511 research outputs found
Generating Interpretable Fuzzy Controllers using Particle Swarm Optimization and Genetic Programming
Autonomously training interpretable control strategies, called policies,
using pre-existing plant trajectory data is of great interest in industrial
applications. Fuzzy controllers have been used in industry for decades as
interpretable and efficient system controllers. In this study, we introduce a
fuzzy genetic programming (GP) approach called fuzzy GP reinforcement learning
(FGPRL) that can select the relevant state features, determine the size of the
required fuzzy rule set, and automatically adjust all the controller parameters
simultaneously. Each GP individual's fitness is computed using model-based
batch reinforcement learning (RL), which first trains a model using available
system samples and subsequently performs Monte Carlo rollouts to predict each
policy candidate's performance. We compare FGPRL to an extended version of a
related method called fuzzy particle swarm reinforcement learning (FPSRL),
which uses swarm intelligence to tune the fuzzy policy parameters. Experiments
using an industrial benchmark show that FGPRL is able to autonomously learn
interpretable fuzzy policies with high control performance.Comment: Accepted at Genetic and Evolutionary Computation Conference 2018
(GECCO '18
Room temperature ferromagnetic-like behavior in Mn-implanted and post-annealed InAs layers deposited by Molecular Beam Epitaxy
We report on the magnetic and structural properties of Ar and Mn implanted
InAs epitaxial films grown on GaAs (100) by Molecular Beam Epitaxy (MBE) and
the effect of Rapid Thermal Annealing (RTA) for 30 seconds at 750C. Channeling
Particle Induced X- ray Emission (PIXE) experiments reveal that after Mn
implantation almost all Mn atoms are subsbtitutional in the In-site of the InAs
lattice, like in a diluted magnetic semiconductor (DMS). All of these samples
show diamagnetic behavior. But, after RTA treatment the Mn-InAs films exhibit
room-temperature magnetism. According to PIXE measurements the Mn atoms are no
longer substitutional. When the same set of experiments were performed with As
as implantation ion all of the layers present diamagnetism without exception.
This indicates that the appearance of room-temperature ferromagnetic-like
behavior in the Mn-InAs-RTA layer is not related to lattice disorder produce
during implantation, but to a Mn reaction produced after a short thermal
treatment. X-ray diffraction patterns (XRD) and Rutherford Back Scattering
(RBS) measurements evidence the segregation of an oxygen deficient-MnO2 phase
(nominally MnO1.94) in the Mn-InAs-RTA epitaxial layers which might be on the
origin of room temperature ferromagnetic-like response observed.Comment: 16 pages, 5 figures. Acepted in J. Appl. Phy
A GAIN in understanding autoproteolytic G protein‐coupled receptors and polycystic kidney disease proteins
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102153/1/embj201251.pd
Chemical History with a Nuclear Microprobe
A nuclear microprobe cannot give direct information on the chemical state of an element, but the spatial distribution of elements in a specimen is often determined by the chemical history of the sample. Fuel cells and minerals are examples of complex systems whose elemental distributions are determined by past chemical history. The distribution of catalyst in used fuel cell electrodes provides direct information on the chemical stability of dispersed catalysts under operating conditions. We have used spatially resolved Rutherford backscattering to measure the migration of platinum and vanadium from intermetallic catalysts and to determine their suitability for use under the extreme operating conditions found in phosphoric acid fuel cells. Geologic materials are complex, heterogeneous samples with small mineral grains. The trace element distribution within the individual mineral grains and between different mineral phases is sensitive to the details of the mineral formation and history. The spatial resolution and sub-100-ppm sensitivity available with a nuclear microprobe open up several new classes of experiments to the geochemist. Geochemistry and electrochemistry are two areas proving particularly fruitful for application of the nuclear microprobe
Influence of Radiation on the Properties and the Stability of Hybrid Perovskites
Organic inorganic perovskites are well suited for optoelectronic applications. In particular, perovskite single and perovskite tandem solar cells with silicon are close to their market entry. Despite their swift rise in efficiency to more than 21 , solar cell lifetimes are way below the needed 25 years. In fact, comparison of the time when the device performance has degraded to 80 of its initial value T80 lifetime of numerous solar cells throughout literature reveals a strongly reduced stability under illumination. The various detrimental effects are discussed. Most notably, moisture and heat related degradation can be mitigated easily by now. Recently however, several photo induced degradation mechanisms have been observed. Under illumination alloyed perovskites tend to phase segregate, while further, oxygen catalyzes deprotonation of the organic cations. Additionally, during illumination photo generated charge can be trapped in the N H antibonding orbitals causing the dissociation of the organic cation. On the other hand, organic inorganic perovskites exhibit a high radiation hardness that is superior to crystalline silicon. This progress report thoroughly reviews proposed degradation mechanisms reported in literature and discusses the microscopic mechanisms and their implications for solar cell
Exchange of substrate and inhibitor specificities between adenylyl and guanylyl cyclases
The active sites of guanylyl and adenylyl cyclases are closely related. The crystal structure of adenylyl cyclase and modeling studies suggest that specificity for ATP or GTP is dictated in part by a few amino acid residues, invariant in each family, that interact with the purine ring of the substrate. By exchanging these residues between guanylyl cyclase and adenylyl cyclase, we can completely change the nucleotide specificity of guanylyl cyclase and convert adenylyl cyclase into a nonselective purine nucleotide cyclase. The activities of these mutant enzymes remain fully responsive to their respective stimulators, sodium nitroprusside and G(s)α. The specificity of nucleotide inhibitors of guanylyl and adenylyl cyclases that do not act competitively with respect to substrate are similarly altered, indicative of their action at the active sites of these enzymes
Structural and dynamic changes in P-Rex1 upon activation by PIP3 and inhibition by IP4
PIP3-dependent Rac exchanger 1 (P-Rex1) is abundantly expressed in neutrophils and plays central roles in chemotaxis and cancer metastasis by serving as a guanine-nucleotide exchange factor (GEF) for Rac. The enzyme is synergistically activated by PIP3 and heterotrimeric Gβγ subunits, but mechanistic details remain poorly understood. While investigating the regulation of P-Rex1 by PIP3, we discovered that Ins(1,3,4,5)P4 (IP4) inhibits P-Rex1 activity and induces large decreases in backbone dynamics in diverse regions of the protein. Cryo-electron microscopy analysis of the P-Rex1·IP4 complex revealed a conformation wherein the pleckstrin homology (PH) domain occludes the active site of the Dbl homology (DH) domain. This configuration is stabilized by interactions between the first DEP domain (DEP1) and the DH domain and between the PH domain and a 4-helix bundle (4HB) subdomain that extends from the C-terminal domain of P-Rex1. Disruption of the DH-DEP1 interface in a DH/PH-DEP1 fragment enhanced activity and led to a more extended conformation in solution, whereas mutations that constrain the occluded conformation led to decreased GEF activity. Variants of full-length P-Rex1 in which the DH-DEP1 and PH-4HB interfaces were disturbed exhibited enhanced activity during chemokine-induced cell migration, confirming that the observed structure represents the autoinhibited state in living cells. Interactions with PIP3-containing liposomes led to disruption of these interfaces and increased dynamics protein-wide. Our results further suggest that inositol phosphates such as IP4 help to inhibit basal P-Rex1 activity in neutrophils, similar to their inhibitory effects on phosphatidylinositol-3-kinase
Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.
Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p < 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization
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