Assessing T cell clonal size distribution: a non-parametric approach

Clonal structure of the human peripheral T-cell repertoire is shaped by a number of homeostatic mechanisms, including antigen presentation, cytokine and cell regulation. Its accurate tuning leads to a remarkable ability to combat pathogens in all their variety, while systemic failures may lead to severe consequences like autoimmune diseases. Here we develop and make use of a non-parametric statistical approach to assess T cell clonal size distributions from recent next generation sequencing data. For 41 healthy individuals and a patient with ankylosing spondylitis, who undergone treatment, we invariably find power law scaling over several decades and for the first time calculate quantitatively meaningful values of decay exponent. It has proved to be much the same among healthy donors, significantly different for an autoimmune patient before the therapy, and converging towards a typical value afterwards. We discuss implications of the findings for theoretical understanding and mathematical modeling of adaptive immunity.Comment: 13 pages, 3 figures, 2 table

СКАНИРУЮЩАЯ ТОРОИДАЛЬНО-БИФОКАЛЬНАЯ ЛИНЗОВАЯ АНТЕННАЯ СИСТЕМА ДИАПАЗОНА 57–64 ГГЦ

Introduction. Currently, one of the most promising approaches to the development of 5th generation mobile wireless systems is the deployment of heterogeneous networks based on existing LTE cellular systems having both large and small cells. Small, low-cost relay stations equipped with highly directional steerable antenna systems to connect small cells with LTE base station serving macrocell can comprise the main elements of such networks. Objective. Since existing solutions are either too expensive or do not allow the flexible rearrangement of current information transmission lines, the objective of this work is to develop antenna equipment for low-cost relay stations based on simple, steerable antenna systems of millimetre wavelength (57-64 GHz), which allow beamsteering on both azimuth and elevation planes. Methods and materials. The developed steerable, bifocal lens antenna system comprises a specially-shaped lens made of high-molecular-weight polyethylene and integrated with a phased array antenna. A key feature of its design is a wide-angle beamsteering in the azimuth plane and ability to adjust the beam in the elevation plane. The calculation of the lens profiles was carried out by means of an approximation of geometrical optics in Matlab, while the main technical characteristics of the lens antenna system were obtained by direct electromagnetic modelling in CST Microwave Studio. Results. A prototype steerable, bifocal lens-array antenna system has been developed and its characteristics studied. The following technical characteristics are achieved in the 57–64 GHz range: beamsteering in the elevation plane – ±3º; beam-steering in the azimuth plane – ±40º; antenna gain – from 20 to 27.5 dBi for all angles. Conclusion. It is shown that the developed antenna system can be successfully used as a component of the receiving and transmission equipment of small relay stations that transmit information in the frequency range of 57-64 GHz over a distance of 100-300 m.Введение. В настоящее время одним из перспективных подходов к построению систем мобильной радиосвязи пятого поколения является развертывание неоднородных сетей на основе существующих систем сотовой связи LTE с большими и малыми сотами. Основными элементами таких сетей могут стать небольшие дешевые релейные станции, оснащенные высоконаправленными сканирующими антенными системами для связи малых сот с базовой станцией LTE, обслуживающей макросоту. Существующие решения во многом слишком дороги или не позволяют гибко перестраивать используемые линии передачи информации. Цель работы. Разработка антенного оборудования для дешевых релейных станций на основе простых сканирующих антенных систем миллиметрового диапазона длин волн (57…64 ГГц), позволяющих управлять главным лучом в двух плоскостях: азимутальной и угломестной. Материалы и методы. Профиль линзы из высокомолекулярного полиэтилена был рассчитан в приближении геометрической оптики в MATLAB. Основные технические характеристики линзовой антенной системы получены прямым электромагнитным моделированием в CST Microwave Studio, а также в ходе экспериментальных исследований с помощью вспомогательной антенны с высоким коэффициентом усиления, расположенной в дальней зоне. Результаты. Разработан и создан прототип сканирующей бифокальной линзовой антенной системы, представляющий собой линзу специальной формы из высокомолекулярного полиэтилена, интегрированную с плоской фазированной антенной решеткой. В диапазоне рабочих частот 57…64 ГГц достигнуты следующие технические показатели: углы сканирования в угломестной плоскости ±3º, в азимутальной плоскости ±40º, коэффициент усиления антенной системы для всех углов сканирования находится в пределах 20…27.5 дБи. Заключение. Разработанная линзовая антенная система может найти практическое применение в качестве приемо-передающего антенного оборудования небольших релейных станций, осуществляющих передачу информации в частотном диапазоне 57…64 ГГц на расстояния 100…300 м

Computational strategies for dissecting the high-dimensional complexity of adaptive immune repertoires

The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV). Adaptive immune receptor repertoire sequencing (AIRR-seq) has driven the quantitative and molecular-level profiling of immune repertoires thereby revealing the high-dimensional complexity of the immune receptor sequence landscape. Several methods for the computational and statistical analysis of large-scale AIRR-seq data have been developed to resolve immune repertoire complexity in order to understand the dynamics of adaptive immunity. Here, we review the current research on (i) diversity, (ii) clustering and network, (iii) phylogenetic and (iv) machine learning methods applied to dissect, quantify and compare the architecture, evolution, and specificity of immune repertoires. We summarize outstanding questions in computational immunology and propose future directions for systems immunology towards coupling AIRR-seq with the computational discovery of immunotherapeutics, vaccines, and immunodiagnostics.Comment: 27 pages, 2 figure

STEERABLE TOROIDAL BIFOCAL LENS-ARRAY ANTENNA IN 57–64 GHZ RANGE

Introduction. Currently, one of the most promising approaches to the development of 5th generation mobile wireless systems is the deployment of heterogeneous networks based on existing LTE cellular systems having both large and small cells. Small, low-cost relay stations equipped with highly directional steerable antenna systems to connect small cells with LTE base station serving macrocell can comprise the main elements of such networks. Objective. Since existing solutions are either too expensive or do not allow the flexible rearrangement of current information transmission lines, the objective of this work is to develop antenna equipment for low-cost relay stations based on simple, steerable antenna systems of millimetre wavelength (57-64 GHz), which allow beamsteering on both azimuth and elevation planes. Methods and materials. The developed steerable, bifocal lens antenna system comprises a specially-shaped lens made of high-molecular-weight polyethylene and integrated with a phased array antenna. A key feature of its design is a wide-angle beamsteering in the azimuth plane and ability to adjust the beam in the elevation plane. The calculation of the lens profiles was carried out by means of an approximation of geometrical optics in Matlab, while the main technical characteristics of the lens antenna system were obtained by direct electromagnetic modelling in CST Microwave Studio. Results. A prototype steerable, bifocal lens-array antenna system has been developed and its characteristics studied. The following technical characteristics are achieved in the 57–64 GHz range: beamsteering in the elevation plane – ±3º; beam-steering in the azimuth plane – ±40º; antenna gain – from 20 to 27.5 dBi for all angles. Conclusion. It is shown that the developed antenna system can be successfully used as a component of the receiving and transmission equipment of small relay stations that transmit information in the frequency range of 57-64 GHz over a distance of 100-300 m

Characteristics of the TCRB libraries.

<p>Sources of libraries: upper block <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Warren1" target="_blank">[6]</a>, middle block <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Britanova1" target="_blank">[12]</a>, bottom block <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Mamedov1" target="_blank">[13]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Britanova2" target="_blank">[15]</a>. Values in the middle block are averages within each group.</p><p>Characteristics of the TCRB libraries.</p

Clonal statistics for an autoimmune patient.

<p>Complementary cumulative clonal frequency distributions (CDF) for an autoimmune patient <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Mamedov1" target="_blank">[13]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Britanova2" target="_blank">[15]</a> in double log scale: right before the treatment (blue), 10 months after (red), and 25 months after (green). Shaded areas indicate CI95 intervals for clonal frequencies. Dashed lines show power law fits , <i>α</i> = −2.07, <i>α</i> = −0.88 and <i>α</i> = −0.99, respectively. Least square fits performed over the interval for the time point before treatments and for the time points after.</p

Power law exponent fits for complementary cumulative clonal frequency distributions and 95% confidence intervals.

<p>Sources of libraries: upper block <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Warren1" target="_blank">[6]</a>, middle block <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Britanova1" target="_blank">[12]</a>, bottom block <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Mamedov1" target="_blank">[13]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Britanova2" target="_blank">[15]</a>. Values in the middle block are averages within each group.</p><p>Power law exponent fits for complementary cumulative clonal frequency distributions and 95% confidence intervals.</p

Power law exponents.

<p>Exponents <i>α</i> of power law fits with respective CI95 indicated vs. age of individuals. Blue circles: healthy donors from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Britanova1" target="_blank">[12]</a>, least square fits performed over the interval or , whichever produced better quality. Red squares: healthy donors from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Warren1" target="_blank">[6]</a>, least square fits performed over the interval . Green triangles: autoimmune patient before and after treatment <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Mamedov1" target="_blank">[13]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108658#pone.0108658-Britanova2" target="_blank">[15]</a>, least square fits performed over the interval for the time point before treatments and for the three time points after.</p