the aspects which have been analyzed. The first part is dedicated to the giant, 2011 Tohoku-Oki earthquake. The main features of the rupture process are first discussed. The earthquake is then used as a case study to test the feasibility Early Warning methodologies for very large events. Limitations of the standard approaches for large events arise in this chapter. The difficulties are related to the real-time magnitude estimate from the first few seconds of recorded signal. An evolutionary strategy for the real-time magnitude estimate is proposed and applied to the single Tohoku-Oki earthquake. In the second part of the thesis a larger number of earthquakes is analyzed, including small, moderate and large events. Starting from the measurement of two Early Warning parameters, the behavior of small and large earthquakes in the initial portion of recorded signals is investigated. The aim is to understand whether small and large earthquakes can be distinguished from the initial stage of their rupture process. A physical model and a plausible interpretation to justify the observations are proposed. The third part of the thesis is focused on practical, real-time approaches for the rapid identification of the potentially damaged zone during a seismic event. Two different approaches for the rapid prediction of the damage area are proposed and tested. The first one is a threshold-based method which uses traditional seismic data. Then an innovative approach using continuous, GPS data is explored. Both strategies improve the prediction of large scale effects of strong earthquakes.

Analisi fosfo-proteomica di campioni di tumore: il problema della stratificazione dei pazienti ed eterogeneità intra-tumorale nell'era della terapia personalizzata

Nella presente tesi indaghiamo la potenzialità di LCM e Reverse Phase Protein microarray negli studi clinici. Si analizza la possibilità di creare una bio banca con line cellular primarie, al fine di conseguire drug test di sensibilità prima di decidere il trattamento da somministrare ai singoli pazienti. Sono stati ottenuti profili proteomici da biopsie pre e post terapia. I risultati dimostrano che questa piattaforma mostra il meccanismo di resistenza acquisito durante la terapia biologica. Questo ci ha portato ad analizzare una possibile stratificazione per pazienti con mCRC . I dati hanno rivelato distinti pathway di attivazione tra metastasi resecabile e non resecabili. I risultati mostrano inoltre due potenziali bersagli farmacologici. Ma la valutazione dell'intero tumore tramite singole biopsie sembra essere un problema a causa dell’eterogeneità intratumorale a livello genomico. Abbiamo indagato questo problema a livello dell'architettura del segnale in campioni di mCRC e ccRCC . I risultati indicano una somiglianza complessiva nei profili proteomici all'interno dello stesso tumore. Considerando che una singola biopsia è rappresentativa di un intera lesione , abbiamo studiato la possibilità di creare linee di cellule primarie, per valutare il profilo molecolare di ogni paziente. Fino ad oggi non c'era un protocollo per creare linee cellulari immortalizzate senza alcuna variazione genetica . abbiamo cosiderato, però, l'approccio innovativo delle CRCs. Ad oggi , non è ancora chiaro se tali cellule mimino il profilo dei tessuti oppure I passaggi in vitro modifichino i loro pathways . Sulla base di un modello di topo , i nostri dati mostrano un profilo di proteomica simile tra le linee di cellule e tessuti di topo LCM. In conclusione, i nostri dati dimostrano l'utilità della piattaforma LCM / RPPA nella sperimentazione clinica e la possibilità di creare una bio - banca di linee cellulari primarie, per migliorare la decisione del trattamento.

Sistemi tecnologici innovativi di involucro per il recupero del patrimonio edilizio recente. L'edilizia scolastica nel Comune di Bologna

