cssi/SciSciGPT-SciSciNet huggingface dataset:
Spectrum Concentration and Performance of the U.S. Wireless Industry

This paper estimates the empirical relationship between concentration in mobile carriers’ holdings of radio spectrum and the performance of the U.S. wireless industry. Reduced-form regressions that use a 2012–2013 cross-section of approximately 700 Cellular Market Areas reveal a robust inverted-U relationship between spectrum HHIs and subscriber penetration rates—a measure of consumer welfare. The marginal effect of spectrum concentration is positive throughout the range of sampled markets—contrary to the conventional concentration-performance hypothesis. This pattern persists when spectrum concentration is separately measured for bands below 1 GHz and for rural areas. It is also shown not to be biased by the potential endogeneity of spectrum HHIs. This paper is distinguished by relating subscriber penetration rates to the quality and coverage of operator networks that supports efficiency explanations for operator size, and hence the benefits of structural concentration. These findings cast doubt on federal policies adopted as early as the 1927 Radio Act that attempt to equalize ownership of spectrum. Instead, our empirical results recommend measures that promote investment in wireless infrastructure and other non-spectrum factors.
Implementation-Neutral Causation in Structural Models

Analysts associated with the Cowles Commission attached great importance to the distinction between structural and reduced-form models: in their view structural models, but not reduced-form models, allow the analysis of causal relations. They did not present clear justification for this view. Here we show that this insight is correct, and make the demonstration of it precise. Causal relations are shown to depend on parameter restrictions that are explicit in the structural form, but not in the reduced form when the coefficients are interpreted as unrestricted constants. The requisite parameter restrictions are those associated with implementation-neutral causation. A graphical procedure is outlined that identifies causal orderings and also the ordering based on implementation-neutral causation. The same procedure applied to reduced form models produces the implementation-neutral causal ordering only if the parameter restrictions are explicitly incorporated in the reduced form. The analysis is applied in investigating the validity of the causal Markov condition.
Pulmonary vascular mechanical consequences of ischemic heart failure and implications for right ventricular function

In this study, we investigate the mechanical consequences of left heart failure with reduced ejection fraction for the pulmonary vasculature and right ventricle. Using comprehensive functional anal...
Sequence and Nuclease Requirements for Breakage and Healing of a Structure-Forming (AT)n Sequence within Fragile Site FRA16D.

Summary Common fragile sites (CFSs) are genomic regions that display gaps and breaks in human metaphase chromosomes under replication stress and are often deleted in cancer cells. We studied an ∼300-bp subregion (Flex1) of human CFS FRA16D in yeast and found that it recapitulates characteristics of CFS fragility in human cells. Flex1 fragility is dependent on the ability of a variable-length AT repeat to form a cruciform structure that stalls replication. Fragility at Flex1 is initiated by structure-specific endonuclease Mus81-Mms4 acting together with the Slx1-4/Rad1-10 complex, whereas Yen1 protects Flex1 against breakage. Sae2 is required for healing of Flex1 after breakage. Our study shows that breakage within a CFS can be initiated by nuclease cleavage at forks stalled at DNA structures. Furthermore, our results suggest that CFSs are not just prone to breakage but also are impaired in their ability to heal, and this deleterious combination accounts for their fragility.
Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs

The biological fingerprint of environmental adversity may be key to understanding health and disease, as it encompasses the damage induced as well as the compensatory reactions of the organism. Metabolic and hormonal changes may be an informative but incomplete window into the underlying biology. We endeavored to identify objective blood gene expression biomarkers for psychological stress, a subjective sensation with biological roots. To quantify the stress perception at a particular moment in time, we used a simple visual analog scale for life stress in psychiatric patients, a high-risk group. Then, using a stepwise discovery, prioritization, validation, and testing in independent cohort design, we were successful in identifying gene expression biomarkers that were predictive of high-stress states and of future psychiatric hospitalizations related to stress, more so when personalized by gender and diagnosis. One of the top biomarkers that survived discovery, prioritization, validation, and testing was FKBP5, a well-known gene involved in stress response, which serves as a de facto reassuring positive control. We also compared our biomarker findings with telomere length (TL), another well-established biological marker of psychological stress and show that newly identified predictive biomarkers such as NUB1, APOL3, MAD1L1, or NKTR are comparable or better state or trait predictors of stress than TL or FKBP5. Over half of the top predictive biomarkers for stress also had prior evidence of involvement in suicide, and the majority of them had evidence in other psychiatric disorders, providing a molecular underpinning for the effects of stress in those disorders. Some of the biomarkers are targets of existing drugs, of potential utility in patient stratification, and pharmacogenomics approaches. Based on our studies and analyses, the biomarkers with the best overall convergent functional evidence (CFE) for involvement in stress were FKBP5, DDX6, B2M, LAIR1, RTN4, and NUB1. Moreover, the biomarker gene expression signatures yielded leads for possible new drug candidates and natural compounds upon bioinformatics drug repurposing analyses, such as calcium folinate and betulin. Our work may lead to improved diagnosis and treatment for stress disorders such as PTSD, that result in decreased quality of life and adverse outcomes, including addictions, violence, and suicide.
Guiding Extractive Summarization with Question-Answering Rewards.

