On the derivation of Fourier's law in stochastic energy exchange systems

We present a detailed derivation of Fourier's law in a class of stochastic energy exchange systems that naturally characterize two-dimensional mechanical systems of locally confined particles in interaction. The stochastic systems consist of an array of energy variables which can be partially exchanged among nearest neighbours at variable rates. We provide two independent derivations of the thermal conductivity and prove this quantity is identical to the frequency of energy exchanges. The first derivation relies on the diffusion of the Helfand moment, which is determined solely by static averages. The second approach relies on a gradient expansion of the probability measure around a non-equilibrium stationary state. The linear part of the heat current is determined by local thermal equilibrium distributions which solve a Boltzmann-like equation. A numerical scheme is presented with computations of the conductivity along our two methods. The results are in excellent agreement with our theory.Comment: 19 pages, 5 figures, to appear in Journal of Statistical Mechanics (JSTAT

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer

Endometrial cancer; Gynecologic cancer; ImmunotherapyCàncer d'endometri; Càncer ginecològic; ImmunoteràpiaCáncer de endometrio; Cáncer ginecológico; InmunoterapiaWhat is this summary about? Dostarlimab, also known by the brand name JEMPERLI, is a medicine that can be used to treat certain types of endometrial cancer. GARNET is an ongoing phase 1 clinical study that is testing the safety and side effects of dostarlimab and the best way to administer it to patients. The results presented in this summary are from a time point in the middle of the study. What were the results? The results from the GARNET study published in 2022 showed how well dostarlimab worked for people participating in the study. Dostarlimab was found to reduce the size of tumors in patients with certain types of endometrial cancer. The patients treated with dostarlimab had side effects that could be managed and few severe side effects. What do the results mean? The results of the GARNET study led to dostarlimab being approved to treat patients with certain types of endometrial cancer. For patients with advanced-stage endometrial cancer, or endometrial cancer that has come back after chemotherapy (recurrent), there are few treatment options. The results suggest that dostarlimab may provide long-term benefits for these patients.This study (NCT02715284) was funded by GSK. Trademarks are owned by or licensed to the GSK group of companies. Full author disclosure information can be found in the original article

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET—a phase I, single-arm study

Immunotherapy; Programmed cell death 1 receptorImmunoteràpia; Receptor de mort cel·lular programada 1Inmunoterapia; Receptor de muerte celular programada 1Background Dostarlimab is a humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. We report interim data from patients with endometrial cancer (EC) participating in a phase I trial of single-agent dostarlimab. Methods GARNET, an ongoing, single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumors, is being undertaken at 123 sites. Two cohorts of patients with EC were recruited: those with dMMR/MSI-H disease (cohort A1) and those with proficient/stable (MMRp/MSS) disease (cohort A2). Patients received dostarlimab 500 mg every 3 weeks for 4 cycles, then dostarlimab 1000 mg every 6 weeks until disease progression. The primary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST V.1.1, as assessed by blinded independent central review. Results Screening began on April 10, 2017, and 129 and 161 patients with advanced EC were enrolled in cohorts A1 and A2, respectively. The median follow-up duration was 16.3 months (IQR 9.5–22.1) for cohort A1 and 11.5 months (IQR 11.0–25.1) for cohort A2. In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses. In cohort A2, ORR was 14.1% (95% CI 9.1% to 20.6%) with three complete responses and 19 partial responses. Median DOR was not reached in either cohort. In the combined cohorts, the majority of treatment-related adverse events (TRAEs) were grade 1–2 (75.5%), most commonly fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%). Grade≥3 TRAEs occurred in 16.6% of patients, and 5.5% discontinued dostarlimab because of TRAEs. No deaths were attributable to dostarlimab. Conclusion Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile

Stubborn Predictions in Primary Visual Cortex

Perceivers can use past experiences to make sense of ambiguous sensory signals. However, this may be inappropriate when the world changes and past experiences no longer predict what the future holds. Optimal learning models propose that observers decide whether to stick with or update their predictions by tracking the uncertainty or "precision" of their expectations. However, contrasting theories of prediction have argued that we are prone to misestimate uncertainty-leading to stubborn predictions that are difficult to dislodge. To compare these possibilities, we had participants learn novel perceptual predictions before using fMRI to record visual brain activity when predictive contingencies were disrupted-meaning that previously "expected" events become objectively improbable. Multivariate pattern analyses revealed that expected events continued to be decoded with greater fidelity from primary visual cortex, despite marked changes in the statistical structure of the environment, which rendered these expectations no longer valid. These results suggest that our perceptual systems do indeed form stubborn predictions even from short periods of learning-and more generally suggest that top-down expectations have the potential to help or hinder perceptual inference in bounded minds like ours

The Transit Light Curve Project. XII. Six Transits of the Exoplanet XO-2b

We present photometry of six transits of the exoplanet XO-2b. By combining the light-curve analysis with theoretical isochrones to determine the stellar properties, we find the planetary radius to be 0.996 +0.031/-0.018 rjup and the planetary mass to be 0.565 +/- 0.054 mjup. These results are consistent with those reported previously, and are also consistent with theoretical models for gas giant planets. The mid-transit times are accurate to within 1 min and are consistent with a constant period. However, the period we derive differs by 2.5 sigma from the previously published period. More data are needed to tell whether the period is actually variable (as it would be in the presence of an additional body) or if the timing errors have been underestimated.Comment: Accepted for publication in AJ. 20 pages, 3 tables, 4 figure

Kinetic model of DNA replication in eukaryotic organisms

We formulate a kinetic model of DNA replication that quantitatively describes recent results on DNA replication in the in vitro system of Xenopus laevis prior to the mid-blastula transition. The model describes well a large amount of different data within a simple theoretical framework. This allows one, for the first time, to determine the parameters governing the DNA replication program in a eukaryote on a genome-wide basis. In particular, we have determined the frequency of origin activation in time and space during the cell cycle. Although we focus on a specific stage of development, this model can easily be adapted to describe replication in many other organisms, including budding yeast.Comment: 10 pages, 6 figures: see also cond-mat/0306546 & physics/030615

A Conceptual Design of Spatio‐Temporal Agent‐ Based Model for Volcanic Evacuation

The understanding of evacuation processes is important for improving the effectiveness of evacuation plans in the event of volcanic disasters. In terms of social processes, the enactment of evacuations in volcanic crises depends on the variability of individual/household responses. This variability of population response is related to the uncertainty and unpredictability of the hazard characteristics of volcanoes—specifically, the exact moment at which the eruption occurs (temporal), the magnitude of the eruption and which locations are impacted (spatial). In order to provide enhanced evacuation planning, it is important to recognise the potential problems that emerge during evacuation processes due to such variability. Evacuation simulations are one approach to understanding these processes. However, experimenting with volcanic evacuations in the real world is risky and challenging, and so an agent‐based model is proposed to simulate volcanic evacuation. This paper highlights the literature gap for this topic and provides the conceptual design for a simulation using an agent‐based model. As an implementation, an initial evacuation model is presented for Mount Merapi in Indonesia, together with potential applications of the model for supporting volcanic evacuation management, discussion of the initial outcomes and suggestions for future work

Long-Term Profile Variability in Active Galactic Nuclei with Double-Peaked Balmer Emission Lines

An increasing number of Active Galactic Nuclei (AGNs) exhibit broad, double-peaked Balmer emission lines,which represent some of the best evidence for the existence of relatively large-scale accretion disks in AGNs. A set of 20 double-peaked emitters have been monitored for nearly a decade in order to observe long-term variations in the profiles of the double-peaked Balmer lines. Variations generally occur on timescales of years, and are attributed to physical changes in the accretion disk. Here we characterize the variability of a subset of seven double-peaked emitters in a model independent way. We find that variability is caused primarily by the presence of one or more discrete "lumps" of excess emission; over a timescale of a year (and sometimes less) these lumps change in amplitude and shape, but the projected velocity of these lumps changes over much longer timescales (several years). We also find that all of the objects exhibit red peaks that are stronger than the blue peak at some epochs and/or blueshifts in the overall profile, contrary to the expectations for a simple, circular accretion disk model, thus emphasizing the need for asymmetries in the accretion disk. Comparisons with two simple models, an elliptical accretion disk and a circular disk with a spiral arm, are unable to reproduce all aspects of the observed variability, although both account for some of the observed behaviors. Three of the seven objects have robust estimates of the black hole masses. For these objects the observed variability timescale is consistent with the expected precession timescale for a spiral arm, but incompatible with that of an elliptical accretion disk. We suggest that with the simple modification of allowing the spiral arm to be fragmented, many of the observed variability patterns could be reproduced.Comment: 74 pages, 4 tables, 35 figure

HST/ACS Photometry of Old Stars in NGC 1569: The Star Formation History of a Nearby Starburst

(abridged) We used HST/ACS to obtain deep V- and I-band images of NGC 1569, one of the closest and strongest starburst galaxies in the Universe. These data allowed us to study the underlying old stellar population, aimed at understanding NGC 1569's evolution over a full Hubble time. We focus on the less-crowded outer region of the galaxy, for which the color-magnitude diagram (CMD) shows predominantly a red giant branch (RGB) that reaches down to the red clump/horizontal branch feature (RC/HB). A simple stellar population analysis gives clear evidence for a more complicated star formation history (SFH) in the outer region. We derive the full SFH using a newly developed code, SFHMATRIX, which fits the CMD Hess diagram by solving a non-negative least squares problem. Our analysis shows that the relative brightnesses of the RGB tip and RC/HB, along with the curvature and color of the RGB, provide enough information to ameliorate the age-metallicity-extinction degeneracy. The distance/reddening combination that best fits the data is E(B-V) = 0.58 +/- 0.03 and D = 3.06 +/- 0.18 Mpc. Star formation began ~ 13 Gyr ago, and this accounts for the majority of the mass in the outer region. However, the initial burst was followed by a relatively low, but constant, rate of star formation until ~ 0.5-0.7 Gyr ago when there may have been a short, low intensity burst of star formation.Comment: 50 pages, including 17 figures. Accepted for publication in A

Three-dimensional magnetohydrodynamic simulations of the evolution of magnetic fields in Fanaroff-Riley class II radio sources

Radio observations of Fanaroff-Riley class II sources often show correlations between the synchrotron emission and the linear-polarimetric distributions. Magnetic position vectors seem to align with the projected emission of both the radio jets and the sources' edges. Using statistics we study such relation as well as its unknown time evolution via synthetic polarisation maps of model FR II sources formed in 3D-MHD numerical simulations of bipolar, hypersonic and weakly magnetised jets. The magnetic field is initially random with a Kolmogorov power spectrum, everywhere. We investigate the structure and evolution of magnetic fields in the sources as a function of the power of jets and the observational viewing angle. Our synthetic polarisation maps agree with observations, showing B-field vectors which are predominantly aligned with the jet axis, and show that magnetic fields inside sources are shaped by the jets' backflow. Polarimetry is found to correlate with time, the viewing angle and the jet-to-ambient density contrast. The magnetic structure inside thin elongated sources is more uniform than inside more spherical ones. We see jets increase the magnetic energy in cocoons in proportion to the jet velocity and the cocoon width. Filaments in the synthetic emission maps suggest turbulence develops in evolved sources.Comment: Accepted for publication in the MNRAS. 21 pages, 11 figure