cssi/SciSciGPT-SciSciNet huggingface dataset:
Field studies reveal a close relative of C. elegans thrives in the fresh figs of Ficus septica and disperses on its Ceratosolen pollinating wasps

Biotic interactions are ubiquitous and require information from ecology, evolutionary biology, and functional genetics in order to be understood. However, study systems that are amenable to investigations across such disparate fields are rare. Figs and fig wasps are a classic system for ecology and evolutionary biology with poor functional genetics; Caenorhabditis elegans is a classic system for functional genetics with poor ecology. In order to help bridge these disciplines, here we describe the natural history of a close relative of C. elegans, Caenorhabditis inopinata, that is associated with the fig Ficus septica and its pollinating Ceratosolen wasps. To understand the natural context of fig-associated Caenorhabditis, fresh F. septica figs from four Okinawan islands were sampled, dissected, and observed under microscopy. C. inopinata was found in all islands where F. septica figs were found. C.i nopinata was routinely found in the fig interior and almost never observed on the outside surface. C. inopinata was only found in pollinated figs, and C. inopinata was more likely to be observed in figs with more foundress pollinating wasps. Actively reproducing C. inopinata dominated early phase figs, whereas late phase figs with emerging wasp progeny harbored C. inopinata dauer larvae. Additionally, C. inopinata was observed dismounting from Ceratosolen pollinating wasps that were placed on agar plates. C. inopinata was not found on non-pollinating, parasitic Philotrypesis wasps. Finally, C. inopinata was only observed in F. septica figs among five Okinawan Ficus species sampled. These are the first detailed field observations of C. inopinata, and they suggest a natural history where this species proliferates in early phase F. septica figs and disperses from late phase figs on Ceratosolen pollinating fig wasps. While consistent with other examples of nematode diversification in the fig microcosm, the fig and wasp host specificity of C. inopinata is highly divergent from the life histories of its close relatives and frames hypotheses for future investigations. This natural co-occurrence of the fig/fig wasp and C. inopinata study systems sets the stage for an integrated research program that can help to explain the evolution of interspecific interactions.
Dynamic Pricing of Limited Inventories with Product Returns

Many online retail channels face high rates of product returns. This poses a new challenge to the sellers’ dynamic pricing problem when some returns in good condition can be resold in the selling s...
Problems of commitment in arming and war: how insecurity and destruction matter

This paper analyzes a guns-versus-butter model in which two agents compete for control over an insecure portion of their combined output. They can resolve this dispute either peacefully through settlement or by military force through open conflict (war). Both types of conflict resolution depend on the agents’ arming choices, but only war is destructive. We find that, insofar as entering into binding contracts on arms is not possible and agents must arm even under settlement to secure a bigger share of the contested output, the absence of long-term commitments need not be essential in understanding the outbreak of destructive war. Instead, the ability to make short-term commitments could induce war. More generally, our analysis highlights how the pattern of war’s destructive effects, the degree of output insecurity and the initial distribution of resources matter for arming decisions and the choice between peace and war. We also explore the implications of transfers for peace.
Game-Based Video-Context Dialogue

Current dialogue systems focus more on textual and speech context knowledge and are usually based on two speakers. Some recent work has investigated static image-based dialogue. However, several real-world human interactions also involve dynamic visual context (similar to videos) as well as dialogue exchanges among multiple speakers. To move closer towards such multimodal conversational skills and visually-situated applications, we introduce a new video-context, many-speaker dialogue dataset based on live-broadcast soccer game videos and chats from Twitch.tv. This challenging testbed allows us to develop visually-grounded dialogue models that should generate relevant temporal and spatial event language from the live video, while also being relevant to the chat history. For strong baselines, we also present several discriminative and generative models, e.g., based on tridirectional attention flow (TriDAF). We evaluate these models via retrieval ranking-recall, automatic phrase-matching metrics, as well as human evaluation studies. We also present dataset analyses, model ablations, and visualizations to understand the contribution of different modalities and model components.
Comparison of Signal Detectors for Time Domain Radio SETI

Thellbourgdetectorspaper. In the absence of prior knowledge concerning the expected signal, SETI detection pipelines necessitate high sensitivity, versatility, and limited computational complexity to maximize the search parameter space and minimize the probability of misses. This paper addresses the SETI detection problem as a binary hypothesis testing problem, and compares four detection schemes exploiting artificial features of the data collected by a single receiver radio telescope. After a theoretical comparison, those detectors are applied to real data collected with the Green Bank Telescope in West Virginia (USA).
A Qualitative Comparison of CoQA, SQuAD 2.0 and QuAC

We compare three new datasets for question answering: SQuAD 2.0, QuAC, and CoQA, along several of their new features: (1) unanswerable questions, (2) multi-turn interactions, and (3) abstractive answers.We show that the datasets provide complementary coverage of the first two aspects, but weak coverage of the third.Because of the datasets’ structural similarity, a single extractive model can be easily adapted to any of the datasets and we show improved baseline results on both SQuAD 2.0 and CoQA. Despite the similarity, models trained on one dataset are ineffective on another dataset, but we find moderate performance improvement through pretraining. To encourage cross-evaluation, we release code for conversion between datasets.
The Productivity J-Curve: How Intangibles Complement General Purpose Technologies

General purpose technologies (GPTs) such as AI enable and require significant complementary investments, including co-invention of new processes, products, business models and human capital. These complementary investments are often intangible and poorly measured in the national accounts, even when they create valuable assets for the firm. We develop a model that shows how this leads to an underestimation of productivity growth in the early years of a new GPT, and how later, when the benefits of intangible investments are harvested, productivity growth will be overestimated. Our model generates a Productivity J-Curve that can explain the productivity slowdowns often accompanying the advent of GPTs, as well as the increase in productivity later. We use our model to analyze empirically the historical roles of intangibles tied to R&D, software, and computer hardware. We find substantial and ongoing Productivity J-Curve effects for software in particular and computer hardware to a lesser extent. Our adjusted measure TFP is 11.3% higher than official measures at the end of 2004, and 15.9% higher than official measures at the end of 2017. We then assess how AI-related intangible capital may be currently affecting measured productivity and find the effects are small but growing.
Small-molecule CaVα1·CaVβ antagonist suppresses neuronal voltage-gated calcium-channel trafficking

Extracellular calcium flow through neuronal voltage-gated Ca V 2.2 calcium channels converts action potential-encoded information to the release of pronociceptive neurotransmitters in the dorsal horn of the spinal cord, culminating in excitation of the postsynaptic central nociceptive neurons. The Ca V 2.2 channel is composed of a pore-forming α 1 subunit (Ca V α 1 ) that is engaged in protein–protein interactions with auxiliary α 2 /δ and β subunits. The high-affinity Ca V 2.2α 1 ⋅Ca V β 3 protein–protein interaction is essential for proper trafficking of Ca V 2.2 channels to the plasma membrane. Here, structure-based computational screening led to small molecules that disrupt the Ca V 2.2α 1 ⋅Ca V β 3 protein–protein interaction. The binding mode of these compounds reveals that three substituents closely mimic the side chains of hot-spot residues located on the α-helix of Ca V 2.2α 1 . Site-directed mutagenesis confirmed the critical nature of a salt-bridge interaction between the compounds and Ca V β 3 Arg-307. In cells, compounds decreased trafficking of Ca V 2.2 channels to the plasma membrane and modulated the functions of the channel. In a rodent neuropathic pain model, the compounds suppressed pain responses. Small-molecule α-helical mimetics targeting ion channel protein–protein interactions may represent a strategy for developing nonopioid analgesia and for treatment of other neurological disorders associated with calcium-channel trafficking.
Bernstein polynomial inequality on a compact subset of the real line

Abstract We prove an analogue of the classical Bernstein polynomial inequality on a compact subset E of the real line. The Lipschitz continuity of the Green function for the complement of E with respect to the extended complex plane and the differentiability at a point of E of a special, associated with E , conformal mapping of the upper half-plane onto the comb domain play crucial role in our investigation.
Binary Decision Diagrams for Bin Packing with Minimum Color Fragmentation.

Bin Packing with Minimum Color Fragmentation (BPMCF) is an extension of the Bin Packing Problem in which each item has a size and a color and the goal is to minimize the sum of the number of bins containing items of each color. In this work, we introduce the BPMCF and present a decomposition strategy to solve the problem, where the assignment of items to bins is formulated as a binary decision diagram and an optimal integrated solutions is identified through a mixed-integer linear programming model. Our computational experiments show that the proposed approach greatly outperforms a direct formulation of BPMCF and that its performance is suitable for large instances of the problem.
Topological Data Analysis of Single-Cell Hi-C Contact Maps

Due to recent breakthroughs in high-throughput sequencing, it is now possible to use chromosome conformation capture (CCC) to understand the three dimensional conformation of DNA at the whole genome level, and to characterize it with the so-called contact maps. This is very useful since many biological processes are correlated with DNA folding, such as DNA transcription. However, the methods for the analysis of such conformations are still lacking mathematical guarantees and statistical power. To handle this issue, we propose to use the Mapper, which is a standard tool of Topological Data Analysis (TDA) that allows one to efficiently encode the inherent continuity and topology of underlying biological processes in data, in the form of a graph with various features such as branches and loops. In this article, we show how recent statistical techniques developed in TDA for the Mapper algorithm can be extended and leveraged to formally define and statistically quantify the presence of topological structures coming from biological phenomena, such as the cell cyle, in datasets of CCC contact maps.
Its all in a name: detecting and labeling bots by their name

Automated social media bots have existed almost as long as the social media environments they inhabit. Their emergence has triggered numerous research efforts to develop increasingly sophisticated means to detect these accounts. These efforts have resulted in a cat and mouse cycle in which detection algorithms evolve trying to keep up with ever evolving bots. As part of this continued evolution, our research proposes a multi-model ‘tool-box’ approach in order to conduct detection at various tiers of data granularity. To support this toolbox approach this research also uses random string detection applied to user names to filter twitter streams for bot accounts and use this as labeled training data for follow on research.
Unconstrained Iris Segmentation Using Convolutional Neural Networks

