The EU requires a more coherent strategy on future sanctions against Russia

Russia, Ukraine, France and Germany met in Minsk on 11 February to negotiate a solution to the ongoing conflict in Ukraine. Anna Wieslander writes on the EU’s use of sanctions against Russia throughout the crisis. She notes that with tough negotiations to come between EU states, it is vital that Europe’s political leaders form a coherent long-term strategy if they are to exert real pressure on Russia

Verification of Dose Calculation Algorithms in Treatment Planning Systems for External Radiation Therapy: A Monte Carlo Approach

This thesis presents a new verification concept, the virtual accelerator, for dose calculation algorithms used in treatment planning systems (TPSs) for external beam radiotherapy. The algorithm input data required to implement a treatment unit in the TPS are generated by Monte Carlo simulations as are the beam reference data needed for the subsequent evaluation of the dose calculation algorithm. The virtual accelerator and its corresponding unit in the TPS can thus be used for comprehensive verification of dose calculation algorithms in the TPS. The virtual accelerator concept provides a new means of verifying dose calculation algorithms in TPSs. Properties that are difficult or even impossible to assess using conventional measurements can be studied. Problems associated with conventional measurements, e.g., detector limitations and accelerator stability, can be circumvented. The flexibility of the virtual accelerator is high since additional beam reference data can be acquired without compromising the consistency of the data. The feasibility of the virtual accelerator concept has been demonstrated by the successful implementation of a virtual photon accelerator and a virtual electron accelerator in commercial TPSs. The success of the implementations was determined by the ability of the dose calculation algorithms to reproduce the algorithm input data, and in most cases the agreement was within [+-]2%. The advantages and usefulness of the virtual photon accelerator have been illustrated in a mediastinum and a hip-prostheses-like geometry. The ability of the virtual photon accelerator to generate both total dose and the primary and phantom-scattered components was used to study the performance of two dose calculation algorithms in the presence of metallic implants. The virtual electron accelerator has been used to study the performance in homogeneous and inhomogeneous phantoms. Studies of the beam model and the handling of patient-specific inserts in the dose calculation algorithm were possible due to the ability of the virtual accelerator to separate the total dose into beam model components. Another advantage of the virtual accelerator that has been utilized for both photons and electrons is the possibility of evaluating the accuracy achievable in anthropomorphic phantoms based on patient X-ray computed tomography data. This feature has been used for photon algorithms in the case of tangential breast treatment and for the electron algorithm in the cases of nose, parotid gland, thorax wall and spinal cord treatment. For the electron cases, an elliptical [gamma]-evaluation was performed in three dimensions. For the 0.02 Gy/2 mm criteria 92% of the volume receiving more than 0.85 Gy per 100 monitor units (MU) has [gamma]-values less than one in the worst case. The corresponding value for the volume receiving more than 0.10 Gy/100 MU is 98%

Mechanisms of mRNA export

AbstractRelease of properly processed and assembled mRNPs from the actively transcribing genes, movement of the mRNPs through the interchromatin and interaction with the Nuclear Pore Complexes, leading to cytoplasmic export, are essential steps of eukaryotic gene expression. Here, we review these intranuclear gene expression steps

Circulating cytokine profile in anti-neutrophilic cytoplasmatic autoantibody-associated vasculitis: prediction of outcome?

AIMS: The anti-neutrophilic cytoplasmatic autoantibody-associated vasculitides (AASV) are diseases of relapsing-remitting inflammation. Here we explore the cytokine profile in different phases of disease, looking for pathogenic clues of possible prognostic value. RESULTS: Interleukin (IL)-6, IL-8 and IL-10 were significantly elevated in plasma. Patients in the stable phase who subsequently developed adverse events had higher IL-8 values. Patients in the stable phase who relapsed within 3 months had lower IL-10 values and higher IL-6 levels. CONCLUSIONS: Patients with AASV have raised circulating cytokine levels compared with healthy controls, even during remission. Raised IL-8 seems associated with poor prognosis. Lower levels of IL-10 and higher levels of IL-6 herald a greater risk of relapse. Patients with systemic vasculitis in clinical remission have persistent disease activity, kept under control by inhibitory cytokines

