An International Comparison of Equity in Accessibility to Jobs: London, São Paulo, and the Randstad

We analyze the impact of different accessibility measures on the interpretation of associated equity analysis using the Gini coefficient and the (pseudo) Palma ratio, and the impact of the method of assigning zonal accessibility on Gini estimation results using four different alternatives. Two types of potential accessibility measures (zonal and person-based) and two ratios of potential jobs to potential population (intra-modal and multi-modal) are estimated for car and transit in the Netherlands' Randstad region, Greater London, and São Paulo relying on network data, schedule-based data, and speed profiles. Gini results are heavily influenced by the accessibility indicator and the method of assignment. The Palma ratio is also influenced by the choice of accessibility indicator, with the person-based potential accessibility measure tending to show greater inequity

Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium

BACKGROUND: Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. METHODOLOGY/PRINCIPAL FINDINGS: Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. CONCLUSIONS: Protection via SLP is associated with transcriptional repression of inflammation/immunity, up-regulation of sarcomeric elements and natriuretic peptides, and modulation of cell stress, growth and development, while conventional protective molecules are unaltered

Normal and Reverse Faulting Driven by the Subduction Zone Earthquake Cycle in the Northern Chilean Forearc

Despite its location in a convergent tectonic setting, the Coastal Cordillera of northern Chile between 21°S and 25°S is dominated by structures demonstrating extension in the direction of plate convergence. In some locations, however, normal faults have been reactivated as reverse faults, complicating the interpretation of long-term strain. In order to place these new observations in a tectonic context, we model stress changes induced on these faults by the subduction earthquake cycle. Our simulations predict that interseismic locking on the plate boundary encourages normal slip on fore-arc faults, which may result from elastic rebound due to interplate earthquakes or from seismic or aseismic motion that takes place within the interseismic period. Conversely, stress generated by strong subduction zone earthquakes, such as the 1995 Mw = 8.1 Antofagasta event, provides a mechanism for the reverse reactivation we document here. Upper plate fault slip in response to the low-magnitude stress changes induced by the subduction earthquake cycle suggests that the absolute level of stress on these faults is very low. Furthermore, seismic hazard analysis for northern Chile requires consideration of not only the plate boundary earthquake cycle but also the cycle on fore-arc faults that may or may not coincide with the interplate pattern. Though the relationships between permanent strain and deformation calculated using elastic models remain unclear, the compatibility of modeled stress fields with the distribution of fore-arc faulting suggests that interseismic strain accumulation and coseismic deformation on the subduction megathrust both play significant roles in shaping structural behavior in the upper plate

Demonstration of quantum-enhanced rangefinding robust against classical jamming

In this paper we demonstrate operation of a quantum-enhanced lidar based on a continuously pumped photon pair source combined with simple detection in regimes with over 5 orders of magnitude separation between signal and background levels and target reflectivity down to -52 dB. We characterise the performance of our detector using a log-likelihood analysis framework, and crucially demonstrate the robustness of our system to fast and slow classical jamming, introducing a new protocol to implement dynamic background tracking to eliminate the impact of slow background changes whilst maintaining immunity to high frequency fluctuations. Finally, we extend this system to the regime of rangefinding in the presence of classical jamming to locate a target with an 11 cm spatial resolution limited only by the detector jitter. These results demonstrate the advantage of exploiting quantum correlations for lidar applications, providing a clear route to implementation of this system in real-world scenarios

Surface Cracks Record Long-Term Seismic Segmentation of the Andean Margin

Understanding the long-term patterns of great earthquake rupture along a subduction zone provides a framework for assessing modern seismic hazard. However, evidence that can be used to infer the size and location of past earthquakes is typically erased by erosion after a few thousand years. Meter-scale cracks that cut the surface of coastal areas in northern Chile and southern Peru preserve a record of earthquakes spanning several hundred thousand years owing to the hyperarid climate of the region. These cracks have been observed to form during and/or shortly after strong subduction earthquakes, are preserved for long time periods throughout the Atacama Desert, demonstrate evidence for multiple episodes of reactivation, and show changes in orientation over spatial scales similar to the size of earthquake segments. Our observations and models show that crack orientations are consistent with dynamic and static stress fields generated by recent earthquakes. While localized structural and topographic processes influence some cracks, the strong preferred orientation over large regions indicates that cracks are primarily formed by plate boundary–scale stresses, namely repeated earthquakes. We invert the crack-based strain data for slip along the well-known Iquique seismic gap segment of the margin and find consistency with gravity anomaly–based inferences of long-term earthquake slip patterns, as well as the magnitude and location of the November 2007 Tocopilla earthquake. We suggest that the meter-scale cracks can be used to map characteristic earthquake rupture segments that persist over many seismic cycles, which encourages future study of cracks and other small-scale structures to better constrain the persistence of asperities in other arid, tectonically active regions

Using Group Model Building to Understand Factors That Influence Childhood Obesity in an Urban Environment

