cssi/SciSciGPT-SciSciNet huggingface dataset:
PCH1 regulates light, temperature, and circadian signaling as a structural component of phytochrome B-photobodies in Arabidopsis

The members of the phytochrome (phy) family of bilin-containing photoreceptors are major regulators of plant photomorphogenesis through their unique ability to photointerconvert between a biologically inactive red light-absorbing Pr state and an active far-red light-absorbing Pfr state. While the initial steps in Pfr signaling are unclear, an early event for the phyB isoform after photoconversion is its redistribution from the cytoplasm into subnuclear foci known as photobodies (PBs), which dissipate after Pfr reverts back to Pr by far-red irradiation or by temperature-dependent nonphotochemical reversion. Here we present evidence that PHOTOPERIODIC CONTROL OF HYPOCOTYL 1 (PCH1) functions both as an essential structural component of phyB-containing PBs and as a direct regulator of thermal reversion that is sufficient to stabilize phyB as Pfr in vitro. By examining the genetic interaction between a constitutively active phyBY276H-YFP allele (YHB-YFP) and PCH1, we show that the loss of PCH1 prevents YHB from coalescing into PBs without affecting its nuclear localization, whereas overexpression of PCH1 dramatically increases PB levels. Loss of PCH1, presumably by impacting phyB-PB assembly, compromises a number of events elicited in YHB-YFP plants, including their constitutive photomorphogenic phenotype, red light-regulated thermomorphogenesis, and input of phyB into the circadian clock. Conversely, elevated levels of both phyB and PCH1 generate stable, yet far-red light–reversible PBs that persisted for days. Collectively, our data demonstrate that the assembly of PCH1-containing PBs is critical for phyB signaling to multiple outputs and suggest that altering PB dynamics could be exploited to modulate plant responses to light and temperature.
E-Cigarette Minimum Legal Sale Age Laws and Traditional Cigarette Use among Rural Pregnant Teenagers

Abstract Teenagers under 18 could legally purchase e-cigarettes until states passed minimum legal sale age laws. These laws may have curtailed teenagers' use of e-cigarettes for smoking cessation. We investigate the effect of e-cigarette minimum legal sale age laws on prenatal cigarette smoking and birth outcomes for underage rural teenagers using data on all births from 2010 to 2016 from 32 states. We find that the laws increased prenatal smoking by 0.6 percentage points (pp) overall. These effects were concentrated in prepregnancy smokers, with no effect on prepregnancy non-smokers. These results suggest that the laws reduced cigarette smoking cessation during pregnancy rather than causing new cigarette smoking initiation. Our results may indicate an unmet need for assistance with smoking cessation among pregnant teenagers.
Pd-Catalyzed C-N Coupling Reactions Facilitated by Organic Bases: Mechanistic Investigation Leads to Enhanced Reactivity in the Arylation of Weakly Binding Amines.

The ability to use soluble organic amine bases in Pd-catalyzed C–N cross-coupling reactions has provided a long-awaited solution to the many issues associated with employing traditional, heterogeneous reaction conditions. However, little is known about the precise function of these bases in the catalytic cycle or about the effect of variations in base structure on catalyst reactivity. We used 19F NMR to analyze the kinetic behavior of C–N coupling reactions facilitated by different organic bases. In the case of aniline coupling reactions employing DBU, the resting state was a DBU-bound oxidative addition complex, LPd(DBU)(Ar)X, and the reaction was found to be inhibited by base. Generally, however, depending on the binding properties of the chosen organic base, increasing the concentration of the base can have a positive or negative influence on the reaction rate. Furthermore, the electronic nature of the aryl triflate employed in the reaction directly affects the reaction rate. The fastest reaction rates...
Dynamics of Gene Expression in Single Root Cells of Arabidopsis thaliana

Single cell RNA sequencing can yield high-resolution cell-type–specific expression signatures that reveal new cell types and the developmental trajectories of cell lineages. Here, we apply this approach to Arabidopsis (Arabidopsis thaliana) root cells to capture gene expression in 3,121 root cells. We analyze these data with Monocle 3, which orders single cell transcriptomes in an unsupervised manner and uses machine learning to reconstruct single cell developmental trajectories along pseudotime. We identify hundreds of genes with cell-type–specific expression, with pseudotime analysis of several cell lineages revealing both known and novel genes that are expressed along a developmental trajectory. We identify transcription factor motifs that are enriched in early and late cells, together with the corresponding candidate transcription factors that likely drive the observed expression patterns. We assess and interpret changes in total RNA expression along developmental trajectories and show that trajectory branch points mark developmental decisions. Finally, by applying heat stress to whole seedlings, we address the longstanding question of possible heterogeneity among cell types in the response to an abiotic stress. Although the response of canonical heat-shock genes dominates expression across cell types, subtle but significant differences in other genes can be detected among cell types. Taken together, our results demonstrate that single cell transcriptomics holds promise for studying plant development and plant physiology with unprecedented resolution.
Investigating Mixed Logit Analysis of Critical Headways at a Single-Lane Instrumented Roundabout

