532 research outputs found
Learning to Chill: The Role of Design Schools and Professional Training to Improve Urban Climate and Urban Metabolism
The increased frequency of heat-related mortality and morbidity in urban environments indicates the importance of urban climate studies. As most of the world’s population lives in cities, the education of designers, planners and policy makers is crucial to promote urban sustainability This paper, firstly, focuses on the different factors causing the urban heat islands in large cities. Secondly, it considers how these factors are reflected in higher education programmes. Examples are shown from courses in UK higher education, explaining the common software tools used for simulating urban spaces, and student field measurements are drawn on to illustrate how urban climate studies are included in higher education curricula. Urban metabolism is used to conceptualise the main approach to systemic resource-use assessments and as a holistic framework to investigate the main drivers of the urban heat island phenomenon. To sum up, this paper reflects on the importance of training climatically-aware graduates from design schools
Total Face Approach (TFA): a novel 3D approach to describe the main cephalometric craniomaxillofacial parameters
The aim of this study is to propose a 3D skeletal classification and relative normal values of reference. Method: from a pool of 271 cone-beam computerized tomography images 108 chinsummit examinations of the skull were selected and divided into 3 traditional skeletal classes. The same Cone-beam Computerized Tomography (CBCT) images were then assessed using the cephalometric multiplanar analysis following the total face approach protocol. Results: the results of this study indicate standard 3D cephalometric norms for the vertical and sagittal evaluation of the skull. Conclusions: data obtained from our measurements allowed the creation of intervals supplying nosological classification that could be used in orthodontics, orthognatic surgery and implant surgery in fully edentulous patients
Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation: Systematic Review and Individual Patient Data Meta-Analysis
Background: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle. Results: The investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08–1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04–1.76, I2 21%). Conclusions: Among patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO
Comment on PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL human leukemia
LB100 does not sensitize CML stem cells to tyrosine kinase inhibitor–induced apoptosis
SI113, a Specific Inhibitor of the Sgk1 Kinase Activity that Counteracts Cancer Cell Proliferation
Background/Aims: Published observations on serum and glucocorticoid regulated kinase 1 (Sgk1) knockout murine models and Sgk1-specific RNA silencing in the RKO human colon carcinoma cell line point to this kinase as a central player in colon carcinogenesis and in resistance to taxanes. Methods: By in vitro kinase activity inhibition assays, cell cycle and viability analysis in human cancer model systems, we describe the biologic effects of a recently identified kinase inhibitor, SI113, characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold, that shows specificity for Sgk1. Results: SI113 was able to inhibit in vitro cell growth in cancer cells derived from tumors with different origins. In RKO cells, this kinase inhibitor blocked insulin-dependent phosphorylation of the Sgk1 substrate Mdm2, the main regulator of p53 protein stability, and induced necrosis and apoptosis when used as a single agent. Finally, SI113 potentiated the effects of paclitaxel on cell viability. Conclusion: Since SI113 appears to be effective in inducing cell death in RKO cells, potentiating paclitaxel sensitivity, we believe that this new molecule could be efficiently employed, alone or in combination with paclitaxel, in colon cancer chemotherapy
ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia
The deregulated kinase activity of p210-BCR/ABL oncoproteins, hallmark of chronic myelogenous leukaemia (CML), induces and sustains the leukaemic phenotype, and contributes to disease progression. Imatinib mesylate, a BCR/ABL kinase inhibitor, is effective in most of chronic phase CML patients. However, a significant percentage of CML patients develop resistance to imatinib and/or still progresses to blast crisis, a disease stage that is often refractory to imatinib therapy. Furthermore, there is compelling evidence indicating that the CML leukaemia stem cell is also resistant to imatinib. Thus, there is still a need for new drugs that, if combined with imatinib, will decrease the rate of relapse, fully overcome imatinib resistance and prevent blastic transformation of CML. We recently reported that the activity of the tumour suppressor protein phosphatase 2A (PP2A) is markedly inhibited in blast crisis CML patient cells and that molecular or pharmacologic re-activation of PP2A phosphatase led to growth suppression, enhanced apoptosis, impaired clonogenic potential and decreased in vivo leukaemogenesis of imatinib-sensitive and -resistant (T315I included) CML-BC patient cells and/or BCR/ABL+ myeloid progenitor cell lines. Thus, the combination of PP2A phosphatase-activating and BCR/ABL kinase-inhibiting drugs may represent a powerful therapeutic strategy for blast crisis CML patients
The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein
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RFX-1, a putative alpha Adducin interacting protein in a human kidney library
Adducin regulates tubular absorption of sodium by modulating the expression levels of the sodium-potassium-ATPase in renal tubular cells. Adducin is a candidate gene in the pathogenesis of hypertension. Yeast two hybrid screen showed a specific interaction between human alpha Adducin and the regulatory factor for X box (RFX-1), a nuclear protein that down regulates the expression of several proteins in non neuronal cells. The interaction was confirmed in cells through co-immunoprecipitation and colocalization experiments. The binding of alpha Adducin to RFX-I and their nuclear co-localization suggests that Adducin can have a role in modulating the transcriptional regulating activity of RFX-I
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