cssi/SciSciGPT-SciSciNet huggingface dataset:
Allele-Specific Quantification of Structural Variations in Cancer Genomes.

One of the hallmarks of cancer genome is aneuploidy, resulting in abnormal copy numbers of alleles. Structural variations (SVs) can further modify the aneuploid cancer genomes into a mixture of rearranged genomic segments with extensive range of somatic copy number alterations (CNAs). Indeed, aneuploid cancer genomes have significantly higher rate of CNAs and SVs. However, although methods have been developed to identify SVs and allele-specific copy number of genome (ASCNG) separately, no existing algorithm can simultaneously analyze SVs and ASCNG. Such integrated approach is particularly important to fully understand the complexity of cancer genomes. Here we introduce a new algorithm called Weaver to provide allele-specific quantification of SVs and CNAs in aneuploid cancer genomes. Weaver uses a probabilistic graphical model by utilizing cancer whole genome sequencing data to simultaneously estimate the digital copy number and inter-connectivity of SVs. Our simulation evaluation, comparison with single-molecule Optical Mapping analysis, and real data applications (including MCF-7, HeLa, and TCGA whole genome sequencing samples) demonstrated that Weaver is highly accurate and can greatly refine the analysis of complex cancer genome structure.
Predictions for the First Parker Solar Probe Encounter

We examine Alfven Wave Solar atmosphere Model (AWSoM) predictions of the first Parker Solar Probe (PSP) encounter. We focus on the 12 day closest approach centered on the first perihelion. AWSoM allows us to interpret the PSP data in the context of coronal heating via Alfven wave turbulence. The coronal heating and acceleration is addressed via outward-propagating low-frequency Alfven waves that are partially reflected by Alfven speed gradients. The nonlinear interaction of these counter-propagating waves results in a turbulent energy cascade. To apportion the wave dissipation to the electron and anisotropic proton temperatures, we employ the results of the theories of linear wave damping and nonlinear stochastic heating as described by Chandran et al. We find that during the first encounter, PSP was in close proximity to the heliospheric current sheet (HCS) and in the slow wind. PSP crossed the HCS two times, at 2018 November 3 UT 01:02 and 2018 November 8 UT 19:09, with perihelion occurring on the south of side of the HCS. We predict the plasma state along the PSP trajectory, which shows a dominant proton parallel temperature causing the plasma to be firehose unstable.
Shared Neural Correlates Underlying Addictive Disorders and Negative Urgency

Negative urgency is a personality trait reflecting the tendency to act rashly in response to extreme negative emotions and is considered a transdiagnostic endophenotype for problematic levels of addictive behaviors. Recent research has begun to identify the neural correlates of negative urgency, many of which appear to overlap with neural circuitry underlying addictive disorders associated with negative urgency. The goal of this qualitative review is to summarize the extant literature concerning the neural correlates of negative urgency, to compare these correlates with those implicated with addictive disorders, and to propose new ways to begin to leverage such findings in treatment and intervention approaches. We also address current limitations in the field and make recommendations for areas for future growth in this research domain. Patterns of structure and function in the ventral striatum, frontal regions, such as the prefrontal cortex (PFC) and orbitofrontal cortex (OFC), and amygdala are common across addictive disorders and are related to both real-world risky behaviors and self-report measures of negative urgency. We propose that the time has come to move past considering this trait and these disorders as completely separate entities, and instead for the field to consider how general patterns of convergence across these disorders can lead to a more transdiagnostic approach to treatment and intervention. We suggest future work utilize these convergent patterns in the development of animal models of negative urgency, in the identification and testing of prime pharmacological and physiological interventions, and as objective biomarkers to be used when testing behavioral, pharmacological, and physiological intervention effectiveness. Little empirical work has been done to date in these areas and advances in these nascent fields would advance understanding and applications of the neuroscience of negative urgency.
A composite neural network that learns from multi-fidelity data: Application to function approximation and inverse PDE problems

