cssi/SciSciGPT-SciSciNet huggingface dataset:
Ru3(CO)9(μ3-η2,η2,η2-C60): A Cluster Face-Capping, Arene-Like Complex of C60

We report the synthesis and first structural characterization of a hexahapto C{sub 60} complex, in which C{sub 60} displays arene-like coordination to the open face of a triruthenium cluster. The bonding of C{sub 60} to a single transition metal center has been analyzed in terms of the familiar Dewar-Chatt-Duncanson donation/back-donation model, with a `double bond` donor orbital largely generated from the HOMO (h{sub u}) and the corresponding acceptor orbital formed from the LUMO (t{sub 1u}). Because of the relatively low energies of the C{sub 60} orbitals (high electron affinity), there is strong charge transfer (back-donation) from the metal center to coordinated C{sub 60}, consistent with experimental data on stable compounds. A qualitatively similar bonding model, in terms of donor/acceptor interactions of C{sub 60} with the Ru{sub 3}(CO){sub 9} fragment, is likely for 1; theoretical studies of the bonding in the benzene complexes 2 and 3 provide analogies. However. the relative contribution of back-donation to bonding with the metal triangle should be higher for C{sub 60} than for benzene, which is consistent with both the higher v{sub CO} values and the shorter Ru-C distances seen for 1 compared with those of 2. 21 refs., 1 fig.
Fe(H2O)2BP2O8·H2O, a First Zeotype Ferriborophosphate with Chiral Tetrahedral Framework Topology

Fe(H2O)2BP2O8·H2O, an ordered zeotype hydrated ferriborophosphate, was synthesized by a mild hydrothermal method. Its structure was characterized by single-crystal X-ray diffraction which has ordered, alternating, vertex-sharing BO4, PO4, and FeO4(H2O)2 groups.
Novel functionalized trisubstituted allylboronates via Hosomi-Miyaura borylation of functionalized allyl acetates.

A series of novel functionalized achiral and chiral allylboronates have been synthesized via the nucleophilic addition of boronates on allyl acetates derived via vinylalumination or Baylis−Hillman reaction of aldehydes. These reagents, upon allylboration with aldehydes, furnish β-substituted-α-methylene-γ-butyrolactones stereoselectively.
A Method for Visualizing Recurrent Topological Substructures in Sets of Active Molecules

We present a method for detecting meaningful common topological substructures among sets of active compounds. A clique-based subgraph detection method is used to find the highest scoring common substructure (HSCS) for each pair of molecules. Only those HSCSs are kept that have a much larger score than would be expected by chance for a randomly selected pair of molecules of the same size. Information on these significant HSCSs is visualized in two complementary ways. Individual HSCSs can be displayed as pairs of molecules with the atoms in the HSCS highlighted. The HSCSs are presented in order of decreasing statistical significance. Alternatively, individual molecules can be displayed such that each atom is labeled with the number of significant HSCSs in which it has appeared. These are presented in order of decreasing maximum number per molecule. Browsing these data gives an impression of what parts of molecules are conserved among actives. The molecules can be simplified by deleting parts that are not co...
IL-10 and ICOS Differentially Regulate T Cell Responses in the Brain during Chronic Toxoplasma gondii Infection.

Control of chronic CNS infection with the parasite Toxoplasma gondii requires ongoing T cell responses in the brain. Immunosuppressive cytokines are also important for preventing lethal immunopathology during chronic infection. To explore the loss of suppressive cytokines exclusively during the chronic phase of infection, we blocked IL-10R in chronically infected mice. Consistent with previous reports, IL-10R blockade led to severe, fatal tissue destruction associated with widespread changes in the inflammatory response, including increased APC activation, expansion of CD4 + T cells, and neutrophil recruitment to the brain. We then sought to identify regulatory mechanisms contributing to IL-10 production, focusing on ICOS, a molecule implicated in IL-10 production. Unexpectedly, ICOS ligand (ICOSL) blockade led to a local expansion of effector T cells in the brain without affecting IL-10 production or APC activation. Instead, we found that ICOSL blockade led to changes in T cells associated with their proliferation and survival. We observed increased expression of IL-2–associated signaling molecules CD25, STAT5 phosphorylation, Ki67, and Bcl-2 in T cells in the brain, along with decreased apoptosis. Interestingly, increases in CD25 and Bcl-2 were not observed following IL-10R blockade. Also, unlike IL-10R blockade, ICOSL blockade led to an expansion of both CD8 + and CD4 + T cells in the brain, with no expansion of peripheral T cells or neutrophil recruitment to the brain and no severe tissue destruction. Overall, these results suggest that IL-10 and ICOS differentially regulate T cell responses in the brain during chronic T. gondii infection.
Oxidation of sulfides by 3‐hydroperoxy‐4,4,5,5‐tetramethyl‐3‐phenyl‐1,2‐dioxolane: Effect of solvent and sulfide substituent

