cssi/SciSciGPT-SciSciNet huggingface dataset:
DeepPINK: reproducible feature selection in deep neural networks

Deep learning has become increasingly popular in both supervised and unsupervised machine learning thanks to its outstanding empirical performance. However, because of their intrinsic complexity, most deep learning methods are largely treated as black box tools with little interpretability. Even though recent attempts have been made to facilitate the interpretability of deep neural networks (DNNs), existing methods are susceptible to noise and lack of robustness. Therefore, scientists are justifiably cautious about the reproducibility of the discoveries, which is often related to the interpretability of the underlying statistical models. In this paper, we describe a method to increase the interpretability and reproducibility of DNNs by incorporating the idea of feature selection with controlled error rate. By designing a new DNN architecture and integrating it with the recently proposed knockoffs framework, we perform feature selection with a controlled error rate, while maintaining high power. This new method, DeepPINK (Deep feature selection using Paired-Input Nonlinear Knockoffs), is applied to both simulated and real data sets to demonstrate its empirical utility.
Explaining the Employment Effect of Exports: Value-Added Content Matters

This paper estimates and decomposes the impact of export opportunities on countries’ employment by using a global input-output analysis, focusing on the U.S., China, and Japan. The greater they export, the greater employment in the exporting countries. However, we first document that the number of jobs created per exports varies substantially across destination countries. We find that exports from sectors with higher domestic value-added contents such as natural resource, textile, and service sectors lead to a greater employment effect. As a result, cross-country differences in sectoral compositions of exports explain a large part of the variations in the employment effects across destination countries. Time series changes in the employment effect of exports come from changes in (1) the labor-to-output ratio, (2) input-output linkages, and (3) sectoral compositions in exports. Results suggest that the first channel worked to reduce the employment effect in all of the three countries we focused but the directions of the last two channels are different across the countries.
Characterization and elimination of stochastically generated persister subpopulation in mycobacteria

Mycobacterium tuberculosis (MTB) is able to persist in the host for long periods of time, even during antibiotic treatment. Eliminating persister cells, which are implicated as the primary reason for treatment failure, is essential for shortening TB treatment regimen. Here, we report a novel methodology, Per-Sort, to identify and sort miniscule numbers of translationally dormant mycobacterial cells within an isogenic mycobacterium population. Using Per-Sort we have discovered that translationally dormant cells pre-exist (under optimal growth conditions) as a fraction of a percent of isogenic mycobacterial cultures, suggesting they are generated stochastically as a bet hedging strategy. We show that this pre-existing translationally dormant subpopulation of cells are tolerant to antibiotics, small in size, low in oxidative metabolism, and expand in number upon nutrient starvation. Finally, through transcriptional profiling at single cell resolution, we have determined that the pre-existing persisters are a heterogeneous mix of vapC30, mazF, and relA/spoT overexpressing cells that are eliminated and sensitized to antibiotic killing through induction of respiration.
Blood–brain-barrier organoids for investigating the permeability of CNS therapeutics

In vitro models of the blood-brain barrier (BBB) are critical tools for the study of BBB transport and the development of drugs that can reach the CNS. Brain endothelial cells grown in culture are often used to model the BBB; however, it is challenging to maintain reproducible BBB properties and function. 'BBB organoids' are obtained following coculture of endothelial cells, pericytes and astrocytes under low-adhesion conditions. These organoids reproduce many features of the BBB, including the expression of tight junctions, molecular transporters and drug efflux pumps, and hence can be used to model drug transport across the BBB. This protocol provides a comprehensive description of the techniques required to culture and maintain BBB organoids. We also describe two separate detection approaches that can be used to analyze drug penetration into the organoids: confocal fluorescence microscopy and mass spectrometry imaging. Using our protocol, BBB organoids can be established within 2-3 d. An additional day is required to analyze drug permeability. The BBB organoid platform represents an accurate, versatile and cost-effective in vitro tool. It can easily be scaled to a high-throughput format, offering a tool for BBB modeling that could accelerate therapeutic discovery for the treatment of various neuropathologies.
The Price of Uncertain Priors in Source Coding

We consider the problem of one-way communication when the recipient does not know exactly the distribution that the messages are drawn from, but has a “prior” distribution that is known to be close to the source distribution, a problem first considered by Juba et al. We consider the question of how much longer the messages need to be in order to cope with the uncertainty about the receiver’s prior and the source distribution, respectively, as compared with the standard source coding problem. We consider two variants of this uncertain priors problem: the original setting of Juba et al. in which the receiver is required to correctly recover the message with probability 1, and a setting introduced by Haramaty and Sudan, in which the receiver is permitted to fail with some probability $\epsilon $ . In both settings, we obtain lower bounds that are tight up to logarithmically smaller terms. In the latter setting, we furthermore present a variant of the coding scheme of Juba et al. with an overhead of $\log \alpha +\log 1/\epsilon +1$ bits, thus also establishing the nearly tight upper bound.
Disclosure incentives when competing firms have common ownership

