cssi/SciSciGPT-SciSciNet huggingface dataset:
Voluntary Disclosures When There Is an Option to Delay Disclosure

What incentives drive managers to disclose immediately when they have an option to delay disclosures? I examine this question in a two‐period setting in which public news that is positively correlated with firm value arrives periodically. I show that, when the manager's likelihood of receiving information is independent of the public news, an informed manager is more likely to disclose immediately when the public news is good. This happens even as the disclosure threshold itself increases in the public news. My model provides a potential explanation for why managers have a higher propensity to provide earnings forecasts when current earnings are high. I also show that, even when disclosures are credible, the average price reaction to a voluntary disclosure is (i) decreasing in the magnitude of the public news and (ii) lower when the manager is more myopic. These results have potential implications for studies that use stock returns to measure the news contained in management disclosures. La communication d'information facultative quand s'offre la possibilite d'en reporter la publication Quelles motivations amenent les dirigeants a communiquer l'information sans attendre lorsque s'offre a eux la possibilite d'en reporter la publication ? L'auteur se penche sur cette question en se concentrant plus particulierement sur deux periodes au cours desquelles des nouvelles publiques affichant une correlation positive avec la valeur de l'entreprise sont periodiquement communiquees. Il constate que, lorsque la probabilite que le gestionnaire recoive de l'information est independante des nouvelles publiees, un gestionnaire eclaire est davantage susceptible de communiquer l'information sans attendre lorsque les nouvelles publiques sont favorables. Il en est ainsi meme lorsque le seuil de publication lui‐meme augmente dans les nouvelles publiques. Le modele de l'auteur fournit une explication potentielle des raisons pour lesquelles les gestionnaires sont davantage enclins a produire des previsions de resultats lorsque les resultats de la periode sont eleves. L'auteur montre egalement que, meme lorsque l'information communiquee est credible, la reaction du cours moyen a la communication d'information facultative a) diminue avec la multiplicite des nouvelles publiques et b) est moins importante lorsque le gestionnaire affiche une plus grande myopie. Ces resultats auront sans doute des repercussions sur les etudes dans lesquelles est utilise le rendement des actions pour l'appreciation des nouvelles contenues dans l'information publiee par la direction.
Dance Education Certification in Alabama: Issues Related to Undergraduate Degree Programming.

ABSTRACTThe 2001 reauthorization of the Elementary and Secondary Education Act defined dance as an art form, designated the arts as core academic subjects, and called for highly qualified instructors in every classroom. These developments provided new opportunities for dance faculty in higher education preparing their students for life after college. Using a case study approach, the author investigated how postsecondary dance programs in the state of Alabama responded to changes in public policy. Informed by the theoretical lens of Anthony Giddens (1984) and the conceptual frame of Lee Bolman and Terrance Deal (2008), the study uncovered issues related to dance education programming and certification in the state of Alabama.
Transfer Learning for Aided Target Recognition: Comparing Deep Learning to other Machine Learning Approaches

Aided target recognition (AiTR), the problem of classifying objects from sensor data, is an important problem with applications across industry and defense. While classification algorithms continue to improve, they often require more training data than is available or they do not transfer well to settings not represented in the training set. These problems are mitigated by transfer learning (TL), where knowledge gained in a well-understood source domain is transferred to a target domain of interest. In this context, the target domain could represents a poorly-labeled dataset, a different sensor, or an altogether new set of classes to identify. While TL for classification has been an active area of machine learning (ML) research for decades, transfer learning within a deep learning framework remains a relatively new area of research. Although deep learning (DL) provides exceptional modeling flexibility and accuracy on recent real world problems, open questions remain regarding how much transfer benefit is gained by using DL versus other ML architectures. Our goal is to address this shortcoming by comparing transfer learning within a DL framework to other ML approaches across transfer tasks and datasets. Our main contributions are: 1) an empirical analysis of DL and ML algorithms on several transfer tasks and domains including gene expressions and satellite imagery, and 2) a discussion of the limitations and assumptions of TL for aided target recognition -- both for DL and ML in general. We close with a discussion of future directions for DL transfer.
Synthesis of benzonorbornadienes: regioselective benzyne formation.

This report details the synthesis of several benzonorbornadienes by Diels−Alder cycloaddition of cyclopentadiene derivatives with substituted benzyne intermediates, which were generated by low-temperature metal−halogen exchange of halobenzenes. General conditions were developed, allowing synthesis of most benzonorbornadienes described herein at the multigram scale with isolated yields approaching 90% in some cases. Cycloaddition of the benzyne produced by substitution of a chlorodifluorobenzene for a bromodifluorobenzene in the metal−halogen exchange reaction unexpectedly gave a different benzonorbornadiene. The benzyne, which resulted by a deprotonation pathway rather than by metal−halogen exchange, formed in a highly regioselective elimination step.
Synthesis of 1-(2-Indolyl)pyridinium salts: a prodrug approach to acetylcholinesterase inhibition

Abstract 1-(2-Indoyl)pyridinium bromide 2 has been synthesized as a potential acetylcholinesterase inhibitor suitable for administration in the form of a dihydropyridine prodrug. The synthesis of salt 3 is also described
Photodissociation of Cu2NH3 and Ag2NH3

