cssi/SciSciGPT-SciSciNet huggingface dataset:
How do legal standards matter? An empirical study of special litigation committees

Abstract We examine how legal standards affect outcomes in shareholder lawsuits where the defendants create Special Litigation Committees (SLCs). We compile a hand-collected sample of SLC associated lawsuits spanning a 26-year period from Jan 1, 1990 through Dec 31, 2015. We produce extensive descriptive statistics on the utilization, role and effect of SLCs. We find evidence that law matters for SLC outcomes: case dismissals are the lowest in Delaware jurisdiction where the courts apply stricter standards of judicial review. But in states with the weakest legal standards for SLC judicial review, SLC cases are more likely to be dismissed. Defense lawyers appear to exploit these differences to obtain dismissals at a higher rate, potentially impacting shareholder value. Our results have implications for the legal standard of review for SLC cases.
A conserved energy for axially symmetric Newman-Penrose-Maxwell scalars on Kerr black holes

We show that there exists a 1-parameter family of positive-definite and conserved energy functionals for axially symmetric NewmanPenroseMaxwell scalars on the maximal space-like hypersurfaces in th...
Preoperative MRI-radiomics features improve prediction of survival in glioblastoma patients over MGMT methylation status alone.

// Florent Tixier 1 , Hyemin Um 1 , Dalton Bermudez 1 , Aditi Iyer 1 , Aditya Apte 1 , Maya S. Graham 2 , Kathryn S. Nevel 2, 3 , Joseph O. Deasy 1 , Robert J. Young 4, 5, * and Harini Veeraraghavan 1, * 1 Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York, USA 2 Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA 3 Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA 4 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA 5 Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA * Co-senior authors Correspondence to: Florent Tixier, email: tixierf@mskcc.org Keywords: magnetic resonance imaging; radiomics; glioblastoma; MGMT; survival analysis Received: October 09, 2018 Accepted: December 22, 2018 Published: January 18, 2019 ABSTRACT Background: Glioblastoma (GBM) is the most common malignant central nervous system tumor, and MGMT promoter hypermethylation in this tumor has been shown to be associated with better prognosis. We evaluated the capacity of radiomics features to add complementary information to MGMT status, to improve the ability to predict prognosis. Methods: 159 patients with untreated GBM were included in this study and divided into training and independent test sets. 286 radiomics features were extracted from the magnetic resonance images acquired prior to any treatments. A least absolute shrinkage selection operator (LASSO) selection followed by Kaplan-Meier analysis was used to determine the prognostic value of radiomics features to predict overall survival (OS). The combination of MGMT status with radiomics was also investigated and all results were validated on the independent test set. Results: LASSO analysis identified 8 out of the 286 radiomic features to be relevant which were then used for determining association to OS. One feature (edge descriptor) remained significant on the external validation cohort after multiple testing (p=0.04) and the combination with MGMT identified a group of patients with the best prognosis with a survival probability of 0.61 after 43 months (p=0.0005). Conclusion: Our results suggest that combining radiomics with MGMT is more accurate in stratifying patients into groups of different survival risks when compared to with using these predictors in isolation. We identified two subgroups within patients who have methylated MGMT : one with a similar survival to unmethylated MGMT patients and the other with a significantly longer OS.
The Effect of an Auditor Identity Disclosure Requirement on Audit Quality: An Experimental Examination Incorporating the Incremental Effect of a Signature Requirement

SUMMARY After considering a proposal to require the engagement partner's signature on the audit report (PCAOB 2009), the Public Company Accounting Oversight Board chose instead to only require the ...
Tumor-intrinsic response to IFNγ shapes the tumor microenvironment and anti-PD-1 response in NSCLC.

Targeting PD-1/PD-L1 is only effective in ∼20% of lung cancer patients, but determinants of this response are poorly defined. We previously observed differential responses of two murine K-Ras–mutant lung cancer cell lines to anti–PD-1 therapy: CMT167 tumors were eliminated, whereas Lewis Lung Carcinoma (LLC) tumors were resistant. The goal of this study was to define mechanism(s) mediating this difference. RNA sequencing analysis of cancer cells recovered from lung tumors revealed that CMT167 cells induced an IFNγ signature that was blunted in LLC cells. Silencing Ifngr1 in CMT167 resulted in tumors resistant to IFNγ and anti–PD-1 therapy. Conversely, LLC cells had high basal expression of SOCS1, an inhibitor of IFNγ. Silencing Socs1 increased response to IFNγ in vitro and sensitized tumors to anti–PD-1. This was associated with a reshaped tumor microenvironment, characterized by enhanced T cell infiltration and enrichment of PD-L1hi myeloid cells. These studies demonstrate that targeted enhancement of tumor-intrinsic IFNγ signaling can induce a cascade of changes associated with increased therapeutic vulnerability.
Annual survey of organometallic metal cluster chemistry for the year 1998

Abstract The synthetic, mechanistic and structural chemistry of organometallic metal cluster compounds is reviewed for the year 1998.
Robust Influence Maximization for Hyperparametric Models

In this paper, we study the problem of robust influence maximization in the independent cascade model under a hyperparametric assumption. In social networks users influence and are influenced by individuals with similar characteristics and as such, they are associated with some features. A recent surging research direction in influence maximization focuses on the case where the edge probabilities on the graph are not arbitrary but are generated as a function of the features of the users and a global hyperparameter. We propose a model where the objective is to maximize the worst-case number of influenced users for any possible value of that hyperparameter. We provide theoretical results showing that proper robust solution in our model is NP-hard and an algorithm that achieves improper robust optimization. We make-use of sampling based techniques and of the renowned multiplicative weight updates algorithm. Additionally, we validate our method empirically and prove that it outperforms the state-of-the-art robust influence maximization techniques.
Direct detection and LHC constraints on a t-channel simplified model of Majorana dark matter at one loop

An interesting class of models posits that the dark matter is a Majorana fermion which interacts with a quark together with a colored scalar mediator. Such a theory can be tested in direct detection experiments, through dark matter scattering with heavy nuclei, and at the LHC, via jets and missing energy signatures. Motivated by the fact that such theories have spin-independent interactions that vanish at tree level, we examine them at one loop (along with RGE improvement to resum large logs), and find that despite its occurrence at a higher order of perturbation theory, the spin-independent scattering searches typically impose the strongest constraints on the model parameter space. We further analyze the corresponding LHC constraints at one loop and find that it is important to take them into account when interpreting the implications of searches for jets plus missing momentum on this class of models, thus providing the corresponding complementary information for this class of models.
Recent results at the tritium systems test assembly

The Tritium Systems Test Assembly (TSTA) project at Los Alamos is charged with developing and demonstrating the tritium technology required for the magnetic fusion energy program. Since June 1987 the project has been operated by Los Alamos National Laboratory under the joint funding of the US Department of Energy (DOE) and the Japan Atomic Energy Research Institute (JAERI). At TSTA the technology under development includes reactor exhaust gas processing technology and safety systems. This project is not currently investigating the processing of tritium extracted from a breeding blanket. The processing of tritium extracted from a breeding blanket is a possible upgrade to TSTA. This possible upgrade is the subject of an ongoing study among Los Alamos, JAERI and the Argonne National Laboratory (ANL). This installing such on upgraded process systems at TSTA in the 1990--1992 time frame. The exhaust gas processing system at TSTA is designed to demonstrate full-scale exhaust gas processing for a fusion machine of a size currently being designed for ITER. Of course, deuterium is also a major component of the exhaust gas. Current gas processing uses a total gas stream comprised of /approximately/65% deuterium, 35% tritium, 1-2% reactive impurities (currently nitrogen and methane) with the remainingmore » gas hydrogen and helium. The tritium inventory required to process through this loop at this rate is about 110 g. The main process loop at TSTA has been operating at this flow rate since July 1987. In addition to the operation of the main process loop, a number of nonloop experiments are underway at TSTA. This paper will update the status of both loop and nonloop studies at Los Alamos.« less
Visible and Infrared Emission from GaN:Er Thin Films Grown by Sputtering

Erbium-doped films were grown on sapphire and silicon substrates by reactive sputtering, with different Er concentrations in the film. GaN films deposited at 800 K were determined to be polycrystalline by x-ray diffraction analysis, and retained their polycrystalline structure after annealing in nitrogen at 1250 K. The Er-doped films showed optical transmission beginning at about 360 nm, and the Er dose and film purity were determined with Rutherford backscattering spectroscopy. Photoluminescence and cathodoluminescence spectroscopy showed sharp emission lines corresponding to Er 3+ intra 4fn shell transitions over the range from 9 - 300 K. At above-bandgap optical and electron excitation, the 4S3/2 and 4F9/2 transition dominate, and are superposed on the "yellow band" emission. The infrared emission line at 1543 nm, corresponding to the Er 4I13/2 to 4I5/2 transition is also observed.
Graph-based Semi-Supervised & Active Learning for Edge Flows

We present a graph-based semi-supervised learning (SSL) method for learning edge flows defined on a graph. Specifically, given flow measurements on a subset of edges, we want to predict the flows on the remaining edges. To this end, we develop a computational framework that imposes certain constraints on the overall flows, such as (approximate) flow conservation. These constraints render our approach different from classical graph-based SSL for vertex labels, which posits that tightly connected nodes share similar labels and leverages the graph structure accordingly to extrapolate from a few vertex labels to the unlabeled vertices. We derive bounds for our method's reconstruction error and demonstrate its strong performance on synthetic and real-world flow networks from transportation, physical infrastructure, and the Web. Furthermore, we provide two active learning algorithms for selecting informative edges on which to measure flow, which has applications for optimal sensor deployment. The first strategy selects edges to minimize the reconstruction error bound and works well on flows that are approximately divergence-free. The second approach clusters the graph and selects bottleneck edges that cross cluster-boundaries, which works well on flows with global trends.
Comparison of unintended pregnancy at 12 months between two contraceptive care programs; a controlled time-trend design.

Abstract Objectives To compare unintended pregnancy rates at 12 months between women receiving structured contraceptive counseling plus usual contraceptive care and women receiving structured contraceptive counseling, healthcare provider education and cost support for long-acting reversible contraceptive (LARC) methods. Study design Using a controlled time-trend study design, we first enrolled 502 women receiving structured contraceptive counseling in addition to usual care (“Enhanced Care”) and subsequently enrolled 506 women receiving counseling plus healthcare provider education and cost support for LARC methods (“Complete CHOICE”) at three federally qualified health centers (FQHCs). Cost support included funds to health centers for “on-the-shelf” LARC methods and no-cost LARC methods for uninsured women. Participants completed in-person baseline surveys and follow-up surveys by telephone at 3, 6 and 12 months. We used Kaplan–Meier survival function to estimate 12-month unintended pregnancy rates and Cox proportional-hazards regression to compare unintended pregnancy rates between the two groups. We imputed pregnancy outcomes for women lost to follow-up (9%) prior to 12 months. Results “Complete CHOICE” participants were less likely to report an unintended pregnancy at 12 months compared to “Enhanced Care”; 5.3 vs. 9.8 pregnancies per 100 women-years (p=.01). After adjusting for confounders (recruitment site, race, age and federal poverty level), women in “Complete CHOICE” had a 40% lower risk of unintended pregnancy at 12 months (adjusted hazard ratio 0.60; 95% confidence interval 0.37–0.99). Conclusions Contraceptive provision that includes cost support and healthcare provider education in addition to patient counseling reduced unintended pregnancy at 12 months compared to counseling plus usual contraceptive care. Implications A program of contraceptive care that includes comprehensive counseling; healthcare provider education; cost support; and on-the-shelf, long-acting reversible contraception can reduce unintended pregnancy compared to contraceptive counseling in addition to usual health center care in the FQHC setting.
One-dimensional polymers and mesogens incorporating multiple bonds between metal atoms.

A synthetic strategy aimed at incorporating metal−metal multiple bonds into one-dimensional polymers and liquid crystals is outlined. Specific examples taken from the use of dimetal tetracarboxylates, where the metals are molybdenum and tungsten, are presented. Depending upon the organic linking group, the one-dimensional polymers may be conducting or charge-storing, and the characterization of discrete dimers of “dimers” is used to illustrate this. The thermotropic and other physicochemical properties of mesogenic M2(O2CR)4 compounds can be related to the intermolecular M2- - -O interactions as a function of M and R.
Water-Compatible Organocatalysts for Direct Asymmetric syn-Aldol Reactions of Dihydroxyacetone and Aldehydes

A novel organocatalyst was developed that effectively catalyzed the reactions of unprotected or protected dihydroxyacetone with a variety of aldehydes to provide syn-aldol products with good yields and ee values up to >99%. Significantly, this amide catalyst was effective with a variety of nonaromatic aldehyde acceptors that had proven difficult in the presence of other catalysts. Reactions of protected dihydroxyacetone proceeded in aqueous media without addition of organic solvents.
Hydrothermal preparation of nickel(II)/uranium(IV) fluorides with one-, two-, and three-dimensional topologies.

A modified compositional diagram for the reactions of Ni(C2H3O2)2·4H2O with UO2(C2H3O2)2·2H2O and HF in aqueous media under mild hydrothermal conditions (200 °C) has been completed to yield three Ni(II)/U(IV) fluorides, Ni(H2O)4UF6·1.5H2O (1), Ni2(H2O)6U3F16·3H2O (2), and Ni(H2O)2UF6(H2O) (3). The structure of 1 consists of one-dimensional columns constructed from two parallel chains of edge-sharing dodecahedral [UF8] units. The sides of the columns are terminated by octahedral Ni(II) units that occur as cis-[Ni(H2O)4F2] polyhedra. In contrast, the crystal structure of 2 reveals a two-dimensional Ni(II)/U(IV) architecture built from edge-sharing tricapped trigonal prismatic [UF9] units. The top and bottom of the sheets are capped by fac-[Ni(H2O)3F3] octahedra. The structure of 3 is formed from [UF8(H2O)] tricapped trigonal prisms that edge share with one another to form one-dimensional chains. These chains are then joined together into a three-dimensional network by corner sharing with trans-[Ni(H2O)2F4] ...
On connectivity, conductance and bootstrap percolation for a random k‐out, age‐biased graph

A uniform attachment graph (with parameter $k$), denoted $G_{n,k}$ in the paper, is a random graph on the vertex set $[n]$, where each vertex $v$ makes $k$ selections from $[v-1]$ uniformly and independently, and these selections determine the edge set. We study several aspects of this graph. Our motivation comes from two similarly constructed, well-studied random graphs: $k$-out graphs and preferential attachment graphs. In this paper, we find the asymptotic distribution of its minimum degree and connectivity, and study the expansion properties of $G_{n,k}$ to show that the conductance of $G_{n,k}$ is of order $(\log n)^{-1}$. We also study the bootstrap percolation on $G_{n,k}$, where, each vertex is either initially infected with probability $p$, independently of others, or gets infected later as a result of having $r$ infected neighbors at some point. We show that, for $2\le r\le k-1$, if $p\ll (\log n)^{-r/(r-1)}$, then, with probability approaching 1, the process ends before all vertices get infected. On the other hand, if $p\ge \omega(\log n)^{-r/(r-1)}$, where $\omega$ is a certain very slowly growing function, then all the vertices get infected with probability approaching 1.
Phototransformations of bridgehead-disubstituted dibenzobarrelenes. Interesting rearrangements of dibenzosemibullvalene intermediates derived from 9-(Hydroxyalkyl)-10-methoxy-substituted dibenzobarrelenes

