cssi/SciSciGPT-SciSciNet huggingface dataset:
An improved model of ethanol and nicotine co-use in female P rats: Effects of naltrexone, varenicline, and the selective nicotinic α6β2* antagonist r-bPiDI

Abstract Background Although pharmacotherapies are available for alcohol (EtOH) or tobacco use disorders individually, it may be possible to develop a single pharmacotherapy to treat heavy drinking tobacco smokers by capitalizing on the commonalities in their mechanisms of action. Methods Female alcohol-preferring (P) rats were trained for EtOH drinking and nicotine self-administration in two phases: (1) EtOH alone (0 vs. 15% EtOH, 2-bottle choice) and (2) concomitant access, during which EtOH access continued with access to nicotine (0.03 mg/kg/infusion, i.v.) using a 2-lever choice procedure (active vs. inactive lever) in which the fixed ratio (FR) requirement was gradually increased to FR30. When stable co-use was obtained, rats were pretreated with varying doses of naltrexone, varenicline, or r-bPiDI, an α6β2* subtype-selective nicotinic acetylcholine receptor antagonist shown previously to reduce nicotine self-administration. Results While EtOH intake was initially suppressed in phase 2 (co-use), pharmacologically relevant intake for both substances was achieved by raising the “price” of nicotine to FR30. In phase 2, naltrexone decreased EtOH and water consumption but not nicotine intake; in contrast, naltrexone in phase 1 (EtOH only) did not significantly alter EtOH intake. Varenicline and r-bPiDI in phase 2 both decreased nicotine self-administration and inactive lever pressing, but neither altered EtOH or water consumption. Conclusions These results indicate that increasing the “price” of nicotine increases EtOH intake during co-use. Additionally, the efficacy of naltrexone, varenicline, and r-bPiDI was specific to either EtOH or nicotine, with no efficacy for co-use. Nevertheless, future studies on combining these treatments may reveal synergistic efficacy.
Groundwater depletion in India: social losses from costly well deepening.

Abstract We develop a dynamic groundwater model that incorporates both groundwater pumping and investment in deeper wells and apply the model to the arid, alluvial aquifer region of Northern India that is experiencing rapid depletion. We compute the potential benefits of regulating groundwater use by comparing the net benefits of groundwater under optimal management to the net benefits under a common pool regime with two different cost structures: one with flat electricity tariffs, which are widespread in India, and a second with full marginal cost electricity pricing. Using numerical simulation, we find that the opportunity to invest in deeper wells significantly exacerbates the common pool problem and suggests the potential for large benefits (66% of common pool benefits) from optimally managing groundwater use or new drilling. Flat tariffs exacerbate the problem, but large gains (almost 23%) remain even if farms are charged the full marginal cost of electricity.
Multicenter Evaluation of NeuMoDx Group B Streptococcus Assay on the NeuMoDx 288 Molecular System

Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis in developed countries. Recommendations for antepartum GBS detection include enriched culture with several options for identifying GBS, some of which are time-consuming. To reduce the time for identification and determination of the maternal GBS colonization status, rapid nucleic acid amplification technologies have been developed and commercialized. For rapid detection of GBS, a three-site clinical study was conducted to evaluate the NeuMoDx GBS assay, a real-time PCR test performed for vaginal/rectal swab specimens in Lim broth enrichment culture on the NeuMoDx 288 molecular system (NeuMoDx system); these data were used to a support 510(k) submission. A total of 1,250 eligible remnant samples were prospectively enrolled and tested during the study. The results of the PCR assay were compared to the results of the Centers for Disease Control and Prevention (CDC)-recommended enriched-culture method, which served as the gold standard reference method for the study. The NeuMoDx GBS assay results yielded a sensitivity of 96.9% (95% confidence interval [CI] = 94.1 to 98.4), specificity of 96.0% (95% CI = 94.6 to 97.1), and a total agreement with the reference method of 96.2% (95% CI = 93.8 to 98.3). NeuMoDx GBS assay results were also compared to results obtained using the BD MAX GBS assay on the BD MAX system. The two systems demonstrated a total percent agreement of 98.0% (95% CI = 95.5 to 100.0). The performance of the NeuMoDx GBS assay implemented on the NeuMoDx system compared favorably to the CDC enriched-culture method and to the BD MAX GBS assay.
Nonsingular Gaussian Conditionally Markov Sequences

Markov processes are widely used in modeling random phenomena/problems. However, they may not be adequate in some cases where more general processes are needed. The conditionally Markov (CM) process is a generalization of the Markov process based on conditioning. There are several classes of CM processes (one of them is the class of reciprocal processes), which provide more capability (than Markov) for modeling random phenomena. Reciprocal processes have been used in many different applications (e.g., image processing, intent inference, intelligent systems). In this paper, nonsingular Gaussian (NG) CM sequences are studied, characterized, and their dynamic models are presented. The presented results provide effective tools for studying reciprocal sequences from the CM viewpoint, which is different from that of the literature. Also, the presented models and characterizations serve as a basis for application of CM sequences, e.g., in motion trajectory modeling with destination information.
Universal relations in composite Higgs models