The extraction of consistent and identifiable features from an image of the human iris is known as iris recognition. Identifying which pixels belong to the iris, known as segmentation, is the first stage of iris recognition. Errors in segmentation propagate to later stages. Current segmentation approaches are tuned to specific environments.
Long-run net distributionary effects of federal disaster insurance: the case of Hurricane Katrina

Abstract Federal disaster insurance–in the form of national flood insurance, the Federal Emergency Management Agency (FEMA), and other programs–is designed to nationally-distribute large geography-specific shocks like earthquakes and hurricanes. This study examines the local long-run distributionary effects of Hurricane Katrina and the subsequent policy response on impacted residents. Using a unique fifteen-year panel of five percent of adult Americans’ credit reports, we find persistently-higher rates of insolvency and lower homeownership among inundated residents of New Orleans ten years after the storm, relative to their non-flooded neighbors. Residents of mostly-white and mostly-black neighborhoods are similarly-impacted in the short and long run, though residents of white neighborhoods are more likely to migrate out of the city. However, residents of the large Gulf Opportunity (GO) Zone surrounding New Orleans, who were also eligible for various federal programs, obtained net financial benefits in the years following Katrina; a decade later, those residents have higher rates of consumption and homeownership, are more likely to have paid off their mortgages, and have lower rates of bankruptcy and foreclosure than residents outside the GO Zone. These net subsidies are found to be progressive—favoring young and low-income residents of the counties surrounding New Orleans—and are broadly similar across black and white neighborhoods.
Do Bilateral Tax Treaties Promote Foreign Direct Investment

We explore the impact of bilateral tax treaties on foreign direct investment using data from OECD countries over the period 1982-1992. We find that recent treaty formation does not promote new investment, contrary to the common expectation. For certain specifications we find that treaty formation may actually reduce investment as predicted by arguments suggesting treaties are intended to reduce tax evasion rather than promote foreign investment.
Factory Productivity and the Concession System of Incorporation in Late Imperial Russia, 1894–1908

In Imperial Russia, incorporation required an expensive special concession, yet over 4,000 Russian firms incorporated before 1914. I identify the characteristics of incorporating firms and measure the productivity gains and growth in machine power enjoyed by corporations using newly-constructed factory-level panel data compiled from Russian factory censuses. Factories owned by corporations were larger, more productive, and more mechanized than unincorporated factories. Higher productivity factories were more likely to incorporate and, after incorporating, added machine power and became even more labor productive. Russian firms sought the corporate form's full set of advantages, not just stock markets access, to obtain scarce long-term financing.
Focus Group Techniques

Frequently misunderstood as a simple discussion group, weak by scientific standards and producing little valid data, focus groups, in fact, make contributions whether combined with more traditional research methods or standing alone as a unique technique. Keywords: focus groups; facilitator; qualitative research
Chapter 4 – Frequency Response

A discussion has been made on a frequency response where digital signal processing is performed. The goal to modify the frequency representation of a signal through filtering is the most elemental signal processing functions. Gradually, the discussion moves toward the responses and the complex exponential factors affecting it. It also touches on how to use a filter to normalize the response, when an input frequency is put through. The chapter also uses digital filter as a linear device to change the amplitude and phase of the input signal.
Shedding light on regional growth and convergence in India

Abstract A large body of research on India’s rapid economic growth since 1991 also documents increasing regional disparities. In this paper, we use unsaturated night light data to challenge this dominant narrative of unequal growth. For 520 districts spanning a 15 year period (1996–2010), we find overwhelming evidence of absolute convergence. Dividing districts further into rural and urban areas, we also show that this catching-up can be attributed mainly to faster growth in rural areas. Geographically disadvantaged districts - those further away from the coast, with lower agricultural suitability, and more rugged terrain also grew faster. The convergence results are not associated with major infrastructure and education initiatives that overlapped with the period of analysis, and also hold for alternative measures of night-lights that cover a longer period of time (1992–2013).
Periodic Control of Unmanned Aerial Vehicles Based on Differential Flatness

Unmanned Aerial Vehicles (UAV) are making increasingly long flights today with significantly longer mission times. This requires the UAVs to have longer endurance as well as have long range capabilities. With regards to this, many researchers have shown the non-optimality of the steady state flight of aircrafts and how periodic trajectories may benefit the cause. This work re-establishes the non-optimality of a steady state flight and proposes a sub-optimal periodic solution using the concept of differential flatness. An example of an Aerosonde UAV is used to illustrate the percentage improvement in cost of the periodic control solutions.
Coordinated host-pathogen transcriptional dynamics revealed using sorted subpopulations and single macrophages infected with Candida albicans

The outcome of fungal infections depends on interactions with innate immune cells. Within a population of macrophages encountering Candida albicans, there are distinct host-pathogen trajectories; however, little is known about the molecular heterogeneity that governs these fates. Here we developed an experimental system to separate interaction stages and single macrophage cells infected with C. albicans from uninfected cells and assessed transcriptional variability in the host and fungus. Macrophages displayed an initial up-regulation of pathways involved in phagocytosis and proinflammatory response after C. albicans exposure that declined during later time points. Phagocytosed C. albicans shifted expression programs to survive the nutrient poor phagosome and remodeled the cell wall. The transcriptomes of single infected macrophages and phagocytosed C. albicans displayed a tightly coordinated shift in gene expression co-stages and revealed expression bimodality and differential splicing that may drive infection outcome. This work establishes an approach for studying host-pathogen trajectories to resolve heterogeneity in dynamic populations.
Distributional Effects of Tobacco Taxation : A Comparative Analysis

Tobacco taxes have positive impacts on health outcomes. However, policy makers often hesitate to use them because of the perception that poorer households are affected disproportionally more than richer households. This study compares the simulated distributional effects of tobacco tax increases in eight low- and middle-income countries. It applies a standardized extended cost-benefit analysis methodology and relies on comparable data sources across countries. The net effect of raising taxes on cigarettes encompasses the direct negative price shock to household budgets and the long-term benefits of improved health outcomes. The distributional incidence is assessed by estimating decile-specific behavioral responses and relative income gains. The comparative results do not support the claim that tobacco taxes are necessarily regressive. Although welfare losses from the first-order price shock disproportionally affect the poor, these negative shocks are attenuated by greater price-responsiveness among lower-income groups and further offset by higher long-term relative gains through reduced medical expenditures and additional years of productive life as taxes dissuade smoking. In several countries, increasing the price of cigarettes is pro-poor and welfare improving for a large share of the population. Along with raising taxes, policy should aim at encouraging responsiveness to price changes and target tobacco-related medical expenses that disproportionally burden the poor.
Pandora's Problem with Nonobligatory Inspection

Martin Weitzman's "Pandora's problem" furnishes the mathematical basis for optimal search theory in economics. Nearly 40 years later, Laura Doval introduced a version of the problem in which the searcher is not obligated to pay the cost of inspecting an alternative's value before selecting it. Unlike the original Pandora's problem, the version with nonobligatory inspection cannot be solved optimally by any simple ranking-based policy, and it is unknown whether there exists any polynomial-time algorithm to compute the optimal policy. This motivates the study of approximately optimal policies that are simple and computationally efficient. In this work we provide the first non-trivial approximation guarantees for this problem. We introduce a family of "committing policies" such that it is computationally easy to find and implement the optimal committing policy. We prove that the optimal committing policy is guaranteed to approximate the fully optimal policy within a 1-1/e = 0.63... factor, and for the special case of two boxes we improve this factor to 4/5 and show that this approximation is tight for the class of committing policies.
On the performance of volatility-managed portfolios

Abstract Using a comprehensive set of 103 equity strategies, we analyze the value of volatility-managed portfolios for real-time investors. Volatility-managed portfolios do not systematically outperform their corresponding unmanaged portfolios in direct comparisons. Consistent with Moreira and Muir (2017), volatility-managed portfolios tend to exhibit significantly positive alphas in spanning regressions. However, the trading strategies implied by these regressions are not implementable in real time, and reasonable out-of-sample versions generally earn lower certainty equivalent returns and Sharpe ratios than do simple investments in the original, unmanaged portfolios. This poor out-of-sample performance for volatility-managed portfolios stems primarily from structural instability in the underlying spanning regressions.
Distributed Quantum Fiber Magnetometry

Nitrogen-vacancy (NV) quantum magnetometers offer exceptional sensitivity and long-term stability. However, their use to date in distributed sensing applications, including remote detection of ferrous metals, geophysics, and biosensing, has been limited due to the need to combine optical, RF, and magnetic excitations into a single system. Existing approaches have yielded localized devices but not distributed capabilities. In this study, we report on a continuous system-in-a-fiber architecture that enables distributed magnetic sensing over extended lengths. Key to this realization is a thermally drawn fiber that has hundreds of embedded photodiodes connected in parallel and a hollow optical waveguide that contains a fluid with NV diamonds. This fiber is placed in a larger coaxial cable to deliver the required RF excitation. We realize this distributed quantum sensor in a water-immersible 90-meter-long cable with 102 detection sites. A sensitivity of 63 nT Hz-1/2 per site, limited by laser shot noise, was established along a 90 m test section. This fiber architecture opens new possibilities as a robust and scalable platform for distributed quantum sensing technologies.
When is it beneficial to provide freelance suppliers with choice? A hierarchical approach for peer-to-peer logistics platforms

Abstract This paper proposes and evaluates a new hierarchical approach to peer-to-peer logistics platforms, recasting the platform’s role as one providing personalized menus of requests to freelance suppliers. A bilevel optimization formulation explicitly models the two stage decision process: first, the platform determines which set of requests to recommend to which suppliers, and second, suppliers have a choice to select which request (if any) to fulfill. By harnessing the problem’s structure, the computationally expensive mixed-integer linear bilevel problem is transformed into an equivalent single-level problem that is computationally superior. A computational study based on ride-sharing quantifies the value of providing suppliers with choices. When a platform’s knowledge of suppliers’ selections is imperfect, our hierarchical approach outperforms existing recommendation methods, namely, centralized, many-to-many stable matching, and decentralized approaches. We show that a platform’s lack of knowledge over suppliers’ selections can be compensated by providing choices in environments with either inflexible suppliers or when suppliers’ utilities have higher variance than the platform’s utilities. In these environments, providing choices and recommending alternatives to more than one supplier can be beneficial to not only the platform, but also freelance suppliers and demand requests.
A scalable estimator of SNP heritability for biobank-scale data.

Motivation Heritability, the proportion of variation in a trait that can be explained by genetic variation, is an important parameter in efforts to understand the genetic architecture of complex phenotypes as well as in the design and interpretation of genome-wide association studies. Attempts to understand the heritability of complex phenotypes attributable to genome-wide single nucleotide polymorphism (SNP) variation data has motivated the analysis of large datasets as well as the development of sophisticated tools to estimate heritability in these datasets. Linear mixed models (LMMs) have emerged as a key tool for heritability estimation where the parameters of the LMMs, i.e. the variance components, are related to the heritability attributable to the SNPs analyzed. Likelihood-based inference in LMMs, however, poses serious computational burdens. Results We propose a scalable randomized algorithm for estimating variance components in LMMs. Our method is based on a method-of-moment estimator that has a runtime complexity O(NMB) for N individuals and M SNPs (where B is a parameter that controls the number of random matrix-vector multiplications). Further, by leveraging the structure of the genotype matrix, we can reduce the time complexity to O(NMBmax( log⁡3N, log⁡3M)). We demonstrate the scalability and accuracy of our method on simulated as well as on empirical data. On standard hardware, our method computes heritability on a dataset of 500 000 individuals and 100 000 SNPs in 38 min. Availability and implementation The RHE-reg software is made freely available to the research community at: https://github.com/sriramlab/RHE-reg.
Synthesis and evaluation of several new (2-chloroethyl)nitrosocarbamates as potential anticancer agents.

Seven new (2-chloroethyl)nitrosocarbamates have been synthesized as potential anticancer alkylating agents. These compounds were designed with carrier moieties that would either act as prodrugs or confer water solubility. All compounds were screened in an in vitro panel of five human tumor cell lines: CAKI-1 (renal), DLD-1 (colon), NCI-H23 (lung), SK-MEL-28 (melanoma), and SNB-7 (CNS). Several agents showed good activity with IC50 values in the range of 1−10 μg/mL against at least two of the cell lines. One compound, carbamic acid, (2-chloroethyl)nitroso-4-acetoxybenzyl ester (3), was selected for further study in vivo against intraperitoneally implanted P388 murine leukemia. In addition to the aforementioned compound, both carbamic acid, (2-chloroethyl)nitroso-4-nitrobenzyl ester (9) and carbamic acid, (2-chloroethyl)nitroso-2,3,4,6-tetra-O-acetyl-1-α,β-d-glucopyranose ester (24) were evaluated against subcutaneously implanted M5076 murine sarcoma in mice. None of these compounds were active in vivo.
N-h insertion reactions of Boc-amino acid amides: solution- and solid-phase synthesis of pyrazinones and pyrazines.

A series of α-diazo-β-ketoesters were reacted with Boc amino acid amides in the presence of rhodium octanoate catalyst. The resulting N−H insertion products were treated with acid, providing the 1,4-azine intermediates, which were oxidized by air to form the corresponding pyrazine-6-one products. The pyrazine-6-ones were further derivatized by N-alkylation or by conversion to the arylpyrazines using sequential bromination and Suzuki coupling reactions.
Anti-dipsotropic isoflavones: the potential therapeutic agents for alcohol dependence.

Daidzin is the active principle of Radix puerariae (RP), an herbal remedy that has been used apparently safely and effectively for the treatment of "alcohol addiction" in China for more than a millennium. It has been shown to reduce alcohol consumption in all animal models tested to date. A link between daidzin's capacity to reduce alcohol consumption and its ability to increase liver mitochondrial monoamine oxidase (MAO): aldehyde dehydrogenase (ALDH-2) activity ratio has been established. Daidzin analogs that potently inhibit ALDH-2 but not MAO are the most anti-dipsotropic, whereas those that also inhibit MAO are not. On the basis of these findings, it was proposed that the liver mitochondrial MAO-ALDH-2 pathway is the primary site of action of daidzin and that a biogenic aldehyde derived from the action of MAO mediates its anti-dipsotropic action. Therefore, to design and synthesize more potent anti-dipsotropic analogs, structural features that would enhance ALDH-2 inhibition and/or decrease MAO inhibition needed to be evaluated. Structure-activity-relationship (SAR) studies have revealed that a sufficient set of criteria for a potent anti-dipsotropic analog is an isoflavone with a free 4'-OH function and a straight-chain alkyl at the 7 position that has a terminal polar function such as -OH, -COOH, or -NH2. The preferable chain lengths for the 7-O-omega-carboxy, 7-O-omega-hydroxy, and 7-O-omega-amino substituents are 5 or = 4, respectively. Analogs that meet these criteria have increased potency for ALDH-2 inhibition and/or decreased potency for MAO inhibition and are, therefore, likely to be potent anti-dipsotropic agents.
Regioselective N/C-Heterocyclization of Allenylindium Bromide Across Aryl Azides: One-Pot Synthesis of 5-Methyl-1,2,3-triazoles

An unprecedented, one-pot regioselective synthesis of 1,5-disubstituted 1,2,3-triazoles through N/C-heterocyclization of allenylindium bromide across aryl azides is described. The synthesis is carried out under mild conditions in aqueous medium and proceeds regioselectively in moderate to good yields.
Regioselective construction of six-membered fused heterocyclic rings via Pd/C-mediated C–C coupling followed by iodocyclization strategy: a new entry to 2H-1,2-benzothiazine-1,1-dioxides

Abstract We describe a practical and elegant method of constructing a thiazine ring fused with benzene under mild reaction conditions. A variety of 4-iodo-2H-benzo[e][1,2]thiazine-1,1-dioxides were prepared with high regioselectivity via a two-step process involving Pd/C-mediated C–C coupling of o-halobenzenesulfonamides with terminal alkynes, followed by iodocyclization of the resulting o-(1-alkynyl)arenesulfonamide using elemental iodine in acetonitrile. The coupling reaction was carried out using 10% Pd/C–PPh3–CuI as a catalyst system in the presence of Et3N. The process worked well for bromides and iodides, and a wide array of terminal alkynes containing alkyl and aryl substituents were employed. The iodocyclization step tolerated a variety of functional groups such as hydroxy, chloro, cyano, and methoxy, producing the six-membered heterocyclic ring selectively. The resulting 4-iodo-2H-benzo[e][1,2]thiazine-1,1-dioxides participated in Sonogashira, Heck, and Suzuki reactions producing a wide range of functionally substituted benzothiazines in good yields.
Homogeneous supported synthesis using ionic liquid supports : Tunable separation properties

We report a homogeneous supported version of Koser's salt based on a room-temperature ionic liquid (RTIL) support. By altering the nature of the RTIL, a material was developed that was stable, recyclable, and readily separable from the tosyloxylated ketone products just by using variations in solvent polarity. A similar approach should be applicable to a wide range of supported catalysts and reagents.
A SIMPLE AND EFFICIENT METHOD FOR PREPARATION OF UNSYMMETRICAL SULFIDES

Abstract A simple and high efficient method for preparation of unsymmetrical sulfides is described.
TOTAL SYNTHESIS OF (-)-TETRAHYDROPALMATINE VIA CHIRAL FORMAMIDINE CARBANIONS : UNEXPECTED BEHAVIOR WITH CERTAIN ORTHO-SUBSTITUTED ELECTROPHILES

A method has been developed by alkylation of chiral lithioformamidines to construct protoberberine alkaloids with a C(9) and C(10) D-ring substitution pattern. This ring pattern was established using an ortho-substituted hydroxymethylbenzene electrophile protected as a silyl ether to ultimately provide (-)-tetrahydropalmatine in 88% ee. Additionally, we have discovered limitations with ortho-substituted electrophiles in the asymmetric formamidine alkylation. These electrophiles have the potential to disrupt the lithium formamidine chelate and cause the selectivity in the alkylation to be uncharacteristically low. The total synthesis of (+/-)-canadine and (-)-tetrahydropalmatine along with the limitations to the formamidine alkylation technology are delineated herein.
Synthesis of butenolides as seed germination stimulants

Syntheses of a series of novel butenolides as seed germination stimulants are described. The key steps include the cyclization reaction of enamine 4 to form a pyran ring, the efficient halogenating reaction and the selective lithiation reaction of butenolides.
Superloser: A Plasmid Shuffling Vector for Saccharomyces cerevisiae with Exceedingly Low Background

Here we report a new plasmid shuffle vector for forcing budding yeast (Saccharomyces cerevisiae) to incorporate a new genetic pathway in place of a native pathway – even an essential one – while maintaining low false positive rates (less than 1 in 108 per cell). This plasmid, dubbed “Superloser,” was designed with reduced sequence similarity to commonly used yeast plasmids (i.e., pRS400 series) to limit recombination, a process that in our experience leads to retention of the yeast gene(s) instead of the desired gene(s). In addition, Superloser utilizes two orthogonal copies of the counter-selectable marker URA3 to reduce spontaneous 5-fluoroorotic acid resistance. Finally, the CEN/ARS sequence is fused to the GAL1-10 promoter, which disrupts plasmid segregation in the presence of the sugar galactose, causing Superloser to rapidly be removed from a population of cells. We show one proof-of-concept shuffling experiment: swapping yeast’s core histones out for their human counterparts. Superloser is especially useful for forcing yeast to use highly unfavorable genes, such as human histones, as it enables plating a large number of cells (1.4x109) on a single 10 cm petri dish while maintaining a very low background. Therefore, Superloser is a useful tool for yeast geneticists to effectively shuffle low viability genes and/or pathways in yeast that may arise in as few as 1 in 108 cells.
One-Pot Two-Step Synthesis of Quinoxalinones and Diazepinones via a Tandem Oxidative Amidation–Deprotection–Cyclization Sequence