The reaction of 3-hydroperoxy-4,4,5,5-tetramethyl-3-phenyl-1,2-dioxolane, 1, with a series of sulfides (2a = thioanisole, 2b = ethyl phenyl sulfide, 2c = 2-chloroethyl phenyl sulfide, and 2d = 2-chloroethyl methyl sulfide) at 34°C in various solvents yielded the corresponding sulfoxides and 3-hydroxy-1,2-dioxolane 3 in quantitative yields. The oxidations showed excellent second-order kinetic behavior overall. In CDCl3, the reactivity order was 2d > 2b > 2a > 2c. For 2a, the relative rate in various solvents was CDCl3 (17); CD3OD (7); C6D6 (∼3); CD3CN (1); CD3C(O)CD3 (∼0.3). Addition of ∼1 equivalent of acetic acid to reactions of 1 and 2a in CDCl3 and C6D6 resulted in small increases in the values of k2. The results are consistent with an electrophilic oxygen-atom transfer mechanism similar to that proposed for oxidations by α-azohydroperoxides. Since the precursor to 1, 3-hydroxy-1,2-dioxolane 3, is regenerated during the oxidation, the system has the potential to be developed as a cyclic process. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:75–78, 1998
Synthesis, structure, and characterization of new Li+-d0-lone-pair-oxides: noncentrosymmetric polar Li6(Mo2O5)3(SeO3)6 and centrosymmetric Li2(MO3)(TeO3) (M = Mo6+ or W6+)

New quaternary lithium-d(0) cation-lone-pair oxides, Li(6)(Mo(2)O(5))(3)(SeO(3))(6) (Pmn2(1)) and Li(2)(MO(3))(TeO(3)) (P2(1)/n) (M = Mo(6+) or W(6+)), have been synthesized and characterized. The former is noncentrosymmetric and polar, whereas the latter is centrosymmetric. Their crystal structures exhibit zigzag anionic layers composed of distorted MO(6) and asymmetric AO(3) (A = Se(4+) or Te(4+)) polyhedra. The anionic layers stack along a 2-fold screw axis and are separated by Li(+) cations. Powder SHG measurements on Li(6)(Mo(2)O(5))(3)(SeO(3))(6) using 1064 nm radiation reveal a SHG efficiency of approximately 170 × α-SiO(2). Particle size vs SHG efficiency measurements indicate Li(6)(Mo(2)O(5))(3)(SeO(3))(6) is type 1 nonphase-matchable. Converse piezoelectric measurements result in a d(33) value of ∼28 pm/V and pyroelectric measurements reveal a pyroelectric coefficient of -0.43 μC/m(2)K at 50 °C for Li(6)(Mo(2)O(5))(3)(SeO(3))(6). Frequency-dependent polarization measurements confirm that Li(6)(Mo(2)O(5))(3)(SeO(3))(6) is nonferroelectric, i.e., the macroscopic polarization is not reversible, or 'switchable'. Infrared, UV-vis, thermogravimetric, and differential thermal analysis measurements and electron localization function calculations were also done for all materials.
Catalytic asymmetric Petasis reactions of vinylboronates.

Binaphthol-catalyzed asymmetric Petasis reactions of salicylaldehydes with dibutyl vinylboronates and secondary amines in the presence of 4 A molecular sieves (MS) afforded products with up to 99% ee in isolated yields of 39–94%. The 99% ee of the product indicated that the reaction by the binaphthol-catalyzed pathway was roughly 500 times faster than the uncatalyzed pathway. NMR experiments (1H and 11B) showed that the amine component played a role in triggering the reaction between the binaphthol catalyst and the vinylboronate in the catalytic reaction sequence. The 4 A MS enhanced both the rate and enantioselectivity by effective removal of water from the reaction system. A novel rearrangement reaction of the unconjugated allylic amine Petasis reaction product to a conjugated allylic amine was also observed.
Evaluation of S1PR1, pSTAT3, S1PR2, FOXP1 Expression in Aggressive, Mature B Cell Lymphomas.

Aggressive, mature B cell lymphomas include Burkitt lymphoma (BL); high-grade B cell lymphomas (HGBL) (e.g., double-hit B cell lymphomas (HGBL-DH: HGBL with MYC and BCL2 and/or BCL6 translocations)); HGBL, not otherwise specified (HGBL, NOS); and diffuse large B cell lymphoma (DLBCL). Overlapping morphologic and immunohistochemical features of these lymphomas pose diagnostic challenges in some cases, and better understanding of potential diagnostic biomarkers and possible therapeutic targets is needed. Sphingosine 1 phosphate receptors (S1PR1-5) are G protein-coupled receptors that bind S1P and influence migration and survival in multiple cell types, including lymphocytes. S1PRs are emerging as biomarkers in B cell biology and interaction between S1PR pathways and STAT3 or FOXP1 has been reported in DLBCL. Our aim was to extend the understanding of S1PR1, STAT3, and S1PR2, FOXP1 expression beyond DLBCL, into additional aggressive, mature B cell lymphomas using immunohistochemical expression analysis of human tissue samples. S1PR1 and S1PR2 showed different expression patterns in mantle zones and follicle centers in reactive lymphoid tissue. BL showed a unique expression pattern compared to HGBL and DLBCL. Additionally, S1PR1 and S1PR2 expression were typically mutually exclusive and were expressed in a low proportion of cases (frequently HGBL involving extranodal sites). FOXP1 was expressed in a high proportion of various case types and pSTAT3 was detected in a significant proportion of HGBL and DLBCL. These findings provide further evidence that S1PR1, pSTAT3, S1PR2, and FOXP1 play a role in a subset of aggressive, mature B cell lymphomas.
A Novel High-Yield Synthesis of Substituted Isoindolequinones.

