1,351 research outputs found
Comparison of Coulomb Blockade Thermometers with the International Temperature Scale PLTS-2000
The operation of the primary Coulomb blockade thermometer (CBT) is based on a
measurement of bias voltage dependent conductance of arrays of tunnel junctions
between normal metal electrodes. Here we report on a comparison of a CBT with a
high accuracy realization of the PLTS-2000 temperature scale in the range from
0.008 K to 0.65 K. An overall agreement of about 1% was found for temperatures
above 0.25 K. For lower temperatures increasing differences are caused by
thermalization problems which are accounted for by numerical calculations based
on electron-phonon decoupling.Comment: 6 pages, 5 figure
Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma
Galectin-1 (Gal1) is a member of a highly conserved family of carbohydrate-binding proteins that modulates innate and adaptive immune responses and fosters tumor-immune escape. Hodgkin lymphoma (HL) Reed-Sternberg (RS) cells overexpress and secrete Gal1, which selectively kills Th1,Th17 and cytotoxic T cells and promotes the immunosuppressive Th2/Treg-predominant HL microenvironment. We developed a sandwich ELISA and assessed serum Gal1 levels in 315 newly diagnosed, previously untreated HL patients enrolled on 3 risk-adapted clinical trials. Serum Gal1 levels were significantly higher in HL patients than in normal controls (p < .0001). Gal1 serum levels also increased with Ann Arbor stage (p < .0001), areas of nodal involvement (p = .0001) and the International Prognostic Score (IPS) (2-7, p = .006). We conclude that Gal1 serum levels are significantly associated with tumor burden and additional adverse clinical characteristics in newly diagnosed HL Patients.Fil: Ouyang, Jing. Dana-Farber Cancer Institute. Department of Medical Oncology; Estados Unidos de América;Fil: Plütschow, Annette. German Hodgkin Study Group; Alemania;Fil: Von Strandmann, Elke Pogge. University Hospital of Cologne. Laboratory for Immunotherapy; Alemania;Fil: Reiners, Katrin S.. University Hospital of Cologne. Laboratory for Immunotherapy; Alemania;Fil: Ponader, Sabine. German Hodgkin Study Group; Alemania;Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina;Fil: Neuberg, Donna. Dana-Farber Cancer Institute. Department of Biostatistics; Estados Unidos de América;Fil: Engert, Andreas. German Hodgkin Study Group; Alemania;Fil: Shipp, Margaret A.. Dana-Farber Cancer Institute. Department of Medical Oncology; Estados Unidos de América
Increased angiogenic factor secretion by decidual natural killer cells from pregnancies with high uterine artery resistance alters trophoblast function.
STUDY QUESTION
Are the concentrations of factors secreted by decidual natural killer (dNK) cells from pregnancies at high risk of poor spiral artery remodelling different to those secreted from pregnancies at low risk?
SUMMARY ANSWER
Expression levels of PLGF, sIL-2R, endostatin and angiogenin were significantly increased by dNK cells from high-risk pregnancies, and angiogenin and endostatin were found to alter trophoblast function.
WHAT IS KNOWN ALREADY
During early pregnancy, maternal uterine spiral arteries are remodelled from small diameter, low-flow, high-resistance vessels into larger diameter, higher flow vessels, with low-resistance. This change is essential for the developing fetus to obtain sufficient oxygen and nutrients. dNK cells have been implicated in this process.
STUDY DESIGN, SIZE, DURATION
dNK cells were isolated from first trimester terminations of pregnancies (obtained with local ethical approval) screened for normal- or high-resistance index, indicative of cases least (21%) likely to have developed pre-eclampsia had the pregnancy not been terminated (n = 18 each group). Secreted factors and the effects of these on the trophoblast cell line, SGHPL-4, were assessed in vitro.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A multiplex assay was used to assess dNK cell-secreted factors. SGHPL-4 cell functions were assessed using time-lapse microscopy, 3D invasion assays, endothelial-like tube formation ability and western blot analysis.
MAIN RESULTS AND THE ROLE OF CHANCE
The expression levels of PLGF (P < 0.01), sIL-2R (P < 0.01), endostatin (P < 0.05) and angiogenin (P < 0.05) were significantly increased by dNK cells from high-risk pregnancies. Endostatin significantly decreased SGHPL-4 invasion (P < 0.05), SGHPL-4 tube formation (P < 0.05) and SGHPL-4 Aktser473 phosphorylation (P < 0.05). Angiogenin significantly decreased SGHPL-4 invasion (P < 0.05), but increased SGHPL-4 tube formation (P < 0.01) and decreased SGHPL-4 Aktser473 phosphorylation (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION
The culture of dNK cells and protein concentrations in vitro may not fully represent the in vivo situation. Although SGHPL-4 cells are extravillous trophoblast derived, further studies would be needed to confirm the roles of angiogenin and endostatin in vivo.
