The Amazon region, being a large source of methane (CH4), contributes significantly to the global annual CH4 budget. For the first time, a forward and inverse modelling framework on regional scale ...for the purpose of assessing the CH4 budget of the Amazon region is implemented. Here, we present forward simulations of CH4 as part of the forward and inverse modelling framework based on a modified version of the Weather Research and Forecasting model with chemistry that allows for passive tracer transport of CH4, carbon monoxide, and carbon dioxide (WRF-GHG), in combination with two different process-based bottom-up models of CH4 emissions from anaerobic microbial production in wetlands and additional datasets prescribing CH4 emissions from other sources such as biomass burning, termites, or other anthropogenic emissions. We compare WRF-GHG simulations on 10 km horizontal resolution to flask and continuous CH4 observations obtained during two airborne measurement campaigns within the Balanço Atmosférico Regional de Carbono na Amazônia (BARCA) project in November 2008 and May 2009. In addition, three different wetland inundation maps, prescribing the fraction of inundated area per grid cell, are evaluated. Our results indicate that the wetland inundation maps based on remote-sensing data represent the observations best except for the northern part of the Amazon basin and the Manaus area. WRF-GHG was able to represent the observed CH4 mixing ratios best at days with less convective activity. After adjusting wetland emissions to match the averaged observed mixing ratios of flights with little convective activity, the monthly CH4 budget for the Amazon basin obtained from four different simulations ranges from 1.5 to 4.8 Tg for November 2008 and from 1.3 to 5.5 Tg for May 2009. This corresponds to an average CH4 flux of 9–31 mg m−2 d−1 for November 2008 and 8–36 mg m−2 d−1 for May 2009.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced, irradiated tumor vaccines induce potent, T-cell-mediated antitumor immune responses in preclinical models. We report the ...initial results of a Phase I trial evaluating this strategy for safety and the induction of immune responses in patients with metastatic renal cell carcinoma (RCC). Patients were treated in a randomized, double-blind dose-escalation study with equivalent doses of autologous, irradiated RCC vaccine cells with or without ex vivo human GM-CSF gene transfer. The replication-defective retroviral vector MFG was used for GM-CSF gene transfer. No dose-limiting toxicities were encountered in 16 fully evaluable patients. GM-CSF gene-transduced vaccines were equivalent in toxicity to nontransduced vaccines up to the feasible limits of autologous tumor vaccine yield. No evidence of autoimmune disease was observed. Biopsies of intradermal sites of injection with GM-CSF gene-transduced vaccines contained distinctive macrophage, dendritic cell, eosinophil, neutrophil, and T-cell infiltrates similar to those observed in preclinical models of efficacy. Histological analysis of delayed-type hypersensitivity responses in patients vaccinated with GM-CSF-transduced vaccines demonstrated an intense eosinophil infiltrate that was not observed in patients who received nontransduced vaccines. An objective partial response was observed in a patient treated with GM-CSF gene-transduced vaccine who displayed the largest delayed-type hypersensitivity conversion. No replication-competent retrovirus was detected in vaccinated patients. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous GM-CSF gene-transduced tumor vaccine for RCC patients.
Summary
In 40% of cases of classical Hodgkin lymphoma (cHL), Epstein–Barr virus (EBV) latency‐II antigens EBV nuclear antigen 1 (EBNA1)/latent membrane protein (LMP)1/LMP2A are present (EBV+cHL) in ...the malignant cells and antigen presentation is intact. Previous studies have shown consistently that HLA‐A*02 is protective in EBV+cHL, yet its role in disease pathogenesis is unknown. To explore the basis for this observation, gene expression was assessed in 33 cHL nodes. Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA‐A*02– versus HLA‐A*02+ EBV+cHL patients, suggesting that LMP2A‐specific CD8+ T cell anti‐tumoral immunity may be relatively ineffective in HLA‐A*02– EBV+cHL. To ascertain the impact of HLA class I on EBV latency antigen‐specific immunodominance, we used a stepwise functional T cell approach. In newly diagnosed EBV+cHL, the magnitude of ex‐vivo LMP1/2A‐specific CD8+ T cell responses was elevated in HLA‐A*02+ patients. Furthermore, in a controlled in‐vitro assay, LMP2A‐specific CD8+ T cells from healthy HLA‐A*02 heterozygotes expanded to a greater extent with HLA‐A*02‐restricted compared to non‐HLA‐A*02‐restricted cell lines. In an extensive analysis of HLA class I‐restricted immunity, immunodominant EBNA3A/3B/3C‐specific CD8+ T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A‐specific responses were confined largely to HLA‐A*02. Our results demonstrate that HLA‐A*02 mediates a modest, but none the less stronger, EBV‐specific CD8+ T cell response than non‐HLA‐A*02 alleles, an effect confined to EBV latency‐II antigens. Thus, the protective effect of HLA‐A*02 against EBV+cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency‐II antigen‐specific CD8+ T cell hierarchies.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Exercise during growth has a positive influence on bone mineral accrual, yet little is known about how bone geometry and strength adapt to loading during growth. Our primary objective was to compare ...changes in proximal femur bone geometry and strength between 31 prepubertal (Tanner Stage 1) boys who participated in a school-based, high-impact circuit intervention (12 min, three times a week) for 20 months and 33 maturity-matched controls. Our secondary objective was to compare changes in total body (TB), proximal femur (PF), and lumbar spine (LS) bone mineral content (BMC) and bone area (BA) in these groups. We assessed geometric variables and bone strength at the narrow neck (NN), intertrochanteric (TR) region, and femoral shaft regions by applying the Hip Structure Analysis program to proximal femur dual energy X-ray absorptiometry scans (DXA, Hologic QDR 4500). Further, we assessed total body, lumbar spine, and proximal femur BMC and BA by DXA and derived total body lean mass and fat mass from total body scans. Intervention (10.2 ± 0.5 years) and control boys (10.1 ± 0.5 years) had similar baseline height (140.8 vs. 141.3 cm) and weight (36.9 vs. 35.4 kg), and average 20-month physical activity scores (Physical Activity Questionnaire for Children, PAQ-C) and calcium intakes (861 vs. 852 mg/day, food frequency questionnaire). Twenty-month height and weight changes were not significantly different between groups; lean mass changed more (P < 0.05) in intervention boys (22.8%) than control boys (18.6%). At the NN region, intervention boys had greater bone expansion on both the periosteal (+2.6%, P = 0.1) and endosteal (+2.7%, P = 0.2) surfaces, resulting in significantly greater changes in section modulus (bone bending strength) (+7.5%, P = 0.02, ANCOVA, adjusting for height change, final Tanner Stage, and baseline bone values). Changes at the intertrochanteric and femoral shaft regions were not significantly different between groups. Femoral neck (FN) BMC changes were significantly greater in intervention boys (+4.3%, P < 0.01); changes in BA and BMC for other regions were not significantly different between groups. In summary, a school-based, high-impact exercise intervention implemented three times a week for 12 min is an effective strategy for site-specific gains in bone strength at the narrow neck region of the proximal femur.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ABSTRACT
Studying the interplay between massive star formation and the interstellar medium (ISM) is paramount to understand the evolution of galaxies. Radio continuum (RC) emission serves as an ...extinction-free tracer of both massive star formation and the energetic components of the ISM. We present a multiband RC survey of the Local Group galaxy M 33 down to ≃30 pc linear resolution observed with the Karl G. Jansky Very Large Array (VLA). We calibrate the star formation rate surface density and investigate the impact of diffuse emission on this calibration using a structural decomposition. Separating the thermal and non-thermal emission components, the correlation between different phases of the ISM, and the impact of massive star formation are being investigated. Radio sources with sizes ≲200 pc constitute about 36 per cent (46 per cent) of the total RC emission at 1.5 GHz (6.3 GHz) in the inner 18 × 18 arcmin2 (or 4 kpc × 4 kpc) disc of M 33. The non-thermal spectral index becomes flatter with increasing star formation rate surface density, indicating the escape of cosmic ray electrons from their birth places. The magnetic field strength also increases with star formation rate following a bi-modal relation, indicating that the small-scale turbulent dynamo acts more efficiently at higher luminosities and star formation rates. Although the correlations are tighter in star-forming regions, the non-thermal emission is also correlated with the more quiescent molecular gas in the ISM. An almost linear molecular star formation law exists in M 33 when excluding diffuse structures. Massive star formation amplifies the magnetic field and increases the number of high-energy cosmic ray electrons, which can help the onset of winds and outflows.
