Complete Genome Sequence of the N2-Fixing Broad Host Range Endophyte Klebsiella pneumoniae 342 and Virulence Predictions Verified in Mice

We report here the sequencing and analysis of the genome of the nitrogen-fixing endophyte, Klebsiella pneumoniae 342. Although K. pneumoniae 342 is a member of the enteric bacteria, it serves as a model for studies of endophytic, plant-bacterial associations due to its efficient colonization of plant tissues (including maize and wheat, two of the most important crops in the world), while maintaining a mutualistic relationship that encompasses supplying organic nitrogen to the host plant. Genomic analysis examined K. pneumoniae 342 for the presence of previously identified genes from other bacteria involved in colonization of, or growth in, plants. From this set, approximately one-third were identified in K. pneumoniae 342, suggesting additional factors most likely contribute to its endophytic lifestyle. Comparative genome analyses were used to provide new insights into this question. Results included the identification of metabolic pathways and other features devoted to processing plant-derived cellulosic and aromatic compounds, and a robust complement of transport genes (15.4%), one of the highest percentages in bacterial genomes sequenced. Although virulence and antibiotic resistance genes were predicted, experiments conducted using mouse models showed pathogenicity to be attenuated in this strain. Comparative genomic analyses with the presumed human pathogen K. pneumoniae MGH78578 revealed that MGH78578 apparently cannot fix nitrogen, and the distribution of genes essential to surface attachment, secretion, transport, and regulation and signaling varied between each genome, which may indicate critical divergences between the strains that influence their preferred host ranges and lifestyles (endophytic plant associations for K. pneumoniae 342 and presumably human pathogenesis for MGH78578). Little genome information is available concerning endophytic bacteria. The K. pneumoniae 342 genome will drive new research into this less-understood, but important category of bacterial-plant host relationships, which could ultimately enhance growth and nutrition of important agricultural crops and development of plant-derived products and biofuels

The TOTEM Experiment at the CERN Large Hadron Collider

The TOTEM Experiment will measure the total pp cross-section with the luminosity independent method and study elastic and diffractive scattering at the LHC. To achieve optimum forward coverage for charged particles emitted by the pp collisions in the interaction point IP5, two tracking telescopes, T1 and T2, will be installed on each side in the pseudorapidity region 3,1 <h< 6,5, and Roman Pot stations will be placed at distances of 147m and 220m from IP5. Being an independent experiment but technically integrated into CMS, TOTEM will first operate in standalone mode to pursue its own physics programme and at a later stage together with CMS for a common physics programme. This article gives a description of the TOTEM apparatus and its performance

Marcapasso responsivo baseado em atividade: Comparaçao entre um aparelho que utiliza acelerômetro e um com cristal piezoelétrico

