Rhymes: a shared virtual memory system for non-coherent tiled many-core architectures

The rising core count per processor is pushing chip complexity to a level that hardware-based cache coherency protocols become too hard and costly to scale. We need new designs of many-core hardware and software other than traditional technologies to keep up with the ever-increasing scalability demands. The Intel Single-chip Cloud Computer (SCC) is a recent research processor exemplifying a new cluster-on-chip architecture which promotes a software-oriented approach instead of hardware support to implementing shared memory coherence. This paper presents a shared virtual memory (SVM) system, dubbed Rhymes, tailored to such a new processor kind of non-coherent and hybrid memory architectures. Rhymes features a two-way cache coherence protocol to enforce release consistency for pages allocated in shared physical memory (SPM) and scope consistency for pages in per-core private memory. It also supports page remapping on a per-core basis to boost data locality. We implement Rhymes on the SCC port of the Barrelfish OS. Experimental results show that our SVM outperforms the pure SPM approach used by Intel's software managed coherence (SMC) library by up to 12 times, with superlinear speedups (due to L2 cache effect) noted for applications with strong data reuse patterns.published_or_final_versio

Extending the Operating Range of Electric Spring using Back-To-Back Converter: Hardware Implementation and Control

This paper presents the first hardware implementation and control of an electric spring based on a back-to-back converter configuration. Because of its ability to provide both active and reactive power compensation, this back-to-back electric spring (ES-B2B) can substantially extend the operating range of the original version of the electric spring (ES-1) and provide enhanced voltage support and suppression functions. The hardware system and control of the ES-B2B have been successfully developed and tested. The experimental results have confirmed the effectiveness of the ES-B2B in supporting and suppressing the mains voltage. Particularly, the voltage suppression ability of the ES-B2B is superior over that of ES-1. The use of ES-B2B in a simulation study of a weak power grid has also been conducted. The ES-B2B has been found to be highly effective in mitigating voltage fluctuation caused by intermittent renewable power generation

An Insight into Life at Geometric Zagora Provided by the Animal Bones

This thesis is a study of the animal bone distribution at the Geometric period settlement of Zagora (ca. 850-700 BC), on the island of Andros. The animal bones were excavated during the 1967-74 University of Sydney excavations and analysed in 1977 by a specialist who compiled a report of her findings. The report is currently in preparation for publication and is the primary source for this thesis. The data it provided was limited but enough could be extracted to identify patterns that permitted a tentative reconstruction of social life and the economy at Zagora. There is a paucity of excavated settlements from the Greek EIA and few of these have published faunal material, an essential element in reconstructing past lifeways. Those preserved settlements from which animal bones have been published are not extensive with good domestic contexts but usually sites of minimal extent. Hence, it has not been possible to conduct an analysis of the spatial distribution of animal bones from such a settlement. Zagora, being an extensive settlement containing mainly domestic structures, is therefore unique and the animal bone report provided the opportunity for such a study to be undertaken. A number of analyses were performed using both statistical and non-statistical methods. Through these it was discovered that there is a relationship between the animal size and the size of the architectural unit within which it was found. Similarly, there appeared to be a relationship between larger architecture and the presence of fish, postulated as being a pelagic species. The patterns observed were interpreted as evidence of ‘special’ meals with a larger than usual number of diners in attendance and hence the need for a larger space to host them. Using the animal bones’ distribution and architectural evidence it is proposed that feasting was an important event at Zagora, conducted at the household level to possibly reinforce bonds of kinship and friendship. The evidence also suggests that the H area could have been inhabited by people of better means than elsewhere in the settlement, particularly by the hypaethral sanctuary. Ideally the animal bones would have been studied in conjunction with associated artefacts, but this was not possible and so this would be something desirable to be performed in the near future. With 21st century excavation techniques, the future Zagora excavations should provide greater granularity in the faunal information obtained from the settlement to allow better precision in subsequent analyses

Inibidores de urease, serapilheira e adensamento do cafeeiro arábica: relações com a matéria orgânica do solo

O uso de tecnologias nas lavouras cafeeiras deve proporcionar melhorias nas condições de manejo, auxiliar na produção vegetal e promover qualidade ao solo e meio ambiente. Neste sentido, as tecnologias fertilizantes inibidores de urease, serapilheira foliar cafeeira e o adensamento cafeeiro foram avaliados atendendo há problemáticas no manejo das lavouras de cafeicultores familiares do Território do Caparaó- ES. O capítulo 1 teve por objetivo verificar o potencial dos inibidores de urease quanto à redução da volatilização NH3 e emissão de CO2 do solo, bem como avaliar a atividade da enzima urese do solo e a influência dos inibiores de urease sobre a matéria orgânica do solo. Os inibidores de urease NBPT e Cu+B mostraram ser promissores na redução da volatilização da NH3, principalmente o NBPT que volatilizou, em função das doses avaliadas, de 1,4 a 5,6 % do total de N aplicado. O efluxo de CO2 seguiu a ordem: Uréia> Uréia+Cu+B > Uréia+NBPT. De modo semelhante, os inibidores de urease reduziram a atividade da enzima urease do solo, sendo a uréia comum, o tratamento que proporcionou maior atividade da enzima. Apesar das fontes e doses de N não influenciarem sobre os teores de C orgânica do solo, verificou-se redução de 5,1 % no seu teor médio dos 16 para os 32 dias, ou seja, um curto período de tempo tem promovido redução na matéria orgânica do solo. O capítulo 2 teve por objetivo verificar o efeito da associação inibidores de urease e serapilheira sobre a volatilização da amônia e emissão de CO2 bem como a taxa de decomposição e liberação de nutrientes da serapilheira e seu efeito na matéria orgânica do solo. A ordem de volatilização da NH3 e emissão de CO2 foi: Uréia> Uréia+Cu+B > Uréia+NBPT. Contudo, o aumento da dose de serapilheira proporciona menor emissão de NH3, porém, maior emissão de CO2 (y=0,95x+3,82). Na dose equivalente a 4,5 Mg ha-1 de serapilheira e após 64 dias de decomposição, a quantidade liberada de C, N, P, K, Ca e Mg foi equivalente a 547,1; 49,0; 1,28; 17,4; 18,2 e 5,0 kg ha-1, respectivamente. Fontes de N e doses de serapilheira não influenciaram no teor de C orgânico total e N total do solo, entretanto, dos 16 aos 64 dias após a aplicação da serapilheira ocorreu redução nos seus teores em 15,4 e 21,1 %, respectivamente. O capítulo 3 teve por objetivo avaliar o efeito dos inibidores de urease juntamente com a serapilheira foliar cafeeira sobre os parâmetros biométricos, teor e acúmulo de N, atividade da urease foliar e % de clorofila no desenvolvimento inicial do cafeeiro IAC 144. Independente da fonte de N avaliada, a dose de 1,2 g vaso-1 de N foi suficiente para proporcionar altura da planta, diâmetro do caule, número de nós, pares de folhas, ramos plagiotrópicos e massa seca igual ou superiores as demais doses. Maiores teores de N foliar foram proporcionados pelos inibidores de urease e na maior dose aplicada impactando também, em maior atividade da enzima urease na folha. Não é recomendada a utilização de serapilheira no plantio do cafeeiro, pois ela proporcionou redução de 9,1; 3,3; 10,5 e 19,3 % na altura, número de nós, diâmetro do caule e número de ramos plagiotrópicos, respectivamente, e reduziu a produção de massa seca e o acúmulo de N na parte aérea. Fontes, doses de N e a serapilheira não influenciaram os teores de clorofila, entretanto, aumento dos teores de clorofila foram verificadas ao longo do tempo após a adubação nitrogenada. Já em condições de campo, o capítulo 4 da tese teve por objetivo determinar a influência do adensamento da lavoura cafeeira sobre os teores e estoques de COT e NT do solo, C e N da biomassa microbiana, matéria orgânica leve, labilidade da matéria orgânica do solo, as substâncias húmicas, densidade, porosidade e as emissões de CO2, temperatura e umidade do solo na região montanhosa do Território do Caparaó - Espírito Santo. O manejo cafeeiro adensado (8333 plantas ha-1) proporcionou aumento da MOL e C-MOL, menor densidade do solo, maior macroporosidade e porosidade total em relação ao cafeeiro convencional (3105 plantas ha-1). Épocas quentes e úmidas do ano favorecem as emissões de CO2 do solo, entretanto, o manejo do cafeeiro sob sistema adensado é o sistema que proporcionou menores emissões de CO2 do solo. A maior quantidade de serapilheira cafeeira do sistema adensado não estimula a atividade microbiológica do solo, entretanto, protege o solo contra erosão, aumenta a umidade e reduz a amplitude térmica. Palavras-chave: Espaçamento, agricultura familiar, volatilização, fertilizantes nitrogenados, Território do Capara