We initiate a phenomenological study of “universal relations” in composite Higgs models, which are dictated by nonlinear shift symmetries acting on the 125 GeV Higgs boson. These are relations among one Higgs couplings with two electroweak gauge bosons (HVV), two Higgses couplings with two electroweak gauge bosons (HHVV), one Higgs couplings with three electroweak gauge bosons (HVVV), as well as triple gauge boson couplings (TGC), which are all controlled by a single input parameter: the decay constant f of the pseudo-Nambu-Goldstone Higgs boson. Assuming custodial invariance in strong sector, the relation is independent of the symmetry breaking pattern in the UV, for an arbitrary symmetric coset G/H. The complete list of corrections to HVV, HHVV, HVVV and TGC couplings in composite Higgs models is presented to all orders in 1/f , and up to four-derivative level, without referring to a particular G/H. We then present several examples of universal relations in ratios of coefficients which could be extracted experimentally. Measuring the universal relation requires a precision sensitive to effects of dimension-8 operators in the effective Lagrangian and highlights the importance of verifying the tensor structure of HHVV interactions in the standard model, which remains untested to date.
Visualizing and Interpreting Single-Cell Gene Expression Datasets with Similarity Weighted Nonnegative Embedding

High-throughput single-cell gene expression profiling has enabled the definition of new cell types and developmental trajectories. Visualizing these datasets is crucial to biological interpretation, and a popular method is t-stochastic neighbor embedding (t-SNE), which visualizes local patterns well but distorts global structure, such as distances between clusters. We developed similarity weighted nonnegative embedding (SWNE), which enhances interpretation of datasets by embedding the genes and factors that separate cell states on the visualization alongside the cells and maintains fidelity when visualizing local and global structure for both developmental trajectories and discrete cell types. SWNE uses nonnegative matrix factorization to decompose the gene expression matrix into biologically relevant factors; embeds the cells, genes, and factors in a 2D visualization; and uses a similarity matrix to smooth the embeddings. We demonstrate SWNE on single-cell RNA-seq data from hematopoietic progenitors and human brain cells. SWNE is available as an R package at github.com/yanwu2014/swne.
Exploring the process by which positive racial identity develops and influences academic performance in Black youth: Implications for social work

ABSTRACTAlthough racial-ethnic socialization and racial-ethnic identity interlink to influence youth's developmental outcomes, the extant research has tended to investigate these constructs and the...
Microscopic details of asphaltenes aggregation onset during waterflooding

We report detailed microscopic studies of asphaltenes aggregation onset during waterflooding of petroleum reservoirs. To achieve this objective, a series of simulations are performed on asp...
Moraxella nonliquefaciens and M. osloensis Are Important Moraxella Species That Cause Ocular Infections

Moraxella is an ocular bacterial pathogen isolated in cases of keratitis, conjunctivitis, and endophthalmitis. Gram-negative brick-shaped diplobacilli from ocular specimens, and slow growth in culture, are early indications of Moraxella ocular infection; however, identifying Moraxella to species can be complex and inconsistent. In this study, bacteria consistent with Moraxella were identified to species using: (1) DNA sequencing coupled with vancomycin susceptibility, (2) MALDI-TOF mass spectrometry, and (3) the Biolog ID system. Study samples consisted of nine ATCC Moraxella controls, 82 isolates from keratitis, 21 isolates from conjunctivitis, and 4 isolates from endophthalmitis. The ATCC controls were correctly identified. For keratitis, 66 (80.5%) were identified as M. nonliquefaciens, 7 (9.0%) as M. lacunata, 5 (6%) as M. osloensis, 2 (2.5%) as Acinetobacter lwoffii, 1 (1.0%) as M. bovis/nonliquefaciens, and 1 (1.0%) as M. osloensis/nonliquefaciens. For conjunctivitis, 9 (43.0%) were identified as M. osloensis, 6 (29.0%) as M. nonliquefaciens, 3 (14.3%) as Roseomonas, 2 (9.5%) as Acinetobacter (parvus, junii), and 1 (4.5%) as M. catarrhalis/nonliquefaciens. From endophthalmitis, 3 of 4 of the isolates were M. nonliquefaciens. Overall, M. nonliquefaciens and M. osloensis were identified in 70% (75 of 107) and 13% (14 of 107) of cases, respectively, totaling 83% (89 of 107). M. nonliquefaciens and M. osloensis are important bacterial pathogens of the eye as determined by DNA sequencing, MALDI-TOF MS, and Biolog. Although Moraxella catarrhalis is a clinical pathogen, other species of Moraxella appear to have a prominent role in eye infections.
Observer-based distributed leader-follower tracking control: a new perspective and results

Leader-follower tracking control design has received significant attention in recent years due to its important and wide applications. Considering a multi-agent system composed of a leader and mult...
Failure Localization in Power Systems via Tree Partitions

Cascading failures in power systems propagate non-locally, making the control and mitigation of outages extremely hard. In this work, we use the emerging concept of the tree partition of transmission networks to provide an analytical characterization of line failure localizability in transmission systems. Our results rigorously establish the well perceived intuition in power community that failures cannot cross bridges, and reveal a finer-grained concept that encodes more precise information on failure propagations within tree-partition regions. Specifically, when a non-bridge line is tripped, the impact of this failure only propagates within well-defined components, which we refer to as cells, of the tree partition defined by the bridges. In contrast, when a bridge line is tripped, the impact of this failure propagates globally across the network, affecting the power flow on all remaining transmission lines. This characterization suggests that it is possible to improve the system robustness by temporarily switching off certain transmission lines, so as to create more, smaller components in the tree partition; thus spatially localizing line failures and making the grid less vulnerable to large-scale outages. We illustrate this approach using the IEEE 118-bus test system and demonstrate that switching off a negligible portion of transmission lines allows the impact of line failures to be significantly more localized without substantial changes in line congestion.
Aqueous synthesis of a small-molecule lanthanide chelator amenable to copper-free click chemistry

The lanthanides (Ln3+), or rare earth elements, have proven to be useful tools for biomolecular NMR, X-ray crystallographic, and fluorescence analyses due to their unique 4f orbitals. However, their utility in biological applications has been limited because site-specific incorporation of a chelating element is required to ensure efficient binding of the free Ln3+ ion. Additionally, current Ln3+ chelator syntheses complicate efforts to directly incorporate Ln3+ chelators into proteins as the multi-step processes and a reliance on organic solvents promote protein denaturation and aggregation which are generally incompatible with direct incorporation into the protein of interest. To overcome these limitations, herein we describe a two-step aqueous synthesis of a small molecule lanthanide chelating agent amenable to site-specific incorporation into a protein using copper-free click chemistry with unnatural amino acids. The bioconjugate combines a diethylenetriaminepentaacetic acid (DTPA) chelating moiety with a clickable dibenzylcyclooctyne-amine (DBCO-amine) to facilitate the reaction with an azide containing unnatural amino acid. Incorporating the DBCO-amine avoids the use of the cytotoxic Cu2+ ion as a catalyst. The clickable lanthanide chelator (CLC) reagent reacted readily with p-azidophenylalanine (paF) without the need of a copper catalyst, thereby demonstrating proof-of-concept. Implementation of the orthogonal click chemistry reaction has the added advantage that the chelator can be used directly in a protein labeling reaction, without the need of extensive purification. Given the inherent advantages of Cu2+-free click chemistry, aqueous synthesis, and facile labeling, we believe that the CLC will find abundant use in both structural and biophysical studies of proteins and their complexes.
Polynomial Methods in Statistical Inference: Theory and Practice

The authors of this monograph survey a suite of techniques based on the theory of polynomials, collectively referred to as polynomial methods. These techniques provide useful tools not only for the design of highly practical algorithms with provable optimality, but also for establishing the fundamental limits of inference problems through moment matching. The authors demonstrate the effectiveness of the polynomial method using concrete problems such as entropy and support size estimation, distinct elements problem, and learning Gaussian mixture models. This monograph provides a comprehensive, yet concise, overview of the theory covering topics such as polynomial approximation, polynomial interpolation and majorization, moment space and positive polynomials, orthogonal polynomials and Gaussian quadrature. The authors proceed to show the applications of the theory in statistical inference. Polynomial Methods in Statistical Inference provides students, and researchers with an accessible and complete treatment of a subject that has recently been used to solve many challenging problems in statistical inference.
Coded Computation Over Heterogeneous Clusters

In large-scale distributed computing clusters, such as Amazon EC2, there are several types of “system noise” that can result in major degradation of performance: system failures, bottlenecks due to limited communication bandwidth, latency due to straggler nodes, and so on. There have been recent results that demonstrate the impact of coding for efficient utilization of computation and storage redundancy to alleviate the effect of stragglers and communication bottlenecks in homogeneous clusters. In this paper, we focus on general heterogeneous distributed computing clusters consist of a variety of computing machines with different capabilities. We propose a coding framework for speeding up distributed computing in heterogeneous clusters by trading redundancy for reducing the latency of computation. In particular, we propose heterogeneous coded matrix multiplication (HCMM) algorithm for performing distributed matrix multiplication over heterogeneous clusters that are provably asymptotically optimal for a broad class of processing time distributions. Moreover, we show that HCMM is unboundedly faster than any uncoded scheme that partitions the total workload among the workers. To demonstrate how the proposed HCMM scheme can be applied in practice, we provide results from numerical studies and Amazon EC2 experiments comparing HCMM with three benchmark load allocation schemes—uniform uncoded, load-balanced uncoded, and uniform coded. In particular, in our numerical studies, HCMM achieves speedups of up to 73%, 56%, and 42%, respectively, over the three benchmark schemes mentioned earlier. Furthermore, we carry out experiments over Amazon EC2 clusters and demonstrate how HCMM can be combined with rateless codes with nearly linear decoding complexity. In particular, we show that HCMM combined with the Luby transform codes can significantly reduce the overall execution time. HCMM is found to be up to 61%, 46%, and 36% faster than the aforementioned three benchmark schemes, respectively. Additionally, we provide a generalization to the problem of optimal load allocation in heterogeneous settings, where we take into account the monetary costs associated with distributed computing clusters. We argue that HCMM is asymptotically optimal for budget-constrained scenarios as well. In particular, we characterize the minimum possible expected cost associated with a computation task over a given cluster of machines. Furthermore, we develop a heuristic algorithm for (HCMM) load allocation for the distributed implementation of budget-limited computation tasks.
Modulation of the Streaming Potential and Slip Characteristics in Electrolyte Flow over Liquid-Filled Surfaces.

