323 research outputs found
Earth-system-model evaluation of cloud and precipitation occurrence for supercooled and warm clouds over the Southern Ocean's Macquarie Island
Over the remote Southern Ocean (SO), cloud feedbacks contribute substantially to Earth system model (ESM) radiative biases. The evolution of low Southern Ocean clouds (cloud-top heights < ∼ 3 km) is strongly modulated by precipitation and/or evaporation, which act as the primary sink of cloud condensate. Constraining precipitation processes in ESMs requires robust observations suitable for process-level evaluations. A year-long subset (April 2016–March 2017) of ground-based profiling instrumentation deployed during the Macquarie Island Cloud and Radiation Experiment (MICRE) field campaign (54.5∘ S, 158.9∘ E) combines a 95 GHz (W-band) Doppler cloud radar, two lidar ceilometers, and balloon-borne soundings to quantify the occurrence frequency of precipitation from the liquid-phase cloud base. Liquid-based clouds at Macquarie Island precipitate ∼ 70 % of the time, with deeper and colder clouds precipitating more frequently and at a higher intensity compared to thinner and warmer clouds. Supercooled cloud layers precipitate more readily than layers with cloud-top temperatures > 0 ∘C, regardless of the geometric thickness of the layer, and also evaporate more frequently. We further demonstrate an approach to employ these observational constraints for evaluation of a 9-year GISS-ModelE3 ESM simulation. Model output is processed through the Earth Model Column Collaboratory (EMC2) radar and lidar instrument simulator with the same instrument specifications as those deployed during MICRE, therefore accounting for instrument sensitivities and ensuring a coherent comparison. Relative to MICRE observations, the ESM produces a smaller cloud occurrence frequency, smaller precipitation occurrence frequency, and greater sub-cloud evaporation. The lower precipitation occurrence frequency by the ESM relative to MICRE contrasts with numerous studies that suggest a ubiquitous bias by ESMs to precipitate too frequently over the SO when compared with satellite-based observations, likely owing to sensitivity limitations of spaceborne instrumentation and different sampling methodologies for ground- versus space-based observations. Despite these deficiencies, the ESM reproduces the observed tendency for deeper and colder clouds to precipitate more frequently and at a higher intensity. The ESM also reproduces specific cloud regimes, including near-surface clouds that account for ∼ 25 % of liquid-based clouds during MICRE and optically thin, non-precipitating clouds that account for ∼ 27 % of clouds with bases higher than 250 m. We suggest that the demonstrated framework, which merges observations with appropriately constrained model output, is a valuable approach to evaluate processes responsible for cloud radiative feedbacks in ESMs.</p
PROGETTO PER UN ECOMUSEO MULTIMEDIALE NELLA BORGATA PARALOUP
Descrizione del progetto di "ecomuseo multimediale per la Borgata Paraloup" un museo, essenzialmente multimediale, che sarà diffuso sul erritorio circostante, sotto forma di stimoli sensoriali e di segnalazioni, ma saprà anche porsi in connessione con luoghi più distanti e significativi, nell’idea di costituire Paraloup quale ganglio di una rete di memoria più ampia e sald
Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium
Background: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. Methods: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). Results: Kaplan\u2013Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02\u20131.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03\u20131.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02\u20131.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01\u20131.25, p = 0.04) and HR 1.10; 95% CI 1.01\u20131.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. Conclusions: HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population
Responsive glyco-poly(2-oxazoline)s: synthesis, cloud point tuning, and lectin binding
A new sugar-substituted 2-oxazoline monomer was prepared using the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Its copolymerization with 2-ethyl-2-oxazoline as well as 2-(dec-9-enyl)-2-oxazoline, yielding well-defined copolymers with the possibility to tune the properties by thiol-ene "click" reactions, is described. Extensive solubility studies on the corresponding glycocopolymers demonstrated that the lower critical solution temperature behavior and pH-responsiveness of these copolymers can be adjusted in water and phosphate-buffered saline (PBS) depending on the choice of the thiol. By conjugation of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose and subsequent deprotection of the sugar moieties, the hydrophilicity of the copolymer could be increased significantly, allowing a cloud-point tuning in the physiological range. Furthermore, the binding capability of the glycosylated copoly(2-oxazoline) to concanavalin A was investigated
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.
Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants
Measurement of Through-Going Particle Momentum By Means Of Multiple Scattering With The ICARUS T600 TPC
The ICARUS collaboration has demonstrated, following the operation of a 600
ton (T600) detector at shallow depth, that the technique based on liquid Argon
TPCs is now mature. The study of rare events, not contemplated in the Standard
Model, can greatly benefit from the use of this kind of detectors. In
particular, a deeper understanding of atmospheric neutrino properties will be
obtained thanks to the unprecedented quality of the data ICARUS provides.
However if we concentrate on the T600 performance, most of the
charged current sample will be partially contained, due to the reduced
dimensions of the detector. In this article, we address the problem of how well
we can determine the kinematics of events having partially contained tracks.
The analysis of a large sample of atmospheric muons collected during the T600
test run demonstrate that, in case the recorded track is at least one meter
long, the muon momentum can be reconstructed by an algorithm that measures the
Multiple Coulomb Scattering along the particle's path. Moreover, we show that
momentum resolution can be improved by a factor two using an algorithm based on
the Kalman Filtering technique
Measurement of the muon decay spectrum with the ICARUS liquid Argon TPC
Examples are given which prove the ICARUS detector quality through relevant
physics measurements. We study the muon decay energy spectrum from a sample of
stopping muon events acquired during the test run of the ICARUS T600 detector.
This detector allows the spatial reconstruction of the events with fine
granularity, hence, the precise measurement of the range and dE/dx of the muon
with high sampling rate. This information is used to compute the calibration
factors needed for the full calorimetric reconstruction of the events. The
Michel rho parameter is then measured by comparison of the experimental and
Monte Carlo simulated muon decay spectra, obtaining rho = 0.72 +/- 0.06(stat.)
+/- 0.08(syst.). The energy resolution for electrons below ~50 MeV is finally
extracted from the simulated sample, obtaining (Emeas-Emc)/Emc =
11%/sqrt(E[MeV]) + 2%.Comment: 16 pages, 8 figures, LaTex, A4. Some text and 1 figure added. Final
version as accepted for publication in The European Physical Journal
Search for anomalies in the neutrino sector with muon spectrometers and large LArTPC imaging detectors at CERN
A new experiment with an intense ~2 GeV neutrino beam at CERN SPS is proposed
in order to definitely clarify the possible existence of additional neutrino
states, as pointed out by neutrino calibration source experiments, reactor and
accelerator experiments and measure the corresponding oscillation parameters.
The experiment is based on two identical LAr-TPCs complemented by magnetized
spectrometers detecting electron and muon neutrino events at Far and Near
positions, 1600 m and 300 m from the proton target, respectively. The ICARUS
T600 detector, the largest LAr-TPC ever built with a size of about 600 ton of
imaging mass, now running in the LNGS underground laboratory, will be moved at
the CERN Far position. An additional 1/4 of the T600 detector (T150) will be
constructed and located in the Near position. Two large area spectrometers will
be placed downstream of the two LAr-TPC detectors to perform charge
identification and muon momentum measurements from sub-GeV to several GeV
energy range, greatly complementing the physics capabilities. This experiment
will offer remarkable discovery potentialities, collecting a very large number
of unbiased events both in the neutrino and antineutrino channels, largely
adequate to definitely settle the origin of the observed neutrino-related
anomalies.Comment: Contribution to the European Strategy for Particle Physics - Open
Symposium Preparatory Group, Kracow 10-12 September 201
Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-α 2b treatment
<p>Abstract</p> <p>Background</p> <p>High-dose interferon-alpha 2b (IFN-α 2b) is the only approved systemic therapy in the United States for the adjuvant treatment of melanoma. The study objective was to explore the immunomodulatory mechanism of action for IFN-α 2b by measuring serum regulatory T cell (Treg), serum transforming growth factor-β (TGF-β), interleukin (IL)-10, and autoantibody levels in patients with melanoma treated with the induction phase of the high-dose IFN-α 2b regimen.</p> <p>Methods</p> <p>Patients with melanoma received IFN-α 2b administered intravenously (20 MU/m<sup>2 </sup>each day from day 1 to day 5 for 4 consecutive weeks). Serum Treg levels were measured as whole lymphocytes in CD4<sup>+ </sup>cells using flow cytometry while TGF-β, IL-10, and autoantibody levels were measured using enzyme-linked immunosorbent assays.</p> <p>Results</p> <p>Twenty-two patients with melanoma received IFN-α 2b treatment and were evaluated for Treg levels. Before treatment, Treg levels were significantly higher in patients with melanoma when compared with data from 20 healthy subjects (<it>P </it>= 0.001; Mann-Whitney test). Although a trend for reduction of Treg levels following IFN-α 2b treatment was observed (average decrease 0.29% per week), statistical significance was not achieved. Subgroup analyses indicated higher baseline Treg levels for stage III versus IV disease (<it>P </it>= 0.082), early recurrence versus no recurrence (<it>P </it>= 0.017), deceased versus surviving patients (<it>P = </it>0.021), and preoperative neoadjuvant versus postoperative adjuvant treatment groups (not significant). No significant effects were observed on the levels of TGF-β, IL-10, and autoantibodies in patients with melanoma treated with IFN-α 2b.</p> <p>Conclusions</p> <p>Patients with melanoma in this study showed increased basal levels of Treg that may be relevant to their disease and its progression. Treg levels shifted in patients with melanoma treated with IFN-α 2b, although no firm conclusions regarding the role of Tregs as a marker of treatment response or outcome can be made at present.</p
Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose Interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma
<p>Abstract</p> <p>Background</p> <p>Interleukin-2 (IL-2) induces durable objective responses in a small cohort of patients with metastatic renal cell carcinoma (RCC) but the antigen(s) responsible for tumor rejection are not known. 5T4 is a non-secreted membrane glycoprotein expressed on clear cell and papillary RCCs. A modified vaccinia virus Ankara (MVA) encoding 5T4 was tested in combination with high-dose IL-2 to determine the safety, objective response rate and effect on humoral and cell-mediated immunity.</p> <p>Methods</p> <p>25 patients with metastatic RCC who qualified for IL-2 were eligible and received three immunizations every three weeks followed by IL-2 (600,000 IU/kg) after the second and third vaccinations. Blood was collected for analysis of humoral, effector and regulatory T cell responses.</p> <p>Results</p> <p>There were no serious vaccine-related adverse events. While no objective responses were observed, three patients (12%) were rendered disease-free after nephrectomy or resection of residual metastatic disease. Twelve patients (48%) had stable disease which was associated with improved median overall survival compared to patients with progressive disease (not reached vs. 28 months, p = 0.0261). All patients developed 5T4-specific antibody responses and 13 patients had an increase in 5T4-specific T cell responses. Although the baseline frequency of Tregs was elevated in all patients, those with stable disease showed a trend toward increased effector CD8+ T cells and a decrease in Tregs.</p> <p>Conclusion</p> <p><b>V</b>accination with MVA-5T4 did not improve objective response rates of IL-2 therapy but did result in stable disease associated with an increase in the ratio of 5T4-specific effector to regulatory T cells in selected patients.</p> <p>Trial registration number</p> <p>ISRCTN83977250</p
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