cssi/SciSciGPT-SciSciNet huggingface dataset:
INTRACELLULAR PROTEIN TOPOGENESIS

Abstract Concurrently with or shortly after their synthesis on ribosomes, numerous specific proteins are unidirectionally translocated across or asymmetrically integrated into distinct cellular membranes. Thereafter, subpopulations of these proteins need to be sorted from each other and routed for export or targeted to other intracellular membranes or compartments. It is hypothesized here that the information for these processes, termed “protein topogenesis,” is encoded in discrete “topogenic” sequences that constitute a permanent or transient part of the polypeptide chain. The repertoire of distinct topogenic sequences is predicted to be relatively small because many different proteins would be topologically equivalent—i.e., targeted to the same intracellular address. The information content of topogenic sequences would be decoded and processed by distinct effectors. Four types of topogenic sequences could be distinguished: signal sequences, stop-transfer sequences, sorting sequences, and insertion sequences. Signal sequences initiate translocation of proteins across specific membranes. They would be decoded and processed by protein translocators that, by virtue of their signal sequence-specific domain and their unique location in distinct cellular membranes, effect unidirectional translocation of proteins across specific cellular membranes. Stop-transfer sequences interrupt the translocation process that was previously initiated by a signal sequence and, by excluding a distinct segment of the polypeptide chain from translocation, yield asymmetric integration of proteins into translocation-competent membranes. Sorting sequences would act as determinants for posttranslocational traffic of subpopulations of proteins, originating in translocation-competent donor membranes (and compartments) and going to translocation-incompetent receiver membranes (and compartments). Finally, insertion sequences initiate unilateral integration of proteins into the lipid bilayer without the mediation of a distinct protein effector. Examples are given for topogenic sequences, either alone or in combination, to provide the information for the location of proteins in any of the intracellular compartments or for the asymmetric orientation of proteins and their location in any of the cellular membranes. Proposals are made concerning the evolution of topogenic sequences and the relationship of protein topogenesis to the precellular evolution of membranes and compartments.
Barriers and facilitators for the implementation of the integrated public policy for alcohol, drug, tobacco, and gambling prevention: a qualitative study

In the field of alcohol, drug, tobacco, and gambling studies, empirical research on the barriers and facilitators for public prevention policies has been scarce. Public policy studies show that the...
Theoretical investigation of size, shape, and aspect ratio effect on the LSPR sensitivity of hollow-gold nanoshells

The change in refractive index around plasmonic nanoparticles upon binding to biomolecules is routinely used in localized surface plasmon resonance (LSPR)-based biosensors and in biosensing platforms. In this study, the plasmon sensitivity of hollow gold (Au) nanoshells is studied using theoretical modeling where the influence of shape, size, shell thickness, and aspect ratio is addressed. Different shapes of hollow Au nanoshells are studied that include sphere, disk, triangular prism, rod, ellipsoid, and rectangular block. Multilayered Mie theory and discrete dipole approximation were used to determine the LSPR peak position and LSPR sensitivity as a function of size, shell thickness, shape, and aspect ratio. The change in LSPR peak wavelength per unit refractive index is defined as the sensitivity, and interesting results were obtained from the analysis. The rectangular block and rod-shaped Au nanoshells have shown maximum LSPR sensitivity when compared to other shaped Au nanoshells. In addition, increased sensitivity was observed for higher aspect ratio as well as for smaller shell thicknesses. The results are rationalized based on the inner and outer surface plasmonic coupling.
Learning to Denoise Distantly-Labeled Data for Entity Typing.

Distantly-labeled data can be used to scale up training of statistical models, but it is typically noisy and that noise can vary with the distant labeling technique. In this work, we propose a two-stage procedure for handling this type of data: denoise it with a learned model, then train our final model on clean and denoised distant data with standard supervised training. Our denoising approach consists of two parts. First, a filtering function discards examples from the distantly labeled data that are wholly unusable. Second, a relabeling function repairs noisy labels for the retained examples. Each of these components is a model trained on synthetically-noised examples generated from a small manually-labeled set. We investigate this approach on the ultra-fine entity typing task of Choi et al. (2018). Our baseline model is an extension of their model with pre-trained ELMo representations, which already achieves state-of-the-art performance. Adding distant data that has been denoised with our learned models gives further performance gains over this base model, outperforming models trained on raw distant data or heuristically-denoised distant data.
A Possible Link between Pyriproxyfen and Microcephaly

The Zika virus is the primary suspect in the large increase in microcephaly cases in 2015-6 in Brazil, however its role is unconfirmed despite individual cases of viral infections found in neural tissue. Here we consider the alternative that the insecticide pyriproxyfen, used in Brazilian drinking water for mosquito control, may actually be the cause. Pyriproxifen is an analog of juvenile hormone, which corresponds in mammals to regulatory molecules including retinoic acid, a vitamin A metabolite, with which it has cross-reactivity and whose application during development causes microcephaly. Methoprene, another juvenile hormone analog approved as an insecticide has metabolites that bind to the retinoid X receptor, and causes developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via activation of the retinoid X receptor. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly — incomplete formation of the anterior cerebral hemispheres — in rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented — it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, where it is not. Given this combination of information we strongly recommend that the use of pyriproxyfen in Brazil be suspended pending further investigation.
Vinylphosphonium Salts and Allenes from Carbonyl Compounds Using Titanium-Substituted Ylides.