This paper examines 29,403 entering vehicles that rejected two or more headways for a total of 69,123 rejected headways. A detailed series of temporal parameters was established and used to estimate a mixed binary logit model and understand rejection/acceptance decisions. This technique allows for the parameter estimates to vary across the population and across the set of decisions that drivers made and suggests that drivers may modify their critical headway as they wait at the yield bar. The results from this paper indicate that future consideration of capacity using a dynamic critical headway could be useful in modeling and capacity estimation.
How do different sources of policy analysis affect policy preferences? Experimental evidence from the United States

Analysis of policy options is often unavailable or only available from non-governmental research organizations (“think tanks”) that may have explicit or implicit political biases. This paper experimentally examines how voters respond to policy analysis and how the response varies when the analysis is produced by a nonpartisan organization versus a liberal or conservative organization. The key result is that individuals, on average, are responsive to all types of analysis, but most strongly responsive to analysis produced by nonpartisan organizations. Analysis from an ideologically slanted organization is less effective because individuals tend to ignore analysis that is produced by a partisan organization that does not share their own ideology. The results suggest that increasing the amount of information that the public receives based on nonpartisan analysis may increase the diffusion of information on policy features into the public and reduce polarization in public opinion.
Premature Ventricular Complex–Induced Cardiomyopathy

Frequent premature ventricular complexes (PVCs) can cause an often reversible form of cardiomyopathy. The mechanism for the development of premature ventricular complex-induced cardiomyopathy (PIC) continues to be investigated, and animal models as well as human clinical trials suggest ventricular dyssynchrony to be an important component. In addition to a high PVC burden, this review will detail other risk factors associated with the development of PIC. PVCs can be a marker for the presence of other underlying disease and a thorough work-up, including cardiac magnetic resonance imaging with delayed contrast enhancement, needs to be considered to rule out the presence of structural heart disease. Management of PIC can involve catheter ablation or pharmacotherapy. Multicenter studies have shown a high success rate paired with a low complication rate with catheter ablation, and hence catheter ablation has emerged as the preferred therapeutic option for most patients with PIC. Advances in ablation strategy and technology have enhanced our ability to address certain challenging PVC locations. Important challenges that remain include understanding the coexistence of PIC with other forms of cardiomyopathy, whether there is an associated risk of sudden cardiac death, and the long-term effects on cardiac substrate of exposure to frequent PVCs.
The Tenets of Teneurin: Conserved Mechanisms Regulate Diverse Developmental Processes in the Drosophila Nervous System.

To successfully integrate a neuron into a circuit, a myriad of developmental events must occur correctly and in the correct order. Neurons must be born and grow out towards a destination, responding to guidance cues to direct their path. Once arrived, each neuron must segregate to the correct sub-region before sorting through a milieu of incorrect partners to identify the correct partner with which they can connect. Finally, the neuron must make a synaptic connection with their correct partner; a connection that needs to be broadly maintained throughout the life of the animal while remaining responsive to modes of plasticity and pruning. Though many intricate molecular mechanisms have been discovered to regulate each step, recent work showed that a single family of proteins, the Teneurins, regulates a host of these developmental steps in Drosophila – an example of biological adaptive reuse. Teneurins first influence axon guidance during early development. Once neurons arrive in their target regions, Teneurins enable partner matching and synapse formation in both the central and peripheral nervous systems. Despite these diverse processes and systems, the Teneurins use conserved mechanisms to achieve these goals, as defined by two tenets: 1) transsynaptic interactions with each other and 2) membrane stabilization via an interaction and regulation of the cytoskeleton. These processes are further distinguished by 1) the nature of the transsynaptic interaction – homophilic interactions (between the same Teneurins) to engage partner matching and heterophilic interactions (between different Teneurins) to enable synaptic connectivity and the proper apposition of pre- and postsynaptic sites and 2) the location of cytoskeletal regulation (presynaptic cytoskeletal regulation in the CNS and postsynaptic regulation of the cytoskeleton at the NMJ). Thus, both the roles and the mechanisms governing them are conserved across processes and synapses. In this review, we will highlight the contributions of Drosophila synaptic biology to our understanding of the Teneurins and discuss the mechanistic conservation that allows the Teneurins to achieve common neurodevelopmental goals. Finally, we will posit the next steps for understanding how this remarkably versatile family of proteins functions to control multiple distinct events in the creation of a nervous system.
Futures commission merchants, customer funds and capital requirements: An organizational analysis of the futures industry

Abstract We study futures commission merchants, or “FCMs,” who are the important intermediaries through which institutional, corporate and retail customers conduct trading in interest rate, currency and commodity futures. We construct and examine a data base of FCM financial information including holdings of customer segregated and secured funds intended to support trading on U.S. and foreign futures exchanges over the period 1995–2018. We find significant industry consolidation including a 68% decline in the number of carrying FCMs. We also find significant structural changes including the increased dominance of bank-affiliated and dually-registered, broker-dealer FCMs, with the latter now accounting for 54% of all FCMs and 92% of customer funds held. We discuss regulatory initiatives potentially influencing the consolidation including those resulting from the 2008 financial crisis as well as from the collapse of notable FCMs due to alleged fraudulent activities and misbehavior involving customer funds. Finally, we analyze associated changes in market concentration and competitiveness.
Exploratory Study of 3 Cases of Corporate Crisis and Stock Market Reaction

