3,246 research outputs found
Lipid specificity of the immune effector perforin
Perforin is a pore forming protein used by cytotoxic T lymphocytes to remove cancerous or virus-infected cells during immune response. During the response, the lymphocyte membrane becomes refractory to perforin function by accumulating densely ordered lipid rafts and externalizing negatively charged lipid species. The dense membrane packing lowers the capacity of perforin to bind, and negatively charged lipids scavenge any residual protein before pore formation. Using atomic force microscopy on model membrane systems, we here provide insight into the molecular basis of perforin lipid specificity
Young stars at large distances from the galactic plane: mechanisms of formation
We have collected from the literature a list of early-type stars, situated at
large distances from the galactic plane, for which evidence of youth seems
convincing. We discuss two possible formation mechanisms for these stars:
ejection from the plane by dynamical interactions within small clusters, and
formation away from the plane, via induced shocks created by spiral density
waves. We identify the stars that could be explained by each mechanism. We
conclude that the ejection mechanism can account for about two thirds of the
stars, while a combination of star formation at z = 500-800 pc from the plane
and ejection, can account for 90 percent of these stars. Neither mechanism, nor
both together, can explain the most extreme examples.Comment: 6 pages, No figures. Sixth Pacific Rim Conference on Stellar
Astrophysics - A tribute to Helmut Abt, (Kluwer
Developmental co-expression and functional redundancy of tyrosine phosphatases with neurotrophin receptors in developing sensory neurons
Receptor-type protein tyrosine phosphatases (RPTPs) have been implicated as direct or indirect regulators of neurotrophin receptors (TRKs). It remains less clear if and how such RPTPs might regulate TRK proteins in vivo during development. Here we present a comparative expression profile of RPTP genes and Trk genes during early stages of murine, dorsal root ganglion maturation. We find little if any specific, temporal mRNA co-regulation between individual RPTP and Ntrk genes between E12.5 and E14.5. Moreover, a double fluorescent in-situ hybridization and immunofluorescence study of seven Rptp genes with Ntrks revealed widespread co-expression of RPTPs in individual neurons, but no tight correlation with Trk expression profiles. No Rptp is expressed in 100% of Ntrk1-expressing neurons, whereas at least 6 RPTPs are expressed in 100% of Ntrk2- and Ntrk3-expressing neurons. An exception is Ptpro, which showed very selective expression. Short hairpin RNA suppression of Ptprf, Ptprs or Ptpro in primary, E13.5 DRG neurons did not alter TRK signalling. We therefore propose that TRK signalling may not be simply dependent on rate-limiting regulation by individual RPTP subtypes during sensory neuron development. Instead, TRK signalling has the potential to be buffered by concurrent inputs from several RPTPs in individual neurons
Exploiting Locally Imposed Anisotropies in (Ga,Mn)As: a Non-volatile Memory Device
Progress in (Ga,Mn)As lithography has recently allowed us to realize
structures where unique magnetic anisotropy properties can be imposed locally
in various regions of a given device. We make use of this technology to
fabricate a device in which we study transport through a constriction
separating two regions whose magnetization direction differs by 90 degrees. We
find that the resistance of the constriction depends on the flow of the
magnetic field lines in the constriction region and demonstrate that such a
structure constitutes a non-volatile memory device
Psychometric properties of the quality of life scale Child Health and Illness Profile-Child Edition in a combined analysis of five atomoxetine trials
Our aim was to evaluate the psychometric properties of the generic quality of life (QoL) scale Child Health and Illness Profile-Child Edition (CHIP-CE) by means of a combined analysis of atomoxetine clinical trials in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Individual patient-level data from five clinical trials were included in the combined analysis. Psychometric properties of the CHIP-CE were explored in terms of internal consistency and structure. Patients (n = 794) aged between 6 and 15 years (mean 9.7) with mean baseline ADHD Rating Scale of 41.8 ± 8.04 were included. On average, 0.7 (SD 2.23) items were missing for the whole CHIP-CE. The internal consistency of the CHIP-CE assessed by Cronbach’s alpha was good for all sub-domains at baseline and at endpoint. Considerable ceiling effects were only observed for the “restricted activity” sub-domain. No considerable floor effects were seen. The factor analysis supported the 12-factor solution for the sub-domains, but not the 5-factor solution for the domains. Our analyses were based on a large sample of non-US patients which allowed the measurement of clear changes in QoL over time. The results support that the CHIP-CE scale is psychometrically robust over time in terms of internal consistency and structure
