cssi/SciSciGPT-SciSciNet huggingface dataset:
Pass-Through as a Test for Market Power: An Application to Solar Subsidies

We formalize pass-through over-shifting as a simple yet under-utilized test for market power. We apply this test in the market for solar energy. Specifically, we estimate the pass-through of solar subsidies to solar system prices using rich micro-level transaction and subsidy data from California. Buyers of solar systems capture nearly the full subsidy, while there is more-than- complete pass-through to lessees. We conclude that solar markets are imperfectly competitive by ruling out alternative explanations for over-shifting, and reinforce this conclusion with a test of solar demand curvature. This procedure can serve to detect market power beyond the solar market.
Causal inference when counterfactuals depend on the proportion of all subjects exposed

The assumption that no subject's exposure affects another subject's outcome, known as the no-interference assumption, has long held a foundational position in the study of causal inference. However, this assumption may be violated in many settings, and in recent years has been relaxed considerably. Often this has been achieved with either the aid of a known underlying network, or the assumption that the population can be partitioned into separate groups, between which there is no interference, and within which each subject's outcome may be affected by all the other subjects in the group via the proportion exposed (the stratified interference assumption). In this article, we instead consider a complete interference setting, in which each subject affects every other subject's outcome. In particular, we make the stratified interference assumption for a single group consisting of the entire sample. We show that a targeted maximum likelihood estimator for the i.i.d. setting can be used to estimate a class of causal parameters that includes direct effects and overall effects under certain interventions. This estimator remains doubly-robust, semiparametric efficient, and continues to allow for incorporation of machine learning under our model. We conduct a simulation study, and present results from a data application where we study the effect of a nurse-based triage system on the outcomes of patients receiving HIV care in Kenyan health clinics.
A Study of Data Store-based Home Automation

Home automation platforms provide a new level of convenience by enabling consumers to automate various aspects of physical objects in their homes. While the convenience is beneficial, security flaws in the platforms or integrated third-party products can have serious consequences for the integrity of a user's physical environment. In this paper we perform a systematic security evaluation of two popular smart home platforms, Google's Nest platform and Philips Hue, that implement home automation "routines" (i.e., trigger-action programs involving apps and devices) via manipulation of state variables in a centralized data store. Our semi-automated analysis examines, among other things, platform access control enforcement, the rigor of non-system enforcement procedures, and the potential for misuse of routines. This analysis results in ten key findings with serious security implications. For instance, we demonstrate the potential for the misuse of smart home routines in the Nest platform to perform a lateral privilege escalation, illustrate how Nest's product review system is ineffective at preventing multiple stages of this attack that it examines, and demonstrate how emerging platforms may fail to provide even bare-minimum security by allowing apps to arbitrarily add/remove other apps from the user's smart home. Our findings draw attention to the unique security challenges of platforms that execute routines via centralized data stores, and highlight the importance of enforcing security by design in emerging home automation platforms.
Steep-Slope Hysteresis-Free Negative-Capacitance 2D Transistors

The so-called Boltzmann Tyranny defines the fundamental thermionic limit of the subthreshold slope (SS) of a metal-oxide-semiconductor field-effect transistor (MOSFET) at 60 mV/dec at room temperature and, therefore, precludes the lowering of the supply voltage and the overall power consumption [1]. Adding a ferroelectric negative capacitor to the gate stack of a MOSFET may offer a promising solution to bypassing this fundamental barrier [2]. Meanwhile, two-dimensional (2D) semiconductors, such as atomically thin transition metal dichalcogenides (TMDs) due to their low dielectric constant, and ease of integration in a junctionless transistor topology, offer enhanced electrostatic control of the channel. Here, we combine these two advantages and demonstrate for the first time a molybdenum disulfide (MOS 2 )2D steep slope transistor with a ferroelectric hafnium zirconium oxide layer (HZO) in the gate dielectric stack [3]. This device exhibits excellent performance in both on- and off-states, with maximum drain current of $510\ \mu \mathrm{A}/\mu \mathrm{m}$ , sub-thermionic subthreshold slope and is essentially hysteresis-free. Negative differential resistance (NDR) was observed at room temperature in the Mos2 negative capacitance field-effect-transistors (NC-FETs) as the result of negative capacitance due to the negative drain-induced-barrier-lowering (DIBL). High on-current induced self-heating effect was also observed and studied. We will also discuss the effect of internal metal gate [4], [5], p-type 2D transistors [6], and ferroelectric switch speed issues [7] in this talk. The work is in close collaborations with Mengwei Si, Wonil Chung, Chun-Jung Su, Chunsheng Jiang, Hong Zhou, Kerry D. Maize, Ali Shakouri, Muhammad A. Alam.
Electrocatalytic Oxidation of Glycerol on Platinum

