Mechanisms of fate decision and lineage commitment during haematopoiesis.

Blood stem cells need to both perpetuate themselves (self-renew) and differentiate into all mature blood cells to maintain blood formation throughout life. However, it is unclear how the underlying gene regulatory network maintains this population of self-renewing and differentiating stem cells and how it accommodates the transition from a stem cell to a mature blood cell. Our current knowledge of transcriptomes of various blood cell types has mainly been advanced by population-level analysis. However, a population of seemingly homogenous blood cells may include many distinct cell types with substantially different transcriptomes and abilities to make diverse fate decisions. Therefore, understanding the cell-intrinsic differences between individual cells is necessary for a deeper understanding of the molecular basis of their behaviour. Here we review recent single-cell studies in the haematopoietic system and their contribution to our understanding of the mechanisms governing cell fate choices and lineage commitment.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/icb.2015.9

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Validación del Nursing Activities Score en unidades de cuidados intensivos portuguesas

Objective: to describe the process of adaptation and validation of the Nursing Activities Score to the Portuguese context. Method: this was a pilot study of adaptation and validation of the Nursing Activities Score with a sample consisting of 67 patients hospitalized in the intensive care units of three Portuguese hospitals. The construct validity was assessed through factor analysis procedures and the internal consistency of the items was measured through the Cronbach’s alpha coeffi cient. Results: a mean workload value of 63.04% (SD = 14.25; Median = 61.30) was obtained. Psychometric data revealed a Cronbach’s alpha of 0.71 in the total scale, indicating an acceptable accuracy. Confi rmatory factor analysis suggested an appropriate adjustment between the model and the data (χ2 (199) = 214.5, p = 0.214; CFI = 0.95; RMSA = 0.035). Conclusion: in the present study, the Portuguese version of the Nursing Activities Score was found to be a valid instrument, enabling a safe assessment of the workload of nurses.Objetivo: descrever o processo de adaptação e validação do Nursing Activities Score para o contexto português. Método: trata-se de um estudo-piloto de adaptação e validação do Nursing Activities Score, com amostra de 67 doentes internados em unidades de cuidados intensivos de três hospitais portugueses. A validade de constructo avaliou-se mediante procedimentos de análise fatorial e a consistência interna dos itens através do coefi ciente Alpha de Cronbach. Resultados: obteve-se um valor médio da carga de trabalho de 63,04% (DP = 14,25; Mediana = 61,30). Os dados psicométricos revelaram um Alpha de Cronbach de 0,71, na escala total, indicando uma fi delidade aceitável. A análise fatorial confi rmatória sugeriu um ajustamento adequado entre o modelo e os dados (χ2(199) = 214,5, p = 0,214; CFI = 0,95; RMSA = 0,035). Conclusão: neste estudo, a versão portuguesa do Nursing Activities Score revelou-se um instrumento válido, permitindo avaliar a carga de trabalho dos enfermeiros com segurançaObjetivo: describir el proceso de adaptación y validación del Nursing Activities Score al contexto portugués. Método: estudio piloto de adaptación y validación del Nursing Activities Score, con muestra de 67 pacientes internados en unidades de cuidados intensivos de tres hospitales portugueses. La validez del constructo se evaluó mediante análisis factorial y por consistencia interna de los ítems evaluados a través del coefi ciente Alpha de Cronbach. Resultados: se obtuvo un valor medio de carga de trabajo de 63,04% (SD=14,25; Mediana=61,30). Los datos psicométricos expresaron un Alpha de Cronbach de 0,71 en la escala total, indicando fi delidad aceptable. El análisis factorial confi rmatorio sugirió un ajuste adecuado entre el modelo y os datos (χ2 (199)=214,5; p=0,214; CFI=0,95; RMSA=0,035). Conclusión: en este estudio, la versión portuguesa del Nursing Activities Score demostró ser un instrumento válido, permitiendo evaluar la carga de trabajo de los enfermeros con precisión