The high-yield, general, one-pot synthesis of substituted isoindolequinones, a group of important radiosensitizers which sensitize hypoxic cells to the lethal effect of radiation in cancer radiotherapy, is described. Primary amines react with 2,3-bis[2-(trimethylsilyl)ethynyl]-5,6-dimethylhydroquinone (2) in methanol at room temperature under an inert atmosphere to give substituted isoindolequinones 2-alkyl-1,3,5,6-tetramethylisoindole-4,7-quinone (4) in almost quantitative yields. Moderate yields of 4 are also obtained using 2,3-diethynyl-5,6-dimethylhydroquinone (3) and amines as reactant and solvent under the similar conditions. Tris(2-aminoethyl)amine (TREN) reacts with 2 in MeOH/THF on reflux to produce the isoindolequinone derivative of TREN. Water with 2 on reflux in MeOH forms an isobenzofuranquinone. This indicates that the formation of similar heterocycles from small molecules (e.g., Group VA and VIA hydrides) and 2 is likely. Readily synthesizable starting materials, ease of chromatographic iso...
Enantiocontrol in Macrocycle Formation from Catalytic Metal Carbene Transformations

The development of catalytic metal carbene transformations for the construction of macrocyclic lactones has dramatically increased their synthetic advantages. This is the first review of this Developing methodology. The research described in this review has been supported by the National Science Foundation, National Institutes of Health, and the Petroleum Research Fund of the American Chemical Society.
Enantioselective Routes to Both Enantiomers of Aryl Alcohols with a Single Catalyst Antipode: Ru and Os Transfer Hydrogenation Catalysts

[reaction--see text] The kinetic resolution of secondary aryl alcohols has been investigated. When (CyRuCl(2))(2), (1R,2S)-(+)-cis-1-amino-2-indanol, and KOH or (t)BuOK (catalyst 1) were combined in the presence of (+/-)-alcohols, ee's > 90% were generally observed. When applied to the kinetic resolution of (+/-)-indanol and (+/-)-tetralol, ee's = 99% (R) were observed. In addition, the asymmetric transfer hydrogenation of ketones was investigated with a catalyst, 2, generated in situ from (CyOsCl(2))(2), (1R,2S)-(+)-cis-1-amino-2-indanol, and (t)BuOK, yielding ee's of up to 98% (S).
Not for Synthesis Only: The Reactions of Organic Halides with Metal Surfaces

Publisher Summary The reaction of alkyl halides with metals has played a crucial role in the development of organo-metallic chemistry. One characteristic property that all organic halides possess is a carbon–halogen bond dipole moment. The halogen atom is always the negative pole of this bond, and determines the extent of the polarity, with some modification by the organic group. Finely divided metals, with their correspondingly larger surface areas, show markedly greater reactivity toward alkyl halides than do corresponding bulk metals. The halogen atoms in organic halides contain electron pairs in their valence shells and behave as Lewis bases. In this respect, organic halides may be considered as analogous to alkyl derivatives of the corresponding elements of the two preceding periodic groups. The lone pairs on the halogen atoms occur in p-orbitals, and readily interact with acceptor orbitals on metals. An adsorbed halide might simply be desorbed or undergo dissociation of the carbon–halogen bond.
A trilactone related to anemonin

Treatment of Anemonin sequentially with two equivalents of the anion 2 and iodine gave the monoalkylated monoiodinated iodolactone t-butyl ester 3. Ester cleavage in anhydrous acedic media followed by treatment with sodium hydrogen carbonate transformed 3 to trilactone 4.
Stereo- and regiocontrolled construction of trisubstituted piperidines using a TpMo(CO)(2)(dihydropyridine) scaffold (Tp = hydridotrispyrazolylborate).

Cationic TpMo(CO)2(dihydropyridine) complexes (Tp = hydridotrispyrazolylborate), readily generated from 3-oxo-3,6-dihydro-2H-pyridine-1-carboxylic acid benzyl ester, represent scaffolds from which (by judicious choice of demetalation conditions) either 2,3,6- or 2,5,6-trisubstituted-1,2,3,6-tetrahydropyridines can be prepared in a regio- and stereodefined way.
Phrank measures phenotype sets similarity to greatly improve Mendelian diagnostic disease prioritization.

Exome sequencing and diagnosis is beginning to spread across the medical establishment. The most time-consuming part of genome-based diagnosis is the manual step of matching the potentially long list of patient candidate genes to patient phenotypes to identify the causative disease. We introduce Phrank (for phenotype ranking), an information theory–inspired method that utilizes a Bayesian network to prioritize candidate diseases or genes, as a stand-alone module that can be run with any underlying knowledgebase and any variant filtering scheme. Phrank outperforms existing methods at ranking the causative disease or gene when applied to 169 real patient exomes with Mendelian diagnoses. Phrank’s greatest improvement is in disease space, where across all 169 patients it ranks only 3 diseases on average ahead of the true diagnosis, whereas Phenomizer ranks 32 diseases ahead of the causal one. Using Phrank to rank all patient candidate genes or diseases, as they start working through a new case, will save the busy clinician much time in deriving a genetic diagnosis.
Multiple poliovirus-induced organelles suggested by comparison of spatiotemporal dynamics of membranous structures and phosphoinositides

At the culmination of poliovirus (PV) multiplication, membranes are observed that contain phosphatidylinositol-4-phosphate (PI4P) and appear as vesicular clusters in cross section. Induction and remodeling of PI4P and membranes prior to or concurrent with genome replication has not been well studied. Here, we exploit two PV mutants, termed EG and GG, which exhibit aberrant proteolytic processing of the P3 precursor that substantially delays the onset of genome replication and/or impairs virus assembly, to illuminate the pathway of formation of PV-induced membranous structures. For WT PV, changes to the PI4P pool were observed as early as 30 min post-infection. PI4P remodeling occurred even in the presence of guanidine hydrochloride, a replication inhibitor, and was accompanied by formation of membrane tubules throughout the cytoplasm. Vesicular clusters appeared in the perinuclear region of the cell at 3 h post-infection, a time too slow for these structures to be responsible for genome replication. Delays in the onset of genome replication observed for EG and GG PVs were similar to the delays in virus-induced remodeling of PI4P pools, consistent with PI4P serving as a marker of the genome-replication organelle. GG PV was unable to convert virus-induced tubules into vesicular clusters, perhaps explaining the nearly 5-log reduction in infectious virus produced by this mutant. Our results are consistent with PV inducing temporally distinct membranous structures (organelles) for genome replication (tubules) and virus assembly (vesicular clusters). We suggest that the pace of formation, spatiotemporal dynamics, and the efficiency of the replication-to-assembly-organelle conversion may be set by both the rate of P3 polyprotein processing and the capacity for P3 processing to yield 3AB and/or 3CD proteins.
The New Materials Science of Catalysis: Toward Controlling Selectivity by Designing the Structure of the Active Site

New self-assembly and nanotechnology synthetic methodology is finding its way into the preparation of heterogeneous catalysts. The new approaches afford better design of active sites to fine-tune t...
Localized structural frustration for evaluating the impact of sequence variants

Population-scale sequencing is increasingly uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions of the genome. The rarity of these variants makes it challenging to evaluate their deleteriousness with conventional phenotype-genotype associations. Protein structures provide a way of addressing this challenge. Previous efforts have focused on globally quantifying the impact of SNVs on protein stability. However, local perturbations may severely impact protein functionality without strongly disrupting global stability (e.g. in relation to catalysis or allostery). Here, we describe a workflow in which localized frustration, quantifying unfavorable local interactions, is employed as a metric to investigate such effects. Using this workflow on the Protein Databank, we find that frustration produces many immediately intuitive results: for instance, disease-related SNVs create stronger changes in localized frustration than non-disease related variants, and rare SNVs tend to disrupt local interactions to a larger extent than common variants. Less obviously, we observe that somatic SNVs associated with oncogenes and tumor suppressor genes (TSGs) induce very different changes in frustration. In particular, those associated with TSGs change the frustration more in the core than the surface (by introducing loss-of-function events), whereas those associated with oncogenes manifest the opposite pattern, creating gain-of-function events.
Selective catalytic oxidative carbonylation of amino alcohols to ureas.

Amino alcohols undergo W(CO)6-catalyzed oxidative carbonylation to the corresponding hydroxyalkylureas without protection of the hydroxyl group. Selected examples of 1,2-, 1,3-, 1,4-, and 1,5-amino alcohols were converted to the ureas in good to excellent yields, with only small amounts of the cyclic carbamates being formed. In contrast, the phosgene derivatives CDI and DMDTC undergo stoichiometric reactions with the amino alcohol substrates to afford ureas and cyclic carbamates with variable selectivity.
Allenes from ynals

Abstract Hydrosilylation of ynals with triethylsilane is catalyzed by RhCl(PPh3)3 and leads to α-triethylsilyl enals. Addition of aryl Grignard reagents takes place to give secondary allylic alcohols which are easily converted to 1,3-disubstituted allenes.
Next-generation sequencing based hospital outbreak investigation yields insight into Klebsiella aerogenes population structure and determinants of carbapenem resistance and pathogenicity.

Klebsiella aerogenes is a nosocomial pathogen associated with drug resistance and outbreaks in intensive care units. In a 5-month period in 2017, we experienced an increased incidence of cultures for carbapenem-resistant K. aerogenes (CR-KA) from an adult cardiothoracic intensive care unit (CICU) involving 15 patients. Phylogenomic analysis following whole-genome sequencing (WGS) identified the outbreak CR-KA isolates to group together as a tight monoclonal cluster (with no more than six single nucleotide polymorphisms [SNPs]), suggestive of a protracted intraward transmission event. No clonal relationships were identified between the CICU CR-KA strains and additional hospital CR-KA patient isolates from different wards and/or previous years. Carbapenemase-encoding genes and drug-resistant plasmids were absent in the outbreak strains, and carbapenem resistance was attributed to mutations impacting AmpD activity and membrane permeability. The CICU outbreak strains harbored an integrative conjugative element (ICE) which has been associated with pathogenic Klebsiella pneumoniae lineages (ICEKp10). Comparative genomics with global K. aerogenes genomes showed our outbreak strains to group closely with global sequence type 4 (ST4) strains, which, along with ST93, likely represent dominant K. aerogenes lineages associated with human infections. For poorly characterized pathogens, scaling analyses to include sequenced genomes from public databases offer the opportunity to identify emerging trends and dominant clones associated with specific attributes, syndromes, and geographical locations.
Synthesis of aromatic phosphates via cycloaddition of phosphate dienes

