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Homogeneous luminescent quantitation of cellular guanosine and adenosine triphosphates (GTP and ATP) using QT-Luc GTP&ATP assay
No full textGuanosine triphosphate (GTP) and adenosine triphosphate (ATP) are essential nucleic acid building blocks and serve as energy molecules for a wide range of cellular reactions. Cellular GTP concentration fluctuates independently of ATP and is significantly elevated in numerous cancers, contributing to malignancy. Quantitative measurement of ATP and GTP has become increasingly important to elucidate how concentration changes regulate cell function. Liquid chromatography-coupled mass spectrometry (LC-MS) and capillary electrophoresis-coupled MS (CE-MS) are powerful methods widely used for the identification and quantification of biological metabolites. However, these methods have limitations related to specialized instrumentation and expertise, low throughput, and high costs. Here, we introduce a novel quantitative method for GTP concentration monitoring (GTP-quenching resonance energy transfer (QRET)) in homogenous cellular extracts. CE-MS analysis along with pharmacological control of cellular GTP levels shows that GTP-QRET possesses high dynamic range and accuracy. Furthermore, we combined GTP-QRET with luciferase-based ATP detection, leading to a new technology, termed QT-LucGTP&ATP, enabling high-throughput compatible dual monitoring of cellular GTP and ATP in a homogenous fashion. Collectively, GTP-QRET and QT-LucGTP&ATP offer a unique, high-throughput opportunity to explore cellular energy metabolism, serving as a powerful platform for the development of novel therapeutics and extending its usability across a range of disciplines
The EU-Japan EPA and the question of formal and informal trade barriers for European businesses in Japan
No full textThis study focuses on how technical barriers to trade (TBT) are addressed in recent EU-Japan Economic Partnership Agreement (EPA). We analyze the pre- and post-EPA trade policies and the contested issues in Japan from the viewpoint of European businesses. An eclectic theoretical approach is adopted to study the economic, political and social aspects of trade barriers. Whereas formal trade barriers, such as tariffs and codified non-tariff barriers are easily discernible, the subtler informal trade barriers derive from social norms that guide administrative practices and are hard to measure, and largely neglected in recent research. Based on expert interviews, policy documents, and European business surveys, we observe that the enforcement of EPA in Japan lags behind concerning certain TBTs such as standards, approvals and testing. The findings suggest that informal trade barriers, often linked with investment barriers, have a bearing in the theorization on trade policies and free trade agreements.</p
Significance of Degree of HLA Disparity Using T-cell Replete Peripheral Blood Stem Cells From Haploidentical Donors With Posttransplantation Cyclophosphamide in AML in First Complete Hematologic Remission: A Study of the Acute Leukemia Working Party of the EBMT
Get PDFAvailability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2-3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2-4 acute graft -versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2-3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2-3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2-4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2-3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS.</p
Planned improvement actions based on patient safety incident reports in Estonian hospitals: a document analysis
Get PDFAim Aim of this study was to describe and analyse associations of incidents and their improvement actions in hospital setting.Methods It was a retrospective document analysis of incident reporting systems' reports registered during 2018-2019 in two Estonian regional hospitals. Data were extracted, organised, quantified and analysed by statistical methods.Results In total, 1973 incident reports were analysed. The most commonly reported incidents were related to patient violent or self-harming behaviour (n=587), followed by patient accidents (n=379), and 40% of all incidents were non-harm incidents (n=782). Improvement actions were documented in 83% (n=1643) of all the reports and they were focused on (1) direct patient care, (2) staff-related actions; (3) equipment and general protocols and (4) environment and organisational issues. Improvement actions were mostly associated with medication and transfusion treatment and targeted to staff. The second often associated improvement actions were related to patient accidents and were mostly focused on that particular patient's further care. Improvement actions were mostly planned for incidents with moderate and mild harm, and for incidents involving children and adolescents.Conclusion Patient safety incidents-related improvement actions need to be considered as a strategy for long-term development in patient safety in organisations. It is vital for patient safety that the planned changes related to the reporting will be documented and implemented more visibly. As a result, it will boost the confidence in managers' work and strengthens all staff's commitment to patient safety initiatives in an organisation.</p
Lucretius, impietas and Religious Deviance
No full textLucretius’ Epicurean manifesto De rerum natura includes criticism of different aspects of ancient culture, such as classical mythology. Although from the textual evidence it is indisputable that he criticises the traditional Roman religion and its customs, the claim, defended in this article, that Lucretius was a religiously deviant thinker in a potentially harmful way for the ruling elite is controversial. It is controversial because there was, to some extent, freedom of religion in the late Roman republic. However, I argue that those in power had weighty reasons to consider De rerum natura as a religiously deviant work and thus Lucretius as an impious thinker (i.e., a person who lacks reverence towards the Roman gods and religious traditions). To be precise, his views are, even in the Roman intellectual context, radical. I use Varro’s theologia tripertita (‘threefold theology’), the sociological definition of religious deviance by Fritz Sack and John Scheid’s terminology of Roman religion to analyse Lucretius’ position.</p
Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer
Get PDFIntroduction Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications. Methods We classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH. Results In the univariate survival analysis for disease-specific survival, the Epstein-Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19-5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA's classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15-2.60], p = 0.009 and HR 1.74 [95% CI 1.06-2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial-mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30-2.77], p Conclusions Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.</p
Retail Vacancies in City Centres – Causes and Consequences: Findings from Turku, Finland
Get PDF This study examines ground-floor retail vacancies in Turku CBD in 2016–2021. It is based on a longitudinal database formed for the study, interviews, discussions with the stakeholders, and documentary analysis. The study found that three fourths of the vacancies were short-term. The long-term vacancies were spaces no longer meeting the requirements of contemporary retailing. In cases where property development was possible, planning disputes may prolong the vacancies for years or even decades. </p
Oodeja Mikalle - Odes to Mika - Оды Мике: Festschrift for Professor Mika Lavento on the occasion of his 60th birthday
No full textPeatlands constitute central habitats for the occurrence of wetland archaeological sites. Consisting of waterlogged organic soils, they also provide advantageous conditions for the preservation of organic materials. The economic utilisation of peatlands has been extensive and long-lasting in mire-rich Finland. Archaeologists urgently seek to develop viable techniques for detecting, monitoring, and studying peatland archaeological sites, before they are deteriorated. One option is to conduct fieldwalking at commercial peat extraction sites, which was opportunistically tested in the detection of Mesolithic sites at southern Lake Saimaa by the University of Helsinki in 2015. In this paper, the main observations and challenges of the survey are reviewed and suggestions for further testing are presented.</p