(E)-Vinylphosphonium salts are conveniently obtained from the reaction of carbonyl compounds with titanium-substituted ylide species (Me2N)3PCHTi(OiPr)Cl2 or (Me2N)3PCHTi(OiPr)2Cl. While a wide var...
[3H]MFZ 2-12: a novel radioligand for the dopamine transporter.

Abstract In an effort to develop a tritiated dopamine transporter radioligand with higher affinity than the widely used [ 3 H]WIN 35,428, we have synthesized [ 3 H]2β-carbomethoxy-3β-(3′,4′-dichlorophenyl)tropane ([ 3 H]MFZ 2-12). Unlabeled MFZ 2-12 and the N -demethylated intermediate (MFZ 2-13) inhibited dopamine uptake by the human dopamine transporter with IC 50 's of 1.1 and 1.4 nM, respectively. The N-nor-intermediate (MFZ 2-13) was treated with CT 3 I resulting in [ 3 H]MFZ 2-12; S.A.=80 Ci/mmol). [ 3 H]MFZ 2-12 reversibly bound with a K D of 2.8 nM to human dopamine transporter expressed heterologously in EM4 cells.
Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions.

The APOBEC3 (A3) family of human cytidine deaminases is renowned for providing a first line of defense against many exogenous and endogenous retroviruses. However, the ability of these proteins to deaminate deoxycytidines in ssDNA makes A3s a double-edged sword. When overexpressed, A3s can mutate endogenous genomic DNA resulting in a variety of cancers. Although the sequence context for mutating DNA varies among A3s, the mechanism for substrate sequence specificity is not well understood. To characterize substrate specificity of A3A, a systematic approach was used to quantify the affinity for substrate as a function of sequence context, length, secondary structure, and solution pH. We identified the A3A ssDNA binding motif as (T/C)TC(A/G), which correlated with enzymatic activity. We also validated that A3A binds RNA in a sequence specific manner. A3A bound tighter to substrate binding motif within a hairpin loop compared to linear oligonucleotide, suggesting A3A affinity is modulated by substrate structure. Based on these findings and previously published A3A–ssDNA co-crystal structures, we propose a new model with intra-DNA interactions for the molecular mechanism underlying A3A sequence preference. Overall, the sequence and structural preferences identified for A3A leads to a new paradigm for identifying A3A’s involvement in mutation of endogenous or exogenous DNA.
Fluorine-substituted derivatives of the carcinogenic dihydrodiol and diol epoxide metabolites of 7-methyl-, 12-methyl- and 7,12-dimethylbenz[a]anthracene

Abstract Stereospecific syntheses of the trans-3,4-dihydrodiol metabolites of 9- and 10-fluoro-7,12-dimethylbenz[a]anthracene, -7-methylbenz[a]anthracene, and -12-methylbenz[a]anthracene are described. These dihydrodiols are putative proximate carcinogenic metabolites that undergo activation by the P-450 microsomal enzymes to ultimate carcinogenic anti- and syn-diol epoxide metabolites that bind to nucleic acids in vivo. Syntheses of several of the anti- diol epoxide metabolites are also described.
Unimolecular Rate Expression for Cyclohexene Decomposition and Its Use in Chemical Thermometry under Shock Tube Conditions

The methods used in deriving the rate expressions from comparative rate single-pulse shock tube studies, recent direct shock tube studies, and high-pressure flow experiments bearing on the data for...
Practical use of NH4X salts for difunctional oxyethylene-based intermediates

A series of tosyl functionalized oxyethylene-based organic compounds were selected to analyze the scope and efficiency of a general substitution method for conversion to difunctional, soluble oxyethylene based intermediates using readily available ammonium salts, glycols and commercially modified ethoxy-ethanols. Straightforward preparation, product purification and low cost reagents are particularly advantageous for compounds incorporating halides, thiocyanates and methoxy groups.
Synthesis and Structure of the Centered Cluster Compound Ba3(Zr6Cl18Be)

Reaction of powdered Zr with ZrCl4, BaCl2 and Be in suitable proportions in a Ta container at 800°C produces the title compound. Suitable monocrystals for X-ray diffraction were obtained from reactions to which a comparable amount of Hg2Cl2 had been added. The structure of Ba3Zr6Cl18Be is a superstructure of the K2ZrCl6 · Zr6Cl18H type (R3c, Z = 6; a = 9.6852 (9) A, c = 52.52 (1) A; R, Rw = 2.7, 3.2% for 826 independent reflections, 2θ ≤ 50°). Trigonally compressed [Zr6(Be)Cl12i]Cl6a clusters are interconnected by six-coordinate barium atoms that lie in Cla antiprisms (a twisted version of the ZrIV site) while (9 + 3)-coordinate barium substitutes for potassium within chlorine layers. Distortions associated with the size and field of barium are responsible for the superstructure and for differences from other analogues. Synthese und Struktur der Cluster-Verbindung Ba3(Zr6Cl18Be) Die Reaktion von gepulvertem Zr mit ZrCl4, BaCl2 und Be in entsprechenden Anteilen in Ta-Ampullen ergibt bei 800°C die Titelverbindung. Geeignete Einkristalle zur Strukturbestimmung wurden aus Reaktionen unter Zusatz einer vergleichbaren Menge von Hg2Cl2 erhalten. Die Struktur des Ba3Zr6Cl18Be ist eine Uberstruktur vom K2ZrCl6 · Zr6Cl18H-Typ (R3C, Z = 6; a = 9, 6852 (9) A, c = 52,52 (1) A; R, Rw = 2,7, 3,2% fur 826 unabhangige Reflexe, 2θ ≤ 50°). Trigonal gestauchte [Zr6(Be)Cl12i]Cl6a-Cluster sind uber sechsfach koordinierte Bariumatome verbunden, die in Cla-Antiprismen liegen (eine verdrehte Version der ZrIV-Lage) wahrend (9 + 3)fachkoordiniertes Barium Kalium substituiert innerhalb der Chlor-Schichten. Mit der Grose und dem Feld der Bariumatome verbundene Verzerrungen sind fur die uberstruktur und fur Unterschiede zu anderen Analoga verantwortlich.
Fused Polycyclic Compounds via Cycloaddition of 4-(1′-Cyclohexenyl)-5-iodo-1,2,3-triazoles with 4-Phenyl-1,2,4-triazoline-3,5-dione: The Importance of a Sacrificial Iodide Leaving Group

4-(1′-Cyclohexenyl)-5-iodo-1,2,3-triazole and 4-phenyl-1,2,4-triazoline-3,5-dione undergo a formal Diels–Alder reaction, which following an SN2′ solvolysis process to displace the iodo group affords a fused polycyclic compound.
Bi2Ti2O7: It Is Not What You Have Read

Coprecipitation synthesis methods followed by microwave sintering techniques were utilized to obtain dense phase pure Bi2Ti2O7 polycrystalline ceramic pellets. No evidence of secondary phases was found in the powder or pellets. This maiden achievement allowed for primary thermophysical, crystallographic, and dielectric characterization of this ceramic compound. Density functional theory was used to model the structure of the pyrochlore, from which the theoretical X-ray diffraction pattern was obtained to determine the purity of the experimental compound. Discrepancies among reports in literature regarding the structure, stability, and supposed ferroelectricity of this material are discussed and clarified. A modification to the phase diagram of the Bi2O3–TiO2 system is proposed based on the results of the present investigation. In addition, and contrary to prior reports, the dielectric characterization of Bi2Ti2O7 reveals a linear dielectric with high permittivity values at room temperature (115 at 500 kHz...
Cerebral Cavernous Malformations Develop Through Clonal Expansion of Mutant Endothelial Cells

Rationale: Vascular malformations arise in vessels throughout the entire body. Causative genetic mutations have been identified for many of these diseases; however, little is known about the mutant...
1,5-Asymmetric Induction in Squarate Cascades. Conformational Control of Helicity by Chiral Amino Substituents during Conrotatory Octatetraene Cyclization Prior to β-Elimination

Both the sigmatropic and electrocyclic rearrangement pathways that can arise when a pair of alkenyl anions are added to a squarate ester have high stereochemical demands. The distinction is nontrivial. When cis addition occurs initially, the stereoinduction that materializes at this point is fully transmitted into the product(s). The more commonly observed trans addition exhibits fleeting stereochemical consequences because of rapid equilibration of the octatetraenyl intermediates. In this instance, product distribution is governed by the relative rates of conrotatory cyclization at this advanced stage. Herein reported is a complete dissection of a squarate cascade when a stereogenic center attached to an amino substituent effects 1,5-asymmetric induction prior to β-elimination of the entire fragment. Deuterium labeling permits a direct measure of the contrasting kinetic imbalances associated with the two possible modes of alkenyl anion addition. Furthermore, quantitative analysis of the partitioning expe...
A unified framework for variance component estimation with summary statistics in genome-wide association studies

Linear mixed models (LMMs) are among the most commonly used tools for genetic association studies. However, the standard method for estimating variance components in LMMs-the restricted maximum likelihood estimation method (REML)-suffers from several important drawbacks: REML requires individual-level genotypes and phenotypes from all samples in the study, is computationally slow, and produces downward-biased estimates in case control studies. To remedy these drawbacks, we present an alternative framework for variance component estimation, which we refer to as MQS. MQS is based on the method of moments (MoM) and the minimal norm quadratic unbiased estimation (MINQUE) criterion, and brings two seemingly unrelated methods-the renowned Haseman-Elston (HE) regression and the recent LD score regression (LDSC)-into the same unified statistical framework. With this new framework, we provide an alternative but mathematically equivalent form of HE that allows for the use of summary statistics. We provide an exact estimation form of LDSC to yield unbiased and statistically more efficient estimates. A key feature of our method is its ability to pair marginal z-scores computed using all samples with SNP correlation information computed using a small random subset of individuals (or individuals from a proper reference panel), while capable of producing estimates that can be almost as accurate as if both quantities are computed using the full data. As a result, our method produces unbiased and statistically efficient estimates, and makes use of summary statistics, while it is computationally efficient for large data sets. Using simulations and applications to 37 phenotypes from 8 real data sets, we illustrate the benefits of our method for estimating and partitioning SNP heritability in population studies as well as for heritability estimation in family studies. Our method is implemented in the GEMMA software package, freely available at www.xzlab.org/software.html.
Proton-Coupled Electron Transfer in Organic Synthesis: Novel Homolytic Bond Activations and Catalytic Asymmetric Reactions with Free Radicals

