101 research outputs found

    Incompatibility of the Digital Economy Act 2010 subscriber appeal process provisions with Article 6 of the ECHR

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    This is the accepted manuscript of an article published by Taylor & Francis in International Review of Law, Computers and Technology on 10 January 2014. The version of record [Romero-Moreno, F. (2014) Incompatibility of the Digital Economy Act 2010 subscriber appeal process provisions with Article 6 of the ECHR', International Review of Law, Computers & Technology, 28(1): 81-97, first published on line January 10, 2014] is available online via doi: http://dx.doi.org/10.1080/13600869.2013.869912Through case-law research, this paper critically assesses the compatibility of the Digital Economy Act 2010 (DEA) subscriber appeal process provisions (Section 13 of the DEA) with Article 6 of the European Convention on Human Rights (ECHR). Drawing on the European Court of Human Rights (ECtHR) case-law, Ofcom's Initial Obligations Code (the Code), and the DEA judicial review decision, namely, BT PLC and Talk Talk PLC v Secretary of State for Business Innovation and Skills and others, this paper focuses on the three Strasbourg Court principles of equality of arms, admissibility of evidence, and presumption of innocence, in an effort to determine whether Section 13 of the DEA infringes them, and whether this constitutes a breach of a subscriber's right to a fair trial under Article 6 of the ECHR. The paper examines these three ECtHR principles. It contrasts such principles with the Code's provisions, and considers the compatibility of Section 13 of the DEA with Article 6 of the ECHR. It concludes that the DEA subscriber appeal process provisions do indeed infringe these principles, thus constituting a violation of subscribers' right to a fair trial. It also recommends that the UK government start taking seriously human rights in general, and Article 6 of the ECHR in particular.Peer reviewe

    Improvement of the realisation of the mass scale

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    The project 19RPT02“Improvement of the realisation of the mass scale”(EMPIR [1] Call 2019 –Energy, Environment, Normative and Research Potential)has just started.Its aim is to improve the quality of one of the most important tasksin mass metrology,the realisation of the mass scale. After the new definition of the kilogram this technique is getting more important

    Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression

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    Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen (pO2), extracellular acidosis (pHe), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron paramagnetic resonance (EPR) technique for in vivoconcurrent assessment of these TME parameters in various mouse models of cancer. While the data support the existence of hypoxic and acidic regions in TME, the most dramatic differences, about 2-fold higher concentrations in tumors vs. normal tissues, were observed for interstitial Pi - the only parameter that also allowed for discrimination between non-metastatic and highly metastatic tumors. Correlation analysis between [Pi], pO2, pHe and tumor volumes reveal an association of high [Pi] with changes in tumor metabolism and supports different mechanisms of protons and Pi accumulation in TME. Our data identifies interstitial inorganic phosphate as a new TME marker for tumor progression. Pi association with tumor metabolism, buffer-mediated proton transport, and a requirement of high phosphorus content for the rapid growth in the “growth rate hypothesis” may underline its potential role in tumorigenesis and tumor progression

    Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression

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    Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen (pO2), extracellular acidosis (pHe), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron paramagnetic resonance (EPR) technique for in vivo concurrent assessment of these TME parameters in various mouse models of cancer. While the data support the existence of hypoxic and acidic regions in TME, the most dramatic differences, about 2-fold higher concentrations in tumors vs. normal tissues, were observed for interstitial Pi - the only parameter that also allowed for discrimination between non-metastatic and highly metastatic tumors. Correlation analysis between [Pi], pO2, pHe and tumor volumes reveal an association of high [Pi] with changes in tumor metabolism and supports different mechanisms of protons and Pi accumulation in TME. Our data identifies interstitial inorganic phosphate as a new TME marker for tumor progression. Pi association with tumor metabolism, buffer-mediated proton transport, and a requirement of high phosphorus content for the rapid growth in the “growth rate hypothesis” may underline its potential role in tumorigenesis and tumor progression

    Острое нарушение мозгового кровообращения по ишемическому типу в послеродовом периоде