Abstract This paper examines whether common ownership – i.e., instances where investors simultaneously own significant stakes in competing firms – affects voluntary disclosure. We argue that common ownership (i) reduces proprietary cost concerns of disclosure, and (ii) incentivizes firms to “internalize” the externality benefits of their disclosure for co-owned peer firms. Accordingly, we find a positive relation between common ownership and disclosure. Evidence from cross-sectional tests and a quasi-natural experiment based on financial institution mergers help mitigate concerns that our results are explained by an omitted variable bias or reverse causality. Finally, we find that common ownership is associated with increased market liquidity.
Measuring cis-regulatory energetics in living cells using allelic manifolds

Gene expression in all organisms is controlled by cooperative interactions between DNA-bound transcription factors (TFs), but quantitatively measuring TF-DNA and TF-TF interactions remains difficult. Here we introduce a strategy for precisely measuring the Gibbs free energy of such interactions in living cells. This strategy centers on the measurement and modeling of 'allelic manifolds', a multidimensional generalization of the classical genetics concept of allelic series. Allelic manifolds are measured using reporter assays performed on strategically designed cis-regulatory sequences. Quantitative biophysical models are then fit to the resulting data. We used this strategy to study regulation by two Escherichia coli TFs, CRP and sigma-70 RNA polymerase. Doing so, we consistently obtained energetic measurements precise to ~0.1 kcal/mol. We also obtained multiple results that deviate from the prior literature. Our strategy is compatible with massively parallel reporter assays in both prokaryotes and eukaryotes, and should therefore be highly scalable and broadly applicable. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that minor issues remain unresolved (see decision letter).
Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. Our findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, we find that a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation.
When Labor’s Lost: Health, Family Life, Incarceration, and Education in a Time of Declining Economic Opportunity for Low-Skilled Men

The economic progress of US men has stagnated in recent decades. The labor force participation rate of men ages 25-54 peaked in the mid-1960s and has declined since then (according to the Bureau of Labor Statistics), while men's real median earnings have been flat since the early 1970s. These population averages mask considerably larger declines in participation among less-educated and non-white men as well as substantial increases in wage inequality. In this paper, we seek to illuminate the broader context in which prime-age men are experiencing economic stagnation. We explore changes for prime-age men over time in education, mortality, morbidity, disability program receipt, family structure, and incarceration rates. We focus on prime-age men, namely those ages 25-54, and on the years 1980-2016 (or 2017 when possible), encompassing much of the period of reduced economic progress for low-skilled men.
Black Markets: A Comparison of the Illegal Ivory and Narcotic Trades

ABSTRACTSimilarities between the illegal wildlife and narcotics trades pose possibilities for an improved understanding of the spatial and temporal gaps identified in illegal ivory trade literature...
Kac-Moody and Virasoro characters from the perturbative Chern-Simons path integral

We evaluate to one loop the functional integral that computes the partition functions of Chern-Simons theories based on compact groups, using the background field method and a covariant gauge fixing. We compare our computation with the results of other, less direct methods. We find that our method correctly computes the characters of irreducible representations of Kac-Moody algebras. To extend the computation to non-compact groups we need to perform an appropriate analytic continuation of the partition function of the compact group. Non-vacuum characters are found by inserting a Wilson loop in the functional integral. We then extend our method to Euclidean Anti-de Sitter pure gravity in three dimensions. The explicit computation unveils several interesting features and lessons. The most important among them is that the very definition of gravity in the first-order Chern-Simons formalism requires non-trivial analytic continuations of the gauge fields outside their original domains of definition.
Family-based quantitative trait meta-analysis implicates rare noncoding variants in DENND1A in polycystic ovary syndrome.

Context Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5-15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. PCOS is highly heritable, but only a small proportion of this heritability can be accounted for by the common genetic susceptibility variants identified to date. Objective The objective of this study was to test whether rare genetic variants contribute to PCOS pathogenesis.Design, Patients, and Methods: We performed whole-genome sequencing on DNA from 261 individuals from 62 families with one or more daughters with PCOS. We tested for associations of rare variants with PCOS and its concomitant hormonal traits using a quantitative trait meta-analysis. Results We found rare variants in DENND1A (P=5.31×10-5, Padj=0.039) that were significantly associated with reproductive and metabolic traits in PCOS families. Conclusions Common variants in DENND1A have previously been associated with PCOS diagnosis in genome-wide association studies. Subsequent studies indicated that DENND1A is an important regulator of human ovarian androgen biosynthesis. Our findings provide additional evidence that DENND1A plays a central role in PCOS and suggest that rare noncoding variants contribute to disease pathogenesis.
Tractable n-Metrics for Multiple Graphs.

Graphs are used in almost every scientific discipline to express relations among a set of objects. Algorithms that compare graphs, and output a closeness score, or a correspondence among their nodes, are thus extremely important. Despite the large amount of work done, many of the scalable algorithms to compare graphs do not produce closeness scores that satisfy the intuitive properties of metrics. This is problematic since non-metrics are known to degrade the performance of algorithms such as distance-based clustering of graphs (Stratis and Bento 2018). On the other hand, the use of metrics increases the performance of several machine learning tasks (Indyk et al. 1999, Clarkson et al. 1999, Angiulli et al. 2002, Ackermann et al. 2010). In this paper, we introduce a new family of multi-distances (a distance between more than two elements) that satisfies a generalization of the properties of metrics to multiple elements. In the context of comparing graphs, we are the first to show the existence of multi-distances that simultaneously incorporate the useful property of alignment consistency (Nguyen et al. 2011), and a generalized metric property. Furthermore, we show that these multi-distances can be relaxed to convex optimization problems, without losing the generalized metric property.
Magnets, Organic/Polymer

Magnetism has enabled the development and exploitation of fundamental science, ranging from quantum mechanics, to probing condensed matter chemistry and physics, to materials science. The control of magnetism has resulted in the availability of low-cost electricity and the use of electric motors, leading to the development of telecommunications devices (microphones, televisions, telephones, etc.), and to magnetic storage for computers. Magnets, due to their myriad properties, are suitable components in sensors and actuators, and hence they must be considered the key components in smart materials and systems of the future. Magnetic materials known from time immemorial are comprised of either transition or rare-earth metals, or their ions with spins residing in d- or f-orbitals, respectively, such as Fe, CrO2, SmCo5, Co17Sm2, and Nd2Fe14B. These materials are prepared by high-temperature metallurgical methods, and generally, they are brittle. In the late twentieth century many metal and ceramic materials were replaced with lightweight polymeric materials. The polymeric materials were designated primarily for structural materials, but examples also abound for electrically conducting and optical materials. More recently, new examples of magnetic materials have been reported. Undoubtedly, in this millennium there will be commercialization of these organic and polymeric magnets. Keywords: Magnets; Applied magnetic field; Hexacyanometallate magnets; High room temperature magnets; Organic/polymer magnets; Uses
Synthesis and Characterization of Two Group 15 Selenometalates: [NEt4][BiSe2] and [Ge(en)3][enH][SbSe4]

[NEt4][BiSe2] has been synthesized from the electrochemical reduction of “BiSnSe4”, a microcrystalline mixture of Bi2SnSe4, SnSe2, and Se, in an electrolyte solution of NEt4Br in ethylenediamine. [Ge(en)3][enH][SbSe4] has been prepared from the dissolution in ethylenediamine of “GeSbSe4”, a microcrystalline mixture of Sb2Se3, GeSe2, and Se. The structures of both compounds have been determined by single-crystal X-ray methods. [NEt4][BiSe2] crystallizes in the rhombohedral space group -R3c with six formula units in a cell of dimensions a = 19.19(1) A, α = 118.375(2)°, and V = 2320(2) A3 (T = 115 K). Final agreement indices for [NEt4][BiSe2] are 0.113 for Rw(Fo2) for all 980 data and 0.054 for R1 for the 787 reflections with Fo2 ≥ 2σ(Fo2) (65 variables). [Ge(en)3][enH][SbSe4] crystallizes in the triclinic space group -P1 with two formula units in a cell of dimensions a = 8.82(2) A, b = 9.60(2) A, c = 14.20(3) A, α = 104.84(7)°, β = 92.66(7)°, γ = 109.44(7)°, and V = 1085.2(4) A3 (T = 115 K). Final agreemen...
A Model for Resource Competition in CRISPR-Mediated Gene Repression

CRISPR-mediated gene regulation is known for its ability to control multiple targets simultaneously due to its modular nature: the same dCas9 effector can target different genes simply by changing the associated gRNA. However, multiplexing requires the sharing of limited amounts of dCas9 protein among multiple gRNAs, leading to resource competition. In turn, competition between gRNAs for the same resource may hamper network function. In this work, we develop a general model that takes into account the sharing of limited amounts of dCas9 protein for arbitrary CRISPR-mediated gene repression networks. We demonstrate that, as a result of resource competition, hidden interactions appear, which modifies the intended network regulations. As a case study, we analyze the effects of these hidden interactions on repression cascades. In particular, we illustrate that perfect adaptation to resource fluctuations can be achieved in cascades with an even number of repressors. In contrast, cascades with an odd number of repressors are substantially impacted by resource competition.
Plasticity of the Electrical Connectome of C. elegans.

Summary The specific patterns and functional properties of electrical synapses of a nervous system are defined by the neuron-specific complement of electrical synapse constituents. We systematically examined the molecular composition of the electrical connectome of the nematode C. elegans through a genome- and nervous-system-wide analysis of the expression patterns of the invertebrate electrical synapse constituents, the innexins. We observe highly complex combinatorial expression patterns throughout the nervous system and found that these patterns change in a strikingly neuron-type-specific manner throughout the nervous system when animals enter an insulin-controlled diapause arrest stage under harsh environmental conditions, the dauer stage. By analyzing several individual synapses, we demonstrate that dauer-specific electrical synapse remodeling is responsible for specific aspects of the altered locomotory and chemosensory behavior of dauers. We describe an intersectional gene regulatory mechanism involving terminal selector and FoxO transcription factors mediating dynamic innexin expression plasticity in a neuron-type- and environment-specific manner.
Metalated nitriles: electrophile-dependent alkylations.