Dois marcapassos responsivos, um EXCELTM VR, equipado com acelerômetro (AC) e outro LEGENDTM, dotado de cristal piezoelétrico (PZ), foram comparados sob condiçoes ergo métricas e durante a subida de escada para verificar a adeqüaçao de suas respostas. Os marcapassos, programados dentro dos parâmetros nominais dos fabricantes de modo a comparar diferentes tecnologias de sensores sob condiçoes idênticas, foram fixados sobre a regiao peitoral média esquerda dos voluntários. O posicionamento dos marcapassos foi randomizado para controlar os efeitos causados pela posiçao. Dez indivíduos sadios (55-72 anos) completaram um teste de esteira graduado para 80% da freqüência cardíaca máxima prevista. Um grupo adicional de dez pacientes (50-66 anos) completou um protocolo de exercício envolvendo o uso de bicicleta ergométrica e subida de escadas. Durante todos os testes, foram monitoradas as freqüências do marcapasso e a dos voluntários (intrínseca). Para o exercício na esteira, as correlaçoes médias entre as freqüências dos marcapassos AC e PZ, para o grupo como um todo, foram r = 0,92 e r = 0,82, respectivamente. Também foram feitas comparaçoes individuais entre a freqüência do marcapasso e a FC intrínseca de cada voluntário. A média das diferenças entre a freqüência intrínseca foi de 11 ppm para o marcapasso AC e de 24 ppm para o PZ. Além disso, a freqüência máxima do marcapasso PZ foi significativamente menor (105 ± 9,6 ppm) do que as outras duas freqüências (AC 137 ± 6 ppm; FC intrínseca 129 ± 2 bpm). Durante o teste na bicicleta ergométrica, a FC intrínseca foi maior do que as freqüências de estimulaçao dos marcapassos AC e PZ. Entretanto, a freqüência do marcapasso AC foi significativamente maior do que a do PZ. Quando os indivíduos subiram escadas, houve uma correlaçao muito próxima entre a FC intrínseca e a do AC, mas a freqüência do marcapasso PZ foi significativamente menor. Nenhum dos marcapassos teve sua freqüência de estimulaçao sobreposta à FC intrínseca durante a descida das escadas. Estes resultados indicam que o marcapasso AC se aproxima mais da FC intrínseca de indivíduos sadios durante a atividade ergométrica e a subida de escadas do que o PZ. Apesar das três atividades avaliadas constituirem uma representaçao pobre de outras tarefas diárias, estes resultados oferecem suporte para que o uso de um marcapasso AC seja considerado. Estes dados também sugerem a necessidade de melhores pesquisas com marcapassos responsivos baseados em atividade, após a otimizaçao dos parâmetros para cada indivíduo, a fim de encontrar os melhores níveis de sensibilidade e especificidade do movimento humano

Presalvage International Staging System Stage and Other Important Outcome Associations in CD34+-Selected Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Despite ongoing therapeutic advances, multiple myeloma (MM) remains largely incurable, and outcomes in patients who develop resistance to immunomodulatory drugs or proteasome inhibitors remain grim. Allogeneic hematopoietic cell transplantation (alloHCT) is an alternative option that may offer potential for cure. Although rates of transplantation-related morbidity and mortality have decreased in recent years, weighing this approach's potential benefits against nontransplantation therapies demands a thoroughly informed pre-alloHCT assessment. Here we assess the impact of pre-alloHCT variables on important clinical outcomes in a large cohort of relapsed refractory MM (RRMM) CD34+-selected alloHCT recipients. We included all patients with MM who underwent CD34+-selected alloHCT at our center between June 2010 and December 2015. Patients were conditioned with busulfan (0.8 mg/kg × 10), melphalan (70 mg/m2 × 2), and fludarabine (25 mg/m2 × 5), followed by infusion of a CD34+-selected peripheral blood stem cell graft, without post-alloHCT graft-versus-host disease (GVHD) prophylaxis. The 73-patient cohort had a median age of 55 years (range, 37 to 66 years). Overall survival (OS) and progression-free survival (PFS) rates were 70% and 53%, respectively, at 1 year (95% confidence interval [CI], 58% to 79% and 41% to 64%) and 50% and 30%, respectively, at 3 years (95% CI, 38% to 62% and 19% to 41%). The cumulative incidence of relapse was 25% at 1 year (95% CI, 15% to 35%) and 47% at 3 years (95% CI, 35% to 58%). Nonrelapse mortality at 1 year was 22% (95% CI, 13% to 32%). The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 7% at 100 days (95% CI, 3% to 14%), and that of any chronic GVHD (cGVHD) was 8% at 1 year (95% CI, 3% to 16%). International Staging System (ISS) stage II-III assessed before salvage therapy was associated with poorer 3-year OS (30% versus 54%; P = .037) and 3-year PFS (9% versus 33%; P = .013), and increased 3-year relapse incidence (72% versus 39%; P = .004). Older age and GVHD before 6 months (aGVHD grade II-IV or cGVHD of any grade) were also associated with poorer OS, and a greater number of pre-alloHCT lines of therapy was also associated with increased relapse incidence. Our findings reinforce that CD34+-selected alloHCT can achieve prolonged disease control and long-term survival in high- risk, heavily treated refractory MM populations. We also identified numerous pre-alloHCT variables associated with OS, PFS, and relapse. Amongst these, presalvage ISS stage II-III was consistently associated with poorer survival and relapse outcomes. Given the lack of established alternate therapies for patients with RRMM, we advocate the identification of adverse pre-alloHCT variables to inform alloHCT decision making rather than to exclude patient cohorts from this potentially curative treatment option

