611 research outputs found

    La diversificazione intraclonale nei geni IGHV nella leucemia linfatica cronica: da un approccio bioinformatico alla clinica.

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    In dependence of the identity of the variable region of the heavy chain of the immunoglobulin (IGHV) gene respect to the germline, chronic lymphocytic leukemia (CLL) may be subdivided into U-CLL and M-CLL. The evaluation of the IGHV is a hallmark in CLL due to the stability during time and its prognostic and predictive value. Despite this, IGHV intraclonal diversification (ID) has been described in the Sanger era. However, in the Next Generation Sequencing era, no author developed a solid and reliable workflow for ID identification and quantification. It follows that ID characterization is still lacking. Moreover, nobody evaluated the clinical impact of ID in CLL yet. Using the NGS technologies we exploited the immunoglobulin repertoire of 1091 CLL samplesto generate a tailored approach for ID evaluation. Using these data, we developed an innovative methodology to identify systematic sequencing errors (SE) on sequencing data of immunological repertoire (RepSeq), correct them and evaluate ID through the calculation of the inverse Simpson Index (iSI). With focused experiments, we demonstrated the robustness of our approach and the full superimposition of corrected data with the gold standard for RepSeq, namely unique molecular identifiers-based amplification protocol. Moreover, we validate our approach by analyzing other B cell malignancies with documented ID producing a classification coherent with the literature. A validated cutoff of 1.2 of iSI was generated to discriminate CLL samples with ID features (I) and samples without (nI). Among 983 CLL patients with iSI score available, only 15% of samples displayed ID according to 8 the iSI 1.2 cutoff. Both M-CLL and U-CLL have sample with ID, despite a significant ID skewing toward M-CLL was found. No variation in IGHV family or gene usage according to the presence/absence of ID was reported. Analyzing the RepSeq data for the identification of molecular signatures compatible with canonical somatic hypermutation (SHM) processes we observed a significant higher presence of mutations based on Activation induced cytidine deaminase (AICDA) in the context of I-CLL. Indeed, a significant higher AICDA mRNA levels was observed in I-M- CLL. Lastly, taking advantage of 685 CLL patients with time to first treatment (TTFT) available, we observed a significantly longer TTFT of I-M-CLL respect to nI-M-CLL, whereas no differences were observed in U-CLL. In conclusion, we succeeded to quantitative characterize the CLL intraclonal diversification phenomenon and to demonstrate its possible clinical correlation.In dependence of the identity of the variable region of the heavy chain of the immunoglobulin (IGHV) gene respect to the germline, chronic lymphocytic leukemia (CLL) may be subdivided into U-CLL and M-CLL. The evaluation of the IGHV is a hallmark in CLL due to the stability during time and its prognostic and predictive value. Despite this, IGHV intraclonal diversification (ID) has been described in the Sanger era. However, in the Next Generation Sequencing era, no author developed a solid and reliable workflow for ID identification and quantification. It follows that ID characterization is still lacking. Moreover, nobody evaluated the clinical impact of ID in CLL yet. Using the NGS technologies we exploited the immunoglobulin repertoire of 1091 CLL samplesto generate a tailored approach for ID evaluation. Using these data, we developed an innovative methodology to identify systematic sequencing errors (SE) on sequencing data of immunological repertoire (RepSeq), correct them and evaluate ID through the calculation of the inverse Simpson Index (iSI). With focused experiments, we demonstrated the robustness of our approach and the full superimposition of corrected data with the gold standard for RepSeq, namely unique molecular identifiers-based amplification protocol. Moreover, we validate our approach by analyzing other B cell malignancies with documented ID producing a classification coherent with the literature. A validated cutoff of 1.2 of iSI was generated to discriminate CLL samples with ID features (I) and samples without (nI). Among 983 CLL patients with iSI score available, only 15% of samples displayed ID according to 8 the iSI 1.2 cutoff. Both M-CLL and U-CLL have sample with ID, despite a significant ID skewing toward M-CLL was found. No variation in IGHV family or gene usage according to the presence/absence of ID was reported. Analyzing the RepSeq data for the identification of molecular signatures compatible with canonical somatic hypermutation (SHM) processes we observed a significant higher presence of mutations based on Activation induced cytidine deaminase (AICDA) in the context of I-CLL. Indeed, a significant higher AICDA mRNA levels was observed in I-M- CLL. Lastly, taking advantage of 685 CLL patients with time to first treatment (TTFT) available, we observed a significantly longer TTFT of I-M-CLL respect to nI-M-CLL, whereas no differences were observed in U-CLL. In conclusion, we succeeded to quantitative characterize the CLL intraclonal diversification phenomenon and to demonstrate its possible clinical correlation

    Klasifikasi Citra MRI Tumor Otak Menggunakan Metode Hibrida CNN-ViT

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    A tumor is an abnormal cell that can grow in any part of the human body. This also includes the brain which is the most important organ for humans. Brain tumors can arise because a cell that should grow and die within a certain period of time remains alive and multiplies abnormally. Brain tumors require fast and accurate medical diagnosis because a patient needs to get immediate treatment. The Convolutional Neural Network (CNN) algorithm is one of the most popular algorithms for image data processing and analysis and has been incorporated into medical image classification. In addition, there is also a Vision Transformer algorithm that divides the image into several patches and tokenizes each pixel of the image. Based on this explanation, the author classifies brain tumor MRI images using the CNN-ViT hybrid method. The result of this research is the accuracy and performance of CNN-ViT hybrid compared to CNN and ViT in classifying brain tumors. The best accuracy results were obtained by CNN-ViT with an average test accuracy of 93%, CNN with an average test accuracy of 90.80% and ViT with an average test accuracy of 84.80%. In addition, the classification report results of the best scenario CNN-ViT obtained with data division 80:10:10, Adam optimization and learning rate 0.0001% are accuracy of 94%, precision of 95%, recall of 94% and f1 score of 94%

    Metabolic Syndrome Associated with Subclinical Hypothyroidism and Vit D Insufficiency - A Case Report and Discussion

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    Metabolic syndrome (MetS) associated with hypothyroidism, was reported in literature. Like-wise association between hypothyroidism and Vit. D deficiency was reported. Hypothyroidism, Vit. D deficiency in DM2 patients was also reported, in the literature. But the occurrence of MetS, hypothyroidism and Vit. D deficiency, together occurring in a case was unreported. The author presented such triple association in a male patient aged 54 years. While Met S itself was a risk factor for CVD (cardiovascular vascular disease) and so were independently, the hypothyroidism and hypovitaminosis D, the triple association would have cumulative risk for CVD. So, it would be  profitable  to screen all MetS cases with hypothyroidism, for Vit. D deficiency also, in view of the possible cumulative risk. Literature was reviewed as to the relationship of MetS to hypothyroidism and Vit D deficiency, as well as the changing diagnostic criteria of MetS and it’s pathogenesis

    Half a century of development economics : a review based on the"Handbook of Development Economics"

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    Development economics has made remarkable progress in 50 years, says the author, summarizing changes in the field since Nehru's first proposals for an independent India. Synthesizing insights about changes in the field from the many contributors to the"Handbook of Development Economics,"the author observes (among other things): 1) Different schools of thought may dominate, but the range of research has broadened. Economics has"hardened"as its practitioners have learned to use data more carefully and to reason more rigorously. 2) The policy message has been turned upside down. Gone is the idea that development is industrialization and that the main policy problem is to manage the interface between country and city. Today urbanization and industrialization are viewed as mere components of an integrated transformation, in which the expansion of foreign trade is central. Traditional institutions are viewed with far more understanding, because overhasty modernization has often proved counterproductive. 3) More than ever, development is seen as a"whole replacement"process, the key to which is mastery of Northern technology--now understood to be both simpler and more complex than previously thought. Simpler, because much technology is uncomplicated, and complex because even simple technology requires ingenuity and a costly investment in adaptations. 4) There has been a radical change in economists'view of market agents and policymakers. Gone are the days when economists thought their advice should be aimed mainly at planners. Policymakers are utility maximizers, too. Employees of state enterprises coalesce into powerful interest groups that block efforts to raise productivity. The new thinking is sometimes modified by evoking the vague concept of"governance,"under which the economist's view is to help design a system of interacting state and private institutions that, led by the state, cooperate in achieving social goals. Whether something useful will come from this line of thinking remains to be seen. The author detects major gaps in economists'undrstanding of development, suggesting a particular need for further study of collective action (a far more pervasive component of human action than is realized) and the selection of roles by individuals and the costly investment this entails (a concept that may shed light on Schumpeter's well-known but little-studied entrepreneur).Labor Policies,Economic Theory&Research,Health Economics&Finance,Environmental Economics&Policies,Decentralization,Health Economics&Finance,Poverty Assessment,Achieving Shared Growth,Economic Theory&Research,Environmental Economics&Policies

    Ta voix vit/Nous vivons : la genèse d’un poème d’Habib Tengour à l’aune de ses avant-textes

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    Cet article entend proposer quelques pistes de réflexion sur le processus de genèse d’un poème de Habib Tengour, auteur algérien. L’analyse de différents avant-textes du poème « Ta voix vit/Nous vivons », à paraître dans la revue Po&sie, permet de mettre en valeur un certain nombre de spécificités de cette écriture.This article intends to propose some reflection tracks on the genetic process of a poem by Algerian author Habib Tengour. The analysis of various foretexts of the poem « Ta voix vit/Nous vivons », about to appear in the review Po&sie, allows to bring out a number Tengour’s writing characteristics

    Towards a Practical Emergent Knowledge Exploitation

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    Provided by the author(s) and NUI Galway in accordance with publisher policies. Please cite the publishe