Sequential carbonyl addition−conjugate addition to oxonitriles generates a C-magnesiated nitrile exhibiting electrophile-dependent alkylation stereoselectivities. Alkylations with alkyl halides, sulfonates, and ketones proceed with retention of stereochemistry, whereas aldehyde and acyl cyanide acylations proceed with inversion of stereochemistry. BuLi-initiated conversion of the C-magnesiated nitrile to the corresponding N-lithiated nitrile reverses the alkylation stereoselectivity, providing a facile route to diastereomeric nitriles that vary at a single, quaternary stereocenter.
Hydrothermal synthesis and structural analysis of new mixed oxyanion borates: Ba11B26O44(PO4)2(OH)6, Li9BaB15O27(CO3) and Ba3Si2B6O16

Abstract Several new borate compounds, Ba11B26O44(PO4)2(OH)6 (1), Li9BaB15O27(CO3) (2), and Ba3Si2B6O16 (3) were synthesized containing other hetero-oxyanion building blocks in addition to the borate frameworks. They were all prepared under hydrothermal conditions and characterized by single crystal and powder X-ray diffraction, and IR spectroscopy. Crystal data: For 1; space group P21/c, a=6.8909 (14) A, b=13.629 (3) A, c=25.851 (5) A, β=90.04 (3)°; For 2; space group P-31c, a=8.8599 (13) A, c=15.148 (3) A; For 3; space group P-1, a=5.0414 (10) A, b=7.5602 (15) A, c=8.5374 (17) A, α=77.15 (3)°, β=77.84 (3)°, γ=87.41 (3)° for 3. Compounds 1 and 2 contain isolated oxyanions [PO4]3− and [CO3]2− respectively, sitting in channels created by the borate framework, while structure 3 has the [SiO4]4− groups directly bonded to the borate groups creating a B–O–Si framework.
Cyclizations of 5-Hexenyl, 6-Heptenyl, 7-Octenyl, and 8-Nonenyl Radicals. The Kinetic and Regiochemical Impact of Fluorine and Oxygen Substituents‖

Using competition kinetic methodology, rate constants for cyclizations of a series of hydrofluorocarbon (HFC) and ether 5-hexenyl, 6-heptenyl, and 7-octenyl radicals have been determined. Remarkably large rate constants (>107 s-1) have been observed for 6-exo-cyclizations of 1,1,2,2-tetrafluoro- and 1,1,2,2,3,3,4,4,-octafluoro-6-heptenyl radicals (>103 those of analogous hydrocarbon radicals), whereas HFC hexenyl and heptenyl ethers exhibit lower cyclization reactivity, as do HFC 7-octenyl radical systems, which cyclize in an endo manner. HFC 8-nonenyl radicals were not observed to cyclize. The results can be rationalized in terms of transition state polar influences, though other factors may also play significant roles.
Rearrangement of Nα-Protected l-Asparagines with Iodosobenzene Diacetate. A Practical Route to β-Amino-l-alanine Derivatives

A general synthetic method for the Hofmann rearrangement of protected asparagines has been developed. Reaction of asparagine derivatives with iodosobenzene diacetate (PIDA) in mixed solvents produces β-amino-l-alanines in good yield. Advantages over the commonly used reagent bis(trifluoroacetoxy)iodobenzene have been discussed.
Biaryl substituted alkylboronate esters as thrombin inhibitors

Abstract Thrombin is a serine protease that plays an important role in the blood coagulation cascade, and is a target enzyme for new therapeutic agents. Ac-(D)-Phe-Pro-boroArg-OH (DuP 714) was found to be a highly effective thrombin inhibitor. In order to reduce the peptidic nature of DuP 714, we have designed a series of novel biaryl substituted alkylboronate esters as potent thrombin inhibitors. The most potent compounds have subnanomolar affinity for thrombin.
Detecting epistasis with the marginal epistasis test in genetic mapping studies of quantitative traits.

Epistasis, commonly defined as the interaction between multiple genes, is an important genetic component underlying phenotypic variation. Many statistical methods have been developed to model and identify epistatic interactions between genetic variants. However, because of the large combinatorial search space of interactions, most epistasis mapping methods face enormous computational challenges and often suffer from low statistical power due to multiple test correction. Here, we present a novel, alternative strategy for mapping epistasis: instead of directly identifying individual pairwise or higher-order interactions, we focus on mapping variants that have non-zero marginal epistatic effects—the combined pairwise interaction effects between a given variant and all other variants. By testing marginal epistatic effects, we can identify candidate variants that are involved in epistasis without the need to identify the exact partners with which the variants interact, thus potentially alleviating much of the statistical and computational burden associated with standard epistatic mapping procedures. Our method is based on a variance component model, and relies on a recently developed variance component estimation method for efficient parameter inference and p-value computation. We refer to our method as the “MArginal ePIstasis Test”, or MAPIT. With simulations, we show how MAPIT can be used to estimate and test marginal epistatic effects, produce calibrated test statistics under the null, and facilitate the detection of pairwise epistatic interactions. We further illustrate the benefits of MAPIT in a QTL mapping study by analyzing the gene expression data of over 400 individuals from the GEUVADIS consortium.
Salt-templated mesoporous solids comprised of interlinked polyoxovanadate clusters.

The utility of molten salts has been demonstrated in the synthesis of the first family of mesoporous salt-inclusion solids featuring [V4O16] and [V5O17] polyoxovanadate (POV) units interlinked by A...
Visible light photooxidative cyclization of amino alcohols to 1,3-oxazines

1,3-Amino alcohols were prepared to examine how structure affects the oxidation of tertiary amines in visible light photocatalysis. These substrates were cyclized to produce oxazines following the photooxidative formation of iminium ions using catalytic Ru(bpy)3Cl2. Amino alcohol derivatives of tetrahydroisoquinoline, tetrahydroquinoline, pyrrolidine, and Δ3-piperidine all were found to be viable substrates. In the case of the unsaturated piperidines, cyclization is accompanied by addition of methanol across the alkene; most likely occurring via a conjugate addition to an intermediate α,β-unsaturated iminium ion prior to oxazine formation.
Computational study of the Zr4+ tetranuclear polymer, [Zr4(OH)8(H2O)16]8+.

The Zr4+ tetramer, [Zr4(OH)8(H2O)16]8+, is thought to be the major component of the Zr4+ polymer system in aqueous solution, present as a dominant ionic cluster species compared to other Zr4+ clust...
Cation‒cation interactions and cation exchange in a series of isostructural framework uranyl tungstates

Abstract The isotypical compounds (UO2)3(WO6)(H2O)5 (1), Ag(UO2)3(WO6)(OH)(H2O)3 (2), K(UO2)3(WO6)OH(H2O)4 (3), Rb(UO2)3(WO6)(OH)(H2O)3.5 (4), and Cs(UO2)3(WO6)OH(H2O)3 (5) were synthesized, characterized, and their structures determined. Each crystallizes in space group Cc. (1): a=12.979 (3), b=10.238 (2), c=11.302 (2), β=102.044 (2); (2): a=13.148 (2), b=9.520 (1), c=11.083 (2), β=101.568 (2); (3): a=13.111 (8), b=9.930 (6), c=11.242 (7), β=101.024 (7); (4): a=12.940 (2), b=10.231 (2), c=11.259(2), β=102.205 (2); (5): a=12.983 (3), b=10.191 (3), c=11.263 (4), β=101.661 (4). Compounds 1–5 are a framework of uranyl and tungsten polyhedra containing cation–cation interactions. The framework has three symmetrically distinct U(VI) cations, one tungsten, sixteen to eighteen oxygen atoms, and in 2–5, one monovalent cation. Each atom occupies a general position. Each U(VI) cation is present as a typical (UO2)2+ uranyl ion in an overall pentagonal bipyramidal coordination environment. Each pentagonal bipyramid shares two equatorial edges with two other pentagonal bipyramids, forming a trimer. Trimers are connected into chains by edge-sharing with WO6 octahedra. Chains are linked through cation–cation interactions between two symmetrically independent uranyl ions. This yields a remarkably complex system of intersecting channels that extend along [0 0 1] and [−1 1 0]. The cation exchange properties of 2 and 3 were characterized at room temperature and at 140 °C.
Synthesis of 5,7-dihydrobenzo[a]phenazin-5-one derivatives

The synthesis, purification and spectroscopic characterization of several phenazines was undertaken with the goal of discovering useful or improved fluorescent probes.
Highly efficient selective monohydrolysis of dialkyl malonates and their derivatives

Abstract The highly efficient selective monohydrolysis of symmetric diesters has been applied to monohydrolysis of several dialkyl malonates and their derivatives. The best conditions apply 0.8–1.2 equiv of aqueous KOH with a co-solvent, THF or acetonitrile, at 0 °C. The procedure is highly practical, yielding the corresponding half-esters in high yields in a straightforward manner, without inducing decarboxylation. It was found that the selectivity tends to become higher with increased hydrophobicity.
Intramolecular carboxylic acid trapping of pyran-4-one derived zwitterions: A novel synthesis of fused bicyclic lactones

Abstract Pyran-4-ones bearing carboxylic acid side chains were prepared either by direct carboxylation with carbon dioxide or through oxidative cleavage of side chain olefins. Irradiation in a non-nucleophilic solvent yielded fused bicyclic lactones. The efficiency of the reaction was not dependent on ring substitution.
Preparation and fungitoxicity of 3-bromo-6-chloro- and 6-bromo-3-chloro-8-quinolinols