Background: Despite increased attention, conventional views of obesity are based upon individual behaviors, and children and parents living with obesity are assumed to be the primary problem solvers. Instead of focusing exclusively on individual reduction behaviors for childhood obesity, greater focus should be placed on better understanding existing community systems and their effects on obesity. The Milwaukee Childhood Obesity Prevention Project is a community-based coalition established to develop policy and environmental change strategies to impact childhood obesity in Milwaukee, Wisconsin. The coalition conducted a Group Model Building exercise to better understand root causes of childhood obesity in its community. Methods: Group Model Building is a process by which a group systematically engages in model construction to better understand the systems that are in place. It helps participants make their mental models explicit through a careful and consistent process to test assumptions. This process has 3 main components: (1) assembling a team of participants; (2) conducting a behavior-over-time graphs exercise; and (3) drawing the causal loop diagram exercise. Results: The behavior-over-time graph portion produced 61 graphs in 10 categories. The causal loop diagram yielded 5 major themes and 7 subthemes. Conclusions: Factors that influence childhood obesity are varied, and it is important to recognize that no single solution exists. The perspectives from this exercise provided a means to create a process for dialogue and commitment by stakeholders and partnerships to build capacity for change within the community

A practical compact source of heralded single photons for a simple detection LIDAR

Optical quantum technologies such as quantum sensing, quantum cryptography and quantum computation all utilize properties of non-classical light, such as precise photon-number and entangled photon-pair states, to surpass technologies based on the classical light. A common route for obtaining heralded single photons is spontaneous four-wave mixing in optical fibers, allowing for a well-defined spatial mode, for high efficiency integration into optical fiber networks. These fibers are typically pumped using large, commercial, pulsed lasers requiring high-power (~10 W) pump lasers and are limited to ~MHz repetition rate. Here we propose a cost- efficient, compact and mobile alternative. Photon pairs at 660 nm and 960 nm will be created using four-wave mixing in commercial birefringent optical fiber, pumped using transform limited picosecond pulses with GHz repetition rates derived from a 785 nm CW laser diode using cavity-enhanced optical frequency comb generation. The pulses are predicted to have average power of 275 mW, a peak power of >40 W, and predicted photon yield of >2000 pairs detected per second. This design will be later utilized to implement a quantum illumination scheme based on a coincidence count between idler and signal photons -- instead of joint measurement between signal and idler. This will allow for quantum advantage over classic LIDAR without the requirement for maintaining an interferometric stability in free space

Early detection of pre-malignant lesions in a KRASG12D-driven mouse lung cancer model by monitoring circulating free DNA.

Lung cancer is the leading cause of cancer-related death. Two-thirds of cases are diagnosed at an advanced stage that is refractory to curative treatment. Therefore, strategies for the early detection of lung cancer are urgently sought. Total circulating free DNA (cfDNA) and tumour-derived circulating tumour DNA (ctDNA) are emerging as important biomarkers within a 'liquid biopsy' for monitoring human disease progression and response to therapy. Owing to the late clinical diagnosis of lung adenocarcinoma, the potential for cfDNA and ctDNA as early detection biomarkers remains unexplored. Here, using a Cre-regulated genetically engineered mouse model of lung adenocarcinoma development, driven by KrasG12D (the KrasLSL-G12D mouse), we serially tracked the release of cfDNA/ctDNA and compared this with tumour burden as determined by micro-computed tomography (CT). To monitor ctDNA, a droplet digital PCR assay was developed to permit discrimination of the KrasLox-G12D allele from the KrasLSL-G12D and KrasWT alleles. We show that micro-CT correlates with endpoint histology and is able to detect pre-malignant tumours with a combined volume larger than 7 mm3 Changes in cfDNA/ctDNA levels correlate with micro-CT measurements in longitudinal sampling and are able to monitor the emergence of lesions before the adenoma-adenocarcinoma transition. Potentially, this work has implications for the early detection of human lung adenocarcinoma using ctDNA/cfDNA profiling.A video abstract for this article is available at https://youtu.be/Ku8xJJyGs3UThis article has an associated First Person interview with the joint first authors of the paper.Medical Research Counci

SPICE, A Dataset of Drug-like Molecules and Peptides for Training Machine Learning Potentials

Machine learning potentials are an important tool for molecular simulation, but their development is held back by a shortage of high quality datasets to train them on. We describe the SPICE dataset, a new quantum chemistry dataset for training potentials relevant to simulating drug-like small molecules interacting with proteins. It contains over 1.1 million conformations for a diverse set of small molecules, dimers, dipeptides, and solvated amino acids. It includes 15 elements, charged and uncharged molecules, and a wide range of covalent and non-covalent interactions. It provides both forces and energies calculated at the {\omega}B97M-D3(BJ)/def2-TZVPPD level of theory, along with other useful quantities such as multipole moments and bond orders. We train a set of machine learning potentials on it and demonstrate that they can achieve chemical accuracy across a broad region of chemical space. It can serve as a valuable resource for the creation of transferable, ready to use potential functions for use in molecular simulations.Comment: 19 pages, 6 figure