cssi/SciSciGPT-SciSciNet huggingface dataset:
Quarkonium production in heavy ion collisions: coupled Boltzmann transport equations

Abstract We develop a set of coupled Boltzmann equations to describe the dynamical evolution of heavy quarks and quarkonia inside the quark-gluon plasma. The quarkonium dissociation and recombination terms are calculated from pNRQCD. Their interplay drives the system to a detailed balance. The heavy quark energy loss term is necessary for the system to reach kinematic thermalization. By coupling the transport equations with initial particles' momenta generated by Pythia and hydrodynamic medium evolutions, we can describe the RAA of ϒ family at both RHIC and LHC energies. The transverse momentum azimuthal anisotropy of ϒ(1S) in 2.76 TeV peripheral Pb-Pb collisions is also studied.
Benchmarking Portfolio Flows

To gauge the amount of portfolio inflows a country can expect to receive, we create a benchmark, a longer-term baseline path around which actual flows fluctuate, for 45 countries for the 2000 to 2017 period. For EMEs, there is a significant long-run relationship between actual portfolio flows and our benchmark, flows adjust strongly toward the benchmark, and our benchmark helps predict 1-year-ahead changes in inflows. For AEs, the benchmark performs well in directional forecasting exercises. In practical terms, when assessing large movements in portfolio flows it is informative to distinguish between movements toward the benchmark and movements away from the benchmark.
Genie: An Open Box Counterfactual Policy Estimator for Optimizing Sponsored Search Marketplace

In this paper, we propose an offline counterfactual policy estimation framework called Genie to optimize Sponsored Search Marketplace. Genie employs an open box simulation engine with click calibration model to compute the KPI impact of any modification to the system. From the experimental results on Bing traffic, we showed that Genie performs better than existing observational approaches that employs randomized experiments for traffic slices that have frequent policy updates. We also show that Genie can be used to tune completely new policies efficiently without creating risky randomized experiments due to cold start problem. As time of today, Genie hosts more than $10000$ optimization jobs yearly which runs more than $30$ Million processing node hours of big data jobs for Bing Ads. For the last 3 years, Genie has been proven to be the one of the major platforms to optimize Bing Ads Marketplace due to its reliability under frequent policy changes and its efficiency to minimize risks in real experiments.
Measuring Job-Finding Rates and Matching Efficiency with Heterogeneous Jobseekers

Matching efficiency is the productivity of the process for matching jobseekers to available jobs. Job-finding is the output; vacant jobs and active jobseekers are the inputs. Measurement of matching efficiency follows the same principles as measuring a Hicks-neutral index of productivity of production. We develop a framework for measuring matching productivity when the population of jobseekers is heterogeneous. The efficiency index for each type of jobseeker is the monthly job-finding rate for the type adjusted for the overall tightness of the labor market. We find that overall matching efficiency declined over the period, at just below its earlier downward trend. We develop a new approach to measuring matching rates that avoids counting short- duration jobs as successes. And we show that the outward shift in the Beveridge curve in the post-crisis period is the result of pre-crisis trends, not a downward shift in matching efficiency attributable to the crisis.
Molecular Mechanisms of H. pylori -Induced DNA Double-Strand Breaks.

Infections contribute to carcinogenesis through inflammation-related mechanisms. H. pylori infection is a significant risk factor for gastric carcinogenesis. However, the molecular mechanism by which H. pylori infection contributes to carcinogenesis has not been fully elucidated. H. pylori-associated chronic inflammation is linked to genomic instability via reactive oxygen and nitrogen species (RONS). In this article, we summarize the current knowledge of H. pylori-induced double strand breaks (DSBs). Furthermore, we provide mechanistic insight into how processing of oxidative DNA damage via base excision repair (BER) leads to DSBs. We review recent studies on how H. pylori infection triggers NF-κB/inducible NO synthase (iNOS) versus NF-κB/nucleotide excision repair (NER) axis-mediated DSBs to drive genomic instability. This review discusses current research findings that are related to mechanisms of DSBs and repair during H. pylori infection.
A Graphical Bayesian Game for Secure Sensor Activation in Internet of Battlefield Things

Abstract In this paper, the problem of secure sensor activation is studied for an Internet of Battlefield Things (IoBT) system in which an attacker compromises a set of the IoBT sensors for the purpose of eavesdropping and acquiring information about the battlefield. In the considered model, each IoBT sensor seeks to decide whether to transmit or not based on its utility. The utility of each sensor is expressed in terms of the redundancy of the data transmitted, the secrecy capacity and the energy consumed. Due to the limited communication range of the IoBT sensors and their uncertainty about the location of the eavesdroppers, the problem is formulated as a graphical Bayesian game in which the IoBT sensors are the players. Then, the utilities of the IoBT sensors are modified to take into account the effect of activating each sensor on the utilities of its neighbors, in order to achieve better system performance. The modified game is shown to be a Bayesian potential game, and a best response algorithm that is guaranteed to find a Nash equilibrium of the game is proposed. Simulation results show the tradeoff between the information transmitted by the IoBT sensors and the desired secrecy level. Simulation results also demonstrate the effectiveness of the proposed approach in reducing the energy consumed compared to the baseline in which all the IoBT sensors are activated. The reduction in energy consumption reaches up to 98% compared to the baseline, when the number of sensors is 5000.
Dynamics of Nanoscale Light Emitters