The topic of overreaction, and reactions in the stock-market is highly important to understand foranybody with a financial background, or with a general interest in the stock-market. To this extend it seemed as authors would agree that overreactions in the stock-market is a common concept, however there is a great deal of uncertainty about how, and when it would happen. Therefore, this paper will have a quantitative exploratory case-study approach, with the purpose of providing more insights in how the market reacts to certain situations. It was chosen to use legitimacy as the criteria for the crisis events, meaning all the cases presented in the paper will have experienced legitimacy issues in relations to the crisis. A theoretical framework will be used for the analysis that highlights some of the important aspects from the crisis situations, which will in the end be used for a combined comparison.What was found in this paper was that the level of uncertainty information and uncertainty risk that a crisis created could play a significant role when it comes to reactions from the market. It was seen that the importance of having a proper response strategy to legitimacy crisis situations was fairly minimal. The case-studies showed that the company who seemed to have the worst response to the event, was also the company that experienced the least impact from the crisis, in terms of stock-market reaction.
Solvent-free synthesis of heterocyclic compounds using microwaves

Microwave-enhanced solvent-free synthetic approach is described that features simplicity, manipulative ease of the operation and conservation of solvents as the main advantages. This eco-friendly approach, which has found application in facile organic functional group transformations, is applied to rapid assembly of heterocyclic compounds. A variety of solid state reactions are described that occur rapidly at ambient pressure under solventless conditions and provide ready access to intermediates such as enamines and α-tosyloxyketones which can be transformed in situ to biologically significant heterocyclic compounds such as isoflav-3-enes, flavones, quinolones, 2-aroylbenzo[b]furans and thiazoles in one-pot operation. Multicomponent reactions under these solvent-free conditions can be adapted for high speed parallel synthesis and are exemplified by assembly of dihydropyrimidine-2(1H)-ones (Biginelli reaction) and imidazo[1,2-a]annulated pyridines, pyrazines and pyrimidines (Ugi reaction) which may have potential in building a library of such compounds.
Highly enantioselective synthesis of rigid, quaternary 1,4-benzodiazepine-2,5-diones derived from proline.

Proline-derived 1,4-benzodiazepine-2,5-diones are extremely useful scaffolds in medicinal chemistry. In this paper, we describe a protocol for retentive C3 alkylation of these materials, thus accomplishing the direct synthesis of enantiopure quaternary 1,4-benzodiazepine-2,5-diones. The high enantioselectivities (up to 99.5%) are attributed to memory of chirality.
Sequenced Reactions with Samarium(II) Iodide. Sequential Intermolecular Carbonyl Addition/Intramolecular Nucleophilic Acyl Substitution for the Preparation of Seven-, Eight-, and Nine-Membered Carbocycles

Samarium(II) iodide has been employed to promote a tandem intermolecular carbonyl addition/intramolecular nucleophilic acyl substitution sequence, generating seven- through nine-membered monocyclic, bicyclic, and tricyclic ring systems with good yields and high diastereoselectivities. This tandem reaction consists of an intermolecular reaction followed by an intramolecular ring expansion that results in a formal [m + n] cycloaddition, starting from extremely simple, readily available substrates. The regioselectivity and stereoselectivity of the process arise from a tuning of the reducing power of samarium(II) iodide with nickel(II) iodide in the first step and irradiation with visible light in the second. By using this method, a variety of structural motifs have been assembled rapidly in good yields.
Synthesis and characterization of uranyl chromate sheet compounds containing edge-sharing dimers of uranyl pentagonal bipyramids

Abstract Eight uranyl chromates have been crystallized from aqueous solution and characterized: Mg(H2O)6[(UO2)2(CrO4)2(OH)2](H2O)3 (1), (NH4)2[(UO2)2(CrO4)2(OH)2](H2O)3, Rb2[(UO2)2(CrO4)2(OH)2](H2O)3 (3), Cs[(UO2)(CrO4)(OH)]H2O (4), Rb[(UO2)(CrO4)(OH)]H2O (5) Co(H2O)4(Co(H2O)6)2[(UO2)4(CrO4)6(OH)2](H2O)4 (6), Li2[(UO2)2(CrO4)3](H2O)7 (7), and Zn(H2O)6[(UO2)2(CrO4)3](H2O)3 (8). The structural units of 1 through 8 each consist of a sheet of uranyl pentagonal bipyramids and (Cr(VI)O4)2− tetrahedra. In each case two uranyl pentagonal bipyramids share an equatorial edge, giving a dimer that is linked into the sheet through vertex sharing with (Cr(VI)O4)2− tetrahedra. The sheets are based upon three distinct sheet anion topologies, and the sheets based on a given anion topology can differ in the orientations of the non-bridging O atoms of (CrO4)2− tetrahedra. The interlayers of these compounds contain either monovalent or divalent cations, as well as H2O groups that are either bonded to the interlayer cation or are held in place by H bonding only. We explore the relationships between sheet topologies and interlayer configuration in these compounds.
Randomized Kaczmarz solver for noisy linear systems

The Kaczmarz method is an iterative algorithm for solving systems of linear equations Ax=b. Theoretical convergence rates for this algorithm were largely unknown until recently when work was done on a randomized version of the algorithm. It was proved that for overdetermined systems, the randomized Kaczmarz method converges with expected exponential rate, independent of the number of equations in the system. Here we analyze the case where the system Ax=b is corrupted by noise, so we consider the system Ax≈b+r where r is an arbitrary error vector. We prove that in this noisy version, the randomized method reaches an error threshold dependent on the matrix A with the same rate as in the error-free case. We provide examples showing our results are sharp in the general context.
Novel quaternary lanthanum bismuth sulfides Pb2LaxBi8-xS14, Sr2LaxBi8-xS14, and Cs2LaxBi10-xS16 with complex structures

The compounds Pb(2)La(x)Bi(8-x)S(14) (I), Sr(2)La(x)Bi(8-x)S(14) (II), and Cs(2)La(x)Bi(10-x)S(16) (III) were synthesized from the corresponding elements or binary sulfides at temperatures above 850 degrees C. Compounds I and II are isostructural, forming a new structure type, while the structure of III is related to the structure of the mineral kobellite. All compounds crystallize in the orthorhombic space group Pnma (No. 62) with a = 21.2592(4) A, b = 4.0418(1) A, c = 28.1718(3) A, Z = 4 for I, a = 21.190(1) A, b = 4.0417(2) A, c = 28.285(2) A, Z = 4 for II and a = 34.893(4) A, b = 4.0697(4) A, c = 21.508(2) A, Z = 4 for III. All compounds exhibit mixed site occupancy between Bi and La. Furthermore, I and II exhibit disorder between the divalent atom (Sr or Pb) and/or La and/or Bi. The structures of I and II consist of thin walls made of two metal-atom-thick NaCl-type blocks running in two opposite directions in the ac plane, forming rhombus-shaped tunnels. These tunnels are filled with Bi(2)Te(3)-type fragments. In the points where the walls intersect they form Gd(2)S(3)-type fragments. The structure of III consists of a complex three-dimensional framework with Cs-filled tunnels. All compounds are semiconductors with band gaps around 1.0 eV, and they melt around 740-860 degrees C.
Shape convergence for aggregate tiles in conformal tilings

Given a substitution tiling $T$ of the plane with subdivision operator $\tau$, we study the conformal tilings $\mathcal{T}_n$ associated with $\tau^n T$. We prove that aggregate tiles within $\mathcal{T}_n$ converge in shape as $n\rightarrow \infty$ to their associated Euclidean tiles in $T$.
Copper(I) 3-methylsalicylate, an efficient catalyst for N-arylation of heterocycles under moderate reaction conditions

Copper(I) 3-methylsalicylate mediates N-arylation reactions of both aliphatic and aromatic heterocycles under moderate reaction conditions. Both electron rich and electron poor aryl bromides and a diverse set of N-heterocycles were allowed to react and gave N-arylation products in high yields which demonstrated the efficiency and utility of this catalyst.
An enantioselective synthesis of phomopsolide D

Abstract A short enantioselective route to the highly functionalized α,β-unsaturated δ-lactone natural product phomopsolide D and three of its stereoisomers, has been accomplished. All of the carbon atoms of phomopsolide D come from tiglic acid and 2-furyl-1-penta-1′,3′-dienylketone (furan plus hexadienal). This approach derives its asymmetry from the sequential use of two catalytic asymmetric reactions; these being a Sharpless dihydroxylation reaction and a Noyori furylketone reduction. The resulting furfuryl alcohols were stereoselectively transformed into α,β-unsaturated δ-lactones via a short highly diastereoselective oxidation and reduction sequence.
Tl2AXTe4 (A = Cd, Hg, Mn; X = Ge, Sn): Crystal Structure, Electronic Structure, and Thermoelectric Properties

The six new compounds Tl2CdGeTe4, Tl2CdSnTe4, Tl2HgGeTe4, Tl2HgSnTe4, Tl2MnGeTe4, and Tl2MnSnTe4 have been synthesized. All six compounds are isostructural and crystallize in the tetragonal space group I-42m with a ≈ 8.3 A and c ≈ 7.1 A. The structure is composed of chains of composition [AXTe4]2- separated by Tl1+ ions, an ordered superstructure of the TlSe structure type. In addition to their syntheses and crystal structures, we report the calculated electronic structures of these six compounds and of the related compounds KInTe2 and TlInTe2. We measured the thermoelectric properties (electrical resistivity, thermopower, and thermal conductivity) of Tl2CdGeTe4, Tl2CdSnTe4, Tl2HgGeTe4, and Tl2HgSnTe4. These compounds are semiconductors with very low thermal conductivities and moderately high thermopowers. However, as currently prepared they have resistivities that are too high for thermoelectric applications. Magnetic susceptibility and resistivity measurements show Tl2MnGeTe4 and Tl2MnSnTe4 to be Mott i...
Map segmentation, automated model-building and their application to the Cryo-EM Model Challenge.

Abstract A recently-developed method for identifying a compact, contiguous region representing the unique part of a density map was applied to 218 Cryo-EM maps with resolutions of 4.5 A or better. The key elements of the segmentation procedure are (1) identification of all regions of density above a threshold and (2) choice of a unique set of these regions, taking symmetry into consideration, that maximize connectivity and compactness. This segmentation approach was then combined with tools for automated map sharpening and model-building to generate models for the 12 maps in the 2016 Cryo-EM Model Challenge in a fully automated manner. The resulting models have completeness from 24% to 82% and RMS distances from reference interpretations of 0.6 A–2.1 A.
Synthesis of the ABCD-rings of the insecticidal indole alkaloid nodulisporic acid

Abstract Lewis acid mediated cyclization of the aldehyde 7 leads to 8, 9 and 10, of which 10 contains the structural and stereochemical elements of the ABC-rings of nodulisporic acid 1.
A convenient and efficient three-step synthesis of α-chloro keto acids

Abstract Efficient three-step syntheses of α-chloro keto acids 1a-c from ω-alkenoic acids 2 and ω-alkenyl alcohols 3 are described, proceeding via epoxidation/chloride-mediated epoxide ring opening/Jones oxidation protocols.
MoMo: discovery of statistically significant post-translational modification motifs.

