BQ-NCO: Bisimulation Quotienting for Efficient Neural Combinatorial Optimization

Despite the success of neural-based combinatorial optimization methods for end-to-end heuristic learning, out-of-distribution generalization remains a challenge. In this paper, we present a novel formulation of Combinatorial Optimization Problems (COPs) as Markov Decision Processes (MDPs) that effectively leverages common symmetries of COPs to improve out-of-distribution robustness. Starting from a direct MDP formulation of a constructive method, we introduce a generic way to reduce the state space, based on Bisimulation Quotienting (BQ) in MDPs. Then, for COPs with a recursive nature, we specialize the bisimulation and show how the reduced state exploits the symmetries of these problems and facilitates MDP solving. Our approach is principled and we prove that an optimal policy for the proposed BQ-MDP actually solves the associated COPs. We illustrate our approach on five classical problems: the Euclidean and Asymmetric Traveling Salesman, Capacitated Vehicle Routing, Orienteering and Knapsack Problems. Furthermore, for each problem, we introduce a simple attention-based policy network for the BQ-MDPs, which we train by imitation of (near) optimal solutions of small instances from a single distribution. We obtain new state-of-the-art results for the five COPs on both synthetic and realistic benchmarks. Notably, in contrast to most existing neural approaches, our learned policies show excellent generalization performance to much larger instances than seen during training, without any additional search procedure

Strong electron-phonon coupling and enhanced phonon Gr\"uneisen parameters in valence-fluctuating metal EuPd2_2Si2_2

We study the valence crossover and strong electron-phonon coupling of EuPd$_2$Si$_2$ by polarization-resolved Raman spectroscopy. The fully-symmetric phonon mode shows strongly asymmetric lineshape at low temperature, indicating Fano-type interaction between this mode and a continuum of electron-hole excitations. Moreover, the frequency and linewidth of the phonon modes exhibit anomalies across the valence-crossover temperature, suggesting the coupling between valence fluctuations and lattice vibration. In particular, two phonon modes show significantly enhanced Gr\"uneisen parameter, suggesting proximity to a critical elasticity regime. The relative contribution of the structural change and valence change to the phonon anomalies is evaluated by density functional theory calculations

The adrenal capsule is a signaling center controlling cell renewal and zonation through <i>Rspo3</i>

Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life

Heterogeneous photocatalytic recycling of FeX2/FeX3 for efficient halogenation of C−H bonds using NaX

Environmental-friendly halogenation of C−H bonds using abundant, non-toxic halogen salts is in high demand in various chemical industries, yet the efficiency and selectivity of laboratory available protocols are far behind the conventional photolytic halogenation process which uses hazardous halogen sources. Here we report an FeX2 (X=Br, Cl) coupled semiconductor system for efficient, selective, and continuous photocatalytic halogenation using NaX as halogen source under mild conditions. Herein, FeX2 catalyzes the reduction of molecular oxygen and the consumption of generated oxygen radicals, thus boosting the generation of halogen radicals and elemental halogen for direct halogenation and indirect halogenation via the formation of FeX3. Recycling of FeX2 and FeX3 during the photocatalytic process enables the halogenation of a wide range of hydrocarbons in a continuous flow, rendering it a promising method for applications

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Extended Glasgow Outcome Scale to Evaluate the Functional Impairment of Patients With Subcortical Band Heterotopia: A Multicentric Cross-sectional Study

Background: Subcortical band heterotopia (SBH) is a rare malformation of the cortical development characterized by a heterotopic band of gray matter between cortex and ventricles. The clinical presentation typically includes intellectual disability and epilepsy. Purpose: To evaluate if the Extended Glasgow Outcome Scale-pediatric version (EGOS-ped) is a feasible tool for evaluating the functional disability of patients with (SBH). Method: Cross-sectional multicenter study of a cohort of 49 patients with SBH (female n = 30, 61%), recruited from 23 Italian centers. Results: Thirty-nine of 49 (80%) cases showed high functional disability at EGOS-ped assessment. In the poor result subgroup (EGOS-ped &gt;3) motor deficit, language impairment, and lower intelligence quotient were more frequent (P &lt; 0.001, P = 0.02, and P = 0.01, respectively); the age at epilepsy onset was remarkably lower (P &lt; 0.001); and the prevalence of epileptic encephalopathy (West syndrome or Lennox-Gastaut-like encephalopathy) was higher (P = 0.04). The thickness and the extension of the heterotopic band were associated with EGOS-ped score (P &lt; 0.01 and P = 0.02). Pachygyria was found exclusively among patients with poor outcome (P &lt; 0.01). Conclusions: The EGOS-ped proved to be a reliable tool for stratifying the functional disability of patients with SBH. According to this score, patients could be dichotomized: group 1 (80%) is characterized by a poor overall functionality with early epilepsy onset, thick heterotopic band, and pachygyria, whereas group 2 (20%) is characterized by a good overall functionality with later epilepsy onset and thinner heterotopic band

