Searching for Gravitational Waves with a Geostationary Interferometer

We analyze the sensitivities of a geostationary gravitational wave interferometer mission operating in the sub-Hertz band. Because of its smaller armlength, in the lower part of its accessible frequency band ($10^{-4} - 2 \times 10^{-2}$ Hz) our proposed Earth-orbiting detector will be less sensitive, by a factor of about seventy, than the Laser Interferometer Space Antenna (LISA) mission. In the higher part of its band instead ($2 \times 10^{-2} - 10$ Hz), our proposed interferometer will have the capability of observing super-massive black holes (SMBHs) with masses smaller than $\sim 10^{6}$ M$_{\odot}$. With good event rates for these systems, a geostationary interferometer will be able to accurately probe the astrophysical scenarios that account for their formation.Comment: 33 pages, 9 eps figure

Comparison of advanced gravitational-wave detectors

We compare two advanced designs for gravitational-wave antennas in terms of their ability to detect two possible gravitational wave sources. Spherical, resonant mass antennas and interferometers incorporating resonant sideband extraction (RSE) were modeled using experimentally measurable parameters. The signal-to-noise ratio of each detector for a binary neutron star system and a rapidly rotating stellar core were calculated. For a range of plausible parameters we found that the advanced LIGO interferometer incorporating RSE gave higher signal-to-noise ratios than a spherical detector resonant at the same frequency for both sources. Spheres were found to be sensitive to these sources at distances beyond our galaxy. Interferometers were sensitive to these sources at far enough distances that several events per year would be expected

Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease

Background:Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection.Methods:Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of São Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles.Results:Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease.Conclusions:The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis

Efeito da Gliricidia sepium sobre nutrientes do solo, microclima e produtividade do milho em sistema agroflorestal no Agreste Paraibano.

Gliricidia sepium é uma leguminosa arbórea que tem sido utilizada em sistemas em aléias no semi-árido nordestino por apresentar bom desenvolvimento em condições de estresse hídrico. Entretanto, há pouca informação disponível sobre o efeito da introdução dessa espécie nos agroecossistemas da região. No presente estudo, objetivou-se avaliar a influência da distância de plantas de Gliricidia sepium sobre características da cultura do milho e do solo e microclima no Agreste Paraibano. O estudo foi realizado no município de Esperança (PB), em área de 0,5 ha, onde, em 1996, foram plantadas fileiras de G. sepium espaçadas 6 m entre si e com 1 m entre as árvores. Nesta área, em 2002, foram delimitadas quatro parcelas de 6 x 8 m e, em cada parcela, foi estabelecido um transeto perpendicular às fileiras de árvores com três posições de amostragem: (1) nas fileiras de árvores (0 m); (2) a 1 m das fileiras de árvores, e (3) a 3 m de distância das fileiras de árvores. O delineamento experimental utilizado foi em blocos casualizados com quatro repetições. A massa seca de folhedo caído embaixo da fileira de árvores foi de 1.390 kg ha-1 e diminuiu, gradativamente, para 270 kg ha-1 a 3 m de distância das árvores. As concentrações de P, K e matéria orgânica leve (MOL) embaixo das árvores foram maiores do que a 1 e 3 m de distância das fileiras. As médias mensais das temperaturas mínimas do ar e do solo embaixo e a 3 m das árvores foram similares. Entretanto, as médias mensais das temperaturas máximas do solo e do ar foram de 6 e 2 °C mais altas a 3 m das árvores, respectivamente, ao longo do período de estudo. A umidade do solo foi significativamente menor embaixo das árvores do que a 1 e 3 m de distância. O milho produziu mais grãos e palha e acumulou mais nutrientes nas posições mais próximas das fileiras de G. sepium

The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells

In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34(+) samples. However, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. Pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. Despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. Here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. We observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34(+) samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. The EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. Our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. Therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients