Atmospheric Density Uncertainty Quantification for Satellite Conjunction Assessment

Conjunction assessment requires knowledge of the uncertainty in the predicted orbit. Errors in the atmospheric density are a major source of error in the prediction of low Earth orbits. Therefore, accurate estimation of the density and quantification of the uncertainty in the density is required. Most atmospheric density models, however, do not provide an estimate of the uncertainty in the density. In this work, we present a new approach to quantify uncertainties in the density and to include these for calculating the probability of collision Pc. For this, we employ a recently developed dynamic reduced-order density model that enables efficient prediction of the thermospheric density. First, the model is used to obtain accurate estimates of the density and of the uncertainty in the estimates. Second, the density uncertainties are propagated forward simultaneously with orbit propagation to include the density uncertainties for Pc calculation. For this, we account for the effect of cross-correlation in position uncertainties due to density errors on the Pc. Finally, the effect of density uncertainties and cross-correlation on the Pc is assessed. The presented approach provides the distinctive capability to quantify the uncertainty in atmospheric density and to include this uncertainty for conjunction assessment while taking into account the dependence of the density errors on location and time. In addition, the results show that it is important to consider the effect of cross-correlation on the Pc, because ignoring this effect can result in severe underestimation of the collision probability.Comment: 15 pages, 6 figures, 5 table

A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

PMCID: PMC3754866Rockefeller University Press grants the public the non-exclusive right to copy, distribute, or display this Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode

НЕСТАНДАРТНЫЕ ФОРМЫ ПРОФЕССИОНАЛЬНОГО РАЗВИТИЯ И САМОРЕАЛИЗАЦИИ СОТРУДНИКОВ: ДАУНШИФТИНГ И ПРЕДПРИНИМАТЕЛЬСКАЯ ДЕЯТЕЛЬНОСТЬ

Transition to postindustrial society is accompanied by the onrush development of new information and communication technologies. Consequently, social capital of humans development becomes necessary and very important. Along with the willing ness to increase social capital many people are interested in realizing their entrepreneurial activities. Spreading of such non-standard forms of employment as remote work, freelancing (in particular, electronic freelancing) and downshifting, providing a new type of social-labor relations, increasing number of people seeking to self-organization labor activity. Thus, detailed consideration of non-standard forms of labor organization, entrepreneurship and ways of employee’s professional development is very actual. The article discusses such phenomena as entrepreneurship and downshifting in context of personality’s professional development, and also exploring reasons and ways of engagement in ideologies of both two phenomena. A distinctive feature of the author’s view is that concepts of “entrepreneurship” and “downshifting” are not in the opposition as different vectors of career development. These methods of labor organization are considered as similar by backgrounds that motivate per son to leave stable job in a global context or in a concrete company. In the article for more complete understanding complementarity of entrepreneurship and downshifting in context of personality’s professional development, there is a brief historical background, regarding history of each phenomena – globally, and particularly in Russia.Переход к постиндустриальному обществу сопровождается стремительным развитием новых информационно-коммуникационных технологий (ИКТ). В связи с этим развитие социального капитала человека становится необходимым и очень важным. Наряду со стремлением людей к приращению социального капитала увеличивается их интерес и к предпринимательской деятельности. Все большее распространение получают такие нестандартные формы занятости, как дистанционная профессиональная деятельность, фриланс (в частности, электронный фриланс), свободная занятость (дауншифтинг), вследствие чего формируется новый тип социально-трудовых отношений, увеличивается количество людей, стремящихся к самоорганизации труда. Таким образом, подробное рассмотрение нестандартных форм организации трудовой деятельности, предпринимательства, а также способов профессионального развития работников является актуальным. В статье рассматриваются особенности таких феноменов, как предпринимательство и дауншифтинг, в контексте путей профессионального развития человека, а также анализируются причины и способы вовлечения как в идеологию предпринимательства, так и в идеологию дауншифтинга. Отличительной чертой авторского взгляда является то, что понятия “предпринимательство” и “дауншифтинг” не противопоставляются как противоположные по смыслу вектора развития карьеры. Эти способы организации трудовой деятельности, наоборот, рассматриваются как схожие между собой в предпосылках, побуждающих оставить стабильную работу в компании, а также в глобальных целях этих изменений. Для более полного понимания комплементарности феноменов в контексте профессионального развития человека приведены краткая историческая справка о возникновении каждого из феноменов, а также экскурс в историю развития каждого из феноменов в России