Glycerol, a surplus byproduct of biodiesel production, is a promising energy source for fuel cells. However, the low selectivity toward the complete-oxidation product, carbon dioxide (CO2), hinders the electro-oxidation of glycerol. In this work, we combine spectro-electrochemical studies of extended surfaces using sum frequency generation and product-resolved electrocatalytic measurements on high-surface-area catalysts under potentiostatic conditions to investigate the glycerol oxidation reaction on platinum (Pt). We observed adsorbing carbon monoxide (CO) as the reaction intermediate at potentials as low as 0.05 V (vs the reversible hydrogen electrode; the same potential scale is used throughout this discussion unless otherwise specified) on polycrystalline Pt electrode, indicating that cleavage of the C–C bond in glycerol is feasible on Pt. This observation is in contradiction to the low selectivity toward CO2 (with a faradaic efficiency of <4%) measured by the electrocatalytic studies on Pt/C. The dis...
A PDE method for estimation of implied volatility

In this paper it is proved that the Black–Scholes implied volatility satisfies a second order non-linear partial differential equation. The obtained PDE is then used to construct an algorithm for f...
Pseudograph associahedra

Given a simple graph G, the graph associahedron KG is a simple polytope whose face poset is based on the connected subgraphs of G. This paper defines and constructs graph associahedra in a general context, for pseudographs with loops and multiple edges, which are also allowed to be disconnected. We then consider deformations of pseudograph associahedra as their underlying graphs are altered by edge contractions and edge deletions.
Proceedings of the 2003 ACM workshop on XML security

These proceedings contain the papers selected for presentation at the ACM Workshop on XML Security, held in conjunction with the 10th ACM Computer and Communications Security Conference, October 31, 2003, in Virginia (USA).In response to the call for papers, 16 papers were submitted to the workshop. These papers were evaluated on the basis of their significance, novelty, and technical quality. Each paper was reviewed by at least two members of the program committee. The program committee meeting was held electronically. Of the papers submitted, 12 were selected for presentation at the workshop. The workshop program also includes an invited talk by Frank Siebenlist.
Volume scavenging of networked droplets

Abstract A system of N spherical-cap fluid droplets protruding from circular openings on a plane is connected through channels. This system is governed by surface tension acting on the droplets and viscous stresses inside the fluid channels. The fluid rheology is given by the Ostwald–de Waele power law, thus permitting shear thinning. The pressure acting on each droplet is caused by capillarity and given in terms of the droplet volume via the Young–Laplace law. Liquid is exchanged along the network of fluid conduits due to an imbalance of the Laplace pressures between the droplets. In this way some droplets gain volume at the expense of others. This mechanism, christened “volume scavenging,” leads to interesting dynamics. Numerical experiments show that an initial droplet configuration is driven to a stable equilibrium exhibiting 1 super-hemispherical droplet and N − 1 sub-hemispherical ones when the initial droplet volumes are large. The selection of this “winning” droplet depends not only on the channel network and the fluid volume, but also notably on the fluid rheology. The rheology is also observed to drastically change the transition to equilibrium. For smaller droplet volumes the long-term behavior is seen to be more complicated since the types of equilibria differ from those arising for larger volumes. These observations motivate our analytical study of equilibria and their stability for the corresponding nonlinear dynamical system. The identification of equilibria is accomplished by locating the zeros of a mass polynomial, defined through the constant volume/mass constraint. The key tool in our stability analysis is a pressure–volume work functional, related to the total surface area, which serves as a Lyapunov function for the dynamical system. This functional is useful since equilibria are typically not hyperbolic and linearization techniques not available. Equilibria will be shown to be hierarchically organized in terms of size of the pressure–volume work functional. For larger droplet volumes this ordering exhibits one hierarchy of equilibria. Two hierarchies exist when the volumes are smaller. The minimizing equilibria in either case are asymptotically stable.
Neyman–Pearson Inference†

The approach to statistical hypothesis testing developed by Jerzy Neyman and Egon Pearson built upon and extended that of Ronald Fisher, and differed from the latter in several important ways. Ideas that distinguish their approach include choosing between possible hypotheses (in contrast to deciding whether or not to reject a single hypothesis); setting, before experimentation, a criterion for deciding which hypothesis to accept; recognizing the two possible ways to draw an incorrect conclusion from a statistical test and taking account of the fact that they are not likely to be equally desirable; and defining the power of a test as the probability of detecting a real effect if there is one. They saw statistical tests as attempts to quantify commonsense notions about the interpretation of probabilistic data and stressed the importance of the exercise of judgment in their application. Keywords: hypothesis testing; error type; sample space; decision criterion; level of significance; critical area; power; likelihood ratio; judgment
Evaluation of the effectiveness of green infrastructure on hydrology and water quality in a combined sewer overflow community.