The spin polarizabilities of the nucleon describe how the spin of the nucleon responds to an incident polarized photon. The most model-independent way to extract the nucleon spin polarizabilities is ...through polarized Compton scattering. Double-polarized Compton scattering asymmetries on the proton were measured in the Δ(1232) region using circularly polarized incident photons and a transversely polarized proton target at the Mainz Microtron. Fits to asymmetry data were performed using a dispersion model calculation and a baryon chiral perturbation theory calculation, and a separation of all four proton spin polarizabilities in the multipole basis was achieved. The analysis based on a dispersion model calculation yields γ(E1E1)=-3.5±1.2, γ(M1M1)=3.16±0.85, γ(E1M2)=-0.7±1.2, and γ(M1E2)=1.99±0.29, in units of 10(-4) fm(4).
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Motor neuron-specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. ...Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons, miR-218 is down-regulated and its mRNA targets are reciprocally up-regulated (derepressed). We further identify the potassium channel
as a new miR-218 direct target that controls neuronal activity. In addition, we screened thousands of ALS genomes and identified six rare variants in the human miR-218-2 sequence. miR-218 gene variants fail to regulate neuron activity, suggesting the importance of this small endogenous RNA for neuronal robustness. The underlying mechanisms involve inhibition of miR-218 biogenesis and reduced processing by DICER. Therefore, miR-218 activity in motor neurons may be susceptible to failure in human ALS, suggesting that miR-218 may be a potential therapeutic target in motor neuron disease.
Photoemission electron microscopy (PEEM) excited by X‐ray and UV sources is used to investigate epitaxial anatase thin films with embedded rutile nanocrystals, a model system for the study of ...heterocatalysis on mixed‐phase TiO2. Both excitation sources show distinct contrast between the two TiO2 phases; however, the contrast is reversed. Rutile nanocrystals appear darker than the anatase film in X‐ray PEEM images but brighter in UV‐PEEM images. We observe that topography‐induced contrast is dominant in X‐ray PEEM imaging, whereas work function and density‐of‐state‐based contrast, dominates in UV‐PEEM. This assertion is confirmed by UPS and conducting AFM data that shows the rutile work function to be 0.2 eV lower and a greater occupied valence band density‐of‐states in rutile (100) than in anatase (001). Since the boundaries between rutile nanocrystals and the anatase film are clearly resolved, these results indicate that PEEM studies of excited state dynamics and heterocatalysis are possible at chemically intriguing mixed‐phase TiO2 interfaces and grain boundaries.
Photoemission electron microscopy (PEEM) image of a mixed‐phase TiO2 thin film grown by oxygen‐plasma‐ assisted molecular beam epitaxy. The bright rutile nanocrystals are embedded in the dark anatase film. Femtosecond laser pulses (3.1 eV) are used to induce photoemission.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Context. Constraints on the origin and propagation of cosmic rays can be achieved by studying the variation in the spectral index of the synchrotron emission across external galaxies. Aims. We ...determine the variation in the nonthermal radio spectral index in the nearby spiral galaxy M 33 at a linear resolution of 360 pc. Methods. We separated the thermal and nonthermal components of the radio continuum emission without the assumption of a constant nonthermal spectral index. Using the Spitzer FIR data at 70 and 160 \mum and a standard dust model, we dereddened the H\alpha emission. The extinction corrected H\alpha emission serves as a template for the thermal free-free radio emission. Subtracting this free-free emission from the observed 3.6 cm and 20 cm emission (Effelsberg and the VLA), we obtained the nonthermal maps. A constant electron temperature used to obtain the thermal radio intensity seems appropriate for M 33, which, unlike the Milky Way, has a shallow metallicity gradient. Results. For the first time, we derive the distribution of the nonthermal spectral index across a galaxy, M 33. We detect strong nonthermal emission from the spiral arms and starforming regions. Wavelet analysis shows that at 3.6 cm the nonthermal emission is dominated by contributions from starforming regions, while it is smoothly distributed at 20 cm. For the whole galaxy, we obtain thermal fractions of 51% and 18% at 3.6 cm and 20 cm, respectively. The thermal emission is slightly stronger in the southern than in the northern half of the galaxy. We find a clear radial gradient of mean extinction in the galactic plane. Conclusions. The nonthermal spectral index map indicates that the relativistic electrons suffer energy loss when diffusing from their origin in starforming regions towards interarm regions and the outer parts of the galaxy. We also conclude that the radio emission is mostly nonthermal at R > 5 kpc in M 33.
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