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The molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target protein communities and the possibility to engineer extracellular signaling. Here, we develop an optoproteomic technology termed LUX-MS that enables the targeted elucidation of acute protein interactions on and in between living cells using light-controlled singlet oxygen generators (SOG). By using SOG-coupled antibodies, small molecule drugs, biologics and intact viral particles, we demonstrate the ability of LUX-MS to decode ligand receptor interactions across organisms and to discover surfaceome receptor nanoscale organization with direct implications for drug action. Furthermore, by coupling SOG to antigens we achieved light-controlled molecular mapping of intercellular signaling within functional immune synapses between antigen-presenting cells and CD8+ T cells providing insights into T cell activation with spatiotemporal specificity. LUX-MS based decoding of surfaceome signaling architectures thereby provides a molecular framework for the rational development of theranostic strategies., Nature Communications, 12 (1), ISSN:2041-1723

Next generation DNA sequencing is used to determine the HLA-A, -B, -C, -DRB1, -DRB3/4/5, and -DQB1 assignments of 1009 unrelated volunteers for the unrelated donor registry in The Netherlands. The analysis characterizes all HLA exons and introns for class I alleles; at least exons 2 to 3 for HLA-DRB1; and exons 2 to 6 for HLA-DQB1. Of the distinct alleles present, there are 229 class I and 71 class II; 36 of these alleles are novel. The majority (approximately 98%) of the cumulative allele frequency at each locus is contributed by alleles that appear three or more times. Alleles encoding protein variation outside of the antigen recognition domains are 0.6% of the class I assignments and 5.3% of the class II assignments.

Background and importance We present the case of a young patient with T lymphoblastic lymphoma (T-LBL) who developed severe toxicity after receiving an anthracycline based protocol that is generally well tolerated by healthy patients. We assume that the substitution of daunorubicin by doxorubicin due to a nationwide shortage of daunorubicin played a crucial role in developing severe toxicity. Aim and objectives The 19-year-old man with no previous illnesses was diagnosed in December 2019 with T-LBL, a rare, aggressive neoplasm of precursor T cells that progresses rapidly and requires prompt diagnosis and medical intervention. T-LBL shows morphological and immunophenotypical similarities to acute lymphoblastic leukaemia (ALL). T-LBL treatment is the same as for ALL. Material and methods The induction protocol consisted of dexamethasone, vincristine, daunorubicin and pegasparaginase. Due to a nationwide shortage, daunorubicin (30 mg/m²) was substituted by doxorubicin (25 mg/m²). Results Chemotherapy was initially well tolerated, but beginning on day 15, the patient developed pronounced mucositis and increased skin toxicity (hand–foot syndrome, grade IV). Moreover, coagulation parameters deteriorated, and repeated transfusions with erythrocytes and platelet concentrates were needed. After administration of pegasparaginase on day 31, liver values increased, and finally, the patient had to be transferred to the intensive care unit due to fulminant pancreatitis. After 3 days, the patient could be transferred back to our ward. However, within 2 weeks, the patient developed sensory disturbances in all extremities, which was classified as chemotherapy associated polyneuropathy. In the further clinical course, the patient‘s general condition improved, and PET-CT showed complete metabolic remission. Due to the severe chemotherapy associated side effects, intensive consolidation treatment, according to the protocol, was cancelled. Instead, a consolidating therapy with nelarabine was carried out without complications. To date (October 2020), the patient is in a good clinical condition and has not developed disease recurrence. Probability assessment using the Naranjo algorithm resulted in ‘probable adverse drug reaction’ (score=6). Conclusion and relevance Our case report underlines the fact that shortages of essential anticancer drugs can have a particular impact on the efficacy and safety of established chemotherapy regimens, as these medicines often have few or no proven effective alternatives. References and/or acknowledgements Patel S, et al. A single-centre experience of the nationwide daunorubicin shortage: substitution with doxorubicin in adult acute lymphoblastic leukaemia. Leuk Lymphoma 2013;54:2231–5. Conflict of interest No conflict of interest

CD20 is a B cell-specific membrane protein and represents an attractive target for therapeutic antibodies. Despite widespread usage of anti-CD20 antibodies for B cell depletion therapies, the biological function of their target remains unclear. Here, we demonstrate that CD20 controls the nanoscale organization of receptors on the surface of resting B lymphocytes. CRISPR/Cas9-mediated ablation of CD20 in resting B cells resulted in relocalization and interaction of the IgM-class B cell antigen receptor with the coreceptor CD19. This receptor rearrangement led to a transient activation of B cells, accompanied by the internalization of many B cell surface marker proteins. Reexpression of CD20 restored the expression of the B cell surface proteins and the resting state of Ramos B cells. Similarly, treatment of Ramos or naive human B cells with the anti-CD20 antibody rituximab induced nanoscale receptor rearrangements and transient B cell activation in vitro and in vivo. A departure from the resting B cell state followed by the loss of B cell identity of CD20-deficient Ramos B cells was accompanied by a PAX5 to BLIMP-1 transcriptional switch, metabolic reprogramming toward oxidative phosphorylation, and a shift toward plasma cell development. Thus, anti-CD20 engagement or the loss of CD20 disrupts membrane organization, profoundly altering the fate of human B cells., Proceedings of the National Academy of Sciences of the United States of America, 118 (7), ISSN:0027-8424, ISSN:1091-6490

CD20 is a B cell specific membrane protein and a target of therapeutic antibodies such as rituximab (RTX). In spite of the prominent usage of anti-CD20 antibodies in the clinic little is known about the biological function of CD202. Here we show that CD20 controls the nanoscale organization of receptors on the surface of resting B lymphocytes. A CRISPR/Cas-based ablation of CD20 in Ramos B cells results in a relocalisation of the IgM B cell antigen receptor (IgM-BCR) and the co-receptor CD19. The resulting IgM-BCR/CD19 signaling synapse leads to transient B cell activation followed by plasma cell differentiation. Similarly to CD20-deficient Ramos cells, naive human B cells treated with rituximab in vitro or isolated from patients during rituximab administration display hallmarks of transient activation characterized by the formation of the IgM-BCR/CD19 signaling synapse, followed by CD19 and IgM-BCR downregulation. Moreover, increased expression of specific plasma cell genes can be observed after rituximab treatment in relapsed CLL patients. In summary we identify CD20 as a gatekeeper of the resting state on human B cells and demonstrate that a disruption of the nanoscale organization of the B cell surface via CD20 deletion or anti-CD20 treatment profoundly alters B cell fate.

Observations taken over the last few decades indicate that dramatic changes are occurring in the ArcticBoreal Zone (ABZ), which are having significant impacts on ABZ inhabitants, infrastructure, flora and fauna, and economies. While suitable for detecting overall change, the current capability is inadequate for systematic monitoring and for improving processbased and largescale understanding of the integrated components of the ABZ, which includes the cryosphere, biosphere, hydrosphere, and atmosphere. Such knowledge will lead to improvements in Earth system models, enabling more accurate prediction of future changes and development of informed adaptation and mitigation strategies. In Duncan et al. (2020), we review the strengths and limitations of current spacebased observational capabilities for several important ABZ components and make recommendations for improving upon these current capabilities. We recommend an interdisciplinary and stepwise approach to develop a comprehensive ABZ Observing Network (ABZON), beginning with an initial focus on observing networks designed to gain processbased understanding for individual ABZ components and systems that can then serve as the building blocks for a comprehensive ABZON.

Hydrodynamic forces on intertidal flats vary over a range of temporal and spatial scales. These spatiotemporal inhomogeneities have implications for intertidal flat morphodynamics and ecology. We determine whether storm events are capable of altering the long-term morphological evolution of intertidal flats, and unravel the contributions of tidal flow, wind-driven flow, waves, and water depth on inhomogeneities in bed level dynamics (bed level changes over ~days) across these areas. We complement decades of bed level measurements on eight intertidal flats in two estuaries in the Netherlands with an extensive 1-month field campaign on one of those flats. Across this intertidal flat, the hydrodynamics and morphodynamics of a storm event were captured, including the post-storm recovery. We show that individual events can persistently alter the morphological evolution of intertidal flats; magnitudes of some bed level changes are even comparable to years of continuous evolution. The morphological impacts of events are largely controlled by the relative timing of the forcing processes, and not solely by their magnitudes. Spatiotemporal variations in bed level dynamics of intertidal flats are driven by a combination of: (1) the inhomogeneous distributions of the hydrodynamic forcing processes (including the under-explored role of the wind); and (2) the linear proportionality between bed level dynamics and the local bed slope.

Reinforcement value enhancement by nicotine of non-nicotine rewards is believed to partially motivate smoking behavior. Recently, we demonstrated that the value-enhancing effects of nicotine are well characterized by reinforcer demand models, and that the value-enhancing effects of the smoking cessation aid bupropion (Zyban®) are distinct from those of nicotine and differ between the sexes (Barrett et al., 2017). The present study evaluated potential sex differences in the enhancement effects of nicotine and varenicline (Chantix®) using a reinforcer demand methodology. The role of α4β2* and α7 nicotinic acetylcholine receptors (nAChRs) in the enhancing effects of nicotine and varenicline are also evaluated. Male and female rats (n=12/sex) were trained to lever-press maintained by sensory reinforcement via visual stimulus (VS) presentations. Changes in VS value following nicotine and varenicline administration were assessed using an established reinforcer demand approach. Subsequently, the effects of antagonism of α4β2* and α7 nAChRs on varenicline and nicotine induced enhancement active lever-pressing was assessed using a progressive ratio schedule. Nicotine and varenicline enhanced VS demand equivalently between the sexes as evaluated by reinforcer demand. However, α4β2* receptor antagonism attenuated value enhancement by nicotine and varenicline in females, but only of nicotine in males.

Changes in snow and glacier melt and precipitation patterns are expected to alter the water flow of rivers at various spatial and temporal scales. Hydropower generation and fisheries are likely to be impacted annually and over the century by seasonal, as well as long-term changes, in hydrological conditions. In order to quantify the effect of climate changes on hydropower and fisheries, we developed an integrated assessment framework that links biophysical models (positive degree-day model, hydrologic model, run-of-river power system model, and fishery suitability index) and economic models. This framework was used to demonstrate the framework’s utility for gaining insights into the impacts of changed river flow on hydropower and fisheries of the Trishuli River in the High Mountain Asia (HMA) Region (from the Hindu Kush and Tien Shan mountain ranges in the west to the Eastern Himalaya). Remotely sensed and in situ data were used to quantify changes in snow and glacier melt in Langtang glacier and resultant change in hydrologic flow in the Trishuli River upstream of the Trishuli hydropower plant. Future discharges were projected using climate data derived from the Cubic Conformal Atmospheric model with 50-km resolution in Representative Concentration Pathway (RCP) 8.5 and RCP 4.5 climate scenarios. Results suggest that, in the future, the Trishuli River will experience modest increases in the economic value of the hydropower resource and fisheries as a result of higher snow and glacial melt. Increased flow in the months of March and April attributed to increased glacier melt translated to an increase in electricity generation. However increased flow in June and July when the snow and glacial melt peak is coupled with monsoon precipitation could not be fully utilized due to hydropower plant capacity constraints. Fishery suitability in the Trishuli River would be greater than 70% of optimal under both RCP 4.5 and RCP 8.5. Power economic results do not vary significantly for the next thirty years because flow increases under RCP 8.5 and resultant energy production are more pronounced in the later part of the century. The framework utilized in this study can be expanded in the future to analyze hydropower infrastructure as well as fisheries conservation in the upstream HMA basins from Afghanistan through Bhutan.

The springtime transition to regional-scale onset of photosynthesis and net ecosystem carbon uptake in boreal and tundra ecosystems are linked to the soil freeze-thaw state. We present evidence from diagnostic and inversion models constrained by satellite fluorescence and airborne CO2 from 2012 to 2014 indicating the timing and magnitude of spring carbon uptake in Alaska correlates with landscape thaw and ecoregion. Landscape thaw in boreal forests typically occurs in late April (DOY 111 ± 7) with a 29 ± 6 day lag until photosynthetic onset. North Slope tundra thaws 3 weeks later (DOY 133 ± 5) but experiences only a 20 ± 5 day lag until photosynthetic onset. These time lag differences reflect efficient cold season adaptation in tundra shrub and the longer dehardening period for boreal evergreens. Despite the short transition from thaw to photosynthetic onset in tundra, synchrony of tundra respiration with snow melt and landscape thaw delays the transition from net carbon loss (at photosynthetic onset) to net uptake by 13 ± 7 days, thus reducing the tundra net carbon uptake period. Two global CO2 inversions using a CASA-GFED model prior estimate earlier northern high latitude net carbon uptake compared to our regional inversion, which we attribute to (i) early photosynthetic-onset model prior bias, (ii) inverse method (scaling factor + optimization window), and (iii) sparsity of available Alaskan CO2 observations. Another global inversion with zero prior estimates the same timing for net carbon uptake as the regional model but smaller seasonal amplitude. The analysis of Alaskan eddy covariance observations confirms regional scale findings for tundra, but indicates that photosynthesis and net carbon uptake occur up to 1 month earlier in evergreens than captured by models or CO2 inversions, with better correlation to above-freezing air temperature than date of primary thaw. Further collection and analysis of boreal evergreen species over multiple years and at additional subarctic flux towers are critically needed.

Methane (CH4) is the second most important greenhouse gas but its emissions from northern regions are still poorly constrained. In this study, we analyze a subset of in situ CH4 aircraft observations made over Alaska during the growing seasons of 2012–2014 as part of the Carbon in Arctic Reservoirs Vulnerability Experiment (CARVE). Net surface CH4 fluxes are estimated using a Lagrangian particle dispersion model which quantitatively links surface emissions from Alaska and the western Yukon with observations of enhanced CH4 in the mixed layer. We estimate that between May and September, net CH4 emissions from the region of interest were 2.2 ± 0.5 Tg, 1.9 ± 0.4 Tg, and 2.3 ± 0.6 Tg of CH4 for 2012, 2013, and 2014, respectively. If emissions are only attributed to two biogenic eco-regions within our domain, then tundra regions were the predominant source, accounting for over half of the overall budget despite only representing 18 % of the total surface area. Boreal regions, which cover a large part of the study region, accounted for the remainder of the emissions. Simple multiple linear regression analysis revealed that, overall, CH4 fluxes were largely driven by soil temperature and elevation. In regions specifically dominated by wetlands, soil temperature and moisture at 10 cm depth were important explanatory variables while in regions that were not wetlands, soil temperature and moisture at 40 cm depth were more important, suggesting deeper methanogenesis in drier soils. Although similar environmental drivers have been found in the past to control CH4 emissions at local scales, this study shows that they can be used to generate a statistical model to estimate the regional-scale net CH4 budget.

Aims: Extracts of Chelidonium majus , extensively used in traditional systems of medicine, have been tested for their possible anti-tumor, hepato-protective and anti-genotoxic effects, to investigate their potential in cancer therapy. Although the highly active antiretroviral therapy (HAART) has changed the natural history of HIV infection, several adverse events may limit its efficacy. Antiretroviral drugs are associated with increased risk of severe hepatotoxicity. These complications increase morbidity and mortality significantly. Current study evaluated the effect of Chelidonium majus on metabolic alterations induced in mice subjected to HAART. Methodology: Four-weeks old male Swiss Webster mice, weighing approximately 28-30 g, provided by the Central Animal Laboratory of the State University of Maringa, were used in the experiments. The drug in the form of mother tincture was prepared with the juice of the root of C. majus , mixed in equal parts of grain alcohol (P.A.) and comprised 12 animals per experimental group: (I) animals treated with HAART diluted in 1.2 mL water gavage/day, (II) animals treated with HAART diluted in 1.2 mL water gavage/day + C. majus diluted 1x10 12 in water 1.0 mL, daily added

This paper describes the atmospheric modeling that underlies the Carbon in Arctic Reservoirs Vulnerability Experiment (CARVE) science analysis, including its meteorological and atmospheric transport components (Polar variant of the Weather Research and Forecasting (WRF) and Stochastic Time Inverted Lagrangian Transport (STILT) models), and provides WRF validation for May–October 2012 and March–November 2013 – the first two years of the aircraft field campaign. A triply nested computational domain for WRF was chosen so that the innermost domain with 3.3 km grid spacing encompasses the entire mainland of Alaska and enables the substantial orography of the state to be represented by the underlying high-resolution topographic input field. Summary statistics of the WRF model performance on the 3.3 km grid indicate good overall agreement with quality-controlled surface and radiosonde observations. Two-meter temperatures are generally too cold by approximately 1.4 K in 2012 and 1.1 K in 2013, while 2 m dewpoint temperatures are too low (dry) by 0.2 K in 2012 and too high (moist) by 0.6 K in 2013. Wind speeds are biased too low by 0.2 m s−1 in 2012 and 0.3 m s−1 in 2013. Model representation of upper level variables is very good. These measures are comparable to model performance metrics of similar model configurations found in the literature. The high quality of these fine-resolution WRF meteorological fields inspires confidence in their use to drive STILT for the purpose of computing surface influences ("footprints") at commensurably increased resolution. Indeed, footprints generated on a 0.1° grid show increased spatial detail compared with those on the more common 0.5° grid, lending itself better for convolution with flux models for carbon dioxide and methane across the heterogeneous Alaskan landscape. Ozone deposition rates computed using STILT footprints indicate good agreement with observations and exhibit realistic seasonal variability, further indicating that WRF-STILT footprints are of high quality and will support accurate estimates of CO2 and CH4 surface–atmosphere fluxes using CARVE observations.

This paper presents results from recent satellite Global Navigation Satellite System-Reflectometry (GNSS-R) experiments in the northern high latitudes. Seasonal changes in the reflected signal are attributed to changes in the freeze/thaw state of the landscape. Here, we describe the unique geometries and sampling strategies that GNSS-R provide, which come with both advantages and limitations vis-a-vis traditional remote sensing techniques for monitoring the freeze/thaw transition. We will compare observational GNSS-R data in the northern high latitudes with cotemporaneous L-band radiometer and radar data to highlight these advantages and limitations.

Melting is mapped over Antarctica at a high spatial resolution using a novel melt detection algorithm based on wavelets and multiscale analysis. The method is applied to Ku-band (13.4 GHz) normalized backscattering measured by SeaWinds onboard the satellite QuikSCAT and spatially enhanced on a 5 km grid over the operational life of the sensor (1999–2009). Wavelet-based estimates of melt spatial extent and duration are compared with those obtained by means of threshold-based detection methods, where melting is detected when the measured backscattering is 3 dB below the preceding winter mean value. Results from both methods are assessed by means of automatic weather station (AWS) air surface temperature records. The yearly melting index, the product of melted area and melting duration, found using a fixed threshold and wavelet-based melt algorithm are found to have a relative difference within 7% for all years. Most of the difference between melting records determined from QuikSCAT is related to short-duration backscatter changes identified as melting using the threshold methodology but not the wavelet-based method. The ability to classify melting based on relative persistence is a critical aspect of the wavelet-based algorithm. Compared with AWS air-temperature records, both methods show a relative agreement to within 10% based on estimated melt conditions, although the fixed threshold generally finds a greater agreement with AWS. Melting maps obtained with the wavelet-based approach are also compared with those obtained from spaceborne brightness temperatures recorded by the Special Sensor Microwave/Image (SSM/I). With respect to passive microwave records, we find a higher degree of agreement (9% relative difference) for the melting index using the wavelet-based approach than threshold-based methods (11% relative difference).

We report the results of a comparative analysis focusing on grain size, mineralogical composition and spectral reflectance values (400-2500 nm) of cryoconite samples collected from Jakobshavn Isbræ, West Greenland, and Canada Glacier, McMurdo Dry Valleys, Antarctica. The samples from the Greenland site were composed of small particles clumped into larger rounded agglomerates, while those from the site in Antarctica contained fragments of different sizes and shapes. Mineralogical analysis indicates that the samples from Jakobshavn Isbræ contained a higher percentage of quartz and albite, whereas those from Canada Glacier contained a higher percentage of amphibole, augite and biotite. Spectral measurements confirmed the primary role of organic material in reducing the reflectance over the measured spectrum. The reflectance of the samples from the Antarctic site remained low after the removal of organic matter because of the higher concentration of minerals with low reflectance. The reflectance of dried cryoconite samples in the visible region was relatively low (e.g. between ∼0.1 and ∼0.4) favouring increased absorbed solar radiation. Despite high reflectance values in the shortwave infrared region, the effect of the presence of cryoconite is negligible at infrared wavelengths where ice reflectance is low.

Despite the growing number of remote-sensing products from satellite sensors, mapping of the combined spatial distribution and temporal variability of inundation in tropical wetlands remains challenging. An emerging innovative approach is offered by Global Navigation Satellite System reflectometry (GNSS-R), a concept that takes advantage of GNSS-transmitting satellites and independent radar receivers to provide bistatic radar observations of Earth’s surface with large-scale coverage. The objective of this paper is to assess the capability of spaceborne GNSS reflections to characterize surface inundation dynamics in a complex wetlands environment in the Peruvian Amazon with respect to current state-of-the-art methods. This study examines contemporaneous ALOS2 PALSAR-2 L-band imaging radar, CYGNSS GNSS reflections, and ground measurements to assess associated advantages and challenges to mapping inundation dynamics, particularly in regions under dense tropical forest canopies. Three derivatives of CYGNSS Delay-Doppler maps (1) peak signal-to-noise ratio (SNR), (2) leading edge slope, and (3) trailing edge slope, demonstrated statistically significant logarithmic relationships with estimated flooded area percentages determined from SAR, with SNR exhibiting the strongest association. Aggregated Delay-Doppler maps SNR time series data examined for inundated regions undetected by imaging radar suggests GNSS-R exhibits a potentially greater sensitivity to inundation state beneath dense forest canopies relative to SAR. Results demonstrate the capability for mapping extent and dynamic wetlands ecosystems in complex tropical landscapes, alone or in combination with other remote-sensing techniques such as those based on imaging radar, contributing to enhanced mapping of these regions. However, several aspects of GNSS-R observations such as noise level, spatial resolution, and signal coherence need to be further examined.

We have developed a marine DMS (dimethylsulfide) module and implemented it in a 1-D coupled atmosphere-ocean-biogeochemical model. In developing the marine sulphur model we have found that several parameters used in the model are not known to even an order of magnitude. Our approach is used to test the model's sensitivity to these parameters. A parameter change of ± 25 % is applied to test the respective range of changes in the DMS fluxes. The model is run for a 3-year time period as well as for the time period of the Subarctic Ecosystem Response to Iron Enrichment Study (SERIES) in July 2002. The simulated seasonal cycle is in agreement with available observations: Near surface DMS concentrations vary from 1.5 nmol L - 1 in winter to 13.5 nmol L - 1 in summer. Simulated DMS production is found to be most sensitive to variations of the S:N ratio and the bacterial consumption rate of DMS. Implementing light or UV limited bacterial activity shows a negligible effect in winter and increases DMS concentrations by 0.2– 0.6 nmol L - 1 in summer. Similarly a yield increase under UV stress increases summer values by 1– 2 nmol L - 1 . The simulated diel cycle in surface DMS concentration is no more than 2.5 nmol L - 1 , even when light-dependent changes in bacterial activity are considered. Simulating the DMS response to iron fertilization with the standard run leads to overestimation during an initial bloom of small phytoplankton. While implementing light-dependent bacterial activity has a minor effect, the implementation of yields that depend on nutrient availability significantly improves the results. The model confirms earlier results showing the importance of including atmospheric DMS concentrations in gas flux calculations when there are high surface concentrations and small atmospheric boundary layer heights. Simulated summer concentrations in the upper layer can be underestimated by 2 nmol L - 1 or more if the atmospheric concentration is set to zero. Our study shows that inclusion of mechanistic DMS modules in comprehensive climate models requires better knowledge of the variation of key parameters in the marine sulphur cycle. Even though there are still open questions, the model reasonably reproduces the mean annual cycle; and including variable DMS yield improves the simulation of the DMS response to iron fertilization during SERIES.

OBJECTIVE To determine the relationship between reduced retinal autofluorescence and the dense scotomas in Stargardt disease. METHOD Retrospective review of patients with Stargardt disease seen between 2000 and 2004 at a tertiary referral center. PATIENTS All 32 patients with Stargardt who underwent both autofluorescence (AF) imaging and scotoma mapping were included. RESULTS Forty-seven percent of eyes had dense scotomas corresponding to the areas of loss of AF (27% corresponding to the area of uniform loss of AF, and 20% corresponding to the area of uniform plus mottled loss of AF). Fifty-three percent of eyes did not have a good correlation of the dense scotoma with the area of loss of AF. Both eyes were judged to be in the same group in 75% of patients. CONCLUSIONS Areas of reduced AF are measurable, but are not equivalent to the area of dense scotoma in 53% of patients. Measures of retinal sensitivity and scotomas are necessary for defining retinal functional involvement in Stargardt disease.