Study of scattered radiation during fluoroscopy in hip surgery

Objetivo: Medir a intensidade da dose de radiação espalhada em diferentes posições simulando uma intervenção cirúrgica no quadril. Materiais e Métodos: Simulou-se uma intervenção cirúrgica no quadril com apoio da fluoroscopia para estudar a distribuição da radiação espalhada no bloco operatório. Para simular o paciente foi utilizado um simulador antropomórfico de corpo inteiro e para medir a radiação utilizou-se um detector específico para medir raios X. Realizaram-se incidências com um equipamento de raios X tipo arco em C móvel, em modo de escopia contínua, com a ampola a 0° (configuração 1) e a 90° (configuração 2). Os parâmetros operacionais utilizados (voltagem, corrente, tempo de exposição) foram determinados por meio de um estudo estatístico resultante da observação de cirurgias ortopédicas de quadril. Resultados: Em todas as medições observaram-se exposições mais elevadas na configuração 2. Nas medições em função da altura, observaram-se os valores máximos da taxa de dose de 1,167 (± 0,023) µSv/s e 2,278 (± 0,023) µSv/s nas configurações 1 e 2, respectivamente, correspondendo à altura do tórax dos profissionais. No estudo em torno do paciente os valores máximos registraramse na posição ocupada pelo médico cirurgião. Conclusão: Concluiu-se que a exposição à radiação dos profissionais é baixa, podendo ainda ser reduzida mediante o uso de equipamentos de proteção individualObjective: To measure the scattered radiation dose at different positions simulating hip surgery. Materials and Methods: We simulated fluoroscopy-assisted hip surgery in order to study the distribution of scattered radiation in the operating room. To simulate the patient, we used a anthropomorphic whole-body phantom, and we used an X-ray-specific detector to quantify the radiation. Radiographs were obtained with a mobile C-arm X-ray system in continuous scan mode, with the tube at 0° (configuration 1) or 90° (configuration 2). The operating parameters employed (voltage, current, and exposure time) were determined by a statistical analysis based on the observation of orthopedic surgical procedures involving the hip. Results: For all measurements, higher exposures were observed in configuration 2. In the measurements obtained as a function of height, the maximum dose rates observed were 1.167 (± 0.023) µSv/s and 2.278 (± 0.023) µSv/s in configurations 1 and 2, respectively, corresponding to the chest level of health care professionals within the operating room. Proximal to the patient, the maximum values were recorded in the position occupied by the surgeon. Conclusion: We can conclude that, in the scenario under study, health care professionals workers are exposed to low levels of radiation, and that those levels can be reduced through the use of personal protective equipmen

A quantum spin transducer based on nano electro-mechancial resonator arrays

Implementation of quantum information processing faces the contradicting requirements of combining excellent isolation to avoid decoherence with the ability to control coherent interactions in a many-body quantum system. For example, spin degrees of freedom of electrons and nuclei provide a good quantum memory due to their weak magnetic interactions with the environment. However, for the same reason it is difficult to achieve controlled entanglement of spins over distances larger than tens of nanometers. Here we propose a universal realization of a quantum data bus for electronic spin qubits where spins are coupled to the motion of magnetized mechanical resonators via magnetic field gradients. Provided that the mechanical system is charged, the magnetic moments associated with spin qubits can be effectively amplified to enable a coherent spin-spin coupling over long distances via Coulomb forces. Our approach is applicable to a wide class of electronic spin qubits which can be localized near the magnetized tips and can be used for the implementation of hybrid quantum computing architectures

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Saccharomyces cerevisiae mutants affected in vacuole assembly or vacuolar H+-ATPase are hypersensitive to lead (Pb) toxicity

Lead is an important environmental pollutant. The role of vacuole, in Pb detoxification, was studied using a vacuolar protein sorting mutant strain (vps16Δ), belonging to class C mutants. Cells disrupted in VPS16 gene, did not display a detectable vacuolar-like structure. Based on the loss of cell proliferation capacity, it was found that cells from vps16Δ mutant exhibited a hypersensitivity to Pb-induced toxicity, compared to wild type (WT) strain. The function of vacuolar H+-ATPase (V-ATPase), in Pb detoxification, was evaluated using mutants with structurally normal vacuoles but defective in subunits of catalytic (vma1Δ or vma2Δ) or membrane domain (vph1Δ or vma3Δ) of V-ATPase. All mutants tested, lacking a functional V-ATPase, displayed an increased susceptibility to Pb, comparatively to cells from WT strain. Modification of vacuolar morphology, in Pb-exposed cells, was visualized using a Vma2p-GFP strain. The treatment of yeast cells with Pb originated the fusion of the medium size vacuolar lobes into one enlarged vacuole. In conclusion, it was found that vacuole plays an important role in the detoxification of Pb in Saccharomyces cerevisiae; in addition, a functional V-ATPase was required for Pb compartmentalization.The authors thank the Fundacao para a Ciencia e a Tecnologia (FCT) through the Portuguese Government for their financial support of this work through the grant PEST-OE/EQB/LA0023/2011 to IBB

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns