cssi/SciSciGPT-SciSciNet huggingface dataset:
Scope of the Intramolecular Imidotitanium−Alkyne [2 + 2] Cycloaddition−Azatitanetine Acylation Sequence. An Efficient Procedure for the Synthesis of 2-(2-Keto-1-alkylidene)tetrahydropyrroles and Related Compounds

Sequential [2 + 2] cycloaddition of transient imidotitanium complexes to tethered alkynes followed by C-acylation of the resulting azatitanetines with acyl cyanides has been shown to provide a rang...
Synthesis of a strained, air-sensitive, polycyclic aromatic hydrocarbon by means of a new 1,4-benzadiyne equivalent

Abstract 9,11,20,22-Tetraphenyltetrabenzo[a,c,l,n]pentacene ( 4 ) was prepared by the pyrolysis of 1,4-bis(phenyliodonio)benzene-2,5-dicarboxylate ( 9 ), a new 1,4-benzadiyne equivalent, in the presence of phencyclone. Although stable as a solid, solutions of 4 must be handled in the dark; otherwise, ambient light promotes its oxygenation to the 10,21-endoperoxide ( 10 ). The X-ray structures of both 4 and 10 were determined, as well as the stuctures of two dihydrophencyclones isolated as byproducts of the pyrolysis. Compound 4 adopts a conformation with approximate C2h symmetry in the solid state, in contrast to the results of gas-phase calculations, which uniformly predict a twisted, D2-symmetric ground state structure.
Less than Meets the Eye: an Analysis of Robert Reich’s Just Giving: Why Philanthropy Is Failing Democracy and How It Can Do Better (2018)

For more than ten years, Prof. Rob Reich has lamented that foundations have been allowed to be “subsidized,” unaccountable, opaque, and powerful – as he and others conceive of foundations and their environment. This lament is presented in his recent book, which positions its purposes on five pillars: (1) philanthropy is repugnant to democracy as described; (2) philanthropy is an “artifact” of the State; (3) foundations are opaque and unaccountable; (4) donor intent and perpetuity are subversive; and (5) the charitable deduction is a “subsidy” with no redeeming value except possibly as a tool to justify reining in foundations and philanthropy. However, each pillar leaves out critical elements and analysis, and the vacillation between theory and practice without noting the switches or fully presenting either creates confusion. Those pillars are intended to support two possible roles – and only two roles – as acceptable for foundations in democracy: discovery and advancing pluralism. However, their positioning neglects important chronologies and histories and suffers from other missing substantive analysis that also does not sufficiently support restricting foundations to these and only these functions. Finally, there seems to be a disconnect between overt objectives, actual presentation, and implicit purposes, which contribute to substantial concerns about critical gaps and missing information and perspective about foundations, philanthropy, and democracy. Ultimately, the theory and its presentation are too confusing, incomplete, and nuanced in part because they neglect substantive ways in which foundations and philanthropy are not only not repugnant to and not failing American representative democracy but are actually consistent with it and even exemplars of it, which is a topic for another day.
Improved Synthesis of Various Isotope Labeled 4-Hydroxyalkenals and Peroxidation Intermediates

Abstract A concise and isotope specific synthesis of perfluorobenzyl 5,5,6,6-tetradeutero-9-oxononanoate and an abbreviated general multiisotope synthesis of 4-hydroxyalkenals is reported.
Reactions of N-(Ethoxycarbonyl)-3-halo-3-(halomethyl)azetidines with DBU. The Halogen Dance

Reaction of N-(ethoxycarbonyl)-3-(bromomethyl)-3-chloroazetidine (3) with DBU results in the formation of two haloalkenes, i.e., N-(ethoxycarbonyl)-3-(bromomethylene)azetidine and N-(ethoxycarbonyl)-3-(chloromethylene)azetidine (4a and 4b, respectively). The results of control experiments suggest that Cl- is capable of promoting nucleophilic displacement of bromine in the CH2Br groups of both 3 and N-(ethoxycarbonyl)-3-bromo-3-(bromomethyl)azetidine (8), but Br- is incapable of displacing chlorine in the CH2Cl groups of both N-(ethoxycarbonyl)-3-chloro-3-(chloromethyl)azetidine (7) and N-carbethoxy-3-bromo-3-(chloromethyl)azetidine (10). Thus, it is suggested that the formation of 4b via reaction of 3 with DBU is a result of DBU-promoted elimination of HCl from 7, a key reaction intermediate. The observations reported herein can be explained without invoking the intermediacy of any bridged halonium ion.
Buy-Many Mechanisms are Not Much Better than Item Pricing

Multi-item revenue optimal mechanisms can be very complex offering many different bundles to the buyer that could even be randomized. Such complexity is thought to be necessary as the revenue gaps between randomized and deterministic mechanisms, or deterministic and simple mechanisms are huge even for additive valuations. We challenge this conventional belief by showing that these large gaps can only happen in unrealistic situations. These are situations where the mechanism overcharges a buyer for a bundle while selling individual items at much lower prices. Arguably this is impractical as the buyer can break his order into smaller pieces paying a much lower price overall. Our main result is that if the buyer is allowed to purchase as many (randomized) bundles as he pleases, the revenue of any multi-item mechanism is at most O(log n) times the revenue achievable by item pricing, where n is the number of items. This holds in the most general setting possible, with an arbitrarily correlated distribution of buyer types and arbitrary valuations. We also show that this result is tight in a very strong sense. Any family of mechanisms of subexponential description complexity cannot achieve better than logarithmic approximation even against the best deterministic mechanism and even for additive valuations. In contrast, item pricing that has linear description complexity matches this bound against randomized mechanisms.
Epistasis and Entropy

