53BP1 acts at the crossroads between DNA repair and p53‐mediated stress response. With its interactors p53 and USP28, it is part of the mitotic surveillance (or mitotic stopwatch) pathway (MSP), a ...sensor that monitors the duration of cell division, promoting p53‐dependent cell cycle arrest when a critical time threshold is surpassed. Here, we show that Polo‐like kinase 1 (PLK1) activity is essential for the time‐dependent release of 53BP1 from kinetochores. PLK1 inhibition, which leads to 53BP1 persistence at kinetochores, prevents cytosolic 53BP1 association with p53 and results in a blunted MSP. Strikingly, the identification of CENP‐F as the kinetochore docking partner of 53BP1 enabled us to show that measurement of mitotic timing by the MSP does not take place at kinetochores, as perturbing CENP‐F‐53BP1 binding had no measurable impact on the MSP. Taken together, we propose that PLK1 supports the MSP by generating a cytosolic pool of 53BP1 and that an unknown cytosolic mechanism enables the measurement of mitotic duration.
Synopsis
Following an abnormally extended mitosis, cells activate p53 via 53BP1. Surprisingly, 53BP1 kinetochore localization is dispensable for this process, whereas PLK1 activity, a negative regulator of 53BP1 localization, appears to be essential.
53BP1 kinetochore localization is dispensable for the mitotic surveillance (or mitotic stopwatch) pathway (MSP).
PLK1 is required for the MSP.
PLK1 activity promotes 53BP1 kinetochore dynamics and 53BP1‐p53 complex formation.
Following an abnormally extended mitosis, cells activate p53 via 53BP1. Surprisingly, 53BP1 kinetochore localization is dispensable for this process, whereas PLK1 activity, a negative regulator of 53BP1 localization, appears to be essential.
Stopwatch is designed to quantify the elapses time between the start activation and deactivation. To ensure the precision of the time taken, calibration of the device is essential. National Institute ...of Standard and Technology (NIST) has provide complete guidelines on the stopwatch and timer calibration. However, the standards guidelines usually use manual calibration personnel hence may possibly cause inefficiency for calibration works. The 'Stopwatch Verification Platform' is a prototype aimed to replace the manual handling of digital stopwatch calibration with an automated timer-controlled device, without interfering with NIST recommended practice. The 'Stopwatch Verification Platform' is able to automatically trigger start and stop the reference and test stopwatches by integrating with precise timer controller and specific relay connections. The timer controller circuitry is integrated with the reference stopwatch circuitry, with 0.001 second resolutionIt is capable in verifying more units of stopwatches by using one reference. The measurement procedures do not contradict with the NIST recommended practice. This prototype does not alter the uncertainties calculation because it is a well-developed standard formula which is set by international standard.
Randomized reachability analysis is an efficient method for detection of safety violations. Due to the under-approximate nature of the method, it excels at quick falsification of models and can ...greatly improve the model-based development process: using lightweight randomized methods early in the development for the discovery of bugs, followed by expensive symbolic verification only at the very end. We show the scalability of our method on a number of timed automata and stopwatch automata models of varying sizes and origin. Among them, we revisit the schedulability problem from the Herschel–Planck industrial case study, where our new method finds the deadline violation three orders of magnitude faster: some cases could previously be analyzed by statistical model checking in 23 h and can now be checked in 23 s. Moreover, a deadline violation is discovered in a number of cases that were previously intractable. We have implemented the Randomized reachability analysis—and made it available—in the tool
Uppaal
. Finally, we provide an evaluation of the strengths and weaknesses of Random reachability analysis exploring exactly which types of model features hamper method’s efficiency.
The main objective of present study was to evaluate inter-rater reliability and concurrent validity of Side Hop Test stopwatch vs. force plates timing, and to determine the number of sessions and ...trials required to minimize the effects of learning on Side Hop Test total time and limb symmetry index. Fifteen healthy male physical education students (mean ± SD: age, 23 ± 3 years; height, 181 ± 9 cm; and weight 72 ± 6 kg) participated. Side Hop Test total time (stopwatch and force plates) of left and right leg, and limb symmetry index (force plates) were obtained over seven sessions conducted 5–7 days apart. Time recordings of two raters were similar (
t
= −0.56,
p
> 0.05) with high reliability (all ICC >0.99 and CV% <0.1) and no systematic bias when compared to force plate data (
p
> 0.05; for rater 1 and 2, respectively). Total time improved across the Sessions (
F
= 25.87,
p
< 0.01,
ω
2
= 0.18) and Trials (
F
= 68.15,
p
< 0.01,
ω
2
= 0.10), with no significant interaction between factors. No between-leg differences were detected (
F
= 0.52,
p
> 0.05,
ω
2
= 0.001). Limb symmetry index ranged from 0.999 to 1.055 across all sessions and trials (all
p
> 0.05 and
ω
2
< 0.00). Due to low coefficient of correlation, high interclass correlation coefficient, and the lack in heteroscedasticity, stopwatch measurements are valid to measure total time in the Side Hop Test. Moreover, stopwatch measurements could be reliably used to measure total time in the Side Hop Test, while the test could be administrated with only one experienced rater. Unlike total times, findings on limb symmetry index suggest it could be reliably assessed after seven familiarization sessions.
Slow gait speed prospectively predicts elevated risk of adverse events such as falls, morbidity, and mortality. Additionally, gait speed under a cognitively demanding challenge (dual-task gait) ...predicts further cognitive decline and dementia incidence. This evidence has been mostly collected using electronic walkways; however, not all clinical set ups have an electronic walkway and comparability with simple manual dual-gait speed testing, like a stopwatch, has not yet been examined. Our main objective was to assess concurrent-validity and reliability of gait speed assessments during dual-tasking using a stopwatch and electronic walkway in older adults with mild and subjective cognitive impairment (MCI and SCI).
Cross-sectional, reliability study.
Clinic based laboratory at an academic hospital in London, ON, Canada.
237 walk tests from 34 community-dwelling participants (mean age 71.84 SD 5.38; 21 female - 62%, 13 male - 38%) with SCI and MCI. were included from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study.
Each participant performed seven walk tests: three single gait walks at their normal pace, three dual-task walks (walking and counting backwards by one, by sevens, and naming animals), and one fast walk.
Gait speed (cm/s) for each walk was measured simultaneously with an electronic walkway (Zeno Mat®) and a handheld stopwatch (Ultrak chronometer®). Dual-task cost (DTC) was calculated for the three individual dual-task walks as ((single gait speed − dual-task gait speed) / single gait speed) ∗ 100. Level of agreement between the two measurement methods was analyzed using Pearson correlations, paired t-tests, and Bland-Altman plots.
Gait speed was consistently lower when measured with the stopwatch than with the electronic walkway (mean speed difference: 10.6 cm/s ± 5.1, p < 0.001). Calculating DTC, however, yielded very similar results with both methods (mean DTC difference: 0.19 ± 1.18, p = 0.872). The higher the DTC, the closer the measurement between methods.
Assessing and calculating DTC with a stopwatch is simple, accessible and reliable. Its validity and reliability were high in this clinical sample of community older adults with SCI and MCI,
•Gait speed is an important vital sign in older populations at risk for dementia.•This study measured dual task cost speed in older adults with cognitive impairment.•Dual-task cost speed is comparable using a stopwatch and an electronic gait mat.•A stopwatch is a reliable and valid way to measure dual-task cost in older adults.•This novel and freely available tool can be used by clinicians measuring gait speed.
The production line system is an important problem for the majority of manufacturing industries in Indonesia. PT XYZ is manufacturing company focuses on general construction and mining products ...supplier. Friction Bolt Stabilizer is one PT XYZ’s superior products. The problem in the friction bolt stabilizer production line is unbalanced distribution of work elements. Based on these problems, in this study a solution is provided by comparing the actual production line with the results of line balancing analysis. There are two methods used, namely Ranked Positional Weight and Killbridge Western Heuristic. The result is that the Killbridge western heuristic method produces the best design with a performance level of 91% line efficiency, 9% balance delay, a total of four workstations and a smoothness index value of 401.55 seconds.
BACKGROUND: Speech recognition is becoming increasingly common in the national healthcare system. One of the first specialties to implement this technology on a large scale was radiology. However, ...the efficiency of voice input and its effect on the length of time required to complete medical records remain unresolved. AIM: To assess the efficiency of speech recognition in generating radiological protocols of different modalities and types. METHODS: The retrospective study was conducted at the Moscow Reference Center of the Research and Practical Clinical Center for Diagnostics and Telemedicine Technologies of the Moscow Department of Health. A total of 12,912 radiological reports on fluorography, mammography, chest computed tomography (CT), contrast-enhanced magnetic resonance imaging (MRI) of the brain, and contrast-enhanced CT of the abdomen and pelvis were included in the study by simple random sampling. The size of all samples exceeded 766 reports, calculated with regard to the size of the general population of over 100,000 reports. The Voice2Med software was used to fill in the radiological protocols. Intergroup comparison was performed using the MannWhitney U-test with a statistical significance level of 0.05. RESULTS: The average duration of generating fluorographic protocols in the keyboard and voice input groups was 189.9 s (0:03:09) and 236.2 s (0:03:56), respectively (p 0.0001). For mammographic reports, the duration was 387.1 s (0:06:27) and 444.8 s (0:07:24), respectively (p 0.0001). For radiographic reports, it amounted to 247.8 s (0:04:07) and 189.0 s (0: 03:09), respectively (p 0.0001), and for chest CT, it was 379.7 s (0:06:19) and 382.7 s (0:06:22), respectively (p=0.12). For MRI of the brain, the protocols were generated for 709.9 s (0:11:49) and 559.9 s (0: 09:19), respectively (p 0.0001), and for contrast-enhanced chest, abdominal, and pelvic CT scans, it took 2714.6 s (0:45:15) and 1778.4 s (0:29:38), respectively. Voice input slowed down the preparation time of mammographic and fluorographic protocols. This is due to the use of a structured electronic medical document in medical facilities to describe the results of the examinations. Speech recognition showed the greatest efficiency in generating MRI and CT protocols. Such reports contain a large number of pathological changes, both target and incidental findings, which requires a detailed description by the radiologist in the examination protocol. CONCLUSIONS: Speech recognition in generating radiological protocols showed different efficiency depending on the modality and type of the radiological protocol filled in using the voice input system. This approach is optimal for describing CT and MRI scans.
Time estimation is an important element of the effort evaluation process, which is indispensable along many phases of business development from bidding for the competitive contract to design and ...production phases. In particular, the time estimates are useful in the resource planning process, especially when the precision of the provided estimates is quantitatively characterised. We propose in this work an approach that combines the techniques developed within predetermined time methods (such as MODAPTS and MINIMOST) with the statistical techniques that use the real data (collected along the stopwatch time measurements). Our approach allows to obtain not only time estimates themselves, but also the confidence intervals for them. This information helps the practitioner to decide whether provided time estimates (coupled with accuracy parameters) meet his criteria. The proposed approach can be used in time estimations for the project containing several operations of different nature, and the application of our methodology is discussed in detail for the case of fenestration industry.
Various information systems have been implemented in most of the customized panel furniture companies in China, resulting in increased production difficulty and informational isolation. Enterprises ...need to adopt more systematic, scientific, and information-based methods to guide the production on the shop floor. Packaging optimization is important because it promotes sustainable development in furniture enterprise. Through the examination of the packaging process in customized panel furniture companies, this study investigated the bottleneck problems of the packaging process, which are predominantly focused on the calculation of the optimal packaging scheme and the upgrade of information systems. After exploring the theories and methods to solve the existing bottleneck problems, the heuristic algorithm was applied to obtain the optimal packaging schemes and complete the upgrade of packaging process information system. Based on the intelligent packaging software in company A, the Taguchi method was applied to find the best optimization parameters, which was proven effective in comparison with the original packaging solution. The number of packaging was decreased by 3.0%, and the amount of packaging corrugated paper decreased by 12.4. The packaging efficiency represented by the total packaging time showed a significant improvement despite the unit packaging time having increased by 2.0%.
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