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo

Antibody stabilization for thermally accelerated deep immunostaining

Antibodies have diverse applications due to their high reaction specificities but are sensitive to denaturation when a higher working temperature is required. We have developed a simple, highly scalable and generalizable chemical approach for stabilizing off-the-shelf antibodies against thermal and chemical denaturation. We demonstrate that the stabilized antibodies (termed SPEARs) can withstand up to 4 weeks of continuous heating at 55 °C and harsh denaturants, and apply our method to 33 tested antibodies. SPEARs enable flexible applications of thermocycling and denaturants to dynamically modulate their binding kinetics, reaction equilibrium, macromolecular diffusivity and aggregation propensity. In particular, we show that SPEARs permit the use of a thermally facilitated three-dimensional immunolabeling strategy (termed ThICK staining), achieving whole mouse brain immunolabeling within 72 h, as well as nearly fourfold deeper penetration with threefold less antibodies in human brain tissue. With faster deep-tissue immunolabeling and broad compatibility with tissue processing and clearing methods without the need for any specialized equipment, we anticipate the wide applicability of ThICK staining with SPEARs for deep immunostaining

Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

The changing seroepidemiology of enterovirus 71 infection among children and adolescents in Singapore

<p>Abstract</p> <p>Background</p> <p>Enterovirus 71 (EV71) has caused recurrent epidemics of hand, foot and mouth disease among children in Singapore. Between August 2008 and July 2010, we conducted a survey to estimate the seroprevalence of EV71 infection among children and adolescents aged 1-17 years. We compared our EV71 seroepidemiologic findings with a previous study conducted in 1996-1997.</p> <p>Methods</p> <p>The survey involved the prospective collection of 1,200 residual sera from Singapore residents aged 1-17 years in two hospitals. Neutralizing antibodies to EV71 were detected by the microneutralization test. The geometric mean titer (GMT) of EV71 antibodies and 95% confidence intervals (CI) were calculated and compared by age groups. Statistical significance was taken as <it>P </it>< 0.05.</p> <p>Results</p> <p>The overall EV71 antibody prevalence was 26.9% (95% CI: 24.5-29.5%). It increased significantly from 14.3% in children aged 1-6 years to 27.8% in those aged 7-12 years, and reached 38.8% in adolescents aged 13-17 years. The seroconversion rate differed by about 12% between the consecutive age groups. The GMT of EV71 antibodies was higher among primary school children aged 7-12 years in our study than that among the 6-12 year age group in the 1996-1997 study.</p> <p>Conclusions</p> <p>Higher antibody titers were observed in children aged 1-6 years than those in the other two age groups, indicating that most of the infections had been acquired during early childhood. EV71 infection is common among children and adolescents in Singapore, with 39% infected by the time they are in secondary school (13-17 years of age).</p