La ricerca è volta a presentare un nuovo approccio integrato, a supporto di operatori e progettisti, per la gestione dell’intero processo progettuale di interventi di riqualificazione energetica e architettonica del patrimonio edilizio recente, mediante l’impiego di soluzioni tecnologiche innovative di involucro edilizio. Lo studio richiede necessariamente l’acquisizione di un repertorio selezionato di sistemi costruttivi di involucro, come base di partenza per l’elaborazione di soluzioni progettuali di recupero delle scuole appartenenti al secondo dopoguerra, in conglomerato cementizio armato, prevalentemente prefabbricate. Il progetto individua procedimenti costruttivi ecocompatibili per la progettazione di componenti prefabbricati di involucro “attivo”, adattabile ed efficiente, da assemblare a secco, nel rispetto dei requisiti prestazionali richiesti dalle attuali normative. La ricerca è finalizzata alla gestione dell’intero processo, supportato da sistemi di rilevazione geometrica, collegati a software di programmazione parametrica per la modellazione di superfici adattabili alla morfologia dei fabbricati oggetto di intervento. Tali strumenti informatizzati CAD-CAM sono connessi a macchine a controllo numerico CNC per la produzione industrializzata degli elementi costruttivi “su misura”. A titolo esemplificativo dell’approccio innovativo proposto, si formulano due possibili soluzioni di involucro in linea con i paradigmi della ricerca, nel rispetto dei principi di sostenibilità, intesa come modularità, rapidità di posa, reversibilità, recupero e riciclo di materiali. In particolare, le soluzioni innovative sono accomunate dall’applicazione di una tecnica basata sull’assemblaggio di elementi prefabbricati, dall’adozione di una trama esagonale per la tassellazione della nuova superficie di facciata, e dall’utilizzo del medesimo materiale termico isolante, plastico e inorganico, riciclato ed ecosostenibile, a basso impatto ambientale (AAM - Alkali Activated Materials). Le soluzioni progettuali proposte, sviluppate presso le due sedi coinvolte nella cotutela (Università di Bologna, Université Paris-Est) sono affrontate secondo un protocollo scientifico che prevede: progettazione del sistema costruttivo, analisi meccanica e termica, sperimentazione costruttiva, verifica delle tecniche di messa in opera e dei requisiti prestazionali.

Kinetische Studien zur OH-Bildung über die Reaktionen von HO 2 mit organischen Peroxyradikalen

Es wurde untersucht, wie sich das Substitutionsmuster organischer Peroxyradikale (RO2) auf die Ratenkonstante k1 und die Verzweigungsverhältnisse α, β und γ der Reaktionen von RO2 mit HO2 auswirkt. Die Effekte der Deuterierung von HO2 wurden ebenfalls studiert. Für zwei RO2 wurde zusätzlich das UV-Absorptionsspektrum bestimmt.rnrn αrnRO2 + HO2 → RO + OH + O2 R1arnrn βrn → RO2H + O2 R1brnrn γrn → ROH + O3 R1crnrnIn dieser Arbeit wurde ein neues Experiment aufgebaut. Für die direkte und zeitaufgelöste Messung der OH-Konzentration wurde das Verfahren der Laser-induzierten Fluoreszenz angewendet. Die Radikalerzeugung erfolgte mittels gepulster Laserphotolyse, wodurch unerwünschte Nebenreaktionen weitgehend unterdrückt werden konnten. Mittels transienter Absorptionsspektroskopie konnten die Menge der photolytisch erzeugten Radikale bestimmt und die Ozonbildung über R1c quantifiziert werden. Für die Auswertung wurden kinetische Modelle numerisch an die Messdaten angepasst. Um die experimentellen Unsicherheiten abzuschätzen, wurde ein Monte-Carlo-Ansatz gewählt.rnrnk1 und α reagieren sehr empfindlich auf Veränderungen des RO2-Substitutionsmusters. Während sich eine OH-Bildung für das unsubstituierte C2H5O2 (EtP) mit α EtP ≤ 5 % nicht nachweisen lässt, stellt R1a bei den α-Oxo-substituierten H3CC(O)O2 (AcP) und HOCH2C(O)O2 (HAP) mit α AcP = (63 ± 11) % bzw. α HAP = (69 ± 12) % den Hauptkanal dar. Wie die mit α HEP = (10 ± 4) % geringfügige OH-Bildung bei HOC2H4O2 (HEP) zeigt, nimmt die OH-Gruppe in β-Stellung weniger Einfluss auf den Wert von α als die Oxogruppe in α-Stellung. Bei der Erzeugung α-Oxo-substituierter RO2 kann ebenfalls OH entstehen (R+O2→RO2/OH). Die Druckabhängigkeit dieser OH-Quelle wurde mit einem innovativen Ansatz bestimmt. Mit γ AcP = (15+5-6) % bzw. γ HAP = (10+2-3) % lässt sich für die Reaktionen der α-Oxo-substituierten RO2 eine erhebliche Ozonbildung nachweisen. Durch die Einführung der α-Oxogruppe steigt k1 jeweils um 1,3 • 10-11 cm3s-1 an, der Effekt der β-Hydroxygruppe ist halb so groß (k1 AcP = (2,0 ± 0,4) • 10-11 cm3s-1, k1 HAP = (2,6 ± 0,4) • 10-11 cm3s-1). Das Verzweigungsverhältnis α steigt weiter, wenn das HO2 deuteriert wird (α AcP,iso = (80 ± 14) %, k1 AcP,iso = (2,1 ± 0,4) • 10-11 cm3s-1). Vergleiche mit älteren Studien zeigen, dass die OH-Bildung über R1a bislang deutlich unterschätzt worden ist. Die möglichen Ursachen für die Unterschiede zwischen den Studien werden ebenso diskutiert wie die Hintergründe der beobachteten Substituenteneffekte.