Epistasis is a key concept in the theory of adaptation. Indicators of epistasis are of interest for large systems where systematic fitness measurements may not be possible. Some recent approaches depend on information theory. We show that considering shared entropy for pairs of loci can be misleading. The reason is that shared entropy does not imply epistasis for the pair. This observation holds true also in the absence of higher order epistasis. We discuss a method for reducing the number of false positives. However, our main conclusion is that entropy-based approaches have serious limitations in this context.
Olefin synthesis by radical methods from xanthate, selenobenzoate and thionocarbonate derivatives of β-hydroxy sulfones.

Abstract β-Hydroxy sulfones have been transformed to the corresponding radicophilic derivatives (xanthales, selenobenzoates, thionocarbonates) These compounds can then be employed in the synthesis of the corresponding olefins by radical methods without the use of tin reagents.
Perivascular signals alter global gene expression profile of glioblastoma and response to temozolomide in a gelatin hydrogel.

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor, with patients exhibiting poor survival (median survival time: 15 months). Difficulties in treating GBM include not only the inability to resect the diffusively-invading tumor cells, but also therapeutic resistance. The perivascular niche (PVN) within the GBM tumor microenvironment contributes significantly to tumor cell invasion, cancer stem cell maintenance, and has been shown to protect tumor cells from radiation and chemotherapy. In this study, we examine how the inclusion of non-tumor cells in culture with tumor cells within a hydrogel impacts the overall gene expression profile of an in vitro artificial perivascular niche (PVN) comprised of endothelial and stromal cells directly cultured with GBM tumor cells within a methacrylamide-functionalized gelatin hydrogel. Using RNA-seq , we demonstrate that genes related to angiogenesis and extracellular matrix remodeling are upregulated in the PVN model compared to hydrogels containing only tumor or perivascular niche cells , while downregulated genes are related to cell cycle and DNA damage repair. Signaling pathways and genes commonly implicated in GBM malignancy, such as MGMT, EGFR, PI3K-Akt signaling, and Ras/MAPK signaling are also upregulated in the PVN model. We describe the kinetics of gene expression within the PVN hydrogels over a course of 14 days, observing the patterns associated with tumor cell-mediated endothelial network co-option and regression. We finally examine the effect of temozolomide, a frontline chemotherapy used clinically against GBM, on the PVN culture. Notably, the PVN model is less responsive to TMZ compared to hydrogels containing only tumor cells. Overall, these results demonstrate that inclusion of cellular and matrix-associated elements of the PVN within an in vitro model of GBM allows for the development of gene expression patterns and therapeutic response relevant to GBM.
A new quasi-one-dimensional ternary chalcogenide: synthesis, crystal structure, and electronic structure of Nb1+xV1-xS5 (x = 0.18).

The new low-dimensional ternary chalcogenide, Nb1+xV1-xS5 (x = 0.18), has been prepared and characterized. This compound crystallizes in the monoclinic space group, h-P21/m with two formula units i...
A Nonparametrized Ab Initio Determination of the Heat of Formation of Hydroxylamine, NH2OH

Large basis set coupled cluster calculations through noniterative triple excitations were used to compute optimized structures, harmonic vibrational frequencies, atomization energies at 0 K and heats of formation at 298 K for hydroxylamine (NH2OH) and three related compounds (NH3, HNO and H2O2). The use of basis sets as large as augmented sextuple zeta resulted in small extrapolations to the complete basis set limit in order to achieve chemical accuracy ( 1 kcal/mol) in the thermodynamic properties. Complete basis set estimates were determined from several simple extrapolation formulas. In addition, four other corrections were applied to the frozen core atomization energies, (1) a zero point vibrational correction: (2) a core/valence correlation correction; (3) a Douglas-Kroll-Hess scalar relativistic correction; and (4) a first order atomic spin-orbit correction. For NH3 and HNO we incorporated a fifth correction term intended to approximate the difference between coupled cluster theory and the full configuration interact result. This correction was based on coupled cluster theory through iterative quadruple excitations (CCSDTQ). Excellent agreement with experiment was found for the heats of formation of NH3, HNO and H2O2. For NH2OH the best current estimate of the heat of formation at 298 K is 10.1 0.3 kcal/mol, which falls roughlymore » midway between two experimental values at 12.0 2.4 and 7.9 1.5 kcal/mol.« less
High Conductivity in Gallium-Doped Zinc Oxide Powders

Gallium-doped zinc oxide powders have been prepared with electrical conductivities at 25 {degrees}C as 300 {Omega}{sup -1} cm{sup -1}, more than 1000 higher than previously reported. All materials prepared can be represented an Zn{sub 1-x}Ga{sub x}O, Zn{sub 1-y}Ga{sub y}O{sub 1+(y/2)}, or a combination of these two. For Zn{sub 1-x}Ga{sub x}O, the room-temperature conductivity increases monotonically with increasing x up to 2.7%, which is the limit of Ga solubility for this formulation at our synthesis temperatures of 1000 to 1200 {degrees}C. Conductivities measured from 4.2 to 500 K showed only a very small temperature dependence. An ESR peak (g=1.96), attributed to the conduction electrons, broadens with increased doping level. The hexagonal unit-cell edges increase with increasing x over the entire range of x. For the low conductivity Zn{sub 1-y}Ga{sub y}O{sub 1+(y/2)} series, the level of Ga substitution can reach at least 4.0%. 16 refs., 19 figs., 1 tab.
A facile preparation of various N-heterocycles using amides and olefins