Abstract Currently the training of neural networks relies on data of comparable accuracy but in real applications only a very small set of high-fidelity data is available while inexpensive lower fidelity data may be plentiful. We propose a new composite neural network (NN) that can be trained based on multi-fidelity data. It is comprised of three NNs, with the first NN trained using the low-fidelity data and coupled to two high-fidelity NNs, one with activation functions and another one without, in order to discover and exploit nonlinear and linear correlations, respectively, between the low-fidelity and the high-fidelity data. We first demonstrate the accuracy of the new multi-fidelity NN for approximating some standard benchmark functions but also a 20-dimensional function that is not easy to approximate with other methods, e.g. Gaussian process regression. Subsequently, we extend the recently developed physics-informed neural networks (PINNs) to be trained with multi-fidelity data sets (MPINNs). MPINNs contain four fully-connected neural networks, where the first one approximates the low-fidelity data, while the second and third construct the correlation between the low- and high-fidelity data and produce the multi-fidelity approximation, which is then used in the last NN that encodes the partial differential equations (PDEs). Specifically, by decomposing the correlation into a linear and nonlinear part, the present model is capable of learning both the linear and complex nonlinear correlations between the low- and high-fidelity data adaptively. By training the MPINNs, we can: (1) obtain the correlation between the low- and high-fidelity data, (2) infer the quantities of interest based on a few scattered data, and (3) identify the unknown parameters in the PDEs. In particular, we employ the MPINNs to learn the hydraulic conductivity field for unsaturated flows as well as the reactive models for reactive transport. The results demonstrate that MPINNs can achieve relatively high accuracy based on a very small set of high-fidelity data. Despite the relatively low dimension and limited number of fidelities (two-fidelity levels) for the benchmark problems in the present study, the proposed model can be readily extended to very high-dimensional regression and classification problems involving multi-fidelity data.
Rationality and Capitalist Schooling

Abstract. In the field of philosophy of mind, the concepts of rational behavior, rational choice theory, and instrumental rationality (the “practical reasoning” version of rationality) are important in trying to make statements and conclusions about human thinking and behavior in general. Rational choice theory is also considered a normative but not a descriptive or positive theory. Much of economic theory is based on the principle that economic agents usually or always behave rationally in maximizing the benefits and/or minimizing the costs of their decisions. Developments in behavioral economics over the last several decades have begun to question this principle with much of the questioning about rationality and rational behavior centering on whether individuals can correctly and adequately assess probabilities and risk/reward. The inability to correctly assess risk/reward limits rational behavior and can yield sub-optimal outcomes for economic agents. This exploratory paper examines the linkages between schooling in a capitalist society and limits on rationality in a monopoly capital economic system. Keywords. Behavioral economics, Capitalist schooling, Monopoly capital, Rationality, Rational choice. JEL. B51, I24.
Warden Procedure in a 77-Year-Old Man

Partial anomalous pulmonary venous return is a rare congenital heart defect characterized by 1 or more but not all of the pulmonary veins draining somewhere other than the left atrium, thereby creating a left-to-right shunt. Over time, right-sided volume overload may develop with its subsequent complications. We present a case of isolated partial anomalous pulmonary venous return in an older patient who underwent a Warden procedure at age 77 years, with rapid improvement in right ventricular size and function.
Wet Etching of Ion-implanted GaN Crystals by AZ-400K Photoresist

The photoresist developer AZ-400K, commonly used to remove AlN encapsulant layers on GaN crystalline films, is found to also etch certain as-grown GaN films. Even as-grown GaN films, which can not be etched in AZ-400K, however can be etched if amorphized by ion implantation. Etch rates of as high as 450 A/min. were observed. The etching proceeds linearly in GaN in the first few minutes to a depth corresponding to the depth of the amorphous region. Subsequently, the etching rate saturates. Annealing of the highly amorphized samples up to 1000°C for one minute in a N2/H2 gas mixture does not reduce the etch rate, but for lower doses we observed a reduction of the etch rate. Observations of etching depth under various ion-implanted conditions could be correlated with the number of displacements per atoms (dpa) required for amorphization.
Genetic Screen in Chlamydia muridarum Reveals Role for an Interferon-Induced Host Cell Death Program in Antimicrobial Inclusion Rupture

ABSTRACT Interferon-regulated immune defenses protect mammals from pathogenically diverse obligate intracellular bacterial pathogens of the genus Chlamydia. Interferon gamma (IFN-γ) is especially important in controlling the virulence of Chlamydia species and thus impacts the modeling of human chlamydial infection and disease in mice. How IFN-γ contributes to cell-autonomous defenses against Chlamydia species and how these pathogens evade IFN-γ-mediated immunity in their natural hosts are not well understood. We conducted a genetic screen which identified 31 IFN-γ-sensitive (Igs) mutants of the mouse model pathogen Chlamydia muridarum. Genetic suppressor analysis and lateral gene transfer were used to map the phenotype of one of these mutants, Igs4, to a missense mutation in a putative chlamydial inclusion membrane protein, TC0574. We observed the lytic destruction of Igs4-occupied inclusions and accompanying host cell death in response to IFN-γ priming or various proapoptotic stimuli. However, Igs4 was insensitive to IFN-γ-regulated cell-autonomous defenses previously implicated in anti-Chlamydia trachomatis host defense in mice. Igs4 inclusion integrity was restored by caspase inhibitors, indicating that the IFN-γ-mediated destruction of Igs4 inclusions is dependent upon the function of caspases or related prodeath cysteine proteases. We further demonstrated that the Igs4 mutant is immune restricted in an IFN-γ-dependent manner in a mouse infection model, thereby implicating IFN-γ-mediated inclusion destruction and host cell death as potent in vivo host defense mechanisms to which wild-type C. muridarum is resistant. Overall, our results suggest that C. muridarum evolved resistance mechanisms to counter IFN-γ-elicited programmed cell death and the associated destruction of intravacuolar pathogens. IMPORTANCE Multiple obligatory intracellular bacteria in the genus Chlamydia are important pathogens. In humans, strains of C. trachomatis cause trachoma, chlamydia, and lymphogranuloma venereum. These diseases are all associated with extended courses of infection and reinfection that likely reflect the ability of chlamydiae to evade various aspects of host immune responses. Interferon-stimulated genes, driven in part by the cytokine interferon gamma, restrict the host range of various Chlamydia species, but how these pathogens evade interferon-stimulated genes in their definitive host is poorly understood. Various Chlamydia species can inhibit death of their host cells and may have evolved this strategy to evade prodeath signals elicited by host immune responses. We present evidence that chlamydia-induced programmed cell death resistance evolved to counter interferon- and immune-mediated killing of Chlamydia-infected cells.
Risk and outcomes of second malignant neoplasms in chronic myeloid leukemia survivors.

Abstract The risk of second malignant neoplasms (SMN) in chronic myeloid leukemia (CML) survivors remains unclear. We utilized the Surveillance, Epidemiology and End Results 18 (SEER 18) registries to evaluate the risk and subsequent outcomes of SMN in CML survivors. There were 3407 patients included. Of these, 170 (4.99%) developed a SMN with SIR of 1.40 (95% C.I. 1.19–1.62). An increased risk was noted for cancers of the respiratory tract, genitourinary (GU) tract and skin excluding basal cell and squamous cell carcinoma. Using 3:1 matching (3 de novo malignancies to 1 post-CML SMN case), we compared survival data for cancers of the respiratory, GU and gastrointestinal (GI) tract. Patients with GU malignancies developing after CML had worse overall survival than patients without prior CML diagnosis (P = 0.018). There was no difference in survival between post-CML and non-post-CML patients with respiratory or GI malignancies.
On Separating Points by Lines

Given a set $$P$$ of n points in the plane, its separability is the minimum number of lines needed to separate all its pairs of points from each other, denoted by $$\mathrm {sep}\left( {P}\right) $$. We show that the minimum number of lines needed to separate n points, picked randomly (and uniformly) in the unit square, is $$\Bigl .{\widetilde{\Theta }}( n^{2/3})$$, where $${\widetilde{\Theta }}$$ hides polylogarithmic factors. In addition, we provide a fast $$O(\log (\mathrm {sep}\left( {P}\right) ))$$-approximation algorithm for computing the separability of a given point set in the plane. Finally, we point out the connection between separability and partitions.
Lower Limb Rigidity Is Associated with Frequent Falls in Parkinson's Disease.

Background and objective The role of muscle rigidity as an etiological factor of falls in Parkinson's disease (PD) is poorly understood. Our objective was to determine whether lower leg rigidity was differentially associated with frequent falls in PD compared to upper limb, neck, and total rigidity measures. Methods We examined the associations between Unified Parkinson's Disease Rating Scale-Part III (motor) rigidity subscores and the history of monthly or more frequent falls in 216 individuals with PD (age, 66 ± 10 years; 36% female; disease duration, 7 ± 5 years) with logistic regression. Results A total of 35 individuals were frequent fallers. Significant associations were identified between lower limb rigidity and frequent falls (P = 0.01) after controlling for age, sex, PD duration, total Unified Parkinson's Disease Rating Scale- Part III score, and presence of freezing of gait. No significant associations (P ≥ 0.14) were identified for total, arm, or neck rigidity. Conclusion Lower limb rigidity is related to frequent falls in people with PD. Further investigation may be warranted into how parkinsonian rigidity could cause falls.
Morphological and transcriptomic evidence for ammonium induction of sexual reproduction in Thalassiosira pseudonana and other centric diatoms