Cycloadditions of phosphate dienes and quinones can be used to generate aromatic phosphates. Diethyl 3-methoxy-1-methylene-2-propenyl phosphate shows reactivity, stability, and regioselectivity comparable to the corresponding silyloxy diene. Because the phosphate ester in the product originates in the diene, cycloadditions with quinones will place this ester regiospecifically in the B-ring and allow facile distinction between the B- and A-ring oxygens of the cycloadduct.
Synthesis of the New Metastable Skutterudite Compound NiSb3 from Modulated Elemental Reactants

A new metastable binary compound with the skutterudite crystal structure has been synthesized from modulated elemental reactants, through an amorphous intermediate, using a novel low-temperature synthesis technique. The amorphous reaction intermediate undergoes nucleation at 87 degrees C, an extremely low temperature for solid-state reactions. When heated above 350 degrees C, the metastable phase NiSb(3) disproportionates into the thermodynamically stable phases NiSb(2) and Sb. Also, if the sum of the individual elemental layer thicknesses is greater than 30 A, a mixture of different phases forms. Simulation of the high-angle powder X-ray diffraction spectrum confirms that NiSb(3) is isostructural with CoSb(3).
Quaternary Germanides Formed in Molten Aluminum: Tb2NiAl4Ge2 and Ce2NiAl6-xGe4-y (x ∼ 0.24, y ∼ 1.34)†

The intermetallic phases Tb2NiAl4Ge2 and Ce2NiAl6-x- Ge4-y (x 0.24, y 1.34) were synthesized in molten Al at tem- peratures below 1000 °C. Both compounds adopt the tetragonal space group I4/mmm with cell parameters of a 4.1346(2) Ac 19.3437(7) Afor Tb2NiAl4Ge2 and a 4.1951(9) Aand c 26.524(7) Afor Ce2NiAl6-xGe4-y. The Tb2NiAl4Ge2 structure fea- tures NiAl4Ge2 layers separated by a double layer of rare earth ions. The Ce2NiAl6-xGe4-y (x 0.24, y 1.34) structure also con- tains the NiAl4Ge2 layers along with a vacancy defect PbO-type Al2-xGe2-y layer, and is related to the Ce2NiGa10 structure type.
Aromatic 3-aza-Cope rearrangement over zeolites

Abstract N-Allyl-2-methyl aniline [ 1a ], N-allyl and N-(2′-methyl allyl)-N-methyl anilines [ 1b & 1 c , respectively] undergo the 3-aza-Cope rearrangement in presence of HY-Zeolite, HEMT and HZeolite beta in hexane at 80°C to give Indoline derivatives as the major product.
Homochiral porous metal-organic frameworks: Why and how?

Abstract This paper highlights the most significant recent advances in the synthesis, characterization, and applications of single-crystalline homochiral porous metal-organic frameworks (MOFs). The motivations for the synthesis of homochiral porous solids and the strategies on how they can be designed are provided. The latest examples of chiral separation and Lewis acid heterogeneous asymmetric catalysis using homochiral porous MOFs are presented.
SYNTHESIS OF NOVEL 3'-C-METHYL-4'-THIO APIONUCLEOSIDES VIA HIGHLY ENANTIOSELECTIVE ELABORATION OF QUATERNARY CARBON BY 3,3-SIGMATROPIC REARRANGEMENT

Abstract Asymmetric synthesis of 3′- C -methyl-4′-thio apionucleosides was accomplished from the chiral intermediate 6 . The chirality of quaternary carbon of the key intermediate 6 was transferred from the chirality of secondary allylic alcohol 5 via [3,3]-sigmatropic Claisen rearrangement with high enantiomeric excess (estimated to be 98.5% ee). The thioglycosyl intermediate 11 was condensed with silylated N 4 -benzoylcytosine followed by deprotection to give the desired nucleoside 12 .
Accurate, Sensitive, and Precise Multiplexed Proteomics Using the Complement Reporter Ion Cluster

Quantitative analysis of proteomes across multiple time points, organelles, and perturbations is essential for understanding both fundamental biology and disease states. The development of isobaric tags (e.g., TMT) has enabled the simultaneous measurement of peptide abundances across several different conditions. These multiplexed approaches are promising in principle because of advantages in throughput and measurement quality. However, in practice, existing multiplexing approaches suffer from key limitations. In its simple implementation (TMT-MS2), measurements are distorted by chemical noise leading to poor measurement accuracy. The current state-of-the-art (TMT-MS3) addresses this but requires specialized quadrupole-iontrap-Orbitrap instrumentation. The complement reporter ion approach (TMTc) produces high accuracy measurements and is compatible with many more instruments, like quadrupole-Orbitraps. However, the required deconvolution of the TMTc cluster leads to poor measurement precision. Here, we in...
Measuring NDC80 binding reveals the molecular basis of tension-dependent kinetochore-microtubule attachments

Proper kinetochore-microtubule attachments, mediated by the NDC80 complex, are required for error-free chromosome segregation. Erroneous attachments are corrected by the tension dependence of kinetochore-microtubule interactions. Here, we present a method, based on fluorescence lifetime imaging microscopy and Forster resonance energy transfer, to quantitatively measure the fraction of NDC80 complexes bound to microtubules at individual kinetochores in living human cells. We found that NDC80 binding is modulated in a chromosome autonomous fashion over prometaphase and metaphase, and is predominantly regulated by centromere tension. We show that this tension dependency requires phosphorylation of the N-terminal tail of Hec1, a component of the NDC80 complex, and the proper localization of Aurora B kinase, which modulates NDC80 binding. Our results lead to a mathematical model of the molecular basis of tension-dependent NDC80 binding to kinetochore microtubules in vivo.
A novel approach to the synthesis of amino-sugars. Routes to selectively protected 3-amino-3-deoxy-aldopentoses based on pyridinium salt photochemistry.