WIDER IMPLICATIONS OF THE FINDINGS
The altered expression of secreted factors of dNK cells may contribute to pregnancy disorders associated with poor spiral artery remodelling.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by the Wellcome Trust (project reference 091550). R.F. was a recipient of a PhD studentship from the Division of Biomedical Sciences, St. George's, University of London. The authors have no conflict of interests
Self-organized critical neural networks
A mechanism for self-organization of the degree of connectivity in model
neural networks is studied. Network connectivity is regulated locally on the
basis of an order parameter of the global dynamics which is estimated from an
observable at the single synapse level. This principle is studied in a
two-dimensional neural network with randomly wired asymmetric weights. In this
class of networks, network connectivity is closely related to a phase
transition between ordered and disordered dynamics. A slow topology change is
imposed on the network through a local rewiring rule motivated by
activity-dependent synaptic development: Neighbor neurons whose activity is
correlated, on average develop a new connection while uncorrelated neighbors
tend to disconnect. As a result, robust self-organization of the network
towards the order disorder transition occurs. Convergence is independent of
initial conditions, robust against thermal noise, and does not require fine
tuning of parameters.Comment: 5 pages RevTeX, 7 figures PostScrip
Active flow control systems architectures for civil transport aircraft
Copyright @ 2010 American Institute of Aeronautics and AstronauticsThis paper considers the effect of choice of actuator technology and associated power systems architecture on the mass cost and power consumption of implementing active flow control systems on civil transport aircraft. The research method is based on the use of a mass model that includes a mass due to systems hardware and a mass due to the system energy usage. An Airbus A320 aircraft wing is used as a case-study application. The mass model parameters are based on first-principle physical analysis of electric and pneumatic power systems combined with empirical data on system hardware from existing equipment suppliers. Flow control methods include direct fluidic, electromechanical-fluidic, and electrofluidic actuator technologies. The mass cost of electrical power distribution is shown to be considerably less than that for pneumatic systems; however, this advantage is reduced by the requirement for relatively heavy electrical power management and conversion systems. A tradeoff exists between system power efficiency and the system hardware mass required to achieve this efficiency. For short-duration operation the flow control solution is driven toward lighter but less power-efficient systems, whereas for long-duration operation there is benefit in considering heavier but more efficient systems. It is estimated that a practical electromechanical-fluidic system for flow separation control may have a mass up to 40% of the slat mass for a leading-edge application and 5% of flap mass for a trailing-edge application.This work is funded by the Sixth European Union Framework Programme as part of the AVERT project (Contract No. AST5-CT-2006-030914
Summary of CPAS EDU Testing Analysis Results
The Orion program's Capsule Parachute Assembly System (CPAS) project is currently conducting its third generation of testing, the Engineering Development Unit (EDU) series. This series utilizes two test articles, a dart-shaped Parachute Compartment Drop Test Vehicle (PCDTV) and capsule-shaped Parachute Test Vehicle (PTV), both of which include a full size, flight-like parachute system and require a pallet delivery system for aircraft extraction. To date, 15 tests have been completed, including six with PCDTVs and nine with PTVs. Two of the PTV tests included the Forward Bay Cover (FBC) provided by Lockheed Martin. Advancements in modeling techniques applicable to parachute fly-out, vehicle rate of descent, torque, and load train, also occurred during the EDU testing series. An upgrade from a composite to an independent parachute simulation allowed parachute modeling at a higher level of fidelity than during previous generations. The complexity of separating the test vehicles from their pallet delivery systems necessitated the use the Automatic Dynamic Analysis of Mechanical Systems (ADAMS) simulator for modeling mated vehicle aircraft extraction and separation. This paper gives an overview of each EDU test and summarizes the development of CPAS analysis tools and techniques during EDU testing
Stability of resilience in times of the COVID‐19 pandemic
There is disagreement among researchers regarding the conceptualization of resilience as a dynamic state or stable trait. Aiming to shed light on the state-versus-trait debate, we explored the stability and construct validity of four of the most frequently utilized state or trait resilience scales in a longitudinal assessment. Additionally, we examined the predictive validity of these scales. Our study was conducted before and during the COVID-19 pandemic, which served as collectively experienced adversity. Correlations among the resilience scales and among resilience scales and Big Five personality traits were strong. All except one scale showed high test-retest correlations. Experience of an additional critical life event during the pandemic led to an increase in resilience. Other than in cross-sectional studies, associations between resilience and psychological distress were weak, because personality and baseline psychological distress were controlled for. Nevertheless, next to personality, resilience explained additional variance in distress change. Our results show relatively high stability of resilience overall. Yet, they also confirm dynamic resilience features, suggesting that resilience change occurs with significant adversity, leading to improved adaptation. To gauge the true association between resilience and mental health, baseline levels of these variables as well as personality traits should be considered
Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial
Background In the HD14 trial, 2× BEACOPPescalated+2× ABVD (2+2) has improved the primary outcome. Compared with 4× ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility. Patients and methods Women ≤45 years in ongoing remission at least 1 year after therapy were included. Hormone parameters, menopausal symptoms, measures to preserve fertility, menstrual cycle, pregnancies, and offspring were evaluated. Results Three hundred and thirty one of 579 women addressed participated (57.2%) and 263 per-protocol treated patients qualified (A=ABVD: 137, B=2+2: 126, mean time after therapy 42 and 43 months, respectively). Regular menstrual cycle after treatment (A: 87%, B: 83%) and time to recovery (≤12 months) were not different. Follicle-stimulating hormone and anti-Muellerian hormone were significantly better in arm A. However, pregnancies after therapy favored arm B (A: 15%, B: 26%, P=0.043) and motherhood rates were equivalent to the German normal population. Multivariate analysis revealed prophylactic use of gonadotropin-releasing hormone (GnRH) analogues as highly significant prognostic factor for preservation of fertility (odds ratio=12.87, P=0.001). Severe menopausal symptoms were frequent in women ≥30 years (A: 21%, B: 25%). Conclusions Hormonal levels after 2+2 indicate a reduced ovarian reserve. However, 2+2 in combination with GnRH analogues does not compromise fertility within the evaluated observation tim
BRCA2 variants and cardiovascular disease in a multi-ethnic study.
