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The idea of “hybrid joints” arises from the need of joining together materials, producing a tough, stiff and lightweight joint. The core concept is: use two different joining techniques, with the aim to increase the strength and gather the advantages of each technique, reducing the drawbacks. This chapter is devoted to clinch–adhesive (also called clinchbonded) joints, which is of particular interest for the chassis manufacturing in vehicles (automotive, trucks, buses, railways) but also of the nautical and ropeways applications. First, an overview of clinching, adhesive bonding and clinch–adhesive joint characteristics is given. The experimental details and the design of experiments plan are then described and the result are shown and discussed comparing the performances in terms of stiffness, strength and energy absorption to failure of simple and hybrid joints. Since one of the most important needs of the industry is the possibility to simulate mechanical behavior of the joint up to failure, damage models have been applied to the finite element analysis of the simple and hybrid joints and the results are shown in the last paragraph.

In general hybrid bonding allows to match together the properties of two different joining techniques, with the aim to obtain a joint with a better set of properties (that could involve strength, energy absorption at failure, cost, etc.) with respect to the simple joints. In the literature, several works dealing with the evaluation of the strength for this kind of joints and a global enhancement of the properties, in terms of static strength, fatigue strength and energy absorption are found. The first hybrid technique “discovered” was the weld bonding and therefore in the literature it is the most deeply analyzed. In terms of mechanical performance, weld-bonding is the hybrid joining technique where better result are obtained with respect to other hybrid joining techniques such as rivet bonding, clinch bonding, etc., but at the same time it is the most troublesome in terms of joint manufacturing (influence of the presence of the adhesive on the welding performance, weld compliant adhesive requirements, etc.). On the opposite, the hybrid techniques which combine adhesive with mechanical fastening (like rivet, clinching, self piercing riveting) give in general a lower enhancement of performance if compared with weld bonded joint, but certainly they are characterized by an easier and trouble less manufacturing. In this chapter, a brief introduction to the rivet bonding technology is given, dealing with why the hybrid joints are useful and which kind of industrial requirements this kind of joints are able to satisfy. Later on, the adhesive requirements are discussed with the aim to find the best adhesive for different purposes. One of the most important benefits of the rivet bonded joints is the ease of manufacture, therefore the way to produce rivet bonded joints is discussed, and a literature example is shown with the aim to emphasize the different manufacture procedure of rivet bonded joints when compared with traditional weld bonding techniques. In this case, a noticeable benefit in terms of manufacture cost is also shown with respect to traditional joining techniques. An example of the evaluation of the strength of rivet bonded joints (pop rivet and self piercing rivet) in comparison with the performances of simple riveted and simple bonded joint, is then given. It is shown how the performance of hybrid joints depend mostly on the strength of the adhesive bond, and that the rivet becomes relevant only when the adhesive performance decreases (i.e. when the service temperature is higher than the adhesive glass transition temperature for example) or in general when the adhesive fails. Finally, the failure mode is discussed for both pop rivet bonded and self piercing rivet bonded joints. The failure of a pop rivet bonded joint is simulated using appropriate damage models for the rivet and for the adhesive. In particular the parameters of the damage models are tuned by comparison with experiments performed on simple joints and they seem to be adequate for the simulation of the failure behaviour of rivet bonded joints.

Il lavoro prende spunto dai risultati di un’analisi sperimentale del comportamento a fatica di giunzioni incollate di materiali compositi laminati di elevato spessore formati da strati di unidirezionale e di tessuto di fibra di carbonio. I giunti sono stati realizzati in modo tale da saggiare l’influenza della lunghezza di sovrapposizione (da 25,4 mm a 110,8 mm), della forma del giunto (con e senza rastremazione), e della composizione degli aderendi (sostituzione di uno degli aderendi in composito con uno in acciaio). Mediante analisi 2D elastiche con il metodo degli elementi finiti sono state ricavate le distribuzioni degli sforzi all’interno dello strato di adesivo, al fine di individuare un parametro utile alla descrizione del comportamento a fatica in termini di sforzi locali - numero di cicli a rottura. Il ruolo della fase di propagazione viene discusso alla luce di osservazioni dell’avanzamento della frattura, condotta su alcuni dei giunti testati.