Abstract We herein report a one pot approach for the synthesis of various nitrogen containing heterocycles including: oxazolines, thiazolines, and dihydro dioxazines via the addition of amides to olefins in the presence of N-iodosuccinimide (NIS) and propionitrile at high temperatures. Thus, the reaction of aryl/heteroaryl amides, thioamides, N-hydroxybenzamide, and phenylurea with various olefins in the presence of NIS and propionitrile at 45 °C afforded the N-heterocycles in good to moderate yields. Reaction of the electron deficient tri-O-acetyl- d -glucal and tri-O-acetyl- d -galactal with benzamide and thiophene-2-carboxamide afforded the N-glycooxazolines in good yields. The newly made heterocycles were tested against various enzymes. Only 3,6-diphenyl-dihydro-1,4,2-dioxazine (1c) was found to moderately inhibit hexokinase II (hHK2).
Syntheses utilizing n-perfluoroalkyl iodides [RFI, CnF2n+1-I] 2000–2010

Abstract This review presents a comprehensive assessment of the synthetic utility of n-perfluoroalkyl iodides (RFI, CnF2n+1-I, where n = 2–14) in the published literature from 2000 through 2010. RFI is a versatile synthetic reagent widely utilized to introduce the perfluoroalkyl functionality and its unique functional characteristics into organic substances. Two distinct analysis tools were employed. First, Reaxys® was employed to examine the versatility and occurrences of RFI in 1356 non-polymeric synthetic transformations. The most common RFI synthetic conversions were (i) free-radical addition to carbon–carbon double or triple bonds, (ii) coupling to aryl halides, and (iii) Grignard, organolithium, or similar RF anion addition to ketones and aldehydes. RFI were also used as a chain transfer reagent in free-radical polymerization reactions of fluorinated and other unsaturated monomers. Second, a complementary Chemical Abstracts’ STN AnaVist® search was employed to summarize the 779 publications describing reaction products that contained n-perfluoroalkyl chains (CnF2n+1-, where n = 2–4). The most common uses for materials into which RFI was incorporated were surfactants, pesticides, electronic materials, pharmaceuticals, liquid crystals, dyes and optical materials, battery electrolytes, repellents, lubricants and polymerization catalysts.
5C-ID: Increased resolution Chromosome-Conformation-Capture-Carbon-Copy with in situ 3C and double alternating primer design.

Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs, and looping interactions. Currently, there is a great need to evaluate the link between chromatin topology and genome function across many biological conditions and genetic perturbations. Hi-C can generate genome-wide maps of looping interactions but is intractable for high-throughput comparison of loops across multiple conditions due to the enormous number of reads (>6 Billion) required per library. Here, we describe 5C-ID, a new version of Chromosome-Conformation-Capture-Carbon-Copy (5C) with restriction digest and ligation performed in the nucleus (in situ Chromosome-Conformation-Capture (3C)) and ligation-mediated amplification performed with a double alternating primer design. We demonstrate that 5C-ID produces higher-resolution 3D genome folding maps with reduced spatial noise using markedly lower cell numbers than canonical 5C. 5C-ID enables the creation of high-resolution, high-coverage maps of chromatin loops in up to a 30 Megabase subset of the genome at a fraction of the cost of Hi-C.
Preparation of 2,6-disubstituted 2,3-Dihydro-4-pyridones: Dehydrogenation of trimethylsilyl enol ethers with palladium (ii) acetate

Abstract The oxidation of silyl enol ethers 2 with palladium(II) acetate is a convenient method for the preparation of synthetically useful 2,6-disubstituted 2,3-dihydro-4-pyridones 3.
Regio- and stereoselectivity in the reactions of organometallic reagents with an electron-deficient and an electron-rich vinyloxirane: applications for sequential bis-allylic substitution reactions in the generation of vicinal stereogenic centers.

Vinyloxiranes provide opportunities for bis-allylic substitution reactions and the generation of new vicinal stereogenic centers if regio- and stereocontrol can be achieved. Ethyl (E)-4,5-epoxy-2-h...
A convenient procedure for converting organic thiols into ethyldithio derivatives

Abstract A procedure has been devised for converting organic thiols into ethyldithio derivatives that requires only filtration and solvent evaporation steps for product isolation.
Stereochemistry and molecular rearrangements of some six-, seven-, and eight-coordinate chelates of early transition metals

Abstract This article is a review of the stereochemistry and molecular rearrangements of selected six-, seven-, and eight-coordinate chelates of early transition metals: primarily, metal β-diketonates, dithiocarbamates, and monothiocarbamates. Dihalobis(β-diketonato)metal complexes M(dik) 2 X 2 (M = Ti, Zr, or Hf) generally have an octahedral cis configuration, but Ti(acac) 2 I 2 and V(dik) 2 X 2 exist in solution as an equilibrium mixture of cis and trans isomers. Nuclear magnetic resonance (NMR) line-shape studies show that the dialkoxy complexes cis -Ti(dik) 2 (OR) 2 rearrange by an intramolecular twisting mechanism whereas the closely related O , O −dimethyl dithiophosphates cis -Ti(Me 2 dtp) 2 (OR) 2 undergo metal-ligand bond rupture. The seven-coordinate complexes Zr(acac) 3 Cl, Ti(S 2 CNMe 2 ) 3 Cl, Ti(SOCNEt 2 )Cl, and CpM(S 2 CNMe 2 ) 3 (M = Ti, Zr, or Hf) have a pentagonal bipyramidal structure with the Cl or Cp ligand in an axial position. Eight-coordinate structures and stereoisomers are described
Megajournal mismanagement: Manuscript decision bias and anomalous editor activity at PLOS ONE

Abstract Since their emergence just a decade ago, nearly 2% of scientific research is now published by megajournals, representing a major industrial shift in the production of knowledge. Such high-throughput production stresses several aspects of the publication process, including the editorial oversight of peer-review. As the largest megajournal, PLOS ONE has relied on a single-tier editorial board comprised of ∼7000 active academics, who thereby face conflicts of interest relating to their dual roles as both producers and gatekeepers of peer-reviewed literature. While such conflicts of interest are also a factor for editorial boards of smaller journals, little is known about how the scalability of megajournals may introduce perverse incentives for editorial service. To address this issue, we analyzed the activity of PLOS ONE editors over the journal's inaugural decade (2006–2015) and find highly variable activity levels. We then leverage this variation to model how editorial bias in the manuscript decision process relates to two editor-specific factors: repeated editor-author interactions and shifts in the rates of citations directed at editors – a form of citation remuneration that is analogue to self-citation. Our results indicate significantly stronger manuscript bias among a relatively small number of extremely active editors, who also feature relatively high self-citation rates coincident in the manuscripts they handle. These anomalous activity patterns are consistent with the perverse incentives and the temptations they offer at scale, which is theoretically grounded in the “slippery-slope” evolution of apathy and misconduct in power-driven environments. By applying quantitative evaluation to the gatekeepers of scientific knowledge, we shed light on various ethics issues crucial to science policy – in particular, calling for more transparent and structured management of editor activity in megajournals that rely on active academics.
Dynamically Composing Domain-Data Selection with Clean-Data Selection by "Co-Curricular Learning" for Neural Machine Translation

Noise and domain are important aspects of data quality for neural machine translation. Existing research focus separately on domain-data selection, clean-data selection, or their static combination, leaving the dynamic interaction across them not explicitly examined. This paper introduces a “co-curricular learning” method to compose dynamic domain-data selection with dynamic clean-data selection, for transfer learning across both capabilities. We apply an EM-style optimization procedure to further refine the “co-curriculum”. Experiment results and analysis with two domains demonstrate the effectiveness of the method and the properties of data scheduled by the co-curriculum.
Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome

The stability of proteins influences their tendency to aggregate, undergo degradation, or become modified in cells. Despite their significance to understanding protein folding and function, quantitative analyses of thermodynamic stabilities have been mostly limited to soluble proteins in purified systems. We have used a highly multiplexed proteomics approach, based on analyses of methionine oxidation rates, to quantify stabilities of ∼10,000 unique regions within ∼3,000 proteins in human cell extracts. The data identify lysosomal and extracellular proteins as the most stable ontological subsets of the proteome. We show that the stability of proteins impacts their tendency to become oxidized and is globally altered by the osmolyte trimethylamine N-oxide (TMAO). We also show that most proteins designated as intrinsically disordered retain their unfolded structure in the complex environment of the cell. Together, the data provide a census of the stability of the human proteome and validate a methodology for global quantitation of folding thermodynamics.
Diastereoselective synthesis of anti-3-hydroxy-2-trifluoromethyl carboxylic acids

Unlike the hydrocarbon analogs, this first report of enolboration–aldolization of 3,3,3-trifluoropropanoic acid provides essentially pure anti-diastereomers of α-trifluoromethyl-β-hydroxy carboxylic acids in 77–90% yields.
Co5BP3O14: The First Borophosphate with Planar BO3 Groups Connected to PO4 Tetrahedra

The first example of a dimer of corner sharing BO3 and PO4 units, BPO64-, occurs in the title compound. The structure is built of layers of such dimers separated by double layers of isolated PO4 tetrahedra. The cobalt atoms are 6-, 5-, and 4-coordinated by the oxygen.
Synthesis of optically active 2-benzyldihydrobenzopyrans for the hypoglycemic agent englitazone

Two syntheses of some optically active 2-benzyl-2,3-dihydro-4H-benzopyrans and benzopyran-4-ones are presented. An asymmetric synthesis starting from D- and L-phenylalanine was used to provide both enantiomers of 2-benzyl-6-(methoxycarbonyl)-2,3-dihydro-4H-benzopyran-4-one 19. Phenylalanine was diazotized in aqueous sulfuric acid to 2-hydroxy-3-phenylpropionic acid 6 which was converted in four steps to 1-bromo-2-(4-methoxycarbonylphenoxy)-3-phenylpropane 11. (4R,S)-Benzamido-2-benzyl-2,3-dihydro-6-(methoxycarbonyl)-4H-1-benzopyran-4-carboxylic acid 16 was prepared from 11 by amidoalkylation with α-hydroxyhippuric acid in methanesulfonic acid solution followed by spiroalkylation to (4R,S)-2-benzyl-2,3-dihydro-6-(methoxycarbonyl)spiro[4H-benzopyran-4,4′-2′-phenyloxazolidin]-5′-one 15. After the phenyloxazolidin-5-one 15 was hydrolyzed to the spirobenzamido carboxylic acid 16, oxidative decarboxylation with sodium hypochlorite yielded optically active 2-benzyl-6-(methoxycarbonyl)-2,3-dihydro-4H-benzopyran-4-one 19. The ketone in 19 was reduced by hydrogenation over palladium on carbon to a methylene group and the ester was converted to the aldehyde to give both isomers of the desired intermediate 2-benzyl-6-(formyl)-2,3-dihydro-4H-benzopyran 25. The second synthesis relied on an enzymatic hydrolysis of ethyl 2,3-dihydrobenzopyran-2-carboxylate 27 with the lipase from P. fluorescens to provide the desired 2R-ester. The ester group in (R)-27 was converted to the triflate (R)-29. Displacement of the triflate group with phenylmagnesium bromide and cuprous bromide as catalyst gave 2R-benzyl-2,3-dihydro-4H-benzopyran (R)-30. Formylation of (R)-30 provided 2R-benzyl-6-(formyl)-2,3-dihydro-4H-benzopyran (R)-25 identical with that from the first synthesis. These optically active intermediates are used in the preparation of the hypoglycemic agent englitazone.
TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment

Variants in the microglial receptor TREM2 confer risk for multiple neurodegenerative diseases. However, it remains unknown how this receptor functions on microglia to modulate these diverse neuropathologies. To understand the role of TREM2 on microglia more generally, we investigated changes in microglial function in Trem2-/- mice. We found that loss of TREM2 impairs normal neurodevelopment, resulting in reduced synapse number across the cortex and hippocampus in 1-month-old mice. This reduction in synapse number was not due directly to alterations in interactions between microglia and synapses. Rather, TREM2 was required for microglia to limit synaptic engulfment by astrocytes during development. While these changes were largely normalized later in adulthood, high fat diet administration was sufficient to reinitiate TREM2-dependent modulation of synapse loss. Together, this identifies a novel role for microglia in instructing synaptic pruning by astrocytes to broadly regulate appropriate synaptic refinement, and suggests novel candidate mechanisms for how TREM2 and microglia could influence synaptic loss in brain injury and disease.
Reproducibility assessment and uncertainty quantification in subjective dust source mapping

Abstract Accurate dust-source characterizations are critical for effectively modeling dust storms. A previous study developed an approach to manually map dust plume-head point sources in a geographic information system (GIS) framework using Moderate Resolution Imaging Spectroradiometer (MODIS) imagery processed through dust-enhancement algorithms. With this technique, the location of a dust source is digitized and recorded if an analyst observes an unobscured plume head in the imagery. Because airborne dust must be sufficiently elevated for overland dust-enhancement algorithms to work, this technique may include up to 10 km in digitized dust-source location error due to downwind advection. However, the potential for error in this method due to analyst subjectivity has never been formally quantified. In this study, we evaluate a version of the methodology adapted to better enable reproducibility assessments amongst multiple analysts to determine the role of analyst subjectivity on recorded dust source location error. Four analysts individually mapped dust plumes in Southwest Asia and Northwest Africa using five years of MODIS imagery collected from 15 May to 31 August. A plume-source location is considered reproducible if the maximum distance between the analyst point-source markers for a single plume is ≤10 km. Results suggest analyst marker placement is reproducible; however, additional analyst subjectivity-induced error (7 km determined in this study) should be considered to fully characterize locational uncertainty. Additionally, most of the identified plume heads (>90%) were not marked by all participating analysts, which indicates dust source maps generated using this technique may differ substantially between users.
Reactivity of an Unusual Amidase May Explain Colibactin's DNA Cross-Linking Activity

Certain commensal and pathogenic bacteria produce colibactin, a small-molecule genotoxin that causes interstrand cross-links in host cell DNA. Although colibactin alkylates DNA, the molecular basis for cross-link formation is unclear. Here, we report that the colibactin biosynthetic enzyme ClbL is an amide bond-forming enzyme that links aminoketone and β-keto thioester substrates in vitro and in vivo. The substrate specificity of ClbL strongly supports a role for this enzyme in terminating the colibactin NRPS-PKS assembly line and incorporating two electrophilic cyclopropane warheads into the final natural product scaffold. This proposed transformation was supported by the detection of a colibactin-derived cross-linked DNA adduct. Overall, this work provides a biosynthetic explanation for colibactin's DNA cross-linking activity and paves the way for further study of its chemical structure and biological roles.
Many Paths to Equilibrium: GANs Do Not Need to Decrease a Divergence At Every Step

