18 research outputs found
Methodology for Landslide Damage Assessment
No full textAbstractThis article focuses on an original methodology for landslide damage assessment of either masonry or reinforced concrete ordinary buildings at the urban scale. In the first step of the methodology, an analysis of the crack patterns is quickly performed for all the buildings by means of the Load Path Method [1]. The second step consists in the filling in of new survey damage forms and it ends with the creation of a landslide damage geotechnical chart of the region under study. This chart includes geomorphological data together with both the damage grade of the buildings and the direction of the possible settlements
Seismic assessment and rehabilitation of a historical theatre based on a macro-element strategy
No full textThe structural and seismic assessment of the 19th-century Petruzzelli theater in Bari (Italy) is presented. The macro-elements strategy was adopted to dismantle the whole structure in parts. The steel dome was verified through dynamic multi-modal analysis based on finite element model. Each masonry macro-element was firstly verified through a kinematic analysis aiming at excluding local collapse mechanisms. Afterwards, a nonlinear static analysis was carried out in order to evaluate its overall seismic capacity. The effectiveness of linear or nonlinear analyses and of the macro-element strategy compared with other modeling techniques is also discussed. After highlighting the structural deficiencies of the theater, upgrading solutions are proposed with consideration of the safety needs and the architectural preservation requirements based on the historical importance of the buildin
The stepwise dissociation of the Zn(II)-bound Atox1 homodimer and its energetic asymmetry
No full textThe copper chaperone Atox1, which is featured by a peculiar CxxC metal-binding motif, is a protein involved in copper trafficking to the Golgi organelle, allowing the delivery of copper ions to specific target proteins in the secretory pathway. Various experimental studies suggest that this cysteine-containing protein may also be implicated in Zn(II) ion binding, functioning as a regulatory factor. However, despite the relevance of this interaction, the mechanism of zinc ion dissociation from the Atox1 homodimer has not yet been elucidated. We herein devised a simulation workflow based on the combination of parallel bias metadynamics and free energy perturbation theory, to predict the dissociation of the zinc ion from the Atox1 homodimer. The freeenergy simulations successfully predicted the dissociation free energy differences of the process, disclosing a mechanism based on a stepwise dissociation pathway of the zinc ion from the Atox1 homodimer
Cytotoxic pathways activated by multifunctional thiosemicarbazones targeting sigma-2 receptors in breast and lung carcinoma cells
No full textBackground: Multifunctional thiosemicarbazones (TSCs) able to bind sigma receptors and chelate metals are considered as a promising avenue for the treatment of pancreatic cancer due to the encouraging results obtained on in vitro and in vivo models. Here, we assessed the biochemical mechanism of these TSCs also on lung (A549) and breast (MCF7) cancer cells. Methods: The density of sigma-2 receptors in normal (BEAS-2B and MCF10A) and in lung and breast (A549 and MCF7) cancer cells was evaluated by flow cytometry. In these cells, cytotoxicity (MTT assay) and activation of ER- and mitochondria-dependent cell death pathways (by spectrofluorimetric assays to measure Caspases 3/7/9; qRT-PCR detection of GRP78, ATF6, IRE1, PERK; MitoSOX, DCFDA-AM and JC-1 staining), induced by the TSCs FA4, MLP44, PS3 and ACThio1, were evaluated. Results: FA4 and PS3 exerted more potent cytotoxicity than MLP44 and ACThio1 in all cancer cell lines, where the density of sigma-2 receptors was higher than in normal cells. Remarkably, FA4 promoted ER- and mitochondria-dependent cell death pathways in both cell models, whereas the other TSCs had variable, cell-dependent effects on the activation of the two proapoptotic pathways. Conclusions: Our data suggest that FA4 is a promising compound that deserves to be further studied for lung and breast cancer treatment. However, the other multifunctional TSCs also hold promise for the development of therapies towards a personalized medicine approach. Indeed, the presence of the sigma-2 receptor-targeting moiety would lead to a more specific tumor delivery embracing the characteristics of individual tumor types
Diagnosis of slow landslides affecting Tectonised clayey slopes (Southern Apennines)
No full textThe assessment of the slope failure mechanisms, along with the identification of the factors promoting the development of the landslide processes, represents the keystone for an effective design of landslide mitigation. The paper outlines some mitigation strategies for some slow-moving landslides, involving heterogeneous and tectonized soils, located in the outer sector of Southern Apennines. These mitigation designs result from a comprehensive analysis of the failure slope scenarios as resulted from field surveys and investigations, slope monitoring and laboratory testing.