The reproductive strategy of diatoms includes asexual and sexual phases, but in many species, including the model centric diatom Thalassiosira pseudonana, sexual reproduction has never been observed. Furthermore, the environmental factors that trigger sexual reproduction in diatoms are not understood. Although genome sequences of a few diatoms are available, little is known about the molecular basis for sexual reproduction. Here we show that ammonium reliably induces the key sexual morphologies, including oogonia, auxospores, and spermatogonia, in two strains of T. pseudonana, T. weissflogii, and Cyclotella cryptica. RNA sequencing revealed 1,274 genes whose expression patterns changed when T. pseudonana was induced into sexual reproduction by ammonium. Some of the induced genes are linked to meiosis or encode flagellar structures of heterokont and cryptophyte algae. The identification of ammonium as an environmental trigger suggests an unexpected link between diatom bloom dynamics and strategies for enhancing population genetic diversity.
Microwave Heating Effects Rapid and Selective Decarboalkoxylation of Mono-Alkylated Malonates and β-Ketoesters

Brief microwave irradiation of mono-alkylated malonates and β-ketoesters at 160-200 °C in wet DMF induces smooth and selective decarboalkoxylation. Observations suggest that this reaction occurs by nucleophilic attack of water at the ester carbonyl carbon (hydrolysis) followed by decarboxylation of the resulting acid. The process occurs despite the absence of traditional acid, base or nucleophile catalysts or reagents.
Total synthesis of the porphyrin mineral abelsonite and related petroporphyrins with five-membered exocyclic rings ☆

A reliable synthesis of porphyrins with five-membered exocyclic rings from b-bilenes has been developed. This methodology has been applied to the first total synthesis of the porphyrin mineral abelsonite, as well as the widespread petroporphyrin deoxophylloerythroetioporphyrin (DPEP) and its 3-desethyl analogue.
Load Balancing Guardrails: Keeping Your Heavy Traffic on the Road to Low Response Times

Load balancing systems, comprising a central dispatcher and a scheduling policy at each server, are widely used in practice, and their response time has been extensively studied in the theoretical literature. While much is known about the scenario where the scheduling at the servers is First-Come-First-Served (FCFS), to minimize mean response time we must use Shortest-Remaining-Processing-Time (SRPT) scheduling at the servers. Much less is known about dispatching polices when SRPT scheduling is used. Unfortunately, traditional dispatching policies that are used in practice in systems with FCFS servers often have poor performance in systems with SRPT servers. In this paper, we devise a simple fix that can be applied to any dispatching policy. This fix, called guardrails, ensures that the dispatching policy yields optimal mean response time under heavy traffic when used in a system with SRPT servers. Any dispatching policy, when augmented with guardrails, becomes heavy-traffic optimal. Our results yield the first analytical bounds on mean response time for load balancing systems with SRPT scheduling at the servers.
Concise Formal Synthesis of Porothramycins A and B via Zincke Pyridinium Ring-Opening/Ring-Closing Cascade

Short formal syntheses of the antitumor antibiotics porothramycins A and B from a commercially available ester of the unnatural amino acid 3-(3-pyridyl)alanine are presented. A rearrangement cascade that presumably involves a Zincke-type pyridinium ring-opening followed by cyclization of a pendant nucleophilic amide generates the salient pyrroline ring of the alkaloids.
A built‐in route leading to a self‐inclusion complex of 6A,6B‐(bis‐O‐p‐allyloxyphenyl)hexakis(2,3‐di‐O‐methyl)‐α‐cyclodextrin

Hexakis(2,3-di-O-methyl)-α-cyclodextrin was treated with 2,4-dimethoxybenzene-1,5-disulfonyl chloride to give 6A,6B-di-O-sulfonated product 5 in only a 3.0% yield. When treated with sodium p-allyloxyphenoxide, 5 gave 6A,6B-(bis-O-p-allyloxyphenyl)hexakis(2,3-di-O-methyl)-α-cyclodextrin (6) in a 57% yield. A careful 1H nmr analysis of 6 shows that one of the allyloxphenyl groups is in the α-cyclodextrin cavity. This is the first intramolecular complex formed from a modified α-cyclodextrin. Molecular modeling was used to explain the experimental facts. A novel built-in route leading to a self-inclusion α-cyclodextrin complex is proposed for this reaction.
Catalytic Tandem Markovnikov Hydroamination–Alkynylation and Markovnikov Hydroamination–Hydrovinylation