Highlighting while reading is a natural behavior for people to track salient content of a document. It would be desirable to teach an extractive summarizer to do the same. However, a major obstacle to the development of a supervised summarizer is the lack of ground-truth. Manual annotation of extraction units is cost-prohibitive, whereas acquiring labels by automatically aligning human abstracts and source documents can yield inferior results. In this paper we describe a novel framework to guide a supervised, extractive summarization system with question-answering rewards. We argue that quality summaries should serve as document surrogates to answer important questions, and such question-answer pairs can be conveniently obtained from human abstracts. The system learns to promote summaries that are informative, fluent, and perform competitively on question-answering. Our results compare favorably with those reported by strong summarization baselines as evaluated by automatic metrics and human assessors.
A review of the community flood risk management literature in the USA: lessons for improving community resilience to floods

This study systematically reviews the diverse body of research on community flood risk management in the USA to identify knowledge gaps and develop innovative and practical lessons to aid flood management decision-makers in their efforts to reduce flood losses. The authors discovered and reviewed 60 studies that met the selection criteria (e.g., study is written in English, is empirical, focuses on flood risk management at the community level in the USA, etc.). Upon reviewing the major findings from each study, the authors identified seven practical lessons that, if implemented, could not only help flood management decision-makers better understand communities’ flood risks, but could also reduce the impacts of flood disasters and improve communities’ resilience to future flood disasters. These seven lessons include: (1) recognizing that acquiring open space and conserving wetlands are some of the most effective approaches to reducing flood losses; (2) recognizing that, depending on a community’s flood risks, different development patterns are more effective at reducing flood losses; (3) considering the costs and benefits of participating in FEMA’s Community Rating System program; (4) engaging community members in the flood planning and recovery processes; (5) considering socially vulnerable populations in flood risk management programs; (6) relying on a variety of floodplain management tools to delineate flood risk; and (7) ensuring that flood mitigation plans are fully implemented and continually revised.
On the Geometry of Nash and Correlated Equilibria with Cumulative Prospect Theoretic Preferences

It is known that the set of all correlated equilibria of an n-player non-cooperative game is a convex polytope and includes all of the Nash equilibria. Furthermore, the Nash equilibria all lie on t...
Domain Agnostic Learning with Disentangled Representations

Unsupervised model transfer has the potential to greatly improve the generalizability of deep models to novel domains. Yet the current literature assumes that the separation of target data into distinct domains is known as a priori. In this paper, we propose the task of Domain-Agnostic Learning (DAL): How to transfer knowledge from a labeled source domain to unlabeled data from arbitrary target domains? To tackle this problem, we devise a novel Deep Adversarial Disentangled Autoencoder (DADA) capable of disentangling domain-specific features from class identity. We demonstrate experimentally that when the target domain labels are unknown, DADA leads to state-of-the-art performance on several image classification datasets.
On the Interaction Between Autonomous Mobility-on-Demand Systems and the Power Network: Models and Coordination Algorithms

We study the interaction between a fleet of electric self-driving vehicles servicing on-demand transportation requests (referred to as autonomous mobility-on-demand, or AMoD, systems) and the electric power network. We propose a joint model that captures the coupling between the two systems stemming from the vehicles’ charging requirements, capturing time-varying customer demand, battery depreciation, and power transmission constraints. First, we show that the model is amenable to efficient optimization. Then, we prove that the socially optimal solution to the joint problem is a general equilibrium if locational marginal pricing is used for electricity. Finally, we show that the equilibrium can be computed by selfish transportation and generator operators (aided by a nonprofit independent system operator) without sharing private information. We assess the performance of the approach and its robustness to stochastic fluctuations in demand through case studies and agent-based simulations. Collectively, these results provide a first-of-a-kind characterization of the interaction between AMoD systems and the power network, and shed additional light on the economic and societal value of AMoD.
Highly regiocontrolled and stereocontrolled syntheses of polysubstituted aminocyclohexanes: mild inverse-electron-demand Diels–Alder cycloadditions of electrophilic 2-pyridones

Abstract Strongly electrophilic N-arenesulfonyl-2-pyridone-3-carboxylate methyl esters complex with zinc dibromide and then react with nucleophilic benzyl vinyl ether or benzyloxyallene to achieve inverse-electron-demand Diels–Alder (IEDDA) cycloadditions. These cycloadducts are produced on gram scale and in 77–89% yields, importantly without the use of high pressure. These 4+2 cycloadditions strongly favor regioselective and stereoselective formation of endo bicyclic lactams as established by X-ray crystallography. These bicyclic lactams undergo useful reactions, including reductive cleavage of the N-sulfonyl group, exo-syn-dihydroxylations, and lactam ring-opening to produce a variety of aminocyclitols.
Motor Cortex Excitability Reflects the Subjective Value of Reward and Mediates Its Effects on Incentive-Motivated Performance