We discusses nanoscale metal-dielectric-semiconductor resonant gain geometries confined in three dimensions used to create a new type of light emitters. When these emitters are driven in a pulsed regime, dynamic hysteresis is observed and characterized. Coupling between two metallo-dielectric nanolasers results in splitting the resonance.
Feedback Stabilization Using Koopman Operator

In this paper, we provide a systematic approach for the design of stabilizing feedback controllers for nonlinear control systems using the Koopman operator framework. The Koopman operator approach provides a linear representation for a nonlinear dynamical system and a bilinear representation for a nonlinear control system. The problem of feedback stabilization of a nonlinear control system is then transformed to the stabilization of a bilinear control system. We propose a control Lyapunov function (CLF)-based approach for the design of stabilizing feedback controllers for the bilinear system. The search for finding a CLF for the bilinear control system is formulated as a convex optimization problem. This leads to a schematic procedure for designing CLF-based stabilizing feedback controllers for the bilinear system and hence the original nonlinear system. Another advantage of the proposed controller design approach outlined in this paper is that it does not require explicit knowledge of system dynamics. In particular, the bilinear representation of a nonlinear control system in the Koopman eigenfunction space can be obtained from time-series data. Simulation results are presented to verify the main results on the design of stabilizing feedback controllers and the data-driven aspect of the proposed approach.
Financial Knowledge and Short-Term and Long-Term Financial Behaviors of Millennials in the United States

This study investigates the role of financial knowledge in various short-term and long-term financial behaviors among Millennials in the United States. Results from the 2015 National Financial Capability Study (NFCS) indicate that Millennials have lower levels of objective financial knowledge and similar levels of perceived financial knowledge as compared to all households. Consistent multivariate results find financial knowledge to be positively associated with performing positive short-term and long-term financial behaviors. Results are found to be robust across different measurements of financial knowledge and behavior, and the issue of the potential for reverse causality is specifically addressed. This study provides a comprehensive financial profile of Millennials with important insight for policymakers as well as financial practitioners.
Dynamic Heterogeneity-Aware Coded Cooperative Computation at the Edge

Cooperative computation is a promising approach for localized data processing at the edge, e.g., for Internet of Things (IoT). Cooperative computation advocates that computationally intensive tasks in a device could be divided into sub-tasks, and offloaded to other devices or servers in close proximity. However, exploiting the potential of cooperative computation is challenging mainly due to the heterogeneous and time-varying nature of edge devices. Coded computation, which advocates mixing data in sub-tasks by employing erasure codes and offloading these sub-tasks to other devices for computation, is recently gaining interest, thanks to its higher reliability, smaller delay, and lower communication costs. In this paper, we develop a coded cooperative computation framework, which we name Coded Cooperative Computation Protocol (C3P), by taking into account the heterogeneous resources of edge devices. C3P dynamically offloads coded sub-tasks to helpers and is adaptive to time-varying resources. We show that (i) task completion delay of C3P is very close to optimal coded cooperative computation solutions, (ii) the efficiency of C3P in terms of resource utilization is higher than 99%, (iii) C3P improves task completion delay significantly as compared to baselines via both simulations and in a test-bed consisting of real Android-based smartphones.
Influence of Metal Substitution on the Pressure-Induced Phase Change in Flexible Zeolitic Imidazolate Frameworks.

Metal–organic frameworks that display step-shaped adsorption profiles arising from discrete pressure-induced phase changes are promising materials for applications in both high-capacity gas storage and energy-efficient gas separations. The thorough investigation of such materials through chemical diversification, gas adsorption measurements, and in situ structural characterization is therefore crucial for broadening their utility. We examine a series of isoreticular, flexible zeolitic imidazolate frameworks (ZIFs) of the type M(bim)2 (SOD; M = Zn (ZIF-7), Co (ZIF-9), Cd (CdIF-13); bim– = benzimidazolate), and elucidate the effects of metal substitution on the pressure-responsive phase changes and the resulting CO2 and CH4 step positions, pre-step uptakes, and step capacities. Using ZIF-7 as a benchmark, we reexamine the poorly understood structural transition responsible for its adsorption steps and, through high-pressure adsorption measurements, verify that it displays a step in its CH4 adsorption isothe...
Racial categories in machine learning

Controversies around race and machine learning have sparked debate among computer scientists over how to design machine learning systems that guarantee fairness. These debates rarely engage with how racial identity is embedded in our social experience, making for sociological and psychological complexity. This complexity challenges the paradigm of considering fairness to be a formal property of supervised learning with respect to protected personal attributes. Racial identity is not simply a personal subjective quality. For people labeled "Black" it is an ascribed political category that has consequences for social differentiation embedded in systemic patterns of social inequality achieved through both social and spatial segregation. In the United States, racial classification can best be understood as a system of inherently unequal status categories that places whites as the most privileged category while signifying the Negro/black category as stigmatized. Social stigma is reinforced through the unequal distribution of societal rewards and goods along racial lines that is reinforced by state, corporate, and civic institutions and practices. This creates a dilemma for society and designers: be blind to racial group disparities and thereby reify racialized social inequality by no longer measuring systemic inequality, or be conscious of racial categories in a way that itself reifies race. We propose a third option. By preceding group fairness interventions with unsupervised learning to dynamically detect patterns of segregation, machine learning systems can mitigate the root cause of social disparities, social segregation and stratification, without further anchoring status categories of disadvantage.
Spectral Zooming and Resolution Limits of Spatial Spectral Compressive Spectral Imagers

The recently introduced Spatial Spectral Compressive Spectral Imager (SSCSI) has been proposed as an alternative to carry out spatial and spectral coding using a binary ON–OFF coded aperture. In SSCSI, the pixel pitch size of the coded aperture, as well as its location with respect to the detector array, plays a critical role in the quality of image reconstruction. In this paper, a rigorous discretization model for this architecture is developed, based on a light propagation analysis across the imager. The attainable spatial and spectral resolution, and the various parameters affecting them, is derived through this process. Much like the displacement of zoom lens components leads to higher spatial resolution of a scene, a shift of the coded aperture in the SSCSI in reference to the detector leads to higher spectral resolution. This allows the recovery of spectrally detailed datacubes by physically displacing the mask toward the spectral plane. To prove the underlying concepts, computer simulations and experimental data are presented in this paper.
Price equations with symmetric supply/demand; implications for fat tails

Abstract Implementing a set of microeconomic criteria, we develop price dynamics equations using a function of demand/supply with key symmetry properties. The function of demand/supply can be linear or nonlinear. The type of function determines the nature of the tail of the distribution based on the randomness in the supply and demand. For example, if supply and demand are normally distributed, and the function is assumed to be linear, then the density of relative price change has behavior x − 2 for large x (i.e., large deviations). The exponent approaches − 1 if the function of supply and demand involves a large exponent. The falloff is exponential, i.e., e − x , if the function of supply and demand is logarithmic.
The Behavioral Economics of Behavioral Law & Economics

Behavioral Law & Economics (BLE) has loudly proclaimed its victory over traditional law & economics methodologies. Nowhere has this proclamation been so loud or self-certain as with respect to claims about consumer financial decision-making. Drawing on a set of casual observations styled as empirical proof, BLE scholars have called for a variety of regulatory interventions that are claimed to be necessary to protect consumers. But examining two detailed case studies here, one involving credit card usage by consumers and the other involving claims about consumer behavior in response to cash discounts and credit card surcharges, it is shown that these claims are simply incredible, in the sense that it is literally difficult to believe that unbiased scholars would find those studies to be even slightly persuasive. Possible explanations for this disconnect between the weakness of the underlying science and the widespread social acceptance of the theories by BLE scholars are discussed.
The Rise of the Dollar and Fall of the Euro as International Currencies

The modern notion of an international currency involves use in areas of international finance and trade that extend well beyond central banks' coffers. In addition to their important roles as foreign exchange reserves, international currencies are most frequently used to denominate corporate and government bonds, bank loans, and import and export invoices. These currencies offer unrivaled liquidity, constituting large shares of the volume on global foreign exchange markets, and are commonly chosen as the anchors targeted by countries with pegged or managed exchange rate regimes. In this short article, we provide evidence suggesting a recent rise in the use of the dollar, and fall of the use in the euro, with similar patterns manifesting across all these aspects of international currency use.
Refinement of Vortex Generators in a Streamline-Traced, External-Compression Supersonic Inlet

Computational simulations of the flow within a streamline-traced, external-compression supersonic inlet for Mach 1.664 without and with vortex generators were performed to refine the characterization of the inlet performance as measured by the total pressure recovery and the radial and circumferential total pressure distortion indices at the engine face. The refinement of the simulations concerned two aspects: 1) refinement of the grid for the simulations to evaluate and reduce uncertainty, and 2) refinement of the modeling and design of the vortex generators. The vortex generators studied were rectangular vane-type vortex generators arranged in co-rotating arrays within the subsonic diffuser. The vortex generator geometric factors of interest included the height, circumferential spacing, and angle-of-incidence. The flow through the inlet was simulated numerically through the solution of the steady-state, Reynolds-averaged Navier-Stokes equations on multi-block, structured grids using the Wind-US flow solver. The vortex generators were simulated using either a vortex generator model or with grids generated about each vortex generator. Statistical methods were used to compute confidence intervals and grid convergence indices to establish the uncertainties of the analyses with respect to grid refinement. Design-of-experiments methods were applied to quantify the effects of the geometric factors of the vortex generators. The analyses of the computed results illustrate the complexities of quantifying the uncertainties of the inlet performance and the implications of the uncertainties for the design of a vortex generator array for the STEX inlet.
La precariedad del contencioso ambiental

Este trabajo sostiene que el contencioso-administrativo de la Ley No 20.600 es un procedimiento “sumarisimo” cuya precariedad genera dos consecuencias negativas: limita tanto el contradictorio de las partes en el juicio como las facultades revisoras del tribunal ambiental. Esto ultimo pese a ser un tribunal altamente especializado.
Network morphism

We present a systematic study on how to morph a well-trained neural network to a new one so that its network function can be completely preserved. We define this as network morphism in this research. After morphing a parent network, the child network is expected to inherit the knowledge from its parent network and also has the potential to continue growing into a more powerful one with much shortened training time. The first requirement for this network morphism is its ability to handle diverse morphing types of networks, including changes of depth, width, kernel size, and even subnet. To meet this requirement, we first introduce the network morphism equations, and then develop novel morphing algorithms for all these morphing types for both classic and convolutional neural networks. The second requirement is its ability to deal with non-linearity in a network. We propose a family of parametric-activation functions to facilitate the morphing of any continuous nonlinear activation neurons. Experimental results on benchmark datasets and typical neural networks demonstrate the effectiveness of the proposed network morphism scheme.
Third-Culture Individuals

Third-culture individuals are men and women who lived in a country other than that of their nationality during their developmental years. Becoming socialized into their home culture and host culture(s) simultaneously, they form a multicultural identity. Since this identity is derived largely from their atypical, mobile upbringing involving multiple transitions as children of corporate employees, military or government personnel, missionaries or aid workers, people with this background generally refer to themselves as third-culture kids. A formal theory of third-culture individuals has yet to emerge, but researchers have recently begun testing assertions made in popular and professional literature about third-culture individuals’ intercultural competence, enhanced adaptability, social sensitivity, open-mindedness, and cultural marginality. This research has produced evidence that their unique intercultural adaptation makes them especially well-equipped to thrive in contexts that require intercultural communication, adaptation, language acquisition, mediation, diplomacy, boundary-spanning, and management of diversity.
CRISPR Gene Drive Efficiency and Resistance Rate Is Highly Heritable with No Common Genetic Loci of Large Effect

Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. Clustered regularly interspaced short palindromic repeat (CRISPR) homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population over time. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would eventually halt the spread of a drive through a population. To investigate the effects of natural genetic variation on resistance formation, we developed a CRISPR homing gene drive in Drosophila melanogaster and crossed it into the genetically diverse Drosophila Genetic Reference Panel (DGRP) lines, measuring several performance parameters. Most strikingly, resistance allele formation postfertilization in the early embryo ranged from 7 to 79% among lines and averaged 42 ± 18%. We performed a genome-wide association study using our results in the DGRP lines, and found that the resistance and conversion rates were not explained by common alleles of large effect, but instead there were several genetic polymorphisms showing weak association. RNA interference knockdown of several genes containing these polymorphisms confirmed their effect, but the small effect sizes imply that their manipulation would likely yield only modest improvements to the efficacy of gene drives.
Covering Uncertain Points in a Tree

We consider a coverage problem for uncertain points in a tree. Let T be a tree containing a set \(\mathcal {P}\) of n (weighted) demand points, and the location of each demand point \(P_i\in \mathcal {P}\) is uncertain but is known to be in one of \(m_i\) points on T each associated with a probability. Given a covering range \(\lambda \), the problem is to find a minimum number of points (called centers) on T to build facilities for serving (or covering) these demand points in the sense that for each uncertain point \(P_i\in \mathcal {P}\), the expected distance from \(P_i\) to at least one center is no more than \(\lambda \). The problem has not been studied before. We present an \(O(|T|+M\log ^2 M)\) time algorithm, where |T| is the number of vertices of T and M is the total number of locations of all uncertain points of \(\mathcal {P}\), i.e., \(M=\sum _{P_i\in \mathcal {P}}m_i\).
Work-focused cognitive behavioral therapy to complement vocational services for people with mental illness: Pilot study outcomes across a 6-month posttreatment follow-up.

OBJECTIVE People with mental illness frequently have trouble obtaining and keeping competitive employment and struggle with on-the-job performance. To address these issues, the manualized, group-based, 12-session Cognitive Behavioral Therapy for Work Success (CBTw) intervention was developed and tested in an open trial. Although posttreatment work outcomes were promising, lasting effects associated with the intervention are unknown. METHOD This article presents the 6-month posttreatment work outcomes of the open trial of CBTw in 52 adults with mental illness who were concurrently receiving VA vocational services. Work outcomes included work status, hours worked and wages earned, steady work status, and work performance and effectiveness. Data were analyzed using repeated measures analysis of variances (ANOVAs) and within groups t tests. RESULTS Findings demonstrate that 75% of unemployed participants at baseline obtained competitive work during the study period. During the 6-month follow-up period, 73% of workers attained steady work status (i.e., working at least 50% of the follow-up period). In addition, during the 6-month follow-up period, working participants averaged significantly more hours of work per week and higher wages earned per hour as compared with the baseline period and the 12-week postintervention period. Finally, among workers, reports of work effectiveness remained high at 6 months and work productivity disruptions remained low at follow-up. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE These findings suggest that CBTw may potentially be a useful tool to enhance the effects of vocational programs. Future work should test CBTw in a randomized controlled trial and examine strategies for implementation in real-world vocational service settings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Territoriality, Jurisdiction, and the Right(s) of Publicity