In view of the ability of neurotensin (NT) to increase glutamate release, the role of NT receptor mechanisms in oxygen-glucose deprivation (OGD)-induced neuronal degeneration in cortical cultures has been evaluated by measuring lactate dehydrogenase (LDH) levels, mitochondrial dehydrogenase activity with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide levels, and microtubule-associated protein 2 (MAP2) immunoreactivity. Apoptotic nerve cell death was analyzed measuring chromatin condensation with Hoechst 33258, annexin V staining, and caspase-3 activity. Furthermore, the involvement of glutamate excitotoxicity in the neurodegeneration-enhancing actions of NT was analyzed by measurement of extracellular glutamate levels. NT enhanced the OGD-induced increase of LDH, endogenous extracellular glutamate levels, and apoptotic nerve cell death. In addition, the peptide enhanced the OGD-induced loss of mitochondrial functionality and increase of MAP2 aggregations. These effects were blocked by the neurotensin receptor 1 (NTR1) antagonist SR48692. Unexpectedly, the antagonist at 100 nM counteracted not only the NT effects but also some OGD-induced biochemical and morphological alterations. These results suggest that NTR1 receptors may participate in neurodegenerative events induced by OGD in cortical cultures, used as an in vitro model of cortical ischemia. The NTR1 receptor antagonists could provide a new tool to explore the clinical possibilities and thus to move from chemical compound to effective drug.

The MItf-Tfe family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors encodes four family members: MItf, Tfe3, TfeB and TfeC. In vitro, each protein of the family binds DNA in a homo- or heterodimeric form with other family members. Tfe3 is involved in chromosomal translocations recurrent in different tumors and it has been demonstrated, by in vivo studies, that it plays, redundantly with MItf, an important role in the process of osteoclast formation, in particular during the transition from mono-nucleated to multi-nucleated osteoclasts. Since mono-nucleated osteoclasts derive from macrophages we investigated whether Tfe3 might play a role upstream during hematopoietic differentiation. Here we show that Tfe3 is able to induce mono-macrophagic differentiation of U937 cells, in association with a decrease of cell proliferation and an increase of apoptosis. We also show that Tfe3 does not act physiologically during commitment of CD34+ hematopoietic stem cells (HSCs), since it is not able to direct HSCs toward a specific lineage as observed by clonogenic assay, but is a strong actor of terminal differentiation since it allows human primary myeloblasts' maturation toward the macrophage lineage.

The purpose of this work is to simulate the evolution of ductile damage and failure involved by plastic strain reversals using damage models based on either continuum damage mechanics (CDM) or porosity evolution. A low alloy steel for pressure vessels (20MnMoNi55) was chosen as reference material. The work includes both experimental and simulation phases. The experimental campaign involves different kinds of specimens and testing conditions. First, monotonic tensile tests have been performed in order to evaluate tensile and ductile damage behaviour. Then, the cyclic yielding behaviour has been characterized performing cyclic plasticity tests on cylindrical bars. Finally, cyclic loading tests in the plastic regime have been made on different round notched bars (RNBs) to study the evolution of plastic deformation and damage under multiaxial stress conditions. The predictions of the different models were compared in terms of both, the specimens macroscopic response and local damage. Special emphasis was laid on predictions of the number of cycles prior to final failure and the crack initiation loci.

Galanin is a neuropeptide involved in a variety of biological functions, including having a strong anticonvulsant activity. To assess a possible role of galanin in modulation of glutamatergic synapses and excitotoxicity, we studied effects of a galanin receptor 2(3) agonist (AR-M1896) on several molecular events induced by glutamate administration in primary neural hippocampal cells. Exposure of cells, after 5 days in vitro, to glutamate 0.5 mM for 10 min caused morphological alterations, including disaggregation of beta-tubulin and MAP-2 cytoskeletal protein assembly, loss of neurites and cell shrinkage. When present in culture medium together with glutamate, 1 and 10 nM of AR-M1896 reduced these alterations. Moreover, AR-M1896 counteracted glutamate-induced c-fos mRNA and c-Fos protein up-regulation after 30-150 min, and 24 h, respectively. Massive nuclear alterations (Hoechst 33258 staining), observed 24 h after glutamate exposure, were also antagonized by AR-M1896 (0.1-100 nM) in a dose-dependent manner. These findings indicate that galanin, probably mainly through its type 2 receptor, interferes with events associated with glutamate toxicity.

