15 research outputs found

    Direct observation of topoisomerase IA gate dynamics

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    Type IA topoisomerases cleave single-stranded DNA and relieve negative supercoils in discrete steps corresponding to the passage of the intact DNA strand through the cleaved strand. Although type IA topoisomerases are assumed to accomplish this strand passage via a protein-mediated DNA gate, opening of this gate has never been observed. We developed a single-molecule assay to directly measure gate opening of the Escherichia coli type IA topoisomerases I and III. We found that after cleavage of single-stranded DNA, the protein gate opens by as much as 6.6 nm and can close against forces in excess of 16 pN. Key differences in the cleavage, ligation, and gate dynamics of these two enzymes provide insights into their different cellular functions. The single-molecule results are broadly consistent with conformational changes obtained from molecular dynamics simulations. These results allowed us to develop a mechanistic model of interactions between type IA topoisomerases and single-stranded DNA

    Power system Vertical Division State Estimation (VDSE) – A parallel processing technique

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    Power system state estimation is very important analysis both for off-line and online purposes. Solving the non-linear large power system equations by iterative solution consumes huge computational time and memory. This paper presents a unique technique to divide the Gain matrix/Jacobian products of the large system into smaller independent Jacobian products at each node area on an imaginary plan. The Jacobian product can be represented in three dimensional form having ‘m’-two dimensional layer arranged on the third axis, where ‘m’ is the total number of system measurements taken. The method of dividing the three dimensional view of Jacobian product from vertically downward is termed as “Vertical Division” technique. The fact is, in any electrical power system, the state of a bus/node depends on the power flow between the neighboring (connected) node/bus. This logic is applied to solve the state estimation which resulted in “Vertical Division” technique for Power system state estimation. In this technique the measurements are grouped and processed independently corresponding to respective Node. The two main focus of this paper is, 1) to evaluate its mathematical formulations and validate its results with standard, established Integrated State Estimation (ISE) technique, and 2) to demonstrate the computational time advantage of Vertical Division technique. The approach is tested on 13 and 30 bus test system for integrated state estimation along with Vertical Division technique and the results are encouraging

    The impact of coronavirus disease 2019 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis

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    The coronavirus disease 2019 (COVID-19) pandemic has changed the epidemiology of respiratory syncytial virus (RSV) infection which accounts for most bronchiolitis and viral pneumonias in infants. This systematic review and meta-analysis aimed to quantitatively assess the effect of the COVID-19 pandemic on RSV-associated bronchiolitis among hospitalized infants. The study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesize the pooled proportion of infants having RSV-associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI). We identified and screened 189 articles and systematically reviewed 50 full texts. Eight qualified studies from Europe and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020–2021 were pooled by random-effects meta-analysis. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 bronchiolitis cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73, 22.43%, 95% prediction interval 0.032, 34.16). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20% (95% CI 12.01, 27.59%, 95% prediction interval 0.046, 42.35). There was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic

    Effect of exercise based interventions on sleep and circadian rhythm in cancer survivors—a systematic review and meta-analysis

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    Background Disrupted circadian rhythm commonly reported in cancer survivors is closely associated with cancer related fatigue, sleep disturbances and compromised quality of life. As more cancer survivors request non-pharmacological treatment strategies for the management of their chronic sleep-related symptoms, there is a need for meta-analyses of various interventions such as exercise on sleep and circadian rhythm disturbances. Methods A search for RCT’s was conducted in April 2020 and updated in July 2023 using relevant keywords for cancer, sleep, circadian rhythm and exercise interventions on PubMed, Scopus, Web of Science, PEDro and CINAHL. Results Thirty-six studies were included for qualitative analysis and 26, for meta-analysis. Thirty-five studies analyzed sleep outcomes, while five analyzed circadian rhythm. RCT’s studying the effect of aerobic exercise, resistance exercise, combined aerobic and resistance exercise, physical activity, yoga, or tai chi were included. Meta-analysis results showed significant exercise-related improvements on sleep quality assessed by Pittsburgh Sleep Quality index (PSQI) (SMD = −0.50 [−0.87, −0.13], p = 0.008), wake after sleep onset (WASO) (SMD = −0.29 [−0.53, −0.05], p = 0.02) and circadian rhythm, assessed by salivary cortisol levels (MD = −0.09 (95% CI [−0.13 to −0.06]) mg/dL, p < 0.001). Results of the meta-analysis indicated that exercise had no significant effect on sleep efficiency, sleep onset latency, total sleep time and circadian rhythm assessed by accelerometry values. Conclusion While some sleep and circadian rhythm outcomes (PSQI, WASO and salivary cortisol) exhibited significant improvements, it is still somewhat unclear what exercise prescriptions would optimize different sleep and circadian rhythm outcomes across a variety of groups of cancer survivors. Implication As exercise does not exacerbate cancer-related circadian rhythm and sleep disturbances, and may actually produce some significant benefits, this meta-analysis provides further evidence for cancer survivors to perform regular exercise
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