On the effect of image denoising on galaxy shape measurements

Weak gravitational lensing is a very sensitive way of measuring cosmological parameters, including dark energy, and of testing current theories of gravitation. In practice, this requires exquisite measurement of the shapes of billions of galaxies over large areas of the sky, as may be obtained with the EUCLID and WFIRST satellites. For a given survey depth, applying image denoising to the data both improves the accuracy of the shape measurements and increases the number density of galaxies with a measurable shape. We perform simple tests of three different denoising techniques, using synthetic data. We propose a new and simple denoising method, based on wavelet decomposition of the data and a Wiener filtering of the resulting wavelet coefficients. When applied to the GREAT08 challenge dataset, this technique allows us to improve the quality factor of the measurement (Q; GREAT08 definition), by up to a factor of two. We demonstrate that the typical pixel size of the EUCLID optical channel will allow us to use image denoising.Comment: Accepted for publication in A&A. 8 pages, 5 figure

Что мы знаем о возможности предсказания потенциальной эффективности и безопасности метотрексата путем определения концентрации его метаболитов при ревматоидном артрите?

Rheumatoid arthritis (RA) is characterized by a progressive course with the formation of joint deformities and the development of severe functional disorders. The most favorable conditions for changing the course of the disease emerge in the first months after its onset. Methotrexate (MTX) occupies a leading position in the treatment of RA. There is a need to develop tools that will be able to predict the efficacy and tolerability of MTX at the earliest stages of RA treatment. The concentration of active metabolites of MTX is considered as a potential biomarker that enables one to predict what response to therapy with this drug will be.The paper analyzes the most relevant works devoted to the study of the concentration of active MTX metabolites polyglutamates (MTX PGs) in patients with RA. It is shown that the presented studies do not cover all the possibilities of therapeutic drug monitoring, in particular the determination of the levels of MTX PGs in mononuclear cells over time. Further investigation is needed to develop an objective approach to prescribing MTX in RA patients.Ревматоидный артрит (РА) характеризуется прогрессирующим течением с формированием деформаций суставов и развитием тяжелых функциональных нарушений. Наиболее благоприятные условия для изменения течения болезни складываются в первые месяцы после ее начала. Метотрексат (МТ) занимает ведущее место в терапии РА. Назрела необходимость в разработке инструментов, которые позволят предсказывать эффективность и переносимость МТ на самых ранних этапах лечения РА. Концентрация активных метаболитов МТ рассматривается как потенциальный биомаркер, с помощью которого возможно предсказать, каким будет ответ на терапию этим препаратом.В статье приводится анализ наиболее актуальных работ, посвященных изучению концентрации активных метаболитов МТ – полиглутаматов (МТПГ) у больных РА. Показано, что представленные исследования не охватывают все возможности терапевтического лекарственного мониторинга, в частности определение содержания МТПГ в мононуклеарах в динамике. Необходимы дальнейшие исследования с целью разработки объективного подхода к назначению МТ у больных РА

Image analysis for cosmology: results from the GREAT10 Galaxy Challenge

In this paper, we present results from the weak-lensing shape measurement GRavitational lEnsing Accuracy Testing 2010 (GREAT10) Galaxy Challenge. This marks an order of magnitude step change in the level of scrutiny employed in weak-lensing shape measurement analysis. We provide descriptions of each method tested and include 10 evaluation metrics over 24 simulation branches. GREAT10 was the first shape measurement challenge to include variable fields; both the shear field and the point spread function (PSF) vary across the images in a realistic manner. The variable fields enable a variety of metrics that are inaccessible to constant shear simulations, including a direct measure of the impact of shape measurement inaccuracies, and the impact of PSF size and ellipticity, on the shear power spectrum. To assess the impact of shape measurement bias for cosmic shear, we present a general pseudo-Cℓ formalism that propagates spatially varying systematics in cosmic shear through to power spectrum estimates. We also show how one-point estimators of bias can be extracted from variable shear simulations. The GREAT10 Galaxy Challenge received 95 submissions and saw a factor of 3 improvement in the accuracy achieved by other shape measurement methods. The best methods achieve sub-per cent average biases. We find a strong dependence on accuracy as a function of signal-to-noise ratio, and indications of a weak dependence on galaxy type and size. Some requirements for the most ambitious cosmic shear experiments are met above a signal-to-noise ratio of 20. These results have the caveat that the simulated PSF was a ground-based PSF. Our results are a snapshot of the accuracy of current shape measurement methods and are a benchmark upon which improvement can be brought. This provides a foundation for a better understanding of the strengths and limitations of shape measurement method

Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement

The identification of low-frequency antigen-specific CD4+ T cells is crucial for effective immunomonitoring across various diseases. However, this task still encounters experimental challenges necessitating the implementation of enrichment procedures. While existing antigen-specific expansion technologies predominantly concentrate on the enrichment of CD8+ T cells, advancements in methods targeting CD4+ T cells have been limited. In this study, we report a technique that harnesses antigen-presenting extracellular vesicles (EVs) for stimulation and expansion of antigen-specific CD4+ T cells. EVs are derived from a genetically modified HeLa cell line designed to emulate professional antigen-presenting cells (APCs) by expressing key costimulatory molecules CD80 and specific peptide–MHC-II complexes (pMHCs). Our results demonstrate the beneficial potent stimulatory capacity of EVs in activating both immortalized and isolated human CD4+ T cells from peripheral blood mononuclear cells (PBMCs). Our technique successfully expands low-frequency influenza-specific CD4+ T cells from healthy individuals. In summary, the elaborated methodology represents a streamlined and efficient approach for the detection and expansion of antigen-specific CD4+ T cells, presenting a valuable alternative to existing antigen-specific T-cell expansion protocols

Основания для отмены базисных противовоспалительных препаратов , генно-инженерных биологических препарато в и тофацитиниба при ревматоидном артрите

Objective: to analyze the reasons for discontinuation of traditional disease-modifying antirheumatic drugs (tDMARDs), biologic agents (BAs), and tofacitinib (TOFA) in patients with rheumatoid arthritis (RA) in real clinical practice.Patients and methods. The authors carried out a retrospective analysis of the data of the patients treated with tDMARDs, BAs, and TOFA, who had been included by the physicians of the V.A. Nasonova Research Institute of Rheumatology (RIR) in the all-Russian register of patients with RA (Group 1) in January 1, 2016 to November 1, 2018, the data of a pharmacology history (information about inefficacy (IE) and adverse reactions (ARs) due to the use of tDMARDs and BAs) in RA patients admitted to the V.A. Nasonova RIR during 2011–2016 for high-tech medical care (Group 2).Results. The main reasons for discontinuation of tDMARDs, BAs, and TOFA were found to be their IE and ARs.Discussion. 20% of patients with early RA never achieve not only remission, but also minimal disease activity, despite the introduction of current guidelines for its treatment. It is believed that one of the potential causes of resistance to treatment in RA is the IE of traditionally used drugs, which is mediated by transporters (ABCB1 and ABCG2) that reduce their concentrations, causing outflow from the intracellular space. The great importance of these transporters in RA is that their substrates are widely used drugs, such as methotrexate, leflunomide, sulfasalazine, aminoquinoline drugs, and prednisolone. The function of ABCB1 and ABCG2 is shown to be increased in patients with active RA, i.e. the disease activity is closely related to this phenomenon.Conclusion. IE and ARs are the most common reasons for discontinuation of tDMARDs, BAs, and TOFA in patients with RA; further investigations are needed to clarify their possible mechanisms.Objective: to analyze the reasons for discontinuation of traditional disease-modifying antirheumatic drugs (tDMARDs), biologic agents (BAs), and tofacitinib (TOFA) in patients with rheumatoid arthritis (RA) in real clinical practice.Patients and methods. The authors carried out a retrospective analysis of the data of the patients treated with tDMARDs, BAs, and TOFA, who had been included by the physicians of the V.A. Nasonova Research Institute of Rheumatology (RIR) in the all-Russian register of patients with RA (Group 1) in January 1, 2016 to November 1, 2018, the data of a pharmacology history (information about inefficacy (IE) and adverse reactions (ARs) due to the use of tDMARDs and BAs) in RA patients admitted to the V.A. Nasonova RIR during 2011–2016 for high-tech medical care (Group 2).Results. The main reasons for discontinuation of tDMARDs, BAs, and TOFA were found to be their IE and ARs.Discussion. 20% of patients with early RA never achieve not only remission, but also minimal disease activity, despite the introduction of current guidelines for its treatment. It is believed that one of the potential causes of resistance to treatment in RA is the IE of traditionally used drugs, which is mediated by transporters (ABCB1 and ABCG2) that reduce their concentrations, causing outflow from the intracellular space. The great importance of these transporters in RA is that their substrates are widely used drugs, such as methotrexate, leflunomide, sulfasalazine, aminoquinoline drugs, and prednisolone. The function of ABCB1 and ABCG2 is shown to be increased in patients with active RA, i.e. the disease activity is closely related to this phenomenon.Conclusion. IE and ARs are the most common reasons for discontinuation of tDMARDs, BAs, and TOFA in patients with RA; further investigations are needed to clarify their possible mechanisms. Цель исследования – анализ причин отмены традиционных базисных противовоспалительных препаратов (тБПВП), генно-инженерных биологических препаратов (ГИБП) и тофацитиниба (ТОФА) у больных ревматоидным артритом (РА) в реальной клинической практике.Пациенты и методы. Проведен ретроспективный анализ данных о больных, получавших тБПВП, ГИБП и ТОФА, которые были внесены врачами НИИР им. В.А. Насоновой с 01.01 2016 г. по 01.11 2017 г. в общероссийский регистр больных РА (1-я группа); данных фармакологического анамнеза (информация о неэффективности – НЭ – и нежелательных реакциях – НР, – обусловленных применением тБПВП и ГИБП), у больных РА, госпитализированных в течение 2011–2016 гг. в НИИР им. В.А. Насоновой для получения высокотехнологичной медицинской помощи (2-я группа).Результаты. Установлено, что основными причинами отмены тБПВП, ГИБП и ТОФА являются НЭ и НР.Обсуждение. 20% больных ранним РА никогда не достигают не только ремиссии, но и минимальной активности болезни, несмотря на внедрение современных рекомендаций по лечению. Полагают, что одной из потенциальных причин резистентности РА к лечению является НЭ традиционно применяемых лекарственных препаратов, опосредуемая транспортерами (ABCB1 и ABCG2), которые снижают их концентрацию, вызывая отток из внутриклеточного пространства. Важное значение этих транспортеров при РА заключается в том, что субстратами для них являются такие широко используемые препараты, как метотрексат, лефлуномид, сульфасалазин, аминохинолиновые препараты, преднизолон. Показано, что у больных активным РА повышена функция ABCB1 и ABCG2, т. е. активность болезни тесно связана с этим феноменом.Выводы. Основными причинами отмены тБПВП, ГИБП и ТОФА у больных РА являются НЭ и НР, для уточнения их возможных механизмов необходимы дальнейшие исследования.Цель исследования – анализ причин отмены традиционных базисных противовоспалительных препаратов (тБПВП), генно-инженерных биологических препаратов (ГИБП) и тофацитиниба (ТОФА) у больных ревматоидным артритом (РА) в реальной клинической практике.Пациенты и методы. Проведен ретроспективный анализ данных о больных, получавших тБПВП, ГИБП и ТОФА, которые были внесены врачами НИИР им. В.А. Насоновой с 01.01 2016 г. по 01.11 2017 г. в общероссийский регистр больных РА (1-я группа); данных фармакологического анамнеза (информация о неэффективности – НЭ – и нежелательных реакциях – НР, – обусловленных применением тБПВП и ГИБП), у больных РА, госпитализированных в течение 2011–2016 гг. в НИИР им. В.А. Насоновой для получения высокотехнологичной медицинской помощи (2-я группа).Результаты. Установлено, что основными причинами отмены тБПВП, ГИБП и ТОФА являются НЭ и НР.Обсуждение. 20% больных ранним РА никогда не достигают не только ремиссии, но и минимальной активности болезни, несмотря на внедрение современных рекомендаций по лечению. Полагают, что одной из потенциальных причин резистентности РА к лечению является НЭ традиционно применяемых лекарственных препаратов, опосредуемая транспортерами (ABCB1 и ABCG2), которые снижают их концентрацию, вызывая отток из внутриклеточного пространства. Важное значение этих транспортеров при РА заключается в том, что субстратами для них являются такие широко используемые препараты, как метотрексат, лефлуномид, сульфасалазин, аминохинолиновые препараты, преднизолон. Показано, что у больных активным РА повышена функция ABCB1 и ABCG2, т. е. активность болезни тесно связана с этим феноменом.Выводы. Основными причинами отмены тБПВП, ГИБП и ТОФА у больных РА являются НЭ и НР, для уточнения их возможных механизмов необходимы дальнейшие исследования.