Recent development in stem cell biology has indicated a new possible approach for the treatment of neurological diseases. However, in spite of tremendous hope generated, we are still on the way to understand if the use of stem cells to repair mature brain and spinal cord is a reliable possibility. In particular, we know very little on the in situ regulation of adult neural stem, and this also negatively impact on cell transplant possibilities. In this chapter we will discuss issues concerning the role and function of stem cells in neurological diseases, with regard to the impact of features of degenerating neurons and glial cells on in situ stem cells. Stem cell location and biology in the adult brain, brain host reaction to transplantation, neural stem cell reaction to experimental injuries and possibilities for exogenous regulation are the main topics discussed.

Damage modelling in ductile metal has received a lot of attention in the last thirty years. Since 1969, many models have been proposed in the literature even though, in most of the cases, the experimental aspects related to the damage parameter evaluation have often been neglected. In this work the procedure to evaluate the damage parameters, for the continuum damage mechanics based model proposed by Bonora, is presented. Here, the ductile damage is experimentally measured in terms of progressive elastic modulus reduction as a function of strain measured in an hourglass-shaped specimen loaded in tension. The proposed technique, which is based on performing multiple, partial unloading, is reliable and relatively simple to implement. Additional tensile testing, performed with a round notch tensile bar, provides critical data that can be used to identify unequivocally the full damage parameter set and to assure their geometry transferability. The procedure presented here has been applied to identify the damage parameters for 20MnMoNi55 steel.

Degenerative diseases represent a severe problem because of the very limited repair capability of the nervous system. To test the potential of using stem cells in the adult central nervous system as "brain-marrow" for repair purposes, several issues need to be clarified. We are exploring the possibility of influencing, in vivo, proliferation, migration, and phenotype lineage of stem cells in the brain of adult animals with selective neural lesions by exogenous administration (alone or in combination) of hormones, cytokines, and neurotrophins. Lesion of the cholinergic system in the basal forebrain was induced in rats by the immunotoxin 192IgG-saporin. Alzet osmotic minipumps for chronic release (over a period of 14 days) of mitogens [epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF)] were implanted in animals with behavioral and biochemical cholinergic defect and connected to an intracerebroventricular catheter. After 14 days of delivery, these pumps were replaced by others delivering nerve growth factor (NGF) for an additional 14 days. At the same time, retinoic acid was added to the rats' food pellets for one month. Whereas the lesion decreased proliferative activity, EGF and bFGF both increased the number of proliferating cells in the subventricular zone in lesioned and nonlesioned animals. These results are indicated by the widespread distribution of BrdUrd-positive nuclei in the forebrain, including in the cholinergic area. Performance in the water maze test was improved in these animals and choline acetyltransferase activity in the hippocampus was increased. These results suggest that pharmacological control of endogenous neural stem cells can provide an additional opportunity for brain repair. These studies also offer useful information for improving integration of transplanted cells into the mature brain.

Damage mechanics has shown a great potential in predicting ductile material failure and, therefore, can be used to develop reliable tools for the design of components undergoing plastic deformation. In spite of the importance of cycling loading in components design, there are few examples of application of damage mechanics to fully reversed cycling. In this paper, the damage model proposed by Bonora [Eng. Fract. Mech. 58 (1997) 11] has been reformulated in order to account for compressive loading by introducing a new internal variable associated to damage. The model has been implemented into commercial finite element codes (MSC/MARC, ABAQUS). It was used to predict single element performance under cycling loading and damage accumulation in a round notched tensile bar. Some preliminary results are also discussed.

Renal oncocytoma is an epithelial tumour of the kidney, originally considered benign neoplasm, but now it is thought have a limited but real malignant or metastatic potential. Usually monolateral, in 6% of cases it is bilateral in a synchronous or metachronous way. A case of bilateral renal oncocytoma in a 56-year-old woman, observed by chance during a follow-up carried out after breast cancer is described. The etiopathogenic and clinical-therapeutic aspects of this neoplasm are examined, and the conclusion is drawn that the most correct therapeutic approach must aim at both the protection of kidney function and complete removal of the tumour.