454 research outputs found
A Neural Networks Committee for the Contextual Bandit Problem
This paper presents a new contextual bandit algorithm, NeuralBandit, which
does not need hypothesis on stationarity of contexts and rewards. Several
neural networks are trained to modelize the value of rewards knowing the
context. Two variants, based on multi-experts approach, are proposed to choose
online the parameters of multi-layer perceptrons. The proposed algorithms are
successfully tested on a large dataset with and without stationarity of
rewards.Comment: 21st International Conference on Neural Information Processin
Interaction of Cisplatin with a CCHC Zinc Finger Motif
The interaction between cisplatin and an 18-residue CCHC zinc finger motif derived from a retroviral nucleocapsid protein
(PyrZf18) has been studied using UV–visible, CD and 1H NMR spectroscopies and ESI-MS spectrometry.
Cisplatin irreversibly blocks the cysteine zinc binding groups in the free peptide and is able to slowly eject zinc from the
zinc–peptide complex. The observed end product of the reaction with cisplatin is a complex in which only one ammonia
molecule is coordinated to platinum. After an initial binding with two cysteine residues and the formation of the (PyrZf18)–
platinum–(NH3)2 complex, a release of one ammonia molecule occurs because of trans-labilization, and the third cysteine is
coordinated, leading to a mixture of isomers and/or conformers of the (PyrZf18)–platinum–NH3 complex. The results are discussed
with respect to the potential antiretroviral activity of platinum(II) compounds and to the possible interaction of cisplatin
with the cellular nucleic acid binding proteins
Shear induced grain boundary motion for lamellar phases in the weakly nonlinear regime
We study the effect of an externally imposed oscillatory shear on the motion
of a grain boundary that separates differently oriented domains of the lamellar
phase of a diblock copolymer. A direct numerical solution of the
Swift-Hohenberg equation in shear flow is used for the case of a
transverse/parallel grain boundary in the limits of weak nonlinearity and low
shear frequency. We focus on the region of parameters in which both transverse
and parallel lamellae are linearly stable. Shearing leads to excess free energy
in the transverse region relative to the parallel region, which is in turn
dissipated by net motion of the boundary toward the transverse region. The
observed boundary motion is a combination of rigid advection by the flow and
order parameter diffusion. The latter includes break up and reconnection of
lamellae, as well as a weak Eckhaus instability in the boundary region for
sufficiently large strain amplitude that leads to slow wavenumber readjustment.
The net average velocity is seen to increase with frequency and strain
amplitude, and can be obtained by a multiple scale expansion of the governing
equations
A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism
The different steps of the human Top1 (topoisomerase I) catalytic cycle have been analysed in the presence of a
pentacyclic-diquinoid synthetic compound. The experiments indicate that it efficiently inhibits the cleavage step of
the enzyme reaction, fitting well into the catalytic site. Surprisingly the compound, when incubated with the binary
topoisomerase–DNA cleaved complex, helps the enzyme to remove itself from the cleaved DNA and close the DNA gap,
increasing the religation rate. The compound also induces the religation of the stalled enzyme–CPT (camptothecin)–
DNA ternary complex. Analysis of the molecule docked over the binary complex, together with its chemical properties,
suggests that the religation enhancement is due to the presence on the compound of two oxygen atoms that act as
hydrogen acceptors. This property facilitates the deprotonation of the 5 DNA end, suggesting that this is the limiting
step in the topoisomerase religation mechanism
Grain boundary motion in layered phases
We study the motion of a grain boundary that separates two sets of mutually
perpendicular rolls in Rayleigh-B\'enard convection above onset. The problem is
treated either analytically from the corresponding amplitude equations, or
numerically by solving the Swift-Hohenberg equation. We find that if the rolls
are curved by a slow transversal modulation, a net translation of the boundary
follows. We show analytically that although this motion is a nonlinear effect,
it occurs in a time scale much shorter than that of the linear relaxation of
the curved rolls. The total distance traveled by the boundary scales as
, where is the reduced Rayleigh number. We obtain
analytical expressions for the relaxation rate of the modulation and for the
time dependent traveling velocity of the boundary, and especially their
dependence on wavenumber. The results agree well with direct numerical
solutions of the Swift-Hohenberg equation. We finally discuss the implications
of our results on the coarsening rate of an ensemble of differently oriented
domains in which grain boundary motion through curved rolls is the dominant
coarsening mechanism.Comment: 16 pages, 5 figure
Legionella detection in water networks as per iso 11731:2017: Can different filter pore sizes and direct placement on culture media influence laboratory results?
Determination of Legionella concentrations in water networks is useful for predicting legionellosis risks. The standard culture technique using concentration with membranes filters is the most commonly used method for environmental surveillance of Legionella. The aim of this study was to verify whether filtration with different filter pore sizes (0.2 and 0.45 \ub5m) according to (ISO) 11731:2017, followed by directly placing them on culture media, can influence Legionella detection. Three laboratories participated in an experimental study that tested a known suspension of Legionella pneumophila (Lpn) serogroup 1 (ATCC 33152) (approximate final cell density of 15 CFU/mL). E. coli (ATCC 11775) and Pseudomonas aeruginosa (ATCC 25668) were included as control tests. The average (95% CI) percentage of recovery of Lpn was 65% using 0.45-\ub5m filters and 15% using 0.2-\ub5m filters (p < 0.0001). For control tests, the average (95% CI) percentage of recovery was higher with 0.45 vs. 0.2 \ub5m filters: 97% vs. 64% for Escherichia coli (p < 0.00001) and 105% vs. 97% (p = 0.0244) for P. aeruginosa. Our results showed that the 0.45-\ub5m filters provided the greatest detection of Legionella. Because the current national guidelines leave the choice of membrane porosity to the operator, experimental studies are important for directing operators towards a conscious choice to standardize Legionella environmental surveillance methods
Physicochemical properties of mixed micellar aggregates containing CCK peptides and Gd complexes designed as tumor specific contrast agents in MRI
New amphiphilic molecules containing a bioactive peptide or a claw moiety have been prepared
in order to obtain mixed micelles as target-specific contrast agents in magnetic resonance imaging. The
first molecule, C18H37CONH(AdOO)2-G-CCK8 (C18CCK8), contains a C18 hydrophobic moiety bound to
the C-terminal cholecystokinin octapeptide amide (CCK 26-33 or CCK8). The second amphiphilic
compound, C18H37CONHLys(DTPAGlu)CONH2 (C18DTPAGlu) or its gadolinium complex, (C18DTPAGlu-
(Gd)), contains the same C18 hydrophobic moiety bound, through a lysine residue, to the DTPAGlu chelating
agent. The mixed aggregates as well as the pure C18DTPAGlu aggregate, in the presence and absence
of Gd, have been fully characterized by surface tension measurements, FT-PGSE-NMR, fluorescence
quenching, and small-angle neutron scattering measurements. The structural characterization of the mixed
aggregates C18DTPAGlu(Gd)-C18CCK8 indicates a spherical arrangement of the micelles with an external
shell of 21 Å and an inner core of 20 Å. Both the DTPAGlu(Gd) complexes and the CCK8 peptides
point toward the external surface. The measured values for relaxivity in saline medium at 20 MHz proton
Larmor frequency and 25 °C are 18.7 mM-1 s-1. These values show a large enhancement in comparison
with the isolated DTPAGlu(Gd) complex
Metal(loid)s role in the pathogenesis of amyotrophic lateral sclerosis: Environmental, epidemiological, and genetic data
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance. In the remaining sporadic cases, a multifactorial origin is supposed in which several predisposing genes interact with environmental factors. The etiological role of environmental factors, such as pesticides, exposure to electromagnetic fields, and metals has been frequently investigated, with controversial findings. Studies in the past two decades have highlighted possible roles of metals, and ionic homeostasis dysregulation has been proposed as the main trigger to motor-neuron degeneration. This study aims at evaluating the possible role of environmental factors in etiopathogenesis of ALS, with a particular attention on metal contamination, focusing on the industrial Briga area in the province of Novara (Piedmont region, North Italy), characterized by: i) a higher incidence of sporadic ALS (sALS) in comparison with the entire province, and ii) the reported environmental pollution. Environmental data from surface, ground and discharge waters, and from soils were collected and specifically analyzed for metal content. Considering the significance of genetic mechanisms in ALS, a characterization for the main ALS genes has been performed to evaluate the genetic contribution for the sALS patients living in the area of study. The main findings of this study are the demonstration that in the Briga area the most common metal contaminants are Cu, Zn, Cr, Ni (widely used in tip-plating processes), that are above law limits in surface waters, discharge waters, and soil. In addition, other metals and metalloids, such as Cd, Pb, Mn, and As show a severe contamination in the same area. Results of genetic analyses show that sALS patients in the Briga area do not carry recurrent mutations or an excess of mutations in the four main ALS causative genes (SOD1, TARDBP, FUS, C9ORF72) and for ATXN2 CAG repeat locus. This study supports the hypothesis that the higher incidence of sALS in Briga area may be related to environmental metal(loid)s contamination, along with other environmental factors. Further studies, implementing analysis of genetic polymorphisms, as well as investigation with long term follow-up, may yield to key aspects into the etiology of ALS. The interplay between different approaches (environmental, chemical, epidemiological, genetic) of our work provides new insights and methodology to the comprehension of the disease etiology
Short-term treatment with atorvastatin reduces platelet CD40 ligand and thrombin generation in hypercholesterolemic patients
Background - Soluble CD40L (sCD40L), a substance that maximally reflects in vivo platelet activation, is increased in patients with hypercholesterolemia. We investigated the relation between sCD40L and platelet CD4OL in hypercholesterolemic patients before and after a short-term treatment with atorvastatin. Methods and Results - Collagen-induced platelet CD40L and plasma levels of sCD40L and prothrombin fragment F1+2, a marker of thrombin generation, were investigated in 30 hypercholesterolemic patients and 20 healthy subjects. Hypercholesterolemic patients were then randomized to either diet ( n = 15; group A) or atorvastatin 10 mg/d ( group B); the aforementioned variables were measured at baseline and after 3 days of treatment. Compared with referents, hypercholesterolemic patients showed higher values of platelet CD40L ( P < 0.005), sCD40L ( P < 0.005), and F1 + 2 ( P < 0.003). Platelet CD40L was significantly correlated with sCD40L ( P < 0.001), and the latter was significantly correlated with F1 + 2 ( P < 0.001). The intervention trial showed no changes in group A but a significant decrease in platelet CD40L ( P < 0.01), sCD40L ( P < 0.002), and F1 + 2 ( P < 0.03) in group B. In vitro studies demonstrated that cholesterol enhanced platelet CD40L and CD40L-mediated clotting activation by human monocytes; also, atorvastatin dose-dependently inhibited platelet CD40L expression and clotting activation by CD40L-stimulated monocytes. Conclusions - This study shows that, in hypercholesterolemia, platelet overexpression of CD40L may account for enhanced plasma levels of sCD40L and F1 + 2. Atorvastatin exerts a direct antithrombotic effect via inhibition of platelet CD40L and CD40L-mediated thrombin generation, independently of its cholesterol-lowering effect
A Policy Gradient Algorithm for Learning to Learn in Multiagent Reinforcement Learning
A fundamental challenge in multiagent reinforcement learning is to learn
beneficial behaviors in a shared environment with other simultaneously learning
agents. In particular, each agent perceives the environment as effectively
non-stationary due to the changing policies of other agents. Moreover, each
agent is itself constantly learning, leading to natural non-stationarity in the
distribution of experiences encountered. In this paper, we propose a novel
meta-multiagent policy gradient theorem that directly accounts for the
non-stationary policy dynamics inherent to multiagent learning settings. This
is achieved by modeling our gradient updates to consider both an agent's own
non-stationary policy dynamics and the non-stationary policy dynamics of other
agents in the environment. We show that our theoretically grounded approach
provides a general solution to the multiagent learning problem, which
inherently comprises all key aspects of previous state of the art approaches on
this topic. We test our method on a diverse suite of multiagent benchmarks and
demonstrate a more efficient ability to adapt to new agents as they learn than
baseline methods across the full spectrum of mixed incentive, competitive, and
cooperative domains.Comment: Accepted to ICML 2021. Code at https://github.com/dkkim93/meta-mapg
and Videos at https://sites.google.com/view/meta-mapg/hom
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