Store-operated Ca2+ entry controls ameloblast cell function and enamel development

Loss-of-function mutations in stromal interaction molecule 1 (STIM1) impair the activation of Ca(2+) release–activated Ca(2+) (CRAC) channels and store-operated Ca(2+) entry (SOCE), resulting in a disease syndrome called CRAC channelopathy that is characterized by severe dental enamel defects. The cause of these enamel defects has remained unclear given a lack of animal models. We generated Stim1/2(K14cre) mice to delete STIM1 and its homolog STIM2 in enamel cells. These mice showed impaired SOCE in enamel cells. Enamel in Stim1/2(K14cre) mice was hypomineralized with decreased Ca content, mechanically weak, and thinner. The morphology of SOCE-deficient ameloblasts was altered, showing loss of the typical ruffled border, resulting in mislocalized mitochondria. Global gene expression analysis of SOCE-deficient ameloblasts revealed strong dysregulation of several pathways. ER stress genes associated with the unfolded protein response were increased in Stim1/2-deficient cells, whereas the expression of components of the glutathione system were decreased. Consistent with increased oxidative stress, we found increased ROS production, decreased mitochondrial function, and abnormal mitochondrial morphology in ameloblasts of Stim1/2(K14cre) mice. Collectively, these data show that loss of SOCE in enamel cells has substantial detrimental effects on gene expression, cell function, and the mineralization of dental enamel

What do we know about the possibility of predicting the potential efficacy and safety of methotrexate, by measuring the concentration of its metabolites in rheumatoid arthritis?