    La vie ne vit pas. Penser l'enfermement par le montage et l'écriture filmique

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    Ce mémoire part du film La vie ne vit pas (réalisé par l'autrice), qui met en scène une femme hospitalisée en psychiatrie après une dépression liée à l’aliénation du travail. L’autrice montre que l’hôpital n’est pas un dehors de la société, mais reproduit les mêmes logiques de contrôle et de normalisation. Le travail du film s’appuie sur le montage comme procédé critique : l’interruption (arrêt, rupture) permet de révéler les tensions invisibles du quotidien. Inspirée par Walter Benjamin, Bertolt Brecht et Sergei Eisenstein, la recherche défend une approche fragmentaire qui refuse une narration linéaire et univoque. Le montage devient ainsi un outil pour questionner la réalité sociale et les rapports de domination. La lenteur, les pauses et les ruptures sont pensées comme des gestes de résistance à la productivité et au rythme marchand. Le mémoire propose l’interruption comme une force de transformation, autant dans la création artistique que dans la vie.This Masterthesis is based on the film La vie ne vit pas (directed by the author), which depicts a woman hospitalized in a psychiatric ward after suffering from depression linked to alienation at work. The author shows that the hospital is not outside society, but reproduces the same logic of control and normalization. The film uses editing as a critical process: interruption (stopping, breaking) reveals the invisible tensions of everyday life. Inspired by Walter Benjamin, Bertolt Brecht, and Sergei Eisenstein, the research advocates a fragmentary approach that rejects linear and univocal narration. Editing thus becomes a tool for questioning social reality and relationships of domination. Slowness, pauses, and breaks are conceived as acts of resistance to productivity and commercial rhythms. The thesis proposes interruption as a force for transformation, both in artistic creation and in life

    Oscillatory Stability of Power Systems with High Shares of Renewable Generation: Investigation of the Effectiveness of Wide-Area Selective Damping Control: NextGen GridOps Knowledge Framework Supporting Future Grid Operations

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    A large contribution to the total share of electricity generated in European power grid will come from renewable sources of energy in the near future due to European initiative to become carbon neutral. RES are connected to the grid with PE devices, which if not modelled correctly provide lower level of system stability and security of supply. The existing power grid with mainly synchronous generators will not be suited to operate in the future, when synchronous machines will become less important sources of energy. An increase in dynamic behaviour of the system could cause significant challenges for the existing system, which calls for new monitoring and control strategies. The aim of the project is twofold; firstly, to enhance system stability by deploying WAMS in power system with a massive share of RES to total electricity generation. Secondly, it focuses on developing and proposing a tool which will improve consultancy in future power grids. A tool developed is Next Generation Grid Operations (NextGen GridOps) Knowledge Framework which is conceptually designed by DNV. The effectiveness of WAMS applications on system stability improvements and damping enhancements will be evaluated by studying rotor angle stability as well as effect of WAMS on damping of electromechanical oscillations. The response to a disturbance of the remaining synchronous generators will be studied to evaluate the effect of different types of control schemes (grid-following, grid forming control) on the rotor angle stability. Rotor angle stability will be examined to show whether different control structures and WAMS will show enhancements of the overall stability through time domain simulations. WAMS structure in this project consists of PMUs as well as WADCs. While PMUs are sensors deployed in the system to provide synchrophasor measurement, WADCs are damping controllers deployed with an intent of enhancing damping in the system. This project build upon findings from Horizon 2020 MIGRATE Project. The effectiveness of grid-following control and grid-forming control on stabilizing the grid with massive penetration of PE devices are conducted to set the base case for evaluating the effect of WAMS. Modelling software used in the project is DIgSILENT PowerFactory 2021 SP1 and the PowerFactory Thesis Licence was provided by DIgSILENT GmbH for research and educational purposes. Based on the off-line numerical simulations conducted in IEEE 39 Bus New England test system it was found that WAMS functionality with corresponding PMUs and WADCs can decrease oscillations in the system. It has been verified that grid-following control enables 60% of RES penetration and grid-forming control enables penetration of RES above 80%. There have been two grid-forming controllers used in the system, where DVC is able to receive the stabilizing signal while VSM grid-forming controller has a supporting role. WAMS and corresponding WADCs deployed on DVCs are able to enhance damping of the low-frequency modes with frequencies below 2.0 Hz, which is supported by time domain simulations and by conducting Prony analysis. Eigenvalue analysis results for some cases with WAMS deployed show no additional enhancements, which is a consequence of newly introduced controllers and interactions among them and existing controllers. The practical implications of this Master's Thesis study have been modelled in the NextGen GridOps Framework with an intent to make a step towards real world implementation of the findings developed during the project. Framework modelling focused on implementing client maturity classification of WAMS deployments, contributing towards development of WAMS roadmaps and further deployment of WAMS solutions for grid operators as part of the DNV Next Generation Grid Operations advisory services. Work done and information implemented will be valuable for DNV while solving the complex process of future grid operations and at the same time bringing newly developed knowledge into practice. The framework development part of the project ties in with scientific contribution by allowing newly developed information to be further explored. Effectiveness of WAMS and WADCs on improving selective damping and consequently enhancing system stability has been identified in this project through use of DVCs. It has been proven that VSM control has a better stabilizing effect and would allow even further enhancement of damping critical oscillation modes. Higher damping in the system increases the stability and consequently higher security of energy supply.<br/
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