FEC killed the cut-through switch

Latency penalty in Ethernet links beyond 10Gb/s is due to forward error correction (FEC) blocks. In the worst case a single-hop penalty approaches the latency of an entire cutthrough switch. Latency jitter is also introduced, making latency prediction harder, with large peak to peak variance. These factors stretch the tail of latency distribution in Rackscale systems and Data Centers, which in turn degrades performance of distributed applications. We analyse the underlying mechanisms, calculate lower bounds and propose a different approach that would reduce the penalty, allow control over latency and feedback for application level optimisation.Rudin foundation, Isaac Newton trust, Leverhulme trust, Microsoft researc

Low-latency wavelength-switched clock-synchronized intra-data center interconnects enabled by hollow core fiber

Fast (nanoseconds) optical wavelength switching is emerging as a viable solution to scaling the size and capacity of intra-data center interconnection. A key enabling technology for such systems is low-jitter optical clock synchronization, which enables sub-nanosecond clock and data recovery for optically switched frames using low-cost methods such as clock phase caching. We propose and demonstrate real-time low-latency wavelength-switched clock-synchronized intra-data center interconnection at 51.2 GBd using a fast tunable laser (with ns scale switching time) and ultra-stable-latency hollow core fiber (HCF) for optically-switched data center networks. For wavelength-switched systems, we achieve a physical layer latency below 46 ns, consisting of 28 ns transceiver latency and a 18 ns inter-packet gap. Finally, we show that by exploiting the low chromatic dispersion and thermally-stable latency features of HCF, active clock phase tracking can be entirely eliminated

Tracking Antigen-Specific T-Cells during Clinical Tolerance Induction in Humans

Allergen immunotherapy presents an opportunity to define mechanisms of induction of clinical tolerance in humans. Significant progress has been made in our understanding of changes in T cell responses during immunotherapy, but existing work has largely been based on functional T cell assays. HLA-peptide-tetrameric complexes allow the tracking of antigen-specific T-cell populations based on the presence of specific T-cell receptors and when combined with functional assays allow a closer assessment of the potential roles of T-cell anergy and clonotype evolution. We sought to develop tools to facilitate tracking of antigen-specific T-cell populations during wasp-venom immunotherapy in people with wasp-venom allergy. We first defined dominant immunogenic regions within Ves v 5, a constituent of wasp venom that is known to represent a target antigen for T-cells. We next identified HLA-DRB1*1501 restricted epitopes and used HLA class II tetrameric complexes alongside cytokine responses to Ves v 5 to track T-cell responses during immunotherapy. In contrast to previous reports, we show that there was a significant initial induction of IL-4 producing antigen-specific T-cells within the first 3–5 weeks of immunotherapy which was followed by reduction of circulating effector antigen-specific T-cells despite escalation of wasp-venom dosage. However, there was sustained induction of IL-10-producing and FOXP3 positive antigen-specific T cells. We observed that these IL-10 producing cells could share a common precursor with IL-4-producing T cells specific for the same epitope. Clinical tolerance induction in humans is associated with dynamic changes in frequencies of antigen-specific T-cells, with a marked loss of IL-4-producing T-cells and the acquisition of IL-10-producing and FOXP3-positive antigen-specific CD4+ T-cells that can derive from a common shared precursor to pre-treatment effector T-cells. The development of new approaches to track antigen specific T-cell responses during immunotherapy can provide novel insights into mechanisms of tolerance induction in humans and identify new potential treatment targets