BACKGROUND: Germline mutations of BRCA1/2 are associated with hereditary breast and ovarian cancer. Recent data suggests excess mortality in mutation carriers beyond that conferred by neoplasia, and recent in vivo and in vitro studies suggest a modulatory role for BRCA proteins in endothelial and cardiomyocyte function. We therefore tested the association of BRCA2 variants with clinical cardiovascular disease (CVD). METHODS: Using data from 1,170 individuals included in two multi-ethnic population-based studies (SHARE and SHARE-AP), the association between BRCA2 variants and CVD was evaluated. 15 SNPs in BRCA2 with minor allele frequencies (MAF) > 0.01 had been previously genotyped using the cardiovascular gene-centric 50 k SNP array. 115 individuals (9.8%) reported a CVD event, defined as myocardial infarction (MI), angina, silent MI, stroke, and angioplasty or coronary artery bypass surgery. Analyses were adjusted for age and sex. The SNPs rs11571836 and rs1799943 were subsequently genotyped using the MassARRAY platform in 1,045 cases of incident MI and 1,135 controls from the South Asian subset of an international case-control study of acute MI (INTERHEART), and rs11571836 was imputed in 4,686 cases and 4500 controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS). RESULTS: Two BRCA2 SNPs, rs11571836 and rs1799943, both located in untranslated regions, were associated with lower risk of CVD (OR 0.47 p = 0.01 and OR 0.56 p = 0.03 respectively) in the SHARE studies. Analysis by specific ethnicities demonstrated an association with CVD for both SNPs in Aboriginal People, and for rs11571836 only in South Asians. No association was observed in the European and Chinese subgroups. A non-significant trend towards an association between rs11571836 and lower risk of MI was observed in South Asians from INTERHEART [OR = 0.87 (95% CI: 0.75-1.01) p = 0.068], but was not evident in PROMIS [OR = 0.96 (95% CI: 0.90-1.03) p = 0.230]. Meta-analysis of both case-control studies resulted in a combined OR of 0.94 (95% CI: 0.89-1.004, p = 0.06). CONCLUSIONS: Although there was an association between two SNPs in BRCA2 and CVD in a multi-ethnic population, these results were not replicated in two South Asian case-control studies of incident MI. Future studies exploring the association between BRCA variants and cardiovascular disorders are needed to clarify the role, if any, for BRCA variants in CVD pathogenesis.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
The N-methyl-d-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat
Long-term morphological synaptic changes associated with homosynaptic long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) in vivo, in awake adult rats were analyzed using three-dimensional (3-D) reconstructions of electron microscope images of ultrathin serial sections from the molecular layer of the dentate gyrus. For the first time in morphological studies, the specificity of the effects of LTP and LTD on both spine and synapse ultrastructure was determined using an N-methyl-d-aspartate (NMDA) receptor antagonist CPP (3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid). There were no differences in synaptic density 24 h after LTP or LTD induction, and CPP alone had no effect on synaptic density. LTP increased significantly the proportion of mushroom spines, whereas LTD increased the proportion of thin spines, and both LTP and LTD decreased stubby spine number. Both LTP and LTD increased significantly spine head evaginations (spinules) into synaptic boutons and CPP blocked these changes. Synaptic boutons were smaller after LTD, indicating a pre-synaptic effect. Interestingly, CPP alone decreased bouton and mushroom spine volumes, as well as post-synaptic density (PSD) volume of mushroom spines.These data show similarities, but also some clear differences, between the effects of LTP and LTD on spine and synaptic morphology. Although CPP blocks both LTP and LTD, and impairs most morphological changes in spines and synapses, CPP alone was shown to exert effects on aspects of spine and synaptic structure
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