Proton-coupled electron transfers (PCET) are unconventional redox processes in which an electron and proton are exchanged together in a concerted elementary step. While these mechanisms are recognized to play a central role in biological redox catalysis, their applications in synthetic organic chemistry have yet to be widely established. In this Account, we highlight two recent examples from our group outlining the use of concerted PCET as a platform for the development of catalytic and enantioselective reactions of neutral ketyl radicals. Central to this work was the recognition that PCET provides a mechanism for independent proton and electron donors to function jointly as a formal hydrogen atom donor competent to activate organic π systems that are energetically inaccessible using conventional H-atom transfer technologies. In addition, we found that neutral ketyls formed in the PCET event are remarkably strong hydrogen-bond donors and remain strongly associated to the conjugate base of the proton donor following the PCET event. When chiral proton donors are used, these successor H-bond complexes provide a basis for asymmetric induction in subsequent reactions of the ketyl radical. 1 Introduction 2 Concerted PCET and Effective Bond Strengths 3 Concerted PCET Activation of Ketones: A Catalytic Protocol for Ketyl–Olefin Coupling and Mechanistic Investigations 4 Enantioselective PCET Catalysis: Development of Catalytic Asymmetric Aza-pinacol Cyclizations 5 Conclusions
Microwave-induced domino-Knoevenagel-hetero Diels–Alder reaction—an easy route to di[1]benzopyrano[2,3-b:4′,3′-d]pyridine

MW-irradiation of a well-ground equimolar mixture of 2-(N-alkynyl-N-aryl)aminochromone-3-carbaldehyde and dimedone underwent domino-Knoevenagel-hetero Diels–Alder (DKHDA) reaction for nonterminal alkynes, whereas conventional heating of the above reaction mixture in ethanol in the presence of pyridine accomplished alkyne-carbonyl metathesis (ACM) reaction or both ACM and DKHDA reaction. Here is the first example of an organo-catalyzed ACM reaction.
Low-Cost Touchscreen Driven Programmable Dual Syringe Pump for Life Science Applications

Abstract Syringe pumps are powerful tools able to automate routine laboratory practices that otherwise consume large amounts of manual labor time. Commercially available syringe pumps are expensive, difficult to customize, and often preset for a narrow range of operations. Here, we show how to build a programmable dual syringe pump (PDSP) that overcomes these limitations. The PDSP is driven by a Raspberry Pi paired with a stepper motor controller to allow maximal customization via Python scripting. The entire setup can be controlled by a touchscreen for use without a keyboard or mouse. Furthermore, the PDSP is structured around 3D printed parts, enabling users to change any component for their specific application. We demonstrate one application of the PDSP by using it to generate whole cell lysates using a cell homogenizer in an automated fashion.
Substituted 2,4-diaminoquinazolines and 2,4-diamino-8-alkylpurines as antagonists of the neurokinin-2 (NK2) receptor

Abstract Modification of the heterocyclic nucleus of a lead pyrrolopyrimidine (1) found to be active as an antagonist at the neurokinin-2 (NK2) receptor is described. Compounds based on the purine nucleus (3) were found to be particularly interesting, and were modified in the C(2), C(4) and C(8) substituents to afford compounds with high potency.
Simulating contact using the elastic foundation algorithm in OpenSim

Abstract Modeling joint contact in OpenSim is not well understood. This study systematically investigated the variables associated with the elastic foundation contact model within OpenSim by performing a series of controlled benchtop experiment and concomitant simulations. Four metal-on-plastic interactions were modeled, including a model of a total knee replacement (TKR). Load-displacement curves were recorded during cyclic loading between 100 and 750 N. Geometries were imported and into OpenSim and contact mechanics were modeled with the on-board elastic foundation algorithm. A hybrid optimization algorithm determined that stiffness and dissipation coefficients for TKR implants were 1.52 × 1010 N/m and 57.7 Ns/m, respectively. Estimations of contact forces were 10.2% of blinded experimental data (average root mean square error: 76.82 ± 11.47 N). In the second portion of this study, freely available eTibia TKR renderings were used to test the ubiquity of the tuning parameters. They were also used to perform a sensitivity analysis of material stiffness and mesh density with regard to penetration depth and computational time. When a stiffness of 1 × 1010 was applied to an eTibia model with 5000 faces, a 100 kg load caused 0.259 mm of penetration. Under the same conditions, the tuned model experienced 0.300 mm of penetration. Material stiffnesses between 1 × 1013 and 1 × 1015 N/m increased computation time by factors of 12–23. This study provides much needed clarity regarding the use of the OpenSim EF algorithm. It also demonstrates the utility of OpenSim to model deformable materials and complex geometries, and this approach can be adapted to make reasonable estimations for both natural and surgically modified joints.
Catalysts for Suzuki−Miyaura Coupling Processes: Scope and Studies of the Effect of Ligand Structure

