Snow accumulation and compaction derived from GPR data near Ross Island, Antarctica

We present an improved method for estimating accumulation and compaction rates of dry snow in Antarctica with ground penetrating radar (GPR). Using an estimate of the emitted waveform from direct measurements, we apply deterministic deconvolution via the Fourier domain to GPR data with a nominal frequency of 500 MHz. This reveals unambiguous reflection horizons which can be observed in repeat measurements made one year apart. At two measurement sites near Scott Base, Antarctica, we extrapolate point measurements of average accumulation from snow pits and firn cores to a larger area by identifying a dateable dust layer horizon in the radargrams. Over an 800 m × 800 m area on the McMurdo Ice Shelf (77°45´ S, 167°17´ E) the average accumulation is found to be 269 ± 9 kg m−2 a−1. The accumulation over an area of 400 m × 400 m on Ross Island (77°40´ S, 167°11´ E, 350 m a.s.l.) is found to be higher (404 ± 22 kg m−2 a−1) and shows increased variability related to undulating terrain. Compaction of snow between 2 m and 13 m depth is estimated at both sites by tracking several internal reflection horizons along the radar profiles and calculating the average change in separation of horizon pairs from one year to the next. The derived compaction rates range from 7 cm m−1 at a depth of 2 m, down to no measurable compaction at 13 m depth, and are similar to published values from point measurements

Human Immunoglobulin M Memory B Cells Controlling Streptococcus pneumoniae Infections Are Generated in the Spleen

Splenectomized and asplenic patients have a high incidence of infections by encapsulated bacteria and do not respond to polysaccharide vaccines. To understand whether the absence of the spleen is associated with a defined B cell defect, we analyzed B cell subsets in the peripheral blood. We found that a population of B cells known as immunoglobulin (Ig)M memory is lacking in patients without spleen. The absence of IgM memory B cells correlates with an impaired immune response to encapsulated bacteria not only in splenectomized patients, but also in individuals with an intact spleen. We show that the physiological and transient predisposition to pneumococcal infections of young children (0–2 yr) is associated with the lack of circulating IgM memory B cells and of serum antipolysaccharide IgM. We also demonstrate that IgM memory B cells are undetectable in a fraction of patients with common variable immunodeficiency, who have recurrent and invasive infections by encapsulated bacteria. IgM memory B cells, therefore, require the spleen for their generation and/or survival and are responsible for the protection against encapsulated bacteria

Vaccination-induced changes in human B-cell repertoire and pneumococcal IgM and IgA antibody at different ages

It is well known that older people are more susceptible to morbidity and mortality from infectious diseases, particularly from pulmonary diseases such as pneumococcal pneumonia where vaccines do not provide efficient protection as in younger populations. We have previously shown that the B-cell repertoire in the old is reduced and hypothesise that this may contribute to the impaired humoral responses of the elderly. Here, we investigated the repertoire and antibody responses to winter vaccination in two age groups, aged 18–49 and 65–89. We found that the serum IgM and IgA pneumococcal responses were significantly impaired in the older group, with no difference in IgG levels. IGHM spectratype analysis seems to be the most promising in terms of its predictive ability for vaccine responses. Spectratypes showed a clear change in the repertoire at day 7 after vaccination, with a return to the baseline levels at day 28. The changes at day 7 reflected expansion of IGH sequences that have smaller, more hydrophilic, CDR3 regions, and these changes were attenuated in the older group. The older group was more likely to have spectratypes indicative of a reduced diversity at day 0 and day 28. On average, the baseline repertoire in the older group was comprised of larger CDR3 regions than in the younger group. In conclusion, IgA and IgM responses are significantly impaired in the elderly pneumococcal response and are likely key mediators of protection. Hydrophilicity and/or small size of the IGH CDR3 appear to be important in these responses

DESMISTIFICANDO ALGORITMOS

O conceito de algoritmo extrapola o contexto de ambientes computacionais. Pode-se definir algoritmo como uma sequência finita de regras, raciocínios e/ou operações, tendo como objetivo a solução de um problema prático. Esse problema pode ser tanto no mundo virtual (computacional) como no mundo real (físico). Todas as pessoas utilizam muitos algoritmos no seu dia a dia e nem se dão conta disso. Por exemplo, ao escovar os dentes, pegar um elevador, dirigir um carro, pegar o ônibus para a escola, jogar um videogame ou assistir e dar um like em um vídeo no Tik Tok, estamos utilizando algoritmos de forma prática. Na computação os algoritmos desempenham um papel extremamente importante, pense nos sites que você acessa no dia a dia, caso você dê um click com o mouse em determinada área cujo essa seja um hyperlink você será direcionado para outro página, caso não for não acontecerá nada. Isso acontece porque tudo que é feito pelo computador consiste em um ciclo de informações que são fornecidas a ele (chamadas de entradas), que são processadas por algoritmos, gerando novas informações (chamadas de saídas), que são devolvidas ao usuário que por sua vez inicia um novo ciclo de iteração. Nosso objetivo é explicar, exemplificar e demonstrar de forma compacta o uso de algoritmos no nosso cotidiano, para a realização das mais variadas tarefas diárias. Para tanto, a apresentação do trabalho está programada para acontecer da seguinte maneira, inicialmente a introdução sobre o conteúdo, o que é algoritmo e como ele está inserido na em nossa realização diária de tarefas. Na sequência, serão apresentados alguns exemplos de algoritmos em computador por meio das ferramentas Python Tutor e Blockly para demonstrar a sequência lógica de passos para a execução de algoritmos para solução de problemas simples. Por fim, iremos adentrar na apresentação e resolução do cubo mágico, criado por Erno Rubik, para mostrar aos seus alunos de arquitetura o conceito da terceira dimensão, e que hoje em dia possui uma série de diferentes algoritmos que podem ser utilizados da sua resolução. Neste estágio, será disposto aos interessados o acesso a um computador com a aplicação Blockly em execução, bem como alguns cubos mágicos, para que possam aprender e experimentar pequenos algoritmos na prática, começando com passos simples e orientação da equipe. Esperamos por meio deste projeto, desmistificar o conceito de algoritmos e a habilidade de empregar raciocínio lógico para a resolução de problemas do dia a dia, de modo que seja despertado nos participantes o interesse em aprender e aplicar algoritmos na resolução dos problemas do mundo real por meio dos computadores

