Aggregation of initially stably structured proteins is involved in more than 20 human amyloid diseases. Despite intense research, however, how this class of proteins assembles into amyloid fibrils ...remains poorly understood, principally because of the complex effects of amino acid substitutions on protein stability, solubility, and aggregation propensity. We address this question using β2-microglobulin (β2m) as a model system, focusing on D76N-β2m that is involved in hereditary amyloidosis. This amino acid substitution causes the aggregation-resilient wild-type protein to become highly aggregation prone in vitro, although the mechanism by which this occurs remained elusive. Here, we identify the residues key to protecting β2m from aggregation by coupling aggregation with antibiotic resistance in E. coli using a tripartite β-lactamase assay (TPBLA). By performing saturation mutagenesis at three different sites (D53X-, D76X-, and D98X-β2m) we show that residue 76 has a unique ability to drive β2m aggregation in vivo and in vitro. Using a randomly mutated D76N-β2m variant library, we show that all of the mutations found to improve protein behavior involve residues in a single aggregation-prone region (APR) (residues 60 to 66). Surprisingly, no correlation was found between protein stability and protein aggregation rate or yield, with several mutations in the APR decreasing aggregation without affecting stability. Together, the results demonstrate the power of the TPBLA to develop proteins that are resilient to aggregation and suggest a model for D76N-β2m aggregation involving the formation of long-range couplings between the APR and Asn76 in a nonnative state.
IntroductionRecovery from substance use disorder requires sustained effort and perseverance. Grit is a resilience factor that may be important for people in recovery. Little research has been ...conducted on grit in patients with substance use disorder, especially in a large and varied sample.ObjectivesTo examine the Short Grit Scale (Grit-S) in patients with substance use disorder, our aims were to analyze its psychometric properties and use demographic and clinical characteristics to predict variance in Grit-S scores.MethodsIn this study of patients in treatment for substance use disorder, participants completed the Grit-S and other self-report measures. The psychometric properties of the Grit-S were assessed in outpatients (N=94) and a hierarchical regression was used to predict Grit-S variance in inpatients (N=1238).ResultsThe Grit-S demonstrated good internal consistency (α=.75) and strong test-retest reliability (unadjusted r=.81, adjusted r=.79, p values<.001). The mean Grit-S score was 3.15, which was lower than other clinical samples reported in the literature. Regression modeling indicated a moderate, statistically significant association between demographic and clinical characteristics and Grit-S scores (R2=15.5%, p<.001).ConclusionsOf particular interest, the positive factor of recovery protection showed the strongest association with grit of all the variables assessed. Hence the positive construct of grit was correlated with other positive constructs, as well as with risks. Longitudinal assessment of grit and substance use could measure the stability and clinical significance of grit throughout recovery.Disclosure of InterestM. Griffin: None Declared, R. Weiss Consultant of: Analgesic Solutions, WCG, & Alkermes, C. Trinh: None Declared
Abstract
We have employed state-of-the-art cross-correlation noise spectroscopy (CCNS) to study carrier dynamics in silicon heterojunction solar cells (SHJ SCs). These cells were composed of a light ...absorbing
n
-doped monocrystalline silicon wafer contacted by passivating layers of
i
-
a
-Si:H and doped
a
-Si:H selective contact layers. Using CCNS, we are able to resolve and characterize four separate noise contributions: (1) shot noise with Fano factor close to unity due to holes tunneling through the np-junction, (2) a 1/
f
term connected to local potential fluctuations of charges trapped in a-Si:H defects, (3) generation-recombination noise with a time constant between 30 and 50 μs and attributed to recombination of holes at the interface between the ITO and
n-a
-Si:H window layer, and (4) a low-frequency generation-recombination term observed below 100 K which we assign to thermal emission over the ITO/
ni
-
a
-Si:H interface barrier. These results not only indicate that CCNS is capable of reveling otherwise undetectable relaxation process in SHJ SCs and other multi-layer devices, but also that the technique has a spatial selectivity allowing for the identification of the layer or interface where these processes are taking place.
A long-standing and profound problem in astronomy is the difficulty in obtaining deep near-infrared observations due to the extreme brightness and variability of the night sky at these wavelengths. A ...solution to this problem is crucial if we are to obtain the deepest possible observations of the early Universe, as redshifted starlight from distant galaxies appears at these wavelengths. The atmospheric emission between 1,000 and 1,800 nm arises almost entirely from a forest of extremely bright, very narrow hydroxyl emission lines that varies on timescales of minutes. The astronomical community has long envisaged the prospect of selectively removing these lines, while retaining high throughput between them. Here we demonstrate such a filter for the first time, presenting results from the first on-sky tests. Its use on current 8 m telescopes and future 30 m telescopes will open up many new research avenues in the years to come.
The implementation of light management textures in thin-film solar cells often simultaneously causes an undesired deterioration of electronic performance. Here, we introduce a simple yet effective ...technique for improved light management in liquid phase crystallized silicon thin-film solar cells on glass. By imprinting pyramidal textures on the sun-facing side of the glass superstrate, absorber and functional layers of the device remain unaffected while light in-coupling is significantly increased. An increase of short-circuit current density by 2.5mA cm2 was observed by texturing the glass in this way, corresponding to an enhanced power conversion efficiency from 12.9% to 13.8%. Optical simulations allow to attribute the increase in equal shares to an anti-reflective effect at the air-glass interface as well as light scattering and multiple passes through the glass. The technology allows for independent optimization of optical performance without compromising on electronic material issues and is therefore useable for any other solar cell technology using a glass superstrate.
The PROSPECT physics program Ashenfelter, J; Balantekin, A B; Band, H R ...
Journal of physics. G, Nuclear and particle physics,
10/2016, Letnik:
43, Številka:
11
Journal Article
Recenzirano
Odprti dostop
The precision reactor oscillation and spectrum experiment, PROSPECT, is designed to make a precise measurement of the antineutrino spectrum from a highly-enriched uranium reactor and probe eV-scale ...sterile neutrinos by searching for neutrino oscillations over a distance of several meters. PROSPECT is conceived as a 2-phase experiment utilizing segmented 6Li-doped liquid scintillator detectors for both efficient detection of reactor antineutrinos through the inverse beta decay reaction and excellent background discrimination. PROSPECT Phase I consists of a movable 3 ton antineutrino detector at distances of 7-12 m from the reactor core. It will probe the best-fit point of the e disappearance experiments at 4 in 1 year and the favored region of the sterile neutrino parameter space at > 3 in 3 years. With a second antineutrino detector at 15-19 m from the reactor, Phase II of PROSPECT can probe the entire allowed parameter space below 10 eV2 at 5 in 3 additional years. The measurement of the reactor antineutrino spectrum and the search for short-baseline oscillations with PROSPECT will test the origin of the spectral deviations observed in recent θ 13 experiments, search for sterile neutrinos, and conclusively address the hypothesis of sterile neutrinos as an explanation of the reactor anomaly.
The requirement of high quality of service (QoS) in multi-priority industrial and domestic sensor networks poses new challenges to the increasing adoption of Internet of Things (IoT). In Multi-event ...Wireless Sensor Networks (MWSNs), nodes generate different types of data packets i.e., urgent (high priority) or normal (low priority), with different traffic proportions. High priority packets require an assurance of faster transmission and higher reliability in the network. In the literature, the existing medium access control (MAC) protocols for MWSNs have limited consideration in supporting data priority with different traffic proportions. Therefore, this paper proposes an energy efficient MAC scheme that incorporates multi-priority of data packets with dynamic traffic proportion, called PriTraCon-MAC. PriTraCon-MAC supports multi-events by considering four different priority levels of data packets and uses a novel approach that adjusts the contention window adaptively. Due to that, Request-To-Send frame of higher priority data can be sent earlier in the contention window, resulting in the corresponding faster acceptance by the receiver. Furthermore, mathematical delay analysis with different priority traffic proportions has also been undertaken. In addition, PriTraCon-MAC has been implemented in OMNET++ Castalia and its performance has been evaluated in terms of packet delay, reliability, and energy consumption, and compared with the existing Timeout Multi-priority based-MAC (TMPQ-MAC) under various network conditions. The simulation results demonstrate that PriTraCon-MAC offers lower average delay and achieves significantly higher packet success rate, while reducing energy consumption by up to 80% when compared with TMPQ-MAC protocol.
We present the first spatially resolved mid-infrared (37.1 m) image of the Fomalhaut debris disk. We use point spread function fitting and subtraction to distinctly measure the flux from the ...unresolved component and the debris disk. We measure an infrared excess in the point source of 0.9 0.2 Jy, consistent with emission from warm dust in an inner disk structure, and inconsistent with a stellar wind origin. We cannot confirm or rule out the presence of a pileup ring near the star. In the cold region, the 37 m imaging is sensitive to emission from small, blowout grains, which is an excellent probe of the dust production rate from planetesimal collisions. Under the assumptions that the dust grains are icy aggregates and the debris disk is in steady state, this result is consistent with the dust production rates predicted by Kenyon & Bromley from theoretical models of icy planet formation. We find a dust luminosity of (7.9 0.8) × 10−4 L and a dust mass of 8-16 lunar masses, depending on grain porosity, with ∼1 lunar mass in grains with radius 1 m-1 mm. If the grains are icy and highly porous, meter-sized objects must be invoked to explain the far-infrared, submm, and mm emission. If the grains are composed of astronomical silicates, there is a dearth of blowout grains and the mass loss rate is well below the predicted dust production values.
In this study, we examine the capabilities of the Landsat 8 Operational Land Imager (OLI), Thermal Infrared Sensor (TIRS), and Aqua Moderate resolution Imaging Spectroradiometer (MODIS) for ...monitoring the environmental impact of the 2015 Hyperion Treatment Plant (HTP) wastewater diversion in Santa Monica Bay, California. From 21 September – 2 November 2015, the HTP discharged approximately 39×103 m3 h-1 of treated wastewater into Santa Monica Bay through their emergency 1-mile outfall pipe. Multi-sensor satellite remote sensing was employed to determine the biophysical impact of discharged wastewater in the shallow nearshore environment. Landsat 8 TIRS observed decreased sea surface temperatures (SST) associated with the surfacing wastewater plume. Chlorophyll-a (chl-a) concentrations derived from Landsat 8 OLI and Aqua MODIS satellite sensors were used to monitor the biological response to the addition of nutrient-rich wastewater. In situ chl-a and in situ remote sensing reflectance (Rrs) were measured before, during, and after the diversion event. These in situ data were paired with coincident OLI and MODIS satellite data to yield a more comprehensive view of the changing conditions in Santa Monica Bay due to the wastewater diversion. Two new local chl-a algorithms were empirically derived using in situ data for the OLI and MODIS sensors. These new local chl-a algorithms proved more accurate at measuring chl-a changes in Santa Monica Bay compared to the standard open ocean OC2 and OC3M algorithms, and the regional southern California CALFIT algorithm, as validated by in situ chl-a measurements. Additionally, the local OLI algorithm outperformed the local MODIS algorithm, especially in the nearshore region. A time series of chl-a, as detected by the local OLI chl-a algorithm, illustrated a very large increase in chl-a concentrations during the wastewater diversion, and a subsequent decrease in chl-a after the diversion. Our study demonstrates the capability of using Landsat 8 TIRS and OLI sensors for the monitoring of SST and surface chl-a concentrations at high spatial resolution in nearshore waters and highlights the value of these sensors for assessing the environmental effects of wastewater discharge in a coastal environment.
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