Performance-based incentives tend to increase an individual9s motivation, resulting in enhancements in behavioral output. While much work has focused on understanding how the brain9s reward circuitry influences incentive-motivated performance, fewer studies have investigated how such reward representations act on the motor system. Here we measured motor cortical excitability with transcranial magnetic stimulation while female and male human participants performed a motoric incentive motivation task for prospective monetary gains and losses. We found that individuals9 performance increased for increasing prospective gains and losses. While motor cortical excitability appeared insensitive to prospective loss, temporal features of motor cortical excitability for prospective gains were modulated by an independent measure of an individual9s subjective preferences for incentive (i.e., loss aversion). Those individuals that were more loss averse had a greater motor cortical sensitivity to prospective gain, closer to movement onset. Critically, behavioral sensitivity to incentive and motor cortical sensitivity to prospective gains were both predicted by loss aversion. Furthermore, causal modeling indicated that motor cortical sensitivity to incentive mediated the relationship between subjective preferences for incentive and behavioral sensitivity to incentive. Together, our findings suggest that motor cortical activity integrates information about the subjective value of reward to invigorate incentive-motivated performance. SIGNIFICANCE STATEMENT Increasing incentives tend to increase motivation and effort. Using a motoric incentive motivation task and transcranial magnetic stimulation, we studied the motor cortical mechanisms responsible for incentive-motivated motor performance. We provide experimental evidence that motor cortical sensitivity to incentive mediates the relationship between subjective preferences for incentive and incentive-motivated performance. These results indicate that, rather than simply being a reflection of motor output, motor cortical physiology integrates information about reward value to motivate performance.
Dications of Fluorenylidenes. Electronic Effects on the Paratropicity/Antiaromaticity of Diphenylmethyl-Substituted Fluorenyl Cations

Oxidation of para-substituted diphenylmethylidenefluorenes results in the formation of antiaromatic fluorenyl cations, as evidenced by the paratropic shift in the 1H NMR spectrum. The magnitude of ...
Developments in Externally Regulated Ring-Opening Metathesis Polymerization

This account details externally regulated ring-opening metathesis polymerization (ROMP) methods. Various external stimuli are discussed which collectively span chemical, thermal, photochemical, electrochemical, and mechanical modes of catalyst activation. Specific attention is also given to the recent development of a metal-free approach to ROMP that includes electro-organic and photoredox-mediated systems. 1 Introduction 2 Externally Regulated Ring-Opening Metathesis Polymerization 2.1 Acid-Activated Ring-Opening Metathesis Polymerization Catalysts 2.2 Thermally Activated Ring-Opening Metathesis Polymerization Catalysts 2.3 Mechanically Activated Ring-Opening Metathesis Polymerization Catalysts 2.4 Photochemically Activated Ring-Opening Metathesis Polymerization Catalysts 2.5 Redox-Activated Ring-Opening Metathesis Polymerization Catalysts 3 Metal-Free Ring-Opening Metathesis Polymerization 3.1 Electro-organic Ring-Opening Metathesis Polymerization 3.2 Photoredox-Mediated Ring-Opening Metathesis Polymerization 4 Conclusions and Outlook
OH+ IN DIFFUSE MOLECULAR CLOUDS

Near ultraviolet observations of OH+ and OH in diffuse molecular clouds reveal a preference for different environments. The dominant absorption feature in OH+ arises from a main component seen in CH+ (that with the highest CH+/CH column density ratio), while OH follows CN absorption. This distinction provides new constraints on OH chemistry in these clouds. Since CH+ detections favor low-density gas with small fractions of molecular hydrogen, this must be true for OH+ as well, confirming OH+ and H2O+ observations with the Herschel Space Telescope. Our observed correspondence indicates that the cosmic ray ionization rate derived from these measurements pertains to mainly atomic gas. The association of OH absorption with gas rich in CN is attributed to the need for a high enough density and molecular fraction before detectable amounts are seen. Thus, while OH+ leads to OH production, chemical arguments suggest that their abundances are controlled by different sets of conditions and that they coexist with different sets of observed species. Of particular note is that non-thermal chemistry appears to play a limited role in the synthesis of OH in diffuse molecular clouds.
Synthesis of 2′,3′-dideoxy-3′-hydroxymethylcytidine: A novel hydroformylation route

2′,3′-Dideoxy-3′-hydroxymethylcytidine (1) has been synthesized via stereoselective Rh-catalyzed hydroformylation of 2′,3′-didehydro-2′,3′-dideoxycytidine 3b. This synthesis incorporates the first successful hydroformylation of a nucleoside olefin.
Lewis Acid-Directed Reactions of Quinones with Styrenyl Systems: The Case of 2-Methoxy-3-methyl-1,4-benzoquinone