La strategia BIM a supporto del progetto della sicurezza nel cantiere edile: il caso dell'ospedale di primo soccorso a Lampedusa.

Throughout this research, the whole life cycle of a building will be analyzed, with a special focus on the most common issues that affect the construction sector nowadays, such as safety. In fact, the goal is to enhance the management of the entire construction process in order to reduce the risk of accidents. The contemporary trend is that of researching new tools capable of reducing, or even eliminating, the most common mistakes that usually lead to safety risks. That is one of the main reasons why new technologies and tools have been introduced in the field. The one we will focus on is the so-called BIM: Building Information Modeling. With the term BIM we refer to wider and more complex analysis tool than a simple 3D modeling software. Through BIM technologies we are able to generate a multi-dimension 3D model which contains all the information about the project. This innovative approach aims at a better understanding and control of the project by taking into consideration the entire life cycle and resulting in a faster and more sustainable way of management. Furthermore, BIM software allows for the sharing of all the information among the different aspects of the project and among the different participants involved thus improving the cooperation and communication. In addition, BIM software utilizes smart tools that simulate and visualize the process in advance, thus preventing issues that might not have been taking into consideration during the design process. This leads to higher chances of avoiding risks, delays and cost increases. Using a hospital case study, we will apply this approach for the completion of a safety plan, with a special focus onto the construction phase.

Modellkomplexe zur Sauerstoffaktivierung auf Basis des 1,3,4-Thiadiazols

Das Ziel der vorliegenden Arbeit waren die Synthese und Untersuchung von Modellverbindungen zur Sauerstoffaktivierung auf der Basis neuer Ligandensysteme des 1,3,4-Thiadiazols unter Ausarbeitung einer Synthesestrategie zur Derivatisierung der heteroaromatischen 1,3,4-Thiadiazol-Liganden, deren Koordinationsverhalten in Abhängigkeit ihres 2,5-Substitutionsmusters untersucht wurde, sowie die fortführende Bearbeitung bereits bekannter Ligandensysteme zur Erzeugung von homo- und heterovalenten Übergangsmetallkomplexverbindungen.rnDie unter der Verwendung der modifizierten Liganden TPDE, H1TPDP und H1BPMP resultierenden dinuklearen Komplexverbindungen zeigen unterschiedlich starke antiferromagnetische Wechselwirkungen in Abhängigkeit der vorhandenen Brückenliganden. In der Verbindung [Fe6O2(OH)(L´)2(OOCMe3)9(OEt)2] trat eine Fragmentierung des Liganden H1TPDP auf. Das cisoide Ligandensubstitutionsmuster der entstandenen sechskernigen Verbindung ist verantwortlich für die interessanten magnetischen Eigenschaften des Komplexes. rnNeue Perspektiven zur Erzeugung von Modellverbindungen zur Sauerstoffaktivierung wurden mit dem Mono-Chelatliganden H1ETHP und den Bis-Chelatliganden HL2H, H2L2H und H2BATP aufgezeigt. Die Umsetzung von H1ETHP mit verschiedenen Übergangsmetallsalzen resultierte für die Metalle Cr(III), Fe(III), Co(III) und Ni(II) in mononuklearen Verbindungen des Typs [M(ETHP)2]X (X = ClO4, FeCl4, OMe, Cl, Br) sowie in zwei tetranuklearen Verbindungen mit Mn(II) und Cu(II). [Mn4(ETHP)6] besitzt ein propellerförmiges, planares [Mn4O6]2+-System mit einen Spingrundzustand von S = 5. In allen Verbindungen von H1ETHP konnte eine mono-κN-Koordination des 1,3,4-Thiadiazol-Rückgrates über eines seiner beiden endozyklischen Stickstoffdonoratome beobachtet werden. rnAus Umsetzungen der Bis-Chelatliganden wurden fast ausschließlich polynukleare Übergangsmetallkomplexe erhalten. Insbesondere der Ligand H2L2H zeigt eine ausgeprägte Tendenz zur Ausbildung trinuklearer, linearer Komplexe, welche auf Grund ihrer ungeraden Anzahl von Übergangsmetallionen einen Spingrundzustand S ≠ 0 aufweisen.rn Die mit dem Liganden HL2H erhaltenen Verbindungen unterstreichen die hohe Flexibilität dieser Systeme hinsichtlich der Erzeugung polynuklearer und heterovalenter Komplexverbindungen. So konnten in Abhängigkeit vom verwendeten Übergangsmetallsalz trinukleare, pentanukleare, aber auch hepta- und oktanukleare Verbindungen synthetisiert werden. Insbesondere die Komplexe des Mangans und des Cobalts zeigen ein heterovalentes [MnIIMnIII4]- bzw. [CoII2CoIII3]-Motiv, was sich in Spingrundzuständen von S ≠ 0 äußert. Der diamagnetische, achtkernige Fe8-Cluster besitzt eine pseudo C3-symmetrische Anordnung der Metall-Zentren, während für die heptanukleare Cu7-Kette durch ihre stark unterschiedlichen Kupfer-Koordinationsgeometrien interessante magnetische Austauschwechselwirkungen beobachtet werden konnten. Der dreikernige µ3-oxo-verbrückte Komplex des Liganden H2BATP zeigt als interessante strukturelle Eigenschaft ein ein µ3-Verbrückungsmuster des eingesetzten Sulfat-Anions. rnIn allen Komplexen der Bis-Chelatliganden HL2H, H2L2H und H2BATP konnte ein µ2-κN,κN-Koordiantionsmodus des 1,3,4-Thiadiazols und somit eine Abhängigkeit der Verbrückung vom Ligandensubstitutionsmuster beobachtet werden.rn

Nanomechanics to drive stem cells in injured tissues: insights from current research and future perspectives

Stem cells reside within tissue, ensuring its natural ability to repair an injury. They are involved in the natural repair of damaged tissue, which encompasses a complex process requiring the modulation of cell survival, extracellular matrix turnover, angiogenesis, and reverse remodeling. To date, the real reparative potential of each tissue is underestimated and noncommittal. The assessment of the biophysical properties of the extracellular environment is an innovative approach to better understand mechanisms underlying stem cell function, and consequently to develop safe and effective therapeutic strategies replacing the loss of tissue. Recent studies have focused on the role played by biomechanical signals that drive stem cell death, differentiation, and paracrinicity in a genetic and/or an epigenetic manner. Mechanical stimuli acting on the shape can influence the biochemistry and gene expression of resident stem cells and, therefore, the magnitude of biological responses that promote the healing of injured tissue. Nanotechnologies have proven to be a revolutionary tool capable of dissecting the cellular mechanosensing apparatus, allowing the intercellular cross-talk to be decoded and enabling the reparative potential of tissue to be enhanced without manipulation of stem cells. This review highlights the most relevant findings of stem cell mechanobiology and presents a fascinating perspective in regenerative medicine.

Current status of drug-eluting stents

First-generation drug-eluting stents (DES) with controlled release of sirolimus or paclitaxel from durable polymers compared with bare-metal stents have been consistently shown to reduce the risk of repeat revascularization procedures due to restenosis. The superior efficacy was found across a wide range of patients and lesion subsets and persisted up to 5 years whereas similar outcomes have been observed in terms of death and myocardial infarction. Newer generation DES have been developed with the goal to further improve upon the safety profile of first-generation DES while maintaining efficacy. These platforms include DES with improved and more biocompatible durable polymers, DES using bioabsorbable polymers for drug release, DES with polymer-free drug release, and fully bioabsorbable DES. Newer generation DES with durable polymers such as zotarolimus-eluting or everolimus-eluting XIENCE V stents have been directly compared with first-generation DES. Most recent results of large scale clinical trials are encouraging in terms of similar or increased efficacy while improving safety by reducing the rates of myocardial infarctions and stent thrombosis. DES using biodegradable polymers for drug release represent the next technological modification and preliminary results are favorable and demonstrate similar angiographic and clinical efficacy as first-generation DES, but only longer term follow-up and investigation in larger patient cohorts will determine whether their use is associated with improved long-term safety. Fully bioabsorbable stents represent another innovative approach. Whether this innovative concept will enter into clinical routine remains yet to be determined.

Towards Self-Learning Radio-Based Localization Systems

Location-awareness indoors will be an inseparable feature of mobile services/applications in future wireless networks. Its current ubiquitous availability is still obstructed by technological challenges and privacy issues. We propose an innovative approach towards the concept of indoor positioning with main goal to develop a system that is self-learning and able to adapt to various radio propagation environments. The approach combines estimation of propagation conditions, subsequent appropriate channel modelling and optimisation feedback to the used positioning algorithm. Main advantages of the proposal are decreased system set-up effort, automatic re-calibration and increased precision.

Temporary hypoxic stress protects the liver from Fas-mediated apoptosis and ischemia reperfusion injury

Molecular responses to hypoxia restore oxygen homeostasis and promote cell survival, and are mainly regulated through the activation of the hypoxia-inducible transcription factor (HIF)-1 and its target genes. In this study we questioned whether surgically depleting the liver s arterial blood supply, by clamping the hepatic artery (HA), would be sufficient to mount a hypoxia-driven molecular response, the up-regulation of hepatoprotective genes and thereby protect the liver from subsequent damaging insults.;;The HA of normal male Balb/c mice was clamped with a micro vascular clip for 2 hours. The liver s saturated oxygen concentration (SO2) was measured using an O2C surface probe (LEA-Medizintechnik) and interstitial fluid was collected with microdialysis membranes to monitor tissue damage. Mice without clamping served as sham operated controls. Interstitial fluid was assessed for lactate pyruvate (L/P) and glycerol content and the mRNA of hepatoprotective genes was analyzed by real time PCR. Subsequently, mice received either a tail vein injection of anti-Fas antibody (Jo2, 0.2 mg/kg) or the liver was made ischemic (60min) followed by 6 hours reperfusion. Caspase 3-activity and cleaved lamin A were used to assess apoptosis. In separate groups, animal were monitored for survival.;;After 30min of clamping the HA the SO2 of the liver decreased and remained at a reduced level for up to 2 hours, without an increase in L/P ratio or glycerol release. We demonstrate the activation of a hypoxia-inducible signaling pathway by the stabilization of HIF-1 protein (Western blot) and by an increase of its target gene, Epo, mRNA. There was an up-regulation of the hepatoprotective genes IL-6, IGFBP-1, HO-1 and A20 mRNA. When subsequently injected with Jo2, animals preconditioned with HA clamping, had a significantly decreased caspase-3 activity (avg21044 vs. avg3637; p=0.001, T-test) and there were fewer positive cells for cleaved Lamin A. The survival probability (10.5 hours, n=12) of mice with HA clamping was significantly higher (3.2 hours, n=13; p=0.014, Logrank test). Likewise, survival after 60 minutes of partial hepatic ischemia and 6 hours of reperfusion was reduced from 86% in mice with pretreatment by HA clamping to 56% in sham treated controls.;;This study demonstrates that a localized hypoxic stress can be achieved by surgically removing the livers arterial blood supply. Furthermore it can stimulate a hepatoprotective response that protects the liver against Fas-mediated apoptosis and ischemia-reperfusion injury. Our findings offer an innovative approach to induce hepatoprotective genes to defend the liver against subsequent insults.

Agentenbasiertes Planungsmodell für die Grobplanung von Kommissioniersystemen

Rechnergestützte Modellansätze, die Logistiksysteme gestalten und generieren, sind eine hochkomplexe Aufgabenstellung. Die bisher in der Praxis existierenden Planungs- und Steuerungsmodelle für Intralogistiksysteme weisen für die aktuellen und zukünftigen Anforderungen wie der Komplexitätsbewältigung, Reaktionsschnelligkeit und Anpassungsfähigkeit Schwachstellen auf. – Ein innovativer Ansatz, diesen Ansprüchen gerecht zu werden, stellen Multiagentensysteme dar. Mit ihrem dezentralen und modularen Charakter sind sie für ein komplexes Problem mit einem geringen Grad an Strukturiertheit geeignet. Außerdem ermöglichen diese computergestützten intelligenten Systeme den Anwendern eine einfache und aufwandsarme Handhabung.

