Luminescence of sapphire single crystals irradiated with high-power ion beams

Optical absorption, photo- and cathodoluminescence of a sapphire single crystal (α-Al 2 O 3 ) exposed to pulsed nanosecond radiation with high-power ion beams C + /H + with an energy of 300 keV and energy density 0.5-1.5 J/cm 2 were first investigated in this work. It was found that under ion irradiation accompanied by heating of sapphire up to melting, the formation of F-type centers and their aggregates associated with oxygen vacancies was observed in the crystals under study. These centers have luminescence bands at 330, 410 and 500 nm which depend on the type and wavelength of the optical excitation. The appearance of a new PL emission at 435 nm, presumably associated with a complex vacancy-impurity defect, was also observed in the photoluminescence spectra. © Published under licence by IOP Publishing Ltd.The work was supported by the initiative scientific project № 16.5186.2017/8.9 of the Ministry of Education and Science of the Russian Federation. Experiments on ion irradiation of sapphire was done at the KIPT as a part of the state task

Micromagnetic modeling of autoresonance oscillations in yttrium-iron garnet films

One of the main problems of magnonics is finding the ways of efficiently spin waves excitation in a magnet. This paper considers the method of nonlinear amplification by phase locking of amplitude of dynamic magnetization in yttrium-iron garnet film performed by micromagnetic modeling with MuMAX3 software taking into account the real materials parameters. It is shown that the excited magnetization precession can be considered as a autoresonance phenomena. The intensity of the autoresonance in ferrimagnetic yttrium-iron garnet films has threshold dependence on the chirp rate of the exciting magnetic field. © Published under licence by IOP Publishing Ltd.Russian Foundation for Basic Research, RFBR: 19-32-90014Ural Branch, Russian Academy of Sciences, UB RAS: МК-4959.2018.2The work was carried out within the framework of the state assignment on the topic "Spin" №АААА-А18-118020290104-2, "Alloys" № АААА-А19-119070890020-3 and project №18-10-2-37 of the Program of the UB RAS, supported by Grant of the President of the Russian Federation № МК-4959.2018.2, also the reported study was funded by RFBR, project number 19-32-90014

Synthesis of porous silicon with silver nanoparticles by low-energy ion implantation

© 2015, Pleiades Publishing, Ltd. In this paper, a new technique is proposed for synthesis of porous silicon (PSi) layers with silver nanoparticles based on the method of low-energy high-dose metal ion implantation into Si. In order to demonstrate this technique, the implantation at room temperature of a polished Si wafer by Ag+ ions with the ion energy of 30 keV, ion dose of 1.5 × 1017 ion/cm2, and ion current density of 8 µA/cm2 is carried out. Using methods of high resolution scanning electron and atomic-force microscopy, electron probe microanalysis, and Raman scattering, it is shown that ion implantation results in the formation, on the surface of irradiated Si, of a thin amorphous layer of PSi with the average pore size of 150–180 nm, a pore depth of about 100 nm, and wall thickness between pores of about 30–60 nm. Moreover, the PSi structure contains Ag nanoparticles 5–15 nm in size. It is established that, during the ion implantation, the sputtering of the Si surface by Ag+ ions takes place, which was not observed previously. Based on the data obtained, it is concluded that, in contrast to chemical techniques, the proposed physical technique for PSi formation can be integrated into the modern advanced process of fabricating and improving electronic circuits based on industrial ion implantation

Properties of the barium strontium titanate film on the silicon substrate

The reported study was supported of the Russian Foundation for Basic Research, research project No. 18-42-160005. The work is partially performed according to the Russian Government Program of Competitive Growth of Kazan Federal University. A.S. Elshin thanks the Russian Foundation for Basic Research for financial support, project No. 17-32-50047

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

Сопряженность экспрессии кальций-транспортирующих белков саркоплазматического ретикулума с их полиморфными вариантами генов и структурно-функциональным состоянием сердца пациентов с фибрилляцией предсердий