Reactions of 2-methoxy-3-methyl-1,4-benzoquinone with various (E)-1-propenylbenzenes promoted by 1 equiv of Ti(IV), as a 1:1 mixture of TiCl4−Ti(O-i-Pr)4, produce rel-(1S,6R,7R,8R)-8-aryl-4,7-dimethyl-3-methoxybicyclo[4.2.0]oct-3-ene-2,5-diones 3 and trans-2-aryl-3,7-dimethyl-6-methoxy-2,3-dihydro-5-benzofuranols 5 as the major products. Reactions promoted by 2 equiv of Ti(IV) as a 1:1 mixture of TiCl4−Ti(O-i-Pr)4 or 1 equiv of either TiCl4, SnCl4, or BF3·OEt2 give regioisomeric rel-(1R,6S,7R,8R)-7-aryl-4,8-dimethyl-3-methoxybicyclo[4.2.0]oct-3-ene-2,5-diones (4) and/or trans-2-aryl-3,6-dimethyl-7-methoxy-2,3-dihydro-5-benzofuranols (6). A mechanism involving regioselective coordination of the various Lewis acids to the quinone is used to explain the formation of the products. These reactions demonstrate the effective regiocontrol exerted over the reactions by the nature of the Lewis acid promoters. Cyclobutanes 3 and 4 cleanly undergo rearrangement to the corresponding benzofuranols 5 and 6 on treatment ...
Transient Kinetic Analysis of SWR1C-Catalyzed H2A.Z Deposition Unravels the Impact of Nucleosome Dynamics and the Asymmetry of Histone Exchange.

The SWR1C chromatin remodeling enzyme catalyzes ATP-dependent replacement of nucleosomal H2A with the H2A.Z variant, regulating key DNA-mediated processes such as transcription and DNA repair. Here, we investigate the transient kinetic mechanism of the histone exchange reaction, employing ensemble FRET, fluorescence correlation spectroscopy (FCS), and the steady-state kinetics of ATP hydrolysis. Our studies indicate that SWR1C modulates nucleosome dynamics on both the millisecond and microsecond timescales, poising the nucleosome for the dimer exchange reaction. The transient kinetic analysis of the remodeling reaction performed under single turnover conditions unraveled a striking asymmetry in the ATP-dependent replacement of nucleosomal dimers, promoted by localized DNA unwrapping. Taken together, our transient kinetic studies identify intermediates and provide crucial insights into the SWR1C-catalyzed dimer exchange reaction and shed light on how the mechanics of H2A.Z deposition might contribute to transcriptional regulation in vivo.
Understanding Sequence Conservation With Deep Learning

Comparative genomics has been a powerful tool for identifying functional elements in the human genome. Millions of conserved elements have been discovered. However, understanding the functional roles of these elements still remain a challenge, especially in noncoding regions. In particular, it is still unclear why these elements are evolutionarily conserved and what kind of functional elements are encoded within these sequences. We present a deep learning framework, DeepCons, to further understand potential functional elements within conserved sequences. DeepCons is a convolutional neural net (CNN) that receives a short segment of DNA sequence as input and outputs the probability of the sequence of being evolutionary conserved. The CNN model utilizes hundreds of convolution kernels, which are analogous to sequence motifs, to extract features from DNA sequences during the training pro- cess. First, we train the model to discriminate 887,577 conserved elements from a matched number of nonconserved elements in the human genome. Then, we use visualization techniques to interpret how the model discriminates between the two classes of sequences, which provides indirect clues to the functional roles of conserved elements. Some kernels significantly match well-known regulatory motifs corresponding to transcription factors. Many kernels show positional biases relative to transcription start sites or transcription end sites. Most of the kernels do not correspond to any known functional element, suggesting that they might represent unknown categories of functional elements. We also utilize Deep- Cons to annotate how changes at individual nucleotides impact the conservation properties of the surrounding sequences, thereby providing an annotation of conserved sequences at an individual nucleotide level. The source code of DeepCons is publicly available at https://github.com/uci-cbcl/DeepCons.
Luminescence as a tool to study lanthanide-catalyzed formation of carbon–carbon bonds

Lanthanide ions have been widely studied in imaging and sensing applications, and they are also strong Lewis acids that have the ability to catalyze organic reactions. Here, we review the spectroscopic properties of lanthanides that enable the calculation of water-coordination numbers. Additionally, the application of these calculations to study the mechanism of lanthanide-catalyzed organic reactions is reviewed.
Arithmeticity vs. non-linearity for irreducible lattices

We establish an arithmeticity vs. nonlinearity alternative for irreducible lattices in suitable product groups, for instance products of topologically simple groups. This applies notably to a (large class of) Kac–Moody groups. The alternative relies heavily on the superrigidity theorem we propose since we follow Margulis’ reduction of arithmeticity to superrigidity.
Microwave assisted Diels-Alder cycloaddition of 2-fluoro-3-methoxy-1,3-butadiene

Abstract The title fluorodiene ( 2 ) reacts with several dienophiles in moderate yields (20–65%, 0.5 h to 3d) when thermal activation is used. When 100 W microwave radiation is used the reaction yields (70–90%, 5–25 min) are greatly improved and the reaction times are much shorter. A microwave procedure is also used for the hydrolysis of vinyl ether cycloadducts to alpha-fluoroketones.
Formation of a 1,4,2,3-dithiadiazine via dimerization of a transient thione-S-imide (thiocarbonyl imine dipole)

N-(p-Tolyl)trichloromethane sulfenamide when treated with potassium hydroxide in an ether-alcohol mixture resulted in the formation in solution of a red, transient thione-S-imide which underwent a head-to-head dimerization to 2,3-di(p-tolyl)-5,5,6,6-tetrachloro-1,4,2,3-dithiadiazine whose structure was established by a single crystal X-ray determination. A variety of sulfenamides derived from aryl-substituted primary aromatic amines and alcoholic potassium hydroxide undergo this reaction with the formation of analogous structures. This thiocarbonyl imine dipole could not be trapped with alkenic or alkynic dipolarophiles.
Revised constitution of sclerophytins A and B.