БИЗНЕС И ОБРАЗОВАНИЕ: ИННОВАЦИОННЫЕ СТРАТЕГИИ

The article is written by postgraduate students of the Sociological Department of the Lomonosov Moscow State University on the results of a general discussion of the possibilities of innovative development through the prism of related fields of knowledge. It reflects the urgency of studying the processes taking place in various institutions of society and causing innovative development. The publication discusses the features of the functioning and interaction between the social institutions of business and education in the context of innovative processes occurring in Russia (low conversion fundamental knowledge in innovation, the inability of young people to engage in science, the specialists outflow from the country, maintaining a balance between traditions and innovations in education, closure of complex industries, and others). The analysis of existing theories and examples of successful interaction between education and business organized to obtain innovative developments are presented (MSU Science Park and others).The data on innovative business models implemented in the countries of the world (Russia, China, Singapore, the United States) and the features of their implementation (the possibility of start-up visas, the problems of protecting the rights of entrepreneurs and investors, the time of launching the project and the idea before production), empirical data on the outflow of specialists From Russia, which is considered as one of the consequences of the lack of innovative production in Russia). The authors proposed the possible directions of the organization of education and innovative business, based on the successful experience of foreign countries. The article considers marketing mechanisms as a way of communication between education, business and government institutions in the creation and implementation of innovative developments in Russia, the peculiarities of marketing in the innovative context, in particular, the key role of marketing in acquiring the final innovative product by buyers.Статья написана аспирантами социологического факультета Московского Государственного Университета имени М.В. Ломоносова по результатам общего обсуждения возможностей инновационного развития сквозь призму смежных областей знаний. Она отображает актуальность изучения процессов, происходящих в различных институтах общества и обуславливающих инновационное развитие. В публикации рассмотрены особенности функционирования и взаимодействия между собой социальных институтов бизнеса и образования в контексте инновационных процессов, происходящих в России (низкая конвертация фундаментальных знаний в инновации, неготовность молодежи заниматься наукой, отток специалистов из страны, сохранение баланса между традициями и инновациями в образовании, закрытие сложных производств, и другие). Проведен анализ существующих теоретических исследований и приведены примеры успешного взаимодействия образования и бизнеса, организованного в целях получения инновационных разработок (Научный парк МГУ и др.).Приведены данные по инновационным моделям бизнеса, реализуемых в странах мира (Россия, Китай, Сингапур, США) и особенностям их реализации (возможности стартап-визы, проблемы защиты прав предпринимателей и инвесторов время запуска проекта и идеи до производства), эмпирические данные по оттоку специалистов из России, которые рассматривается как одно из следствий отсутствия инновационных производств в России). Авторами предложены возможные направления организации образования и инновационного бизнеса, основанные на успешном опыте зарубежных стран. Рассмотрены маркетинговые механизмы как способ коммуникации между институтами образования, бизнеса и государства при создании и реализации инновационных разработок в России, особенности маркетинга в инновационном контексте, в частности – ключевая роль маркетинга в приобретении покупателями итогового инновационного продукта

Phenotypic Characterization of Autoreactive B Cells—Checkpoints of B Cell Tolerance in Patients with Systemic Lupus Erythematosus

DNA-reactive B cells play a central role in systemic lupus erythematosus (SLE); DNA antibodies precede clinical disease and in established disease correlate with renal inflammation and contribute to dendritic cell activation and high levels of type 1 interferon. A number of central and peripheral B cell tolerance mechanisms designed to control the survival, differentiation and activation of autoreactive B cells are thought to be disturbed in patients with SLE. The characterization of DNA-reactive B cells has, however, been limited by their low frequency in peripheral blood. Using a tetrameric configuration of a peptide mimetope of DNA bound by pathogenic anti-DNA antibodies, we can identify B cells producing potentially pathogenic DNA-reactive antibodies. We, therefore, characterized the maturation and differentiation states of peptide, (ds) double stranded DNA cross-reactive B cells in the peripheral blood of lupus patients and correlated these with clinical disease activity. Flow cytometric analysis demonstrated a significantly higher frequency of tetramer-binding B cells in SLE patients compared to healthy controls. We demonstrated the existence of a novel tolerance checkpoint at the transition of antigen-naïve to antigen-experienced. We further demonstrate that patients with moderately active disease have more autoreactive B cells in both the antigen-naïve and antigen-experienced compartments consistent with greater impairment in B cell tolerance in both early and late checkpoints in these patients than in patients with quiescent disease. This methodology enables us to gain insight into the development and fate of DNA-reactive B cells in individual patients with SLE and paves the way ultimately to permit better and more customized therapies

Antibody Repertoires in Humanized NOD-scid-IL2Rγnull Mice and Human B Cells Reveals Human-Like Diversification and Tolerance Checkpoints in the Mouse

Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγnull engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH) and light (IGK and IGL) genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγnull mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3) repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential DH-JH pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by genetic factors intrinsic to human B cells and are principally unaltered by differences between mouse and human stromal microenvironments

Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses

Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is a crucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important as these antibodies may target conserved epitopes on the HIV envelope gp160 protein. To this end we have used a clade B YU-2 gp140 trimeric antigen and single-cell antibody cloning methods to obtain 189 new anti-gp140 antibodies representing 51 independent B cell clones from the IgG memory B cells of 3 patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing a diverse antibody response to HIV gp140 envelope protein, characterized by differentially expanded B-cell clones producing highly hypermutated antibodies with heterogenous gp140-specificity and neutralizing activity. In addition to their high-affinity binding to the HIV spike, the vast majority of the new anti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VRC01 or PG9, two clonally-related antibodies isolated from a clade A HIV-1 infected donor, directed against the gp120 variable loop 3, rank in the top 5% of the neutralizers identified in our large collection of 185 unique gp140-specific antibodies in terms of breadth and potency

Comparison of Antibody Repertoires Produced by HIV-1 Infection, Other Chronic and Acute Infections, and Systemic Autoimmune Disease

Background Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M)Abs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the VH genes of five of them encode a long (≥20 aa) third complementarity-determining region (CDR-H3). This led us to question whether long CDR-H3s and high levels of somatic mutation (SM) are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general. Methodology and Principal Findings We assembled a VH-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral) infections (ChI), acute (bacterial and viral) infections (AcI), and systemic autoimmune diseases (SAD), and compared their CDR-H3 length, number of SMs and germline VH-gene usage. We found that anti-HIV Abs, regardless of their neutralization breadth, tended to have long CDR-H3s and high numbers of SMs. However, these features were also common among Abs associated with other chronic viral infections. In contrast, Abs from acute viral infections (but not bacterial infections) tended to have relatively short CDR-H3s and a low number of SMs, whereas SAD Abs were generally intermediate in CDR-H3 length and number of SMs. Analysis of VH gene usage showed that ChI Abs also tended to favor distal germline VH-genes (particularly VH1-69), especially in Abs bearing long CDR-H3s. Conclusions and Significance The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and VH1-69 gene usage may be preferentially selected during persistent infection

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases