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Preferred Molecular Orientation of Coumarin 343 on TiO2 Surfaces: Application to Dye-Sensitized Solar Cells.
The dye···TiO2 interfacial structure in working electrodes of dye-sensitized solar cells (DSCs) is known to influence its photovoltaic device performance. Despite this, direct and quantitative reports of such structure remain sparse. This case study presents the application of X-ray reflectometry to determine the preferred structural orientation and molecular packing of the organic dye, Coumarin 343, adsorbed onto amorphous TiO2. Results show that the dye molecules are, on average, tilted by 61.1° relative to the TiO2 surface, and are separated from each other by 8.2 Ă
. These findings emulate the molecular packing arrangement of a monolayer of Coumarin 343 within its crystal structure. This suggests that the dye adsorbs onto TiO2 in one of its lowest energy configurations; that is, dye···TiO2 self-assembly is driven more by thermodynamic rather than kinetic means. Complementary DSC device tests illustrate that this interfacial structure compromises photovoltaic performance, unless a suitably sized coadsorbant is interdispersed between the Coumarin 343 chromophores on the TiO2 surface.J. M.-G. acknowledges ANSTO for a part-funded PhD studentship. J. M. C. is grateful to the 1851 Royal Commission for the 2014 Design Fellowship, and Argonne National Laboratory where work done was supported by DOE Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.This is the author accepted manuscript. The final version is available from ACS via http://dx.doi.org/10.1021/acsami.5b0357
Intragraft gene expression profile associated with the induction of tolerance
<p>Abstract</p> <p>Background</p> <p>Xenotransplantation holds the promise of providing an unlimited supply of donor organs for terminal patients with organ failure. Pre-existing natural antibodies to the Galα1,3GalÎČ1,4GlcNac-R (αGal) carbohydrate xenoantigen, however, bind rapidly to the graft endothelium and initiate hyperacute rejection of wild type pig grafts in humans. Experimental procedures designed to prevent xenoantibody-mediated rejection have been tested in gal knockout mice. These mice produce anti-gal xenoantibodies and are widely used as small animal models for xenotransplantation research. In this model, chimerism for cells expressing the gal carbohydrate can be achieved by transplantation of mixed cells or by transduction of bone marrow cells with viral vectors expressing a functional α1,3 galactosyltransferase gene. Chimerism induces tolerance to heart grafts expressing αGal. The mechanisms by which tolerance is achieved include systemic changes such as clonal deletion and/or anergy. Intragraft changes that occur during the early stages of tolerance induction have not been characterized.</p> <p>Results</p> <p>Cytoprotective genes heme oxygenase-1 (HO-1), Bcl2, and A20 that have been reported to contribute to long-term graft survival in various models of accommodation were not expressed at high levels in tolerant heart grafts. Intragraft gene expression at both early (Day 10) and late (>2 month) time points after heart transplant were examined by real-time PCR and microarray analysis was used to identify changes associated with the induction of tolerance. Intragraft gene expression profiling using microarray analysis demonstrated that genes identified in the functional categories of stress and immunity and signal transduction were significantly up-regulated in early tolerant grafts compared with syngeneic control grafts. Biological process classification showed lower binomial p-values in the categories of "response to biotic stimulus, defense response, and immune response" suggesting that up-regulated genes identified in these grafts promote survival in the presence of an immune response. The expression of the incompatible carbohydrate antigen (αGal) was reduced by 2 months post-transplant when compared with the expression of this gene at Day 10 post-transplant. These results suggest that the gal carbohydrate antigen is downmodulated over time in grafts that demonstrate tolerance.</p> <p>Conclusion</p> <p>Our study suggests that tolerance is associated with intragraft gene expression changes that render the heart resistant to immune-mediated rejection. Genes associated with stress and immunity are up-regulated, however cytoprotective genes HO-1, Bcl2 and A20 were not up-regulated. The expression of the gal carbohydrate, the key target initiating an immune response in this model, is down-regulated in the post-transplant period.</p
Modeling Spitzer observations of VV Ser. I. The circumstellar disk of a UX Orionis star
We present mid-infrared Spitzer-IRS spectra of the well-known UX Orionis star
VV Ser. We combine the Spitzer data with interferometric and spectroscopic data
from the literature covering UV to submillimeter wavelengths. The full set of
data are modeled by a two-dimensional axisymmetric Monte Carlo radiative
transfer code. The model is used to test the prediction of (Dullemond et al.
2003) that disks around UX Orionis stars must have a self-shadowed shape, and
that these disks are seen nearly edge-on, looking just over the edge of a
puffed-up inner rim, formed roughly at the dust sublimation radius. We find
that a single, relatively simple model is consistent with all the available
observational constraints spanning 4 orders of magnitude in wavelength and
spatial scales, providing strong support for this interpretation of UX Orionis
stars. The grains in the upper layers of the puffed-up inner rim must be small
(0.01-0.4 micron) to reproduce the colors (R_V ~ 3.6) of the extinction events,
while the shape and strength of the mid-infrared silicate emission features
indicate that grains in the outer disk (> 1-2 AU) are somewhat larger (0.3-3.0
micron). From the model fit, the location of the puffed-up inner rim is
estimated to be at a dust temperature of 1500 K or at 0.7-0.8 AU for small
grains. This is almost twice the rim radius estimated from near-infrared
interferometry. A best fitting model for the inner rim in which large grains in
the disk mid-plane reach to within 0.25 AU of the star, while small grains in
the disk surface create a puffed-up inner rim at ~0.7-0.8 AU, is able to
reproduce all the data, including the near-infrared visibilities. [Abstract
abridged]Comment: 12 pages, accepted for publication in Ap
Protostellar holes: Spitzer Space Telescope observations of the protostellar binary IRAS16293-2422
Mid-infrared (23-35 micron) emission from the deeply embedded "Class 0"
protostar IRAS16293-2422 is detected with the Spitzer Space Telescope infrared
spectrograph. A detailed radiative transfer model reproducing the full spectral
energy distribution (SED) from 23 micron to 1.3 mm requires a large inner
cavity of radius 600 AU in the envelope to avoid quenching the emission from
the central sources. This is consistent with a previous suggestion based on
high angular resolution millimeter interferometric data. An alternative
interpretation using a 2D model of the envelope with an outflow cavity can
reproduce the SED but not the interferometer visibilities. The cavity size is
comparable to the centrifugal radius of the envelope and therefore appears to
be a natural consequence of the rotation of the protostellar core, which has
also caused the fragmentation leading to the central protostellar binary. With
a large cavity such as required by the data, the average temperature at a given
radius does not increase above 60-80 K and although hot spots with higher
temperatures may be present close to each protostar, these constitute a small
fraction of the material in the inner envelope. The proposed cavity will also
have consequences for the interpretation of molecular line data, especially of
complex species probing high temperatures in the inner regions of the envelope.Comment: Accepted for publication in ApJ Letter
Questioning context: a set of interdisciplinary questions for investigating contextual factors affecting health decision making
Objectiveâ To combine insights from multiple disciplines into a set of questions that can be used to investigate contextual factors affecting health decision making. Backgroundâ Decisionâmaking processes and outcomes may be shaped by a range of nonâmedical or âcontextualâ factors particular to an individual including social, economic, political, geographical and institutional conditions. Research concerning contextual factors occurs across many disciplines and theoretical domains, but few conceptual tools have attempted to integrate and translate this wideâranging research for health decisionâmaking purposes. Methodsâ To formulate this tool we employed an iterative, collaborative process of scenario development and question generation. Five hypothetical health decisionâmaking scenarios (preventative, screening, curative, supportive and palliative) were developed and used to generate a set of exploratory questions that aim to highlight potential contextual factors across a range of health decisions. Findingsâ We present an exploratory tool consisting of questions organized into four thematic domains â Bodies, Technologies, Place and Work (BTPW) â articulating wideâranging contextual factors relevant to health decision making. The BTPW tool encompasses healthârelated scholarship and research from a range of disciplines pertinent to health decision making, and identifies concrete points of intersection between its four thematic domains. Examples of the practical application of the questions are also provided. Conclusionsâ These exploratory questions provide an interdisciplinary toolkit for identifying the complex contextual factors affecting decision making. The set of questions comprised by the BTPW tool may be applied wholly or partially in the context of clinical practice, policy development and healthârelated research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86973/1/j.1369-7625.2010.00618.x.pd
C2D Spitzer-IRS spectra of disks around T Tauri stars: I. Silicate emission and grain growth
Infrared ~5--35 um spectra for 40 solar-mass T Tauri stars and 7
intermediate-mass Herbig Ae stars with circumstellar disks were obtained using
the Spitzer Space Telescope as part of the c2d IRS survey. This work
complements prior spectroscopic studies of silicate infrared emission from
disks, which were focused on intermediate-mass stars, with observations of
solar-mass stars limited primarily to the 10 um region. The observed 10 and 20
um silicate feature strengths/shapes are consistent with source-to-source
variations in grain size. A large fraction of the features are weak and flat,
consistent with um-sized grains indicating fast grain growth (from 0.1--1.0 um
in radius). In addition, approximately half of the T Tauri star spectra show
crystalline silicate features near 28 and 33 um indicating significant
processing when compared to interstellar grains. A few sources show large
10-to-20 um ratios and require even larger grains emitting at 20 um than at 10
um. This size difference may arise from the difference in the depth into the
disk probed by the two silicate emission bands in disks where dust settling has
occurred. The 10 um feature strength vs. shape trend is not correlated with age
or Halpha equivalent width, suggesting that some amount of turbulent mixing and
regeneration of small grains is occurring. The strength vs. shape trend is
related to spectral type, however, with M stars showing significantly flatter
10 um features (larger grain sizes) than A/B stars. The connection between
spectral type and grain size is interpreted in terms of the variation in the
silicate emission radius as a function of stellar luminosity, but could also be
indicative of other spectral-type dependent factors (e.g, X-rays, UV radiation,
stellar/disk winds, etc.).Comment: 17 pages, 13 figures, accepted for publication by ApJ, formatted with
emulateapj using revtex4 v4.
