If you can't be with the one you love, love the one you're with: How individual habituation of agent interactions improves global utility

Simple distributed strategies that modify the behaviour of selfish individuals in a manner that enhances cooperation or global efficiency have proved difficult to identify. We consider a network of selfish agents who each optimise their individual utilities by coordinating (or anti-coordinating) with their neighbours, to maximise the pay-offs from randomly weighted pair-wise games. In general, agents will opt for the behaviour that is the best compromise (for them) of the many conflicting constraints created by their neighbours, but the attractors of the system as a whole will not maximise total utility. We then consider agents that act as 'creatures of habit' by increasing their preference to coordinate (anti-coordinate) with whichever neighbours they are coordinated (anti-coordinated) with at the present moment. These preferences change slowly while the system is repeatedly perturbed such that it settles to many different local attractors. We find that under these conditions, with each perturbation there is a progressively higher chance of the system settling to a configuration with high total utility. Eventually, only one attractor remains, and that attractor is very likely to maximise (or almost maximise) global utility. This counterintutitve result can be understood using theory from computational neuroscience; we show that this simple form of habituation is equivalent to Hebbian learning, and the improved optimisation of global utility that is observed results from wellknown generalisation capabilities of associative memory acting at the network scale. This causes the system of selfish agents, each acting individually but habitually, to collectively identify configurations that maximise total utility

Moving Mirrors and Thermodynamic Paradoxes

Quantum fields responding to "moving mirrors" have been predicted to give rise to thermodynamic paradoxes. I show that the assumption in such work that the mirror can be treated as an external field is invalid: the exotic energy-transfer effects necessary to the paradoxes are well below the scales at which the model is credible. For a first-quantized point-particle mirror, it appears that exotic energy-transfers are lost in the quantum uncertainty in the mirror's state. An accurate accounting of these energies will require a model which recognizes the mirror's finite reflectivity, and almost certainly a model which allows for the excitation of internal mirror modes, that is, a second-quantized model.Comment: 7 pages, Revtex with Latex2

`Operational' Energy Conditions

I show that a quantized Klein-Gordon field in Minkowski space obeys an `operational' weak energy condition: the energy of an isolated device constructed to measure or trap the energy in a region, plus the energy it measures or traps, cannot be negative. There are good reasons for thinking that similar results hold locally for linear quantum fields in curved space-times. A thought experiment to measure energy density is analyzed in some detail, and the operational positivity is clearly manifested. If operational energy conditions do hold for quantum fields, then the negative energy densities predicted by theory have a will-o'-the-wisp character: any local attempt to verify a total negative energy density will be self-defeating on account of quantum measurement difficulties. Similarly, attempts to drive exotic effects (wormholes, violations of the second law, etc.) by such densities may be defeated by quantum measurement problems. As an example, I show that certain attempts to violate the Cosmic Censorship principle by negative energy densities are defeated. These quantum measurement limitations are investigated in some detail, and are shown to indicate that space-time cannot be adequately modeled classically in negative energy density regimes.Comment: 18 pages, plain Tex, IOP macros. Expanded treatment of measurement problems for space-time, with implications for Cosmic Censorship as an example. Accepted by Classical and Quantum Gravit

In vivo E2F reporting reveals efficacious schedules of MEK1/2–CDK4/6 targeting and mTOR–s6 resistance mechanisms

Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein. These data were supported by phospho-S6 staining of melanoma biopsies from patients treated with CDK4/6i plus targeted inhibitors. Enhanced phospho-S6 in resistant tumors provided a therapeutic window for the mTORC1/2 inhibitor AZD2014. Mechanistically, upregulation or mutation of NRAS was associated with resistance in in vivo models and patient samples, respectively, and mutant NRAS was sufficient to enhance resistance. This study utilizes an in vivo reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance. SIGnIFICAnCE: Mutant BRAF and NRAS melanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling. This resistance mechanism provides the preclinical basis to utilize mTORC1/2 inhibitors to improve MEKi plus CDK4/6i drug regimens

Identification of single-site gold catalysis in acetylene hydrochlorination

There remains considerable debate over the active form of gold under operating conditions of a recently validated gold catalyst for acetylene hydrochlorination. We have performed an in situ x-ray absorption fine structure study of gold/carbon (Au/C) catalysts under acetylene hydrochlorination reaction conditions and show that highly active catalysts comprise single-site cationic Au entities whose activity correlates with the ratio of Au(I):Au(III) present. We demonstrate that these Au/C catalysts are supported analogs of single-site homogeneous Au catalysts and propose a mechanism, supported by computational modeling, based on a redox couple of Au(I)-Au(III) species. View Full Tex

NRQCD Analysis of Bottomonium Production at the Tevatron

Recent data from the CDF collaboration on the production of spin-triplet bottomonium states at the Tevatron p \bar p collider are analyzed within the NRQCD factorization formalism. The color-singlet matrix elements are determined from electromagnetic decays and from potential models. The color-octet matrix elements are determined by fitting the CDF data on the cross sections for Upsilon(1S), Upsilon(2S), and Upsilon(3S) at large p_T and the fractions of Upsilon(1S) coming from chi_b(1P) and chi_b(2P). We use the resulting matrix elements to predict the cross sections at the Tevatron for the spin-singlet states eta_b(nS) and h_b(nP). We argue that eta_b(1S) should be observable in Run II through the decay eta_b -> J/psi + J/psi.Comment: 20 pages, 3 figure

WALLABY Early Science - I. The NGC 7162 Galaxy Group

We present Widefield ASKAP L-band Legacy All-sky Blind Survey (WALLABY) early science results from the Australian Square Kilometre Array Pathfinder (ASKAP) observations of the NGC 7162 galaxy group. We use archival HIPASS and Australia Telescope Compact Array (ATCA) observations of this group to validate the new ASKAP data and the data reduction pipeline ASKAPsoft. We detect six galaxies in the neutral hydrogen (HI) 21-cm line, expanding the NGC 7162 group membership from four to seven galaxies. Two of the new detections are also the first HI detections of the dwarf galaxies, AM 2159-434 and GALEXASC J220338.65-431128.7, for which we have measured velocities of $cz=2558$ and $cz=2727$ km s$^{-1}$, respectively. We confirm that there is extended HI emission around NGC 7162 possibly due to past interactions in the group as indicated by the $40^{\circ}$ offset between the kinematic and morphological major axes for NGC 7162A, and its HI richness. Taking advantage of the increased resolution (factor of $\sim1.5$) of the ASKAP data over archival ATCA observations, we fit a tilted ring model and use envelope tracing to determine the galaxies' rotation curves. Using these we estimate the dynamical masses and find, as expected, high dark matter fractions of $f_{\mathrm{DM}}\sim0.81-0.95$ for all group members. The ASKAP data are publicly available.Comment: 20 pages, 11 figures, accepted for publication in MNRA

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike

Chiral Extrapolation, Renormalization, and the Viability of the Quark Model

The relationship of the quark model to the known chiral properties of QCD is a longstanding problem in the interpretation of low energy QCD. In particular, how can the pion be viewed as both a collective Goldstone boson quasiparticle and as a valence quark antiquark bound state where universal hyperfine interactions govern spin splittings in the same way as in the heavy quark systems. We address this issue in a simplified model which; however, reproduces all features of QCD relevant to this problem. A comparison of the many-body solution to our model and the constituent quark model demonstrates that the quark model is sufficiently flexible to describe meson hyperfine splitting provided proper renormalization conditions and correct degrees of freedom are employed consistently.Comment: 6 pages, 2 eps figures, uses revtex. Version to appear in Phys. Rev. Let