Gigantismo delle infrastrutture e microsistemi urbani. Il ruolo del progetto

Between nature and landscape there may be an intrinsic solidarity, but the relation between landscape and infrastructure, landscape and urban territories is not so reassuring and taken for granted, since this relation is all too often based upon the basic needs of use that do not contemplate the natural value of the places and the needs of the weak urban conglomerates. This is a reality stemming from diachronistic staggering touching different links between infrastructural giants and the hope for survival of scattered urban areas. Within this framework, the project finds itself immersed in a complex and always fluctuating experiment. Design strategies and techniques are not aimed at constructing finished, unambiguous solutions, but at structuring transformation rules, conditions of coherence that may produce a vision able to integrate an overall view and the focus on urban micro-dimensions. An exemplary case where these unbalances emerge with strength may be found in the environmental system of the river-bed of the Esino river where the Sentino creek flows into the river (Gola della Rossa Park) in the portion between the Genga Stazione district and the San Vittore delle Chiuse hamlet, in the province of Ancona. It is a complex mix between landscape with a strong character and towns that are subject to the intersection of a huge bundle of railway and road infrastructures. It is a segment full of connections between natural landmarks, with a historical and natural value, and artificial ones, that may be clearly become an issue for the whole environment

Processo creativo e invenzioni della tecnica

Il rapporto con le tecniche è generalmente incentrato sull’impiego strumentale delle stesse. Si considera l’universo dei mezzi come un repertorio già a disposizione per garantire l’operatività di un procedimento ideativo o di un progetto, da indirizzare in ragione di un fine che non è implicito nel mezzo stesso, ma che si giustifica nel risultato che per suo tramite è reso possibile. Il fine è la riuscita qualitativa di un’idea e nel nostro caso dell’architettura. Ribaltando questa consuetudine di pensiero è viceversa pensabile un meccanismo inverso, nel quale è l’architettura stessa, la scommessa formale e funzionale da lei avanzata, a mettere in movimento il mondo delle tecniche. Le quali non sono già date, ma vanno ricercate in quanto ancora da scoprire o inventare. Il rischio della forma si gioca come possibilità del suo trasferimento nel mondo di una tecnologia in attesa, ancora da scoprire e verificare. E’ in questa prospettiva che la composizione architettonica e la pratica progettuale possono avere a che fare con lo strumentario delle tecniche. Non solo quando si ottimizza l’uso di ciò che è già a disposizione, ma anche in quanto capacità di avviare la ricerca e la scoperta di nuovi procedimenti radicati in un fine. Sono questi il significato e la rilevanza del trasferimento tecnologico per la disciplina del progetto di architettura, intesa non solo come il luogo dove le tecniche si inverano, ma come fattore di stimolo per il rinnovamento delle stesse. In questi anni, l’autrice ha condotto un paziente lavoro ai confini delle due discipline, senza rinunciare alla sfida di far interagire l’idea iniziale e il pensiero progettuale che la governa con l’invenzione di una nuova tecnologia costruttiva, che trova il suo significato, non nell’espressione in sé dell’apparato tecnico-funzionale ma nella sua stessa immagine finale. In questo senso la tecnica, in questa ricerca, non si dispone come strumento già dato, come mezzo indipendente dai fini, quanto piuttosto concresce in essa prendendo forma coerente nello sviluppo unitario dell’indagine e del risultato progettuale

Progetto e infrastruttura: le trasformazioni dell’interfaccia città-porto-canale a Senigallia

 Senigallia is one of the several average-sized coast towns that, in the last decade, paid attention to redesign and reorganize their interface spaces between urban contexts and seafront activities. It is an attempt to re-establish a continuity between the urban fabric, the functional areas along the coastline, and the infrastructural system. Today, Senigallia’s morphological scenery shows a mixed seafront border line, whose characters have been alternatively determined by defense and protection needs, and, more recently, by trading and commercial functions. The town is crossed by the Misa river, a major linear infrastructure, which imposes its unfathomable laws of floods and flows, while claims some instruments for water control; the town is also dramatically split by the railway line, whose disruptive and excluding presence affects Senigallia and a great part of the Adriatic coast. In such terms, urban design, as a field of experimentation, is a powerful technical instrument, together with an appropriate management and control of urban policies, to elaborate operative proposals for sewing up the fracture – apparently incurable –, caused by the functional alienation of river banks, the decay of wildly urbanized coasts, and a poor integration of infrastructures into the urban dynamics. Several design experimentations have already been made in such direction; this is a proof of an important change in design trends, which could be applied to Senigallia’s situation too, in the frame of a vast program of urban refurbishment, promoted by the Municipality. Two noticeable interventions of this kind are: the enlargement and technical/functional upgrading of the port, and the project of a new tourist and residential district, designed by Paolo Portoghesi, to be built in ‘Sacelit/ex Italcementi’ area, one of the many in-between areas, dismissed and left for a long time abandoned, as a memory of a bygone productive season. In all these enterprises, the topic of infrastructures plays a dominant role. The need to re-balance and re-establish a relationship with the town definitely requires a new planning of existing tracks, accesses, and relational spaces.Come altre realtà urbane di costa, anche Senigallia, nell’ultimo decennio, si colloca tra quelle città d’acqua, di medie dimensioni, attente a ridisegnare e riorganizzare gli spazi di interfaccia tra contesti urbani e gli ambiti delle attività fronte mare. Un tentativo di ricomporre una continuità tra le trame della città, le aree funzionali della costa e delle sponde e il sistema delle sue infrastrutture. Lo scenario morfologico che appare oggi, per Senigallia, racconta una città i cui confini si affermano sul fronte mare, variamente segnati dalla richiesta di protezione e difesa sulla linea della costa o viceversa incalzati, in tempi più recenti, dalle ragioni dello scambio e dei commerci. Una città divisa dalla cesura del fiume Misa, primaria infrastruttura lineare, che impone le leggi insondabili delle piene e dei reflussi mentre reclama gli strumenti per il controllo delle acque, una città spezzata dalla lacerazione imposta dalla linea ferrata, sistema dirompente ed escludente (per Senigallia e per lunga parte della costa adriatica). In questi termini il progetto, come campo di sperimentazione, si prefigura, insieme ad adeguate gestioni e controllo delle politiche urbane, come valido strumento tecnico-operativo per esplorare risposte progettuali in grado di ricucire l’apparente insanabile frattura che l’estraneità funzionale delle rive del fiumi o il degrado di coste malamente urbanizzate o infrastrutture non perfettamente integrate nella dinamica urbana hanno determinato. La registrazione da più parti di esperimenti progettuali che vanno in questa direzione ci avverte di un significativo cambiamento dei paradigmi progettuali applicabili alla realtà senigalliese inseriti in un vasto programma di riqualificazione da parte dell’Amministrazione cittadina. Tra questi, il progetto dell’ampliamento del porto e del suo adeguamento tecnico funzionale e il progetto del quartiere turistico-residenziale progettato da Paolo Portoghesi che si realizzera’ nell’area Sacelit ex Italcementi, una delle tante aree residuali, dismesse e lasciate a lungo a memoria In questo contesto il Piano Regolatore Portuale per Senigallia raccoglie le implicazioni e le criticità che derivano dall’istanza di una strategia pianificatoria che affida alle concrete potenzialità della disciplina del progetto gli strumenti in grado di amministrare le condizioni poste dalla attualizzazione di probabili configurazioni spaziali e futuri concreti scenari, dove e’ il porto che diventa luogo, polo urbano condensatore di interessi civici. In tutte queste iniziative il tema dell’infrastrutture gioca un ruolo fondamentale e la necessità di riequilibrare e ricostituire un rapporto con la città chiede una sicura rivisitazione dei tracciati esistenti, degli accessi, degli spazi di relazione

The microfluidic trainer: Design, fabrication and validation of a tool for testing and improving manual skills

Microfluidic principles have been widely applied for more than 30 years to solve biological and micro-electromechanical problems. Despite the numerous advantages, microfluidic devices are difficult to manage as their handling comes with several technical challenges. We developed a new portable tool, the microfluidic trainer (MT), that assesses the operator handling skills and that may be used for maintaining or improving the ability to inject fluid in the inlet of microfluidic devices for in vitro cell culture applications. After several tests, we optimized the MT tester cell to reproduce the real technical challenges of a microfluidic device. In addition to an exercise path, we included an overfilling indicator and a correct infilling indicator at the inlet (control path). We manufactured the MT by engraving a 3 mm-high sheet of methacrylate with 60W CO2 laser plotter to create multiple capillary paths. We validated the device by enrolling 21 volunteers (median age 33) to fill both the MT and a commercial microfluidic device. The success rate obtained with MT significantly correlated with those of a commercial microfluidic culture plate, and its 30 min-continuous use for three times significantly improved the performance. Overall, our data demonstrate that MT is a valid assessment tool of individual performances in using microfluidic devices and may represent a low-cost solution to training, improve or warm up microfluidic handling skills

Notch signaling sustains the expression of Mcl-1 and the activity of eIF4E to promote cell survival in CLL