A tandem hydroamination–alkynylation was developed as a unique mode of accessing tetrasubstituted propargylic amines. The first equivalent of an alkyne acts as the electrophile in a Markovnikov hydroamination. The resultant ketimine intermediate is attacked by the second equivalent of alkyne in its nucleophilic copper acetylide form. Studies on the role of each component indicate that the overall reaction is first-order in copper, amine, and alkyne. In addition, a tandem hydroamination–hydrovinylation provides for an unprecedented one-step synthesis of a 1-amino-1,3-butadiene from phenylacetylene and morpholine.
Modulation of Ether-à-Go-Go Related Gene (ERG) Current Governs Intrinsic Persistent Activity in Rodent Neocortical Pyramidal Cells

While cholinergic receptor activation has long been known to dramatically enhance the excitability of cortical neurons, the cellular mechanisms responsible for this effect are not well understood. We used intracellular recordings in rat (both sexes) neocortical brain slices to assess the ionic mechanisms supporting persistent firing modes triggered by depolarizing stimuli following cholinergic receptor activation. We found multiple lines of evidence suggesting that a component of the underlying hyperexcitability associated with persistent firing reflects a reduction in the standing (leak) K+ current mediated by Ether-a-go-go-Related Gene (ERG) channels. Three chemically diverse ERG channel blockers (terfenadine, ErgToxin-1, and E-4031) abolished persistent firing and the underlying increase in input resistance in deep pyramidal cells in temporal and prefrontal association neocortex. Calcium accumulation during triggering stimuli appears to attenuate ERG currents, leading to membrane potential depolarization and increased input resistance, two critical elements generating persistent firing. Our results also suggest that ERG current normally governs cortical neuron responses to depolarizing stimuli by opposing prolonged discharges and by enhancing the poststimulus repolarization. The broad expression of ERG channels and the ability of ERG blocks to abolish persistent firing evoked by both synaptic and intracellular step stimuli suggest that modulation of ERG channels may underlie many forms of persistent activity observed in vivoSIGNIFICANCE STATEMENT Persistent activity, where spiking continues beyond the triggering stimulus, is a common phenomenon observed in many types of neurons. Identifying the mechanism underlying this elementary process of memory is a step forward in understanding higher cognitive function including short-term memory. Our results suggest that a reduction in the currents normally mediated by Ether-a-go-go-Related Gene (ERG) K+ channels contributes to persistent firing in neocortical pyramidal cells. ERG currents have been previously studied primarily in the heart; relatively little is known about ERG function in the brain, although mutations in ERG channels have recently been linked to schizophrenia. The present study is among the first to describe its role in neocortex in relation to biophysical correlates of memory function.
Coupling of aryl halides with aryl boronic acids with P(C6H5)(2-C6H4Cl)2 as the supporting ligand

The chlorinated triarylphosphine P(C6H5)(2-C6H4Cl)2 (1) has been used as a supporting ligand in the Suzuki−Miyaura coupling of aryl boronic acids with aryl halides. Aryl bromides without ortho substituents were successfully coupled at room temperature, while reactions involving sterically hindered aryl bromides required slight heating (70 °C). Electron-deficient aryl chlorides were also successfully coupled with heating (90 °C). Key reaction parameters such as order of addition, choice of mineral base, solvent volume, temperature, 1/Pd ratio, as well as electronic and steric variation of the aryl halide have been investigated and are reported.
Facile synthesis of sulfonyl chlorides

Abstract A method for the synthesis of sulfonyl chlorides and bromides from the corresponding sulfonate salts is described. The method gives good yields of the acid halides under very mild conditions, and is compatible with both acid and base sensitive functionalities.
Synthesis of a 1,8‐naphthyridin‐5‐one derivative via an intramolecular 1,3‐dipolar cycloaddition reaction

Synthesis of a 1,8-naphthyridin-5-one derivative [(5,6,7,8-tetrahydro-(3-chloro-6-hydroxymethyl-8-methyl)-1,8-naphthyridin-5-one (9)] is described starting from 2-chloronicotinic acid using an intramolecular 1,3-dipolar cycloaddition reaction as the key step.
dBBQs: dataBase of Bacterial Quality scores.