This report discloses novel concise syntheses of quinoxalinones and diazepinones via a tandem oxidative amidation–deprotection–cyclization sequence. A selenium dioxide mediated oxidative amidation of arylglyoxals with secondary amines was carried out under microwave irradiation to give the corresponding α-keto amides, followed by an acid-promoted deprotection and cyclization to afford the desired products in moderate to good yields.
Fluorinated Natural Products with Clinical Significance

The modification of natural products in an effort to alter their biochemical capacity is a common technique utilized by synthetic and medicinal chemists. Fluorine substitution imparts unique and advantageous physiochemical properties that can be shrewdly employed to constructively alter pharmacological agents. The adornment of natural products with fluorine has proven beneficial in several examples. This overview discusses several of the most relevant fluorinated natural products under current examination.
The electrochemical synthesis of telluride Zintl anions

Abstract A novel electrochemical synthetic technique has been developed recently for the generation of heteropolyatomic Zintl anion clusters via the cathodic dissolution of telluride electrodes. Whereas previous synthetic techniques for the generation of these compounds have relied on high temperature fusion of the elements and/or extraction methods, this technique simply relies on the constantly increasing concentration of anions as they are discharged from a cathode, is performed at room temperature and in many cases yields X-ray quality single crystals in as little as 3–5 days. In the process of our study of this technique, it has also been shown that it allows for the preparation of Zintl anions which have not been and may not be accessible by these standard high temperature and extraction techniques. The versatility of this synthetic technique has been demonstrated by the isolation of small six- to seven-atom anions, larger 15-atom cluster anions and one-dimensional chain materials from the Au, Ga, In, Sn, As and Sb telluride systems. Ongoing research suggests that the synthesis of additional materials should be possible.
Rearrangements of (chloromethyl)organylsilanes induced by Lewis acids or by Lewis bases: Regioselective methylenation of allylic systems†‡

In order to study the scope and mechanisms of the migration of organyl groups from silicon to its adjacent methylene carbon, a series of derivatives of the type RSiMe2CH2Cl were synthesized, where R is vinyl, benzyl, methallyl, phenylethynyl, aryloxy, and N-methylanilino. Attempts were then undertaken to induce such Si C shifts by either the Lewis acid, methylaluminum dichloride, or the Lewis base, potassium fluoride. Under Lewis acidic conditions, only the benzyl and methylallyl groups could be induced to migrate; clearly, in the case of benzyl (and probably in the case of methallyl), migration was accompanied by allylic rearrangement to produce the o-tolyl group. Under the agency of KF, all the groups investigated underwent rearrangement to produce FSiMe2CH2R. By a crossover experiment, it was shown that, when R = aryloxy, the rearrangement occurs intermolecularly. Experimental evidence indicates that all KF-induced migrations are probably intermolecular and all MeAlCl2-induced migrations considered here are intramolecular. The advantages for organosilicon synthesis of utilizing so-called “relay substitution reactions” with the ClSiR2CH2Cl system are discussed: With unsymmetrical allylic systems, regioselective methylenation now becomes possible, simply by inducing the Si C rearrangement by MeAlCl2 or by KF.
Oxidation of pyrrole α-methyl to methoxymethyl with ceric triflate

Abstract Pyrrole α-methyl methyl ethers can be prepared in high yield by oxidation of pyrrole α-methyl groups with ceric triflate in methanol when the pyrrole ring also has an α-carboxylic acid ester group, and high yields of dipyrrylmethanes may be obtained in a one-pot oxidation-solvolysis reaction.
Tetrasubstituted pyrrolidines via a tandem aza-Payne/hydroamination reaction.

A facile tandem aza-Payne/hydroamination reaction of aziridinol is reported, which yields highly functionalized pyrrolidines. Addition of alkynyl Grignards to 2,3-aziridinals yields, in most cases,...
Generation and Cycloaddition Behavior of Spirocyclic Carbonyl Ylides. Application to the Synthesis of the Pterosin Family of Sesquiterpenes

The Rh(II)-catalyzed reaction of 1-acetyl-1-(diazoacetyl)cyclopropane and ethyl 3-(1-acetyl-cyclopropyl)-2-diazo-3-oxopropiolate with various dipolarophiles afforded dipolar cycloadducts in good yield. The reaction involves the formation of a rhodium carbenoid and subsequent transannular cyclization of the electrophilic carbon onto the adjacent keto group to generate a five-membered cyclic carbonyl ylide which undergoes a subsequent dipolar cycloaddition reaction. The regiochemical results encountered can be rationalized on the basis of FMO considerations. For carbonyl ylides, the HOMO dipole is dominant for reactions with electron deficient dipolarophiles, while the LUMO becomes important for cycloaddition to more electron rich species. A short synthesis of several members of the pterosin family of sesquiterpenes is described in which the key step involves a dipolar cycloaddition using a carbonyl ylide. The Rh(II)-catalyzed reaction of 1-acetyl-1-(diazoacetyl)cyclopropane with cyclopentenone afforded a d...
Radical mediated synthesis of 6‐arylphenanthridines via benzotriazole ring‐opening