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Background: The polytene nuclei of the dipteran Chironomus tentans (Ch. tentans) with their Balbiani ring (BR) genes constitute an exceptional model system for studies of the expression of endogenous eukaryotic genes. Here, we report the first draft genome of Ch. tentans and characterize its gene expression machineries and genomic architecture of the BR genes. Results: The genome of Ch. tentans is approximately 200 Mb in size, and has a low GC content (31%) and a low repeat fraction (15%) compared to other Dipteran species. Phylogenetic inference revealed that Ch. tentans is a sister clade to mosquitoes, with a split 150-250 million years ago. To characterize the Ch. tentans gene expression machineries, we identified potential orthologus sequences to more than 600 Drosophila melanogaster (D. melanogaster) proteins involved in the expression of protein-coding genes. We report novel data on the organization of the BR gene loci, including a novel putative BR gene, and we present a model for the organization of chromatin bundles in the BR2 puff based on genic and intergenic in situ hybridizations. Conclusions: We show that the molecular machineries operating in gene expression are largely conserved between Ch. tentans and D. melanogaster, and we provide enhanced insight into the organization and expression of the BR genes. Our data strengthen the generality of the BR genes as a unique model system and provide essential background for in-depth studies of the biogenesis of messenger ribonucleoprotein complexes

Antibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults

Autoantibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults. Forty-seven adults with urinary tract infection (UTI), 9 with recent acute pyelonephritis and 38 with previous renal infection, were investigated for the presence of autoantibodies to Tamm-Horsfall protein (THP). All patients except 6 had or had had vesicoureteric reflux (VUR). In patients with recent acute pyelonephritis, only IgA antibodies were significantly elevated. Among the patients with previous UTI, more than 6 months before the time of testing, a graded response was found for IgG and IgM specific antibodies, with the lowest value in those with renal damage and elevated serum creatinine and the highest in those with a normal X-ray. A negative correlation was found between IgG antibodies to THP and elevated serum creatinine (r = -0.76, P < 0.02). No significant correlation was found between VUR itself and antibodies to THP. A low IgG antibody level to THP in patients with a history of previous UTI seems to be a useful indicator of renal scarring. Possible immunologic mechanisms behind the low antibody level and the renal damage are discussed.Auto-anticorps anti-protéine de Tamm-Horsfall associés à des lésions rénales et à des infections urinaires chez l'adulte Quarante-sept adultes atteints d'infection urinaire, 9 ayant une pyélonéphrite aiguë récente et 38 une infection rénale antérieure ont été étudiés pour la présence d'auto-anticorps anti-protéine de Tamm-Horsfall (THP). Tous les malades sauf six avaient ou avaient eu un reflux vésico-urétéral. Chez les malades ayant un antécédent récent de pyélonéphrite seul les anti-corps IgA étaient significativement élevés. Parmi les malades dont l'antécédent d'infection urinaire remontait à plus de six mois une réponse a été obtenue pour les anti-corps spécifiques IgG et IgM, avec la valeur la plus faible chez ceux qui étaient atteints de lésions rénales et avaient une créatininémie élevée et la valeur la plus élevée chez ceux qui étaient indemnes de lésions radiologiques. Une corrélation négative a été observée entre les anti-corps IgG anti THP et l'augmentation de la créatininémie (r = -0,76, P < 0,02). Il n'a pas été observé de corrélation significative entre le reflux par lui-même et les anti-corps anti THP. Un taux faible d'anti-corps IgG anti THP chez des malades ayant des antécédents d'infection urinaire peut être un indicateur utile de lésions rénales. Les mécanismes immunologiques qui peuvent sous tendre le taux faible d'anti-corps et les lésions rénales sont discutés