Generative adversarial networks (GANs) are a family of generative models that do not minimize a single training criterion. Unlike other generative models, the data distribution is learned via a game between a generator (the generative model) and a discriminator (a teacher providing training signal) that each minimize their own cost. GANs are designed to reach a Nash equilibrium at which each player cannot reduce their cost without changing the other players' parameters. One useful approach for the theory of GANs is to show that a divergence between the training distribution and the model distribution obtains its minimum value at equilibrium. Several recent research directions have been motivated by the idea that this divergence is the primary guide for the learning process and that every step of learning should decrease the divergence. We show that this view is overly restrictive. During GAN training, the discriminator provides learning signal in situations where the gradients of the divergences between distributions would not be useful. We provide empirical counterexamples to the view of GAN training as divergence minimization. Specifically, we demonstrate that GANs are able to learn distributions in situations where the divergence minimization point of view predicts they would fail. We also show that gradient penalties motivated from the divergence minimization perspective are equally helpful when applied in other contexts in which the divergence minimization perspective does not predict they would be helpful. This contributes to a growing body of evidence that GAN training may be more usefully viewed as approaching Nash equilibria via trajectories that do not necessarily minimize a specific divergence at each step.
REAL-TIME ANALYSIS OF LARGE ASTRONOMICAL IMAGES

Forthcoming instruments designed for high-cadence large-area surveys, such as the Dark Energy Survey and Large Synoptic Survey Telescope, will generate several GB of data products every few minutes during survey operations. Since such surveys are designed to operate with minimal observer interaction, automated real-time analysis of these large images is necessary to ensure uninterrupted production of science-quality data. We describe a software infrastructure suite designed to support such surveys, focusing particularly on ImageHealth, a tool for near-real-time processing of large images. These image manipulation and analysis algorithms were applied to simulated data from the Dark Energy Survey, as well as observed data collected by the Y4KCam on the CTIO 1 m telescope and the Mosaic camera on the Blanco telescope. The accuracy and speed of the ImageHealth code in particular were benchmarked against results from SourceExtractor, a standard image analysis tool ubiquitous in the astronomical community. ImageHealth is shown to provide comparable accuracy to SourceExtractor when examining bright objects in the focal plane, but with significantly shorter execution time. Based on the importance of real-time analysis in reaching the Dark Energy Survey's science goals, ImageHealth and other aspects of this analysis package were incorporated (in modified form) into the Survey Image System Process Integration, the Dark Energy Camera software control environment. The original ImageHealth code, however, is completely instrument-independent, and is freely available for use within other observational data-taking environments.
Proofs of Power Sum and Binomial Coefficient Congruences Via Pascal's Identity

A well-known and frequently cited congruence for power sums is where n ≥ 1 and p is prime. We survey the main ingredients in several known proofs. Then we give an elementary proof, using an identit...
DECOMPOSING ELEMENTS OF A RIGHT SELF-INJECTIVE RING

It was proved independently by both Wolfson [An ideal theoretic characterization of the ring of all linear transformations, Amer. J. Math.75 (1953) 358–386] and Zelinsky [Every linear transformation is sum of nonsingular ones, Proc. Amer. Math. Soc.5 (1954) 627–630] that every linear transformation of a vector space V over a division ring D is the sum of two invertible linear transformations except when V is one-dimensional over ℤ2. This was extended by Khurana and Srivastava [Right self-injective rings in which each element is sum of two units, J. Algebra Appl.6(2) (2007) 281–286] who proved that every element of a right self-injective ring R is the sum of two units if and only if R has no factor ring isomorphic to ℤ2. In this paper we prove that if R is a right self-injective ring, then for each element a ∈ R there exists a unit u ∈ R such that both a + u and a - u are units if and only if R has no factor ring isomorphic to ℤ2 or ℤ3.
Fast Embedding for JOFC Using the Raw Stress Criterion

ABSTRACTThe joint optimization of fidelity and commensurability (JOFC) manifold matching methodology embeds an omnibus dissimilarity matrix consisting of multiple dissimilarities on the same set of objects. One approach to this embedding optimizes the preservation of fidelity to each individual dissimilarity matrix together with commensurability of each given observation across modalities via iterative majorization of a raw stress error criterion by successive Guttman transforms. In this article, we exploit the special structure inherent to JOFC to exactly and efficiently compute the successive Guttman transforms, and as a result we are able to greatly speed up the JOFC procedure for both in-sample and out-of-sample embedding. We demonstrate the scalability of our implementation on both real and simulated data examples.
Max vs Min: Tensor Decomposition and ICA with nearly Linear Sample Complexity

We present a simple, general technique for reducing the sample complexity of matrix and tensor decomposition algorithms applied to distributions. We use the technique to give a polynomialtime algorithm for standard ICA with sample complexity nearly linear in the dimension, thereby improving substantially on previous bounds. The analysis is based on properties of random polynomials, namely the spacings of an ensemble of polynomials. Our technique also applies to other applications of tensor decompositions, including spherical Gaussian mixture models.
Projectivity of Bridgeland Moduli Spaces on Del Pezzo Surfaces of Picard Rank 2

We prove that, for a natural class of Bridgeland stability conditions on $\mathbb{P}^1\times\mathbb{P}^1$ and the blow-up of $\mathbb{P}^2$ at a point, the moduli spaces of Bridgeland semistable objects are projective. Our technique is to find suitable regions of stability conditions with hearts that are (after "rotation") equivalent to representations of a quiver. The helix and tilting theory is well-behaved on Del Pezzo surfaces and we conjecture that this program (begun in arXiv:1203.0316) runs successfully for all Del Pezzo surfaces, and the analogous Bridgeland moduli spaces are projective.
Spin and hyperelliptic structures of log twisted differentials