3-Bromo-6-chloro- and 6-bromo-3-chloro-8-nitro, -8-amino-, and -8-hydroxyquinolines along with 3-bromo- and 3-chloroquinolin-6,8-diols were prepared and tested for antifungal activity against six fungi (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, Trichophyton mentagrophytes) inSabouraud dextrose broth. Compounds with chlorine in the 3 position were generally more fungitoxic than the corresponding analogues with bromine. 6-Bromo-3-chloro-8-quinolinol inhibited four fungi at levels below 1 µg/ml andA. niger andM. cirinelloides at 2 µg/ml each.
FunSPU: A versatile and adaptive multiple functional annotation-based association test of whole-genome sequencing data

Despite ongoing large-scale population-based whole-genome sequencing (WGS) projects such as the NIH NHLBI TOPMed program and the NHGRI Genome Sequencing Program, WGS-based association analysis of complex traits remains a tremendous challenge due to the large number of rare variants, many of which are non-trait-associated neutral variants. External biological knowledge, such as functional annotations based on the ENCODE, Epigenomics Roadmap and GTEx projects, may be helpful in distinguishing causal rare variants from neutral ones; however, each functional annotation can only provide certain aspects of the biological functions. Our knowledge for selecting informative annotations a priori is limited, and incorporating non-informative annotations will introduce noise and lose power. We propose FunSPU, a versatile and adaptive test that incorporates multiple biological annotations and is adaptive at both the annotation and variant levels and thus maintains high power even in the presence of noninformative annotations. In addition to extensive simulations, we illustrate our proposed test using the TWINSUK cohort (n = 1,752) of UK10K WGS data based on six functional annotations: CADD, RegulomeDB, FunSeq, Funseq2, GERP++, and GenoSkyline. We identified genome-wide significant genetic loci on chromosome 19 near gene TOMM40 and APOC4-APOC2 associated with low-density lipoprotein (LDL), which are replicated in the UK10K ALSPAC cohort (n = 1,497). These replicated LDL-associated loci were missed by existing rare variant association tests that either ignore external biological information or rely on a single source of biological knowledge. We have implemented the proposed test in an R package "FunSPU".
SRSF shape analysis for sequencing data reveal new differentiating patterns.

Abstract Motivation Sequencing-based methods to examine fundamental features of the genome, such as gene expression and chromatin structure, rely on inferences from the abundance and distribution of reads derived from Illumina sequencing. Drawing sound inferences from such experiments relies on appropriate mathematical methods to model the distribution of reads along the genome, which has been challenging due to the scale and nature of these data. Results We propose a new framework (SRSFseq) based on square root slope functions shape analysis to analyse Illumina sequencing data. In the new approach the basic unit of information is the density of mapped reads over region of interest located on the known reference genome. The densities are interpreted as shapes and a new shape analysis model is proposed. An equivalent of a Fisher test is used to quantify the significance of shape differences in read distribution patterns between groups of density functions in different experimental conditions. We evaluated the performance of this new framework to analyze RNA-seq data at the exon level, which enabled the detection of variation in read distributions and abundances between experimental conditions not detected by other methods. Thus, the method is a suitable supplement to the state-of-the-art count based techniques. The variety of density representations and flexibility of mathematical design allow the model to be easily adapted to other data types or problems in which the distribution of reads is to be tested. The functional interpretation and SRSF phase-amplitude separation technique give an efficient noise reduction procedure improving the sensitivity and specificity of the method.
Synthesis of new 2,3-perfluoroalkyl- and perfluoroaryl-1,4-diazabutadienes (α-diimines)

Abstract Reaction of either decafluorobenzil or perfluorobiacetyl with two equivalents of Li[N(SiMe3)2], followed by quenching with ClSiMe3, provides N,N′-bis(trimethylsilyl)-1,2-bis(pentafluorophenyl)ethanediimine 1 and N,N′-bis(trimethylsilyl)-1,1,1,4,4,4-hexafluoro-2,3-butanediimine 2, respectively. These represent the first examples of perfluoroalkyl- and perfluoroaryl-substituted diazabutadienes. Both compounds have been characterized based on 13C NMR, IR, elemental analysis and, for 1, single crystal X-ray crystallographic structure determination. Compound 1 crystallizes in the C2 c space group, with a=20.3203(9) X, b=6.0758(3) X, c=19.7948(9) X, α=90°, β=106.2903(7)°, γ=90°.
Flux Synthesis of K2Cu2P4Se10: A Layered Selenophosphate with a New Cyclohexane-like [P4Se10]4- Group

The stabilization of the unprecedented cyclohexane-like [P4Se10]4- ligand in the layered K2Cu2P4Se10 has been achieved. The layers consist of infinite chains of corner-sharing CuSe4 tetrahedra that propagate along the b axis, being interstitched in two dimensions by cyclic [P4Se10]4- groups.
Use antibiotics in cell culture with caution: genome-wide identification of antibiotic-induced changes in gene expression and regulation

Standard cell culture guidelines often use media supplemented with antibiotics to prevent cell contamination. However, relatively little is known about the effect of antibiotic use in cell culture on gene expression and the extent to which this treatment could confound results. To comprehensively characterize the effect of antibiotic treatment on gene expression, we performed RNA-seq and ChIP-seq for H3K27ac on HepG2 cells, a human liver cell line commonly used for pharmacokinetic, metabolism and genomic studies, cultured in media supplemented with penicillin-streptomycin (PenStrep) or vehicle control. We identified 209 PenStrep-responsive genes, including transcription factors such as ATF3 that are likely to alter the regulation of other genes. Pathway analyses found a significant enrichment for “xenobiotic metabolism signaling” and “PXR/RXR activation” pathways. Our H3K27ac ChIP-seq identified 9,514 peaks that are PenStrep responsive. These peaks were enriched near genes that function in cell differentiation, tRNA modification, nuclease activity and protein dephosphorylation. Our results suggest that PenStrep treatment can significantly alter gene expression and regulation in a common liver cell type such as HepG2, advocating that antibiotic treatment should be taken into account when carrying out genetic, genomic or other biological assays in cultured cells.
svtools: population-scale analysis of structural variation.

SUMMARY Large-scale human genetics studies are now employing whole genome sequencing with the goal of conducting comprehensive trait mapping analyses of all forms of genome variation. However, methods for structural variation (SV) analysis have lagged far behind those for smaller scale variants, and there is an urgent need to develop more efficient tools that scale to the size of human populations. Here, we present a fast and highly scalable software toolkit (svtools) and cloud-based pipeline for assembling high quality SV maps-including deletions, duplications, mobile element insertions, inversions and other rearrangements-in many thousands of human genomes. We show that this pipeline achieves similar variant detection performance to established per-sample methods (e.g. LUMPY), while providing fast and affordable joint analysis at the scale of ≥100 000 genomes. These tools will help enable the next generation of human genetics studies. AVAILABILITY AND IMPLEMENTATION svtools is implemented in Python and freely available (MIT) from https://github.com/hall-lab/svtools. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Correlated individual differences suggest a common mechanism underlying metacognition in visual perception and visual short-term memory.

Adaptive behaviour depends on the ability to introspect accurately about one's own performance. Whether this metacognitive ability is supported by the same mechanisms across different tasks is uncl...
Synthesis of some halogenated and disubstituted amino benzylacyclouridine derivatives

1'-Halogenomethyl, 1'-azidomethyl and 1'-disubstituted aminomethyl derivatives of BAU (5-benzylacyclouridine) and BBAU (5-benzyloxybenzylacyclouridine) were synthesized in the course of our studies of benzylacyclouridines. Two new and more convenient preparations of the previously known aminomethyl-and hydroxyymethyl-parent compounds of these two series, AM-BAU, AM-BBAU and HM-BBAU are also reported. These compounds were synthesized during a search for potential antiviral agents and pyrimidine phosphorylase inhibitors
Second-generation method for analysis of chromatin binding with formaldehyde-cross-linking kinetics

Formaldehyde-cross-linking underpins many of the most commonly used experimental approaches in the chromatin field, especially in capturing site-specific protein-DNA interactions. Extending such assays to assess the stability and binding kinetics of protein-DNA interactions is more challenging, requiring absolute measurements with a relatively high degree of physical precision. We previously described an experimental framework called the cross-linking kinetics (CLK) assay, which uses time-dependent formaldehyde-cross-linking data to extract kinetic parameters of chromatin binding. Many aspects of formaldehyde behavior in cells are unknown or undocumented, however, and could potentially affect CLK data analyses. Here, we report biochemical results that better define the properties of formaldehyde-cross-linking in budding yeast cells. These results have the potential to inform interpretations of "standard" chromatin assays, including chromatin immunoprecipitation. Moreover, the chemical complexity we uncovered resulted in the development of an improved method for measuring binding kinetics with the CLK approach. Optimum conditions included an increased formaldehyde concentration and more robust glycine-quench conditions. Notably, we observed that formaldehyde-cross-linking rates can vary dramatically for different protein-DNA interactions in vivo Some interactions were cross-linked much faster than the in vivo macromolecular interactions, making them suitable for kinetic analysis. For other interactions, we found the cross-linking reaction occurred on the same time scale or slower than binding dynamics; for these interactions, it was sometimes possible to compute the in vivo equilibrium-binding constant but not binding on- and off-rates. This improved method yields more accurate in vivo binding kinetics estimates on the minute time scale.
Using Maximum Entropy Production to Describe Microbial Biogeochemistry Over Time and Space in a Meromictic Pond