Spectroscopic reevaluation of sclerophytin B, the acetate of sclerophytin A, has demonstrated unequivocally that these coral metabolites are not composed of two ether bridges.
Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases

During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity. Guidance issued by CDC on active monitoring was a cornerstone of its response to the West Africa Ebola outbreak. There are limited data on how to balance the costs and performance of this important public health activity. We present a framework that estimates the risks and costs of specific durations of active monitoring for pathogens of significant public health concern. We analyze data from New York City's Ebola active monitoring program over a 16-month period in 2014-2016. For monitored individuals, we identified unique durations of active monitoring that minimize expected costs for those at "low (but not zero) risk" and "some or high risk": 21 and 31 days, respectively. Extending our analysis to smallpox and MERS-CoV, we found that the optimal length of active monitoring relative to the median incubation period was reduced compared to Ebola due to less variable incubation periods. Active monitoring can save lives but is expensive. Resources can be most effectively allocated by using exposure-risk categories to modify the duration or intensity of active monitoring.
Radical cleavage of a β-hydroxy azide: a reversal of regioselectivity in the oxidative fragmentation of hydroindoles

Treatment of hydroindole 17 with PhI(OAc)2/I2 leads to oxidative fragmentation of the β-hydroxy azide moiety and results in the exclusive formation of keto nitrile 18 via radical cleavage of the lateral ring C–C bond.
Neonatal gut and respiratory microbiota: coordinated development through time and space

Postnatal development of early life microbiota influences immunity, metabolism, neurodevelopment, and infant health. Microbiome development occurs at multiple body sites, with distinct community compositions and functions. Associations between microbiota at multiple sites represent an unexplored influence on the infant microbiome. Here, we examined co-occurrence patterns of gut and respiratory microbiota in pre- and full-term infants over the first year of life, a period critical to neonatal development. Gut and respiratory microbiota collected as longitudinal rectal, throat, and nasal samples from 38 pre-term and 44 full-term infants were first clustered into community state types (CSTs) on the basis of their compositional profiles. Multiple methods were used to relate the occurrence of CSTs to temporal microbiota development and measures of infant maturity, including gestational age (GA) at birth, week of life (WOL), and post-menstrual age (PMA). Manifestation of CSTs followed one of three patterns with respect to infant maturity: (1) chronological, with CST occurrence frequency solely a function of post-natal age (WOL), (2) idiosyncratic to maturity at birth, with the interval of CST occurrence dependent on infant post-natal age but the frequency of occurrence dependent on GA at birth, and (3) convergent, in which CSTs appear first in infants of greater maturity at birth, with occurrence frequency in pre-terms converging after a post-natal interval proportional to pre-maturity. The composition of CSTs was highly dissimilar between different body sites, but the CST of any one body site was highly predictive of the CSTs at other body sites. There were significant associations between the abundance of individual taxa at each body site and the CSTs of the other body sites, which persisted after stringent control for the non-linear effects of infant maturity. Canonical correlations exist between the microbiota composition at each pair of body sites, with the strongest correlations between proximal locations. These findings suggest that early microbiota is shaped by neonatal innate and adaptive developmental responses. Temporal progression of CST occurrence is influenced by infant maturity at birth and post-natal age. Significant associations of microbiota across body sites reveal distal connections and coordinated development of the infant microbial ecosystem.
Disease Heritability Enrichment of Regulatory Elements Is Concentrated in Elements with Ancient Sequence Age and Conserved Function across Species

Regulatory elements, e.g., enhancers and promoters, have been widely reported to be enriched for disease and complex trait heritability. We investigated how this enrichment varies with the age of the underlying genome sequence, the conservation of regulatory function across species, and the target gene of the regulatory element. We estimated heritability enrichment by applying stratified LD score regression to summary statistics from 41 independent diseases and complex traits (average N = 320K) and meta-analyzing results across traits. Enrichment of human putative enhancers and promoters was larger in elements with older sequence age, assessed via alignment with other species irrespective of conserved functionality: putative enhancer elements with ancient sequence age (older than the split between marsupial and placental mammals) were 8.8× enriched (versus 2.5× for all putative enhancers; p = 3e−14), and promoter elements with ancient sequence age were 13.5× enriched (versus 5.1× for all promoters; p = 5e−16). Enrichment of human putative enhancers and promoters was also larger in elements whose regulatory function was conserved across species, e.g., human putative enhancers that were enhancers in ≥5 of 9 other mammals were 4.6× enriched (p = 5e−12 versus all putative enhancers). Enrichment of human promoters was larger in promoters of loss-of-function intolerant genes: 12.0× enrichment (p = 8e−15 versus all promoters). The mean value of several measures of negative selection within these genomic annotations mirrored all of these findings. Notably, the annotations with these excess heritability enrichments were jointly significant conditional on each other and on our baseline-LD model, which includes a broad set of coding, conserved, regulatory, and LD-related annotations.
Classification of RNA‐Seq data via Gaussian copulas