Using stable log maps, we introduce log twisted differentials extending the notion of abelian differentials to the Deligne–Mumford boundary of stable curves. The moduli stack of log twisted differentials provides a compactification of the strata of abelian differentials. The open strata can have up to three connected components, due to spin and hyperelliptic structures. We prove that the spin parity can be distinguished on the boundary of the log compactification. Moreover, combining the techniques of log geometry and admissible covers, we introduce log twisted hyperelliptic differentials, and prove that their moduli stack provides a toroidal compactification of the hyperelliptic loci in the open strata.
A Fast 2-Approximation Algorithm for Guarding Orthogonal Terrains

Terrain Guarding Problem(TGP), which is known to be NP-complete, asks to find a smallest set of guard locations on a terrain $T$ such that every point on $T$ is visible by a guard. Here, we study this problem on 1.5D orthogonal terrains where the edges are bound to be horizontal or vertical. We propose a 2-approximation algorithm that runs in O($n \log m$) time, where $n$ and $m$ are the sizes of input and output, respectively. This is an improvement over the previous best algorithm, which is a 2-approximation with O($n^2$) running time.
Minimax lower bounds for linear independence testing

Linear independence testing is a fundamental information-theoretic and statistical problem that can be posed as follows: given n points {(X i , Y i )} i=1 n from a p+q dimensional multivariate distribution where X i ∈ ℝp and Y i ∈ ℝq, determine whether aTX and bT Y are uncorrelated for every a ∈ ℝp; b ∈ ℝq or not. We give minimax lower bound for this problem (when p + q, n → ∞, (p + q)/n ≥ κ XY ∥ F 2 for any procedure (test) to have non-trivial power, where Σ XY is the cross-covariance matrix of X, Y. We also provide evidence that the lower bound is tight, by connections to two-sample testing and regression when q = 1.
Differential TD learning for value function approximation

Value functions arise as a component of algorithms as well as performance metrics in statistics and engineering applications. Computation of the associated Bellman equations is numerically challenging in all but a few special cases.
Performance Bounds for Graphical Record Linkage.

Record linkage involves merging records in large, noisy databases to remove duplicate entities. It has become an important area because of its widespread occurrence in bibliometrics, public health, official statistics production, political science, and beyond. Traditional linkage methods directly linking records to one another are computationally infeasible as the number of records grows. As a result, it is increasingly common for researchers to treat record linkage as a clustering task, in which each latent entity is associated with one or more noisy database records. We critically assess performance bounds using the Kullback-Leibler (KL) divergence under a Bayesian record linkage framework, making connections to Kolchin partition models. We provide an upper bound using the KL divergence and a lower bound on the minimum probability of misclassifying a latent entity. We give insights for when our bounds hold using simulated data and provide practical user guidance.
A summation formula for triples of quadratic spaces

Abstract Let V 1 , V 2 , V 3 be a triple of even dimensional vector spaces over a number field F equipped with nondegenerate quadratic forms Q 1 , Q 2 , Q 3 , respectively. Let Y ⊂ ∏ i = 1 V i be the closed subscheme consisting of ( v 1 , v 2 , v 3 ) on which Q 1 ( v 1 ) = Q 2 ( v 2 ) = Q 3 ( v 3 ) . Motivated by conjectures of Braverman and Kazhdan and related work of Lafforgue, Ngo, and Sakellaridis we prove an analogue of the Poisson summation formula for certain functions on this space.
High-order Filtered Schemes for the Hamilton-Jacobi Continuum Limit of Nondominated Sorting

We investigate high-order finite difference schemes for the Hamilton-Jacobi equation continuum limit of nondominated sorting. Nondominated sorting is an algorithm for sorting points in Euclidean space into layers by repeatedly removing minimal elements. It is widely used in multi-objective optimization, which finds applications in many scientific and engineering contexts, including machine learning. In this paper, we show how to construct filtered schemes, which combine high order possibly unstable schemes with first order monotone schemes in a way that guarantees stability and convergence while enjoying the additional accuracy of the higher order scheme in regions where the solution is smooth. We prove that our filtered schemes are stable and converge to the viscosity solution of the Hamilton-Jacobi equation, and we provide numerical simulations to investigate the rate of convergence of the new schemes.
Domination and Upper Domination of Direct Product Graphs

Abstract Let X Z ∕ n Z denote the unitary Cayley graph of Z ∕ n Z . We present results on the tightness of the known inequality γ ( X Z ∕ n Z ) ≤ γ t ( X Z ∕ n Z ) ≤ g ( n ) , where γ and γ t denote the domination number and total domination number, respectively, and g is the arithmetic function known as Jacobsthal’s function. In particular, we construct integers n with arbitrarily many distinct prime factors such that γ ( X Z ∕ n Z ) ≤ γ t ( X Z ∕ n Z ) ≤ g ( n ) − 1 . We give lower bounds for the domination numbers of direct products of complete graphs and present a conjecture for the exact values of the upper domination numbers of direct products of balanced, complete multipartite graphs.
Using ciliate operations to construct chromosome phylogenies

Whole genome sequencing has revealed several examples where genomes of different species are related by permutation. The number of certain types of rearrangements needed to transform one permuted list into another can measure the distance between such lists. Using an algorithm based on three basic DNA editing operations suggested by a model for ciliate micronuclear decryption, this study defines the distance between two permutations to be the number of ciliate operations the algorithm performs during such a transformation. Combining wellknown clustering methods with this distance function enables one to construct corresponding phylogenies. These ideas are illustrated by exploring the phylogenetic relationships among the chromosomes of eight fruit fly (Drosophila) species, using the well-known UPGMA algorithm on the distance function provided by the ciliate operations.
The free splitting complex of a free group, II: Loxodromic outer automorphisms

