The building information modeling for the retrofitting of existing buildings. A case study in the University of Cagliari.

Italy's very consistent buildings stock has become the major field for real estate investments and for the related projects and actions. The urge of working on built environment is however facing some crucial issues. The first is the lack of documentation on the construction history and on the real constructive layout of existing buildings (in terms of components, installations, plants, etc.). The second is the poor activity in surveying their current status, with reference to use (energy behaviour, real consumptions, etc.) and maintenance (conservation status, previous maintenance works, compliance with current regulations, etc.). These obstacles cause a deep inefficiency in the planning, programming and controlling of requalification and/or refunctionalisation works. Starting from these assumptions, this paper shows the findings of a research shared by the Politecnico of Milan and the Department of Civil and Environmental Engineering and Architecture of the University of Cagliari. It is aimed at testing the use of building information modeling (BIM) to structure the necessary knowledge to evaluate intervention scenarios. The research is focused on the Mandolesi Pavilion of the University of Cagliari, designed by Enrico Mandolesi. It is a highly stimulating architectural object because it incorporates values that require a conservative approach, but at the same time, like most contemporary buildings, it was designed and built for innovation and not for “long duration”. The work has actually led to the realization of a BIM model of the case study. It represents the first prefiguration of an approach that develops from construction history and continues with advanced diagnostics on the statical and energy performances of the building. The model formalizes knowledge and information on a significant building, aimed at its management. It allows also the setting of intervention scenarios that can be evaluated with real-time simulations of cost, time and ROI

Association of junctional adhesion molecule with calcium/calmodulin-dependent serine protein kinase (CASK/LIN-2) in human epithelial caco-2 cells.

We report here that junctional adhesion molecule (JAM) interacts with calcium/calmodulin-dependent serine protein kinase (CASK), a protein related to membrane-associated guanylate kinases. In Caco-2 cells, JAM and CASK were coprecipitated and found to colocalize at intercellular contacts along the lateral surface of the plasma membrane. Association of JAM with CASK requires the PSD95/dlg/ZO-1 (PDZ) domain of CASK and the putative PDZ-binding motif Phe-Leu-Val(COOH) in the cytoplasmic tail of JAM. Temporal dissociation in the junctional localization of the two proteins suggests that the association with CASK is not required for recruiting JAM to intercellular junctions. Compared with mature intercellular contacts, junction assembly was characterized by both enhanced solubility of CASK in Triton X-100 and reduced amounts of Triton-insoluble JAM-CASK complexes. We propose that JAM association with CASK is modulated during junction assembly, when CASK is partially released from its cytoskeletal associations

Characterization of fast-twitch and slow-twitch skeletal muscles of calsequestrin 2 (CASQ2)-knock out mice: unexpected adaptive changes of fast-twitch muscles only

This study investigates the functional role of calsequestrin 2 (CASQ2) in both fast-twitch and slow-twitch skeletal muscles by using CASQ2 12/ 12 mice; CASQ2 is expressed throughout life in slow-twitch muscles, but only in the developmental and neonatal stages in fast-twitch muscles. CASQ2 12/ 12 causes increase in calsequestrin 1 (CASQ1) expression, but without functional changes in both muscle types. CASQ2 12/ 12 mice have ultrastructural changes in fast-twitch muscles only, i.e., formation of pentads and stacks in the sarcoplasmic reticulum

Junctional Adhesion Molecule, a Novel Member of the Immunoglobulin Superfamily That Distributes at Intercellular Junctions and Modulates Monocyte Transmigration

Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane–membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration

Dissection of PIM serine/threonine kinases in FLT3-ITD–induced leukemogenesis reveals PIM1 as regulator of CXCL12–CXCR4-mediated homing and migration

FLT3-ITD–mediated leukemogenesis is associated with increased expression of oncogenic PIM serine/threonine kinases. To dissect their role in FLT3-ITD–mediated transformation, we performed bone marrow reconstitution assays. Unexpectedly, FLT3-ITD cells deficient for PIM1 failed to reconstitute lethally irradiated recipients, whereas lack of PIM2 induction did not interfere with FLT3-ITD–induced disease. PIM1-deficient bone marrow showed defects in homing and migration and displayed decreased surface CXCR4 expression and impaired CXCL12–CXCR4 signaling. Through small interfering RNA–mediated knockdown, chemical inhibition, expression of a dominant-negative mutant, and/or reexpression in knockout cells, we found PIM1 activity to be essential for proper CXCR4 surface expression and migration of cells toward a CXCL12 gradient. Purified PIM1 led to the phosphorylation of serine 339 in the CXCR4 intracellular domain in vitro, a site known to be essential for normal receptor recycling. In primary leukemic blasts, high levels of surface CXCR4 were associated with increased PIM1 expression, and this could be significantly reduced by a small molecule PIM inhibitor in some patients. Our data suggest that PIM1 activity is important for homing and migration of hematopoietic cells through modification of CXCR4. Because CXCR4 also regulates homing and maintenance of cancer stem cells, PIM1 inhibitors may exert their antitumor effects in part by interfering with interactions with the microenvironment

Epitope-Tagged P0Glycoprotein Causes Charcot-Marie-Tooth–Like Neuropathy in Transgenic Mice

In peripheral nerve myelin, the intraperiod line results from compaction of the extracellular space due to homophilic adhesion between extracellular domains (ECD) of the protein zero (P0) glycoprotein. Point mutations in this region of P0 cause human hereditary demyelinating neuropathies such as Charcot-Marie-Tooth. We describe transgenic mice expressing a full-length P0 modified in the ECD with a myc epitope tag. The presence of the myc sequence caused a dysmyelinating peripheral neuropathy similar to two distinct subtypes of Charcot-Marie-Tooth, with hypomyelination, altered intraperiod lines, and tomacula (thickened myelin). The tagged protein was incorporated into myelin and was associated with the morphological abnormalities. In vivo and in vitro experiments showed that P0myc retained partial adhesive function, and suggested that the transgene inhibits P0-mediated adhesion in a dominant-negative fashion. These mice suggest new mechanisms underlying both the pathogenesis of P0 ECD mutants and the normal interactions of P0 in the myelin sheath