RNA-sequencing (RNA-Seq) has become a preferred option to quantify gene expression, because it is more accurate and reliable than microarrays. In RNA-Seq experiments, the expression level of a gene is measured by the count of short reads that are mapped to the gene region. Although some normal-based statistical methods may also be applied to log-transformed read counts, they are not ideal for directly modeling RNA-Seq data. Two discrete distributions, Poisson distribution and negative binomial distribution, have been commonly used in the literature to model RNA-Seq data, where the latter is a natural extension of the former with allowance of overdispersion. Due to the technical difficulty in modeling correlated counts, most existing classifiers based on discrete distributions assume that genes are independent of each other. However, as we show in this paper, the independence assumption may cause non-ignorable bias in estimating the discriminant score, making the classification inaccurate. To this end, we drop the independence assumption and explicitly model the dependence between genes using Gaussian copula. We apply a Bayesian approach to estimate covariance matrix and the overdispersion parameter in negative binomial distribution. Both synthetic data and real data are used to demonstrate the advantages of our model.
Full Bayesian Comparative Phylogeography from Genomic Data

A challenge to understanding biological diversification is accounting for community-scale processes that cause multiple, co-distributed lineages to co-speciate. Such processes predict non-independent, temporally clustered divergences across taxa. Approximate-likelihood Bayesian computation (ABC) approaches to inferring such patterns from comparative genetic data are very sensitive to prior assumptions and often biased toward estimating shared divergences. We introduce a full-likelihood Bayesian approach, ecoevolity, which takes full advantage of information in genomic data. By analytically integrating over gene trees, we are able to directly calculate the likelihood of the population history from genomic data, and efficiently sample the model-averaged posterior via Markov chain Monte Carlo algorithms. Using simulations, we find that the new method is much more accurate and precise at estimating the number and timing of divergence events across pairs of populations than existing approximate-likelihood methods. Our full Bayesian approach also requires several orders of magnitude less computational time than existing ABC approaches. We find that despite assuming unlinked characters (e.g., unlinked single-nucleotide polymorphisms), the new method performs better if this assumption is violated in order to retain the constant characters of whole linked loci. In fact, retaining constant characters allows the new method to robustly estimate the correct number of divergence events with high posterior probability in the face of character-acquisition biases, which commonly plague loci assembled from reduced-representation genomic libraries. We apply our method to genomic data from four pairs of insular populations of Gekko lizards from the Philippines that are not expected to have co-diverged. Despite all four pairs diverging very recently, our method strongly supports that they diverged independently, and these results are robust to very disparate prior assumptions.
Enantioselective Synthesis of the Papulacandin Ring System: Conversion of the Mannose Diastereoisomer into a Glucose Stereoisomer

An enantioselective synthesis of three diastereoisomers of the C-arylglycoside tricyclic spiroketal nucleus of the papulacandins has been achieved, in which the initial asymmetry was introduced via...
Palladium-Controlled β-Selective Glycosylation in the Absence of the C(2)-Ester Participatory Group

The development of a new glycosylation method for the stereoselective synthesis of β-glycosides in the absence of the traditional C(2)-ester neighboring group effect is described. This process relies on the ability of the cationic palladium catalyst, Pd(PhCN)2(OTf)2 generated in situ from Pd(PhCN)2Cl2 and AgOTf, to direct β-selectivity. The new glycosylation reaction is highly β-selective and proceeds under mild conditions with 1−2 mol % of catalyst loading. This β-glycosylation method has been applied to a number of glucose donors with benzyl, allyl, and p-methoxybenzyl groups incorporated at the C(2)-position as well as tribenzylated xylose and quinovose donors to prepare various disaccharides and trisaccharides with good to excellent β-selectivity. Mechanistic studies suggest that the major operative pathway is likely to proceed via a seven-membered ring intermediate, wherein the cationic palladium complex coordinates to both the C(1)-imidate nitrogen and C(2)-oxygen of the trichloroacetimidate donor. ...
An efficient method for the preparation of amidinoureas

Abstract A mild and efficient method for the preparation of amidinoureas by reaction of an acyl-S-methylisothiourea with an amine followed by removal of the acyl groups is described.
Predicting the impact of non-coding variants on DNA methylation

DNA methylation plays a crucial role in the establishment of tissue-specific gene expression and the regulation of key biological processes. However, our present inability to predict the effect of genome sequence variation on DNA methylation precludes a comprehensive assessment of the consequences of non-coding variation. We introduce CpGenie, a sequence-based framework that learns a regulatory code of DNA methylation using a deep convolutional neural network and uses this network to predict the impact of sequence variation on proximal CpG site DNA methylation. CpGenie produces allele-specific DNA methylation prediction with single-nucleotide sensitivity that enables accurate prediction of methylation quantitative trait loci (meQTL). We demonstrate that CpGenie prioritizes validated GWAS SNPs, and contributes to the prediction of functional non-coding variants, including expression quantitative trait loci (eQTL) and disease-associated mutations. CpGenie is publicly available to assist in identifying and interpreting regulatory non-coding variants.
Reproducible big data science: A case study in continuous FAIRness.

Big biomedical data create exciting opportunities for discovery, but make it difficult to capture analyses and outputs in forms that are findable, accessible, interoperable, and reusable (FAIR). In response, we describe tools that make it easy to capture, and assign identifiers to, data and code throughout the data lifecycle. We illustrate the use of these tools via a case study involving a multi-step analysis that creates an atlas of putative transcription factor binding sites from terabytes of ENCODE DNase I hypersensitive sites sequencing data. We show how the tools automate routine but complex tasks, capture analysis algorithms in understandable and reusable forms, and harness fast networks and powerful cloud computers to process data rapidly, all without sacrificing usability or reproducibility—thus ensuring that big data are not hard-to-(re)use data. We evaluate our approach via a user study, and show that 91% of participants were able to replicate a complex analysis involving considerable data volumes.
Stereoselective synthesis of tetrahydropyran-4-ones from dioxinones catalyzed by scandium(III) triflate.

A scandium triflate catalyzed, diastereoselective cyclization between aldehydes and β-hydroxy dioxinones has been discovered. This process capitalizes on the untapped nucleophilicity of the embedded enol ether within the dioxinone core. The bicyclic compounds from the resulting cyclization can be isolated, or alternatively, alkoxide nucleophiles can be directly added. This in situ addition fragments the dioxinone rings and delivers the 3-carboxy-substituted tetrahydropyran-4-ones in good yields with high levels of diastereoselectivity.
Novel synthesis of Nα-methyl-arginine and Nα-methyl-ornithine derivatives

Nα-Boc-Nα-methyl-Nω,ω′-bis(benzyloxycarbonyl)-L-arginine and Nα-Boc-Nα-methyl-Nδ-benzyloxycarbonyl-L-ornithine have been synthesized starting with Boc-L-Gln. The γ-carboxamide of Boc-L-Gln was dehydrated to a nitrile group and the resulting compound is selectively methylated providing N-Boc-2-methylamino-4-cyanobutyric acid. The nitrile is then reduced to an amine furnishing the key intermediate Nα-Boc-Nα-methyl-L-ornithine.
KLF6 and STAT3 co-occupy regulatory DNA and functionally synergize to promote axon growth in CNS neurons

The failure of axon regeneration in the CNS limits recovery from damage and disease. Members of the KLF family of transcription factors can exert both positive and negative effects on axon regeneration, but the underlying mechanisms are unclear. Here we show that forced expression of KLF6 promotes axon regeneration by corticospinal tract neurons in the injured spinal cord. RNA sequencing identified 454 genes whose expression changed upon forced KLF6 expression in vitro, including sub-networks that were highly enriched for functions relevant to axon extension including cytoskeleton remodeling, lipid synthesis, and bioenergetics. In addition, promoter analysis predicted a functional interaction between KLF6 and a second transcription factor, STAT3, and genome-wide footprinting using ATAC-Seq data confirmed frequent co-occupancy. Co-expression of the two factors yielded a synergistic elevation of neurite growth in vitro. These data clarify the transcriptional control of axon growth and point the way toward novel interventions to promote CNS regeneration.
Metal-mediated reactions of aryl isocyanates with dimethoxycarbene to form isatin derivatives

Abstract Hydantoin derivatives have been established as the observed product in the reaction of aryl isocyanates with dimethoxycarbene. A change in the reactivity profile of dimethoxycarbene with aryl isocyanates was observed upon the addition of a metal species. Methodology has been developed in which the outcome of nucleophilic carbene reactions with isocyanates can be controlled with simple changes to reaction conditions.
A Thermodynamic History of the Solar Constitution — I: The Journey to a Gaseous Sun

History has the power to expose the origin and evolution of scientific ideas. How did humanity come to visualize the Sun as a gaseous plasma? Why is its interior thought to contain blackbody radiation? Who were the first people to postulate that the density of the solar body varied greatly with depth? When did mankind first conceive that the solar surface was merely an illusion? What were the foundations of such thoughts? In this regard, a detailed review of the Sun’s thermodynamic history provides both a necessary exposition of the circumstance which accompanied the acceptance of the gaseous models and a sound basis for discussing modern solar theories. It also becomes an invitation to reconsider the phase of the photosphere. As such, in this work, the contributions of Pierre Simon Laplace, Alexander Wilson, William Herschel, Hermann von Helmholtz, Herbert Spencer, Richard Christopher Carrington, John Frederick William Herschel, Father Pietro Angelo Secchi, Herve August Etienne Albans Faye, Edward Frankland, Joseph Norman Lockyer, Warren de la Rue, Balfour Stewart, Benjamin Loewy, and Gustav Robert Kirchhoff, relative to the evolution of modern stellar models, will be discussed. Six great pillars created a gaseous Sun: 1) Laplace’s Nebular Hypothesis, 2) Helmholtz’ contraction theory of energy production, 3) Andrew’s elucidation of critical temperatures, 4) Kirchhoff’s formulation of his law of thermal emission, 5) Plucker and Hittorf’s discovery of pressure broadening in gases, and 6) the evolution of the stellar equations of state. As these are reviewed, this work will venture to highlight not only the genesis of these revolutionary ideas, but also the forces which drove great men to advance a gaseous Sun.
Keeping It Real: How Perceived Brand Authenticity Affects Product Perceptions