Suzuki−Miyaura coupling reactions of aryl and heteroaryl halides with aryl-, heteroaryl- and vinylboronic acids proceed in very good to excellent yield with the use of 2-(2‘,6‘-dimethoxybiphenyl)dicyclohexylphosphine, SPhos (1). This ligand confers unprecedented activity for these processes, allowing reactions to be performed at low catalyst levels, to prepare extremely hindered biaryls and to be carried out, in general, for reactions of aryl chlorides at room temperature. Additionally, structural studies of various 1·Pd complexes are presented along with computational data that help elucidate the efficacy that 1 imparts on Suzuki−Miyaura coupling processes. Moreover, a comparison of the reactions with 1 and with 2-(2‘,4‘,6‘-triisopropylbiphenyl)diphenylphosphine (2) is presented that is informative in determining the relative importance of ligand bulk and electron-donating ability in the high activity of catalysts derived from ligands of this type. Further, when the aryl bromide becomes too hindered, an ...
Synthesis of aryl 3-(2-imidazolyl)propyl ketones†

The approach to the title compounds was via lithiation-substitution of N-methyl or N-(triphenylmethyl)-imidazole by some iodo ketals. 4-Chloro-4′-halobutyrophenones (halo = F, Cl, Br) were converted by sodium iodide to the corresponding aliphatic iodides which were subsequently ketalized with ethylene glycol to provide the corresponding iodo ketals. Lithiation of either 1-methyl- or 1-(triphenylmethyl)imid-azole with N-butyllithium generated the corresponding 2-lithioimidazoles, in situ, which were then reacted with these iodo ketals to form the corresponding C-2 substituted imidazoles. Dilute aqueous acid hydrolysis released the ketone from the ketal. For N-triphenylmethyl protected imidazoles, the triphenylmethyl group was also hydrolyzed to give triphenylmethanol and 3-(2-imidazolyl)propyl 4-haloaryl ketones. These N-unsubstituted imidazolyl ketones can be alkylated independently with triphenylmethyl chloride to form the corresponding N-triphenylmethyl imidazole derivatives.
Studies towards the total synthesis of palau'amine. Formation of 4,5-dihydropyrrole-2-carboxylate intermediates by alkene–enamide ring-closing metathesis

Abstract A highly functionalized 4,5-dihydropyrrole-2-carboxylate is assembled by alkene–enamide ring-closing metathesis. Subsequent intramolecular azomethine imine dipolar cycloaddition provides a triazacyclopenta[ cd ]pentalene intermediate of potential use in a total synthesis of palau'amine.
Clostridium difficile Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization.

ABSTRACT Susceptibility to Clostridium difficile infection (CDI) is primarily associated with previous exposure to antibiotics, which compromise the structure and function of the gut bacterial community. Specific antibiotic classes correlate more strongly with recurrent or persistent C. difficile infection. As such, we utilized a mouse model of infection to explore the effect of distinct antibiotic classes on the impact that infection has on community-level transcription and metabolic signatures shortly following pathogen colonization and how those changes may associate with persistence of C. difficile. Untargeted metabolomic analysis revealed that C. difficile infection had significantly larger impacts on the metabolic environment across cefoperazone- and streptomycin-pretreated mice, which became persistently colonized compared to clindamycin-pretreated mice, where infection quickly became undetectable. Through metagenome-enabled metatranscriptomics, we observed that transcripts for genes associated with carbon and energy acquisition were greatly reduced in infected animals, suggesting that those niches were instead occupied by C. difficile. Furthermore, the largest changes in transcription were seen in the least abundant species, indicating that C. difficile may “attack the loser” in gut environments where sustained infection occurs more readily. Overall, our results suggest that C. difficile is able to restructure the nutrient-niche landscape in the gut to promote persistent infection. IMPORTANCEClostridium difficile has become the most common single cause of hospital-acquired infection over the last decade in the United States. Colonization resistance to the nosocomial pathogen is primarily provided by the gut microbiota, which is also involved in clearing the infection as the community recovers from perturbation. As distinct antibiotics are associated with different risk levels for CDI, we utilized a mouse model of infection with 3 separate antibiotic pretreatment regimens to generate alternative gut microbiomes that each allowed for C. difficile colonization but varied in clearance rate. To assess community-level dynamics, we implemented an integrative multi-omics approach that revealed that infection significantly changed many aspects of the gut community. The degree to which the community changed was inversely correlated with clearance during the first 6 days of infection, suggesting that C. difficile differentially modifies the gut environment to promote persistence. This is the first time that metagenome-enabled metatranscriptomics have been employed to study the behavior of a host-associated microbiota in response to an infection. Our results allow for a previously unseen understanding of the ecology associated with C. difficile infection and provide the groundwork for identification of context-specific probiotic therapies.
The Synthesis of 3-pyrazinyl-pyrazolo [1,5-a] pyridines from an enol ether

The synthesis of 3-(6-chloropyrazin-2-yl)pyrazolo[1,5-a]pyridine from an enol ether and 4-substituted 1-aminopyridinim iodides via a 3+2 cycloaddition is presented. A high throughput reaction screen was used to optimize the yield of the cycloaddition. This protocol is operationally simple, scalable, proceeds at room temperature, and the reaction profiles are very clean.
Collision-Induced Dissociation of Mass-Selected Ethylene Cluster Ions (n = 2−9)