We report on the reactions of copper and silver dimers with ammonia in the gas phase near room temperature and on photodissociation of the 1:1 complexes. Photodissociation action spectra in the range 295−360 nm and emission spectra of metal dimers produced by photodissociation are described. The binding energies of NH3 on Cu2 and Ag2 have been determined, and spectroscopic data and theoretical results have been used to infer a quasi-linear or end-on coordination geometry for the complexes. A simple picture of the bonding mechanism is presented, and comparisons are made with ammonia adsorbed on copper and silver atoms and bulk surfaces.
Ultraconserved Elements Occupy Specific Arenas of Three-Dimensional Mammalian Genome Organization

Summary This study explores the relationship between three-dimensional genome organization and ultraconserved elements (UCEs), an enigmatic set of DNA elements that are perfectly conserved between the reference genomes of distantly related species. Examining both human and mouse genomes, we interrogate the relationship of UCEs to three features of chromosome organization derived from Hi-C studies. We find that UCEs are enriched within contact domains and, further, that the subset of UCEs within domains shared across diverse cell types are linked to kidney-related and neuronal processes. In boundaries, UCEs are generally depleted, with those that do overlap boundaries being overrepresented in exonic UCEs. Regarding loop anchors, UCEs are neither overrepresented nor underrepresented, but those present in loop anchors are enriched for splice sites. Finally, as the relationships between UCEs and human Hi-C features are conserved in mouse, our findings suggest that UCEs contribute to interspecies conservation of genome organization and, thus, genome stability.
Temperature drives Zika virus transmission: evidence from empirical and mathematical models.

Temperature is a strong driver of vector-borne disease transmission. Yet, for emerging arboviruses we lack fundamental knowledge on the relationship between transmission and temperature. Current mo...
Direct conversion of aryl halides to phenols using high-temperature or near-critical water and microwave heating

The direct conversion of aryl halides to the corresponding phenols has been achieved using microwave heating. High-temperature or near-critical water is used as the solvent in conjunction with a copper catalyst and a mineral base.
Pressure-Induced Amorphization and Phase Transformations in β-LiAlSiO4

Τhis work presents a comprehensive study on pressure-induced amorphization (PIA) in β-eucryptite (LiAlSiO4) and on the equilibrium states of so-formed amorphous phase at elevated temperatures. Our ...
Marine Natural Products as Antituberculosis Agents

Abstract In an attempt to characterize additional structural classes that could serve as lead antituberculosis agents, 48 structurally diverse marine-derived natural and semisynthetic compounds were examined for in vitro activity against Mycobacterium tuberculosis . Three new classes of compounds including C-19 hydroxy steroids, scalarin sesquiterpenoids and tetrabromo spirocyclohexadienylisoxazolines have been identified as having potential as leads for continued investigations as new antituberculosis agents. New additions to the established antituberculosis structural classes quinone-methide and peptide are also reported.
The synthesis of substituted [1]benzothieno[2,3‐c]quinolines and their N‐methyl quaternary salts

Four substituted [1]benzothieno[2,3-c]quinolines 14a-14d were prepared by photocyclization of the appropriate carboxamides 8a-8d to the corresponding [1]benzothieno[2,3-c]quinolin-6(5H)-ones 12a-12d followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 13a-13d and dechlorination resulting in the title compounds. Treatment of 14a-14d with iodomethane furnished the corresponding N-methyl quaternary salts 5a-5d.
Inverse design of large-area metasurfaces.

We present a computational framework for efficient optimization-based “inverse design” of large-area “metasurfaces” (subwavelength-patterned surfaces) for applications such as multi-wavelength/multi-angle optimizations, and demultiplexers. To optimize surfaces that can be thousands of wavelengths in diameter, with thousands (or millions) of parameters, the key is a fast approximate solver for the scattered field. We employ a “locally periodic” approximation in which the scattering problem is approximated by a composition of periodic scattering problems from each unit cell of the surface, and validate it against brute-force Maxwell solutions. This is an extension of ideas in previous metasurface designs, but with greatly increased flexibility, e.g. to automatically balance tradeoffs between multiple frequencies or to optimize a photonic device given only partial information about the desired field. Our approach even extends beyond the metasurface regime to non-subwavelength structures where additional diffracted orders must be included (but the period is not large enough to apply scalar diffraction theory).
Investigation of a novel sequential 1,5 O→O silyl migration/Horner–Wadsworth–Emmons reaction

Abstract A study and application of a sequential 1,5 O→O silyl migration/Horner–Wadsworth–Emmons reaction is presented.
Transcriptional responses of Escherichia coli during recovery from inorganic or organic mercury exposure

The protean chemical properties of mercury have long made it attractive for diverse applications, but its toxicity requires great care in its use, disposal, and recycling. Mercury occurs in multiple chemical forms, and the molecular basis for the distinct toxicity of its various forms is only partly understood. Global transcriptomics applied over time can reveal how a cell recognizes a toxicant and what cellular subsystems it marshals to repair and recover from the damage. The longitudinal effects on the transcriptome of exponential phase E. coli were compared during sub-acute exposure to mercuric chloride (HgCl2) or to phenylmercuric acetate (PMA) using RNA-Seq. Differential gene expression revealed common and distinct responses to the mercurials throughout recovery. Cultures exhibited growth stasis immediately after each mercurial exposure but returned to normal growth more quickly after PMA exposure than after HgCl2 exposure. Correspondingly, PMA rapidly elicited up-regulation of a large number of genes which continued for 30 min, whereas fewer genes were up-regulated early after HgCl2 exposure only some of which overlapped with PMA up-regulated genes. By 60 min gene expression in PMA-exposed cells was almost indistinguishable from unexposed cells, but HgCl2 exposed cells still had many differentially expressed genes. Relative expression of energy production and most metabolite uptake pathways declined with both compounds, but nearly all stress response systems were up-regulated by one or the other mercurial during recovery. Sub-acute exposure influenced expression of ~45% of all genes with many distinct responses for each compound, reflecting differential biochemical damage by each mercurial and the corresponding resources available for repair. This study is the first global, high-resolution view of the transcriptional responses to any common toxicant in a prokaryotic model system from exposure to recovery of active growth. The responses provoked by these two mercurials in this model bacterium also provide insights about how higher organisms may respond to these ubiquitous metal toxicants.
Fine scale mapping of genomic introgressions within the Drosophila yakuba clade.

The process of speciation involves populations diverging over time until they are genetically and reproductively isolated. Hybridization between nascent species was long thought to directly oppose speciation. However, the amount of interspecific genetic exchange (introgression) mediated by hybridization remains largely unknown, although recent progress in genome sequencing has made measuring introgression more tractable. A natural place to look for individuals with admixed ancestry (indicative of introgression) is in regions where species co-occur. In west Africa, D. santomea and D. yakuba hybridize on the island of Sao Tome, while D. yakuba and D. teissieri hybridize on the nearby island of Bioko. In this report, we quantify the genomic extent of introgression between the three species of the Drosophila yakuba clade (D. yakuba, D. santomea), D. teissieri). We sequenced the genomes of 86 individuals from all three species. We also developed and applied a new statistical framework, using a hidden Markov approach, to identify introgression. We found that introgression has occurred between both species pairs but most introgressed segments are small (on the order of a few kilobases). After ruling out the retention of ancestral polymorphism as an explanation for these similar regions, we find that the sizes of introgressed haplotypes indicate that genetic exchange is not recent (>1,000 generations ago). We additionally show that in both cases, introgression was rarer on X chromosomes than on autosomes which is consistent with sex chromosomes playing a large role in reproductive isolation. Even though the two species pairs have stable contemporary hybrid zones, providing the opportunity for ongoing gene flow, our results indicate that genetic exchange between these species is currently rare.
Determination of hexamethylene bisacetamide, an antineoplastic compound, in mouse and human plasma by LC-MS/MS.

Hexamethylene bisacetamide (HMBA) is a polar compound which has recently been discovered to have antineoplastic activity by up-regulating the expression of an endogenous antiproliferative breast cancer protein, HEXIM1 (hexamethylene bisacetamide inducible protein 1) in vivo. HMBA has been shown in the past to induce terminal differentiation in multiple leukemia types at a concentration of 2-5 mM, but its phase I and II clinical trials were largely unsuccessful due to serious side effects (notably, thrombocytopenia) with dose escalation. In this work, a sensitive and simple LC-MS/MS method for direct determination of HMBA in mouse and human plasma is described. Plasma samples were prepared by deproteinization with acetonitrile. Separation was achieved on a Waters Atlantis® T3 (2.1 mm × 50 mm, 3 µm) column with retention times of 2.2 and 3.7 min for HMBA and 7MBA (internal standard), respectively. The quantitation was carried out by tandem mass spectrometry using positive MRM mode. The linear range of the method was 0.500-100 ng/mL in both mouse and human plasma with injection volume of 5 µL. This method has been validated in accordance with the US Food and Drug Administration (FDA) guidelines for bioanalytical method development and applied to the determination of HMBA concentrations in FVB mice over time after a single dose of HMBA in saline (0.9% NaCl) at 10 mg/kg.
Developmental system drift in motor ganglion patterning between distantly related tunicates

The larval nervous system of the solitary tunicate Ciona is a simple model for the study of chordate neurodevelopment. The development and connectivity of the Ciona motor ganglion have been studied in fine detail, but how this important structure develops in other tunicates is not well known. By comparing gene expression patterns in the developing MG of the distantly related tunicate Molgula occidentalis, we found that its patterning is highly conserved compared to the Ciona MG. MG neuronal subtypes in Molgula were specified in the exact same positions as in Ciona, though the timing of subtype-specific gene expression onset was slightly shifted to begin earlier, relative to mitotic exit and differentiation. In transgenic Molgula embryos electroporated with Dmbx reporter plasmids, we were also able to characterize the morphology of the lone pair of descending decussating neurons (ddNs) in Molgula, revealing the same unique contralateral projection seen in Ciona ddNs and their putative vertebrate homologs the Mauthner cells. Although Dmbx expression labels the ddNs in both species, cross-species transgenic assays revealed significant changes to the regulatory logic underlying Dmbx transcription. We found that Dmbx cis-regulatory DNAs from Ciona can drive highly specific reporter gene expression in Molgula ddNs, but Molgula sequences are not active in Ciona ddNs. This acute divergence in the molecular mechanisms that underlie otherwise functionally conserved cis-regulatory DNAs supports the recently proposed idea that the extreme genetic plasticity observed in tunicates may be attributed to the extreme rigidity of the spatial organization of their embryonic cell lineages.
Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival

Outcomes for cancer patients vary greatly even within the same tumor type, and characterization of molecular subtypes of cancer holds important promise for improving prognosis and personalized treatment. This promise has motivated recent efforts to produce large amounts of multidimensional genomic (multi-omic) data, but current algorithms still face challenges in the integrated analysis of such data. Here we present Cancer Integration via Multikernel Learning (CIMLR), a new cancer subtyping method that integrates multi-omic data to reveal molecular subtypes of cancer. We apply CIMLR to multi-omic data from 36 cancer types and show significant improvements in both computational efficiency and ability to extract biologically meaningful cancer subtypes. The discovered subtypes exhibit significant differences in patient survival for 27 of 36 cancer types. Our analysis reveals integrated patterns of gene expression, methylation, point mutations, and copy number changes in multiple cancers and highlights patterns specifically associated with poor patient outcomes.
Pervasive Positive and Negative Feedback Regulation of Insulin-Like Signaling in Caenorhabditis elegans

The Caenorhabditis elegans insulin-like signaling network supports homeostasis and developmental plasticity. The genome encodes 40 insulin-like peptides and one known receptor. Feedback regulation has been reported, but the extent of feedback and its effect on signaling dynamics in response to changes in nutrient availability has not been determined. We measured messenger RNA expression for each insulin-like peptide, the receptor daf-2, components of the PI3K pathway, and its transcriptional effectors daf-16/FoxO and skn-1/Nrf at high temporal resolution during transition from a starved, quiescent state to a fed, growing state in wild type and mutants affecting daf-2/InsR and daf-16/FoxO. We also analyzed the effect of temperature on insulin-like gene expression. We found that most PI3K pathway components and insulin-like peptides are affected by signaling activity, revealing pervasive positive and negative feedback regulation at intra- and intercellular levels. Reporter gene analysis demonstrated that the daf-2/InsR agonist daf-28 positively regulates its own transcription and that the putative agonist ins-6 cross-regulates DAF-28 protein expression through feedback. Our results show that positive and negative feedback regulation of insulin-like signaling is widespread, giving rise to an organismal FoxO-to-FoxO signaling network that supports homeostasis during fluctuations in nutrient availability.
On the reaction of (S)‐trifluoroacetoxysuccinic anhydride with amines to produce hydroxysuccinamic (malamic) acid derivatives

L-Malic acid (2) reacts with trifluoroacetic anhydride under anhydrous conditions to give (S)-trifluoroacetoxy-succinic acid anhydride (3). The anhydride 3 undergoes regioselective ring opening with an excess of anilines or primary aliphatic amines leading to N-substituted-(S)-3-hydroxy-succinamic acids (4a–g). Structural elucidation of the reaction products 4a–g was based on analytical and spectroscopic data and on an X-ray structure analysis of 4b. Secondary aliphatic amines react with 3 by condensation and subsequent elimination to furnish N,N′-disubstituted fumaric acid amides 5a, b. Some N-substituted-2-hydroxysuccinamic acids (7a,b) were also prepared for spectral comparison with the 3-hydroxy compounds.
Synthesis and Metal Ion Complexation Studies of [60]Fullerene Derivatives of Tetrathiafulvalene Crown Ethers

The synthesis of two novel [60]fullerene derivatives containing the electron donor tetrathiafulvalene and metal-complexing crown ethers is described, and their complexation ability with alkali metal cations is studied by solid-liquid extraction techniques, cyclic voltammetry and 1H NMR spectroscopy.
Adaptive Learning Material Recommendation in Online Language Education

In online language education, it is challenging to recommend learning materials that match the student’s knowledge since we typically lack information about the difficulty of materials and the abilities of each student. We propose a refined hierarchical structure to model vocabulary knowledge in a corpus and introduce an adaptive algorithm to recommend reading texts for online language learners. We evaluated our approach with a Japanese learning tool, finding that adding adaptivity into material recommendation significantly increased engagement.
Biphenyldialkylsilyl chlorides: reagents for the formation of crystalline derivatives of small terminal alkynes

Abstract Biphenyldimethylsilyl chloride (BDMS-Cl) and biphenytdiisopropylsilyl chloride (BDIPS-Cl) are readily prepared reagents for the introduction of the BDMS and BDIPS protecting groups onto small terminal alkynes, leading to stable, solid, and easily recrystallizable derivatives of these thermally unstable molecules.
Structure and Stability of Boron Nitrides: Isomers of B12N12

A number of recent studies have explored the energetics of intermediate-sized clusters, such as small fullerenes. For example, the isomer energies of C20 have proven difficult to ascertain as different theoretical methods give widely varying results. For cluster sizes around 20−30 atoms, it is not immediately clear whether a monocyclic, graphitic, or fullerene structure is energetically preferred. In the present work, the isomers of B12N12, a ring, a “graphitic” sheet, and a fullerene-like cage of four- and six-membered rings, are examined by theoretical means. The energies of the three isomers are calculated using Hartree−Fock theory and density functional theory (DFT) in local and gradient-corrected forms. The Dunning correlation-consistent basis sets are used, with geometries optimized up to the triple-ζ level and energies calculated at the quadruple-ζ level. The effects of the basis set, as well as the effects of local versus nonlocal DFT, are discussed. The results are compared to those of similar st...
Driving the Scalability of DNA-Based Information Storage Systems

The extreme density of DNA presents a compelling advantage over current storage media; however, to reach practical capacities, new systems for organizing and accessing information are needed. Here, we use chemical handles to selectively extract unique files from a complex database of DNA mimicking 5 TB of data and design and implement a nested file address system that increases the theoretical maximum capacity of DNA storage systems by five orders of magnitude. These advancements enable the development and future scaling of DNA-based data storage systems with modern capacities and file access capabilities.
Indium mediated reactions in water: Synthesis of β-hydroxyl esters

Abstract A variety of β-hydroxyl esters were synthesized efficiently through indium mediated carbon-carbon bond formation in water followed by ozonolysis.
Synthesis of 7,6‐Fused Bicyclic Lactams for Use as Beta‐Turn Mimics

Abstract An improved synthesis of the 7,6‐fused bicyclic lactam is presented starting from readily available chiral starting materials. (S)‐allylglycine is protected as the phthalimide derivative and coupled with (S)‐2‐amino‐6‐hydroxyhexanoic acid methyl ester. Oxidation of the hydroxyl group to the aldehyde followed by enamide synthesis and acyl iminium ion cyclization provide the bicyclic system as a single diastereomer in good overall yield.
Illumina TruSeq synthetic long-reads empower de novo assembly and resolve complex, highly-repetitive transposable elements

High-throughput DNA sequencing technologies have revolutionized genomic analysis, including the de novo assembly of whole genomes. Nevertheless, assembly of complex genomes remains challenging, in part due to the presence of dispersed repeats which introduce ambiguity during genome reconstruction. Transposable elements (TEs) can be particularly problematic, especially for TE families exhibiting high sequence identity, high copy number, or complex genomic arrangements. While TEs strongly affect genome function and evolution, most current de novo assembly approaches cannot resolve long, identical, and abundant families of TEs. Here, we applied a novel Illumina technology called TruSeq synthetic long-reads, which are generated through highly-parallel library preparation and local assembly of short read data and which achieve lengths of 1.5–18.5 Kbp with an extremely low error rate (0.03% per base). To test the utility of this technology, we sequenced and assembled the genome of the model organism Drosophila melanogaster (reference genome strain y; cn, bw, sp) achieving an N50 contig size of 69.7 Kbp and covering 96.9% of the euchromatic chromosome arms of the current reference genome. TruSeq synthetic long-read technology enables placement of individual TE copies in their proper genomic locations as well as accurate reconstruction of TE sequences. We entirely recovered and accurately placed 4,229 (77.8%) of the 5,434 annotated transposable elements with perfect identity to the current reference genome. As TEs are ubiquitous features of genomes of many species, TruSeq synthetic long-reads, and likely other methods that generate long-reads, offer a powerful approach to improve de novo assemblies of whole genomes.
The preparation of 4-oxo-N-aryl-4H-1-benzopyran-2-acetamides by the condensation/cyclization of trilithiated acetoacetanilides with lithiated methyl salicylates

Several acetoacetanilides were trilithiated in excess lithium diisopropylamide, and the resulting polylithiated intermediates were regioselectively condensed with lithiated methyl salicylates followed by acid cyclization to substituted 4-oxo-N-aryl-4H-1-benzopyran-2-acetamides (benzopyranone-2-acetamides).
Mechanism and scope of salen bifunctional catalysts in asymmetric aldehyde and α-ketoester alkylation

Abstract Metal complexes of C2-symmetric Lewis acid/Lewis base salen ligands provide bifunctional activation resulting in rapid rates in the enantioselective addition of diethylzinc to aldehydes (up to 92% ee). Further experiments probed the reactivity of the individual Lewis acid and Lewis base components of the catalyst and established that both moieties are essential for asymmetric catalysis. These catalysts are also effective in the asymmetric addition of diethylzinc to α-ketoesters. This finding is significant because α-ketoesters alone serve as their own ligands to accelerate racemic 1,2-carbonyl addition of Et2Zn and racemic carbonyl reduction. The latter proceeds via a metalloene pathway, and often accounts for the predominant product. Singular Lewis acid catalysts do not accelerate enantioselective 1,2-addition over these two competing paths. The bifunctional amino salen catalysts, however, rapidly provide enantioenriched 1,2-addition products in excellent yield, complete chemoselectivity, and good enantioselectivity (up to 88% ee). A library of the bifunctional amino salens was synthesized and evaluated in this reaction. The utility of the α-ketoester method has been demonstrated in the synthesis of an opiate antagonist.
2-Benzamidoethyl group--a novel type of phosphate protecting group for oligonucleotide synthesis.

A number of 5‘-O-(4,4‘-dimethoxytrityl)thymidine N,N-diisopropylamino phosphoramidites protected at P(III) with derivatives of 2-benzamidoethanol were synthesized and incorporated into synthetic oligonucleotides. Depending on substitution patterns at the alkyl chain, amido group, and phenyl ring, the time required for removal of these protecting groups using concentrated ammonium hydroxide varied from 48 h at 55 °C to 25 min at 25 °C. Of the 11 groups studied, 2-[N-isopropyl-N- (4-methoxybenzoyl)amino]ethyl- (H) and ω-(thionobenzoylamino)alkyl protections (I and K) were most easily removed. Derivatives of the 2-[N-methyl-N-benzoylamino]ethyl group (E−G) demonstrated moderate stability, but those of the 2-(N-benzoylamino)ethyl group (A−C) were the most stable. For the most reactive group, H, a phosphitylating reagent, bisamidite 60, was synthesized and used in the preparation of four deoxynucleoside phosphoramidites 28 and 65−67, plus the 2‘-O-(2-methoxyethyl)-5-methyluridine phosphoramidite 68. All of the...
Predicting the Energetics, Phase Stability, and Morphology Evolution of Faceted and Spherical Anatase Nanocrystals

Inconsistencies in experimental thermochemical analysis of the anatase to rutile phase transition have led to various studies in order to elucidate the physical and chemical parameters affecting the stability of TiO2 at the nanoscale. Using a thermodynamic model, we present predictions of the transition enthalpy of nanocrystalline anatase and rutile as a function of shape, size, and degree of surface passivation, showing that thermochemical results can differ for various faceted or spherical nanoparticles.
Syntheses of β,β-Diarylvinyl Phenyl Ketones by Benzotriazole-Mediated Tandem Coupling-Elimination

â,â-Diarylvinyl phenyl ketones are frequently observed in natural products and are widely used versatile organic synthons; for example, (i) they can be epoxidized1,2 and then converted into cumarones and flavones,2 (ii) they can be added to aromatics to give polyaryl substituted ketones,3 or (iii) they can be simply hydrogenated to give ketones.4 The most important synthesis of â,â-diarylvinyl phenyl ketones, direct aldol condensation, suffers limitations due to cross-coupling and Michael-type reactions, which cannot be always overcome by recent alternatives.5,6 The well-known acylation of olefins to such R,â-enones is frequently limited by the formation of numerous byproducts.7 Photodecarbonylation of aryl-substituted furanones affords â,â-diarylvinyl phenyl ketones in good yields.8,9 A recent comprehensive review10 confirms that additional general and versatile pathways to â,â-diarylvinyl phenyl ketones would be valuable. We now present a new benzotriazole-mediated route to â-substituted R,â-enones utilizing the corresponding diarylmethanols or diarylmethyl halides and R-bromoacetophenone.
Core Genes Evolve Rapidly in the Long-Term Evolution Experiment with Escherichia coli

Bacteria can evolve rapidly under positive selection owing to their vast numbers, allowing their genes to diversify by adapting to different environments. We asked whether the same genes that evolve rapidly in the long-term evolution experiment (LTEE) with Escherichia coli have also diversified extensively in nature. To make this comparison, we identified ∼2000 core genes shared among 60 E. coli strains. During the LTEE, core genes accumulated significantly more nonsynonymous mutations than flexible (i.e., noncore) genes. Furthermore, core genes under positive selection in the LTEE are more conserved in nature than the average core gene. In some cases, adaptive mutations appear to modify protein functions, rather than merely knocking them out. The LTEE conditions are novel for E. coli, at least in relation to its evolutionary history in nature. The constancy and simplicity of the environment likely favor the complete loss of some unused functions and the fine-tuning of others.
Numerical and spatial patterning of yeast meiotic DNA breaks by Tel1

The Spo11-generated double-strand breaks (DSBs) that initiate meiotic recombination are dangerous lesions that can disrupt genome integrity, so meiotic cells regulate their number, timing, and distribution. Mechanisms of this regulation remain poorly understood. Here, we use Spo11-oligonucleotide complexes, a byproduct of DSB formation, to reveal aspects of the contribution of the Saccharomyces cerevisiae DNA damage-responsive kinase Tel1 (ortholog of mammalian ATM). A tel1Δ mutant has globally increased amounts of Spo11-oligonucleotide complexes and altered Spo11-oligonucleotide lengths, consistent with conserved roles for Tel1 in control of DSB number and processing. A kinase-dead tel1 mutation similarly increases Spo11-oligonucleotide levels but mutating known Tel1 phosphotargets on Hop1 and Rec114 does not, implicating Tel1 kinase activity and clarifying roles of Tel1 phosphorylation substrates. Deep sequencing of Spo11 oligonucleotides demonstrates that Tel1 shapes the genome-wide DSB landscape in unexpected ways. Early in meiosis, Tel1 absence causes widespread changes in DSB distributions across large chromosomal domains. Many of these changes are erased as meiosis proceeds, however, illustrating homeostatic behavior of DSB regulatory systems. We further find that effects of Tel1 are distinct but partially overlapping with previously described contributions of the recombination regulator Cst9 (also known as Zip3). Finally, we provide evidence indicating that Tel1-dependent DSB interference influences the population-average DSB landscape but also demonstrate that locally inhibitory effects of an artificial hotspot insertion can be both Tel1-independent and chromosomal context-dependent. Our findings delineate Tel1 roles in regulating number and location of DSBs and illuminate the complex interplay between Tel1 and other pathways for DSB control.
A novel method of synthesis of 2,4-diamino-6-arylmethylquinazolines using palladium(0)-catalyzed organozinc chemistry.

Palladium-catalyzed cross-coupling reactions offer a powerful approach to the creation of a carbon-carbon bond between an electrophile C-X (e.g., X ) Cl, Br, I, OTf) and an organometallic species C-M (e.g., M ) Li, Mg, Zn, B, Si).1 Organozinc reagents are extremely useful in this context because they can tolerate a wide range of functionality in the electrophilic partner.2 A large number of organozinc reagents are available commercially as standardized solutions in THF or can prepared easily from organic halides and a highly reactive grade of metallic zinc (“Rieke zinc”),3 which is likewise commercially available. Thus, organozinc reagents in combination with palladium reagents are advantageous in the synthesis of complex molecules containing multiple functional groups, such as natural products. Of particular note are that the reaction requires only a catalytic amount of palladium and that, in contrast to the Heck reaction, the saturated carbon-carbon is generated directly, without the need to first reduce a double or triple bond. Thus, palladium-catalyzed cross-coupling reactions using organozinc reagents are expected to enjoy increasing popularity in organic synthesis and medicinal chemistry. Piritrexim (1),4 a lipophilic inhibitor of the key metabolic enzyme dihydrofolate reductase (DHFR), has been studied intensively as an anticancer drug5 and, more recently, was identified as a potent inhibitor of the enzyme from Pneumocystis carinii (Pc) and Toxoplasma gondii (Tg), two opportunistic parasites known to be potentially life-threatening in patients with acquired immunodeficiency syndrome (AIDS).6 A notable structural feature of 1 is the CH2 bridge between the two halves of the molecule. This bridge is also present in trimethoprim (2),7 another lipophilic DHFR inhibitor widely used for anti-Pc and anti-Tg prophylaxis and therapy in AIDS patients, usually in combination with a sulfa drug to enhance the efficacy.8 Two other members of this class that have been used clinically against these infections are pyrimethamine (3),7,9 in which the two halves of the molecule are linked without a CH2 bridge, and trimetrexate (4),10,11 which contains a CH2NH bridge. In addition to the fact that it contains a longer bridge, 4 differs from 1 in being a quinazoline as opposed to a pyrido[2,3-d]pyrimidine. The structures of these four prototypical examples of clinically active lipophilic antifolates are shown in Figure 1. Although there are a number of examples in the literature of lipophilic DHFR inhibitors in which the fused 2,4-diaminopyrimidine ring system and the aryl side chain are separated by a short O or S bridge, as in 5 and 6,12,13 the only quinazoline antifolates described to date in which this bridge is CH2 are the 5,6,7,8-tetrahydro derivatives 7.14 In the present paper, we report a novel and remarkably straightforward method of synthesis of analogues of 7 in which the B-ring is aromatic.
Feeding Rapidly Alters Microbiome Composition and Gene Transcription in the Clownfish Gut

ABSTRACT Diet is a major determinant of intestinal microbiome composition. While studies have evaluated microbiome responses to diet variation, less is understood about how the act of feeding influences the microbiome, independent of diet type. Here, we use the clownfish Premnas biaculeatus, a species reared commonly in ornamental marine aquaculture, to test how the diversity, predicted gene content, and gene transcription of the microbiome vary over a 2-day diurnal period with a single daily feeding event. This study used fish fed four times daily, once daily, or every 3 days prior to the diurnal period, allowing us also to test how feeding frequency affected microbiome diversity. The amount of time between feedings had no effect on baseline diversity of the microbiome. In contrast, the act of feeding itself caused a significant short-term change in the microbiome, with microbiome diversity, predicted gene content, and gene transcription varying significantly between time points immediately before and 1.5 hours postfeeding. Variation was driven by abundance shifts involving exact sequence variants (ESVs), with one ESV identified as Photobacterium sp. increasing from IMPORTANCE Despite extensive study of intestinal microbiome diversity and the role of diet type in structuring gut microbial communities, we know very little about short-term changes in the intestinal microbiome as a result of feeding alone. Sampling microbiomes over a feeding cycle will allow us to differentiate opportunistic, feeding-responsive microbes from resident, potentially commensal members of the gut community. Also, since feeding has the potential to alter microbiome structure, sampling at different points relative to the last feeding event will likely yield different conclusions about microbiome composition and function. This variation should be addressed in comparative microbiome studies. Our study contributes to knowledge of short-term changes in the gut microbiome associated with feeding events.
Surgical management of the patient living with autism.

Abstract Background Although 1 in 59 children currently born are diagnosed with autism spectrum disorder (ASD), little is known on how to best manage those patients who require surgical intervention. The purpose of this study is to (1) investigate the best care strategies for surgical patients living with autism spectrum disorder (2) provide recommendations on how to apply those strategies to clinical practice. Methods A literature review was conducted to investigate the best clinical practices for optimizing surgical care for individuals living with autism spectrum disorder. Relevant articles were selected and examined, and individual references from those articles were manually searched using Ovid Medline and Google Scholar. Results The wide spectrum of symptoms associated with autism spectrum disorder pose unique challenges for surgical management. Early coordination with the patient and family optimizes the development of an effective care plan. Strategies include identifying triggers for anxiety as well as soothing mechanisms, performing surgery in the morning, completing preoperative paperwork prior to surgery, choosing appropriate analgesia and anxiolytics, and fast resumption of normal routines. Based on these findings a surgical checklist was created to aid in treating the patient with autism spectrum disorder. The checklist provides insight into navigating the surgical experience and emphasizes planning surgical interventions to most effectively fit individual patient needs. Conclusion The surgical treatment of those living with autism spectrum disorder poses unique challenges for the health care team. The widespread adoption of such individualized approaches encompassing pre/intra/post-operative will become more important as these children grow into adults with increased needs for surgical services.
Longitudinal increases in structural connectome segregation and functional connectome integration are associated with better recovery after mild TBI

Traumatic brain injury damages white matter pathways that connect brain regions, disrupting transmission of electrochemical signals and causing cognitive and emotional dysfunction. Connectome-level mechanisms for how the brain compensates for injury have not been fully characterized. Here, we collected serial MRI-based structural and functional connectome metrics and neuropsychological scores in 26 mild traumatic brain injury subjects (29.4 ± 8.0 years, 20 males) at 1 and 6 months postinjury. We quantified the relationship between functional and structural connectomes using network diffusion (ND) model propagation time, a measure that can be interpreted as how much of the structural connectome is being utilized for the spread of functional activation, as captured via the functional connectome. Overall cognition showed significant improvement from 1 to 6 months (t25 = -2.15, p = .04). None of the structural or functional global connectome metrics was significantly different between 1 and 6 months, or when compared to 34 age- and gender-matched controls (28.6 ± 8.8 years, 25 males). We predicted longitudinal changes in overall cognition from changes in global connectome measures using a partial least squares regression model (cross-validated R2 = .27). We observe that increased ND model propagation time, increased structural connectome segregation, and increased functional connectome integration were related to better cognitive recovery. We interpret these findings as suggesting two connectome-based postinjury recovery mechanisms: one of neuroplasticity that increases functional connectome integration and one of remote white matter degeneration that increases structural connectome segregation. We hypothesize that our inherently multimodal measure of ND model propagation time captures the interplay between these two mechanisms.
Efficient Size Estimation and Impossibility of Termination in Uniform Dense Population Protocols

We study uniform population protocols: networks of anonymous agents whose pairwise interactions are chosen at random, where each agent uses an identical transition algorithm that does not depend on the population size n. Many existing polylog(n) time protocols for leader election and majority computation are nonuniform: to operate correctly, they require all agents to be initialized with an approximate estimate of n (specifically, the value lfloorlog n\rfloor). Our first main result is a uniform protocol for calculating log(n) \pm O(1) with high probability in O(log^2 n) time and O(log^4 n) states (O(log log n) bits of memory). The protocol is not terminating : it does not signal when the estimate is close to the true value of log n. If it could be made terminating with high probability, this would allow composition with protocols requiring a size estimate initially. We do show how our main protocol can be indirectly composed with others in a simple and elegant way, based on leaderless phase clocks, demonstrating that those protocols can in fact be made uniform. However, our second main result implies that the protocol cannot be made terminating, a consequence of a much stronger result: a uniform protocol for any task requiring more than constant time cannot be terminating even with probability bounded above 0, if infinitely many initial configurations are dense : any state present initially occupies Omega(n) agents. (In particular no leader is allowed.) Crucially, the result holds no matter the memory or time permitted.
A Polynomial-time Solution for Robust Registration with Extreme Outlier Rates

We propose a robust approach for the registration of two sets of 3D points in the presence of a large amount of outliers. Our first contribution is to reformulate the registration problem using a Truncated Least Squares (TLS) cost that makes the estimation insensitive to a large fraction of spurious point-to-point correspondences. The second contribution is a general framework to decouple rotation, translation, and scale estimation, which allows solving in cascade for the three transformations. Since each subproblem (scale, rotation, and translation estimation) is still non-convex and combinatorial in nature, out third contribution is to show that (i) TLS scale and (component-wise) translation estimation can be solved exactly and in polynomial time via an adaptive voting scheme, (ii) TLS rotation estimation can be relaxed to a semidefinite program and the relaxation is tight in practice, even in the presence of an extreme amount of outliers. We validate the proposed algorithm, named TEASER (Truncated least squares Estimation And SEmidefinite Relaxation), in standard registration benchmarks showing that the algorithm outperforms RANSAC and robust local optimization techniques, and favorably compares with Branch-and-Bound methods, while being a polynomial-time algorithm. TEASER can tolerate up to 99% outliers and returns highly-accurate solutions.
A vanishing theorem and asymptotic regularity of powers of ideal sheaves

Abstract Let I be an ideal sheaf on P n . In the first part of this paper, we bound the asymptotic regularity of powers of I as s p ⩽ reg I p ⩽ s p + e , where e is a constant and s is the s-invariant of I . We also give the same upper bound for the asymptotic regularity of symbolic powers of I under some conditions. In the second part, by using multiplier ideal sheaves, we give a vanishing theorem of powers of I when it defines a local complete intersection subvariety with log canonical singularities.