High-resolution record reveals climate-driven environmental and sedimentary changes in an active rift

Young rifts are shaped by combined tectonic and surface processes and climate, yet few records exist to evaluate the interplay of these processes over an extended period of early rift-basin development. Here, we present the longest and highest resolution record of sediment flux and paleoenvironmental changes when a young rift connects to the global oceans. New results from International Ocean Discovery Program (IODP) Expedition 381 in the Corinth Rift show 10s–100s of kyr cyclic variations in basin paleoenvironment as eustatic sea level fluctuated with respect to sills bounding this semi-isolated basin, and reveal substantial corresponding changes in the volume and character of sediment delivered into the rift. During interglacials, when the basin was marine, sedimentation rates were lower (excepting the Holocene), and bioturbation and organic carbon concentration higher. During glacials, the basin was isolated from the ocean, and sedimentation rates were higher (~2–7 times those in interglacials). We infer that reduced vegetation cover during glacials drove higher sediment flux from the rift flanks. These orbital-timescale changes in rate and type of basin infill will likely influence early rift sedimentary and faulting processes, potentially including syn-rift stratigraphy, sediment burial rates, and organic carbon flux and preservation on deep continental margins worldwide

High-resolution record revealsclimate-driven environmental andsedimentary changes in an active rift

Young rifts are shaped by combined tectonic and surface processes and climate, yet few records exist to evaluate the interplay of these processes over an extended period of early rift-basin development. Here, we present the longest and highest resolution record of sediment flux and paleoenvironmental changes when a young rift connects to the global oceans. New results from International Ocean Discovery Program (IODP) Expedition 381 in the Corinth Rift show 10s–100s of kyr cyclic variations in basin paleoenvironment as eustatic sea level fluctuated with respect to sills bounding this semi-isolated basin, and reveal substantial corresponding changes in the volume and character of sediment delivered into the rift. During interglacials, when the basin was marine, sedimentation rates were lower (excepting the Holocene), and bioturbation and organic carbon concentration higher. During glacials, the basin was isolated from the ocean, and sedimentation rates were higher (~2–7 times those in interglacials). We infer that reduced vegetation cover during glacials drove higher sediment flux from the rift flanks. These orbital-timescale changes in rate and type of basin infill will likely influence early rift sedimentary and faulting processes, potentially including syn-rift stratigraphy, sediment burial rates, and organic carbon flux and preservation on deep continental margins worldwide.publishedVersio

Expedition 381 Summary

The primary objective of International Ocean Discovery Program Expedition 381 was to retrieve a record of early continental rifting and basin evolution from the Corinth rift, central Greece. Continental rifting is fundamental for the formation of ocean basins, and active rift zones are dynamic regions of high geohazard potential. However, the detailed spatial and temporal evolution of a complete rift system needed to understand rift development from the fault to plate scale is poorly resolved. In the active Corinth rift, deformation rates are high, the recent synrift succession is preserved and complete offshore, and earlier rift phases are preserved onshore. Additionally, a dense seismic database provides high-resolution imaging of the fault network and seismic stratigraphy around the basin. As the basin has subsided, its depositional environment has been affected by fluctuating global sea level and its absolute position relative to sea level, and the basin sediments record this changing environment through time. In Corinth, we can therefore achieve an unprecedented precision of timing and spatial complexity of rift-fault system development, rift-controlled drainage system evolution, and basin fill in the first few million years of rift history. The following are the expedition themes: High-resolution fault slip and rift evolution history, Surface processes in active rifts, High-resolution late Quaternary Eastern Mediterranean paleoclimate and paleoenvironment of a developing rift basin, and Geohazard assessment in an active rift. These objectives were and will be accomplished as a result of successful drilling, coring, and logging at three sites in the Gulf of Corinth, which collectively yielded 1645 m of recovered core over a 1905 m cored interval. Together, these cores provide (1) a long rift history (Sites M0078 and M0080), (2) a high-resolution record of the most recent phase of rifting (Site M0079), and (3) the spatial variation of rift evolution (comparison of sites in the central and eastern rift). The sediments contain a rich and complex record of changing sedimentation, sediment and pore water geochemistry, and environmental conditions from micropaleontological assemblages. The preliminary chronology developed by shipboard analyses will be refined and improved during postexpedition research, providing a high-resolution chronostratigraphy down to the orbital timescale for a range of tectonic, sedimentological, and paleoenvironmental studies. This chronology will provide absolute timing of key rift events, rates of fault movement, rift extension and subsidence, and the spatial variations of these parameters. The core data will also allow us to investigate the relative roles of and feedbacks between tectonics, climate, and eustasy in sediment flux, basin evolution, and basin environment. Finally, the Corinth rift boreholes will provide the first long Quaternary record of Mediterranean-type climate in the region. The potential range of scientific applications for this unique data set is very large, encompassing tectonics, sedimentary processes, paleoenvironment, paleoclimate, paleoecology, geochemistry, and geohazards