The structure and chemical identity of ethylene van der Waals cluster ions, (C2H4)n=2-9+, have been studied using triple quadrupole mass spectrometry. The collision-induced dissociation mass spectra reveal that cluster ions with n = 2−5 may undergo uncatalyzed cationic polymerization to form covalently bonded cationic oligomers (i.e., CnH2n+, n = 2−5). This has been confirmed by comparison of ethylene cluster ion mass spectra to those of known covalently bonded ions. Cluster ions with n > 5 consist of C10H20+ oligomer cores solvated by an appropriate number of ethylene monomers. Uncatalyzed cationic polymerization of ethylene appears to cease beyond n = 5 because of a “kinetic bottleneck”. As the proposed structures of the n = 2−4 cluster ions are either linear or simple cyclic while the n = 5 ion is proposed to be branched, this kinetic effect is likely due to inhibition of further intracluster polymerization by steric hindrance.
An efficient method for para-methoxybenzyl ether formation with lanthanum triflate

PMB ethers of alcohols are prepared in high yields and short reaction times using the trichloroacetimidate of PMB alcohol and lanthanum triflate. The mild conditions allow protection of acid-sensitive alcohols.
Relative Rates of Hydrosilylation of Representative Alkenes and Alkynes by Cp*2YMe·THF and [CpTMS2YMe]2

Reactivity in the hydrosilylation of alkenes and alkynes catalyzed by the organoyttrium catalysts Cp*2YMe·THF and [CpTMS2YMe]2 is generally determined by the steric environment of the substrate. Alkynes and conjugated alkenes show an increased reaction rate because of electronic effects; the magnitude of this increase is highly substrate dependent. The electron rich pyrrole system is particularly reactive, especially with the sterically open [CpTMS2YMe]2 precatalyst. For nonconjugated substrates, Cp*2YMe·THF is generally a more selective catalyst than [CpTMS2YMe]2.
Synthesis of peptide-diazeniumdiolate conjugates: towards enzyme activated antitumor agents

Abstract The development of NO donors with site-specific and time-controlled properties is of great interest. We have designed a novel prodrug class as possible agents against metastatic prostate cancer by coupling a diazeniumdiolate to the terminal carboxyl groups of amino acids or peptides, such as Ser-Ser-Tyr-Tyr, Ser-Ser-Phe-Tyr, and Gly-Ile-Ser-Ser-Phe-Tyr. These prodrugs can be activated by α-chymotrypsin or prostate specific antigen and are potentially potent compounds for prostatic cancer.
YAMDA: thousandfold speedup of EM-based motif discovery using deep learning libraries and GPU.

Motivation Motif discovery in large biopolymer sequence datasets can be computationally demanding, presenting significant challenges for discovery in omics research. MEME, arguably one of the most popular motif discovery software, takes quadratic time with respect to dataset size, leading to excessively long runtimes for large datasets. Therefore, there is a demand for fast programs that can generate results of the same quality as MEME. Results Here we describe YAMDA, a highly scalable motif discovery software package. It is built on Pytorch, a tensor computation deep learning library with strong GPU acceleration that is highly optimized for tensor operations that are also useful for motifs. YAMDA takes linear time to find motifs as accurately as MEME, completing in seconds or minutes, which translates to speedups over a thousandfold. Availability and implementation YAMDA is freely available on Github (https://github.com/daquang/YAMDA). Supplementary information Supplementary data are available at Bioinformatics online.
Six-membered bis(azaphosphorinane), readily available ligand for highly enantioselective asymmetric hydrogenations

A new six-membered bis(azaphosphorinane) ligand has been readily prepared starting from an inexpensive chiral epoxide; excellent enantioselectivities (up to over 99% ee) have been achieved in the Rh-catalyzed asymmetric hydrogenations of β-dehydroamino acid derivatives and α-arylenamides.
COPPER (II) BROMIDE ON ALUMINA : A NEW REAGENT FOR BROMOLACTONIZATION

Abstract Copper (II) bromide supported on alumina has been found to be a new and effective reagent for bromolactonization.
Hedge fund hold ’em

Abstract Hedge fund managers who do well in poker tournaments have better fund performance. This effect is stronger for tournaments with more entrants, larger buy-ins, larger cash prizes, and for managers who place higher or win multiple tournaments. After tournament wins, net flows to the manager’s fund increase significantly. These increases are higher for tournaments with media coverage, when the tournament win is bigger, and for more prestigious tournaments. Along with higher net flows, fund alpha also decreases following the tournament win. Given this, hedge fund investors would be better off investing in an otherwise similar manager without poker tournament success.
The Concordance Genus of 11--Crossing Knots

The concordance genus of a knot is the least genus of any knot in its concordance class. It is bounded above by the genus of the knot, and bounded below by the slice genus, two well-studied invariants. In this paper we consider the concordance genus of 11-crossing prime knots. This analysis resolves the concordance genus of 533 of the 552 prime 11-crossing knots. The appendix to the paper gives concordance diagrams for 59 knots found to be concordant to knots of lower genus, including null-concordances for the 30 11-crossing knots known to be slice.
BRAID GROUP REPRESENTATIONS ARISING FROM THE YANG–BAXTER EQUATION