A significant enhancement in the streaming potential (Vs) was obtained in experiments considering the flow of electrolyte over liquid-filled surfaces (LFSs), where the grooves in patterned substrates are filled with electrolyte immiscible oils. Such LFSs yield larger Vs (by a factor of 1.5) compared to superhydrophobic surfaces, with air-filled grooves, and offer tunability of electrokinetic flow. It is shown that the density, viscosity, conductivity, as well as the dielectric constant of the filling oil, in the LFS, determine Vs. Relating a hydrodynamic slip length to the obtained Vs offers insight into flow characteristics, as modulated by the liquid interfaces in the LFS.
Complete assignment of the 1H and 13C NMR Spectra of 11,12‐Dimethoxy[1]benzothieno[3,2‐a]‐4,7‐phenanthroline and its 8‐Chloro Analogue: Concerted Use of Two‐Dimensional NMR Techniques

The 1H and 13C nmr spectra of 11,12-dimethoxy[1]benzothieno[3,2-a]-4,7-phenanthroline and its 8-chloro precursor were totally assigned using a combination of two-dimensional nmr techniques. After correlation of the majority of the proton signals by a COSY spectrum and one-bond heteronuclear correlation, the full assignment of the 1H and 13C nmr spectra of the novel heterocyclic compounds required the application of long-range CH coupling information particularly for quaternary carbon resonance assignments and the orientations of individual spin systems relative to one another. Key long-range heteronuclear couplings in both compounds served to confirm the one-bond heteronuclear correlations. Unequivocal interpretation of the spectral data leads to the complete assignments of the resonances.
Are You Convinced? Choosing the More Convincing Evidence with a Siamese Network.

With the advancement in argument detection, we suggest to pay more attention to the challenging task of identifying the more convincing arguments. Machines capable of responding and interacting with humans in helpful ways have become ubiquitous. We now expect them to discuss with us the more delicate questions in our world, and they should do so armed with effective arguments. But what makes an argument more persuasive? What will convince you? In this paper, we present a new data set, IBM-EviConv, of pairs of evidence labeled for convincingness, designed to be more challenging than existing alternatives. We also propose a Siamese neural network architecture shown to outperform several baselines on both a prior convincingness data set and our own. Finally, we provide insights into our experimental results and the various kinds of argumentative value our method is capable of detecting.
Highly diastereocontrolled synthesis of the C1–C25 domain of sanglifehrin A

Abstract We report a diastereoselective synthesis of 2 containing the core structure of the entire eastern sector of sanglifehrin A. The route proceeds by directed chain extension of appropriate building blocks, their timely convergent amalgamation, and ultimate coupling to a preformed tripeptide subunit.
Inductive determination of allele frequency spectrum probabilities in structured populations

Abstract We present a method for inductively determining exact allele frequency spectrum (AFS) probabilities for samples derived from a population comprising two demes under the infinite-allele model of mutation. This method builds on a labeled coalescent argument to extend the Ewens sampling formula (ESF) to structured populations. A key departure from the panmictic case is that the AFS conditioned on the number of alleles in the sample is no longer independent of the scaled mutation rate ( θ ). In particular, biallelic site frequency spectra, widely-used in explorations of genome-wide patterns of variation, depend on the mutation rate in structured populations. Variation in the rate of substitution across loci and through time may contribute to apparent distortions of site frequency spectra exhibited by samples derived from structured populations.
Identifying conserved genomic elements and designing universal bait sets to enrich them

Summary Targeted enrichment of conserved genomic regions is a popular method for collecting large amounts of sequence data from non-model taxa for phylogenetic, phylogeographic and population genetic studies. For example, two available bait sets each allow enrichment of thousands of orthologous loci from >20 000 species (Faircloth et al. Systematic Biology, 61, 717–726, 2012; Molecular Ecology Resources, 15, 489–501, 2015). Unfortunately, few open-source workflows are available to identify conserved genomic elements shared among divergent taxa and to design enrichment baits targeting these regions. Those that do exist require extensive bioinformatics expertise and significant amounts of time to use. These shortcomings limit the application of targeted enrichment methods to additional organismal groups. Here, I describe a universal workflow for identifying conserved genomic regions in available genomic data and for designing targeted enrichment baits to collect data from these conserved regions. These methods require less expertise, less time and better use commonly available information to identify conserved loci and design baits to capture them. I apply this computational approach to the understudied arthropod groups Arachnida, Coleoptera, Diptera, Hemiptera or Lepidoptera to identify thousands of conserved loci in each group and design target enrichment baits to capture these loci. I then use in silico analyses to demonstrate that targeted enrichment of the conserved loci can be used to reconstruct the accepted relationships among genome sequences from the focal arthropod orders. The software workflow I created allowed me to identify thousands of conserved loci in five diverse arthropod groups and design sequence capture baits to target them. This suite of capture bait designs should enable collection of phylogenomic data from >900 000 arthropod species. Although the examples in this manuscript focus on understudied arthropod groups, the approach I describe is applicable to all organismal groups having some form of pre-existing genomic information (e.g. other invertebrates, plants, fungi and microbes). Finally, the documentation, design steps, software code and bait sets developed here are available under an open-source license for restriction-free testing, use, and additional modification by any research group.
The use of potassium alkynyltrifluoroborates in Mannich reactions