Motivation Post-translational modifications (PTMs) of proteins are associated with many significant biological functions and can be identified in high throughput using tandem mass spectrometry. Many PTMs are associated with short sequence patterns called 'motifs' that help localize the modifying enzyme. Accordingly, many algorithms have been designed to identify these motifs from mass spectrometry data. Accurate statistical confidence estimates for discovered motifs are critically important for proper interpretation and in the design of downstream experimental validation. Results We describe a method for assigning statistical confidence estimates to PTM motifs, and we demonstrate that this method provides accurate P-values on both simulated and real data. Our methods are implemented in MoMo, a software tool for discovering motifs among sets of PTMs that we make available as a web server and as downloadable source code. MoMo re-implements the two most widely used PTM motif discovery algorithms-motif-x and MoDL-while offering many enhancements. Relative to motif-x, MoMo offers improved statistical confidence estimates and more accurate calculation of motif scores. The MoMo web server offers more proteome databases, more input formats, larger inputs and longer running times than the motif-x web server. Finally, our study demonstrates that the confidence estimates produced by motif-x are inaccurate. This inaccuracy stems in part from the common practice of drawing 'background' peptides from an unshuffled proteome database. Our results thus suggest that many of the papers that use motif-x to find motifs may be reporting results that lack statistical support. Availability and implementation The MoMo web server and source code are provided at http://meme-suite.org. Supplementary information Supplementary data are available at Bioinformatics online.
Chirality provides a direct fitness advantage and facilitates intermixing in cellular aggregates.

Chirality in shape and motility can evolve rapidly in microbes and cancer cells. To determine how chirality affects cell fitness, we developed a model of chiral growth in compact aggregates such as microbial colonies and solid tumors. Our model recapitulates previous experimental findings and shows that mutant cells can invade by increasing their chirality or switching their handedness. The invasion results either in a takeover or stable coexistence between the mutant and the ancestor depending on their relative chirality. For large chiralities, the coexistence is accompanied by strong intermixing between the cells, while spatial segregation occurs otherwise. We show that the competition within the aggregate is mediated by bulges in regions where the cells with different chiralities meet. The two-way coupling between aggregate shape and natural selection is described by the chiral Kardar-Parisi-Zhang equation coupled to the Burgers’ equation with multiplicative noise. We solve for the key features of this theory to explain the origin of selection on chirality. Overall, our work suggests that chirality could be an important ecological trait that mediates competition, invasion, and spatial structure in cellular populations.
Iodination of organotrifluoroborates: synthesis of vinyl and alkynyl iodides

Abstract Vinyl- and alkynyltrifluoroborates are rapidly converted to vinyl and alkynyl iodides under mild conditions using sodium iodide in the presence of chloramine-T. The reaction is stereospecific and proceeds in excellent yield.
Sequence capture of ultraconserved elements from bird museum specimens

New DNA sequencing technologies are allowing researchers to explore the genomes of the millions of natural history specimens collected prior to the molecular era. Yet, we know little about how well specific next-generation sequencing (NGS) techniques work with the degraded DNA typically extracted from museum specimens. Here, we use one type of NGS approach, sequence capture of ultraconserved elements (UCEs), to collect data from bird museum specimens as old as 120 years. We targeted 5060 UCE loci in 27 western scrub-jays (Aphelocoma californica) representing three evolutionary lineages that could be species, and we collected an average of 3749 UCE loci containing 4460 single nucleotide polymorphisms (SNPs). Despite older specimens producing fewer and shorter loci in general, we collected thousands of markers from even the oldest specimens. More sequencing reads per individual helped to boost the number of UCE loci we recovered from older specimens, but more sequencing was not as successful at increasing the length of loci. We detected contamination in some samples and determined that contamination was more prevalent in older samples that were subject to less sequencing. For the phylogeny generated from concatenated UCE loci, contamination led to incorrect placement of some individuals. In contrast, a species tree constructed from SNPs called within UCE loci correctly placed individuals into three monophyletic groups, perhaps because of the stricter analytical procedures used for SNP calling. This study and other recent studies on the genomics of museum specimens have profound implications for natural history collections, where millions of older specimens should now be considered genomic resources.
Insights into impact of DNA copy number alteration and methylation on the proteogenomic landscape of human ovarian cancer via a multi-omics integrative analysis