Suppression of circulating IgD+CD27+ memory B cells in infants living in a malaria-endemic region of Kenya

Background: Plasmodium falciparum infection leads to alterations in B cell subset distribution. During infancy, development of peripheral B cell subsets is also occurring. However, it is unknown if infants living a malaria endemic region have alterations in B cell subsets that is independent of an age effect. Methods: To evaluate the impact of exposure to P. falciparum on B cell development in infants, flow cytometry was used to analyse the distribution and phenotypic characteristic of B cell subsets in infant cohorts prospectively followed at 12, 18 and 24 months from two geographically proximate regions in western Kenya with divergent malaria exposure i.e. Kisumu (malaria-endemic, n = 24) and Nandi (unstable malaria transmission, n = 21). Results: There was significantly higher frequency and absolute cell numbers of CD19+ B cells in Kisumu relative to Nandi at 12(p = 0.0440), 18(p = 0.0210) and 24 months (p = 0.0493). No differences were observed between the infants from the two sites in frequencies of naïve B cells (IgD+CD27-) or classical memory B cells (IgD-CD27+). However, immature transitional B cells (CD19+CD10+CD34-) were higher in Kisumu relative to Nandi at all three ages. In contrast, the levels of non-class switched memory B cells (CD19+IgD+CD27+) were significantly lower overall in Kisumu relative to Nandi at significantly at 12 (p = 0.0144), 18 (p = 0.0013) and 24 months (p = 0.0129). Conclusions: These data suggest that infants living in malaria endemic regions have altered B cell subset distribution. Further studies are needed to understand the functional significance of these changes and long-term impact on ability of these infants to develop antibody responses to P. falciparum and heterologous infections

IgM memory B cells: a mouse/human paradox

Humoral memory is maintained by two types of persistent cells, memory B cells and plasma cells, which have different phenotypes and functions. Long-lived plasma cells can survive for a lifespan within a complex niche in the bone marrow and provide continuous protective serum antibody levels. Memory B cells reside in secondary lymphoid organs, where they can be rapidly mobilized upon a new antigenic encounter. Surface IgG has long been taken as a surrogate marker for memory in the mouse. Recently, however, we have brought evidence for a long-lived IgM memory B cell population in the mouse, while we have also argued that, in humans, these same cells are not classical memory B cells but marginal zone (MZ) B cells which, as opposed to their mouse MZ counterpart, recirculate and carry a mutated B cell receptor. In this review, we will discuss these apparently paradoxical results

Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

Background: The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings: Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions: The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens

Assessment of splenic function

Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological, haematological and scintigraphic parameters that can be used to measure splenic function. IgM memory B cells are a potential parameter for assessing splenic function; however, more studies are necessary for its validation. Detection of Howell–Jolly bodies does not reflect splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well-evaluated method and seems a good first-line investigation for assessing splenic function. When assessing spleen function, 99mTc-labelled, heat-altered, autologous erythrocyte scintigraphy with multimodality single photon emission computed tomography (SPECT)-CT technology is the best approach, as all facets of splenic function are evaluated. In conclusion, although scintigraphic methods are most reliable, they are not suitable for screening large populations. We therefore recommend using the percentage of pitted erythrocytes, albeit suboptimal, as a first-line investigation and subsequently confirming abnormal readings by means of scintigraphy. More studies evaluating the value of potentially new markers are needed

A distinct role for B1b lymphocytes in T cell-independent immunity

Pathogenesis of infectious disease is not only determined by the virulence of the microbe but also by the immune status of the host. Vaccination is the most effective means to control infectious diseases. A hallmark of the adaptive immune system is the generation of B cell memory, which provides a long-lasting protective antibody response that is central to the concept of vaccination. Recent studies revealed a distinct function for B1b lymphocytes, a minor subset of mature B cells that closely resembles that of memory B cells in a number of aspects. In contrast to the development of conventional B cell memory, which requires the formation of germinal centers and T cells, the development of B1b cell-mediated long-lasting antibody responses occurs independent of T cell help. T cell-independent (TI) antigens are important virulence factors expressed by a number of bacterial pathogens, including those associated with biological threats. TI antigens cannot be processed and presented to T cells and therefore are known to possess restricted T cell-dependent (TD) immunogenicity. Nevertheless, specific recognition of TI antigens by B1b cells and the highly protective antibody responses mounted by them clearly indicate a crucial role for this subset of B cells. Understanding the mechanisms of long-term immunity conferred by B1b cells may lead to improved vaccine efficacy for a variety of TI antigens