Об устойчивости движения математического маятника, взаимодействующего со струной

В линейной и нелинейной постановках решена задача об устойчивости стационарных движений однозвенного маятника в гибридной модели механической системы, состоящей из горизонтально закрепленной струны, нагруженной колеблющейся сосредоточенной массой.У лінійній і нелінійній постановках розв'язано задачу про стійкість стаціонарних рухів одноланкового маятника в гібридній моделі механічної системи, яка складається з горизонтально розміщеної струни, навантаженої коливною зосередженою масою.The problem of stability of the stationary motions of a single-mass pendulum in the hybrid model of one mechanical system is solved in the linear and nonlinear statements. The mechanical system consists of a string which is horizontally disposed and loaded by an oscillating localized mass

Local conservation scores without a priori assumptions on neutral substitution rates

<p>Abstract</p> <p>Background</p> <p>Comparative genomics aims to detect signals of evolutionary conservation as an indicator of functional constraint. Surprisingly, results of the ENCODE project revealed that about half of the experimentally verified functional elements found in non-coding DNA were classified as unconstrained by computational predictions. Following this observation, it has been hypothesized that this may be partly explained by biased estimates on neutral evolutionary rates used by existing sequence conservation metrics. All methods we are aware of rely on a comparison with the neutral rate and conservation is estimated by measuring the deviation of a particular genomic region from this rate. Consequently, it is a reasonable assumption that inaccurate neutral rate estimates may lead to biased conservation and constraint estimates.</p> <p>Results</p> <p>We propose a conservation signal that is produced by local Maximum Likelihood estimation of evolutionary parameters using an optimized sliding window and present a Kullback-Leibler projection that allows multiple different estimated parameters to be transformed into a conservation measure. This conservation measure does not rely on assumptions about neutral evolutionary substitution rates and little a priori assumptions on the properties of the conserved regions are imposed. We show the accuracy of our approach (KuLCons) on synthetic data and compare it to the scores generated by state-of-the-art methods (phastCons, GERP, SCONE) in an ENCODE region. We find that KuLCons is most often in agreement with the conservation/constraint signatures detected by GERP and SCONE while qualitatively very different patterns from phastCons are observed. Opposed to standard methods KuLCons can be extended to more complex evolutionary models, e.g. taking insertion and deletion events into account and corresponding results show that scores obtained under this model can diverge significantly from scores using the simpler model.</p> <p>Conclusion</p> <p>Our results suggest that discriminating among the different degrees of conservation is possible without making assumptions about neutral rates. We find, however, that it cannot be expected to discover considerably different constraint regions than GERP and SCONE. Consequently, we conclude that the reported discrepancies between experimentally verified functional and computationally identified constraint elements are likely not to be explained by biased neutral rate estimates.</p

Neurotoxicity with high dose disulfiram and vorinostat used for HIV latency reversal

OBJECTIVE: To examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is safe and can enhance HIV latency reversal. DESIGN: Vorinostat and disulfiram, can increase HIV transcription in people with HIV (PWH) on antiretroviral therapy (ART). Together these agents may lead to significant HIV latency reversal. METHODS: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated (CA) unspliced (US) RNA as a marker of latency reversal, HIV DNA in CD4+ T-cells, plasma HIV RNA and plasma concentrations of ART, vorinostat and disulfiram. RESULTS: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4- and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8-37 (peak 81 copies/mL) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. CONCLUSIONS: The combination of prolonged high dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal

Discovery of Rubidium, Strontium, Molybdenum, and Rhodium Isotopes

Currently, thirty-one rubidium, thirty-five strontium, thirty-five molybdenum and thirty-eight rhodium isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.Comment: To be published in Atomic Data and Nuclear Data Table

Daily rhythms of the sleep-wake cycle

The amount and timing of sleep and sleep architecture (sleep stages) are determined by several factors, important among which are the environment, circadian rhythms and time awake. Separating the roles played by these factors requires specific protocols, including the constant routine and altered sleep-wake schedules. Results from such protocols have led to the discovery of the factors that determine the amounts and distribution of slow wave and rapid eye movement sleep as well as to the development of models to determine the amount and timing of sleep. One successful model postulates two processes. The first is process S, which is due to sleep pressure (and increases with time awake) and is attributed to a 'sleep homeostat'. Process S reverses during slow wave sleep (when it is called process S'). The second is process C, which shows a daily rhythm that is parallel to the rhythm of core temperature. Processes S and C combine approximately additively to determine the times of sleep onset and waking. The model has proved useful in describing normal sleep in adults. Current work aims to identify the detailed nature of processes S and C. The model can also be applied to circumstances when the sleep-wake cycle is different from the norm in some way. These circumstances include: those who are poor sleepers or short sleepers; the role an individual's chronotype (a measure of how the timing of the individual's preferred sleep-wake cycle compares with the average for a population); and changes in the sleep-wake cycle with age, particularly in adolescence and aging, since individuals tend to prefer to go to sleep later during adolescence and earlier in old age. In all circumstances, the evidence that sleep times and architecture are altered and the possible causes of these changes (including altered S, S' and C processes) are examined

Flavopiridol Pharmacogenetics: Clinical and Functional Evidence for the Role of SLCO1B1/OATP1B1 in Flavopiridol Disposition

Flavopiridol is a cyclin-dependent kinase inhibitor in phase II clinical development for treatment of various forms of cancer. When administered with a pharmacokinetically (PK)-directed dosing schedule, flavopiridol exhibited striking activity in patients with refractory chronic lymphocytic leukemia. This study aimed to evaluate pharmacogenetic factors associated with inter-individual variability in pharmacokinetics and outcomes associated with flavopiridol therapy.Thirty-five patients who received single-agent flavopiridol via the PK-directed schedule were genotyped for 189 polymorphisms in genes encoding 56 drug metabolizing enzymes and transporters. Genotypes were evaluated in univariate and multivariate analyses as covariates in a population PK model. Transport of flavopiridol and its glucuronide metabolite was evaluated in uptake assays in HEK-293 and MDCK-II cells transiently transfected with SLCO1B1. Polymorphisms in ABCC2, ABCG2, UGT1A1, UGT1A9, and SLCO1B1 were found to significantly correlate with flavopiridol PK in univariate analysis. Transport assay results indicated both flavopiridol and flavopiridol-glucuronide are substrates of the SLCO1B1/OATP1B1 transporter. Covariates incorporated into the final population PK model included bilirubin, SLCO1B1 rs11045819 and ABCC2 rs8187710. Associations were also observed between genotype and response. To validate these findings, a second set of data with 51 patients was evaluated, and overall trends for associations between PK and PGx were found to be consistent.Polymorphisms in transport genes were found to be associated with flavopiridol disposition and outcomes. Observed clinical associations with SLCO1B1 were functionally validated indicating for the first time its relevance as a transporter of flavopiridol and its glucuronide metabolite. A second 51-patient dataset indicated similar trends between genotype in the SLCO1B1 and other candidate genes, thus providing support for these findings. Further study in larger patient populations will be necessary to fully characterize and validate the clinical impact of polymorphisms in SLCO1B1 and other transporter and metabolizing enzyme genes on outcomes from flavopiridol therapy

Measuring teachers' enjoyment, anger, and anxiety : The Teacher Emotions Scales (TES)

The emotions of teachers are considered relevant not only for their own well-being but also for the functioning of classrooms. Nevertheless, research on teacher emotions has been slow to emerge, and scales for their assessment via self-report are generally lacking. In the present research we developed four-item scales for three emotions considered most relevant in the context of teaching: enjoyment, anger, and anxiety (Teacher Emotions Scales, TES). Based on data of 944 teachers, we tested German and English language versions of the TES for reliability, internal and external validity, and cross-language equivalence, while exploring the utility of both a general and a student-group specific variant. All scales proved to be highly reliable, and confirmatory factor analysis supported internal validity by showing that three-factor models (enjoyment, anger, and anxiety) were superior to single-factor or two-factor (positive vs. negative affect) models. The external validation analyses provided consistent evidence for theoretically meaningful relations with teachers' general affect, burnout, job satisfaction, and teacher self-efficacy. These findings were robust across multiple studies. In addition, consistent relationships with student ratings of teaching behaviors were found. Analyses of measurement invariance revealed that the English and the German language versions were fully structurally equivalent und displayed metric invariance

Optimized cross-layer forward error correction coding for H.264 AVC video transmission over wireless channels

Forward error correction (FEC) codes that can provide unequal error protection (UEP) have been used recently for video transmission over wireless channels. These video transmission schemes may also benefit from the use of FEC codes both at the application layer (AL) and the physical layer (PL). However, the interaction and optimal setup of UEP FEC codes at the AL and the PL have not been previously investigated. In this paper, we study the cross-layer design of FEC codes at both layers for H.264 video transmission over wireless channels. In our scheme, UEP Luby transform codes are employed at the AL and rate-compatible punctured convolutional codes at the PL. In the proposed scheme, video slices are first prioritized based on their contribution to video quality. Next, we investigate the four combinations of cross-layer FEC schemes at both layers and concurrently optimize their parameters to minimize the video distortion and maximize the peak signal-to-noise ratio. We evaluate the performance of these schemes on four test H.264 video streams and show the superiority of optimized cross-layer FEC design.Peer reviewedElectrical and Computer Engineerin

'I'm not going to tell you cos you need to think about this': A conversation analysis study of managing advice resistance and supporting autonomy in undergraduate supervision

This is an accepted manuscript of an article published by Springer in Postdigital Science and Education, available online at: https://doi.org/10.1007/s42438-020-00194-5 The accepted version of the publication may differ from the final published version.This article firstly, critically analyses a face-to-face supervision meeting between an undergraduate and a supervisor, exploring how the supervisor handles the twin strategies of fostering autonomy while managing resistance to advice. Conversation Analysis is used as both a theory and a method, with a focus on the use of accounts to support or resist advice. The main contribution is the demonstration of how both the supervisor and student are jointly responsible for the negotiation of advice, which is recycled and calibrated in response to the student’s resistance. The supervisor defuses complaints by normalising them, and moving his student on to practical solutions, often with humour. He lists his student’s achievements as the foundation on which she can assert agency and build the actions he recommends. Supervisor-student relationships are investigated through the lens of the affective dimensions of learning, to explore how caring or empathy may serve to reduce resistance and make advice more palatable. By juxtaposing physically present supervision with digitally-mediated encounters, while acknowledging their mutual entanglement, the postdigital debate is furthered. In the context of Covid-19, and rapid decisions by universities to bring in digital platforms to capture student-teacher interactions, the analysis presented is in itself an act of resistance against the technical control systems of the academy and algorithmic capitalism