Abstract Potassium alkynyltrifluoroborates react with amines and salicylaldehydes in the presence of benzoic acid to generate highly functionalized amines. Ionic liquids such as butylmethylimidazolium tetrafluoroborate (BmimBF 4 ) are suitable solvents for the reaction.
High-throughput characterization of protein–protein interactions by reprogramming yeast mating

High-throughput methods for screening protein-protein interactions enable the rapid characterization of engineered binding proteins and interaction networks. While existing approaches are powerful, none allow quantitative library-on-library characterization of protein interactions in a modifiable extracellular environment. Here, we show that sexual agglutination of Saccharomyces cerevisiae can be reprogrammed to link interaction strength with mating efficiency using synthetic agglutination (SynAg). Validation of SynAg with 89 previously characterized interactions shows a log-linear relationship between mating efficiency and protein binding strength for interactions with Kds ranging from below 500 pM to above 300 μM. Using induced chromosomal translocation to pair barcodes representing binding proteins, thousands of distinct interactions can be screened in a single pot. We demonstrate the ability to characterize protein interaction networks in a modifiable environment by introducing a soluble peptide that selectively disrupts a subset of interactions in a representative network by up to 800-fold. SynAg enables the high-throughput, quantitative characterization of protein-protein interaction networks in a fully defined extracellular environment at a library-on-library scale.
Nonlinear Optical Chromophores as Nanoscale Emitters for Single-Molecule Spectroscopy

Fluorescence imaging of single molecules at room temperature is a powerful technique for studying complex condensed phase systems and revealing structure and dynamics hidden by ensemble measurements. Successful single-molecule spectroscopic experiments rely upon strong emitters that can be detected at the level of individual copies above the relevant background signals. This Account discusses a class of nonlinear optical chromophores that not only are well-suited for single-molecule imaging but also offer additional beneficial properties such as a significant ground-state dipole moment, moderate hyperpolarizability, and sensitivity to local environment. An overview of the photophysical properties of several members of this class of molecules as well as a mechanism to help understand the environmental sensitivity is presented. Some preliminary applications of the chromophores as single-molecule reporters in cellular and polymer systems are discussed, along with detection of the emitters by two-photon fluorescence.
Charmonium Production in Fermilab E789

Using a sample of > 105 J/ψ → μ+ μ- decays, Fermilab experiment 789 has studied production of J/ψ and ψ′ in 800 GeV proton-nucleon collisions. Differential cross sections and nuclear dependences have been measured for charmonium as well as for charm and beauty production. While charm and beauty production are consistent with perturbative QCD calculations, charmonium cross sections exceed the predictions of the color-singlet model by large factors, suggesting that additional mechanisms (such as color-octet production) may play important roles. Nuclear dependences of production cross sections may offer a new tool for the detailed understanding of charmonium production.
Vinylation of aryl bromides using an inexpensive vinylpolysiloxane.

A mild and general method for the palladium-catalyzed vinylation of aryl bromides has been developed. The use of tetrabutylammonium fluoride (TBAF) as the activator and an inexpensive and nontoxic vinyl donor, 1,3,5,7-tetramethyl-1,3,5,7-tetravinylcyclotetrasiloxane (D4V, 1), allows for a general and high-yielding preparation of substituted styrenes.
Predicting enhancer-promoter interaction from genomic sequence with deep neural networks

In the human genome, distal enhancers are involved in regulating target genes through proximal promoters by forming enhancer-promoter interactions. Although recently developed high-throughput experimental approaches have allowed us to recognize potential enhancer-promoter interactions genome-wide, it is still largely unclear to what extent the sequence-level information encoded in our genome help guide such interactions. Here we report a new computational method (named “SPEID”) using deep learning models to predict enhancer-promoter interactions based on sequence-based features only, when the locations of putative enhancers and promoters in a particular cell type are given. Our results across six different cell types demonstrate that SPEID is effective in predicting enhancer-promoter interactions as compared to state-of-the-art methods that only use information from a single cell type. As a proof-of-principle, we also applied SPEID to identify somatic non-coding mutations in melanoma samples that may have reduced enhancer-promoter interactions in tumor genomes. This work demonstrates that deep learning models can help reveal that sequence-based features alone are sufficient to reliably predict enhancer-promoter interactions genome-wide.
Processing of auditory novelty across the cortical hierarchy: An intracranial electrophysiology study.

Abstract Under the predictive coding hypothesis, specific spatiotemporal patterns of cortical activation are postulated to occur during sensory processing as expectations generate feedback predictions and prediction errors generate feedforward signals. Establishing experimental evidence for this information flow within cortical hierarchy has been difficult, especially in humans, due to spatial and temporal limitations of non-invasive measures of cortical activity. This study investigated cortical responses to auditory novelty using the local/global deviant paradigm, which engages the hierarchical network underlying auditory predictive coding over short (‘local deviance’; LD) and long (‘global deviance’; GD) time scales. Electrocorticographic responses to auditory stimuli were obtained in neurosurgical patients from regions of interest (ROIs) including auditory, auditory-related and prefrontal cortex. LD and GD effects were assayed in averaged evoked potential (AEP) and high gamma (70–150 Hz) signals, the former likely dominated by local synaptic currents and the latter largely reflecting local spiking activity. AEP LD effects were distributed across all ROIs, with greatest percentage of significant sites in core and non-core auditory cortex. High gamma LD effects were localized primarily to auditory cortex in the superior temporal plane and on the lateral surface of the superior temporal gyrus (STG). LD effects exhibited progressively longer latencies in core, non-core, auditory-related and prefrontal cortices, consistent with feedforward signaling. The spatial distribution of AEP GD effects overlapped that of LD effects, but high gamma GD effects were more restricted to non-core areas. High gamma GD effects had shortest latencies in STG and preceded AEP GD effects in most ROIs. This latency profile, along with the paucity of high gamma GD effects in the superior temporal plane, suggest that the STG plays a prominent role in initiating novelty detection signals over long time scales. Thus, the data demonstrate distinct patterns of information flow in human cortex associated with auditory novelty detection over multiple time scales.
Rps3/uS3 promotes mRNA binding at the 40S ribosome entry channel and stabilizes preinitiation complexes at start codons.