Abstract Evaluation of the effectiveness of green infrastructure (GI) practices on improving site hydrology and water quality and their associated cost could provide valuable information for decision makers when creating development/re-development strategies. In this study, a watershed scale rainfall-runoff model (the Long-Term Hydrologic Impact Analysis - Low Impact Development model, the L-THIA-LID 2.1 model) was enhanced to improve its simulation of urban water management practices including GI practices. The enhanced model (L-THIA-LID 2.2) is capable of: simulating in more detail impervious surfaces including sidewalks, roads, driveways, and parking lots; conducting cost calculations for converting these impervious surfaces to porous pavements; and, selecting suitable areas for bioretention in the study area. The effectiveness of GI practices on improving hydrology and water quality in a combined sewer overflow urban watershed—the Darst Sewershed in the City of Peoria, IL—was examined in eleven simulation scenarios using 8 practices. The total cost and the cost effectiveness for each scenario considering a 20-year practice lifetime were calculated. Results showed: combined implementation of GI practices performed better than applying individual practices alone; adoption levels and combinations of GI practices could potentially reduce runoff volume by 0.2–23.5%, TSS by 0.18–30.8%, TN by 0.2–27.9%, and TP by 0.2 to 28.1%; adding more practices did not necessarily achieve substantial runoff and pollutant reductions based on site characteristics; the most cost-effective scenario out of eleven considered had an associated cost of $9.21 to achieve 1 m3 runoff reduction per year and $119 to achieve 1 kg TSS reduction per year assuming residents' cooperation in implementing GI practices on their properties; adoption of GI practices on all possible areas could potentially achieve the greatest runoff and pollutant reduction, but would not be the most cost-effective option. This enhanced model can be applied to different locations to support assessing the beneficial uses of GI practices.
Hedging Macroeconomic and Financial Uncertainty and Volatility

Abstract We study the pricing of shocks to uncertainty and volatility using a wide-ranging set of options contracts covering a variety of different markets. If uncertainty shocks are viewed as bad by investors, they should carry negative risk premiums. Empirically, however, uncertainty risk premiums are positive in most markets. Instead, it is the realization of large shocks to fundamentals that has historically carried a negative premium. In other words, we find that the return premium for gamma is negative, while that for vega is positive. These results imply that it is jumps, for which exposure is measured by gamma, not forward-looking uncertainty shocks, measured by vega, that drive investors’ marginal utility. In further support of the jump interpretation, the return patterns are more extreme for deeper out-of-the-money options.
The demographics of dog bites in the United States

Abstract Dog bites are a significant public health issue. There is no comprehensive study of dog bite demographics. It was the purpose of this study to perform such an analysis across the US. The National Electronic Injury Surveillance System All Injury Program data for the years 2005 through 2013 was accessed; dog bite injuries were extracted and analyzed. Statistical analyses were performed with SUDAAN 11.0.01™ software to account for the weighted, stratified nature of the data. Incidence values were calculated using population data from the US Census Bureau. A P 85 years of age, 4.88 [2.89, 8.24] 75–84 years, and 2.79 [1.77, 4.39] those ≤4 years of age, with the 10–14 year age group the reference group. The average annual incidence was 1.1 per 1,000, and was slightly higher in males (1.18 vs 1.02 per 1,000). The estimated cost was at least 400 million US$ per year. Potential prevention strategies are educational programs directed at both children and parents/caretakers outlining the responsibilities of owning a dog. This information can be disseminated in health care facilities, radio/TV/Internet venues, and dog kennels/shelters.
Public Disclosures and Information Asymmetry: A Theory of the Mosaic

ABSTRACT We model an information mosaic in which multiple signals—one gathered by an informed trader and the other publicly disclosed by the manager of the firm—are combined to estimate firm value....
Arrow, Hausdorff, and Ambiguities in the Choice of Preferred States in Complex Systems

Arrow's `impossibility' theorem asserts that there are no satisfactory methods of aggregating individual preferences into collective preferences in many complex situations. This result has ramifications in economics, politics, i.e., the theory of voting, and the structure of tournaments. By identifying the objects of choice with mathematical sets, and preferences with Hausdorff measures of the distances between sets, it is possible to extend Arrow's arguments from a sociological to a mathematical setting. One consequence is that notions of reversibility can be expressed in terms of the relative configurations of patterns of sets.
Cross-cultural differences in creativity: A process-based view through a prism of cognition, motivation and attribution

Abstract Global innovation capabilities including effective leverage of employee’s creative potential across various cultural contexts have become increasingly important. Although widely recognized among researchers and practitioners, cross-cultural differences in creativity are yet to be comprehensively explored. The paper examines differences in creativity from a process perspective and identifies distinct mechanisms that underlie differences in creativity across cultures. Specifically, the theoretical framework depicts the effects of motivational, cognitive and attribution preferences on information processing strategies at every step of the creativity process and outlines how these differences result in a qualitatively different creative outcome. The perspective presented in the paper traces differences in the degree of novelty and usefulness of a creative idea to the information processing strategies that occur at every given step of the creative process. The proposed model complements prevalent social or normative approaches in the cross-cultural creativity field to provide a process-based explanation for the differences in the degree of creativity that were observed by researchers in the past.
The economic benefits of technology transfer from U.S. federal laboratories

In this paper we review the legislative emphasis on technology transfers from U.S. federal laboratories, and we present a framework to describe how private sector firms benefit from the adoption of technologies from federal laboratories. We conclude that if a federal laboratory can provide the technology being transferred more efficiently than the private sector can develop it, there is a social gain from the federal laboratory doing so. The social gain will be realized in part by increased profits for the private firms using the technology and in part by consumers who have higher reservation prices for higher quality products and services and who pay lower prices because firms’ costs are lower.
Quick installation of a 1,4-difunctionality via regioselective nickel-catalyzed reductive coupling of ynoates and aldehydes.