The photochemistry of 11,12-dibenzoyl-9,10-dihydro-9-(hydroxymethyl)-10-methoxy-9,10-ethenoanthracene and 11,12-dibenzoyl-9,19-dihydro-9-(1-hydroxyethyl)-10-methoxy-9,10-ethenoanthracene has been studied through steady-state photolysis, product analysis, and laser flash photolysis. Irradiation of 7a in benzene, methanol, or acetone gave 69-72% yields of a dibenzopentalene ketone 11a, arising through a dibenzosemibullvalene precursor. Irradiation of 7b, which exists in equilibrium with its cyclic form 7b{prime}, gave a mixture of the dibenzopentalene ketone 11b (41%) and the dibenzopentalenopyran derivative, 16b{prime} (26%). The photochemistry of 11,12-dibenzoyl-9,10-dihydro-9,10-dimethoxy-9,10-ethenoanthracene (17) has been reinvestigated. Irradiation of 17 in benzene and methanol gives a 90% yield of an isomeric pentacyclic product 24, formed through the rearrangement of a dibenzosemibullvalene precursor. Irradiation of 17 in aqueous methanol gives a mixture of the dibenzopentalene ketone 22 (40%) and a pentacyclic methanol adduct 21 (34%). The structures of 7b{prime}, 11a,b,16b{prime},21, and 24 were confirmed through X-ray crystallographic analysis. The 308 nm laser flash photolysis of 1a,b in benzene results in the formation of their triplets ({phi}{sup T} = 0.55-0.76). These triplets possess short lifetimes (0.45-0.75 {mu}s) and are quenched by oxygen, 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO), 4-hydroxy-2,2,6,6- tetramethylpiperidinyl-1-oxy (HTEMPO), ferrocene, and {beta}-carotene at rates in the range (0.26-4.7) x 10{sup 9} M{sup -1} s{sup -1}. 21 refs., 1 fig., 1 tab.
2-tert-butyl-3-methyl-2,3-dihydroimidazol- 4-one-N-oxide: a new nitrone-based chiral glycine equivalent.

Cycloaddition reactions between a new homochiral imidazolone-derived nitrone afford cycloadducts in high yield and with high stereoselectivity. Subsequent cycloadduct elaboration affords the γ-lact...
Rearrangement of o-alkynyl substituted α-diazoacetophenones. Conversion to β-naphthols via arylketene intermediates

Abstract In contrast to the rhodium (II) mediated cycloisomerization of o-alkynyl substituted α-diazoacetophenones, irradiation leads to β-naphthols which are formed via cyclization of an arylketene intermediate.
Trait heritability in major transitions.

Increases in biological complexity and the origins of life’s hierarchical organization are described by the “major transitions” framework. A crucial component of this paradigm is that after the transition in complexity or organization, adaptation occurs primarily at the level of the new, higher-level unit. For collective-level adaptations to occur, though, collective-level traits—properties of the group, such as collective size—must be heritable. Since collective-level trait values are functions of lower-level trait values, collective-level heritability is related to particle-level heritability. However, the nature of this relationship has rarely been explored in the context of major transitions. We examine relationships between particle-level heritability and collective-level heritability for several functions that express collective-level trait values in terms of particle-level trait values. For clonal populations, when a collective-level trait value is a linear function of particle-level trait values and the number of particles per collective is fixed, the heritability of a collective-level trait is never less than that of the corresponding particle-level trait and is higher under most conditions. For more complicated functions, collective-level heritability is higher under most conditions, but can be lower when the environment experienced by collectives is heterogeneous. Within-genotype variation in collective size reduces collective-level heritability, but it can still exceed particle-level heritability when phenotypic variance among particles within collectives is large. These results hold for a diverse sample of biologically relevant traits. Rather than being an impediment to major transitions, we show that, under a wide range of conditions, the heritability of collective-level traits is actually higher than that of the corresponding particle-level traits. High levels of collective-level trait heritability thus arise “for free,” with important implications not only for major transitions but for multilevel selection in general.
Applications of SAT Solvers to Cryptanalysis of Hash Functions.

Several standard cryptographic hash functions were broken in 2005. Some essential building blocks of these attacks lend themselves well to automation by encoding them as CNF formulas, which are within reach of modern SAT solvers. In this paper we demonstrate effectiveness of this approach. In particular, we are able to generate full collisions for MD4 and MD5 given only the differential path and applying a (minimally modified) off-the-shelf SAT solver. To the best of our knowledge, this is the first example of a SAT-solver-aided cryptanalysis of a non-trivial cryptographic primitive. We expect SAT solvers to find new applications as a validation and testing tool of practicing cryptanalysts.
On the Adjoint Markov Policies in Stochastic Differential Games

We consider time-homogeneous uniformly nondegenerate stochastic differential games in domains and propose constructing $\varepsilon$-optimal strategies and policies by using adjoint Markov strategies and adjoint Markov policies which are actually time-homogeneous Markov, however, relative not to the original process but to a couple of processes governed by a system consisting of the main original equation and of an adjoint stochastic equations of the same type as the main one. We show how to find $\varepsilon$-optimal strategies and policies in these classes by using the solvability in Sobolev spaces of not the original Isaacs equation but of its appropriate modification. We also give an example of a uniformly nondegenerate game where our assumptions are not satisfied and where we conjecture that there are no not only optimal Markov but even $\varepsilon$-optimal adjoint (time-homogeneous) Markov strategies for one of the players.
Total syntheses of (+)-australine and (-)-7-epialexine.

Three approaches were examined for the synthesis of 3-(hydroxymethyl)pyrrolizidines, a class of compounds that includes the polyhydroxylated pyrrolizidine alkaloids alexine (1), australine (2), and various stereoisomers of thereof. In the first approach, the intramolecular cycloaddition of an azide onto an electron-rich 1, 3-diene bearing a terminal alkoxymethyl substituent (i.e., 21) afforded the dehydropyrrolizidines 22a and 22b, with 22a predominating. A rationale for this stereoselectivity was proposed. Transformation of the major diastereomer 22a into a natural 3-(hydroxymethyl)pyrrolizidine was not possible due to difficulties encountered in transforming the phenyl vinyl sulfide functionality into other useful functional groups. A second approach was examined, wherein the intramolecular cycloaddition of an azide with an optically pure S-t-Bu-substituted diene (i.e., 30) was found to produce the pyrrolizidine 31. In this case, the alkoxymethyl substituent was incorporated into the tether between the azide and the diene, rather than on the diene itself. A key transformation in the synthesis of the diene 30 was the use of the allylic borane R(2)BCH(2)CH=C(TMS)(StBu) for the stereoselective conversion of the D-arabinose-derived azido aldehyde 28 to the E-isomer of 30. The cyclization of 30 to 31 also produced the bicyclic triazene 32, the result of 1,3-dipolar cycloaddition of the azide onto the distal double bond of the diene. Again, difficulties in transformation of the vinyl sulfide functionality of 31 into useful oxygen functionality limited this approach to naturally occurring 3-(hydroxymethyl)pyrrolizidines. A third approach to these compounds was successful. The transformation of L-xylose into the azido epoxy tosylate 46 was accomplished using two Wittig reactions and an epoxidation, in addition to other standard functional group manipulations. Reductive double-cyclization of 46 afforded the pyrrolizidines 47a and 47b, which were debenzylated to afford (+)-australine 2 and (-)-7-epialexine 4, respectively. In the preliminary report of this work, erroneous spectroscopic data in the original literature on the structural assignment of australine led to the conclusion that the synthetic material obtained herein was actually (+)-7-epiaustraline. Recently corrected spectroscopic data have appeared which verify that (+)-australine 2 was indeed synthesized for the first time.
Ceric ammonium nitrate promoted oxidation of oxazoles.

The ceric ammonium nitrate promoted oxidations of 4,5-diphenyloxazoles and oxazoles with various substitution patterns have been investigated. This transformation results in the formation of the corresponding imide in good yield and tolerates a wide variety of functional groups and substituents on the oxazole moiety.
Regulation of the Erythrobacter litoralis DSM 8509 general stress response by visible light.

Extracytoplasmic function (ECF) sigma factors are environmentally responsive transcriptional regulators. In Alphaproteobacteria, σEcfG activates general stress response (GSR) transcription and protects cells from multiple stressors. A phosphorylation-dependent protein partner switching mechanism, involving HWE/HisKA_2-family histidine kinases, underlies σEcfG activation. The identity of these sensor kinases and the signals that regulate them remain largely uncharacterized. We have developed the aerobic anoxygenic photoheterotroph (AAP), Erythrobacter litoralis DSM 8509, as a comparative genetic model to investigate GSR. Using this system, we sought to define the role of visible light and a photosensory HWE kinase, LovK, in regulation of GSR transcription. We identified three HWE kinase genes that collectively control GSR: gsrK and lovK are activators, while gsrP is a repressor. In wild-type cells, GSR transcription is activated in the dark and nearly off in the light, and the opposing activities of gsrK and gsrP are sufficient to modulate GSR transcription in response to illumination. In the absence of gsrK and gsrP, lovK alone is sufficient to activate GSR transcription. lovK is a more robust activator in the dark, and light-dependent regulation by LovK requires that its N-terminal LOV domain be photochemically active. Our studies establish a role for visible light and an ensemble of HWE kinases in light-dependent regulation of GSR transcription in E. litoralis.
An Asymmetric Route to Novel Chiral Cyclohexenones with Spiro-Connected Cyclopentenes. Further Utility of Chiral Bicyclic Thiolactams and the [3,3] Thio-Claisen Products.

Sequential allylation of chiral, nonracemic thiolactam 8 affords clean thio-Claisen [3,3] products 11. The stereoselectivity of the rearrangement was found to be on the order of 10−11:1, with the exo-endo products responsible for the mixture. Addition of hydride or methyllithium−cerium chloride gave clean addition to the thiolactam in the form of its iminium salts 12. Hydrolysis gave 4,4-dialkylcyclohexenones 15, which were cyclized to the cyclopentene derivatives 16 using Grubbs' catalyst.
Ytterbium trichloride-catalyzed allylation of aldehydes with allyltrimethylsilane

Abstract Ytterbium chloride (YbCl 3 ) is found to be an effective catalyst for the allylation of both aromatic and aliphatic aldehydes using allyltrimethylsilane.
Chemogenetic Manipulations of Ventral Tegmental Area Dopamine Neurons Reveal Multifaceted Roles in Cocaine Abuse

Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles in addiction-related behaviors are still debated. Here, we targeted VTA DA neurons for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, and relapse-related behaviors in male rats, querying the roles of DA neuron inhibitory and excitatory G-protein signaling in these processes. Designer receptor stimulation of Gq signaling, but not Gs signaling, in DA neurons enhanced cocaine seeking via functionally distinct projections to forebrain limbic regions. In contrast, engaging inhibitory Gi/o signaling in DA neurons blunted the reinforcing and priming effects of cocaine, reduced stress-potentiated reinstatement, and altered behavioral strategies for cocaine seeking and taking. Results demonstrate that DA neurons play several distinct roles in cocaine seeking, depending on behavioral context, G-protein-signaling cascades, and DA neuron efferent targets, highlighting their multifaceted roles in addiction.SIGNIFICANCE STATEMENT G-protein-coupled receptors are crucial modulators of ventral tegmental area (VTA) dopamine neuron activity, but how this metabotropic signaling impacts the complex roles of dopamine in reward and addiction is poorly understood. Here, we bidirectionally modulate dopamine neuron G-protein signaling with DREADDs (designer receptors exclusively activated by designer drugs) during a variety of cocaine-seeking behaviors, revealing nuanced, pathway-specific roles in cocaine reward, effortful seeking, and relapse-like behaviors. Gq and Gs stimulation activated dopamine neurons, but only Gq stimulation robustly enhanced cocaine seeking. Gi/o inhibitory signaling reduced some, but not all, types of cocaine seeking. Results show that VTA dopamine neurons modulate numerous distinct aspects of cocaine addiction- and relapse-related behaviors, and point to potential new approaches for intervening in these processes to treat addiction.
Total Synthesis of the Antitumor Marine Sponge Alkaloid Agelastatin A

The first total synthesis of the cytotoxic marine metabolite agelastatin A (1) has been achieved in about 14 steps performed in 12 operations in approximately 7% overall yield starting from cyclopentadiene. Hetero Diels−Alder cycloaddition of cyclopentadiene with N-sulfinyl methyl carbamate (7) afforded cycloadduct 8, which without purification was converted to allylic sulfoxide 9 and then by a [2,3]-sigmatropic rearrangement into bicyclic oxazolidinone 11. The C-5a nitrogen was introduced into the oxazolidinone Boc derivative 16 by a Sharpless/Kresze allylic amination with SES sulfodiimide 12c. Palladium-promoted cyclization of 2-acyl pyrroles 20 and 21 via a π-allylpalladium intermediate 22 led to ABC-tricycles 23 and 24, respectively. A hydroxyl urea D-ring model system was constructed by hydroborating 24, leading eventually to keto amide 31 and then to tetracycle 33. A modified strategy was developed for synthesis of the pivotal tricyclic ketone 58, involving as key steps a chemoselective hydrolysis o...
COSMIC ACCELERATION AND MODIFIED GRAVITY

I briefly discuss some attempts to construct a consistent modification to general relativity (GR) that might explain the observed late-time acceleration of the Universe and provide an alternative to dark energy. I describe the issues facing extensions to GR, illustrate these with a specific example, and discuss the resulting observational and theoretical obstacles.
Short DNA sequence patterns accurately identify broadly active human enhancers

Enhancers are DNA regulatory elements that influence gene expression. There is substantial diversity in enhancers’ activity patterns: some enhancers drive expression in a single cellular context, while others are active across many. Sequence characteristics, such as transcription factor (TF) binding motifs, influence the activity patterns of regulatory sequences; however, the regulatory logic through which specific sequences drive enhancer activity patterns is poorly understood. Recent analysis of Drosophila enhancers suggested that short dinucleotide repeat motifs (DRMs) are general enhancer sequence features that drive broad regulatory activity. However, it is not known whether the regulatory role of DRMs is conserved across species. We performed a comprehensive analysis of the relationship between short DNA sequence patterns, including DRMs, and human enhancer activity in 38,538 enhancers across 411 different contexts. In a machine-learning framework, the occurrence patterns of short sequence motifs accurately predicted broadly active human enhancers. However, DRMs alone were weakly predictive of broad enhancer activity in humans and showed different enrichment patterns than in Drosophila. In general, GC-rich sequence motifs were significantly associated with broad enhancer activity, and consistent with this enrichment, broadly active human TFs recognize GC-rich motifs. Our results reveal the importance of specific sequence motifs in broadly active human enhancers, demonstrate the lack of evolutionary conservation of the role of DRMs, and provide a computational framework for investigating the logic of enhancer sequences.
Study of Differences in the Reactivity of Alkyl and Aryl Nitrones Derived from 4-oxo-4H-1-Benzopyran-3-Carboxaldehyde:

On hydrolysis with 70% H2SO4, aliphatic nitrones 2a–d produce the corresponding carboxylic acids 4 but aromatic nitrones 2e, f give aldehyde 1. On heating under reflux in dry MeOH, 2a–d rearrange t...
Regioselective [2 + 2 + 2] cycloaddition of a nickel-benzyne complex with 1,3-diynes.

Reactions of nickel(0)−benzyne complexes with a range of symmetrically substituted 1,3-diynes in the presence of triethylphosphine lead to the regioselective formation of 2,3-dialkynyl naphthalenes. The regioselectivity can be reversed when the diyne possesses substituents of high steric bulk, allowing selective formation of either symmetric dialkynyl naphthalene.
"Fleximers". Design and synthesis of two novel split nucleosides.

A new class of shape-modified nucleosides is introduced. The purine heterobases of adenosine and guanosine have been split into their imidazole and pyrimidine components, thereby introducing flexibility while retaining the elements necessary for recognition. As a consequence, these novel “fleximers” should find use as bioprobes for investigating enzyme−coenzyme binding sites as well as nucleic acid and protein interactions. Their design and synthesis is described.
Electronic and steric effects in thermal denitrosation of N-nitrosoamides.

N-Alkyl-N-nitrosoamides undergo competitive reactions whose rates are dependent upon the interplay of a number of factors. There already exists a significant body of work delineating the effects of pH on the partitioning of the nitrosoamides along their deaminative (-N(2)) and denitrosative (-"NO(+)") pathways. In this paper, the issue of pH dependence is discussed with particular attention to nitrosoamide decompositions in nonaqueous media. The role of the acidity of the medium in the partitioning of the nitrosoamide between deamination and denitrosation and in the choice of deaminative pathways is revisited. In nonaqueous media under near-neutral conditions, the partitioning's pH dependence is evidently accompanied by a sensitivity to structural features in the nitrosoamide. Thus, diminution of steric crowding around the N-nitroso moiety as well as the presence of strongly electron-withdrawing acyl units (i.e., those derived from strong acids, e.g., tosyl and trifyl) increase the relative yield of amides by encouraging the denitrosative pathway. A mechanism for thermal denitrosation of nitrosoamides under near-neutral conditions is proposed in which rapid protonation at the acyl O rather than slow protonation at the amidic N is the first step in the reaction profile. A rate-limiting, bimolecular reaction between the O-conjugate acid and adventitious nucleophiles at the nitrosyl group then occurs followed by rapid tautomerization to amide.
Novel Methodology for the Synthesis of N-Alkoxyamines

We report a new methodology for the synthesis of the N-alkoxyamines, which can be used as initiators in “living” free radical polymerization. Silyl radical abstraction from alkyl halides allows the synthesis of N-alkoxyamines inaccessible by other methods.
Stereoselective synthesis of 4-aryl-2-(benzyloxy)carbonyl-3-hydroxy tetrahydrofurans from aryl epoxides

Abstract The stereoselective synthesis of 4-aryl substituted tetrahydrofurans from benzyl diazoacetate and aryl epoxides is described.
STEREOCONTROL IN ONE-POT SYNTHESES OF 1,3-DIOLS

Abstract Titanium mediated aldol addition reduction sequence is described for the synthesis of stereodefined 1,3-diols. Diastereochemical control is surprisingly achieved through the careful selection of starting materials used.
Selective monosulfonylation of internal 1,2-diols catalyzed by di-n-butyltin oxide

Abstract The reaction of internal 1,2-diols with catalytic n-Bu2SnO, p-TsCl (1.05 equiv.) and Et3N (1.1 equiv.) led to selective monotosylation. In the case of cyclic substrates, the cis-1,2-diol moiety appeared best suited for optimal results, supporting the intermediacy of a five-membered chelate.
A Probability Distribution over Latent Causes, in the Orbitofrontal Cortex

The orbitofrontal cortex (OFC) has been implicated in both the representation of “state,” in studies of reinforcement learning and decision making, and also in the representation of “schemas,” in studies of episodic memory. Both of these cognitive constructs require a similar inference about the underlying situation or “latent cause” that generates our observations at any given time. The statistically optimal solution to this inference problem is to use Bayes9 rule to compute a posterior probability distribution over latent causes. To test whether such a posterior probability distribution is represented in the OFC, we tasked human participants with inferring a probability distribution over four possible latent causes, based on their observations. Using fMRI pattern similarity analyses, we found that BOLD activity in the OFC is best explained as representing the (log-transformed) posterior distribution over latent causes. Furthermore, this pattern explained OFC activity better than other task-relevant alternatives, such as the most probable latent cause, the most recent observation, or the uncertainty over latent causes. SIGNIFICANCE STATEMENT Our world is governed by hidden (latent) causes that we cannot observe, but which generate the observations we see. A range of high-level cognitive processes require inference of a probability distribution (or “belief distribution”) over the possible latent causes that might be generating our current observations. This is true for reinforcement learning and decision making (where the latent cause comprises the true “state” of the task), and for episodic memory (where memories are believed to be organized by the inferred situation or “schema”). Using fMRI, we show that this belief distribution over latent causes is encoded in patterns of brain activity in the orbitofrontal cortex, an area that has been separately implicated in the representations of both states and schemas.
α-Phosphono Lactone Analogues of Cytidine and Cytosine Arabinoside Diphosphates: Synthesis via Ring Closing Metathesis

alpha-Phosphono lactone derivatives of the nucleosides cytidine and cytosine arabinoside have been prepared from the corresponding nucleoside aldehydes. The stereochemical outcome of allylation reactions with these aldehydes was found to be dependent upon both the choice of protecting groups for the 2'- and 3'-hydroxyl groups and, to some extent, the nature of the Lewis acid catalyst employed. Ultimately, conditions were found that favored either the 5'R or 5'S diastereomer from different cytidine aldehydes, and gave some stereoselectivity in additions to an aldehyde derivative of ara-C. The resulting homoallylic alcohols were used as substrates in attempted Knovenagel and Horner-Wadsworth-Emmons condensations, but elimination was found to predominate over lactone formation under the conditions employed. The desired alpha-phosphono lactones could be prepared through a reaction sequence that included ring-closing metathesis on acrylate esters of the homoallylic alcohols, followed by reduction of the resulting alpha,beta-unsaturated lactones and carbon-phosphorus bond formation on enolates generated from the saturated lactones.
Enantioselective formation of quaternary stereocenters using the catalytic intramolecular Stetter reaction

Abstract Asymmetric formation of quaternary stereocenters has been accomplished using the catalytic intramolecular Stetter reaction. A variety of tethered aldehydes and Michael acceptors are cyclized in excellent yields and enantioselectivities.
A potentially general method to control relative stereochemistry in enone–olefin 2+2-photocycloaddition reactions by using eniminium salt surrogates†

Abstract A new strategy to control the stereochemistry of enone–olefin 2+2-photocycloaddition reactions, based on the use of eniminium salt surrogates, is experimentally tested. In contrast to enone–olefin photocycloadditions, which emanate from enone triplet excited states and follow non-concerted pathways, analogous reactions of conjugated eniminium salts can occur by singlet, concerted routes and, as a result, would deliver cyclobutane ring containing products with complete control of relative stereochemistry. This proposal was tested by using a series of eniminium salts, which contain electron rich and electron poor olefin tethers. The results show that intramolecular 2+2-photocycloadditions of these substrates display moderate to high degrees of stereospecificity.
Estimation of allele-specific fitness effects across human protein-coding sequences and implications for disease

A central challenge in human genomics is to understand the cellular, evolutionary, and clinical significance of genetic variants. Here, we introduce a unified population-genetic and machine-learning model, called Linear Allele-Specific Selection InferencE (LASSIE), for estimating the fitness effects of all observed and potential single-nucleotide variants, based on polymorphism data and predictive genomic features. We applied LASSIE to 51 high-coverage genome sequences annotated with 33 genomic features and constructed a map of allele-specific selection coefficients across all protein-coding sequences in the human genome. This map is generally consistent with previous inferences of the bulk distribution of fitness effects but reveals pervasive weak negative selection against synonymous mutations. In addition, the estimated selection coefficients are highly predictive of inherited pathogenic variants and cancer driver mutations, outperforming state-of-the-art variant prioritization methods. By contrasting our estimated model with ultrahigh coverage ExAC exome-sequencing data, we identified 1118 genes under unusually strong negative selection, which tend to be exclusively expressed in the central nervous system or associated with autism spectrum disorder, as well as 773 genes under unusually weak selection, which tend to be associated with metabolism. This combination of classical population genetic theory with modern machine-learning and large-scale genomic data is a powerful paradigm for the study of both human evolution and disease.
The impact of unexpected natural disasters on insurance markets

In this paper, we examine the impact of unexpected natural disasters on the insurance industry. The industry is exposed to greater risks in states with large populations. Hence, we normalize the un...
Sticking Probability of High-Energy Methane on Crystalline, Amorphous, and Porous Amorphous Ice Films

We present research detailing the sticking probability of CH4 on various D2O ices of terrestrial and astrophysical interest using a combination of time-resolved, in situ reflection absorption infra...
Existence results for the nonlinear Hodge minimal surface energy

Given a compact Riemannian manifold $$(M^n,g)$$ and a fixed cohomology class, $$[\alpha ^*] \in H^k(M)$$ , we consider the existence of a minimizer $$\alpha \in [\alpha ^*]$$ of the generalized minimal surface energy $$\int _M \sqrt{1+|\alpha |^2} dV_g$$ . When $$k = 1$$ , we prove the existence of unique minimizers for every cohomology class $$[\alpha ^*]$$ . Next, when $$k > 1$$ , we construct examples of singular solutions for finite cohomology class $$[\alpha ^*] \in H^k(S^k \times S^k,g)$$ , where g is conformal to the standard metric on $$S^k \times S^k$$ . Additionally, we show that when $$k=2$$ , these singular solutions are also solutions to the Born Infeld equation.
Rank aggregation: New bounds for MCx

Abstract The rank aggregation problem has received significant recent attention within the computer science community. Its applications today range far beyond the original aim of building metasearch engines to problems in machine learning, recommendation systems and more. Several algorithms have been proposed for these problems, and in many cases approximation guarantees have been proven for them. However, it is also known that some Markov chain based algorithms (MC1, MC2, MC3, MC4) perform extremely well in practice, yet had no known performance guarantees. We prove supra-constant lower bounds on approximation guarantees for all of them. Nevertheless, we show that in particular ways, MC4 can be seen as a generalization of Copeland score.
An inequality for sums of binary digits, with application to Takagi functions

Abstract Let ϕ ( x ) = 2 inf { | x − n | : n ∈ Z } , and define for α > 0 the function f α ( x ) = ∑ j = 0 ∞ 1 2 α j ϕ ( 2 j x ) . Tabor and Tabor [J. Tabor, J. Tabor, Takagi functions and approximate midconvexity, J. Math. Anal. Appl. 356 (2) (2009) 729–737] recently proved the inequality f α ( x + y 2 ) ⩽ f α ( x ) + f α ( y ) 2 + | x − y | α , for α ∈ [ 1 , 2 ] . By developing an explicit expression for f α at dyadic rational points, it is shown in this paper that the above inequality can be reduced to a simple inequality for weighted sums of binary digits. That inequality, which seems of independent interest, is used to give an alternative proof of the result of Tabor and Tabor, which captures the essential structure of f α .