Aim. To investigate the relationship between the expression of Ca2+ handling proteins of the sarcoplasmic reticulum, polymorphic variants of their genes, and structural and functional parameters of the heart in patients with atrial fibrillation (AF).Materials and methods. The study included patients with AF. The patients underwent radiofrequency ablation, during which a myocardial biopsy was taken. The patients underwent echocardiography (EchoCG) before surgery. Polymorphic variants rs1860561 of the ATP2A2 gene and rs6684209 and rs7521023 of the CASQ2 gene were determined in the patients by real-time polymerase chain reaction (PCR), and the level of expression of SERCA2a and CASQ2 proteins in the myocardium was detected by immunoblotting.Results. Carriers of the GG genotype at rs1860561 of the ATP2A2 gene and CC genotype at rs6684209 of the CASQ2 gene were characterized by significantly higher expression of the corresponding proteins. Using cluster analysis, we identified groups of patients by the level of SERCA2a and CASQ2 expression: group 1 – patients with low protein content; group 2 – patients with high protein content. According to clinical and anamnestic parameters, the patients in the selected groups were homogeneous. In patients with high SERCA2a levels, the end systolic and diastolic volumes of the left ventricle (LV) were significantly higher than those in patients with low levels of this protein. The rates of early (peak E) and late left ventricular diastolic filling (peak A) were significantly lower in the group with high SERCA2a expression. A comparative analysis of EchoCG data of patients distributed by the level of CASQ2 expression in the myocardium did not reveal significant differences between the groups.Conclusion. The polymorphic variant rs1860561 of the ATP2A2 gene and rs6684209 of the CASQ2 gene can modulate the level of SERCA2a and CASQ2 expression. SERCA2a expression is associated with the functional and structural parameters of the heart in patients with AF.Цель. Исследовать взаимосвязь между экспрессией Са2+-транспортирующих белков саркоплазматического ретикулума, полиморфными вариантами их генов и структурно-функциональным состоянием сердца пациентов с фибрилляцией предсердий (ФП).Материалы и методы. В исследование включили пациентов с ФП. Больным проведена радиочастотная аблация, во время которой была взята биопсия миокарда. Пациентам проводили эхокардиографию (ЭхоКГ) до оперативного вмешательства. У больных определены полиморфные варианты rs1860561 гена ATP2A2 и rs6684209, rs7521023 гена CASQ2 методом полимеразной цепной реакции в режиме реального времени и уровень экспрессии белков SERCA2a и CASQ2 в миокарде методом иммуноблоттинга.Результаты. Для носителей генотипов GG rs1860561 гена ATP2A2 и CC rs6684209 гена CASQ2 характерны значимо более высокие экспрессии соответствующих белков. С помощью кластерного анализа были выявлены группы пациентов по уровню экспрессии SERCА2a и CASQ2: 1 – пациенты с низким содержанием белков; 2 – с высоким содержанием белков. По клинико-анамнестическим показателям пациенты отобранных групп оказались практически однородны. У пациентов с высоким уровнем SERCА2a величины конечного систолического и диастолического объемов левого желудочка (ЛЖ) были значимо больше, чем таковые у больных с низким уровнем этого белка. Скорости раннего (пик Е) и позднего диастолического наполнения (пик А) ЛЖ были статистически значимо ниже в группе с высоким уровнем экспрессии SERCА2a. Сравнительный анализ данных ЭхоКГ пациентов, распределенных по уровню экспрессии CASQ2 в миокарде, не выявил значимых различий между группами.Заключение. Генотипы rs1860561 гена ATP2A2 и rs6684209 гена CASQ2 могут модулировать уровень экспрессии SERCA2a и CASQ2. Экспрессия SERCA2a сопряжена с функционально-структурными показателями сердца пациентов с ФП.

Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype

The role that mechanical forces play in shaping the structure and function of the heart is critical to understanding heart formation and the etiology of disease but is challenging to study in patients. Engineered heart tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes have the potential to provide insight into these adaptive and maladaptive changes. However, most EHT systems cannot model both preload (stretch during chamber filling) and afterload (pressure the heart must work against to eject blood). Here, we have developed a new dynamic EHT (dyn-EHT) model that enables us to tune preload and have unconstrained contractile shortening of >10%. To do this, three-dimensional (3D) EHTs were integrated with an elastic polydimethylsiloxane strip providing mechanical preload and afterload in addition to enabling contractile force measurements based on strip bending. Our results demonstrated that dynamic loading improves the function of wild-type EHTs on the basis of the magnitude of the applied force, leading to improved alignment, conduction velocity, and contractility. For disease modeling, we used hiPSC-derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy due to mutations in the desmoplakin gene. We demonstrated that manifestation of this desmosome-linked disease state required dyn-EHT conditioning and that it could not be induced using 2D or standard 3D EHT approaches. Thus, a dynamic loading strategy is necessary to provoke the disease phenotype of diastolic lengthening, reduction of desmosome counts, and reduced contractility, which are related to primary end points of clinical disease, such as chamber thinning and reduced cardiac output

Феномен “несоответствия” режимов T2 и Т2-FLAIR как нейровизулизационный биомаркер генетического профиля анапластических астроцитом