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    During pregnancy and delivery, the risk of cerebrovascular disorders increases due to several physiological changes. The elevated level of estrogen stimulates the production of clotting factors, which deteriorates the risk of thromboembolism. Increased plasma volume and total blood volume lead to the risk of hypertension, and the high level of progesterone in the third trimester of pregnancy promotes the permeability of small blood vessels. The risk of developing cerebrovascular complications remains high in the postpartum period. The article describes two clinical cases of postpartum ischemic stroke as a complication after surgical delivery in young women with an aggravated somatic medical history. The treatment and follow-up of these patients during their stay in the intensive care unit included changes in management tactics, use of antiplatelet, anticoagulant, and metabolic therapy, and subsequent rehabilitation. This article describes the case-management interventions and changes in neurological symptoms of these patients, also it discusses the most likely etiological factors of cerebrovascular disorders in these casesБеременность и роды характеризуются более высоким риском цереброваскулярных нарушений, что обусловлено определенными физиологическими изменениями. Повышенный уровень эстрогена стимулирует выработку факторов свертывания крови, что увеличивает риск тромбоэмболии. Увеличение объема плазмы и общего объема крови повышает риск развития гипертензии, а повышенный уровень прогестерона в третьем триместре беременности способствует увеличению проницаемости мелких кровеносных сосудов. Риск развития цереброваскулярных осложнений остается высоким и в послеродовой период. В статье представлены два клинических наблюдения развития острого нарушения мозгового кровообращения по ишемическому типу после оперативного родоразрешения у молодых женщин с отягощенным соматическим анамнезом. Лечение и наблюдение этих пациенток во время пребывания в отделении реанимации и интенсивной терапии подразумевало изменение тактики ведения, включение антиагрегантной, антикоагулянтной, метаболической терапии и последующей реабилитации. Статья содержит описание комплексов лечебных мероприятий и динамики неврологической симптоматики этих пациенток, а также обсуждение наиболее вероятных этиологических факторов цереброваскулярных нарушений в данных случая

    Infiltrazione macrofagica e densità capillare nel carcinoma della laringe. Studio su 52 casi

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    L’angiogenesi è uno dei sei principali meccanismi alla base del cancro, ed è stato studiato approfonditamente negli ultimi 20 anni. L’obiettivo del presente studio è stato quello di determinare sia la densità capillare sia l’infiltrato macrofagico nei campioni di carcinoma laringeo e di determinarne la correlazione con gli aspetti clinici e patologici. Sia la densità capillare (CD34) sia l’infiltrato macrofagico (CD68) sono stati determinati con metodiche immunoistochimiche mediante microarray. Il nostro campione ha mostrato una densità capillare media di 14,27 ± 12,92 vasi su campo ingrandito a 200×, e l’infiltrato macrofagico medio è stato di 5,19 ± 4,32. La densità capillare si è dimostrata superiore nei pazienti metastatici. Inoltre uno studio di regressione lineare ha mostrato che l’entità dell’infiltrato macrofagico poteva predire la densità capillare del campione di carcinoma laringeo preso in esame. Non abbiamo invece individuato una correlazione fra ambo i fattori studiati e l’incidenza delle recidive o gli altri fattori clinici presi in esame. Il nostro studio aggiunge dati ad un problema che per quanto studiato a fondo negli ultimi 20 anni resta nella sostanza controverso

    Trans-mitochondrial coordination of cristae at regulated membrane junctions

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    Reminiscent of bacterial quorum sensing, mammalian mitochondria participate in inter-organelle communication. However, physical structures that enhance or enable interactions between mitochondria have not been defined. Here we report that adjacent mitochondria exhibit coordination of inner mitochondrial membrane cristae at inter-mitochondrial junctions (IMJs). These electron-dense structures are conserved across species, resistant to genetic disruption of cristae organization, dynamically modulated by mitochondrial bioenergetics, independent of known inter-mitochondrial tethering proteins mitofusins and rapidly induced by the stable rapprochement of organelles via inducible synthetic linker technology. At the associated junctions, the cristae of adjacent mitochondria form parallel arrays perpendicular to the IMJ, consistent with a role in electrochemical coupling. These IMJs and associated cristae arrays may provide the structural basis to enhance the propagation of intracellular bioenergetic and apoptotic waves through mitochondrial networks within cells

    Cytokine Levels Correlate with Immune Cell Infiltration after Anti-VEGF Therapy in Preclinical Mouse Models of Breast Cancer

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    The effect of blocking VEGF activity in solid tumors extends beyond inhibition of angiogenesis. However, no studies have compared the effectiveness of mechanistically different anti-VEGF inhibitors with respect to changes in tumor growth and alterations in the tumor microenvironment. In this study we use three distinct breast cancer models, a MDA-MB-231 xenograft model, a 4T1 syngenic model, and a transgenic model using MMTV-PyMT mice, to explore the effects of various anti-VEGF therapies on tumor vasculature, immune cell infiltration, and cytokine levels. Tumor vasculature and immune cell infiltration were evaluated using immunohistochemistry. Cytokine levels were evaluated using ELISA and electrochemiluminescence. We found that blocking the activation of VEGF receptor resulted in changes in intra-tumoral cytokine levels, specifically IL-1β, IL-6 and CXCL1. Modulation of the level these cytokines is important for controlling immune cell infiltration and ultimately tumor growth. Furthermore, we demonstrate that selective inhibition of VEGF binding to VEGFR2 with r84 is more effective at controlling tumor growth and inhibiting the infiltration of suppressive immune cells (MDSC, Treg, macrophages) while increasing the mature dendritic cell fraction than other anti-VEGF strategies. In addition, we found that changes in serum IL-1β and IL-6 levels correlated with response to therapy, identifying two possible biomarkers for assessing the effectiveness of anti-VEGF therapy in breast cancer patients

    Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma: rethinking cancer immunotherapy

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    Review article[Abstract] The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy
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