When Professors Rothman and Ginsburg asked me to speak here on the issues surrounding territoriality, jurisdiction, choice of law, and the like in the law of publicity, I confessed that I knew little about the developing law of publicity rights. Having taught Copyright Law for many years, I had come across the well-known foundational publicity rights cases—the cases involving Tom Waits, Vanna White, and Bette Midler—because of the problematic relationship between those decisions (under California state law) and federal copyright law. But I had not studied the publicity doctrine, or the main corpus of cases and statutes, with any great care. I had, however, done some thinking over the years about territoriality and jurisdiction in other contexts. I was happy to have the opportunity to dive in and spend a couple of months immersing myself in the publicity cases and commentary to try to discover how those questions played themselves out in this particular corner of the legal universe. I found the results “alarming.” I use the term advisedly, so let me try to explain what I mean by it.
Supporting software engineering research and education by annotating public videos of developers programming

Software engineering has long studied how software developers work, building a body of work which forms the foundation of many software engineering best practices, tools, and theories. Recently, some developers have begun recording videos of themselves engaged in programming tasks contributing to open source projects, enabling them to share knowledge and socialize with other developers. We believe that these videos offer an important opportunity for both software engineering research and education. In this paper, we discuss the potential use of these videos as well as open questions for how to best enable this envisioned use. We propose creating a central repository of programming videos, enabling analyzing and annotating videos to illustrate specific behaviors of interest such as asking and answering questions, employing strategies, and software engineering theories. Such a repository would offer an important new way in which both software engineering researchers and students can understand how software developers work.
Electrosynthesis of substituted 1H-indoles from o-nitrostyrenes.

A novel procedure has been devised for the synthesis of derivatives of 1H-indole that is based on the direct, room-temperature electrochemical reduction of substituted o-nitrostyrenes at carbon cat...
Temperature-dependent transitions between normal and inverse isotope effects pertaining to the interaction of H-H and C-H bonds with transition metal centers.

Deuterium kinetic isotope effects (KIEs) serve as versatile tools to infer details about reaction mechanisms and the nature of transition states, while equilibrium isotope effects (EIEs) associated with the site preferences of hydrogen and deuterium enable researchers to study aspects of molecular structure. Researchers typically interpret primary deuterium isotope effects based on two simple guidelines: (i) the KIE for an elementary reaction is normal (kH/kD > 1) and (ii) the EIE is dictated by deuterium preferring to be located in the site corresponding to the highest frequency oscillator. In this Account, we evaluate the applicability of these rules to the interactions of H−H and C−H bonds with a transition metal center. Significantly, experimental and computational studies question the predictability of primary EIEs in these systems based on the notion that deuterium prefers to occupy the highest frequency oscillator. In particular, the EIEs for (i) formation of σ-complexes by coordination of H−H and ...
On Constructing Parallel Pseudorandom Generators from One-Way Functions.

We study pseudorandom generator (PRG) constructions Gf : {0, 1}l → {0, 1}l+s from one-way functions f : {0, 1}n → {0, 1}m. We consider PRG constructions of the form Gf (x) = C(f(q1) . . . f(qpoly(n))) where C is a polynomial-size constant depth circuit (i.e. AC 0 ) and C and the q’s are generated from x arbitrarily. We show that every black-box PRG construction of this form must have stretch s bounded as s ≤ l · (log n)/m + O(1) = o(l). This holds even if the PRG construction starts from a one-to-one function f : {0, 1}n → {0, 1}m where m ≥ 5n. This shows that either adaptive queries or sequential computation are necessary for black-box PRG constructions with constant factor stretch (i.e. s = Ω(l)) from one-way functions, even if the functions are one-to-one. On the positive side we show that if there is a one-way function f : {0, 1}n → {0, 1}m that is regular (i.e. the number of preimages of f(x) depends on |x| but not on x) and computable by polynomial-size constant depth circuits then there is a PRG : {0, 1}l → {0, 1}l+1 computable by polynomial-size constant depth circuits. This complements our negative result above because one-to-one functions are regular. We also study constructions of average-case hard functions starting from worst-case hard ones, i.e. hardness amplifications. We show that if there is an oracle procedure Ampf in the polynomial time hierarchy (PH) such that Ampf is average-case hard for every worst-case hard f , then there is an average-case hard function in PH unconditionally. Bogdanov and Trevisan (FOCS ’03) and Viola (CCC’03) show related but incomparable negative results.
Palladium-Catalyzed Stereoselective Formation of α-O-Glycosides

A novel method for palladium-catalyzed stereoselective formation of α-O-glycosides has been developed. This strategy relies on the palladium−biaryl phosphine catalyst−glycal donor complexation to control the anomeric selectivity. It does not depend on the nature of the protecting groups on the substrates, thus eliminating the need for cumbersome protecting group manipulations.
Development of an in vitro pre-mRNA splicing assay using plant nuclear extract.