Ultra-Sensitive Hot-Electron Nanobolometers for Terahertz Astrophysics
The background-limited spectral imaging of the early Universe requires
spaceborne terahertz (THz) detectors with the sensitivity 2-3 orders of
magnitude better than that of the state-of-the-art bolometers. To realize this
sensitivity without sacrificing operating speed, novel detector designs should
combine an ultrasmall heat capacity of a sensor with its unique thermal
isolation. Quantum effects in thermal transport at nanoscale put strong
limitations on the further improvement of traditional membrane-supported
bolometers. Here we demonstrate an innovative approach by developing
superconducting hot-electron nanobolometers in which the electrons are cooled
only due to a weak electron-phonon interaction. At T<0.1K, the electron-phonon
thermal conductance in these nanodevices becomes less than one percent of the
quantum of thermal conductance. The hot-electron nanobolometers, sufficiently
sensitive for registering single THz photons, are very promising for
submillimeter astronomy and other applications based on quantum calorimetry and
photon counting.Comment: 19 pages, 3 color figure
Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.
INTRODUCTION: Neovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic/lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids. METHODS: An ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score. RESULTS: Power Doppler showed a good correlation with histological vascular area (Spearman r--0.73) and angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied. CONCLUSION: Ultrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice
Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis.
Background:
We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres.
Methods:
Prospective cohort study of 3 year old children, with and without congenital toxoplasmosis, who were identified by prenatal or neonatal screening for toxoplasmosis in 11 centres in 7 countries. Parents were mailed a questionnaire that comprised all or part of existing validated tools. We determined the effect of characteristics of the centre and child on response, age at questionnaire completion, and response to child drawing tasks.
Results:
The questionnaire took 21 minutes to complete on average. 67% (714/1058) of parents responded. Few parents (60/1058) refused to participate. The strongest determinants of response were the score for organisational attributes of the study centre (such as direct involvement in follow up and access to an address register), and infection with congenital toxoplasmosis. Age at completion was associated with study centre, presence of neurological abnormalities in early infancy, and duration of prenatal treatment. Completion rates for individual questions exceeded 92% except for child completed drawings of a man (70%), which were completed more by girls, older children, and in certain centres.
Conclusion:
Differences in response across European centres were predominantly related to the organisation of follow up and access to correct addresses. The questionnaire was acceptable in all six countries and offers a low cost tool for assessing development, behaviour, and parental concerns and anxiety, in multinational studies
In situ epitaxial MgB2 thin films for superconducting electronics
A thin film technology compatible with multilayer device fabrication is
critical for exploring the potential of the 39-K superconductor magnesium
diboride for superconducting electronics. Using a Hybrid Physical-Chemical
Vapor Deposition (HPCVD) process, it is shown that the high Mg vapor pressure
necessary to keep the MgB phase thermodynamically stable can be achieved
for the {\it in situ} growth of MgB thin films. The films grow epitaxially
on (0001) sapphire and (0001) 4H-SiC substrates and show a bulk-like of
39 K, a (4.2K) of A/cm in zero field, and a
of 29.2 T in parallel magnetic field. The surface is smooth with a
root-mean-square roughness of 2.5 nm for MgB films on SiC. This deposition
method opens tremendous opportunities for superconducting electronics using
MgB
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