We study the loxodromic elements for the action of $Out(F_n)$ on the free splitting complex of the rank $n$ free group $F_n$. We prove that each outer automorphism is either loxodromic, or has bounded orbits without any periodic point, or has a periodic point; and we prove that all three possibilities can occur. We also prove that two loxodromic elements are either co-axial or independent, meaning that their attracting/repelling fixed point pairs on the Gromov boundary of the free splitting complex are either equal or disjoint as sets. Each of the alternatives in these results is also characterized in terms of the attracting/repelling lamination pairs of an outer automorphism. As an application, each attracting lamination determines its corresponding repelling lamination independent of the outer automorphism. As part of this study we describe the structure of the subgroup of $Out(F_n)$ that stabilizes the fixed point pair of a given loxodromic outer automorphism, and we give examples which show that this subgroup need not be virtually cyclic. As an application, the action of $Out(F_n)$ on the free splitting complex is not acylindrical, and its loxodromic elements do not all satisfy the WPD property of Bestvina and Fujiwara.
Semi-supervised k-means++

ABSTRACTTraditionally, practitioners initialize the k-means algorithm with centres chosen uniformly at random. Randomized initialization with uneven weights (k-means++) has recently been used to improve the performance over this strategy in cost and run-time. We consider the k-means problem with semi-supervised information, where some of the data are pre-labelled, and we seek to label the rest according to the minimum cost solution. By extending the k-means++ algorithm and analysis to account for the labels, we derive an improved theoretical bound on expected cost and observe improved performance in simulated and real-data examples. This analysis provides theoretical justification for a roughly linear semi-supervised clustering algorithm.
Secure Distributed State Estimation of an LTI System Over Time-Varying Networks and Analog Erasure Channels

We study the problem of collaboratively estimating the state of an LTI system monitored by a network of sensors (nodes), subject to the following important practical considerations: (i) certain sensors might be arbitrarily compromised by an adversary and (ii) the underlying communication graph governing the flow of information across sensors might be time-varying. We first analyze a scenario involving intermittent communication losses that preserve certain information flow patterns over bounded intervals of time. By equipping the sensors with adequate memory, we show that one can obtain a fully distributed, provably correct state estimation algorithm that accounts for arbitrary adversarial behavior, provided certain conditions are met by the network topology. We then argue that our approach can handle bounded communication delays as well. Next, we explore a case where each communication link stochastically drops packets based on an analog erasure channel model. For this setup, we propose state estimate update and information exchange rules, along with conditions on the network topology and packet drop probabilities, that guarantee mean-square stability despite arbitrary adversarial attacks.
Combinatorics and the rigidity of CAD systems

We study the rigidity of body-and-cad frameworks which capture the majority of the geometric constraints used in 3D mechanical engineering CAD software. We present a combinatorial characterization of the generic minimal rigidity of a subset of body-and-cad frameworks in which we treat 20 of the 21 body-and-cad constraints, omitting only point-point coincidences. While the handful of classical combinatorial characterizations of rigidity focus on distance constraints between points, this is the first result simultaneously addressing coincidence, angular, and distance constraints. Our result is stated in terms of the partitioning of a graph into edge-disjoint spanning trees. This combinatorial approach provides the theoretical basis for the development of deterministic algorithms (that will not depend on numerical methods) for analyzing the rigidity of body-and-cad frameworks.
Modeling of multicomponent three-dimensional vesicles

Abstract In many interfacial flow systems, variations of surface properties lead to novel and interesting behaviors. In this work a three-dimensional model of flow dynamics for multicomponent vesicles is presented. The surface composition is modeled using a two-phase surface Cahn–Hilliard system, while the interface is captured using a level set jet scheme. The interface is coupled to the surrounding fluid via a variation of energy approach. Sample energies considered include the total bending, surface tension, and phase segregation energy. The fully coupled system for surface inhomogeneities, and thus varying interface material properties is presented, as are the associated numerical methods. Numerical convergence and sample results demonstrate the validity of the model.
Fast Compatibility Testing for Rooted Phylogenetic Trees

We present a new graph-based approach to the following basic problem in phylogenetic tree construction. Let $$\mathcal {P}= \{T_1, \ldots , T_k\}$$ be a collection of rooted phylogenetic trees over various subsets of a set of species. The tree compatibility problem asks whether there is a phylogenetic tree T with the following property: for each $$i \in \{1, \dots , k\}$$ , $$T_i$$ can be obtained from the restriction of T to the species set of $$T_i$$ by contracting zero or more edges. If such a tree T exists, we say that $$\mathcal {P}$$ is compatible and that T displays $$\mathcal {P}$$ . Our approach leads to a $$O(M_\mathcal {P}\log ^2 M_\mathcal {P})$$ algorithm for the tree compatibility problem, where $$M_\mathcal {P}$$ is the total number of nodes and edges in $$\mathcal {P}$$ . Our algorithm either returns a tree that displays $$\mathcal {P}$$ or reports that $$\mathcal {P}$$ is incompatible. Unlike previous algorithms, the running time of our method does not depend on the degrees of the nodes in the input trees. Thus, our algorithm is equally fast on highly resolved and highly unresolved trees.