This paper examines the effects of firm motivation (an intrinsic or extrinsic interest in their product) on perceptions of brand authenticity and anticipated product quality. Specifically, studies 1 and 2 show that an intrinsic motivation increases authenticity perceptions which, in turn, increase perceived product quality, even for negatively regarded products. Studies 3a and 3b demonstrate that motivation affects perceived product quality (through perceived authenticity) by influencing deliberate attribute-level inferences consumers make about the product, and Study 4 demonstrates that the positive effect of intrinsic motivation (through authenticity) disappears in the presence of objective product attribute information, when such inferences are no longer necessary. These findings suggest that authenticity perceptions are malleable, and they shed light on the mechanism through which brand authenticity leads consumers to anticipate that a brand’s products will be higher in quality.
Optical metamaterials at near and mid-IR range fabricated by nanoimprint lithography

Two types of optical metamaterials operating at near-IR and mid-IR frequencies, respectively, have been designed, fabricated by nanoimprint lithography (NIL), and characterized by laser spectroscopic ellipsometry. The structure for the near-IR range was a metal/dielectric/metal stack “fishnet” structure that demonstrated negative permittivity and permeability in the same frequency region and hence exhibited a negative refractive index at a wavelength near 1.7 μm. In the mid-IR range, the metamaterial was an ordered array of fourfold symmetric L-shaped resonators (LSRs) that showed both a dipole plasmon resonance resulting in negative permittivity and a magnetic resonance with negative permeability near wavelengths of 3.7 μm and 5.25 μm, respectively. The optical properties of both metamaterials are in agreement with theoretical predictions. This work demonstrates the feasibility of designing various optical negative-index metamaterials and fabricating them using the nanoimprint lithography as a low-cost, high-throughput fabrication approach.
Synthesis of 3β-aryl-8-azabicyclo[3.2.1]octanes with high binding affinities and selectivities for the serotonin transporter site

A novel entry to tropane analogs of cocaine was developed based on the reaction of rhodium-stabilized vinylcarbenoids with pyrroles. These analogs were tested in binding to dopamine, serotonin (5-HT), and norepinephrine transporters in membranes from rat striatum and frontal cortex. In all the analogs, the aryl group at the 3 position was directly bound to the tropane ring and an ethyl ketone moiety was present at the 2 position. By appropriate modification of the aryl and nitrogen substituents, highly potent and 5-HT selective tropanes were prepared. The most potent and selective compound was 3 beta-[4-(1-methylethenyl)phenyl]-2 beta-propanoyl-8-azabicyclo[3.2.1]octane (13b) which had a Ki of 0.1 nM at 5-HT transporters and was 150 times more potent at 5-HT vs dopamine transporters and almost 1000 times more potent at 5-HT vs norepinephrine transporters.
Mechanistic Distinctions between Cation Radical and Carbocation Propagated Polymerization

The polymerization of bis[4-(1-propenyl)phenyl] ether in the presence of tris(4-bromophenyl)aminium hexachloroantimonate is found to occur by competing cation radical and carbocation pathways. These pathways involve, respectively, cyclobutanation and linear addition. Methods for favoring each mechanistic type are proposed and explored.
Gas-Phase Molecular Structures of Third Row Transition-Metal Hexafluorides WF6, ReF6, OsF6, IrF6, and PtF6. An Electron-Diffraction and ab Initio Study

The molecular structures of WF6, ReF6, OsF6, IrF6, and PtF6 have been measured by electron diffraction from the gases, the last from both PtF6 itself and from a vapor assumed to consist of a mixtur...
Using a proxy state to improve the accuracy of truncated hyperpolarizability calculations

We present a simple algorithm for defining a single proxy state that accounts for state truncation in the sum-over-states calculations of the dispersion of the molecular hyperpolarizabilities. The transition strengths between the proxy state and the truncated set of states are determined using the Thomas-Reiche-Kuhn sum rules further constrained by the zero-frequency linear polarizability. This proxy state method can augment experimentally determined parameters or finite-state theories to allow for a more accurate prediction of the nonlinear optical properties of molecular systems. We benchmark this approach by comparison to exact perturbation calculations of one-dimensional power law potentials.
APPLICATIONS OF FREE RADICALS IN ORGANIC SYNTHESIS

A summary of studies on the generation of acyl radicals and their subsequent use in intermolecular, intramolecular, macrocyclization, and tandem alkene addition reactions is provided. Similarly, the use of intramolecular free radical cyclization reactions in the total synthesis of (+)-CC-1065 and a series of structurally related analogs is summarized.
Reaction of optically active α-aminoallenylstannanes with aldehydes formed in situ from the lewis-acid-catalyzed rearrangement of epoxides

Reaction of optically active α-oxazolidinonylallenylstannanes with oxiranes in the presence of BF3·OEt2 produced β-hydroxypropargylamines with high syn diastereoselectivity and high enantioselectiv...
Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis

AbstractEnvironmental exposures to hazardous chemicals are associated with a variety of human diseases and disorders, including cancers. Phase I metabolic activation and detoxification reactions ca...