The development of efficient methods for the synthesis of molecules with 1,4-difunctionalities has been a dire need of the synthetic community. In this work, intermolecular reductive coupling of ynoates and aldehydes (in the presence of a silane) has been accomplished for the first time using catalytic amounts of Ni(COD)2, an N-heterocyclic carbene ligand, and PPh3. High regioselectivity has been demonstrated for the multicomponent coupling reactions, and more than a dozen invaluable silyl-protected γ-hydroxy-α,β-enoates have been synthesized. This methodology provides a quick entry to many other 1,4-difunctional compounds and oxygen-containing five-membered rings. The intermediacy of metallacycles in the catalytic process has been established by deuterium-labeling experiments.
Bayesian-Estimated Hierarchical HMMs Enable Robust Analysis of Single-Molecule Kinetic Heterogeneity.

Abstract Single-molecule kinetic experiments allow the reaction trajectories of individual biomolecules to be directly observed, eliminating the effects of population averaging and providing a powerful approach for elucidating the kinetic mechanisms of biomolecular processes. A major challenge to the analysis and interpretation of these experiments, however, is the kinetic heterogeneity that almost universally complicates the recorded single-molecule signal versus time trajectories (i.e., signal trajectories). Such heterogeneity manifests as changes and/or differences in the transition rates that are observed within individual signal trajectories or across a population of signal trajectories. Because characterizing kinetic heterogeneity can provide critical mechanistic information, we have developed a computational method that effectively and comprehensively enables such analysis. To this end, we have developed a computational algorithm and software program, hFRET, that uses the variational approximation for Bayesian inference to estimate the parameters of a hierarchical hidden Markov model, thereby enabling robust identification and characterization of kinetic heterogeneity. Using simulated signal trajectories, we demonstrate the ability of hFRET to accurately and precisely characterize kinetic heterogeneity. In addition, we use hFRET to analyze experimentally recorded signal trajectories reporting on the conformational dynamics of ribosomal pre-translocation (PRE) complexes. The results of our analyses demonstrate that PRE complexes exhibit kinetic heterogeneity, reveal the physical origins of this heterogeneity, and allow us to expand the current model of PRE complex dynamics. The methods described here can be applied to signal trajectories generated using any type of signal and can be easily extended to the analysis of signal trajectories exhibiting more complex kinetic behaviors. Moreover, variations of our approach can be easily developed to integrate kinetic data obtained from different experimental constructs and/or from molecular dynamics simulations of a biomolecule of interest.
Synthetically engineered Medea gene drive system in the worldwide crop pest Drosophila suzukii

Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii We demonstrate that this drive system, based on an engineered maternal "toxin" coupled with a linked embryonic "antidote," is capable of biasing Mendelian inheritance rates with up to 100% efficiency. However, we find that drive resistance, resulting from naturally occurring genetic variation and associated fitness costs, can be selected for and hinder the spread of such a drive. Despite this, our results suggest that this gene drive could maintain itself at high frequencies in a wild population and spread to fixation if either its fitness costs or toxin resistance were reduced, providing a clear path forward for developing future such systems in this pest.
Preparation of the first tricoordinate silyl cation

The preparation of the first tricoordinate silyl cation was made possible by a sequence of discoveries over a 20 year period. The extremely high electrophilicity of the material required protection from all manner of nucleophiles. Only arenes had sufficiently low nucleophilicity to serve as solvent. Tetrakis(pentafluorophenyl) borate provided the least nucleophilic anion. All manipulations had to be carried out in an inert atmosphere, primarily as protection from moisture. Sterically bulky substituents such as mesityl were needed to protect the cation even from the optimized solvent and anion. The trimesitylsilylium ion was produced from allyltrimesitylsilane by reaction of electrophiles with the allyl double bond and extrusion of the allyl adduct. Copyright © 2001 John Wiley & Sons, Ltd.
Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons.

Alternative RNA processing plays an essential role in shaping cell identity and connectivity in the central nervous system. This is believed to involve differential regulation of RNA processing in various cell types. However, in vivo study of cell type-specific post-transcriptional regulation has been a challenge. Here, we describe a sensitive and stringent method combining genetics and CLIP (crosslinking and immunoprecipitation) to globally identify regulatory interactions between NOVA and RNA in the mouse spinal cord motoneurons. We developed a means of undertaking motoneuron-specific CLIP to explore motoneuron-specific protein–RNA interactions relative to studies of the whole spinal cord in mouse. This allowed us to pinpoint differential RNA regulation specific to motoneurons, revealing a major role for NOVA in regulating cytoskeleton interactions in motoneurons. In particular, NOVA specifically promotes the palmitoylated isoform of the cytoskeleton protein Septin 8 in motoneurons, which enhances dendritic arborization. Our study demonstrates that cell type-specific RNA regulation is important for fine tuning motoneuron physiology and highlights the value of defining RNA processing regulation at single cell type resolution.
What drives phenotypic divergence among coral clonemates of Acropora palmata

