Finite-Size Scaling in the Energy-Entropy Plane for the 2D +- J Ising Spin Glass

For $L \times L$ square lattices with $L \le 20$ the 2D Ising spin glass with +1 and -1 bonds is found to have a strong correlation between the energy and the entropy of its ground states. A fit to the data gives the result that each additional broken bond in the ground state of a particular sample of random bonds increases the ground state degeneracy by approximately a factor of 10/3. For $x = 0.5$ (where $x$ is the fraction of negative bonds), over this range of $L$, the characteristic entropy defined by the energy-entropy correlation scales with size as $L^{1.78(2)}$. Anomalous scaling is not found for the characteristic energy, which essentially scales as $L^2$. When $x= 0.25$, a crossover to $L^2$ scaling of the entropy is seen near $L = 12$. The results found here suggest a natural mechanism for the unusual behavior of the low temperature specific heat of this model, and illustrate the dangers of extrapolating from small $L$.Comment: 9 pages, two-column format; to appear in J. Statistical Physic

Mitochondrial Electron Transport Is the Cellular Target of the Oncology Drug Elesclomol

Elesclomol is a first-in-class investigational drug currently undergoing clinical evaluation as a novel cancer therapeutic. The potent antitumor activity of the compound results from the elevation of reactive oxygen species (ROS) and oxidative stress to levels incompatible with cellular survival. However, the molecular target(s) and mechanism by which elesclomol generates ROS and subsequent cell death were previously undefined. The cellular cytotoxicity of elesclomol in the yeast S. cerevisiae appears to occur by a mechanism similar, if not identical, to that in cancer cells. Accordingly, here we used a powerful and validated technology only available in yeast that provides critical insights into the mechanism of action, targets and processes that are disrupted by drug treatment. Using this approach we show that elesclomol does not work through a specific cellular protein target. Instead, it targets a biologically coherent set of processes occurring in the mitochondrion. Specifically, the results indicate that elesclomol, driven by its redox chemistry, interacts with the electron transport chain (ETC) to generate high levels of ROS within the organelle and consequently cell death. Additional experiments in melanoma cells involving drug treatments or cells lacking ETC function confirm that the drug works similarly in human cancer cells. This deeper understanding of elesclomol's mode of action has important implications for the therapeutic application of the drug, including providing a rationale for biomarker-based stratification of patients likely to respond in the clinical setting

Multi-site assessment of the precision and reproducibility of multiple reaction monitoring–based measurements of proteins in plasma

Verification of candidate biomarkers relies upon specific, quantitative assays optimized for selective detection of target proteins, and is increasingly viewed as a critical step in the discovery pipeline that bridges unbiased biomarker discovery to preclinical validation. Although individual laboratories have demonstrated that multiple reaction monitoring (MRM) coupled with isotope dilution mass spectrometry can quantify candidate protein biomarkers in plasma, reproducibility and transferability of these assays between laboratories have not been demonstrated. We describe a multilaboratory study to assess reproducibility, recovery, linear dynamic range and limits of detection and quantification of multiplexed, MRM-based assays, conducted by NCI-CPTAC. Using common materials and standardized protocols, we demonstrate that these assays can be highly reproducible within and across laboratories and instrument platforms, and are sensitive to low µg/ml protein concentrations in unfractionated plasma. We provide data and benchmarks against which individual laboratories can compare their performance and evaluate new technologies for biomarker verification in plasma

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Locally-made or Imported? Identifying Ceramic Composition Variation in the San Francisco Presidio Jurisdiction

In the late 18th century, representatives of the Spanish empire occupied the San Francisco Bay Area and rapidly transformed the region through the introduction of agriculture, animal husbandry, Roman Catholicism, the Spanish language, and the use of pottery. This paper focuses on the latter, evaluating questions of local manufacture or importation of ceramic materials among missions, the presidio, and pueblos within the San Francisco Presidio Jurisdiction. Through the application of instrumental neutron activation analysis of ceramic materials, local production of earthenwares at each of the missions is shown whereas glazed ware patterns reveal a mix of local and nonlocal sources. These patterns provide insights into the manufacture, supply, and exchange of ceramics in the San Francisco Bay Area, and through them a window on the materiality of the colonial encounter

Locally-made or Imported? Identifying Ceramic Composition Variation in the San Francisco Presidio Jurisdiction

In the late 18th century, representatives of the Spanish empire occupied the San Francisco Bay Area and rapidly transformed the region through the introduction of agriculture, animal husbandry, Roman Catholicism, the Spanish language, and the use of pottery. This paper focuses on the latter, evaluating questions of local manufacture or importation of ceramic materials among missions, the presidio, and pueblos within the San Francisco Presidio Jurisdiction. Through the application of instrumental neutron activation analysis of ceramic materials, local production of earthenwares at each of the missions is shown whereas glazed ware patterns reveal a mix of local and nonlocal sources. These patterns provide insights into the manufacture, supply, and exchange of ceramics in the San Francisco Bay Area, and through them a window on the materiality of the colonial encounter