68 research outputs found

    Soil Moisture Retrieval with Airborne PALS Instrument over Agricultural Areas in SMAPVEX16

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    NASA's SMAP (Soil Moisture Active Passive) calibration and validation program revealed that the soil moisture products are experiencing difficulties in meeting the mission requirements in certain agricultural areas. Therefore, the mission organized airborne field experiments at two core validation sites to investigate these anomalies. The SMAP Validation Experiment 2016 included airborne observations with the PALS (Passive Active L-band Sensor) instrument and intensive ground sampling. The goal of the PALS measurements are to investigate the soil moisture retrieval algorithm formulation and parameterization under the varying (spatially and temporally) conditions of the agricultural domains and to obtain high resolution soil moisture maps within the SMAP pixels. In this paper the soil moisture retrieval using the PALS brightness temperature observations in SMAPVEX16 is presented

    What drives amyloid molecules to assemble into oligomers and fibrils?

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    We develop a general theory for three states of equilibrium of amyloid peptides: the monomer, oligomer, and fibril. We assume that the oligomeric state is a disordered micelle-like collection of a few peptide chains held together loosely by hydrophobic interactions into a spherical hydrophobic core. We assume that fibrillar amyloid chains are aligned and further stabilized by `steric zipper' interactions -- hydrogen bonding and steric packing, in addition to specific hydrophobic sidechain contacts. The model makes a broad set of predictions, consistent with experiments: (i) Similar to surfactant micellization, amyloid oligomerization should increase with bulk peptide concentration. (ii) The onset of fibrillization limits the concentration of oligomers in the solution. (iii) The average fibril length \emph{vs.} monomer concentration agrees with data on α\alpha-synuclein, (iv) Full fibril length distributions follow those of α\alpha-synuclein, (v) Denaturants should `melt out' fibrils, and (vi) Added salt should stabilize fibrils by reducing repulsions between amyloid peptide chains. Interestingly, small changes in solvent conditions can: (a) tip the equilibrium balance between oligomer and fibril, and (b) cause large changes in rates, through effects on the transition-state barrier. This model may provide useful insights into the physical processes underlying amyloid diseases

    The contribution of caregiver psychosocial factors to distress associated with behavioural and psychological symptoms in dementia

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    Copyright © 2016 John Wiley & Sons, Ltd. Objective: The objective of the study is to examine caregiver factors as predictors of BPSD-related distress and their potential mechanisms. Method: Informal caregivers of people with dementia (n = 157) recruited from 28 community mental health teams in six NHS Trusts across England completed questionnaires regarding psychosocial factors (relationship quality, competence, guilt, health-related quality of life in the caregiver and person with dementia, reactivity to behavioural and psychological symptoms in dementia [BPSD] and burden) and frequency of BPSD. Analyses of BPSD-related distress include hierarchical multiple regression, mediation, moderation and path analysis. Results: Caregiver psychosocial factors explained 56% of the variance in BPSD-related distress. After controlling for these factors, frequency of BPSD was not a significant predictor of BPSD-related distress. Caregiver reactivity to BPSD, burden, competence and relationship quality directly influenced BPSD-related distress. Guilt influenced distress indirectly via competence, burden and reactivity to BPSD. The final model accounted for 41% of the variance in BPSD-related distress and achieved a good fit to the data (χ 2 = 23.920, df = 19, p = 0.199). Conclusions: Caregiver psychosocial factors including sense of competence, guilt, burden and reactivity to BPSD contribute to BPSD-related distress. Tailored interventions for managing behaviour problems in family settings could focus on these factors associated with BPSD-related distress to minimise distress in families. Copyright © 2016 John Wiley & Sons, Ltd

    Analysis of Soil Freeze/Thaw Signatures During Slapex F/T Campaign

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    Permanently frozen and seasonally frozen soils occur over a large portion of the Earth's land surface. Changes in the freeze/thaw state of the land surface reflects major changes in thermal and hydraulic properties as well as acting as a "switch" for many ecological processes. In short, soil freeze/thaw state is a fundamental land surface variable in the water and energy cycles, and it connects to the carbon cycle. Surface freeze/thaw state is observable by passive and active microwave sensors. For example, NASA's Soil Moisture Active Passive (SMAP) mission includes a freeze/thaw data product. Such satellite sensing offers routine all-season and all-weather global observations of soil freeze/thaw state with the application of suitable algorithms. We describe early finding from the SLAPex Freeze/Thaw campaign, believed to be the first airborne campaign of its type, focusing on soil freeze/thaw

    SLAPex Freeze/Thaw 2015: The First Dedicated Soil Freeze/Thaw Airborne Campaign

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    Soil freezing and thawing is an important process in the terrestrial water, energy, and carbon cycles, marking the change between two very different hydraulic, thermal, and biological regimes. NASA's Soil Moisture Active/Passive (SMAP) mission includes a binary freeze/thaw data product. While there have been ground-based remote sensing field measurements observing soil freeze/thaw at the point scale, and airborne campaigns that observed some frozen soil areas (e.g., BOREAS), the recently-completed SLAPex Freeze/Thaw (F/T) campaign is the first airborne campaign dedicated solely to observing frozen/thawed soil with both passive and active microwave sensors and dedicated ground truth, in order to enable detailed process-level exploration of the remote sensing signatures and in situ soil conditions. SLAPex F/T utilized the Scanning L-band Active/Passive (SLAP) instrument, an airborne simulator of SMAP developed at NASA's Goddard Space Flight Center, and was conducted near Winnipeg, Manitoba, Canada, in October/November, 2015. Future soil moisture missions are also expected to include soil freeze/thaw products, and the loss of the radar on SMAP means that airborne radar-radiometer observations like those that SLAP provides are unique assets for freeze/thaw algorithm development. This paper will present an overview of SLAPex F/T, including descriptions of the site, airborne and ground-based remote sensing, ground truth, as well as preliminary results

    A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation

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    Nanoparticles introduced in living cells are capable of strongly promoting the aggregation of peptides and proteins. We use here molecular dynamics simulations to characterise in detail the process by which nanoparticle surfaces catalyse the self- assembly of peptides into fibrillar structures. The simulation of a system of hundreds of peptides over the millisecond timescale enables us to show that the mechanism of aggregation involves a first phase in which small structurally disordered oligomers assemble onto the nanoparticle and a second phase in which they evolve into highly ordered beta-sheets as their size increases

    A Helical Structural Nucleus Is the Primary Elongating Unit of Insulin Amyloid Fibrils

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    Although amyloid fibrillation is generally believed to be a nucleation-dependent process, the nuclei are largely structurally uncharacterized. This is in part due to the inherent experimental challenge associated with structural descriptions of individual components in a dynamic multi-component equilibrium. There are indications that oligomeric aggregated precursors of fibrillation, and not mature fibrils, are the main cause of cytotoxicity in amyloid disease. This further emphasizes the importance of characterizing early fibrillation events. Here we present a kinetic x-ray solution scattering study of insulin fibrillation, revealing three major components: insulin monomers, mature fibrils, and an oligomeric species. Low-resolution three-dimensional structures are determined for the fibril repeating unit and for the oligomer, the latter being a helical unit composed of five to six insulin monomers. This helical oligomer is likely to be a structural nucleus, which accumulates above the supercritical concentration used in our experiments. The growth rate of the fibrils is proportional to the amount of the helical oligomer present in solution, suggesting that these oligomers elongate the fibrils. Hence, the structural nucleus and elongating unit in insulin amyloid fibrillation may be the same structural component above supercritical concentrations. A novel elongation pathway of insulin amyloid fibrils is proposed, based on the shape and size of the fibrillation precursor. The distinct helical oligomer described in this study defines a conceptually new basis of structure-based drug design against amyloid diseases

    Characterization of Oligomers of Heterogeneous Size as Precursors of Amyloid Fibril Nucleation of an SH3 Domain: An Experimental Kinetics Study

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    Correction: Characterization of Oligomers of Heterogeneous Size as Precursors of Amyloid Fibril Nucleation of an SH3 Domain: An Experimental Kinetics Study. PLoS ONE 9(1): 10.1371/annotation/dbb84118-9ada-43e4-8734-8f8322be1a59. doi: 10.1371/annotation/dbb84118-9ada-43e4-8734-8f8322be1a59Understanding the earliest molecular events during nucleation of the amyloid aggregation cascade is of fundamental significance to prevent amyloid related disorders. We report here an experimental kinetic analysis of the amyloid aggregation of the N47A mutant of the α-spectrin SH3 domain (N47A Spc-SH3) under mild acid conditions, where it is governed by rapid formation of amyloid nuclei. The initial rates of formation of amyloid structures, monitored by thioflavine T fluorescence at different protein concentrations, agree quantitatively with high-order kinetics, suggesting an oligomerization pre-equilibrium preceding the rate-limiting step of amyloid nucleation. The curves of native state depletion also follow high-order irreversible kinetics. The analysis is consistent with the existence of low-populated and heterogeneous oligomeric precursors of fibrillation that form by association of partially unfolded protein monomers. An increase in NaCl concentration accelerates fibrillation but reduces the apparent order of the nucleation kinetics; and a double mutant (K43A, N47A) Spc-SH3 domain, largely unfolded under native conditions and prone to oligomerize, fibrillates with apparent first order kinetics. On the light of these observations, we propose a simple kinetic model for the nucleation event, in which the monomer conformational unfolding and the oligomerization of an amyloidogenic intermediate are rapidly pre-equilibrated. A conformational change of the polypeptide chains within any of the oligomers, irrespective of their size, is the rate-limiting step leading to the amyloid nuclei. This model is able to explain quantitatively the initial rates of aggregation and the observed variations in the apparent order of the kinetics and, more importantly, provides crucial thermodynamic magnitudes of the processes preceding the nucleation. This kinetic approach is simple to use and may be of general applicability to characterize the amyloidogenic intermediates and oligomeric precursors of other disease-related proteins.This work was financed by the Andalucía Government (grant FQM-02838), the Spanish Ministry of Science and Innovation (grant BIO2009-07317), and the European Regional Development Fund of the European Union. D. Ruzafa is recipient of a research fellowship from the F.P.U. program of the Spanish Ministry of Education. L. Varela is financed by the G.R.E.I.B. program of the University of Granada

    An Aged Canid with Behavioral Deficits Exhibits Blood and Cerebrospinal Fluid Amyloid Beta Oligomers

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    Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behaviour and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behaviour of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog’s blood and cerebrospinal fluid via anti-oligomer- and anti-Aβ specific binders. Importantly, our results reveal the potent neurotoxic effects of the dog’s cerebrospinal fluid on cell viability and the seeding efficiency of the cerebrospinal fluid-borne soluble oligomers on the thermodynamic activity and the aggregation kinetics of synthetic human Aβ. The value of further characterising the naturally occurring Alzheimer-like neuropathology in dogs using genetic and molecular tools is discussed

    Application of HEC-HMS in a Cold Region Watershed and Use of RADARSAT-2 Soil Moisture in Initializing the Model

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    This paper presents an assessment of the applicability of using RADARSAT-2-derived soil moisture data in the Hydrologic Modelling System developed by the Hydrologic Engineering Center (HEC-HMS) for flood forecasting with a case study in the Sturgeon Creek watershed in Manitoba, Canada. Spring flooding in Manitoba is generally influenced by both winter precipitation and soil moisture conditions in the fall of the previous year. As a result, the soil moisture accounting (SMA) and the temperature index algorithms are employed in the simulation. Results from event and continuous simulations of HEC-HMS show that the model is suitable for flood forecasting in Manitoba. Soil moisture data from the Manitoba Agriculture field survey and RADARSAT-2 satellite were used to set the initial soil moisture for the event simulations. The results confirm the benefit of using satellite data in capturing peak flows in a snowmelt event. A sensitivity analysis of SMA parameters, such as soil storage, maximum infiltration, soil percolation, maximum canopy storage and tension storage, was performed and ranked to determine which parameters have a significant impact on the performance of the model. The results show that the soil moisture storage was the most sensitive parameter. The sensitivity analysis of initial soil moisture in a snowmelt event shows that cumulative flow and peak flow are highly influenced by the initial soil moisture setting of the model. Therefore, there is a potential to utilize RADARSAT-2-derived soil moisture for hydrological modelling in other snow-dominated Manitoba watersheds
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