The TOTEM GEM Telescope (T2) at the LHC

16sireservedThe TOTEM T2 telescope will measure inelastically produced charged particles in the forward region of the LHC Interaction Point 5. Each arm of the telescope consists in a set of 20 triple-GEM (Gas Electron Multiplier) detectors with tracking and trigger capabilities. The GEM technology has been considered for the design of TOTEM very forward T2 telescopes thanks to its characteristics: large active areas, good position and timing resolution, excellent rate capability and radiation hardness. Each of the four T2 half arms has been fully assembled and equipped with electronics at CERN and systematically tested in the SPS beam line H8 in 2008/09. After some optimization, the operation of the GEM chambers was fully satisfactory and the T2 telescopes were installed and commissioned in their final positions at the LHC interaction point. During the first LHC run (December 2009) the T2 telescopes have collected data, at 900 GeV and 2.36 TeV. We will present here the performances of the detector and the preliminary results obtained using the data collected.mixedQuinto, M.; Berretti, Mirko; David, E.; Garcia, F.; Greco, V.; Heino, J.; Hilden, T.; Kurvinen, K.; Lami, S.; Latino, G.; Lauhakangas, R.; Oliveri, Eraldo; Ropelewski, L.; Scribano, Angelo; Turini, Nicola; van Stenis, M.Quinto, M.; Berretti, Mirko; David, E.; Garcia, F.; Greco, V.; Heino, J.; Hilden, T.; Kurvinen, K.; Lami, S.; Latino, G.; Lauhakangas, R.; Oliveri, Eraldo; Ropelewski, L.; Scribano, Angelo; Turini, Nicola; van Stenis, M

A C. elegans-based foam for rapid on-site detection of residual live virus.

In the response to and recovery from a critical homeland security event involving deliberate or accidental release of biological agents, initial decontamination efforts are necessarily followed by tests for the presence of residual live virus or bacteria. Such 'clearance sampling' should be rapid and accurate, to inform decision makers as they take appropriate action to ensure the safety of the public and of operational personnel. However, the current protocol for clearance sampling is extremely time-intensive and costly, and requires significant amounts of laboratory space and capacity. Detection of residual live virus is particularly problematic and time-consuming, as it requires evaluation of replication potential within a eukaryotic host such as chicken embryos. The intention of this project was to develop a new method for clearance sampling, by leveraging Sandia's expertise in the biological and material sciences in order to create a C. elegans-based foam that could be applied directly to the entire contaminated area for quick and accurate detection of any and all residual live virus by means of a fluorescent signal. Such a novel technology for rapid, on-site detection of live virus would greatly interest the DHS, DoD, and EPA, and hold broad commercial potential, especially with regard to the transportation industry

Compassionate Honesty

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85107/1/jpm_2010_9777.pd

The TOTEM T2 telescope based on triple-GEM chambers

The TOTEM experiment at LHC has chosen the triple Gas Electron Multiplier (GEM) technology for its T2 telescope which will provide charged track reconstruction in the pseudorapidity range 5.3<|η|<6.5 and a fully inclusive trigger for inelastic events. GEMs are gas filled detectors which combine good spatial resolution with very high rate capability and a good resistance to radiation. Preliminary results of cosmic ray tests performed at CERN on final T2 modules before installation are here presented. Comparisons between real and simulated detector performance are also shown