A Geomechanical Approach to Landslide Hazard Assessment: The Multiscalar Method for Landslide Mitigation
No full textAbstractThe landslide hazard assessment, when based on the deterministic diagnosis of the processes, can be pursued only through the interpretation and the geo-hydro-mechanical modelling of the slope equilibrium. In practice, though, landslide hazard assessment is still seldom dealt with slope modelling, in particular when it addresses vast areas, where either heuristic or statistical methods do not entail any geo-hydro-mechanical knowledge of slope features and stability. The Multiscalar Method for Landslide Mitigation (MMLM) is an original methodological approach for intermediate to regional landslide hazard assessment. It is based on the geo-hydro-mechanical knowledge achieved from the application of a stage-wise diagnostic methodology of the landslide mechanism at the slope scale. The paper discusses the main steps of the MMLM aiming at diagnoses of landslide hazard based on hydro-mechanics, for small scale hazard mapping (at the large area)
First-In-Class Thiosemicarbazone Metal Complexes Targeting the Sigma-2 Receptor (S2R) as an Innovative Strategy against Pancreatic Cancer
No full textPancreatic cancer, with its increasing incidence and lowest 5-year survival rate, is predicted to become the second
leading cause of cancer deaths by 2030. Current clinical trials have shown limited improvement, highlighting the need for new therapies. The sigma-2 receptor (S2R), with roles in tumor progression, is a target for novel thiosemicarbazones (TSCs). FA4 has shown potent activity against pancreatic cancer in vivo. We synthesized complexes of FA4 with Cu(II) and Pt(II), and compared their efficacy with complexes of the non-S2R-targeting TSC 1. TSC-Cu exhibited over 50-fold higher in vitro cytotoxicity than TSCs-Pt, which was less active than TSCs. FA4-Cu induced
apoptotic cell death via ER and mitochondrial stress showing more potent activity than FA4. This in vitro effect was replicated in the preclinical PANC-1 model, where FA4-Cu was more potent than FA4, 1, and 1-Cu. These results support further exploration of FA4-Cu as a potential therapy for pancreatic cancer
The perspective value of emotional intelligence in human resource management
No full textMaģistra darba tēmas aktualitāti pamato informācijas un zināšanu laikmeta uzņēmumu jaunā savstarpējā konkurences fāze, kad visefektīvākā un visnozīmīgākā konkurētspējas priekšrocība ir uzņēmuma intelektuālais kapitāls. Intelektuālā kapitāla viens no vissvarīgākajiem komponentiem ir cilvēkresursi, viņu zināšanas, prasmes un kompetences.
Maģistra darbā tiek apskatīta cilvēkresursu evolūcija un emocionālās inteliģences teorētiskie aspekti. Pētījumā tiek analizētas bankas DnB NORD darbinieku emocionālās inteliģences līmeņa savstarpējās sakarības ar dažādiem indivīda darba un dzīves ietekmējošiem faktoriem. Noslēgumā darba autore secina, ka indivīda emocionālā inteliģence veido mūsdiena darbinieka konkurējošo priekšrocību.
Atslēgvārdi: cilvēkresursi, cilvēkresursu vadība, cilvēkkapitāls, emocionālā inteliģence, emocionālās kompetences.Topicality of the Master thesis is based by new competition phase in the new information and knowledge era, where the most effective competing power among companies is their intellectual capital. One of the most influential components of intellectual capital is human resources, their knowledge, capabilities and competences.
Paper explores evolution of human resources and theoretical issues of emotional intelligence, which propose research, revealing emotional intelligence of employees in bank DnB NORD and correlations among emotional intelligence, its components and different factors of life and work. Author of paper concludes that emotional intelligence of individual creates the competitive advantage of the modern employee.
Keywords: emotional competences, emotional intelligence, human capital, human resources, human resource management
Tryptophan regulates Drosophila zinc stores
No full textSignificance Zinc deficiency in the human population, a major public health concern, can also be a consequence of nutritional deficiency in protein uptake. The discovery that tryptophan metabolites 3 hydroxykynurenine and xanthurenic acid are major zinc binding ligands in insect cells establishes the kynurenine pathway as a regulator of systemic zinc homeostasis. Many biological processes influenced by zinc and the kynurenine pathway, including the regulation of innate and acquired immune responses to viral infections, have not been studied in light of the direct molecular links revealed in this study. Abstract Zinc deficiency is commonly attributed to inadequate absorption of the metal. Instead, we show that body zinc stores in Drosophila melanogaster depend on tryptophan consumption. Hence, a dietary amino acid regulates zinc status of the whole insect a finding consistent with the widespread requirement of zinc as a protein cofactor. Specifically, the tryptophan metabolite kynurenine is released from insect fat bodies and induces the formation of zinc storage granules in Malpighian tubules, where 3 hydroxykynurenine and xanthurenic acid act as endogenous zinc chelators. Kynurenine functions as a peripheral zinc regulating hormone and is converted into a 3 hydroxykynurenine zinc chloride complex, precipitating within the storage granules. Thus, zinc and the kynurenine pathway well known modulators of immunity, blood pressure, aging, and neurodegeneration are physiologically connecte
Design, Synthesis, and Biological Evaluation of Novel Heteroaryl, Squaramide, and Indolcarboxamide Derivatives as Formyl Peptide Receptor 2 Agonists to Target Neuroinflammation
No full text: Recent research reveals Formyl Peptide Receptor 2 (FPR2) as a relevant G Protein-Coupled Receptor involved in the resolution phase of inflammation. Therefore, FPR2 agonists are promising agents to tackle neuroinflammatory-based diseases, such as Alzheimer's Disease or Autism Spectrum Disorder. Here, we describe the synthesis and biological evaluation of novel FPR2 agonists designed through the bioisosteric replacement of the phenyl urea function in the potent FPR2 agonist (S)-1-(3-(4-cyanophenyl)-1-(indolin-1-yl)-1-oxopropan-2-yl)-3-(4-fluorophenyl)urea (5), obtaining novel heteroaryl, squaramide, and indolcarboxamide derivatives. The structural modification had a profound effect on FPR2 agonist potency, metabolic stability, aqueous solubility, and cell permeability, resulting in compounds with distinct profiles. Computational studies have shown that the new compounds exhibit the same contacts with key amino acids in the binding site as the starting FPR2 agonist 5. However, subtle differences in the orientation or the presence and position of heteroatoms in the selected scaffolds translate to substantial differences in FPR2 potency. Among the new compounds, (S)-9a, (S)-12a, and (S)-16b demonstrated neuroprotective, anti-inflammatory, and pro-resolving properties in mouse primary microglial cells, stimulated with lipopolysaccharide. Although the replacement of the phenyl urea with different scaffolds did not lead to the identification of a bioisostere, compounds (S)-9a, (S)-12a, and (S)-16b represent a starting point for the development of a new class of FPR2 agonists