Evolutionary rescue of populations depends on their ability to produce phenotypic variation that is heritable and adaptive. DNA mutations are the best understood mechanisms to create phenotypic variation, but other, less well-studied mechanisms exist. Marine benthic foundation species provide opportunities to study these mechanisms because many are dominated by isogenic stands produced through asexual reproduction. For example, Caribbean acroporid corals are long lived and reproduce asexually via breakage of branches. Fragmentation is often the dominant mode of local population maintenance. Thus, large genets with many ramets (colonies) are common. Here, we observed phenotypic variation in stress responses within genets following the coral bleaching events in 2014 and 2015 caused by high water temperatures. This was not due to genetic variation in their symbiotic dinoflagellates (Symbiodinium "fitti") because each genet of this coral species typically harbours a single strain of S. "fitti". Characterization of the microbiome via 16S tag sequencing correlated the abundance of only two microbiome members (Tepidiphilus, Endozoicomonas) with a bleaching response. Epigenetic changes were significantly correlated with the host's genetic background, the location of the sampled polyps within the colonies (e.g., branch vs. base of colony), and differences in the colonies' condition during the bleaching event. We conclude that long-term microenvironmental differences led to changes in the way the ramets methylated their genomes, contributing to the differential bleaching response. However, most of the variation in differential bleaching response among clonemates of Acropora palmata remains unexplained. This research provides novel data and hypotheses to help understand intragenet variability in stress phenotypes of sessile marine species.
Critical role of water content in the formation and reactivity of uranium, neptunium, and plutonium iodates under hydrothermal conditions: implications for the oxidative dissolution of spent nuclear fuel.

The reactions of 237NpO2 with excess iodate under acidic hydrothermal conditions result in the isolation of the neptunium(IV), neptunium(V), and neptunium(VI) iodates, Np(IO3)4, Np(IO3)4·nH2O·nHIO3, NpO2(IO3), NpO2(IO3)2(H2O), and NpO2(IO3)2·H2O, depending on both the pH and the amount of water present in the reactions. Reactions with less water and lower pH favor reduced products. Although the initial redox processes involved in the reactions between 237NpO2 or 242PuO2 and iodate are similar, the low solubility of Pu(IO3)4 dominates product formation in plutonium iodate reactions to a much greater extent than does Np(IO3)4 in the neptunium iodate system. UO2 reacts with iodate under these conditions to yield uranium(VI) iodates solely. The isotypic structures of the actinide(IV) iodates, An(IO3)4 (An = Np, Pu), are reported and consist of one-dimensional chains of dodecahedral An(IV) cations bridged by iodate anions. The structure of Np(IO3)4·nH2O·nHIO3 is constructed from NpO9 tricapped-trigonal prisms ...
Synthesis and Properties of 2,3‐Dihydro‐1H‐corannuleno[2,3‐cd]pyridine (=2,3‐Dihydro‐1H‐dibenzo[1,10 : 6,7]fluorantheno[3,4‐cd]pyridine) Derivatives: Heterocyclic peri‐Anellated Corannulenes

The anellation of a 6-membered ring to the 2,3-position of corannulene (=dibenzo[ghi,mno]fluoranthene; 1) leads to curved aromatic compounds with a significantly higher bowl-inversion barrier than corannulene (see Fig. 1). If the bridge is −CH2−NR−CH2−, a variety of linkers can be introduced at the N(2) atom, and the corresponding curved aromatics act as versatile building blocks for larger structures (see Scheme). The locked bowl, in combination with an amide bond (see 9 and 10), gives rise to corannulene derivatives with chiral ground-state conformations, which possess the ability to adapt to their chiral environment by shifting their enantiomer equilibrium slightly in favor of one enantiomeric conformer. Rim annulation of corannulene seems to display a significantly lower electron-withdrawing effect than facial anellation on [5,6]fullerene-C60-Ih, as determined by an investigation of the basicity at the N-atom of CH2−NR−CH2 (see 4vs. 15 in Fig. 2).
New Ferrimagnetic Oxide CaCu3Cr2Sb2O12: High-Pressure Synthesis, Structure, and Magnetic Properties

A new perovskite-type oxide, CaCu 3 Cr 2 Sb 2 O 1 2 , has been synthesized at 10 GPa and 1100 °C. This compound crystallizes in space group Pn3 and shows simultaneous cation ordering on both A and B sites. Magnetization measurements indicate that an interaction between A-site Cu(II) and B-site Cr(III) cations dominates over possible antiferromagnetic couplings between Cu(II)-Cu(II) ions or Cr(III)-Cr(III) ions and induces net spontaneous magnetic moment below ∼160 K. The lack of significant hysteresis in the isothermal magnetization curves suggests that CaCu 3 Cr 2 Sb 2 O 1 2 is a soft ferrimagnet, which is consistent with the thermomagnetic irreversibility and magnetic susceptibility behavior. Interestingly, the experimentally determined effective magnetic moment of ∼1.4 μ B at 5 K is significantly smaller than the expected value of 3 μ B estimated assuming an antiparallel alignment of the spins of Cu(II) and Cr(III). Significant spin canting may account for the small magnetic moment. Such an anomalously small magnetization is similar to that of CuCr 2 O 4 spinel showing a non-unidirectional spin canting behavior.
Direct Measurements of the Kinetics of 3-exo Radical Cyclizations Using Radical Reporter Groups

