43 research outputs found

    TOWARDS DIGITAL TWINS FOR OPTIMIZING METRICS IN DISTRIBUTED STORAGE SYSTEMS - A REVIEW

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    With the exponential data growth, there is a crucial need for highly available, scalable, reliable, and cost-effective Distributed Storage Systems (DSSs). To ensure such efficient and fault tolerant systems, replication and erasure coding techniques are typically used in traditional DSSs. However, these systems are prone to failure and require different failure prevention and recovery algorithms. Failure recovery of DSS and data reconstruction techniques take into consideration different performance metrics optimization in the recovery process. In this paper, DSS performance metrics are introduced. Several recent papers related to adopting erasure coding in DSSs are surveyed together with highlighting related performance metrics introduced in the context of these papers. Next, we present recent literature where Digital Twins (DTs) are involved in monitoring DSSs and assisting the data center managers in intelligent decision-making. Finally, important open issues are identified to inspire future studies for fully efficient DSSs

    Transfer rna dynamics and transfer-messenger rna accommodation in bacterial ribosomes at the single-molecule level

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    Single-molecule spectroscopy, protein-induced fluorescence enhancement (PIFE), fluorescence resonance energy transfer (FRET), and several biochemical tools were applied to study transfer RNA (tRNA) dynamics and transfer-messenger RNA (tmRNA) accommodation inside ribosomes. In the first project of this thesis work, structural characterization of the tRNA-like domain of tmRNA (TLD) in complex with SmpB protein was carried out, and the results reveal no change in the global conformation or the flexibility of the TLD upon SmpB binding. In contrast, magnesium ions induce a compaction of the TLD structure, suggesting that flexibility in the H2a stem of TLD may allow different conformations of tmRNA, as the TLD and mRNA-like domain (MLD) need to be positioned differently while moving through the ribosome. In the second project, an assay was developed to study the dynamics of tRNA and tmRNA accommodation inside ribosomes. The results from this project reveal fluorescence intensity changes of a dye-labeled tRNA (Cy3-tRNA) because of changes in the fluorophore environment. These changes are sensitive to both magnesium concentration and the presence of antibiotics. Interestingly, these changes can be correlated to spontaneous ribosomal ratcheting. Monitoring tmRNA entrance and accommodation was also studied at the single-molecule level. The data reveal that the accommodation of tmRNA occurs in a multistep process, in which three major FRET states are present. The low FRET state might represent the initial binding of tmRNA. The mid and high FRET states are believed to represent the pre-accommodation and full accommodation, respectively, of tmRNA inside the ribosome. These states were successfully assigned by using specific antibiotics that allow stalling at each FRET state. Overall, our data suggest that the accommodation of tmRNA occurs in the same manner as a canonical tRNA. These results have allowed the successful dissection of the first step of the tmRNA task inside ribosomes, which is important for understanding further steps in the pathway and unraveling the mystery of this RNA function. Such results could be beneficial toward developing antibiotics that are urgently needed for targeting pathogenic bacteria

    FAMAID: A TOOL FOR AIDING PEOPLE WITH DISABILITY

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    People with disabilities suffer from discrimination and obstacles that restrict them from participating in society on an equal basis with others every day. They are deprived of their rights to be included in ordinary school systems and even in the work market. In the process of raising awareness, facilitating dailyroutines, and developing guidance, the idea of assisting such people with handy tools/software arose and was implemented in the FamAid tool. FamAid offers people with hearing disability the opportunity to be engaged in the society through many facilities. In this work, we implemented a web application that serves as a community for people with disability who can use sign language to access the app. The app uses hand gesture recognition technique which is considered an active research field in Human-Computer Interaction technology to perform sign language translation to text. Afterwards, the text will be provided as input to the app where the output will be generated based on the request of the user. This research presents an application which is considered a gift for people with speaking and/or hearing disability as it makes their lives easier

    Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation

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    Cytomegalovirus (CMV) remains a major cause of morbidity following allogeneic hematopoietic stem cell transplant. Natural killer cells expressing NKG2C have been shown to play a role in the immune surveillance of human CMV. We studied NKG2C copy number in the donor graft and the risk of CMV reactivation after double umbilical cord blood transplantation (DUCBT) in 100 CMV seropositive DUCBT recipients and their corresponding cord blood (CB) grafts (n = 200). In the setting of DUCBT, the combined graft may contain 0–4 functional copies of NKG2C gene. Sixteen patients received a combined graft with 1 or 2 NKG2C copies and 84 patients were recipients of a combined graft with 3 or 4 NKG2C copies. The 6-month cumulative incidence of CMV reactivation for the two groups was 93.7 and 58.4%, respectively (p = 0.0003). In multivariate analysis, low NKG2C copies in the graft was an independent predictor of CMV reactivation (HR = 2.72, CI = 1.59–4.64; p < 0.0001). Our study points to an important role for donor NKG2C for protection against CMV reactivation after DUCBT. These novel findings may help identify patients at a higher risk of CMV reactivation after DUCBT. Donor NKG2C genotype may be used as a potential criterion in the algorithm for graft selection for DUCBT

    Integration of oncology and palliative care : a Lancet Oncology Commission

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    Full integration of oncology and palliative care relies on the specific knowledge and skills of two modes of care: the tumour-directed approach, the main focus of which is on treating the disease; and the host-directed approach, which focuses on the patient with the disease. This Commission addresses how to combine these two paradigms to achieve the best outcome of patient care. Randomised clinical trials on integration of oncology and palliative care point to health gains: improved survival and symptom control, less anxiety and depression, reduced use of futile chemotherapy at the end of life, improved family satisfaction and quality of life, and improved use of health-care resources. Early delivery of patient-directed care by specialist palliative care teams alongside tumour-directed treatment promotes patient-centred care. Systematic assessment and use of patient-reported outcomes and active patient involvement in the decisions about cancer care result in better symptom control, improved physical and mental health, and better use of health-care resources. The absence of international agreements on the content and standards of the organisation, education, and research of palliative care in oncology are major barriers to successful integration. Other barriers include the common misconception that palliative care is end-of-life care only, stigmatisation of death and dying, and insufficient infrastructure and funding. The absence of established priorities might also hinder integration more widely. This Commission proposes the use of standardised care pathways and multidisciplinary teams to promote integration of oncology and palliative care, and calls for changes at the system level to coordinate the activities of professionals, and for the development and implementation of new and improved education programmes, with the overall goal of improving patient care. Integration raises new research questions, all of which contribute to improved clinical care. When and how should palliative care be delivered? What is the optimal model for integrated care? What is the biological and clinical effect of living with advanced cancer for years after diagnosis? Successful integration must challenge the dualistic perspective of either the tumour or the host, and instead focus on a merged approach that places the patient's perspective at the centre. To succeed, integration must be anchored by management and policy makers at all levels of health care, followed by adequate resource allocation, a willingness to prioritise goals and needs, and sustained enthusiasm to help generate support for better integration. This integrated model must be reflected in international and national cancer plans, and be followed by developments of new care models, education and research programmes, all of which should be adapted to the specific cultural contexts within which they are situated. Patient-centred care should be an integrated part of oncology care independent of patient prognosis and treatment intention. To achieve this goal it must be based on changes in professional cultures and priorities in health care

    Fluorescence Characterization of the Transfer RNA-like Domain of Transfer Messenger RNA in Complex with Small Binding Protein B

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    Transfer messenger RNA (tmRNA) and small binding protein B (SmpB) are the main components of the trans-translation rescue machinery that releases stalled ribosomes from defective mRNAs. Little is known about how SmpB binding affects the conformation of the tRNA-like domain (TLD) of tmRNA. It has been previously hypothesized that the absence of a D stem in the TLD provides flexibility in the elbow region of tmRNA, which can be stabilized by its interaction with SmpB. Here, we have used Förster resonance energy transfer to characterize the global structure of the tRNA-like domain of tmRNA in the presence and absence of SmpB and as a function of Mg<sup>2+</sup> concentration. Our results show tight and specific binding of SmpB to tmRNA. Surprisingly, our data show that the global conformation and flexibility of tmRNA do not change upon SmpB binding. However, Mg<sup>2+</sup> ions induce an 11 Å compaction in the tmRNA structure, suggesting that the flexibility in the H2a stem may allow different conformations of tmRNA as the TLD and mRNA-like domain need to be positioned differently while moving through the ribosome
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