4,993 research outputs found
Constructing a price deflator for R&D: calculating the price of knowledge investments as a residual
Working Pape
Chronic Myelogenus Leukemia: approaches to pharmacological resistance
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by the reciprocal t (9:22) chromosomal translocation. This rearrangement produces the socalled Philadelphia chromosome carrying the chimeric Bcr-Abl oncoprotein, p210, responsible of disease progression [1].
Because of its critical role in pathogenesis, the scientific community had focused on targeting Bcr\u2013Abl for treatment of CML. For many years Imatinib (IM), as selective inhibitor of the Tyr-Kinase activity of the oncoprotein, was used to treat CML patients [2].
From 2000 some data relative to IM resistance were available. There are many mechanisms responsible of IM resistance, more often point mutations that cause the progression to blast crisis and death in few months. To circumvent them, more potent TKIs have been subsequently approved [3]. However, another problem arise: these compounds don\u2019t work on all patients because of the different IMresistant mutants of BCR-ABL[4].
Therefore, there is a continous need for new drugs and combinations that could improve responses and survival rates for CML. Moreover, because of the complexity of signalling pathways and the overexpression of many of them on tumour cells, the simultaneous use of different drugs to target alternative signalling may produce an higher therapeutic success accompanied by less toxicity
A Multi-disciplinary Approach to Interactive Information Retrieval upon Semi-structured Data Sets
The so called logic and probabilistic views on IR can be reconciled by a unifying framework for IIR. I present a proposal for a PhD research according to a multidisciplinary perspective and I discuss some of its consequences for IR as a discipline
Sustainability, stakeholders and business. Editorial
Over the past 20 years, there has been an increasing attention on the drivers of value in organizations. Both the strategic management literature and practice have remarked the importance for managers to be aware of the impact of firm activities, products and services on either the external and internal environment and, more generally, on all firm stakeholders. The emergence of the notions of “sustainable development” and “sustainability” reflects a profound change in global thinking, which forces firms to move beyond trade-offs between business and society
Natural Compounds: Molecular Weapons against Leukemia\u2019s
Nowadays cancer is one of the main reasons of death all over the world and it is estimated that deaths caused by cancer will grow dramatically in the next decades. Even if chemotherapy is the election therapy for solid tumors, as well as leukemias and lymphomas, cancer treatments are in continuous evolution trying to solve the problem of resistance mainly due to low accumulation of the drug in tumor cells (MDR). Natural compounds represent a valid alternative to treat several disease and recently the scientific community focus on these natural compounds and plant metabolites with therapeutic activities and low toxicities compared with synthetic ones.
A combination therapy, that join conventional chemotherapy with natural plant metabolites, is now considered a new promising strategy to overcome MDR and reduce cellular toxicity; in particular, in leukemia due to its very complex origin and development of leukemogenesis.
Here, we want to summarize and update the recent applications of natural compounds in the treatment of leukemia
Ecosystem Services, Green Infrastructure and Spatial Planning
Ecosystem services and green infrastructure do not appear to inform spatial policies and plans. National governments hardly identify their ecological networks or make an effort to integrate them into their spatial policies and plans. Under this perspective, an important scientific and technical issue is to focus on preserving corridors for enabling species mobility and on achieving connectivity between natural protected areas. In this respect, this Special Issue takes a step forward insofar as it aims at proposing a theoretical and methodological discussion on the definition and implementation of ecological networks that, besides guaranteeing wildlife movements, also provide a wide range of ecosystem services. The social and economic profile of this question is also relevant since in the long run, savings in public spending (e.g., due to the reduced need for grey infrastructures aiming at contrasting soil erosion or at managing flood risk), savings in private spending (e.g., on water treatment costs) and the potential creation of green jobs are foreseeable. Moreover, indirect and less easily quantifiable social and health benefits (e.g., due to improved natural pollution abatement) are likely to occur as well
Hypoxia and HIF signaling: One axis with divergent effects
The correct concentration of oxygen in all tissues is a hallmark of cellular wellness, and the negative regulation of oxygen homeostasis is able to affect the cells and tissues of the whole organism. The cellular response to hypoxia is characterized by the activation of multiple genes involved in many biological processes. Among them, hypoxia-inducible factor (HIF) represents the master regulator of the hypoxia response. The active heterodimeric complex HIF α/β, binding to hypoxia-responsive elements (HREs), determines the induction of at least 100 target genes to restore tissue homeostasis. A growing body of evidence demonstrates that hypoxia signaling can act by generating contrasting responses in cells and tissues. Here, this dual and controversial role of hypoxia and the HIF signaling pathway is discussed, with particular reference to the effects induced on the complex activities of the immune system and on mechanisms determining cell and tissue responses after an injury in both acute and chronic human diseases related to the heart, lung, liver, and kidney
- …