In this work, we propose iProFun, an integrative analysis tool to screen for proteogenomic functional traits perturbed by DNA copy number alterations (CNAs) and DNA methylations. The goal is to characterize functional consequences of DNA copy number and methylation alterations in tumors and to facilitate screening for cancer drivers contributing to tumor initiation and progression. Specifically, we consider three functional molecular quantitative traits: mRNA expression levels, global protein abundances, and phosphoprotein abundances. We aim to identify those genes whose CNAs and/or DNA methylations have cis-associations with either some or all three types of molecular traits. Compared with analyzing each molecular trait separately, the joint modeling of multi-omics data enjoys several benefits: iProFun experienced enhanced power for detecting significant cis-associations shared across different omics data types, and it also achieved better accuracy in inferring cis-associations unique to certain type(s) of molecular trait(s). For example, unique associations of CNAs/methylations to global/phospho protein abundances may imply posttranslational regulations. We applied iProFun to ovarian high-grade serous carcinoma tumor data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium and identified CNAs and methylations of 500 and 121 genes, respectively, affecting the cis-functional molecular quantitative traits of the corresponding genes. We observed substantial power gain via the joint analysis of iProFun. For example, iProFun identified 117 genes whose CNAs were associated with phosphoprotein abundances by leveraging mRNA expression levels and global protein abundances. By comparison, analyses based on phosphoprotein data alone identified none. A network analysis of these 117 genes revealed the known oncogene AKT1 as a key hub node interacting with many of the rest. In addition, iProFun identified one gene, BIN2, whose DNA methylation has cis-associations with its mRNA expression, global protein, and phosphoprotein abundances. These and other genes identified by iProFun could serve as potential drug targets for ovarian cancer.
Novel and Efficient Insertions of Carbons Carrying O-, S-, and N-Linked Substituents: Synthesis of α-Alkoxyalkyl, α-(Alkylthio)alkyl, and α-(Carbazol-9-yl)alkyl Ketones

A wide variety of benzotriazolyl-stabilized anions 2, obtained by the lithiation of 1-(α-alkoxyalkyl)-, 1-[α-(alkylthio)alkyl]-, and 1-[α-(carbazol-9-yl)alkyl]benzotriazoles 1, on reaction with ali...
Isolation and Structures of Nostopeptolides A1, A2 and A3 from the Cyanobacterium Nostoc sp. GSV224

Abstract The isolation and total structure determinations of nostopeptolides A1 (1), A2 (2) and A3 (3) are described. These cyclic depsipeptides, which are devoid of cytotoxic, antifungal and inhibition of protease activities, are characteristic constituents of the cryptophycin-producing cyanobacterium Nostoc sp. GSV224. Structure elucidation by NMR analysis was made more challenging by the existence of each nostopeptolide in three conformations. One-dimensional TOCSY experiments proved to be very useful in isolating and identifying the nine amino acid residues and the butyryl group in each compound. The absolute stereochemistries of 1–3 were determined by comparing the amino acids in the acid hydrolyzates directly with authentic standards.
An Asymmetric Aldol−Ring-Closing Metathesis Strategy for the Enantioselective Construction of Oxygen Heterocycles: An Efficient Approach to the Enantioselective Synthesis of (+)-Laurencin

A strategy is described for the enantioselective construction of medium-ring cyclic ethers by merging the asymmetric aldol addition of glycolates with a ring-closing metathesis reaction. Cyclic ethers of seven-, eight-, and nine-membered rings are readily available through a ring-closing metathesis without cyclic conformational constraints, by exploiting the acyclic conformational bias of the gauche effect. A short formal synthesis of the eight-membered ether (+)-laurencin, a red algae metabolite, has been accomplished utilizing the aldol−metathesis combination.
Cofilin-actin rod formation in neuronal processes after brain ischemia

Functional impairment after brain ischemia results in part from loss of neuronal spines and dendrites, independent of neuronal death. Cofilin-actin rods are covalently linked aggregates of cofilin-1 and actin that form in neuronal processes (neurites) under conditions of ATP depletion and oxidative stress, and which cause neurite degeneration if not disassembled. ATP depletion and oxidative stress occur with differing severity, duration, and time course in different ischemic conditions. Here we evaluated four mouse models of brain ischemia to define the conditions that drive formation of cofilin-actin rods. Three of the models provide early reperfusion: transient middle cerebral artery occlusion (MCAo), transient bilateral common carotid artery occlusion (CCAo), and cardiac arrest / cardiopulmonary resuscitation (CA/CPR). Early reperfusion restores ATP generating capacity, but also induces oxidative stress. The fourth model, photothrombotic cortical infarction, does not provide reperfusion. Cofilin-actin rods were formed in each of these models, but with differing patterns. Where acute reperfusion occurred, rod formation was maximal within 4 hours after reperfusion. Where infarction occurred, rods continued to form for at least 24 hours after ischemic onset, and extended into the adjacent non-ischemic tissue. Interventions that limit cofilin-actin rod formation may help to preserve integrity of neuronal processes in permanent ischemia.
Strengthening New Infrastructure Assets : A Cost-Benefit Analysis