Rheumatoid arthritis (RA) is characterized by a progressive course with the formation of joint deformities and the development of severe functional disorders. The most favorable conditions for changing the course of the disease emerge in the first months after its onset. Methotrexate (MTX) occupies a leading position in the treatment of RA. There is a need to develop tools that will be able to predict the efficacy and tolerability of MTX at the earliest stages of RA treatment. The concentration of active metabolites of MTX is considered as a potential biomarker that enables one to predict what response to therapy with this drug will be.The paper analyzes the most relevant works devoted to the study of the concentration of active MTX metabolites polyglutamates (MTX PGs) in patients with RA. It is shown that the presented studies do not cover all the possibilities of therapeutic drug monitoring, in particular the determination of the levels of MTX PGs in mononuclear cells over time. Further investigation is needed to develop an objective approach to prescribing MTX in RA patients

Rationales for discontinuation of disease-modifying antirheumatic drugs, biologic agents, and tofacitinib in rheumatoid arthritis

Objective: to analyze the reasons for discontinuation of traditional disease-modifying antirheumatic drugs (tDMARDs), biologic agents (BAs), and tofacitinib (TOFA) in patients with rheumatoid arthritis (RA) in real clinical practice.Patients and methods. The authors carried out a retrospective analysis of the data of the patients treated with tDMARDs, BAs, and TOFA, who had been included by the physicians of the V.A. Nasonova Research Institute of Rheumatology (RIR) in the all-Russian register of patients with RA (Group 1) in January 1, 2016 to November 1, 2018, the data of a pharmacology history (information about inefficacy (IE) and adverse reactions (ARs) due to the use of tDMARDs and BAs) in RA patients admitted to the V.A. Nasonova RIR during 2011–2016 for high-tech medical care (Group 2).Results. The main reasons for discontinuation of tDMARDs, BAs, and TOFA were found to be their IE and ARs.Discussion. 20% of patients with early RA never achieve not only remission, but also minimal disease activity, despite the introduction of current guidelines for its treatment. It is believed that one of the potential causes of resistance to treatment in RA is the IE of traditionally used drugs, which is mediated by transporters (ABCB1 and ABCG2) that reduce their concentrations, causing outflow from the intracellular space. The great importance of these transporters in RA is that their substrates are widely used drugs, such as methotrexate, leflunomide, sulfasalazine, aminoquinoline drugs, and prednisolone. The function of ABCB1 and ABCG2 is shown to be increased in patients with active RA, i.e. the disease activity is closely related to this phenomenon.Conclusion. IE and ARs are the most common reasons for discontinuation of tDMARDs, BAs, and TOFA in patients with RA; further investigations are needed to clarify their possible mechanisms.Objective: to analyze the reasons for discontinuation of traditional disease-modifying antirheumatic drugs (tDMARDs), biologic agents (BAs), and tofacitinib (TOFA) in patients with rheumatoid arthritis (RA) in real clinical practice.Patients and methods. The authors carried out a retrospective analysis of the data of the patients treated with tDMARDs, BAs, and TOFA, who had been included by the physicians of the V.A. Nasonova Research Institute of Rheumatology (RIR) in the all-Russian register of patients with RA (Group 1) in January 1, 2016 to November 1, 2018, the data of a pharmacology history (information about inefficacy (IE) and adverse reactions (ARs) due to the use of tDMARDs and BAs) in RA patients admitted to the V.A. Nasonova RIR during 2011–2016 for high-tech medical care (Group 2).Results. The main reasons for discontinuation of tDMARDs, BAs, and TOFA were found to be their IE and ARs.Discussion. 20% of patients with early RA never achieve not only remission, but also minimal disease activity, despite the introduction of current guidelines for its treatment. It is believed that one of the potential causes of resistance to treatment in RA is the IE of traditionally used drugs, which is mediated by transporters (ABCB1 and ABCG2) that reduce their concentrations, causing outflow from the intracellular space. The great importance of these transporters in RA is that their substrates are widely used drugs, such as methotrexate, leflunomide, sulfasalazine, aminoquinoline drugs, and prednisolone. The function of ABCB1 and ABCG2 is shown to be increased in patients with active RA, i.e. the disease activity is closely related to this phenomenon.Conclusion. IE and ARs are the most common reasons for discontinuation of tDMARDs, BAs, and TOFA in patients with RA; further investigations are needed to clarify their possible mechanisms