Pre-mRNA splicing is an essential post-transcriptional process in all eukaryotes. In vitro splicing systems using nuclear or cytoplasmic extracts from mammalian cells, yeast, and Drosophila have provided a wealth of mechanistic insights into assembly and composition of the spliceosome, splicing regulatory proteins and mechanisms of pre-mRNA splicing in non-plant systems. The lack of an in vitro splicing system prepared from plant cells has been a major limitation in splicing research in plants. Here we report an in vitro splicing assay system using plant nuclear extract. Several lines of evidence indicate that nuclear extract derived from Arabidopsis seedlings can convert pre-mRNA substrate (LHCB3) into a spliced product. These include: (1) generation of an RNA product that corresponds to the size of expected mRNA, (2) a junction-mapping assay using S1 nuclease revealed that the two exons are spliced together, (3) the reaction conditions are similar to those found with non-plant extracts and (4) finally mutations in conserved donor and acceptor sites abolished the production of the spliced product. This first report on the plant in vitro splicing assay opens new avenues to investigate plant spliceosome assembly and composition, and splicing regulatory mechanisms specific to plants.
Neural oscillations during conditional associative learning.

Abstract Associative learning requires mapping between complex stimuli and behavioural responses. When multiple stimuli are involved, conditional associative learning is a gradual process with learning based on trial and error. It is established that a distributed network of regions track associative learning, however the role of neural oscillations in human learning remains less clear. Here we used scalp EEG to test how neural oscillations change during learning of arbitrary visuo-motor associations. Participants learned to associative 48 different abstract shapes to one of four button responses through trial and error over repetitions of the shapes. To quantify how well the associations were learned for each trial, we used a state-space computational model of learning that provided a probability of each trial being correct given past performance for that stimulus, that we take as a measure of the strength of the association. We used linear modelling to relate single-trial neural oscillations to single-trial measures of association strength. We found frontal midline theta oscillations during the delay period tracked learning, where theta activity was strongest during the early stages of learning and declined as the associations were formed. Further, posterior alpha and low-beta oscillations in the cue period showed strong desynchronised activity early in learning, while stronger alpha activity during the delay period was seen as associations became well learned. Moreover, the magnitude of these effects during early learning, before the associations were learned, related to improvements in memory seen on the next presentation of the stimulus. The current study provides clear evidence that frontal theta and posterior alpha/beta oscillations play a key role during associative memory formation.
Higher-Order Organization Principles of Pre-translational mRNPs

Compared to noncoding RNAs (ncRNAs), such as rRNAs and ribozymes, for which high-resolution structures abound, little is known about the tertiary structures of mRNAs. In eukaryotic cells, newly made mRNAs are packaged with proteins in highly compacted mRNA particles (mRNPs), but the manner of this mRNA compaction is unknown. Here, we developed and implemented RIPPLiT (RNA immunoprecipitation and proximity ligation in tandem), a transcriptome-wide method for probing the 3D conformations of RNAs stably associated with defined proteins, in this case, exon junction complex (EJC) core factors. EJCs multimerize with other mRNP components to form megadalton-sized complexes that protect large swaths of newly synthesized mRNAs from endonuclease digestion. Unlike ncRNPs, wherein strong locus-specific structures predominate, mRNPs behave more like flexible polymers. Polymer analysis of proximity ligation data for hundreds of mRNA species demonstrates that nascent and pre-translational mammalian mRNAs are compacted by their associated proteins into linear rod-like structures.
Antiviral Nucleoside Analogues with Axial Chirality

Abstract Chemistry and biological activity of nucleoside analogues comprising a chiral axis will be reviewed with emphasis on anti-HIV agent adenallene (1a) and anti-HIV/HBV analogue cytallene (1b). Possible mechanism of action, activity toward the enzymes of nucleic acid metabolism and structure-activity relationships will be discussed.
Synthesis and reactivity of 3-(1-hydroxy-3-buten-1-yl)chromone

Zn-induced allylation of chromone-3-carbaldehyde 1 produces 3-(1-hydroxy-3-butene-1-yl)chromone 2, which gives back 1 on treatment with formalin under acidic conditions, and reacts differently towards nitrogenous nucleophiles.
Detection of Shared Balancing Selection in the Absence of Trans-Species Polymorphism

Trans-species polymorphism has been widely used as a key sign of long-term balancing selection across multiple species. However, such sites are often rare in the genome and could result from mutational processes or technical artifacts. Few methods are yet available to specifically detect footprints of trans-species balancing selection without using trans-species polymorphic sites. In this study, we develop summary- and model-based approaches that are each specifically tailored to uncover regions of long-term balancing selection shared by a set of species by using genomic patterns of intraspecific polymorphism and interspecific fixed differences. We demonstrate that our trans-species statistics have substantially higher power than single-species approaches to detect footprints of trans-species balancing selection, and are robust to those that do not affect all tested species. We further apply our model-based methods to human and chimpanzee whole-genome sequencing data. In addition to the previously established major histocompatibility complex and malaria resistance-associated FREM3/GYPE regions, we also find outstanding genomic regions involved in barrier integrity and innate immunity, such as the GRIK1/CLDN17 intergenic region, and the SLC35F1 and ABCA13 genes. Our findings not only echo the significance of pathogen defense but also reveal novel candidates in maintaining balanced polymorphisms across human and chimpanzee lineages. Finally, we show that these trans-species statistics can be applied to and work well for an arbitrary number of species, and integrate them into open-source software packages for ease of use by the scientific community.
The Autism-Associated Gene Scn2a Contributes to Dendritic Excitability and Synaptic Function in the Prefrontal Cortex

Autism spectrum disorder (ASD) is strongly associated with de novo gene mutations. One of the most commonly affected genes is SCN2A. ASD-associated SCN2A mutations impair the encoded protein NaV1.2, a sodium channel important for action potential initiation and propagation in developing excitatory cortical neurons. The link between an axonal sodium channel and ASD, a disorder typically attributed to synaptic or transcriptional dysfunction, is unclear. Here we show that NaV1.2 is unexpectedly critical for dendritic excitability and synaptic function in mature pyramidal neurons in addition to regulating early developmental axonal excitability. NaV1.2 loss reduced action potential backpropagation into dendrites, impairing synaptic plasticity and synaptic strength, even when NaV1.2 expression was disrupted in a cell-autonomous fashion late in development. These results reveal a novel dendritic function for NaV1.2, providing insight into cellular mechanisms probably underlying circuit and behavioral dysfunction in ASD.
The effect of ortho methyl groups on cumyl systems

Abstract The reactions of 2-mesityl-2-propanol (2) and 2-mesityl-1-propene (6) have been investigated with the objective of evaluating the effect of ortho methyl groups on chemical reactivity. The 13C NMR spectrum of 2-mesityl-2-propyl cation (3) indicates the expected steric inhibition to resonance.
Screening of Excitons in Single, Suspended Carbon Nanotubes

Resonant Raman spectroscopy of single carbon nanotubes suspended across trenches displays red-shifts of up to 30 meV of the electronic transition energies as a function of the surrounding dielectric environment. We develop a simple scaling relationship between the exciton binding energy and the external dielectric function and thus quantify the effect of screening. Our results imply that the underlying particle interaction energies change by hundreds of meV.
Bond Valence Sums in Coordination Chemistry. Calculation of the Oxidation State of Chromium in Complexes Containing Only Cr−O Bonds and a Redetermination of the Crystal Structure of Potassium Tetra(peroxo)chromate(V)

A simple method for calculating the oxidation state of Cr in complexes containing only Cr−O bonds is presented. A total of 242 CrOn fragments with n = 3−6 were retrieved from the Cambridge Structural Database (CSD) and, together with the data for K3CrO8, were analyzed using the bond valence sum method. New R0 values for Cr(II) of 1.739(21) A, Cr(III) of 1.708(7) A, Cr(V) of 1.762(14) A, and Cr(VI) of 1.793(7) A were derived. An average R0 value of 1.724 A for Cr−O reproduces the oxidation state of 96 of the 110 Cr(II), Cr(III), and Cr(IV) CrOn complexes (n = 3−6) and that of K3CrO8 within 0.30 valence units. The crystal structure of K3CrO8 was redetermined at 173 K to provide accurate data for a Cr complex with both high oxidation state and coordination number. Potassium tetraperoxochromate(V), K3CrO8, is tetragonal, Space group Ī42m, a = b = 6.6940(3) A, c = 7.7536(5) A, Z = 2. The difficulties with fitting the observed valence for Cr(V) and Cr(VI) complexes with coordination numbers 4 and 5 are discusse...
Synthesis of new 2,4‐diamino‐7H‐pyrrolo[2,3‐d]pyrimidines via the Taylor ring transformation/ring annulation strategy

Selected examples 2,4-diamino-7H-pyrrolo[2,3-d]pyrimidines with a phenyl or benzyl group at the 5-position were synthesized as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii and Toxoplasma gondii, two potentially life-threatening opportunistic pathogens associated with AIDS and other disorders of the immune system. Aldol condensation of paraformaldehyde with substituted benzaldehydes or with phenylacetaldehyde afforded α-hydroxyketones with a phenyl or benzyl group at the 4-position. Further reaction of the hydroxyketones with malononitrile afforded 2-aminofuran-3carbonitriles, which upon heating with guanidine underwent ring transformation/ring annulation to produce 2,4-diamino-7H-pyrrolo[2,3-d]pyrimidines rather than 2,4-diaminofuro[2,3-d]pyrimidines. One of the target compounds obtained in this manner, 2,4-diamino-5-(3,4,5-trimethoxyphenyl)-7Hpyrrolo[2,3-d]pyrimidine (1d), may be viewed as a conformationally restricted analogue of trimethoprim, an antimicrobial agent widely used in combination with a sulfa drug to treat P. carinii and T. gondii opportunistic infections in patients with AIDS. Compound 1d inhibited P. carinii and T. gondii DHFR with IC50 values of 8.3 and 14 μM, respectively. This potency was somewhat greater than that of trimethoprim. However, because this compound was also more potent than trimethoprim against mammalian (rat liver) DHFR rat liver it lacked species selectivity. The other 2,4-diamino-7H-pyrrolo[2,3-d]pyrimidines synthesized were neither potent nor selective.
Doublecotin-Like Kinase 1 Increases Chemoresistance of Colorectal Cancer Cells through the Anti-Apoptosis Pathway.