A new approach for the synthesis of selectively blocked 3-amino-3-deoxyaldopentoses is presented. The strategy is based on employment of a pyridinium salt photocyclization−aziridine ring-opening sequence to prepare stereochemically defined, enantiomerically enriched aminocyclopentendiol derivatives. Ring-opening reactions transform these substances into terminally differentiated aminopolyols, which serve as precursors to the target amino-aldopentoses. The utility of this strategy is demonstrated by its application to the syntheses of protected derivatives of d- and l-3-amino-3-deoxyxylose, l-3-amino-3-deoxyarabinose, and a late-stage intermediate in a potential route to N-acetylneuraminic acid.
The genomics of local adaptation in trees: are we out of the woods yet?

There is substantial interest in uncovering the genetic basis of the traits underlying adaptive responses in tree species, as this information will ultimately aid conservation and industrial endeavors across populations, generations, and environments. Fundamentally, the characterization of such genetic bases is within the context of a genetic architecture, which describes the mutlidimensional relationship between genotype and phenotype through the identification of causative variants, their relative location within a genome, expression, pleiotropic effect, environmental influence, and degree of dominance, epistasis, and additivity. Here, we review theory related to polygenic local adaptation and contextualize these expectations with methods often used to uncover the genetic basis of traits important to tree conservation and industry. A broad literature survey suggests that most tree traits generally exhibit considerable heritability, that underlying quantitative genetic variation (QST) is structured more so across populations than neutral expectations (FST) in 69% of comparisons across the literature, and that single-locus associations often exhibit small estimated per-locus effects. Together, these results suggest differential selection across populations often acts on tree phenotypes underlain by polygenic architectures consisting of numerous small to moderate effect loci. Using this synthesis, we highlight the limits of using solely single-locus approaches to describe underlying genetic architectures and close by addressing hurdles and promising alternatives towards such goals, remark upon the current state of tree genomics, and identify future directions for this field. Importantly, we argue, the success of future endeavors should not be predicated on the shortcomings of past studies and will instead be dependent upon the application of theory to empiricism, standardized reporting, centralized open-access databases, and continual input and review of the community’s research.
Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment.

Malaria parasites have small extremely AT-rich genomes: microsatellite repeats (1-9 bp) comprise 11% of the genome and genetic variation in natural populations is dominated by repeat changes in microsatellites rather than point mutations. This experiment was designed to quantify microsatellite mutation patterns in Plasmodium falciparum. We established 31 parasite cultures derived from a single parasite cell and maintained these for 114-267 days with frequent reductions to a single cell, so parasites accumulated mutations during ∼13,207 cell divisions. We Illumina sequenced the genomes of both progenitor and end-point mutation accumulation (MA) parasite lines in duplicate to validate stringent calling parameters. Microsatellite calls were 99.89% (GATK), 99.99% (freeBayes), and 99.96% (HipSTR) concordant in duplicate sequence runs from independent sequence libraries, whereas introduction of microsatellite mutations into the reference genome revealed a low false negative calling rate (0.68%). We observed 98 microsatellite mutations. We highlight several conclusions: microsatellite mutation rates (3.12 × 10-7 to 2.16 × 10-8/cell division) are associated with both repeat number and repeat motif like other organisms studied. However, 41% of changes resulted from loss or gain of more than one repeat: this was particularly true for long repeat arrays. Unlike other eukaryotes, we found no insertions or deletions that were not associated with repeats or homology regions. Overall, microsatellite mutation rates are among the lowest recorded and comparable to those in another AT-rich protozoan (Dictyostelium). However, a single infection (>1011 parasites) will still contain over 2.16 × 103 to 3.12 × 104 independent mutations at any single microsatellite locus.
EfficientNet: Rethinking Model Scaling for Convolutional Neural Networks

Convolutional Neural Networks (ConvNets) are commonly developed at a fixed resource budget, and then scaled up for better accuracy if more resources are available. In this paper, we systematically study model scaling and identify that carefully balancing network depth, width, and resolution can lead to better performance. Based on this observation, we propose a new scaling method that uniformly scales all dimensions of depth/width/resolution using a simple yet highly effective compound coefficient. We demonstrate the effectiveness of this method on scaling up MobileNets and ResNet. To go even further, we use neural architecture search to design a new baseline network and scale it up to obtain a family of models, called EfficientNets, which achieve much better accuracy and efficiency than previous ConvNets. In particular, our EfficientNet-B7 achieves state-of-the-art 84.3% top-1 accuracy on ImageNet, while being 8.4x smaller and 6.1x faster on inference than the best existing ConvNet. Our EfficientNets also transfer well and achieve state-of-the-art accuracy on CIFAR-100 (91.7%), Flowers (98.8%), and 3 other transfer learning datasets, with an order of magnitude fewer parameters. Source code is at this https URL.
Analyzing and supporting adaptation of online code examples

Developers often resort to online QA adaptation of those examples is necessary to integrate them to production code. As a consequence, the process of adapting online code examples is done over and over again, by multiple developers independently. Our work extensively studies these adaptations and variations, serving as the basis for a tool that helps integrate these online code examples in a target context in an interactive manner. We perform a large-scale empirical study about the nature and extent of adaptations and variations of SO snippets. We construct a comprehensive dataset linking SO posts to GitHub counterparts based on clone detection, time stamp analysis, and explicit URL references. We then qualitatively inspect 400 SO examples and their GitHub counterparts and develop a taxonomy of 24 adaptation types. Using this taxonomy, we build an automated adaptation analysis technique on top of GumTree to classify the entire dataset into these types. We build a Chrome extension called ExampleStack that automatically lifts an adaptation-aware template from each SO example and its GitHub counterparts to identify hot spots where most changes happen. A user study with sixteen programmers shows that seeing the commonalities and variations in similar GitHub counterparts increases their confidence about the given SO example, and helps them grasp a more comprehensive view about how to reuse the example differently and avoid common pitfalls.
Integrating Alternative Data (Also Known as ESG Data) in Investment Decision Making

ABSTRACTWhat is environmental, social, and governance (ESG) data and how do we evaluate its quality and effectiveness? This form of evaluation is important, as it is a precondition for investors tr...
Quantum statistics and spacetime topology: Quantum surgery formulas

Abstract To formulate the universal constraints of quantum statistics data of generic long-range entangled quantum systems, we introduce the geometric-topology surgery theory on spacetime manifolds where quantum systems reside, cutting and gluing the associated quantum amplitudes, specifically in 2+1 and 3+1 spacetime dimensions. First, we introduce the fusion data for worldline and worldsheet operators capable of creating anyonic excitations of particles and strings, well-defined in gapped states of matter with intrinsic topological orders. Second, we introduce the braiding statistics data of particles and strings, such as the geometric Berry matrices for particle–string Aharonov–Bohm, 3-string, 4-string, or multi-string adiabatic loop braiding process, encoded by submanifold links, in the closed spacetime 3-manifolds and 4-manifolds. Third, we derive new “quantum surgery” formulas and constraints, analogous to Verlinde formula associating fusion and braiding statistics data via spacetime surgery, essential for defining the theory of topological orders, 3d and 4d TQFTs and potentially correlated to bootstrap boundary physics such as gapless modes, extended defects, 2d and 3d conformal field theories or quantum anomalies. This article is meant to be an extended and further detailed elaboration of our previous work Wang, Wen and Yau (2016) [1] and Chapter 6 of Wang (2015) [2] . Our theory applies to general quantum theories and quantum mechanical systems, also applicable to, but not necessarily requiring the quantum field theory description.
SqueezeNext: Hardware-Aware Neural Network Design

One of the main barriers for deploying neural networks on embedded systems has been large memory and power consumption of existing neural networks. In this work, we introduce SqueezeNext, a new family of neural network architectures whose design was guided by considering previous architectures such as SqueezeNet, as well as by simulation results on a neural network accelerator. This new network is able to match AlexNet's accuracy on the ImageNet benchmark with 112× fewer parameters, and one of its deeper variants is able to achieve VGG-19 accuracy with only 4.4 Million parameters, (31× smaller than VGG-19). SqueezeNext also achieves better top-5 classification accuracy with 1.3× fewer parameters as compared to MobileNet, but avoids using depthwise-separable convolutions that are inefficient on some mobile processor platforms. This wide range of accuracy gives the user the ability to make speed-accuracy tradeoffs, depending on the available resources on the target hardware. Using hardware simulation results for power and inference speed on an embedded system has guided us to design variations of the baseline model that are 2.59×/8.26× faster and 2.25×/7.5× more energy efficient as compared to SqueezeNet/AlexNet without any accuracy degradation.
The Trio Identity for Quasi-Monte Carlo Error

Monte Carlo methods approximate integrals by sample averages of integrand values. The error of Monte Carlo methods may be expressed as a trio identity: the product of the variation of the integrand, the discrepancy of the sampling measure, and the confounding. The trio identity has different versions, depending on whether the integrand is deterministic or Bayesian and whether the sampling measure is deterministic or random. Although the variation and the discrepancy are common in the literature, the confounding is relatively unknown and under-appreciated. Theory and examples are used to show how the cubature error may be reduced by employing the low discrepancy sampling that defines quasi-Monte Carlo methods. The error may also be reduced by rewriting the integral in terms of a different integrand. Finally, the confounding explains why the cubature error might decay at a rate different from that of the discrepancy.
SOME COROLLARIES OF MANTUROV'S PROJECTION THEOREM

In our works with Stoimenow, Vdovina and with Byberi, we introduced the virtual canonical genus gvc(K) and the virtual bridge number vb(K) invariants of virtual knots. One can see from the definitions that for a classical knot K the values of these invariants are less than or equal to the classical canonical genus gc(K) and the bridge number b(K) respectively. We use Manturov's projection from the category of virtual knot diagrams to the category of classical knot diagrams, to show that for every classical knot type K we have gvc(K) = gc(K) and vb(K) = b(K).
Abelian Properties of Anick Spaces

The Anick spaces play a key role in an unstable filtration of the stable homotopy of V(0) to produce secondary EHP sequences. This work establishes that the Anick spaces are homotopy associative and homotopy commutative H-spaces, and that they have a universal mapping property for maps into a homotopy commutative and homotopy associative H-space with a (necessary) condition on the growth of the p torsion. This is utilized to establish an unstable composition theory. The techniques involve generalized Whitehead products based on co-H spaces, calculations in a congruence category that lies between the unstable category and the stable category, and a controlled version of the extension theorem for principal fibrations.
Support vector algorithms for optimizing the partial area under the roc curve

The area under the ROC curve AUC is a widely used performance measure in machine learning. Increasingly, however, in several applications, ranging from ranking to biometric screening to medicine, performance is measured not in terms of the full area under the ROC curve but in terms of the partial area under the ROC curve between two false-positive rates. In this letter, we develop support vector algorithms for directly optimizing the partial AUC between any two false-positive rates. Our methods are based on minimizing a suitable proxy or surrogate objective for the partial AUC error. In the case of the full AUC, one can readily construct and optimize convex surrogates by expressing the performance measure as a summation of pairwise terms. The partial AUC, on the other hand, does not admit such a simple decomposable structure, making it more challenging to design and optimize tight convex surrogates for this measure. Our approach builds on the structural SVM framework of Joachims 2005 to design convex surrogates for partial AUC and solves the resulting optimization problem using a cutting plane solver. Unlike the full AUC, where the combinatorial optimization needed in each iteration of the cutting plane solver can be decomposed and solved efficiently, the corresponding problem for the partial AUC is harder to decompose. One of our main contributions is a polynomial time algorithm for solving the combinatorial optimization problem associated with partial AUC. We also develop an approach for optimizing a tighter nonconvex hinge loss-based surrogate for the partial AUC using difference-of-convex programming. Our experiments on a variety of real-world and benchmark tasks confirm the efficacy of the proposed methods.
Excited Random Walks with Non-nearest Neighbor Steps

Let W be an integer-valued random variable satisfying \(E[W] =: \delta \ge 0\) and \(P(W 0\), and consider a self-interacting random walk that behaves like a simple symmetric random walk with the exception that on the first visit to any integer \(x\in \mathbb Z\), the size of the next step is an independent random variable with the same distribution as W. We show that this self-interacting random walk is recurrent if \(\delta \le 1\) and transient if \(\delta >1\). This is a special case of our main result which concerns the recurrence and transience of excited random walks (or cookie random walks) with non-nearest neighbor jumps.
On the growth of local intersection multiplicities in holomorphic dynamics: a conjecture of Arnold

We show by explicit example that local intersection multiplicities in holomorphic dynamical systems can grow arbitrarily fast, answering a question of V. I. Arnold. On the other hand, we provide results showing that such behavior is exceptional, and that typically local intersection multiplicities grow subexponentially.
A Uniform Sobolev Inequality Under Ricci Flow

Let ${\bf M}$ be a compact Riemannian manifold and the metrics $g=g(t)$ evolve by the Ricci flow. We prove the following result. The Sobolev imbedding by Aubin or Hebey, perturbed by a scalar curvature term and modulo sharpness of constants, holds uniformly for $({\bf M}, g(t))$ for all time if the Ricci flow exists for all time; and if the Ricci flow develops a singularity in finite time, then the same Sobolev imbedding holds uniformly after a standard normalization. As a consequence, long time non-collapsing results are derived, which improve Perelman's local non-collapsing results. An application to 3-d Ricci flow with surgery is also presented.
Hochster’s small MCM conjecture for three-dimensional weakly F-split rings

We prove Hochster’s small maximal Cohen–Macaulay conjecture for three-dimensional complete F-pure rings. We deduce this from a more general criterion, and show that only a weakening of the notion of F-purity is needed, to wit, being weakly F-split. We conjecture that any complete ring is weakly F-split.
Diagram calculus for a type affine C Temperley–Lieb algebra, I

Abstract In this paper, we present an infinite dimensional associative diagram algebra that satisfies the relations of the generalized Temperley–Lieb algebra having a basis indexed by the fully commutative elements (in the sense of Stembridge) of the Coxeter group of type affine C . Moreover, we provide an explicit description of a basis for the diagram algebra. In the sequel to this paper, we show that this diagrammatic representation is faithful. The results of this paper and its sequel will be used to construct a Jones-type trace on the Hecke algebra of type affine C , allowing us to non-recursively compute leading coefficients of certain Kazhdan–Lusztig polynomials.
Controllability of continuum ensemble of formation systems over directed graphs

Abstract We propose in the paper a novel framework about using a common control input to simultaneously steer an infinite ensemble of networked control systems. We address the problem of co-designing information flow topology and network dynamics of every individual networked system so that a continuum ensemble of such systems is controllable. To keep the problem tractable, we focus in the paper on a special class of ensembles systems, namely ensembles of multi-agent formation systems. Specifically, we consider an ensemble of formation systems indexed by a parameter in a compact real, analytic manifold. Every individual formation system in the ensemble is composed of N agents. These agents evolve in R n and can access relative positions of their neighbors. The information flow topology within every individual formation system is, by convention, described by a directed graph where the vertices correspond to the N agents and the directed edges indicate the information flow. For simplicity, we assume in the paper that all the individual formation systems share the same information flow topology described by a common digraph G . Amongst other things, we establish a sufficient condition for approximate path-controllability of the continuum ensemble of formation systems. We show that if the digraph G is strongly connected and the number N of agents in each individual formation system is greater than ( n + 1 ) , then every such system in the ensemble is simultaneously approximately path-controllable over a path-connected, open dense subset.