It is well-known that genome sequencing technologies are becoming significantly cheaper and faster. As a result of this, the exponential growth in sequencing data in public databases allows us to explore ever growing large collections of genome sequences. However, it is less known that the majority of available sequenced genome sequences in public databases are not complete, drafts of varying qualities. We have calculated quality scores for around 100,000 bacterial genomes from all major genome repositories and put them in a fast and easy-to-use database. Prokaryotic genomic data from all sources were collected and combined to make a non-redundant set of bacterial genomes. The genome quality score for each was calculated by four different measurements: assembly quality, number of rRNA and tRNA genes, and the occurrence of conserved functional domains. The dataBase of Bacterial Quality scores (dBBQs) was designed to store and retrieve quality scores. It offers fast searching and download features which the result can be used for further analysis. In addition, the search results are shown in interactive JavaScript chart framework using DC.js. The analysis of quality scores across major public genome databases find that around 68% of the genomes are of acceptable quality for many uses. dBBQs (available at http://arc-gem.uams.edu/dbbqs ) provides genome quality scores for all available prokaryotic genome sequences with a user-friendly Web-interface. These scores can be used as cut-offs to get a high-quality set of genomes for testing bioinformatics tools or improving the analysis. Moreover, all data of the four measurements that were combined to make the quality score for each genome, which can potentially be used for further analysis. dBBQs will be updated regularly and is freely use for non-commercial purpose.
Synthesis of N,N-Bis(nonaflyl) Squaric Acid Diamide and its Application to Organic Reactions † †

As a continuing effort to develop strong Bronsted acids based on the squaric acid scaffold, it was expected that replacement of Tf group with a longer perfluoro-alkanesulfonyl group would be able to tune the physical pro-perties, such as solubilities in organic solvents and fluoro-philicity, without loss of reactivity (Figure 1). Herein, we report the development of a new Bronsted acid based on the squaric acid scaffold carrying two nonafluorobutanesulfonyl (Nf) groups and the preliminary results of its reactivity to various organic reactions.Squaric acid diamide
Synthesis of skipped enynes via phosphine-promoted couplings of propargylcopper reagents

Abstract An electron-rich phosphine additive is critical and sufficient for propargyl-selective couplings of propargylcopper reagents and alkenyl halides. This method is complementary to those previously described, in which high allenyl selectivity is observed in analogous coupling reactions. While the basis of the phosphine effect requires further investigation, the information gained in these studies enables the synthesis of complex molecules by way of skipped enyne intermediates.
NMR Spectroscopy in Electrochemistry

The sections in this article are Introduction Principles of Solid-State Surface EC-NMR Spectroscopy Metal NMR Basics EC-NMR Instrumentation Applications of Solid-state Surface EC-NMR Spectroscopy 195Pt NMR of Carbon-supported Electrocatalysts and a Potential-scan- generated Sintering Effect Correlation between the Knight Shift of a Platinum Surface and the Electronegativity of the Adsorbate Correlation between the Clean-surface EF-LDOS of Metals and the Knight Shift of Adsorbates Coupling EC-NMR with In Situ Infrared Spectroelectrochemistry Surface Diffusion Isotopic Labeling for Site Selectivity Potential-dependent EC-NMR Future Perspectives Acknowledgments
A new convenient synthesis of propargylic fluorohydrins and 2,5-disubstituted furans from fluoropropargyl chloride.

Fluoropropargyl chloride reacted with carbonyl compounds to give propargylic fluorohydrins under mild conditions and in good yields; however, at higher temperatures and longer reaction times, 2,5-d...
The preparation of 4,5-dihydro-2H-benz[e]indazoles from dilithiated 2-tetralone phenylhydrazone and aromatic esters

The phenylhydrazone of 2-tetralone was dilithiated with excess lithium diisopropylamide followed by condensation with several aromatic esters, and the resulting intermediates were acid cyclized to 4,5-dihydro-2H-benz[e]indazoles.
Cation−Cation Interactions and Antiferromagnetism in Na[Np(V)O2(OH)2]: Synthesis, Structure, and Magnetic Properties