Background: Colorectal Cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer-related deaths in the United States. Cancer Stem Cells (CSCs) are believed to be the primary reason for the recurrence of CRC. Specific stem cell marker, doublecortin-like kinase 1 (DCLK1) plays critical roles in the tumorigenesis and progression of CRC. Up-regulation of DCLK1 is correlated with poor prognosis. Whether DCLK1 is correlated with enhanced chemoresistance of CRC cells is unclear. We aim to reveal the association of DCLK1 with chemoresistance of CRC cells and the underlying molecular mechanisms. Methods: Stable DCLK1 over-expression cells (DCLK1+) were established using the HCT116 cells (WT). DCLK1+ and WT cells were treated with 5-Fluorouracil (5-Fu) at different doses for 24 or 48 hours. MTT assay was used to evaluate cell viability and IC50 of 5-Fu was determined. Quantitative real-time PCR was applied to determine the gene expression of caspase-3 (casp-3), casp-4, and casp-10. Cleaved casp-3 expression was investigated using Western blot and immunofluorescence. Results: Our results demonstrated that IC50 of 5-Fu for the DCLK1+ cells was significantly higher than that of the WT cells for both 24 and 48-hour treatment (p=0.002 and 0.048 respectively), indicating increased chemoresistance of the DCLK1+ cells. Gene expression of casp-3, casp-4, and casp-10 were significantly inhibited in the DCLK1+ cells after 5-Fu treatment compared to the WT cells (p=7.616e-08, 1.575e-05 and 5.307e-08, respectively). Cleaved casp-3 amount and casp-3 positive cells were significantly decreased in the DCLK1+ cells after 5-Fu treatment compared to the WT cells (p=0.015). Conclusions: In conclusion, our results demonstrated that DCLK1 overexpression enhanced the chemoresistance of CRC cells to 5-Fu treatment by suppressing gene expression of key caspases in the apoptosis pathway and activation of the apoptosis pathway. DCLK1 can be an intriguing therapeutic target for the effective treatment of CRC patients.
Preparation of 2‐(1H‐pyrazol‐5‐yl)benzenesulfonamides from polylithiated C(α),N‐carbo‐tert‐butoxyhydrazones and methyl 2‐(aminosulfonyl)benzoate

Select C(α), N-carbo-tert-butoxyhydrazones were dilithiated with excess lithium diisopropylamide followed by condensation with methyl 2-(aminosulfonyl)benzoate, acid cyclization, hydrolysis, and decarboxylation to afford new 2-(1H-pyrazol-5-yl)benzenesulfonamides, [NH-pyrazolyl-ortho-benzene-sulfonamides].
QTL mapping of natural variation reveals that the developmental regulator bruno reduces tolerance to P-element transposition in the Drosophila female germline.

Transposable elements (TEs) are obligate genetic parasites that propagate in host genomes by replicating in germline nuclei, thereby ensuring transmission to offspring. This selfish replication not only produces deleterious mutations—in extreme cases, TE mobilization induces genotoxic stress that prohibits the production of viable gametes. Host genomes could reduce these fitness effects in two ways: resistance and tolerance. Resistance to TE propagation is enacted by germline-specific small-RNA-mediated silencing pathways, such as the Piwi-interacting RNA (piRNA) pathway, and is studied extensively. However, it remains entirely unknown whether host genomes may also evolve tolerance by desensitizing gametogenesis to the harmful effects of TEs. In part, the absence of research on tolerance reflects a lack of opportunity, as small-RNA-mediated silencing evolves rapidly after a new TE invades, thereby masking existing variation in tolerance. We have exploited the recent historical invasion of the Drosophila melanogaster genome by P-element DNA transposons in order to study tolerance of TE activity. In the absence of piRNA-mediated silencing, the genotoxic stress imposed by P-elements disrupts oogenesis and, in extreme cases, leads to atrophied ovaries that completely lack germline cells. By performing quantitative trait locus (QTL) mapping on a panel of recombinant inbred lines (RILs) that lack piRNA-mediated silencing of P-elements, we uncovered multiple QTL that are associated with differences in tolerance of oogenesis to P-element transposition. We localized the most significant QTL to a small 230-kb euchromatic region, with the logarithm of the odds (LOD) peak occurring in the bruno locus, which codes for a critical and well-studied developmental regulator of oogenesis. Genetic, cytological, and expression analyses suggest that bruno dosage modulates germline stem cell (GSC) loss in the presence of P-element activity. Our observations reveal segregating variation in TE tolerance for the first time, and implicate gametogenic regulators as a source of tolerant variants in natural populations.