The E and Z isomers of the 4-(2,2-diphenylcyclopropyl)-3-butenyl radical (1), produced by laser flash photolysis of the corresponding PTOC esters in THF, cyclized to the (2,2-diphenylcyclopropyl)(cyclopropyl)methyl radical (2) that rapidly opened to 1,1-diphenyl-4-cyclopropyl-3-butenyl radicals (3). Radicals 3 were monitored by UV spectroscopy, but the observed rate constants were for the initial, relatively slow cyclizations of radicals 1 to radical 2. The Arrhenius functions determined in the temperature range of 20−58 °C were log(k/s-1) = (11.46 ± 0.38) − (9.10 ± 0.54)/θ for (E)-1 and log(k/s-1) = (12.34 ± 0.32) − (10.10 ± 0.45)/θ for (Z)-1 where θ = 2.3RT in kcal/mol and errors are at 2σ. Radical (Z)-1 cyclizes somewhat faster than radical (E)-1 as a result of a more favorable entropy of activation and despite the fact that the activation energy for cyclization of (Z)-1 through the requisite syn-transition state is greater than that for cyclization of (E)-1 through an anti-transition state.
A simple and concise synthesis of LY231514(MTA)

Abstract The pyrrolo[2,3- d ]pyrimidine anticancer agent LY231514 (MTA, 1) has been prepared utilizing, as a key sequence, Michael condensation of 2,6-diamino-4(3 H )-pyrimidinone (as the donor) with the nitro olefin 8, followed by a Nef reaction that leads to the annulated pyrrole ring of 1.
Pathogenic budding yeasts isolated outside of clinical settings

Budding yeasts are distributed across a wide range of habitats, including as human commensals. However, under some conditions, these commensals can cause superficial, invasive, and even lethal infections. Despite their importance to human health, little is known about the ecology of these opportunistic pathogens, aside from their associations with mammals and clinical environments. During a survey of approximately 1000 non-clinical samples across the United States of America, we isolated 54 strains of budding yeast species considered opportunistic pathogens, including Candida albicans and Candida (Nakaseomyces) glabrata. We found that, as a group, pathogenic yeasts were positively associated with fruits and soil environments, whereas the species Pichia kudriavzevii (syn. Candida krusei syn. Issatchenkia orientalis) had a significant association with plants. Of the four species that cause 95% of candidiasis, we found a positive association with soil. These results suggest that pathogenic yeast ecology is more complex and diverse than is currently appreciated and raises the possibility that these additional environments could be a point of contact for human infections.
Design and evaluation of novel nonsteroidal dissociating glucocorticoid receptor ligands

Abstract A novel class of phenylpyrazole fused Wieland–Miescher ketone derivatives are high affinity, receptor specific, selective modulators of glucocorticoid receptor (GR) mediated transcription in vitro, dissociating transactivation, AP-1 repression, and NF-κB repression from each other.
The Galactic Halo’s O VI Resonance Line Intensity

We used FUSE to observe ultraviolet emission from diffuse O VI in the hot gas in the Galactic halo. By comparing our result with another, nearby observation blocked by an opaque cloud at a distance of 230 pc, we could subtract off the contribution from the Local Bubble, leading to an apparent halo intensity of I = 4680 photons cm-2 s-1 sr-1. A correction for foreground extinction leads to an intrinsic intensity that could be as much as twice this value. Assuming T ~ 3 × 105 K, we conclude that the electron density, ne, is 0.01-0.02 cm-3, that the thermal pressure, p/k, is 7000-10,000 cm-3 K, and that the hot gas is spread over a length of 50-70 pc, implying a small filling factor for O VI-rich gas. ROSAT observations of emission at 1/4 keV in the same direction indicate that the X-rays are weaker by a factor of 1.1-4.7, depending on the foreground extinction. Simulated supernova remnants evolving in low-density gas have similar O VI to X-ray ratios when the remnant plasma is approaching collisional ionizational equilibrium and the physical structures are approaching dynamical "middle age." Alternatively, the plasma can be described by a temperature power law. Assuming that the material is approximately isobaric and the length scales according to Tβd ln T, we find β = 1.5 ± 0.6 and an upper temperature cutoff of 106.6(+0.3,-0.2) K. The radiative cooling rate for the hot gas, including that which is too hot to hold O VI, is 6 × 1038 ergs s-1 kpc-2. This rate implies that ~70% of the energy produced in the disk and halo by SN and pre-SN winds is radiated by the hot gas in the halo.
An in situ procedure for catalytic, enantioselective acetate aldol addition. Application to the synthesis of (R)-(−)-epinephrine

Abstract We report an in situ preparation of catalyst 3 which substantially simplifies the experimental procedure for the enantioselective, catalytic acetate aldol addition reaction. The addition of Me3SiCl and Et3N circumvents the azeotropic removal of the released isopropanol upon treating ligands 1 and 2 with Ti(OiPr)4. Importantly, this new procedure maintains the salient features of the catalytic process we originally described: high yields and enantioselectivities, low catalyst loads, and convenient reaction times and temperatures. We have applied the new procedure to an efficient synthesis of (R)-(−)-epinephrine from commercially reagents in an overall yield of 45%.
MetaR: simple, high-level languages for data analysis with the R ecosystem

11 Data analysis tools have become essential to the study of biology. Tools available today were constructed with layers of technology developed over decades. Here, we explain how some of the principles used to develop this technology are sub-optimal for the construction of data analysis tools for biologists. In contrast, we applied language workbench technology (LWT) to create a data analysis language, called MetaR, tailored for biologists with no programming experience, as well as expert bioinformaticians and statisticians. A key novelty of this approach is its ability to blend user interface with scripting in such a way that beginners and experts alike can analyze data productively in the same analysis platform. While presenting MetaR, we explain how a judicious use of LWT eliminates problems that have historically contributed to data analysis bottlenecks. These results show that language design with LWT can be a compelling approach for developing intelligent data analysis tools. 12
Synthesis of diastereomeric ketoconazole analogs

Syntheses of trans-isomers of ketoconazole, and the corresponding des-acetyl, 1-methyl-, 1-formyl and 1-methanesulfonyl analogs were investigated. These isomers, along with the corresponding cis-diastereomers were characterized by their carbon-13 nmr spectra.
Novel and potent transforming growth factor beta type I receptor kinase domain inhibitor: 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolines.

A novel series of 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolines was synthesized and their TβR-1 inhibitory, p38 MAPK inhibitory, and TβR-1-dependent cellular activity were evaluated. Compound 5a was found to be a highly potent in the enzyme assay and TβR-1-dependent cellular assays. In addition, dimer (4g), with a urea linker, shows a similar enzyme and cellular activity despite a bulky substitution.
Rapid Quantitative Pharmacodynamic Imaging with Bayesian Estimation

We recently described rapid quantitative pharmacodynamic imaging, a novel method for estimating sensitivity of a biological system to a drug. We tested its accuracy in simulated biological signals with varying receptor sensitivity and varying levels of random noise, and presented initial proof-of-concept data from functional MRI (fMRI) studies in primate brain. However, the initial simulation testing used a simple iterative approach to estimate pharmacokinetic-pharmacodynamic (PKPD) parameters, an approach that was computationally efficient but returned parameters only from a small, discrete set of values chosen a priori. Here we revisit the simulation testing using a Bayesian method to estimate the PKPD parameters. This improved accuracy compared to our previous method, and noise without intentional signal was never interpreted as signal. We also reanalyze the fMRI proof-of-concept data. The success with the simulated data, and with the limited fMRI data, is a necessary first step toward further testing of rapid quantitative pharmacodynamic imaging.
Novel routes for the generation of structurally diverse labdane diterpenes from andrographolide

Andrographolide 1, the major constituent of the Indian medicinal plant Andrographis paniculata (Acanthaceae) was converted into the key intermediate 4 by selective oxidative degradation of the C-12,13 olefin bond. The aldehyde functional group present in 4 has been utilized for synthesizing a number of structurally diverse labdane diterpenes. Synthesis and in vitro cytotoxic activity results of the compounds prepared are discussed.
Ruthenium tetroxide oxidation of Grundmann's ketone derived from vitamin D3

Abstract The reaction of Grundmann's ketone 2a with ruthenium tetroxide, generated in situ from ruthenium trichloride and sodium metaperiodate, has been investigated. In addition to the main 25-hydroxylated compound 2b the minor oxidation products have been isolated and identified. The examined catalytic process results in the oxidation of methylene groups and hydroxylation at teriary positions occurring with retention of configuration.
Inferring Intracellular Signal Transduction Circuitry from Molecular Perturbation Experiments

The development of network inference methodologies that accurately predict connectivity in dysregulated pathways may enable the rational selection of patient therapies. Accurately inferring an intracellular network from data remains a very challenging problem in molecular systems biology. Living cells integrate extremely robust circuits that exhibit significant heterogeneity, but still respond to external stimuli in predictable ways. This phenomenon allows us to introduce a network inference methodology that integrates measurements of protein activation from perturbation experiments. The methodology relies on logic-based networks to provide a predictive approximation of the transfer of signals in a network. The approach presented was validated in silico with a set of test networks and applied to investigate the epidermal growth factor receptor signaling of a breast epithelial cell line, MFC10A. In our analysis, we predict the potential signaling circuitry most likely responsible for the experimental readouts of several proteins in the mitogen-activated protein kinase and phosphatidylinositol-3 kinase pathways. The approach can also be used to identify additional necessary perturbation experiments to distinguish between a set of possible candidate networks.
Efficient routes to novel molecular architectures. Template-directed synthesis of mechanically interlocked suitanes

The design and synthesis of two recently reported examples of a new class of mechanically interlocked molecules - suitanes - is described. Suitanes consist of a rigid "body" template that is wrapped up in an all-in-one "suit" that fits the body to a T such that the two cannot be separated. These architecturally distinct interlocked molecular compounds are synthesized from a pool of components through a template-directed self-assembly process by taking advantage of dynamic covalent bond formation.
SYNTHESIS AND EVALUATION OF A CARBOCYCLIC ANALOGUE OF THE CC-1065 AND DUOCARMYCIN ALKYLATION SUBUNITS : ROLE OF THE VINYLOGOUS AMIDE AND IMPLICATIONS ON DNA ALKYLATION CATALYSIS

