365 research outputs found
The Percolation Signature of the Spin Glass Transition
Magnetic ordering at low temperature for Ising ferromagnets manifests itself
within the associated Fortuin-Kasteleyn (FK) random cluster representation as
the occurrence of a single positive density percolating network. In this paper
we investigate the percolation signature for Ising spin glass ordering -- both
in short-range (EA) and infinite-range (SK) models -- within a two-replica FK
representation and also within the different Chayes-Machta-Redner two-replica
graphical representation. Based on numerical studies of the EA model in
three dimensions and on rigorous results for the SK model, we conclude that the
spin glass transition corresponds to the appearance of {\it two} percolating
clusters of {\it unequal} densities.Comment: 13 pages, 6 figure
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Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and α-Synuclein Proteotoxicity.
Hsp104 is an AAA+ protein disaggregase, which can be potentiated via diverse mutations in its autoregulatory middle domain (MD) to mitigate toxic misfolding of TDP-43, FUS, and α-synuclein implicated in fatal neurodegenerative disorders. Problematically, potentiated MD variants can exhibit off-target toxicity. Here, we mine disaggregase sequence space to safely enhance Hsp104 activity via single mutations in nucleotide-binding domain 1 (NBD1) or NBD2. Like MD variants, NBD variants counter TDP-43, FUS, and α-synuclein toxicity and exhibit elevated ATPase and disaggregase activity. Unlike MD variants, non-toxic NBD1 and NBD2 variants emerge that rescue TDP-43, FUS, and α-synuclein toxicity. Potentiating substitutions alter NBD1 residues that contact ATP, ATP-binding residues, or the MD. Mutating the NBD2 protomer interface can also safely ameliorate Hsp104. Thus, we disambiguate allosteric regulation of Hsp104 by several tunable structural contacts, which can be engineered to spawn enhanced therapeutic disaggregases with minimal off-target toxicity
Auger Recombination in Semiconductor Quantum Wells
The principal mechanisms of Auger recombination of nonequilibrium carriers in
semiconductor heterostructures with quantum wells are investigated. It is shown
for the first time that there exist three fundamentally different Auger
recombination mechanisms of (i) thresholdless, (ii) quasi-threshold, and (iii)
threshold types. The rate of the thresholdless Auger process depends on
temperature only slightly. The rate of the quasi-threshold Auger process
depends on temperature exponentially. However, its threshold energy essentially
varies with quantum well width and is close to zero for narrow quantum wells.
It is shown that the thresholdless and the quasi-threshold Auger processes
dominate in narrow quantum wells, while the threshold and the quasi-threshold
processes prevail in wide quantum wells. The limiting case of a
three-dimensional (3D)Auger process is reached for infinitely wide quantum
wells. The critical quantum well width is found at which the quasi-threshold
and threshold Auger processes merge into a single 3D Auger process. Also
studied is phonon-assisted Auger recombination in quantum wells. It is shown
that for narrow quantum wells the act of phonon emission becomes resonant,
which in turn increases substantially the coefficient of phonon-assisted Auger
recombination. Conditions are found under which the direct Auger process
dominates over the phonon-assisted Auger recombination at various temperatures
and quantum well widths.Comment: 38 pages, 7 figure
A multi-scale comparison of modeled and observed seasonal methane emissions in northern wetlands
Wetlands are the largest global natural methane (CH4) source, and emissions between 50 and 70° N latitude contribute 10–30% to this source. Predictive capability of land models for northern wetland CH4 emissions is still low due to limited site measurements, strong spatial and temporal variability in emissions, and complex hydrological and biogeochemical dynamics. To explore this issue, we compare wetland CH4 emission predictions from the Community Land Model 4.5 (CLM4.5-BGC) with siteto regional-scale observations. A comparison of the CH4 fluxes with eddy flux data highlighted needed changes to the model’s estimate of aerenchyma area, which we implemented and tested. The model modification substantially reduced biases in CH4 emissions when compared with CarbonTracker CH4 predictions. CLM4.5 CH4 emission predictions agree well with growing season (May–September) CarbonTracker Alaskan regional-level CH4 predictions and sitelevel observations. However, CLM4.5 underestimated CH4 emissions in the cold season (October–April). The monthly atmospheric CH4 mole fraction enhancements due to wetland emissions are also assessed using the Weather Research and Forecasting-Stochastic Time-Inverted Lagrangian Transport (WRF-STILT) model coupled with daily emissions from CLM4.5 and compared with aircraft CH4 mole fraction measurements from the Carbon in Arctic Reservoirs Vulnerability Experiment (CARVE) campaign. Both the tower and aircraft analyses confirm the underestimate of cold-season CH4 emissions by CLM4.5. The greatest uncertainties in predicting the seasonal CH4 cycle are from the wetland extent, coldseason CH4 production and CH4 transport processes. We recommend more cold-season experimental studies in highlatitude systems, which could improve the understanding and parameterization of ecosystem structure and function during this period. Predicted CH4 emissions remain uncertain, but we show here that benchmarking against observations across spatial scales can inform model structural and parameter improvements
Small Heat Shock Proteins Potentiate Amyloid Dissolution by Protein Disaggregases from Yeast and Humans
The authors define how small heat-shock proteins synergize to regulate the assembly and disassembly of a beneficial prion, and then they exploit this knowledge to identify the human amyloid depolymerase
A Percolation-Theoretic Approach to Spin Glass Phase Transitions
The magnetically ordered, low temperature phase of Ising ferro- magnets is
manifested within the associated Fortuin-Kasteleyn (FK) random cluster
representation by the occurrence of a single positive density percolating
cluster. In this paper, we review our recent work on the percolation signature
for Ising spin glass ordering -- both in the short-range Edwards-Anderson (EA)
and infinite-range Sherrington-Kirkpatrick (SK) models -- within a two-replica
FK representation and also in the different Chayes-Machta-Redner two-replica
graphical representation. Numerical studies of the EA model in
dimension three and rigorous results for the SK model are consistent in
supporting the conclusion that the signature of spin-glass order in these
models is the existence of a single percolating cluster of maximal density
normally coexisting with a second percolating cluster of lower density.Comment: Based on lectures given at the 2007 Paris Summer School "Spin
Glasses." 12 pages, 3 figure
Host resources and parasite traits interact to determine the optimal combination of host parasite-mitigation strategies.
Organisms have evolved diverse strategies to manage parasite infections. Broadly, hosts may avoid infection by altering behaviour, resist infection by targeting parasites or tolerate infection by repairing associated damage. The effectiveness of a strategy depends on interactions between, for example, resource availability, parasite traits (virulence, life-history) and the host itself (nutritional status, immunopathology). To understand how these factors shape host parasite-mitigation strategies, we developed a mathematical model of within-host, parasite-immune dynamics in the context of helminth infections. The model incorporated host nutrition and resource allocation to different mechanisms of immune response: larval parasite prevention; adult parasite clearance; damage repair (tolerance). We also considered a non-immune strategy: avoidance via anorexia, reducing intake of infective stages. Resources not allocated to immune processes promoted host condition, whereas harm due to parasites and immunopathology diminished it. Maximising condition (a proxy for fitness), we determined optimal host investment for each parasite-mitigation strategy, singly and combined, across different environmental resource levels and parasite trait values. Which strategy was optimal varied with scenario. Tolerance generally performed well, especially with high resources. Success of the different resistance strategies (larval prevention or adult clearance) tracked relative virulence of larval and adult parasites: slowly maturing, highly damaging larvae favoured prevention; rapidly maturing, less harmful larvae favoured clearance. Anorexia was viable only in the short term, due to reduced host nutrition. Combined strategies always outperformed any lone strategy: these were dominated by tolerance, with some investment in resistance. Choice of parasite mitigation strategy has profound consequences for hosts, impacting their condition, survival and reproductive success. We show that the efficacy of different strategies is highly dependent on timescale, parasite traits and resource availability. Models that integrate such factors can inform the collection and interpretation of empirical data, to understand how those drivers interact to shape host immune responses in natural systems
How Awareness Changes the Relative Weights of Evidence During Human Decision-Making
A combined behavioral and brain imaging study shows how sensory awareness and stimulus visibility can influence the dynamics of decision-making in humans
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