The eukaryotic 43S preinitiation complex (PIC) bearing Met-tRNAiMet in a ternary complex (TC) with eukaryotic initiation factor (eIF)2-GTP scans the mRNA leader for an AUG codon in favorable “Kozak” context. AUG recognition provokes rearrangement from an open PIC conformation with TC bound in a state not fully engaged with the P site (“POUT”) to a closed, arrested conformation with TC tightly bound in the “PIN” state. Yeast ribosomal protein Rps3/uS3 resides in the mRNA entry channel of the 40S subunit and contacts mRNA via conserved residues whose functional importance was unknown. We show that substitutions of these residues reduce bulk translation initiation and diminish initiation at near-cognate UUG start codons in yeast mutants in which UUG selection is abnormally high. Two such substitutions—R116D and R117D—also increase discrimination against an AUG codon in suboptimal Kozak context. Consistently, the Arg116 and Arg117 substitutions destabilize TC binding to 48S PICs reconstituted in vitro with mRNA harboring a UUG start codon, indicating destabilization of the closed PIN state with a UUG–anticodon mismatch. Using model mRNAs lacking contacts with either the mRNA entry or exit channels of the 40S subunit, we demonstrate that Arg116/Arg117 are crucial for stabilizing PIC–mRNA contacts at the entry channel, augmenting the function of eIF3 at both entry and exit channels. The corresponding residues in bacterial uS3 promote the helicase activity of the elongating ribosome, suggesting that uS3 contacts with mRNA enhance multiple phases of translation across different domains of life.
Synthesis of the Enantiomeric Furobenzofurans, Late Precursors for the Synthesis of (+)- and (-)-Aflatoxins B1, B2, G1, and G2

Enantiomeric tetrahydrofuro[2,3-b]benzofurans, representing the ABC tricyclic portion of aflatoxins B 1 , B 2 , G 1 , and G 2 , were generated from the oxaza-Cope rearrangement of a suitably functionalized O-aryl- oxime. The O-aryloxime was, in turn, made from the condensation of an enantiomerically pure aldehyde derived from glutamic acid and a substi- tuted phenoxyamine. High regioselectivity with respect to the A-ring substituents of the ABC tricycle was achieved through the use of elec- trochemistry. The regioselective electrochemical cleavage of 4,6-bis (tosyloxy)-2-(methoxycarbonyl)-2,3,3a,8a-tetrahydrofuro[2,3-b]benzofuran (22) resulted in a 97/3 mixture of regioisomeric phenols. The regio- chemical assignements of the resulting phenols were determined by 2D NOESY NMR. The enantiomeric ratio of the final product was determined to be 96/4 by NMR analysis of diastereomers resulting from the coupling of (31a) to (+)- and (±)phenethylamine
Room temperature Ni-catalyzed reduction of aryl tosylates by borane hydrides

Abstract Mild Ni-catalyzed homogeneous reductions of aryl tosylates are described for the first time. The catalytic system Ni(PPh3)2Cl2 and PCy3 is shown to be general for hydrogenolysis of a wide range of tosylates, including hindered, deactivated, heterocyclic, and bifunctional examples.
The Arabidopsis kinesin-4, FRA1, requires a high level of processive motility to function correctly

Processivity is important for kinesins that mediate intracellular transport. Structure-function analyses of N-terminal kinesins (i.e. kinesins comprising their motor domains at the N-terminus) have identified several non-motor regions that affect processivity in vitro However, whether these structural elements affect kinesin processivity and function in vivo is not known. Here, we used an Arabidopsis thaliana kinesin-4, called Fragile Fiber 1 (FRA1, also known as KIN4A), which is thought to mediate vesicle transport, to test whether mutations that alter processivity in vitro lead to similar changes in behavior in vivo and whether processivity is important for the function of FRA1. We generated several FRA1 mutants that differed in their 'run lengths' in vitro and then transformed them into the fra1-5 mutant for complementation and in vivo motility analyses. Our data show that the behavior of processivity mutants in vivo can differ dramatically from in vitro properties, underscoring the need to extend structure-function analyses of kinesins in vivo In addition, we found that a high density of processive motility is necessary for the physiological function of FRA1.
Genomic loci modulating retinal ganglion cell death following elevated IOP in the mouse.

The present study was designed to identify genomic loci modulating the susceptibility of retinal ganglion cells (RGC) to elevated intraocular pressure (IOP) in the BXD recombinant inbred mouse strain set. IOP was elevated by injecting magnetic microspheres into the anterior chamber and blocking the trabecular meshwork using a handheld magnet to impede drainage. The IOP was then measured over the next 21 days. Only animals with IOP greater than 25 mmHg for two consecutive days or an IOP above 30 mmHg on a single day after microsphere-injection were used in this study. On day 21, mice were sacrificed and the optic nerve was processed for histology. Axons were counted for both the injected and the control eye in 49 BXD strains, totaling 181 normal counts and 191 counts associated with elevated IOP. The axon loss for each strain was calculated and the data were entered into genenetwork.org. The average number of normal axons in the optic nerve across all strains was 54,788 ± 16% (SD), which dropped to 49,545 ± 20% in animals with artificially elevated IOP. Interval mapping demonstrated a relatively similar genome-wide map for both conditions with a suggestive Quantitative Trait Locus (QTL) on proximal Chromosome 3. When the relative axon loss was used to generate a genome-wide interval map, we identified one significant QTL (p < 0.05) on Chromosome 18 between 53.6 and 57 Mb. Within this region, the best candidate gene for modulating axon loss was Aldh7a1. Immunohistochemistry demonstrated ALDH7A1 expression in mouse RGCs. ALDH7A1 variants were not significantly associated with glaucoma in the NEIGHBORHOOD GWAS dataset, but this enzyme was identified as part of the butanoate pathway previously associated with glaucoma risk. Our results suggest that genomic background influences susceptibility to RGC degeneration and death in an inducible glaucoma model.
Macrocyclic ligands for Fe(II) paraCEST and chemical shift MRI contrast agents

Abstract Fe(II) macrocyclic complexes are a relatively new addition to the class of MRI contrast agents that function through paraCEST (paramagnetic chemical exchange saturation transfer) or paraCSI (paramagnetic complex chemical shift imaging). Both methods require relatively narrow and highly shifted ligand proton resonances. For paraCEST, the protons are exchangeable with water (NH or OH); for paraCSI the protons are non-exchangeable and are on carbons (CH). We report on several macrocyclic ligands for Fe(II) including those based on CYCLEN (1,4,7,10-tetraazacyclododecane) and TACN (1,4,7-triazacyclononane) with attached pendent arms containing either benzimidazole, pyridine or amide donor groups. Paramagnetic proton NMR spectra and paraCEST spectra are reported for these complexes. Challenges include fluxionality of the macrocyclic complexes in solution which broadens the macrocycle proton resonances, especially for amide pendent groups. Despite this dynamic process, the exchangeable NH proton resonances of the amide pendent groups remain relatively sharp. These amide complexes are thus suitable for paraCEST but not paraCSI. The dynamic process is arrested in complexes containing pendent pyridine groups that lock the TACN macrocyclic Fe(II) complex into a single diastereomeric form over the temperature range of 15–45 °C to produce an Fe(II) complex that is promising for paraCSI.
The Squarate Ester−Polyquinane Connection. An Analysis of the Capacity of Achiral Divinyl Adducts To Rearrange Spontaneously to Polycyclic Networks Housing Multiple Stereogenic Centers

The condensation of diisopropyl squarate and related cyclobutene-1,2-diones with 2 equiv of the same alkenyl anion or 1 equiv each of two different alkenyl anions can be a very effective method for...
High-Temperature Synthesis of Two New Aluminophosphates, NaRb2Al2(PO4)3 and NaCs2Al(PO4)2, in Molten Alkali Metal Chloride Media

Two new aluminophosphate (AlPO) phases have been isolated via conventional solid-state reactions employing molten alkali metal chloride salts. Their structures have been determined by single-crystal X-ray diffraction methods. Crystal data: NaRb2Al2(PO4)3 1, P21/c (no. 14), a = 4.849(2) A, b = 8.216(2) A, c = 28.317(3) A, β = 90.52(2)°, and Z = 4; NaCs2Al(PO4)2 2, P21/c (no. 14), a = 10.992(2) A, b = 9.192(2) A, c = 18.998(2) A, β = 90.35(1)°, and Z = 8. 1 adopts a new structure type that contains puckered slabs of vertex-sharing AlO4, AlO5, and PO4 polyhedral units. The slab structure is made of interlinked [Al2P3O16] structural units resulting in a new 4 × 6 × 8 network of alternating Al3+ and P5+ cations. It exhibits a unique Al3P2 trigonal bipyramidal chain of fused butterfly-like Al2P3 units. 2 represents a new three-dimensional compound of the Al(PO4)23- type that consists of alternating, vertex-sharing AlO4 and PO4 units. The framework possesses a helical structure embracing around the mixed Na+ an...
WindSTORM: Robust online image processing for high-throughput nanoscopy

High-throughput nanoscopy becomes increasingly important for unraveling complex biological processes from a large heterogeneous cell population at a nanoscale resolution. High-density emitter localization combined with a large field of view and fast imaging frame rate is commonly used to achieve a high imaging throughput, but the image processing speed and the presence of heterogeneous background in the dense emitter scenario remain a bottleneck. Here, we present a simple non-iterative approach, referred to as WindSTORM, to achieve high-speed high-density emitter localization with robust performance for various image characteristics. We demonstrate that WindSTORM improves the computation speed by two orders of magnitude on CPU and three orders of magnitude upon GPU acceleration to realize online image processing, without compromising localization accuracy. Further, WindSTORM is highly robust to maximize the localization accuracy and minimize the image artifacts in the presence of nonuniform background. WindSTORM paves the way for next generation high-throughput nanoscopy.
Copper-catalyzed C–N coupling of amides and nitrogen-containing heterocycles in the presence of cesium fluoride