STAT5 activation promotes progression and chemotherapy-resistance in early T-cell precursor acute lymphoblastic leukemia
IL-7 supports the growth and chemoresistance of T-cell acute lymphoblastic leukemia (T-ALL), particularly the early T-cell precursor subtype (ETP-ALL), which frequently has activating mutations of IL-7 signaling. STAT5 is an attractive therapeutic target because it is almost universally activated in ETP-ALL, even in the absence of mutations of upstream activators such as the IL-7R, JAK and FLT3. To examine the role of activated STAT5 in ETP-ALL, we have used a Lmo2-transgenic (Lmo2Tg) mouse model in which we can monitor chemoresistant pre-leukemia (pre-LSCs) and leukemia stem cells (LSCs) that drive T-ALL development and relapse following chemotherapy. Using IL-7R-deficient Lmo2Tg mice, we show that IL-7 signaling was not required for the formation of pre-LSCs but essential for their expansion and clonal evolution into LSCs to generate T-ALL. Activated STAT5B was sufficient for the development of T-ALL in IL-7R; Lmo2Tg mice, indicating that inhibition of STAT5 is required to block the supportive signals provided by IL-7. To further understand the role of activated STAT5 in LSCs of ETP-ALL, we developed a new transgenic mouse that enables T-cell specific and doxycycline-inducible expression of the constitutively activated STAT5B1â6 mutant. Expression of STAT5B1â6 in T-cells had no effect alone but promoted expansion and chemoresistance of LSCs in Lmo2Tg mice. Pharmacologic inhibition of STAT5 with Pimozide induced differentiation and loss of LSCs, whilst enhancing response to chemotherapy. Furthermore, Pimozide significantly reduced leukemia burden in vivo and overcame chemoresistance of patient-derived ETP-ALL xenografts. Overall, our results demonstrate that STAT5 is an attractive therapeutic target for eradicating LSCs in ETP-ALL
Ices in the edge-on disk CRBR 2422.8-3423: Spitzer spectroscopy and Monte Carlo radiative transfer modeling
We present 5.2-37.2 micron spectroscopy of the edge-on circumstellar disk
CRBR 2422.8-3423 obtained using the InfraRed Spectrograph (IRS) of the Spitzer
Space Telescope. The IRS spectrum is combined with ground-based 3-5 micron
spectroscopy to obtain a complete inventory of solid state material present
along the line of sight toward the source. We model the object with a 2D
axisymmetric (effectively 3D) Monte Carlo radiative transfer code. It is found
that the model disk, assuming a standard flaring structure, is too warm to
contain the very large observed column density of pure CO ice, but is possibly
responsible for up to 50% of the water, CO2 and minor ice species. In
particular the 6.85 micron band, tentatively due to NH4+, exhibits a prominent
red wing, indicating a significant contribution from warm ice in the disk. It
is argued that the pure CO ice is located in the dense core Oph-F in front of
the source seen in the submillimeter imaging, with the CO gas in the core
highly depleted. The model is used to predict which circumstances are most
favourable for direct observations of ices in edge-on circumstellar disks. Ice
bands will in general be deepest for inclinations similar to the disk opening
angle, i.e. ~70 degrees. Due to the high optical depths of typical disk
mid-planes, ice absorption bands will often probe warmer ice located in the
upper layers of nearly edge-on disks. The ratios between different ice bands
are found to vary by up to an order of magnitude depending on disk inclination
due to radiative transfer effects caused by the 2D structure of the disk.
Ratios between ice bands of the same species can therefore be used to constrain
the location of the ices in a circumstellar disk. [Abstract abridged]Comment: 49 pages, accepted for publication in Ap
Breast cancer risk reduction:is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?
BackgroundBreast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reductionThis study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP).MethodsA 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity. At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women¿s, coaches and radiographers¿ experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effectResultsA pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58¿±¿5.6 years, mean BMI was 29.2¿±¿7.0 kg/m2 and many (44%) reported a family history of breast cancer.The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95%CI ¿3.24 kg to ¿0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others.ConclusionsRecruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects.Trial registrationThe trial was registered with Current Controlled Trials (ISRCTN56223933)
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