Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

АНАЛИЗ ПЕРЕДАЧИ ДЕФОРМАЦИИ В ВЫСОКОТЕМПЕРАТУРНОМ ПЛЕНОЧНОМ ТЕНЗОРЕЗИСТОРЕ

The bases of measured deformation transfer to sensing element of resistive strain sensor and deformation conversion to electric signal was considered. The methodology of study of deformation transfer in the resistive strain sensor was presented. This methodology is based on photoelasticity effect that is a property of some materials of double refraction while mechanical loads. The results of experimental research with polycarbonate model of resistive strain sensor are applied. The isochromatic curves of different model loads are presented. The comparison of two methods: the experimental research with polarization method based on photoelasticity effect and finite element method was carried out. The results of calculation of deformation transfer in the high-temperature film resistive strain sensor are presented. The coefficient of deformation transfer in the polycarbonate model of resistive strain sensor and respective coefficient of film resistive strain sensor under different temperatures were presented.Рассмотрены основы передачи измеряемой деформации чувствительному элементу тензорезистора и преобразования ее в приращение его электрического сигнала. Приведена методика исследования передачи деформации в тензорезисторе методом фотоупругости, использующей свойство некоторых материалов двойного лучепреломления при механическом нагружении. Предлагаются результаты экспериментального исследования модели тензорезистора из поликарбоната. Представлены картины изохром при различном нагружении модели тензорезистора. Проведено сравнение результатов экспериментального исследования поляризационным методом с данными расчета нагружения той же модели, полученными методом конечных элементов. Приведены результаты расчета передачи деформации в высокотемпературном пленочном тензорезисторе. Представлен коэффициент передачи деформации модели тензорезистора из поликарбоната, а также соответствующий коэффициент пленочного тензорезистора при различных температурных условиях его работы

Dielectric properties of addition and metathesis polynorbornenes with bulky side-substituents

© 2020 Elsevier Ltd Structure-property study of polynorbornenes for low dielectric permittivity materials was performed. Dielectric properties of various polynorbornenes bearing F-, Si- and alkenyl-side groups were investigated. The incorporation of both fluoroorganic- and Me3Si-groups as side substituents was found to be a fruitful tool to tune dielectric properties and to obtain polymeric materials with low values of dielectric relative permittivity (hereinafter dielectric permittivity) and the dissipation factors. Addition polynorbornenes with Me3Si- or alkenyl-side groups disclosed dielectric permittivity in the range of 2.07–2.34. Polynorbornenes containing fluouroorganic groups exhibited dielectric permittivity as low as 1.94–2.78. To the best of our knowledge, the achieved values of dielectric permittivity are the lowest ones among published for polynorbornenes. The investigated polymers also exhibited low or moderate values of the dissipation factor. The obtained results are considered and discussed along with the data of wide-angle X-ray diffraction, positron annihilating lifetime spectroscopy, low temperature nitrogen adsorption/desorption investigations

Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial

Background: Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4·5 h after symptom onset. Methods: We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0–1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0–1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. Findings: Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89–89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1·47, 95% CI 0·93 to 2·32; p=0·10). The difference in the rate of favourable outcome at day 90 was 9·5% (95% CI –1·7 to 20·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0·044). Interpretation: Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. Funding: The Russian Academy of Sciences. © 2021 Elsevier Lt