Lithiation of diarylbenzotriazol-1-ylmethanes followed by addition of copper(I) iodide gave 6-arylphenanthridine derivatives in moderate yields. When the two aryl groups were the same or contained very different electron densities, only one product was obtained. However, when the two aryl groups exhibited electron densities of similar magnitude, two isomers were afforded. According to the substituent effect, we believe that the reactions proceed via radical intermediates formed by copper(I) iodide.
ScreenCube: A 3D Printed System for Rapid and Cost-Effective Chemical Screening in Adult Zebrafish

Abstract Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish. Using prefilled screening plates, the system enables dosing of 96 fish in ∼3 min, with a 10-fold reduction in drug quantity compared to that used in previous chemical screens in adult zebrafish. We characterize water quality kinetics during immersion in the system and use these kinetics to rationally design intermittent dosing regimens that result in 100% fish survival. As a demonstration of system fidelity, we show the potential to identify two known chemical inhibitors of adu...
Geometry of antiparallel microtubule bundles regulates relative sliding and stalling by PRC1 and Kif4A

Motor and non-motor crosslinking proteins play critical roles in determining the size and stability of microtubule-based architectures. Currently, we have a limited understanding of how geometrical properties of microtubule arrays, in turn, regulate the output of crosslinking proteins. Here we investigate this problem in the context of microtubule sliding by two interacting proteins: the non-motor crosslinker PRC1 and the kinesin Kif4A. The collective activity of PRC1 and Kif4A also results in their accumulation at microtubule plus-ends (‘end-tag’). Sliding stalls when the end-tags on antiparallel microtubules collide, forming a stable overlap. Interestingly, we find that structural properties of the initial array regulate microtubule organization by PRC1-Kif4A. First, sliding velocity scales with initial microtubule-overlap length. Second, the width of the final overlap scales with microtubule lengths. Our analyses reveal how micron-scale geometrical features of antiparallel microtubules can regulate the activity of nanometer-sized proteins to define the structure and mechanics of microtubule-based architectures.
Convergent total synthesis of khafrefungin and its inhibitory activity of fungal sphingolipid syntheses

A convergent total synthesis of khafrefungin, a novel inhibitor of fungal sphingolipid syntheses isolated from the fermentation culture MF6020, has been developed. Alkenylboronic acid 5 and alkenyliodide 6, key fragments for the total synthesis, were prepared from the corresponding achiral aldehydes using tin(II)-catalyzed and Zr(IV)-catalyzed asymmetric aldol reactions, respectively. The Suzuki coupling reaction of these two fragments was successfully performed to give 17 in good yield. Through the total synthesis, epimerization of the C4 position having a rather highly acidic proton did not occur, indicating that khafrefungin was under strict conformational constraints to prevent the epimerization process. This characteristic stability of khafrefungin has also been discussed using semiempirical calculation and synthesis. Finally, khafrefungin derivatives have also been synthesized, and their antifungal activities have been measured to obtain information on the structure−activity relationships.
Preparation of 2′-aminoacetophenones: A one-pot hydration and reduction of 1-ethynyl-2-nitrobenzenes

Abstract The reductive hydration of 1-ethynyl-2-nitrobenzenes to the corresponding 2′-aminoacetophenones with a range of common reducing agents is described.
Cancer classification and pathway discovery using non-negative matrix factorization

Abstract Objectives Extracting genetic information from a full range of sequencing data is important for understanding disease. We propose a novel method to effectively explore the landscape of genetic mutations and aggregate them to predict cancer type. Design We applied non-smooth non-negative matrix factorization (nsNMF) and support vector machine (SVM) to utilize the full range of sequencing data, aiming to better aggregate genetic mutations and improve their power to predict disease type. More specifically, we introduce a novel classifier to distinguish cancer types using somatic mutations obtained from whole-exome sequencing data. Mutations were identified from multiple cancers and scored using SIFT, PP2, and CADD, and collapsed at the individual gene level. nsNMF was then applied to reduce dimensionality and obtain coefficient and basis matrices. A feature matrix was derived from the obtained matrices to train a classifier for cancer type classification with the SVM model. Results We have demonstrated that the classifier was able to distinguish four cancer types with reasonable accuracy. In five-fold cross-validations using mutation counts as features, the average prediction accuracy was 80% (SEM = 0.1%), significantly outperforming baselines and outperforming models using mutation scores as features. Conclusion Using the factor matrices derived from the nsNMF, we identified multiple genes and pathways that are significantly associated with each cancer type. This study presents a generic and complete pipeline to study the associations between somatic mutations and cancers. The proposed method can be adapted to other studies for disease status classification and pathway discovery.
Intrinsic temporal tuning of neurons in the optic tectum is shaped by multisensory experience

We use dynamic clamp to show that individual neurons in the tectum of Xenopus tadpoles are selectively tuned to either shorter (more synchronous) or longer (less synchronous) synaptic inputs. We al...