This paper explores the benefits and the costs of strengthening infrastructure assets to make them more resilient, reducing the repair costs and infrastructure disruptions caused by natural hazards. Strengthening infrastructure assets in low- and middle-income countries would increase investment needs in power, transport, and water and sanitation by between $11 billion and $65 billion a year, i.e. 3 percent of baseline infrastructure investment needs. The uncertainty pertaining to the costs and benefits of infrastructure resilience makes it difficult to provide a single estimate for the benefit-cost ratio of strengthening exposed infrastructure assets. To manage this uncertainty, this paper explores the benefit-cost ratio in 3,000 scenarios, combining uncertainties in all parameters of the analysis. The benefit-cost ratio is higher than 1 in 96 percent of the scenarios, larger than 2 in 77 percent of them, and higher than 4 in half of them. The net present value of these investments over the lifetime of new infrastructure assets -- or, equivalently, the cost of inaction -- exceeds $2 trillion in 75 percent of the scenarios and $4.2 trillion in half of them. Moreover, climate change makes the strengthening of infrastructure assets even more important, doubling the median benefit-cost ratio.
Recent developments in guanylating agents

Guanidines are important molecules with a wide range of interesting properties. In this overview we summarize recent advances in the development of guanylating reagents which we define as compounds forming a guanidine structure by a chemical transformation. We cover important classes of guanylating agents developed in the last two decades and representative examples are reported.
Hydrodynamics of linear acceleration in bluegill sunfish, Lepomis macrochirus.

ABSTRACT In their natural habitat, fish rarely swim steadily. Instead they frequently accelerate and decelerate. Relatively little is known about how fish produce extra force for acceleration in routine swimming behavior. In this study, we examined the flow around bluegill sunfish Lepomis macrochirus during steady swimming and during forward acceleration, starting at a range of initial swimming speeds. We found that bluegill produce vortices with higher circulation during acceleration, indicating a higher force per tail beat, but they do not substantially redirect the force. We quantified the flow patterns using high speed video and particle image velocimetry and measured acceleration with small inertial measurement units attached to each fish. Even in steady tail beats, the fish accelerates slightly during each tail beat, and the magnitude of the acceleration varies. In steady tail beats, however, a high acceleration is followed by a lower acceleration or a deceleration, so that the swimming speed is maintained; in unsteady tail beats, the fish maintains the acceleration over several tail beats, so that the swimming speed increases. We can thus compare the wake and kinematics during single steady and unsteady tail beats that have the same peak acceleration. During unsteady tail beats when the fish accelerates forward for several tail beats, the wake vortex forces are much higher than those at the same acceleration during single tail beats in steady swimming. The fish also undulates its body at higher amplitude and frequency during unsteady tail beats. These kinematic changes likely increase the fluid dynamic added mass of the body, increasing the forces required to sustain acceleration over several tail beats. The high amplitude and high frequency movements are also likely required to generate the higher forces needed for acceleration. Thus, it appears that bluegill sunfish face a trade-off during acceleration: the body movements required for acceleration also make it harder to accelerate.
Embedding Imputation with Grounded Language Information.

Due to the ubiquitous use of embeddings as input representations for a wide range of natural language tasks, imputation of embeddings for rare and unseen words is a critical problem in language processing. Embedding imputation involves learning representations for rare or unseen words during the training of an embedding model, often in a post-hoc manner. In this paper, we propose an approach for embedding imputation which uses grounded information in the form of a knowledge graph. This is in contrast to existing approaches which typically make use of vector space properties or subword information. We propose an online method to construct a graph from grounded information and design an algorithm to map from the resulting graphical structure to the space of the pre-trained embeddings. Finally, we evaluate our approach on a range of rare and unseen word tasks across various domains and show that our model can learn better representations. For example, on the Card-660 task our method improves Pearson’s and Spearman’s correlation coefficients upon the state-of-the-art by 11% and 17.8% respectively using GloVe embeddings.
Organic phase conversion of bulk (wurtzite) ZnO to nanophase (wurtzite and zinc blende) ZnO

Abstract We describe the all-organic phase conversion of bulk commercial ZnO in the wurtzite modification to sub-30 nm ZnO that we find to be partially in the zinc blende [ F 4 ¯ 3 m , a = 4.568 ( 3 ) A ] modification. The conversion involves refluxing ZnO in 2,4-pentanedione (acetylacetone) at 413 K to form the zinc 2,4-pentanedionate, which is decomposed by heating at 573 K in an appropriate high-temperature solvent such as dibenzylether to form nanophase ZnO. This nanophase, partially zinc blende ZnO can also be obtained in a single step by heating commercial zinc 2,4-pentanedionate in refluxing dibenzylether. Thermodiffractometry suggests that the conversion of zinc blende ZnO to wurtzite ZnO commences near 650 K.
Suzuki reactions catalyzed by palladium complexes bearing the bulky (2,6-dimesitylphenyl)dimethylphosphine

A new bulky and stable phosphine (2,6-dimesitylphenyl)dimethylphosphine, and representative palladium complexes have been prepared and structurally characterized; some of these complexes prove efficient for coupling of aryl chlorides with arylboronic acids.
Intermetallic Frameworks: Synthesis, Characterization, and Bonding of K0.4Cd2 and Na26Cd141

Two new compounds have been synthesized and characterized in the systems A−Cd where A = Na or K. They have identical ratios of alkali-metal to cadmium but have remarkably different structures. The ...
Tandem Nucleophilic Addition/Fragmentation of Vinylogous Acyl Nonaflates for the Synthesis of Functionalized Alkynes, with New Mechanistic Insight

Vinylogous acyl nonaflates, like the corresponding triflates, are subject to nucleophile-triggered fragmentation as part of a tandem process for generating functionalized alkynes. Advantages to the use of nonaflates in lieu of triflates include cost and stability. Computational analysis supports a postulated fragmentation mechanism involving a closed (cyclic) transition state with concerted extrusion of lithium sulfonate.
Synthesis of Cryptothilone 1, the First Cryptophycin−Epothilone Hybrid

A hybrid structure was synthesized in which one portion is characteristic of a cryptophycin and a second sector bears the signature of an epothilone. The hybrid, in contrast to parent cryptophycin and epothilone systems, showed no effect on the tubulin assembly reaction.
Defect-facilitated buckling in supercoiled double-helix DNA.