We have developed a 1-D atmosphere–ocean-biogeochemical model to investigate the coupling between atmosphere–ocean exchanges and the planktonic ecosystem during the Subarctic Ecosystem Response to Iron Enrichment Study (SERIES) in 2002. The atmospheric Single Column Model (SCM) is based on the Canadian Centre for Climate Modelling and Analysis (CCCma) Atmospheric General Circulation Model (AGCM). The ocean component employs the General Ocean Turbulence Model (GOTM). A seven-component ecosystem model is embedded in GOTM, which includes nitrogen, organic and inorganic carbon, silica and oxygen cycling. We use observations from SERIES combined with atmospheric reanalysis data to initiate and force the coupled physical model. We found that atmospheric temperatures and humidities are higher and the stratification more stable if nudged to National Centre of Environmental Prediction (NCEP) rather than to European Centre for Medium-Range Weather Forecasts (ECMWF) 40-yr reanalysis data. Doubling the vertical resolution in the atmosphere improved the representation of mixing and the thermal structure, affecting cloudiness and radiative fluxes at the ocean surface as well as planetary boundary layer heights and gas dispersion in the lower atmosphere. From observed ocean-surface dimethyl sulphide (DMS) concentrations (outside the patch) we simulated DMS dispersion in the atmospheric boundary layer by applying a first-order loss term, with turnover times ranging from 1 to 4 days. During SERIES, shallow boundary-layer heights that occurred when DMS production was highest prevented dispersion into the atmosphere beyond several 100 m. Finally, successive model runs with iron fertilization starting on June 25, July 10 and 25 showed that the general nature of the response to iron enrichment at OSP (SERIES) is robust, but the strength as well as length of the response depend strongly on short-term atmospheric conditions (wind and radiative fluxes).

A set of three GIS-based models from the field of agricultural economy (ProLand), ecology (YELL) and hydrology (SWAT-G) was applied in the mountainous mesoscale watershed of the Aar, Germany. In a joint modelling exercise a sequence of land use change scenarios was analysed. It was assumed that the average field size for land use systems increases due to changes in the economic and administrative framework. ProLand calculated the spatial distribution of the new production systems on a grid basis. The resulting land use maps were analysed with YELL with regard to the habitat suitability for Emberiza citrinella and with the model SWAT-G in terms of the effects of land use change on hydrologic processes. Multi-functional trade-off relations between economic, ecological and hydrological landscape functions were compiled.

PurposeQuantification of tissue stiffness may facilitate identification of abnormalities in orofacial muscle tone and thus contribute to differential diagnosis of dysarthria. Tissue stiffness is affected by muscle tone as well as age-related changes in muscle and connective tissue.MethodThe Myoton-3 measured tissue stiffness in 40 healthy adults, including equal numbers of men and women in each of two age groups: 18–40 years and 60+ years. Data were collected from relaxed muscles at the masseter, cheek, and lateral tongue surfaces in two positions: reclined on the side and seated with head tilted.ResultsTissue stiffness differed across age, sex, and measurement site with multiple interaction effects. Overall, older subjects exhibited higher stiffness coefficients and oscillation frequency measures than younger subjects whereas sex differences varied by tissue site. Effects of body position were inconsistent across tissue site and measurement.ConclusionsAlthough older subjects were expected to have lower muscle tone, age-related nonmuscular tissue changes may have contributed to yield a net effect of higher stiffness. These data raise several considerations for the development of accurate normative data and for future diagnostic applications of tissue stiffness assessment.

To determine if the severity of diabetic macular edema influences the effectiveness of subthreshold micropulse (STMP) laser treatment.A total of 63 eyes of 58 patients with diabetic macular edema were divided into two groups based on their initial central foveal thickness (CFT). Group 1 had CFT ≤400 μm, group 2 had CFT400 μm. The change from baseline in CFT and visual acuity were compared at 3, 6 and 12 months follow-up. Patients were considered for retreatment with micropulse laser at 3 months if macular edema had not improved. Patients were considered for rescue anti-VEGF injections if there was clinically significant macular edema at 6 months follow-up. Number of laser retreatments, injections, and any adverse effects from STMP laser were recorded.Group 1 (n=33) experienced an average of 55 μm reduction in CFT and 0.2 log MAR gain in visual acuity at 12 months (P0.001). No patient required rescue anti-VEGF injections. Group 2 (n=30) experienced no significant change in CFT or visual acuity by 6 months despite retreatment with STMP in 19 eyes. From 6 to 12 months follow-up, all the patients in group 2 received rescue Bevacizumab injections that resulted in 307 μm reduction in CFT and 0.3 log MAR improvement in visual acuity (P0.001). No adverse effects from STMP laser were recorded.Severity of edema can influence the effects of STMP laser. STMP monotherapy is safe and effective in treating edema of mild to moderate severity.

To evaluate the visual outcomes and macular thickness change in patients with symptomatic chronic central serous chorioretinopathy after treatment with a subthreshold MicroPulse diode laser.In this retrospective, interventional case series, 10 patients were treated with the subthreshold 810-nm diode MicroPulse laser. Selected patients had symptomatic disease that may or may not have involved the foveal center. The MicroPulse laser was applied to the areas of leakage seen on fluorescein angiogram, over the areas of clinical neurosensory detachment, and/or pigment epithelial detachments. Pretreatment and posttreatment vision, change in maximum macular thickness, number of treatment sessions, and number of laser spot applications were recorded. Patients were excluded if they did not attend follow-up, had other confounding macular diseases, were using steroid medications, or application of another treatment modality had been used (i.e., photodynamic therapy or anti-vascular endothelial growth factor medication).Ten patients met the inclusion criteria, with 1 patient treated in both eyes. Three patients were excluded for lack of follow-up, one for the use of systemic steroids, and one for treatment with anti-vascular endothelial growth factor injection. Maximum macular thickness decreased after subthreshold MicroPulse laser treatment between 20 μm and 338 μm (mean = 97 μm decrease, P = 0.0046) in 11 treated eyes.Subthreshold diode MicroPulse laser is a potential treatment option for patients with symptomatic chronic central serous chorioretinopathy.

At this early stage of modeling marine ecosystems and biogeochemical cycles in the Pacific Arctic Region (PAR), numerous challenges lie ahead. Observational data used for model development and validation remain sparse, especially across seasons and under a variety of environmental conditions. Field data are becoming more available, but at the same time PAR is rapidly changing. Biogeochemical models can provide the means to capture some of these changes. This study introduces and synthesizes ecosystem modeling in PAR by discussing differences in complexity and application of one-dimensional, regional, and global earth system models. Topics include the general structure of ecosystem models and specifics of the combined benthic, pelagic, and ice PAR ecosystems, the importance of model validation, model responses to climate influences (e.g. diminishing sea ice, ocean acidification), and the impacts of circulation and stratification changes on PAR ecosystems and biogeochemical cycling. Examples of modeling studies that help place the region within the context of the Pan-Arctic System are also discussed. We synthesize past and ongoing PAR biogeochemical modeling efforts and briefly touch on decision makers’ use of ecosystem models and on necessary future developments.

Ziele: Ziel der Studie war die Erprobung eines multiparametrischen Protokolls mit diffusionsgewichteter (DWI)-, BOLD- und dynamischer kontrastverstarkter MRT (DCE-MRI) zur praoperativen Abbildung von Zellularitat, Oxygenierung, Perfusion and Permeabilitat des Nierenzellkarzinoms (RCC). Methode: Vierzehn Patienten mit klarzelligem und 4 Patienten mit papillarem RCC wurden mit DWI, BOLD und DCE-MRI bei einer Feldstarke von 1,5 Tesla untersucht. Der apparente Diffusionskoeffizient (ADC, 10–3mm2/s) wurde mit einer monoexponentiellen Analyse berechnet (b=0,500). Parametrische R2*-Karten (ms-1) wurde mit einer Gradientenecho-Sequenz (12 Echos, 5–49ms) berechnet. Die DCE-MRI (1 Bild/Sekunde uber 4 Minuten) wurde mit einem 2-Kompartment-Modell ausgewertet, welches die Unterscheidung von Perfusion (Plasmafluss FP ml/100ml/min, Plasmavolumen VP ml/100ml), Permeabilitat (Extraktionsfluss FE ml/100ml/min) und extrazellularem Volumen (VE, ml/100ml) erlaubt. Die statistische Auswertung wurde mit dem Wilcoxon-Vorzeichen-Rang-Test und mit Pearson's Korrelation berechnet. Ergebnis: Klarzellige RCC wiesen einen hoheren ADC (1,45±0,16 vs. 1,38±0.15), niedrigeres R2* (14,2±7,5 vs. 21,7±10,9) und hoheres VP (36,5±23,9 vs. 10,01±10,3) als papillare Tumoren auf. FP klarzelliger RCC war signifikant hoher (189,1±126,4 vs. 21,1±16,4). Hoher FP und VP korrelierten moderat, aber signifikant (p

In the past few decades, there has been enormous growth in scientific studies of physical, chemical, and biological interactions among reservoirs in polar regions. This has come, in part, as a result of a few significant discoveries: There is dramatic halogen chemistry that occurs on and above the sea ice in the springtime that destroys lower tropospheric ozone and mercury [Simpson et al., 2007; Steffen et al., 2008], the sunlit snowpack is very photochemically active [Grannas et al., 2007], biology as a source of organic compounds plays a pivotal role in these processes, and these processes are occurring in the context of rapidly changing polar regions under climate feedbacks that are as of yet not fully understood [Serreze and Barry, 2011]. Stimulated by the opportunities of the International Polar Year (IPY, 2007-2009), a number of large-scale field studies in both polar environments have been undertaken, aimed at the study of the complex biotic and abiotic processes occurring in all phases (see Figure 1). Sea ice plays a critical role in polar environments: It is a highly reflective surface that interacts with radiation; it provides a habitat for mammals and micro-organisms alike, thus playing a key role in polar trophic processes and elemental cycles; and it creates a saline environment for chemical processes that facilitate release of halogenated gases that contribute to the atmosphere's ability to photochemically cleanse itself in an otherwise low-radiation environment. Ocean-air and sea ice-air interfaces also produce aerosol particles that provide cloud condensation nuclei.

[1] We report measurements of ablation rates of the bottom of two supraglacial lakes and of temperatures at different depths collected during the summers of 2010 and 2011 in west Greenland. To our knowledge, this is the first time that such data sets are reported and discussed in the literature. The measured ablation rates at the bottom of the two lakes are of the order of ∼6 cm/day, versus a rate of ∼2.5–3 cm/day in the case of bare ice of surrounding areas. Though our measurements suggest the presence of a vertical temperature gradient, it is not possible to draw final conclusions as the measured gradient is smaller than the accuracy of our temperature sensors. In-situ measurements are compared with the results of a thermodynamic model forced with the outputs of a regional climate model. In general, the model is able to satisfactorily reproduce the measured quantities with RMSE of the order of 3–4 cm for the ablation and ∼1.5°C in the case of water temperature. Our results confirm that the ablation at the bottom of supraglacial lakes plays an important role on the overall lake volume with the ablation in the case of ice covered by a lake being 110–135% of that over bare ice at nearby locations. Beside ice sheet hydrological implications, melting at the bottom of a supraglacial lake might affect estimates of lake volume from spaceborne visible and near-infrared measurements.