The aim of the study was to assess T2/T2-FLAIR mismatch phenomenon as a predictor of particular genetic profile in the anaplastic astrocytoma group, including those tumors demonstrating contrast enhancement on MRI.Materials and methods. It is a retrospective study. All MR images were anonymized.MRI analysis. We studied 242 MRIs of patients with anaplastic astrocytomas (AA) and anaplastic oligodendrogliomas (AO) who were surgically treated at Burdenko Neurosurgery Center from 01.01.2017 to 31.12.2019. Among 242 patients we identified 23 (9.5%) whose MRI fulfilled the criteria for T2/FLAIR mismatch sign. The images were studied by 3 experienced neuroradiologist and patients were allocated to the T2/FLAIR mismatch group only upon consensus. Readers evaluated T2WI and FLAIR sequences of each MRI examination. They determined thr following characteristics of the tumours, using a binary scoring system for each: 1) presence or absence of homogeneous signal intensity on T2WI; 2) presence or absence of complete/near-complete hyperintence signal on T2WI, and relatively hypointence on FLAIR except for a hyperintense peripheral rim; 3) margins of lesion sharp or indistinct; 4) presence or absence of peritumoral edema. Discordant results were resolved by consensus with more experienced neuroradiologist.Histological examination and molecular markers. Histological examination was carried out by 2 qua lified pathologists after staining the preparations with hematoxylin and eosin and calculating the index of proliferative activity. The final diagnosis was established on the basis of a combination of morphological and molecular genetic studies. The material for the study was 242 biopsies from patients operated on at Burdenko Neurosurgery Center with anaplastic astrocytomas and anaplastic oligodendrogliomas WHO Grade III, fixed in 10% neutral formalin and embedded in Histomax (Leica) paraffin. Among 23 patients with T2 / FLAIR mismatch in 4 archival cases was performed an immunohistochemical study with Anti-IDH1 R132H (clone H09) (dianova) antibodies to establish the mutational status of the IDH-1 gene; in 19 remaining cases the IDH1 R132H mutation was studied by real-time PCR using self-selected primers and probes. One of the samples showed the wild type IDH1 R132H and it was further investigated by Sanger sequencing to determine the mutational status of the IDH1 and IDH2 genes using direct primers.Determination of 1p / 19q co-deletion was performed by in situ fluorescence hybridization using a ZytoLight Glioma 1p / 19q Probe Set (ZytoVision).Study results. T2/T2-FLAIR mismatch sign was found in 23 patients with AA, in 8 cases tumors demonstrated contrast enhancement, including 3 of them with substantial enhancement. The mean age in the T2/T2-FLAIR mismatch group was lower than in the main group (34 vs. 42.7 years), as well as percentage of patients with contrastenhancing tumors (36.4% vs. 55.8%). The proportion of tumors with substantial contrast enhancement was similar in both groups (37.5% vs. 46.7%).DiscussionS.H. Patel et al. in their pioneer paper demonstrated 12% frequency of T2/FLAIR mismatch sign in the experimental group (125 patients) and 17% in validation group (60 patients). M.P.G. Broen et al. present with a higher rate of the sign – 25%. S. Deguchi et al. have demonstrated even higher frequency of T2/FLAIR mismatch among IDHmutant grade II astrocytomas -45%. Our results revealed 9.5% rate of this sign.The first article declaring less than 100% specificity of T2/FLAIR mismatch sign, after great success and acknowledgement of this predictive diagnostic method, was published by T.A. Juratli et al. 2019: the sign was observed in 73% of patients (versus 12% in Patel’s group). Herewith, 29% of patients with T2/FLAIR mismatch sign demonstrated both IDH-1 mutation and 1p/19q co-deletion. The reason for this phenomenon were less strict inclusion criteria in Juratli’s study. Moreover, authors did not specify the number of patients with contrast-enhancing tumors, although according to R. Jain et al., all these tumors must be excluded from the study. It is noteworthy, that even with these non-strict inclusion criteria, T2/FLAIR mismatch sign has demonstrated 100% predictive value for IDH-1 mutation in Jurartli’s study (none of the patients presented with IDH-wild type tumour). In the meta-analysis performed by Goyal et al. 2019, based on several T2/FLAIR mismatch studies with 746 patients, authors demonstrated high specificity (98.5%) and low sensitivity (33.7%) of this sign for detecting IDH-1+ and 1p/19q- cooperation. The main conclusion of this paper is that T2/FLAIR mismatch sign has high specificity and low sensitivity for detecting IDH-1 mutation, but not 1p/19q co-deletion, although there might be exceptions from this rule.Recent studies devoted to the T2/FLAIR mismatch sign included mostly grade II gliomas and a small amount of AA and AO, emphasizing that those tumors did not demonstrate contrast enhancement M.P.G. Broen, S.H. Patel. Moreover, this characteristic is referred as a necessary qualification for T2/FLAIR mismatch sign, since contrastenhancing parts of the tumor may overlap area of interest and confound MRI signal in other sequences.Results of our study convincingly demonstrate possibility of T2/FLAIR mismatch sign in grade III gliomas with contrast enhancement. We observed this phenomenon in 8 cases out of 22 (36.4%). Moreover, among those8 patients, 3 presented with intensive contrast enhancement. Comparing main group with control one, we revealed, that mean age in the group with T2/FLAIR mismatch sign was lower (34 vs. 42.7). and among 8 patients with contrast enhancement only 1 was older than 40 years. Tumors from the main group demonstrated contrast enhancement significantly on a more frequent basis (55.8% vs. 36.4%), meanwhile rate of intensive contrast enhancement was similar (46.7% vs. 37.5%). Thus, we demonstrated correlation between tumour grade and contrast enhancement and T2/FLAIR mismatch sign.Earlier studies made attempts to predict tumor mutational status upon MRI: for instance, frontal lobe tumours, not spreading to the midline structures more often demonstrate IDH mutation Z.L. Sun, A. Lai. Moreover, it is wellknown fact, that IDH+ gliomas present with more distinct borders, more homogeneous MR-signal and less frequently demonstrate contrast enhancement A. Lai, G. Reyes-Botero. However, all these characteristics are very subjective and only advisory. More explicit results can be revealed by using MR-perfusion P. Kickingereder, MR-spectroscopy (2-hydroxyglutarat) M.I. de la Fuente and PET B. Suchorska 2017. However, abovementioned methods are not so widespread, unlike MRI, which is capable to predict genetic profile (IDH and 1p/19q status) with almost 100% accuracy. Unconditioned weakness of this method is qualitative, not quantitative his nature, sometimes demanding discussion and still not unambiguous. Probably, future achievements in neuroradiology will allow to perform quantitative analysis of MR-signal and formalize T2/FLAIR mismatch sign.It is difficult to overestimate T2/FLAIR mismatch sign for diagnosis, surgery planning and overall treatment strategy. These aspects were disputed for grade II gliomas Sofietti, A.S. Jakola, M.M.J. Wijnenga. Anaplastic tumours possess worse prognosis and this additional information might be of extreme use. T. Kawaguchi et al. evaluated correlation between radical resection and prognosis of treatment for AA tumours with and without IDHmutation: it turned out, that for IDH-negative tumors radical surgery did not significantly affect overall survival (although these groups demonstrated different OS). On the contrary, radical resection significantly affected OS for IDH+ gliomas. Our study has demonstrated capability T2/FLAIR mismatch sign detection for anaplastic gliomas regardless of tumour contrast enhancement.It is still unclear why not all IDH-positive 1p/19q-negative gliomas demonstrate T2/FLAIR mismatch sign. These “exceptions” were documented earlier by S.H. Patel, M.P.G. Broen for grade II gliomas and in our study for grade III gliomas: only 23 out of 26 patients with above-mentioned molecular profile presented with T2/FLAIR mismatch sign. S.H. Patel et al. speculate about activation of pathways by mTOR protein, which is involved in IDH-positive gliomas malignant change H. Wakimoto, but lack of data precludes authors from statistically significant conclusions.Conclusion. Study results confirm the hypothesis of relevance of T2/T2-FLAIR mismatch sign for anaplastic atrocytomas with contrast enhancement on MRI as highly specific biomarker for tumor genetic profile. In some cases information provided by MRI in this group of patients may improve preoperative diagnostic and affect treatment strategy. Цель исследования: оценка релевантности феномена несоответствия режимов T2 и T2-FLAIR (T2-FLAIR mismatch) в качестве предиктора генетического профиля анапластических астроцитом, в том числе накапливающих контрастный препарат при МРТ-исследовании.Материал и методы. Ретроспективно были проанализированы МР-изображения 242 пациентов, проходивших лечение в ФГАУ “НМИЦ нейрохирургии имени Н.Н. Бурденко” Минздрава России с диагнозом “анапластическая астроцитома” или “анапластическая олигодендроглиома”, тремя нейрорентгенологами на предмет выявления признака T2-FLAIR mismatch и наличия/отсутствия гомогенного повышенного сигнала на Т2-изображениях. Пациенты были включены в основную группу только в случае единого мнения всех трех специалистов относительно названных особенностей изображений опухоли.Результаты. Признак T2-FLAIR mismatch был выявлен у 23 пациентов, у 8 из них опухоль накапливала контрастный препарат при МР-исследовании, в том числе в 3 случаях – выраженно. Возраст пациентов в подгруппе с признаком T2-FLAIR mismatch был достоверно ниже, чем в основной группе (34 года против 42,7 года), как и доля пациентов с контрастируемыми опухолями (36,4% против 55,8%); при этом процент опухолей, выраженно контрастирующихся по МРТ, оказался сопоставим (37,5% против 46,7%).Заключение. Результаты нашего исследования подтверждают релевантность феномена T2-FLAIR mismatch в оценке анапластических астроцитом, в том числе накапливающих контрастный препарат, как высокоспецифичного неинвазивного биомаркера генетического профиля опухоли. Полученные данные в ряде случаев позволят изменить подход к дооперационной диагностике и планированию лечения для определенной части пациентов с анапластическими астроцитомами.

Laser writing of coherent colour centres in diamond

Optically active point defects in crystals have gained widespread attention as photonic systems that can find use in quantum information technologies [1,2]. However challenges remain in the placing of individual defects at desired locations, an essential element of device fabrication. Here we report the controlled generation of single nitrogen-vacancy (NV) centres in diamond using laser writing [3]. The use of aberration correction in the writing optics allows precise positioning of vacancies within the diamond crystal, and subsequent annealing produces single NV centres with up to 45% success probability, within about 200 nm of the desired position. Selected NV centres fabricated by this method display stable, coherent optical transitions at cryogenic temperatures, a pre-requisite for the creation of distributed quantum networks of solid-state qubits. The results illustrate the potential of laser writing as a new tool for defect engineering in quantum technologies