We present a statistical-mechanical model for stretched twisted double-helix DNA, where thermal fluctuations are treated explicitly from a Hamiltonian without using any scaling hypotheses. Our model applied to defect-free supercoiled DNA describes the coexistence of multiple plectoneme domains in long DNA molecules at physiological salt concentrations ($\ensuremath{\approx}0.1\phantom{\rule{0.16em}{0ex}}\mathrm{M} {\mathrm{Na}}^{+}$) and stretching forces ($\ensuremath{\approx}1\phantom{\rule{0.16em}{0ex}}\mathrm{pN})$. We find a higher (lower) number of domains at lower (higher) ionic strengths and stretching forces, in accord with experimental observations. We use our model to study the effect of an immobile point defect on the DNA contour that allows a localized kink. The degree of the kink is controlled by the defect size, such that a larger defect further reduces the bending energy of the defect-facilitated kinked end loop. We find that a defect can spatially pin a plectoneme domain via nucleation of a kinked end loop, in accord with experiments and simulations. Our model explains previously reported magnetic tweezer experiments [A. Dittmore et al., Phys. Rev. Lett. 119, 147801 (2017)] showing two buckling signatures: buckling and ``rebuckling'' in supercoiled DNA with a base-unpaired region. Comparing with experiments, we find that under 1 pN force, a kinked end loop nucleated at a base-mismatched site reduces the bending energy by $\ensuremath{\approx}0.7 {k}_{B}T$ per unpaired base. Our model predicts the coexistence of three states at the buckling and rebuckling transitions, which warrants new experiments.
DOCSDN: Dynamic and Optimal Configuration of Software-Defined Networks

Networks are designed with functionality, security, performance, and cost in mind. Tools exist to check or optimize individual properties of a network. These properties may conflict, so it is not always possible to run these tools in series to find a configuration that meets all requirements. This leads to network administrators manually searching for a configuration.
State of the practice in pavement structural design/analysis codes relevant to airfield pavement design

Abstract An airfield pavement structure is designed to support aircraft live loads for a specified pavement design life. Computer codes are available to assist the engineer in designing an airfield pavement structure. Pavement structural design is generally a function of five criteria: the pavement structural configuration, materials, the applied loading, ambient conditions, and how pavement failure is defined. The two typical types of pavement structures, rigid and flexible, provide load support in fundamentally different ways and develop different stress distributions at the pavement – base interface. Airfield pavement structural design is unique due to the large concentrated dynamic loads that a pavement structure endures to support aircraft movements. Aircraft live loads that accompany aircraft movements are characterized in terms of the load magnitude, load area (tire-pavement contact surface), aircraft speed, movement frequency, landing gear configuration, and wheel coverage. The typical methods used for pavement structural design can be categorized into three approaches: empirical methods, analytical (closed-form) solutions, and numerical (finite element analysis) approaches. This article examines computational approaches used for airfield pavement structural design to summarize the state-of-the-practice and to identify opportunities for future advancements. United States and non-U.S. airfield pavement structural codes are reviewed in this article considering their computational methodology and intrinsic qualities.
Sensitivity and Specificity of the Stemmer Sign for Lymphedema: A Clinical Lymphoscintigraphic Study.

Background The Stemmer sign is a physical examination finding used to diagnose lymphedema. If the examiner cannot pinch the skin of the dorsum of the foot or hand then this positive finding is associated with lymphedema. The purpose of the study was to determine the accuracy of the Stemmer sign to predict lymphedema. Methods All patients referred to our Lymphedema Program between 2016 and 2018 were tested for the Stemmer sign and underwent lymphoscintigraphy to define the patient's lymphatic function. Patient age, lymphedema type (primary and secondary), disease location (arm and leg), lymphoscintigraphy findings, stage, severity, and body mass index were recorded. Comparison of predictive variables and Stemmer sign result was performed using Fisher's exact test and Student's t test. Results One hundred ten patients were studied: patients with a positive Stemmer sign (n = 87) exhibited abnormal (n = 80) or normal (n = 7) lymphatic function by lymphoscintigraphy (sensitivity = 92%). False-positive Stemmer signs included individuals with obesity (n = 6) or spinal muscle atrophy (n = 1). Subjects with a negative Stemmer sign (n = 23) had normal (n = 13) or abnormal (n = 10) lymphatic function by imaging (specificity = 57%). Patients with a false-negative Stemmer sign were more likely to have a normal body mass index (P = 0.02) and Stage 1 disease (P = 0.01). Conclusions A positive Stemmer sign is a sensitive predictor for primary and secondary lymphedema of the arms or legs and, thus, is a useful part of the physical examination. Because the test exhibits moderate specificity, lymphoscintigraphy should be considered for patients with a high suspicion of lymphedema that have a negative Stemmer sign.