Abstract The copper-catalyzed C–N coupling of amides to aryl halides usually requires the use of strong alkali metal bases, such as K2CO3, K3PO4, and Cs2CO3, at high temperature. We discovered that CsF is sufficiently basic to promote the cross-coupling of amides and carbamates with aryl halides. Most aryl iodides coupled in high yield at room temperature. This alternative base may be a suitable replacement for substrates that are incompatible with high temperature and strongly basic conditions and can further enhance the chemoselectivity of this reaction.
Cu(II) 2-quinoxalinol salen catalyzed oxidation of propargylic, benzylic, and allylic alcohols using tert-butyl hydroperoxide in aqueous solutions

Abstract The synthesis of carbonyl compounds by oxidation of alcohols is a key reaction in organic synthesis. Such oxidations are typically conducted using catalysts featuring toxic metals and hazardous organic solvents. Considering green and sustainable chemistry, a copper(II) complex of sulfonated 2-quinoxalinol salen (sulfosalqu) has been characterized as an efficient catalyst for the selective oxidation of propargylic, benzylic, and allylic alcohols to the corresponding carbonyl compounds in water when in combination with the oxidant tert-butyl hydroperoxide. The reactions proceed under mild conditions (70 °C in water) to produce yields up to 99% with only 1 mol % of catalyst loading. This reaction constitutes of a rare example of propargylic alcohol oxidation in water, and it makes this process greener by eliminating the use of hazardous organic solvents. Excellent selectivity was achieved with this catalytic protocol for the oxidation of propargylic, benzylic, and allylic alcohols over aliphatic alcohols. The alcohol oxidation is thought to go through a radical pathway.
An Average-Case Sublinear Exact Li and Stephens Forward Algorithm

Hidden Markov models of haplotype inheritance such as the Li and Stephens model allow for computationally tractable probability calculations using the forward algorithms as long as the representative reference panel used in the model is sufficiently small. Specifically, the monoploid Li and Stephens model and its variants are linear in reference panel size unless heuristic approximations are used. However, sequencing projects numbering in the thousands to hundreds of thousands of individuals are underway, and others numbering in the millions are anticipated. To make the Li and Stephens forward algorithm for these datasets computationally tractable, we have created a numerically exact version of the algorithm with observed average case O(nk^{0.35}) runtime in number of genetic sites n and reference panel size k. This avoids any tradeoff between runtime and model complexity. We demonstrate that our approach also provides a succinct data structure for general purpose haplotype data storage. We discuss generalizations of our algorithmic techniques to other hidden Markov models.
Glucopyranosides derived from 6-aryl-5-cyano-2-(methylthio)pyrimidin-4(3H)ones.

ABSTRACT The reaction of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide with a 6-aryl-5-cyano-2-(methylthio)pyrimidin-4(3H)one in aqueous acetone in the presence of KOH furnishes a 4-(β-D-glucopyranosyloxy)pyrimidine and a 3-(β-D-glucopyranosyl)pyrimidine as the major and minor product, respectively.
Engineering a Decoy Substrate in Soybean to Enable Recognition of the Soybean Mosaic Virus NIa Protease

In Arabidopsis, recognition of the AvrPphB effector protease from Pseudomonas syringae is mediated by the disease resistance (R) protein RPS5, which is activated by AvrPphB-induced cleavage of the Arabidopsis protein kinase PBS1. The recognition specificity of RPS5 can be altered by substituting the AvrPphB cleavage site within PBS1 with cleavage sequences for other proteases, including proteases from viruses. AvrPphB also activates defense responses in soybean (Glycine max), suggesting that soybean may contain an R protein analogous to RPS5. It was unknown, however, whether this response is mediated by cleavage of a soybean PBS1-like protein. Here, we show that soybean contains three PBS1 orthologs and that their products are cleaved by AvrPphB. Further, transient expression of soybean PBS1 derivatives containing a five-alanine insertion at their AvrPphB cleavage sites activated cell death in soybean protoplasts, demonstrating that soybean likely contains an AvrPphB-specific resistance protein that is activated by a conformational change in soybean PBS1 proteins. Significantly, we show that a soybean PBS1 decoy protein modified to contain a cleavage site for the soybean mosaic virus (SMV) NIa protease triggers cell death in soybean protoplasts when cleaved by this protease, indicating that the PBS1 decoy approach will work in soybean, using endogenous PBS1 genes. Lastly, we show that activation of the AvrPphB-dependent cell death response effectively inhibits systemic spread of SMV in soybean. These data also indicate that decoy engineering may be feasible in other crop plant species that recognize AvrPphB protease activity.
Synthesis of functional bisphosphonates via new palladium-catalyzed bis-hydrophosphorylation reactions

Abstract A series of functional bisphosphonates have been synthesized in good isolated yields via new palladium-catalyzed bis-hydrophosphorylation reactions of terminal alkynes and dialkyl phosphites. The scope and mechanism for such a bis-hydrophosphorylation process are also discussed.