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Tutela e Valorizzazione dei siti UNESCO in Iran: Una proposta metodologica per il piano di gestione di Naqshe Jahan
No full textThe policy of preservation of cities and monuments in Iran is going through a review process. The traditional formulas adopted till now are inadequate to ensure the integrity of the tangible and intangible values of the historical and artistic heritage present in Iran. UNESCO has drawn the attention to some iranian sites that are threatened with degradation and that, despite the recent recommendations contained in the Memorandum of Wien (2004) and in the Budapest’s Declaration (2002), some iranians sites are still lacking of a Management plan.
Analyzing the Management plans prepared till now in Iran, I noted that there is not a reference model and that the documents prepared are simple descriptive and iconographic texts that do not provide an action plan and a list of intervention aimed to protect and enhancing the sites.
Amoung the different UNESCO sites in Iran, I decided to analyze the most representative of the persians city: the 89600 square meters Naqshe Jahan complex, the first iranian site to be inscribed in the world heritage list in 1979 and the one able to show the historical evolution that Iran has experienced. Naqshe Jahan complex is situated in the ancient city of Isfahan, capital of the Safavid dynasty during the XVI century. The city is the most complete example of Persian city in which it is still possible to distinguish monuments and buildings dating back from different centuries, from the X, XIV and XVI century. The social and economical hart of the city is represented by the big square of Naqshe Jahan, built by Shah Abbas during in the 1590 and still considered the symbol of the whole city
TRANSCRIPTIONAL LANDSCAPE OF NEURONAL and CANCER STEM CELLS
No full textTumor mass is composed by heterogeneous cell population including a subset of “cancer stem cells” (CSC).
Oncogenic signals foster CSC by transforming tissue stem cells or by reprogramming progenitor/differentiated
cells towards stemness. Thus, CSC share features with cancer and stem cells (e.g. self-renewal, hierarchical
developmental program leading to differentiated cells, epithelial/mesenchimal transition) and these latter are
maintained by the constitutive activation of stemness-promoting signals. CSC could trigger tumor formation,
drive to resistance to conventional therapeutics and underlie patients’ relapse. Indeed, stem cell signatures
have been associated with poor prognosis in various.
This background makes the identification of CSC molecular features mandatory to highlight the survival inner
working and to design novel CSC specific therapeutic strategies.
Medulloblastoma (MB) is the most common childhood malignant brain tumor and a leading cause of cancerrelated
morbidity and mortality. Current multimodal therapies are effective in about 50% of patients but often
cause long-term side effects, i.e. developmental, neurological, neuroendocrine and psychosocial deficits
(Northcott PA Nature Rev cancer 2012). For many years, MB treated as a single tumor entity despite the
divergent tumor histology, patients’ outcome and drug sensitivity, and also by the diversity of the stem cell of
origin. Very recently the scenario of human MB has dramatically changed since its heterogeneous biology has
been addressed by high-throughput gene expression analysis (oligonucleotide microarrays) or by the powerful
genomic next-generation sequencing. These led to the identification of four tumor subgroups (WNT, SHH,
Group 3 and Group 4) uncovering the existence of a highly diverse mutational spectra and gene expression.
However a quantitative approach has not yet been applied to the transcriptional landscape of Medulloblastoma
stem cells (MbSC) through RNA Next Generation Sequencing (RNA-Seq) technology. This is a relevant issue,
since RNA-Seq is able to interrogate the genome wide global transcriptome including new transcripts,
alternative spliced isoforms and non-coding RNAs.
Lower rhombic lip progenitors of the dorsal brainstem are considered the trigger cells in WNT tumors; in SHH
subgroup initiation cells are Prominin1+ CD15+ stem cells from the subventricular zone requiring the
commitment to Math1+ granule cell progenitors [GCP] of the external granule cell layer [EGL]; while Math1+ or
Math1- EGL-GCP or Prominin1+/lineage-negative stem cells sustain the MYC driven Group 3.
MbSC derived from SHH tumors and postnatal normal cerebellar stem cells (NcSC) have been reported to
share several features. A key signal for both of them is Hedgehog. Furthermore, both NcSC and MbSC display
up-regulation of stemness genes (e.g Sox2, Nestin, Nanog, Prom1). Finally, constitutive activation of the Shh
pathway by conditional deletion of Ptch1 inhibitory receptor in NcSC, promote medulloblastoma in vivo,
producing a mouse model of the human SHH tumor. Acquisition of stemness features may therefore represent
the first step of oncogenic conversion. Cooperation with additional oncogenic signals is however needed to
enhance MbSC tumorigenicity.
In order to understand the MbSCs transcriptional programs, we analyze by RNA-Seq, MbSC derived from
Ptch1+/- tumors (Ptch1+/- MbSC). This choice, of a genetically determined model of MB, has allowed us to
work with Ptch1+/- MbSC together with appropriate NcSC counterpart, and to analyze biological replicates
doing statistical analysis.
We identify a number of transcripts, annotated ones, novel isoforms, and long non-coding RNAs,
characterizing MbSC and/or NcSC. Some of these genes control stemness or are cancer related and
conserved in human medulloblastomas. Interestingly a subset of them, belonging to cell stress response, are
of prognostic relevance being significantly related to clinical outcome. Correlation of genes expression
characterizing MbSC with survival information from our human medulloblastomas database further
demonstrates the significance of these findings. Our data suggest that the modulation of normal and cancer
stem cell functions observed in vitro is effective in dissecting the transcriptional programs underlying the in
vivo behavior of human medulloblastomas
A robust architecture for Interval Valid queries in dynamic distributed systems, formal proofs, experimental evaluation and cloud application
No full textThis thesis studies the problem of answering system-wide queries, satisfying the interval validity semantics, in a distributed system prone to continuous arrival and departure of participants. The interval validity semantic states that the query answer must be calculated considering contributions of at least all processes that remain in the distributed system for the whole query duration. It is impossible to satisfy this semantics in systems experiencing unbounded churn due to the lack of connectivity and path stability between processes. This thesis presents a novel architecture, named Virtual Tree, for building and maintaining a structured overlay network with guaranteed connectivity and path stability in settings characterized by bounded churn rate. The architecture includes a simple query answering algorithm that provides interval valid answers. The overlay network generated by the Virtual Tree architecture is a tree-shaped topology with virtual nodes constituted by clusters of processes and virtual links constituted by multiple communication links connecting processes located in adjacent virtual nodes. A bound has been formally proved on the churn rate for interval valid queries and it has been carried out an extensive experimental evaluation that shows the degree of robustness of the overlay network generated by the virtual tree architecture under different churn rates. The thesis also provide an application scenario of the proposed architecture in the field of the volunteer computing. The application scenario shows that Virtual Tree represents a fundamental building block for the architecture of a volunteer computing platform and its capability of offering valid queries enhances the performance of the system providing a better accuracy in the task-scheduling procedure
Genetic dissection of meiotic cytokinesis in Drosophila melanogaster males
No full textStudies in a variety of organisms indicate that membrane traffic to the cleavage furrow is an essential facet of cytokinesis involving components of the secretory and endocytic/recycling trafficking pathways, as well as the membrane fusion machinery.
My PhD project focused around the characterization of two genes required for cleavage furrow formation and ingression in male meiotic cells namely sauron and Cog7 which encode the Drosophila orthologues of two known players of membrane trafficking pathways.
Sauron is the Drosophila orthologue of Golgi phosphoprotein 3 (GOLPH3) which has recently been recognized as a potent oncogene amplified in many human cancers. Studies in both yeast and mammalian cells have implicated this protein in several vesicle trafficking events.
I show that Sau/dGOLPH3 is required during the early steps of spermatocyte cytokinesis playing an essential role in both contractile ring assembly and vesicle trafficking during furrow ingression. Consistently my work suggests that Sau/dGOLPH3 might interact with components of both the contractile apparatus and the membrane trafficking machinery in male germ cells.
The conserved oligomeric Golgi (COG) Complex plays essential roles for Golgi function, vesicle trafficking and glycosylation. Mutations in the genes encoding human COG1, COG4-COG8 have been associated with congenital disorders of glycosylation (CDG). Deletions of human COG7 are associated with a rare multisystemic congenital disorder of glycosylation causing mortality within the first year of life. I show that, similar to Drosophila Cog5, Cog7 controls furrow ingression during cytokinesis. Importantly, Cog7 is required to localize the small GTPase Rab11 and the phosphatidylinositol transfer protein (PITP) Giotto (Gio) to the cleavage site of spermatocytes. In addition Gio coimmunoprecipitates with both Cog7 and Rab11 in Drosophila testes suggesting that these proteins may interact in male germ cells
GROWTH AND APOPTOSIS PATHWAYS IN HUMAN CUTANEOUS MELANOMA: IN VITRO AND IN VIVO STUDIES BY USING BIOLOGICAL AND PROTEOMICS APPROACHES
No full textPurpose. Melanoma is the most aggressive cutaneous cancer without effective treatment. Diagnosis is achieved very often too late and prognosis is poor. Aim of this work is to identify proteomic pathways potentially involved in melanoma aggressiveness.