DNA Damage Responses Regulate Macrophage Function During Innate Immune Responses

Activated macrophages produce genotoxins such as reactive oxygen and nitrogen intermediates that are critical for the eradication of pathogens. Here we show that one of these agents, nitric oxide (NO), damages macrophage genomic DNA, resulting in the activation of DNA damage responses (DDR). The DDR is primarily initiated through DNA double-strand break (DSB) intermediates and depends on the PI3-like kinases ATM and DNA-PKcs. In response to Listeria monocytogenes infection, ATM and DNA-PKcs regulate a tissue-specific genetic program that includes the expression of inflammatory cytokines, chemokines and cell surface receptors, several of which are critical for cell migration during immune responses to bacterial infection. These kinases also regulate inflammasome activation and production of the inflammatory cytokines IL-1β and IL-18. Due to the near-complete block in IL-18 production by DNA-PKcs- deficient macrophages, these cells are unable to optimally stimulate NK cells to produce IFN-γ, which is important for controlling early L. monocytogenes infection. These findings establish DNA damage, and the initiation of DDR by this damage, as important signaling intermediates in the innate immune responses mediated by macrophages

New administration formula of parasiticide fungi spores to prevent infection by gastrointestinal nematodes in pasturing horses

Dissertação de Mestrado Integrado em Medicina VeterináriaAnthelmintic resistance in horses has increased in recent years and the continuous search for alternative control methods has led to the development of complementary approaches such as biological control. This approach can make use of parasiticide fungi, such as Duddingtonia flagrans and Mucor circinelloides, in parasite population control and recent research has been focused on the development of new administration methods. Following this line of research, a new and alternative formula has been developed by using a lyophilized product that contained both D. flagrans and M. circinelloides spores for the control of gastrointestinal nematodes in horses. After the product manufacture and the normal spore morphology were assessed, these were tested for in vitro growth. A total of 20 Petri dishes were assembled with a mix of 0.1 g of product and 0.5 ml of water in solid media. The assembled plaques were kept at 25ºC in total darkness and all showed the development of new fungi spores after 10 days. Following the in vitro assessment, the product was administered per os to horses in order to observe their effect in the faecal egg count (FEC) of eggs per gram (EPG). Thus, one group of 5 horses in a pasture was chosen to receive 10 g of product (with M. circinelloides spores and a total of around 105 D. flagrans chlamydospores per horse), 3 days a week starting in September, and another group of 7 horses in an adjacent pasture remained as control. Following treatment with Ivermectin pour-on in September 2017, a faecal sample was collected from each horse on a monthly basis and FEC was assessed using a Modified McMaster technique. Only gastrointestinal nematode eggs, namely strongyle eggs, were observed with this technique. The EPG average from each group was compared for each individual month and overall to see the reduction effect achieved with the fungi treatment. Statistically significant differences were found between the two groups in February (72% reduction), March (64% reduction), and overall, 66% reduction. The horses in the test group only reached a cut-off value of 300 EPG two months after the horses in the control group. In November and January, faecal culture method was applied to all faecal samples, showing only the presence of cyathostomin larvae. This study allowed the successful development of a new formula for the administration of parasiticide fungi to horses, based on lyophilized product, which increases the possibilities for future product development and application. New and improved ways of biological control should be developed and implemented to increase parasite control and reduce anthelmintic resistance cases.RESUMO - NOVA FÓRMULA DE ADMINISTRAÇÃO DE FUNGOS PARASITICIDAS PARA PREVENIR INFEÇÃO POR NEMÁTODES GASTROINTESTINAIS EM CAVALOS DE PASTOREIO (LUGO, ESPANHA) - A resistência a anti-helmínticos em cavalos tem vindo a aumentar recentemente e a procura por métodos de controlo alternativos levou ao desenvolvimento de abordagens complementares como o controlo biológico. Esta abordagem usa fungos parasiticidas, como Duddingtonia flagrans e Mucor circinelloides, no controlo da população parasitária e estudos recentes têm-se focado no desenvolvimento de novos métodos de administração. Seguindo esta tendência, uma fórmula nova e alternativa foi desenvolvida utilizando um produto liofilizado que contém esporos de D. flagrans e M. circinelloides para o controlo de nematodes gastrointestinais em cavalos. Após fabrico do produto e verificação da morfologia normal dos esporos, estes foram testados para crescimento in vitro. Um total de 20 placas de Petri foram semeadas com uma mistura de 0.1 g de produto e 0.5 ml de água em meio sólido. As placas foram mantidas a 25ºC em escuridão total e todas demonstraram desenvolvimento de novos esporos passados 10 dias. Após a verificação in vitro, o produto foi administrado per os a cavalos para observar o seu efeito nas contagens fecais de ovos (CFO) por grama (OPG). Assim, um grupo de 5 cavalos em pastoreio foi escolhido para receber 10 g de produto cada (com esporos de M. circinelloides e um total de cerca 105 clamidosporos de D. flagrans por cavalo) 3 vezes por semana, de setembro a março. Outro grupo de 7 cavalos numa pastagem adjacente foi utilizado como controlo. Após tratamento com unção contínua de Ivermectina em setembro de 2017, uma amostra fecal de cada cavalo foi colhida mensalmente e o CFO foi avaliado utilizando a técnica de McMaster modificado. Apenas ovos de nemátodes gastrointestinais, nomeadamente estrongilídeos, foram observados com esta técnica. A média de OPG de cada grupo foi comparada para cada mês e no total do estudo para observar o efeito de redução do tratamento fúngico. Diferenças estatisticamente significativas entre os dois grupos foram observadas em fevereiro, redução de 72%, março, redução de 64%, e no total, 66% de redução. Cavalos no grupo de teste só passaram o limiar de 300 OPG dois meses depois dos cavalos do grupo controlo. Em novembro e janeiro foram realizadas culturas fecais em todas as amostras, demonstrando apenas a existência de larvas de ciatostomíneos. Este estudo permitiu com sucesso o desenvolvimento de uma nova fórmula para administração oral de fungos parasiticidas para cavalos com base num produto liofilizado, aumentando as futuras possibilidades de desenvolvimento e aplicações de produtos. Novas e aperfeiçoadas formas de controlo biológico devem ser desenvolvidas e implementadas para aumentar o controlo de parasitas e diminuir os casos de resistência a anti-helmínticos.N/