In chronic lymphocytic leukemia (CLL), Notch1 and Notch2 signaling is constitutively activated and contributes to apoptosis resistance. We show that genetic inhibition of either Notch1 or Notch2, through small-interfering RNA, increases apoptosis of CLL cells and is associated with decreased levels of the anti-apoptotic protein Mcl-1. Thus, Notch signaling promotes CLL cell survival at least in part by sustaining Mcl-1 expression. In CLL cells, an enhanced Notch activation also contributes to the increase in Mcl-1 expression and cell survival induced by IL-4.Mcl-1 downregulation by Notch targeting is not due to reduced transcription or degradation by caspases, but in part, to increased degradation by the proteasome. Mcl-1 downregulation by Notch targeting is also accompanied by reduced phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), suggesting that this protein is another target of Notch signaling in CLL cells.Overall, we show that Notch signaling sustains CLL cell survival by promoting Mcl-1 expression and eIF4E activity, and given the oncogenic role of these factors, we underscore the therapeutic potential of Notch inhibition in CLL

Influence of Androgen Receptor Gene CAG and GGC Polymorphisms on Male Sexual Function: A Cross-Sectional Study

Background. No study has assessed the possible involvement of GGC androgen receptor (AR) polymorphism in sexual function. Our aim is to evaluate the association between CAG and GGC AR polymorphisms in this function. Methods. We retrospectively examined eighty-five outpatients. Clinical, biochemical, and genetic parameters were considered. Sexual assessment was performed using the International Index of Erectile Function (IIEF) which evaluates erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS). Results. In the whole sample, CAG repeats were inversely correlated with EF, OF, and total IIEF-15 score, whereas GGC tracts did not show any significant correlation with sexual function. CAG relationship with IIEF items retained significance only in the eugonadal but not in the hypogonadal cohort. On the other hand, GGC tracts were not found to be significantly correlated with IIEF variables in either eugonadal or hypogonadal subjects. In eugonadal subjects, logistic regression pointed out that a higher number of CAG triplets were associated with lower values of EF, OF, SD, OS, and total IIEF independently from other confounders. Conclusions. GGC polymorphism seems not to exert any influence on sexual function, whereas CAG polymorphism appears to affect sexual parameters only in eugonadal subjects

Order, complexity, measure. The project between architecture and nature

The paper aims to show how modern technologies, including those coming from established habits – today with great possibilities – have shifted towards new building horizons with an ‘ecological conscience’, avoiding uncritically referring to nature as a salvific model, to be imitated and evoked, perhaps with formal and superficial operations. The paper contains some varied project experiences. Even though the projects start from different premises, they develop experimental solutions identifying nature as a principle to elaborate by updating its rules. Among these, we find both a prototype of urban micro-design that incorporates vegetal processes and rules its aesthetic and functional benefits, where nature is integrated into the building technique, and projects with an indigenous origin important for the implementation of the symbiosis between nature and architecture in the built environment

Acid microenvironment promotes cell survival of human bone sarcoma through the activation of cIAP proteins and NF-κB pathway

Extracellular acidification is a very common cause of stress in tumor microenvironment and of Darwinian pressure. In acid areas of the tumor, most cancer cells are-albeit slowly proliferating-more resistant to cell death than those in well-perfused regions. Tumor acidosis can directly regulate the expression of pro-survival proteins since a low extracellular pH activates the caspase-dependent cell death machinery. This mechanism has never been explored in bone sarcomas. We cultured osteosarcoma and Ewing sarcoma cells under low pH (pH 6.5), and we performed deep-sequencing and protein analysis. Both in in vitro and in vivo models, acidification activity enhanced tumor cells survival. However, we did not observe any change in ERK1 phosphorylation. On the contrary, both at the mRNA and protein level, we found a significant induction of TRAF adaptor proteins and of cIAP proteins (BIRC2 and/or BIRC3). As a consequence, the downstream nuclear transcription factor kappa B (NF-κB) survival pathway was increased. Furthermore, the treatment with the cIAP inhibitor LCL161 reverted the protection from apoptosis under low pH. In vitro results were confirmed both in Ewing sarcoma xenograft and in osteosarcoma patients, since the analysis of tumor tissues demonstrated that the levels of expression of TRAF1 or NF-κB1 significantly correlate with the level of expression of the vacuolar ATPase (V-ATPase), the most important proton pump in eukaryotes. Moreover, in the tissue sections of xenograft model, the nuclear translocation of RelB, a key subunit of the NF-κB transcriptional complex, localized in the tumor region that also corresponded to the acid microenvironment associated with the highest levels of expression of LAMP2 and V-ATPase, in the internal area of the tumor, as revealed by immunohistochemistry. Our data confirm that tumor acid microenvironment activates a stress-regulated switch to promote cell survival of bone sarcoma, and support the hypothesis that this mechanism is mediated by the recruitment of TRAF/cIAP complexes. Altogether, these results suggest that TRAF/cIAP can be considered as a target for anti-cancer therapies

Mesenchymal cells recruit and regulate T regulatory cells

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