Evaluative Morphology in Georgian

With examples drawn from over 200 world languages, this ground-breaking volume presents a state-of-the-art overview of evaluative morphology. Offering an innovative approach to major theoretical questions, the Edinburgh Handbook analyses the field from a cross-linguistic perspective, considering semantic, pragmatic and sociolinguistic aspects, as well as word-formation processes and evaluative morphology acquisition. Complementing the synchronic approach with a diachronic perspective, this study establishes a picture of intriguing diversity in evaluative morphology manifestations, and offers a comprehensive analysis of the situation in dozens of languages and language families. Divided into 2 distinct parts, the handbook begins with 13 chapters discussing evaluative morphology in relation to areas such as pragmatics, semantics, linguistic universals and sociolinguistics. The second part is comprised of descriptive chapters, broken into the following subsets: Eurasia, South- East Asia and Oceania, Australia-New Guinea, Africa, North America and South America.

Effect of Health Risk Assessment and Counselling on Health Behaviour and Survival in Older People: A Pragmatic Randomised Trial.

BACKGROUND Potentially avoidable risk factors continue to cause unnecessary disability and premature death in older people. Health risk assessment (HRA), a method successfully used in working-age populations, is a promising method for cost-effective health promotion and preventive care in older individuals, but the long-term effects of this approach are unknown. The objective of this study was to evaluate the effects of an innovative approach to HRA and counselling in older individuals for health behaviours, preventive care, and long-term survival. METHODS AND FINDINGS This study was a pragmatic, single-centre randomised controlled clinical trial in community-dwelling individuals aged 65 y or older registered with one of 19 primary care physician (PCP) practices in a mixed rural and urban area in Switzerland. From November 2000 to January 2002, 874 participants were randomly allocated to the intervention and 1,410 to usual care. The intervention consisted of HRA based on self-administered questionnaires and individualised computer-generated feedback reports, combined with nurse and PCP counselling over a 2-y period. Primary outcomes were health behaviours and preventive care use at 2 y and all-cause mortality at 8 y. At baseline, participants in the intervention group had a mean ± standard deviation of 6.9 ± 3.7 risk factors (including unfavourable health behaviours, health and functional impairments, and social risk factors) and 4.3 ± 1.8 deficits in recommended preventive care. At 2 y, favourable health behaviours and use of preventive care were more frequent in the intervention than in the control group (based on z-statistics from generalised estimating equation models). For example, 70% compared to 62% were physically active (odds ratio 1.43, 95% CI 1.16-1.77, p = 0.001), and 66% compared to 59% had influenza vaccinations in the past year (odds ratio 1.35, 95% CI 1.09-1.66, p = 0.005). At 8 y, based on an intention-to-treat analysis, the estimated proportion alive was 77.9% in the intervention and 72.8% in the control group, for an absolute mortality difference of 4.9% (95% CI 1.3%-8.5%, p = 0.009; based on z-test for risk difference). The hazard ratio of death comparing intervention with control was 0.79 (95% CI 0.66-0.94, p = 0.009; based on Wald test from Cox regression model), and the number needed to receive the intervention to prevent one death was 21 (95% CI 12-79). The main limitations of the study include the single-site study design, the use of a brief self-administered questionnaire for 2-y outcome data collection, the unavailability of other long-term outcome data (e.g., functional status, nursing home admissions), and the availability of long-term follow-up data on mortality for analysis only in 2014. CONCLUSIONS This is the first trial to our knowledge demonstrating that a collaborative care model of HRA in community-dwelling older people not only results in better health behaviours and increased use of recommended preventive care interventions, but also improves survival. The intervention tested in our study may serve as a model of how to implement a relatively low-cost but effective programme of disease prevention and health promotion in older individuals. TRIAL REGISTRATION International Standard Randomized Controlled Trial Number: ISRCTN 28458424.