This paper aims to determine the images of the braid group under representations afforded by the Yang–Baxter equation when the solution is a non-trivial 4 × 4 matrix. Making the assumption that all the eigenvalues of the Yang–Baxter solution are roots of unity, leads to the conclusion that all the images are finite. Using results of Turaev, we have also identified cases in which one would get a link invariant. Finally, by observing the group algebra generated by the image of the braid group sometimes factor through known algebras, in certain instances we can identify the invariant as particular specializations of a known invariant.
Grasp Pose Detection in Point Clouds

Recently, a number of grasp detection methods have been proposed that can be used to localize robotic grasp configurations directly from sensor data without estimating object pose. The underlying i...
Étale stacks as prolongations

Abstract We give a complete and categorical characterization of etale stacks (generalized orbifolds) in various geometric contexts, including differentiable stacks and topological stacks. This characterization states that etale stacks are precisely those stacks that arise as prolongations of stacks on a site of spaces and local homeomorphisms, and makes no mention of an atlas or groupoid presentation. Moreover, we show that the bicategory of etale differentiable stacks and local diffeomorphisms is equivalent to the bicategory of stacks on the site of smooth manifolds and local diffeomorphisms. An analogous statement holds for other flavors of manifolds (topological, C k , complex, super...), and topological spaces locally homeomorphic to a given space X. A slight modification of this result also holds in an even more general context, including all etale topological stacks, and Zariski etale stacks, which are analogues of Deligne-Mumford stacks for the Zariski topology, and we also sketch a proof of an analogous characterization of classical Deligne-Mumford algebraic stacks (which we prove in full in [7] by different methods). We go on to characterize effective etale stacks (e.g. reduced orbifolds) as precisely those stacks arising as the prolongations of sheaves of sets (rather than stacks of groupoids). It follows that etale stacks (and in particular orbifolds) induce a small gerbe over their effective part, and all gerbes over effective etale stacks arise in this way. We show that well known Lie groupoids from foliation theory literature can be reproduced from this framework as natural presentations for moduli stacks of certain geometric structures. For example, there exists a classifying stack for Riemannian metrics, presented by Haefliger's groupoid RΓ [13] and submersions into this stack classify Riemannian foliations, and similarly for symplectic structures, with the role of RΓ replaced with Γ S p . We also prove some unexpected results, for example: the category of smooth n-manifolds and local diffeomorphisms has binary products.
Subspace Network: Deep Multi-Task Censored Regression for Modeling Neurodegenerative Diseases

Over the past decade a wide spectrum of machine learning models have been developed to model the neurodegenerative diseases, associating biomarkers, especially non-intrusive neuroimaging markers, with key clinical scores measuring the cognitive status of patients. Multi-task learning (MTL) has been commonly utilized by these studies to address high dimensionality and small cohort size challenges. However, most existing MTL approaches are based on linear models and suffer from two major limitations: 1) they cannot explicitly consider upper/lower bounds in these clinical scores; 2) they lack the capability to capture complicated non-linear interactions among the variables. In this paper, we propose Subspace Network, an efficient deep modeling approach for non-linear multi-task censored regression. Each layer of the subspace network performs a multi-task censored regression to improve upon the predictions from the last layer via sketching a low-dimensional subspace to perform knowledge transfer among learning tasks. Under mild assumptions, for each layer the parametric subspace can be recovered using only one pass of training data. Empirical results demonstrate that the proposed subspace network quickly picks up the correct parameter subspaces, and outperforms state-of-the-arts in predicting neurodegenerative clinical scores using information in brain imaging.
Should Robots be Obedient

Intuitively, obedience -- following the order that a human gives -- seems like a good property for a robot to have. But, we humans are not perfect and we may give orders that are not best aligned to our preferences. We show that when a human is not perfectly rational then a robot that tries to infer and act according to the human's underlying preferences can always perform better than a robot that simply follows the human's literal order. Thus, there is a tradeoff between the obedience of a robot and the value it can attain for its owner. We investigate how this tradeoff is impacted by the way the robot infers the human's preferences, showing that some methods err more on the side of obedience than others. We then analyze how performance degrades when the robot has a misspecified model of the features that the human cares about or the level of rationality of the human. Finally, we study how robots can start detecting such model misspecification. Overall, our work suggests that there might be a middle ground in which robots intelligently decide when to obey human orders, but err on the side of obedience.
Efficient Model Identification for Tensegrity Locomotion

This paper aims to identify in a practical manner unknown physical parameters, such as mechanical models of actuated robot links, which are critical in dynamical robotic tasks. Key features include the use of an off-the-shelf physics engine and the Bayesian optimization framework. The task being considered is locomotion with a high-dimensional, compliant Tensegrity robot. A key insight, in this case, is the need to project the space of models into an appropriate lower dimensional space for time efficiency. Comparisons with alternatives indicate that the proposed method can identify the parameters more accurately within the given time budget, which also results in more precise locomotion control.
On the complexity of computing Kronecker coefficients