Supraglacial lakes form from meltwater on the Greenland ice sheet in topographic depressions on the surface, affecting both surface and sub-glacial processes. As the reflectance in the visible and near-infrared regions of a column of water is modulated by its height, retrieval techniques using spaceborne remote sensing data (e.g. Landsat, MODIS) have been proposed in the literature for the detection of lakes and estimation of their volume. These techniques require basic assumptions on the spectral properties of the water as well as the bottom of the lake, among other things. In this study, we report results obtained from the analysis of concurrent in-situ multi-spectral and depth measurements collected over a supraglacial lake during early July 2010 in West Greenland (Lake Olivia, 69°36'35" N, 49°29'40" W) and aim to assess some of the underlying hypotheses in remote sensing based bathymetric approaches. In particular, we focus our attention on the analysis of the lake bottom albedo and of the water attenuation coefficient. The analysis of in-situ data (collected by means of a remotely controlled boat equipped with a GPS, a sonar and a spectrometer) highlights the exponential trend of the water-leaving reflectance with lake depth. The values of the attenuation factor obtained from in-situ data are compared with those computed using approaches proposed in the literature. Also, the values of the lake bottom albedo from in-situ measurements are compared with those obtained from the analysis of reflectance of shallow waters. Finally, we quantify the error between in-situ measured and satellite-estimated lake depth values for the lake under study.

Microvariation within the DR1 Ag family has created two DR molecules which differ only at beta-chain residues 85 (Val/Ala) and 86 (Gly/Val). TCR utilized by human alloproliferative T lymphocyte clones which can distinguish between these microvariants have been characterized by cDNA sequencing. The alpha- and beta-chain cDNA utilize a diverse set of variable (V) gene segments although the same V segment may be used by different individuals suggesting that V segment usage by the alloreactive T lymphocyte clones is nonrandom. There appears to be no difference in the repertoire of V segments utilized by T lymphocytes that preferentially recognize specific DR1 allelic products (DR(alpha,beta 1*0101) or DR(alpha,beta 1*0102)) and T lymphocytes that recognize both DR1 molecules. In contrast, the junctional regions of both alpha- and beta-chains are diverse in length and sequence although some common elements can be observed among TCR which share V gene segments. Two TCR which share V alpha and V beta gene segments differ in fine specificity for specific DR1 allelic products implicating the junctional regions of alpha- and beta-chains in the recognition of differentially bound peptides and/or in recognition of DR beta-chain residues 85 and 86. The stimulation of many diverse TCR by the limited allelic variation between DR(alpha,beta 1*0101) and DR(alpha,beta 1*0102) molecules suggests that the effect of DR microvariation on human immune responsiveness may be substantial.

Broadband wireless systems often operate under channel conditions that are characterized by a sparse channel impulse response. When the amount of training is given by the standard, compressed sensing channel estimation can exploit this sparsity to improve the quality of the channel estimate. In this paper, we analyze and compare the hardware complexity and denoising performance of three greedy algorithms for the 3GPP LTE system. The complexity/performance trade-off is analyzed using parameterized designs with varying configurations. One configuration of each algorithm is fabricated in a 180nm process and measured.

Bacteria play an important role in determining the properties and behavior of clay minerals in natural environments and such interactions have great potential for creating stable biofilms and carbon storage sites in soils, but our knowledge of these interactions are far from complete. The purpose of this study was to understand better the effects of bacteria-generated biofilms on clay interlayer expansion. Mixtures of a colloidal, 2-water hectorite clay and Pseudomonas syringae in a minimal media suspension evolve into a polysaccharide-rich biofilm aggregate in time-series experiments lasting up to 1 week. X-ray diffraction analysis reveals that upon aggregation, the clay undergoes an initial interlayer contraction. Short-duration experiments, up to 72 h, result in a decrease in the d001 value from 1.50 to 1.26 nm. The initial interlayer contraction is followed in long-duration (up to 1 week) experiments by an expansion of the d001 value of 1.84 nm. The expansion is probably a result of large, biofilm-produced, polymeric molecules being emplaced in the interlayer site. The resultant organo-clay could provide a possible storage medium for carbon in a microbial colony setting.

Improvement of algorithms for the retrieval of inherent optical properties (IOPs) as well as concentrations of chlorophyll (CHL) and minerals from the recorded reflectance spectra remains an important issue in the analysis of water quality in coastal zones. It is expected that the retrievals could be improved if both UV and NIR channels are added to the existing VIS bands. This paper examines the performance of over constrained linear matrix inversion with statistical selection algorithm when additional information from UV and NIR channels is added to the retrievals for both synthetic and field data.

Plus de 70% des patients cancereux presentent des douleurs lorsque la maladie est avancee. La majorite de ces patients ont plus de 60 ans. L'echelle de traitement proposee par l'Organisation mondiale de la Sante, diffusee en Suisse par la Ligue suisse contre le Cancer, permet — lorsque les medicaments, salicyles, codeine et morphine sont donnes a doses adaptees et a heures fixes — de controler plus de 90% des douleurs. En phase terminale, la dyspnee, l'agitation ou la confusion et l'angoisse posent de difficiles problemes aux medecins, mais actuellement des traitements simples permettent d'y pallier.