The New Hampshire, Vol. 105, No. 25 (Feb. 1, 2016)

An independent student produced newspaper from the University of New Hampshire

Spartan Daily, March 2, 1990

Volume 94, Issue 25https://scholarworks.sjsu.edu/spartandaily/7955/thumbnail.jp

Effects of Mycobacterium vaccae NCTC 11659 (standard or recombinant) on cytokine production by human and murine cells

Killed M. vaccae is in clinical trials as an immunotherapeutic agent and adjuvant, but understanding of its mode of action is incomplete. To test its potential as a recombinant carrier organism and the nature of the responses evoked, recombinant strains were generated that expressed p27 of SFV. In mice these primed for specific production of IFNγ in the presence of p27, and induced serum IgG2a and, at higher doses, IgG1 responses to M. vaccae sonicate. Flow cytometry for intracellular cytokines after a single subcutaneous injection of 109 M. vaccae revealed accumulation of IFNγ-secreting CD8+ cells in lymph nodes. This finding, together with data generated simultaneously by another research group, implied an unusual adjuvant effect, not shared by other killed mycobacteria. In order to investigate this adjuvanticity the effects of killed M. vaccae on cytokine release from the human THP-1 monocyte line were investigated. M. vaccae, BCG and soluble bacterial preparations were all able to induce IL-12, IL-10 and TNFγ production in vitro to varying extents. Dose of mycobacterium and the addition of IFNγ influenced the balance of cytokines. Attempts to define active components in the IL-12 induction system were not successful, but it was noted that M. vaccae differed strikingly from the other killed mycobacteria in that its induction of IL-12 was greatly enhanced by exposure to lysozyme. The induction of IL-12 proved sufficiently reproducible to be used as a potency assay for material manufactured for clinical use. In conclusion, M. vaccae has been shown to be a potent Th1 inducer at appropriate doses, with the added ability to induce expansion of the CD8+ IFNγ+ population, perhaps via IL-12 release following exposure to lysozyme in vivo. CD8+ cells are strongly implicated in the clinical situations where M. vaccae has shown benefit