We study the complexity of computing Kronecker coefficients$${g(\lambda,\mu,\nu)}$$g(ź,μ,ź). We give explicit bounds in terms of the number of parts $${\ell}$$l in the partitions, their largest part size N and the smallest second part M of the three partitions. When M = O(1), i.e., one of the partitions is hook-like, the bounds are linear in log N, but depend exponentially on $${\ell}$$l. Moreover, similar bounds hold even when $${M=e^{O(\ell)}}$$M=eO(l). By a separate argument, we show that the positivity of Kronecker coefficients can be decided in O(log N) time for a bounded number $${\ell}$$l of parts and without restriction on M. Related problems of computing Kronecker coefficients when one partition is a hook and computing characters of Sn are also considered.
Finiteness conditions on the Yoneda algebra of a monomial algebra

Abstract Let A be a connected graded noncommutative monomial algebra. We associate to A a finite graph Γ ( A ) called the CPS graph of A . Finiteness properties of the Yoneda algebra Ext A ( k , k ) including Noetherianity, finite GK dimension, and finite generation are characterized in terms of Γ ( A ) . We show that these properties, notably finite generation, can be checked by means of a terminating algorithm.
An Alternate Approach to the Lie Bracket on Hochschild Cohomology

We define Gerstenhaber's graded Lie bracket directly on complexes other than the bar complex, under some conditions. The Koszul complex of a Koszul algebra in particular satisfies our conditions. As examples we recover the Schouten-Nijenhuis bracket for a polynomial ring and the Gerstenhaber bracket for a group algebra of a cyclic group of prime order.
Uncertainty quantification for cargo hold fires

The purpose of this study is twofold – first, to introduce the application of high-order discontinuous Galerkin methods to buoyancy-driven cargo hold fire simulations; second, to explore statistical variation in the fluid dynamics of a cargo hold fire given parameterized uncertainty in the fire source location and temperature. Cargo hold fires represent a class of problems that require highly-accurate computational methods to simulate faithfully. Hence, we use an in-house discontinuous Galerkin code to treat these flows. Cargo hold fires also exhibit a large amount of uncertainty with respect to the boundary conditions. Thus, the second aim of this paper is to use tools from the uncertainty quantification community to ensure that our efforts require a minimal number of simulations. We expect that the results of this study will provide statistical insight into the effects of fire location and temperature on cargo fires, and also assist in the optimization of fire detection system placement.
No interesting sequential groups

Abstract We prove that it is consistent with ZFC that no sequential topological groups of intermediate sequential orders exist. This shows that the answer to a 1981 question of P. Nyikos is independent of the standard axioms of set theory. The model constructed also provides consistent answers to several questions of D. Shakhmatov, S. Todorcevic and Uzcategui. In particular, we show that it is consistent with ZFC that every countably compact sequential group is Frechet–Urysohn.
Machine Learning for Public Administration Research, With Application to Organizational Reputation

Machine learning methods have gained a great deal of popularity in recent years among public administration scholars and practitioners. These techniques open the door to the analysis of text, image and other types of data that allow us to test foundational theories of public administration and to develop new theories. Despite the excitement surrounding machine learning methods, clarity regarding their proper use and potential pitfalls is lacking. This paper attempts to fill this gap in the literature through providing a machine learning "guide to practice" for public administration scholars and practitioners. Here, we take a foundational view of machine learning and describe how these methods can enrich public administration research and practice through their ability develop new measures, tap into new sources of data and conduct statistical inference and causal inference in a principled manner. We then turn our attention to the pitfalls of using these methods such as unvalidated measures and lack of interpretability. Finally, we demonstrate how machine learning techniques can help us learn about organizational reputation in federal agencies through an illustrated example using tweets from 13 executive federal agencies.
Learning Sight from Sound: Ambient Sound Provides Supervision for Visual Learning

The sound of crashing waves, the roar of fast-moving cars--sound conveys important information about the objects in our surroundings. In this work, we show that ambient sounds can be used as a supervisory signal for learning visual models. To demonstrate this, we train a convolutional neural network to predict a statistical summary of the sound associated with a video frame. We show that, through this process, the network learns a representation that conveys information about objects and scenes. We evaluate this representation on several recognition tasks, finding that its performance is comparable to that of other state-of-the-art unsupervised learning methods. Finally, we show through visualizations that the network learns units that are selective to objects that are often associated with characteristic sounds. This paper extends an earlier conference paper, Owens et al. (in: European conference on computer vision, 2016b), with additional experiments and discussion.
Statistical Learning Theory Approach for Data Classification with ℓ -diversity.

Corporations are retaining ever-larger corpuses of personal data; the frequency or breaches and corresponding privacy impact have been rising accordingly. One way to mitigate this risk is through use of anonymized data, limiting the exposure of individual data to only where it is absolutely needed. This would seem particularly appropriate for data mining, where the goal is generalizable knowledge rather than data on specific individuals. In practice, corporate data miners often insist on original data, for fear that they might "miss something" with anonymized or differentially private approaches. This paper provides a theoretical justification for the use of anonymized data. Specifically, we show that a support vector classifier trained on anatomized data satisfying l-diversity should be expected to do as well as on the original data. Anatomy preserves all data values, but introduces uncertainty in the mapping between identifying and sensitive values, thus satisfying l-diversity. The theoretical effectiveness of the proposed approach is validated using several publicly available datasets, showing that we outperform the state of the art for support vector classification using training data protected by k-anonymity, and are comparable to learning on the original data.