Materials and Methods. We analyzed 5 human metastatic melanoma cell lines and human keratinocyte and melanocyte cell lines as a control. Their proliferation and apoptotic behaviors under serum stimulation and starvation were analyzed in order to identify the most aggressive one. Melanoma cell proteome from the most aggressive cell line (A375), compared to the less aggressive one (SK mel 28), was analyzed by means of two complementary approaches: 1) multiplexed assay to measure the levels of 27 cytokines both in cell extracts and in conditioned media; 2) proteomic study through LC-MS/MS analysis of cell extracts. Data obtained were analyzed using bioinformatic analysis.
Results. A375 cells were found to possess the highest growth rate both under serum stimulation and under serum starvation, while SK mel 28 cells under similar conditions were significantly less aggressive, confirmed also by invasion assays. The effect was markedly cell-density dependent, suggesting that cell-cell interaction and/or secretory signals dependent phenomena are important. Proteome analyses indicated that several proteins are differentially expressed and possibly related the aggressiveness. Some of these proteins have been identified as transport and proteasome components. The Bio-Plex analysis of the melanoma cell lines under study indicated that melanoma cells contain significantly (p<0.001) different levels of some inflammatory cytokines and angiogenic growth factors: the most significantly modified factors were IL-6, Il-7, RANTES and VEGF, suggesting a novel interesting viewpoint to explain melanoma cell aggressiveness.
Conclusions. The reported results show that transport, proteasome components and an altered cytokine balance may be responsible for human melanoma aggressiveness
Structural and functional characterization of Nucleophosmin domain associated with Acute Myeoloid Leukemia
No full textNucleophosmin is a shuttleing protein mainly localizated in nucleolus. It is involved in many different cellular processes like ribogenesis, centrosome duplication, apoptotic response. In more then 35% of Acute Myeloyd Leukemic patient with Normal Kariotype, the Nucleophosmin gene is mutated, causing aberrant cytoplasmatic accumulation, imparing DNA binding activity. In this work we describe the structural and functional feuteres of Nucleophosmin DNA binding domain, to better understand its activy both in phisiological and pathologial conditions.AIR
Near-IR Integral Field Spectroscopy Of High-Redshift Quasar Host Galaxies
No full textIn this thesis I exploit near-infrared integral field spectroscopic observations of a
sample of high redshift quasars to investigate the properties of their host galaxies and
their relation with the nuclear activity. The [OIII]5007 prominent emission line, red-
shifted into the near-IR is used to trace the kinematics of the host galaxy of z
∼ 2.5
quasars. One of the most important results is the detection and mapping of prominent
outflows driven by the quasar radiation pressure, which were expected by most mod-
els of galaxy evolution invoking quasar feedback to quench star formation in massive
galaxies. These are among the first maps of quasar-driven outflows at such high red-
shift, around the peak of cosmic star formation, where quasar feedback is supposed to
be more effective.
The inferred outflow rates are very large and can effectively expel most of the gas
in the quasar host galaxies on short timescales. The kinetic energies involved in the
outflows are also extremely high, and consistent with the models expectations.
We also use Hα to trace star formation in the host galaxy. Some quasar host galax-
ies show intensive star formation. However, the major discovery is the detection of
a suppression of star formation in the regions mostly affected by the quasar driven
outflow. This has been regarded as the first direct observational evidence of quasar out-
flows quenching star formation in their host galaxies, as predicted by models of galaxy
evolution invoking quasar negative feedback. Not all quasars display evidence for out-
flows. For some of them the kinematics is dominated by normal galaxy rotation, while
some show disordered dynamics indicative of ongoing or recent merging.
We also observed a sample of obscured quasars at high redshift, selected in the hard
X-rays. For a fraction of them we detect a broad component of the Hα line (redshifted
into the near-IR), tracing the reddened Broad Line Region. We have used the broad
Hα, along with the hard X-ray emission, to determine the black hole mass hosted in
their nuclei. Together with additional data in the literature, and by inferring the stellar
masses from broad band photometry, we could for the first time, infer the MBH
− Mstar
relation for obscured AGNs at high redshift, which represent the bulk of the AGN pop-
ulation. We found that high-z obscured AGNs follow the same MBH
− Mstar relation
as local galaxies. This is in contrast with several previous studies targeting the un-
obscured AGN population at high redshift (which easier to investigate, but much less
abundant) that have been found to deviate significantly from the local relation, by host-
ing over-massive black holes. Our new result suggests either that such previous studies
on obscured AGNs were seriously biased in favour of massive black holes, or that there
is an evolutionary sequence, in terms of BH-galaxy coevolution, between unobscured
and obscured AGNs, but in a sense which is opposite with respect to what expected by
most of the previous models.Marie Cure FP7 fellowship
Chiral Supramolecular Chemistry of Basket Resorc[4]arenes
No full textChiral Basket Resorc[4]arenes are well known chiral solvating agents that can induce enantiodiscrimination towards aminoacids, peptides and nucleosides. We synthesized both enantiomer of some basket resorc[4]arenes capable of forming stable diasteromeric host-guest complexes with some nucleosides like cytidine and cytarabine. The reactivity and the structures of the complexes were investigated in gas-phase (ESI-IRMPD, ESI-FT-ICR) and in solution (DOSY, ROESY). Different "in" and "out" structures were found both in solution and in gas-phase, moreover the results were supported by theoretical calculations
Valutazione dei fenomeni neurodegenerativi cerebrali nella Malattia di Alzheimer attraverso metodiche combinate di Risonanza Magnetica Non Convenzionale
No full textImproved methods for early diagnosis and non-invasive surrogates of disease severity in Alzheimer's disease (AD) are becoming a modern challenge. Magnetic resonance (MR) techniques are being evaluated as possible surrogate measures of disease progression. The purpose of this work was to correlate the results of combined advanced MRtechniques with neuropsychological performance in order to identify a sensible and sensitive imaging approach to neurodegenerative quantification disease progression. We enrolled 19 patientswith Alzheimer's disease (9 males and 10 females, with a mean age of 74±8). Mean MMSE score of AD patients was 20 ±6.
All the AD patients underwent a brain magnetic resonance imaging examinations and a battery of neuropsychological test which included Milan Overoll Dementia Assessment (MODA), Raven's Progressive Matrices, Visual Search, Digit Span, Rey list, prose memory, constructional apraxia, phonological and semantic fluency, and trail making. We measured regional cortical thickness, surfaces and volumes using a set of automated tools (Freesurfer) to reconstruct the brain's cortical surface from T1-weighted three-dimensional volumetric brain magnetic resonance imaging.
Magnetic resonance spectroscopy was carried out in the temporal lobes, parietal lobes and frontal lobes; the evaluated metabolites were N-acetylaspartate (NAA),choline (Cho), creatine (Cr).
We used Spearman coefficient to analyze the correlation among the different factors.
We analyzed the relationship of the regional measure of cortical thickness and volume of vulnerable AD area to severity of symptoms of cognitive impairment. MMSE was directly correlated with the thickness of right brain entorinal cortex, fusiform area, inferior superior and temporal pole (P >0.01). Other significative correlation were observed between left brain vulnerable area and ReyTest and Raven's Progressive Matrices. Sperman’s Rho analisys of MRS ratios NAA/Cr demonstrated an higher significant correlation between the battery of neuropsychological test and right frontal withe matter and left frontal grey matter. Sperman’s Rho analisys of MRS ratios Cho/Cr demonstrated an higher significant correlation between the battery of neuropsychological test and mesial occipital grey matter(Tab.1).We observed a selective correlation between FA measured in corpus callosum (CC) and MMSE, MODA and Rey Test and a preferred correlation between FA evaluated in right fronto-parietal and temporal structures with the major test for cognitive evaluation. Finally with multimodal imaging analysis we observed a combined relationship between FA value of CC, it’s volume and MMSE
Combining non conventional magnetic resonance imaging, including morphometry, spectroscopy, MD and FA evaluation, provide a novel framework for both anatomical, metabolic and ultratructural evaluation of neurodegeneration in AD.NoneNon
“Trattamento delle neoplasie del colon destro.Tecniche a confronto:chirurgia robotica versus laparoscopica. Nostra esperienza”
No full textCONFRONTO TRA TECNICA ROBOTICA E LAPAROSCOPICA NELL'EMICOLECTOMIA DX PER CANCRO SU 74 PAZIENTI TRATTATI DAL LUGLIO DEL 2009 ALL'AGOSTO DEL 2013, VALUTAZIONE DI TEMPI OPERATORI, DEGENZA MEDIA, RIPRESA DELLE FUNZIONI FISIOLOGICHE, ESAME ISTOLOGIC