The synthesis and chemical properties of 1,2,9,9a-tetrahydro-1H-cyclopropa[c]benz[e]inden-4-one (CBIn, 10), a carbocyclic C-ring analogue of the alkylation subunits of CC-1065 and the duocarmycins, are detailed. The core structure of CBIn was prepared with an intramolecular Heck reaction for assembly of the key tricyclic skeleton and a final Winstein Ar-3' spirocyclization to install the reactive cyclopropane. A study of the CBIn solvolysis reactivity, regioselectivity, and mechanism revealed that removal of the nitrogen and resulting vinylogous amide stabilization increased the reactivity 3200× (pH 3) and reversed the inherent regioselectivity, but did not alter the SN2 reaction mechanism. Thus, the vinylogous amide found in the naturally occurring alkylation subunits is responsible for their unusual stability and significantly impacts the regioselectivity without altering the inherent SN2 mechanism of nucleophilic addition. More importantly, this solvolysis reactivity proved independent of pH throughout...
The Lupus Susceptibility Locus Sgp3 Encodes the Suppressor of Endogenous Retrovirus Expression SNERV.

Elevated endogenous retrovirus (ERV) transcription and anti-ERV antibody reactivity are implicated in lupus pathogenesis. Overproduction of non-ecotropic ERV (NEERV) envelope glycoprotein gp70 and resultant nephritis occur in lupus-prone mice, but whether NEERV mis-expression contributes to lupus etiology is unclear. Here we identified suppressor of NEERV (Snerv) 1 and 2, Kruppel-associated box zinc-finger proteins (KRAB-ZFPs) that repressed NEERV by binding the NEERV long terminal repeat to recruit the transcriptional regulator KAP1. Germline Snerv1/Snerv2 deletion increased activating chromatin modifications, transcription, and gp70 expression from NEERV loci. F1 crosses of lupus-prone New Zealand Black (NZB) and 129 mice to Snerv1/Snerv2-/- mice failed to restore NEERV repression, demonstrating that loss of SNERV underlies the lupus autoantigen gp70 overproduction that promotes nephritis in susceptible mice and that SNERV encodes for Sgp3 (in NZB mice) and Gv-1 loci (in 129 mice). Increased ERV expression in lupus patients inversely correlated with three putative ERV-suppressing KRAB-ZFPs, suggesting that loss of KRAB-ZFP-mediated ERV control may contribute to human lupus pathogenesis.
GenomeDISCO: a concordance score for chromosome conformation capture experiments using random walks on contact map graphs.

Motivation The three-dimensional organization of chromatin plays a critical role in gene regulation and disease. High-throughput chromosome conformation capture experiments such as Hi-C are used to obtain genome-wide maps of three-dimensional chromatin contacts. However, robust estimation of data quality and systematic comparison of these contact maps is challenging due to the multi-scale, hierarchical structure of chromatin contacts and the resulting properties of experimental noise in the data. Measuring concordance of contact maps is important for assessing reproducibility of replicate experiments and for modeling variation between different cellular contexts. Results We introduce a concordance measure called DIfferences between Smoothed COntact maps (GenomeDISCO) for assessing the similarity of a pair of contact maps obtained from chromosome conformation capture experiments. The key idea is to smooth contact maps using random walks on the contact map graph, before estimating concordance. We use simulated datasets to benchmark GenomeDISCO's sensitivity to different types of noise that affect chromatin contact maps. When applied to a large collection of Hi-C datasets, GenomeDISCO accurately distinguishes biological replicates from samples obtained from different cell types. GenomeDISCO also generalizes to other chromosome conformation capture assays, such as HiChIP. Availability and implementation Software implementing GenomeDISCO is available at https://github.com/kundajelab/genomedisco. Supplementary information Supplementary data are available at Bioinformatics online.
Montmorillonite K10 clay-catalyzed synthesis of homoallylic silyl ethers: an efficient and environmentally friendly Hosomi–Sakurai reaction

Aromatic aldehydes react with allyltrimethylsilane in the presence of activated Montmorillonite K10 clay to give homoallylic silyl ethers in good to excellent yields.
Effective 1,4-Asymmetric C−C/C−O Stereoinduction in Indium-Promoted Coupling Reactions of Aldehydes to Protected and Unprotected [1-(Bromomethyl)vinyl] Alkanols. The Status of Intramolecular Chelation within Functionalized Allylindium Reagents

The stereochemistry of the coupling reactions of oxygen-substituted bromides 8−10 with isobutyraldehyde, benzaldehyde, and cyclohexanecarboxaldehyde in water is described. The examples involving the O-silylated derivatives 8 exhibit moderate anti stereoselectivity. In contrast, rather high (most often in excess of 80:20) syn diastereofacial bias is observed when hydroxy bromides 10 are involved. Consequently, stereocontrolled 1,4-asymmetric induction under aqueous conditions can be realized in either direction on demand. These results are considered to reflect the fact that the siloxy systems enter into C−C bond formation via conventional Felkin−Anh transition state arrangements. The crossover observed for the unprotected analogues is believed to be a consequence of the preferred adoption of chelated transition states, these interactions likely being fundamental to aqueous organometallic chemistry.