Determining how microbial communities organize and function at the ecosystem level is essential to understanding and predicting how they will respond to environmental change. Mathematical models can be used to describe these communities, but properly representing all the biological interactions in extremely diverse natural microbial ecosystems in a mathematical model is challenging. We examine a complementary approach based on the maximum entropy production (MEP) principle, which proposes that systems with many degrees of freedom will likely organize to maximize the rate of free energy dissipation. In this study, we develop an MEP model to describe biogeochemistry observed in Siders Pond, a phosphate limited meromictic system located in Falmouth, MA that exhibits steep chemical gradients due to density-driven stratification that supports anaerobic photosynthesis as well as microbial communities that catalyze redox cycles involving O, N, S, Fe and Mn. The MEP model uses a metabolic network to represent microbial redox reactions, where biomass allocation and reaction rates are determined by solving an optimization problem that maximizes entropy production over time, and a 1D vertical profile constrained by an advection-dispersion-reaction model. We introduce a new approach for modeling phototrophy and explicitly represent oxygenic photoautotrophs, photoheterotrophs and anoxygenic photoautotrophs. The metabolic network also includes reactions for aerobic organoheterotrophic bacteria, sulfate reducing bacteria, sulfide oxidizing bacteria and aerobic and anaerobic grazers. Model results were compared to observations of biogeochemical constituents collected over a 24 hour period at 8 depths at a single 15 m deep station in Siders Pond. Maximizing entropy production over long (3 day) intervals produced results more similar to field observations than short (0.25 day) interval optimizations, which support the importance of temporal strategies for maximizing entropy production over time. Furthermore, we found that entropy production must be maximized locally instead of globally where energy potentials are degraded quickly by abiotic processes, such as light absorption by water. This combination of field observations and modeling results indicate that natural microbial systems can be modeled by using the maximum entropy production principle applied over time and space using many fewer parameters than conventional models.
Microporous manganese oxides

Abstract Several types of new materials including tunnel and layer structures of porous manganese oxides have recently been reported. New developments in the characterization and application of such materials are also of current interest. Manganese doped oxide systems are sometimes useful models for these microporous materials.
Matrix infrared spectroscopic and theoretical of the difluoroamino metal fluoride molecules: F2NMF (M = Cu, Ag, Au).

The difluoroamino coinage metal fluoride molecules F2NMF (M = Cu, Ag, Au) have been made via spontaneous reactions of coinage metals and NF3 in solid argon and neon matrixes during sample annealing...
The transition state in heterogeneous catalysis

Predictability of the outcome of catalytic reactions depends critically on the understanding of their molecular mechanism. The transition state provides the link between reactants and products on a reaction pathway which involves simultaneous motion of several to very many atoms. The description of the transition state (TS) aims primarily at the determination of the barrier height and the direction of the transition vector, the movement of atoms on the passage through the transition state. Once known, these parameters of the molecular conversion help explain selectivity of interface reactions to valuable, often not thermodynamically most stable, products. The challenges encountered in heterogeneous catalysis are (a) the mechanism may or may not be similar to those in the uniform phase such as a liquid or gas; (b) the real size of the TS in terms of the number of interacting atoms may be very large. Experiments have provided guidance as to the nature of the TS, first from kinetics and product structure, which are known to lead to ambiguous interpretation and admit several mechanisms, and next refined by isotope flow and in the case of asymmetric centers by chirality inversion or retention, but with little certainty about the magnitude of the barrier that determines the reaction rate. In this paper theoretical approaches are exemplified which in selected cases do account for the TS energy and rate, and further specify features of the mechanistic picture that could only be qualitatively assessed from experiment. Emphasis is on synthetic catalyzed reactions, with an omission of a very large scope of hydrocarbon cracking and isomerizations.
Deformation Induced Solid−Solid Phase Transitions in Gamma Boron

We predict three new polymorphs of boron by applying density functional theory (PBE flavor) to large shear deformations starting from the recently discovered γ-B_(28) boron phase (stable above 9 GPa and 1000 K). We find that continuous deformation along the (100)/⟨001⟩ slip system leads to two new phases, named here as γ-B_(12)–(B_(2))_(6) and γ-B_(12)–(B···B)_(6). We show that these γ-B_(12)–(B_(2))_(6) and γ-B_(12)–(B···B)_(6) phases can also be obtained from uniaxial tensile and compressive deformations of the γ-B28 phase along the ⟨101⟩ direction, respectively. However, the reverse compressive loading on the newly formed γ-B_(12)–(B_(2))_(6) phase transforms it to itself, not the γ-B28 phase, because of the transferability of the three-center two-electron bond under deformation. This makes the new phase γ-B_(12)–(B_(2))_(6) a special type of superelastic material. In addition, application of reverse tensile deformation on the newly formed γ-B_(12)–(B···B)_(6) phase, transforms it to a third new phase, named α-B_(12)–BB, that is metallic, suggesting increased ductility that might make α-B_(12)–BB important for applications in electronic devices. We compared the structural character, mechanical properties, and electronic properties of these new phases to each other and to other phases of boron. We show that the three new phases are dynamically stable at zero pressure. These results show how modifying the connections between boron icosahedra using one to two atom chains can lead to dramatically different mechanical and electronic properties.