Na[NpO2(OH)2] (1) crystallizes from the hydrothermal reaction of Np(V) and NaOH, in an aqueous solution with a pH of 14, over 3 days at 120 °C. The single-crystal X-ray structure was solved by direct methods and refined via full-matrix least-squares on F2. The compound crystallizes in the orthorhombic space group P212121, a = 5.8904(3) A, b = 7.6297(4) A, c = 8.1540(4) A, Z = 4, with R(F) = 1.52%, wR2(F2) = 3.51% obtained using 63 refined parameters and 1400 reflections. The three-dimensional structure is built from (Np(V)O2)O(OH)4 pentagonal bipyramids that are linked through bridging hydroxyl groups to form a one-dimensional chain substructure, analogous to chains observed in the U(VI) phases of moctezumite, [PbUO2(TeO3)2], and (UO2)Cl2(H2O). Each chain extends along the b-axis and is rotated approximately 60° from neighboring chains, thus permitting the bonding of a dioxo ligand on a neptunyl in one chain as an equatorial ligand of a neighboring NpO2+ ion in an adjacent chain. This unusual bonding conf...
A One-Pot Synthesis of 3-Nitro-and 3,5-Dinitro-2-Picolines

Abstract 3-Nitro- and 3,5-dinitro-2-picoline were each prepared in a one-pot synthesis in high yield by treatment of the respective 2-chloro- 3-nitro- and 2-chloro-3,5-dinitropyridines with diethyl sodiomalonate, followed by hydrolysis and decarboxylation with 50% sulfuric acid.
Principles that govern competition or co-existence in Rho-GTPase driven polarization.

Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry. Some such models display rapid winner-takes-all competition between clusters, yielding a unipolar outcome. Other models allow prolonged co-existence of clusters. We investigate the behavior of a simple class of models and show that while the timescale of competition varies enormously depending on model parameters, a single factor explains a large majority of this variation. The dominant factor concerns the degree to which the maximal active GTPase concentration in a cluster approaches a “saturation point” determined by model parameters. We suggest that both saturation and the effect of saturation on competition reflect fundamental properties of the Rho-GTPase polarity machinery, regardless of the specific feedback mechanism, which predict whether the system will generate unipolar or multipolar outcomes.
A regiocontrolled intramolecular O-cyclization

Abstract Tributyltinlithium-directed sequential alkylation of alkenones with 1,4-dibromo-2-butene shows regiospecific intramolecular O-cyclization and provides an efficient method for the preparation of γ-hydroxyketones.
Dual catalyst control in the amino acid-peptide-catalyzed enantioselective Baylis-Hillman reaction.

Nucleophile-loaded peptides and proline have been found to function synergistically as cocatalysts for the asymmetric ketone-based Baylis−Hillman reaction. Although neither compound is effective independently in terms of rate or enantioselectivity, their combination leads to catalysis where enantioselectivities up to 81% have been observed.
A strategy for the solution-phase parallel synthesis of N-(pyrrolidinylmethyl)hydroxamic acids.

Both five- and six-membered iminocyclitols have proven to be useful transition-state analogue inhibitors of glycosidases. They also mimic the transition-state sugar moiety of the nucleoside phosphate sugar in glycosyltransferase-catalyzed reactions. Described here is the development of a general strategy toward the parallel synthesis of a five-membered iminocyclitol linked to a hydroxamic acid group designed to mimic the transition state of GDP-fucose complexed with Mn(II) in fucosyltransferase reactions. The iminocyclitol 8 containing a protected hydroxylamine unit was prepared from d-mannitol. The hydroxamic acid moiety was introduced via the reaction of 8 with various acid chlorides. The strategy is generally applicable to the construction of libraries for identification of glycosyltransferase inhibitors.
Improving LoRa Signal Coverage in Urban and Sub-Urban Environments with UAVs

LoRa technology enables long-range communication with low-power consumption for the Internet-of-Things (IoT) devices in the urban and suburban environment. However, due to terrestrial structures in urban and suburban environments, the link distance of LoRa transmissions can be reduced. In this paper, we report signal strength measurements for the in-building and inter-building LoRa links and provide insights on factors that affect signal quality such as the spreading factor and antenna orientation. Subsequently, we also provide measurement results in urban and suburban environments when the LoRa transmitter is deployed at different heights using an unmanned aerial vehicle (UAV). Our findings show that the UAV deployment height is critical for improving coverage in the suburban environment and antenna orientation affects the communication range.
Neurofeedback helps to reveal a relationship between context reinstatement and memory retrieval

Abstract Theories of mental context and memory posit that successful mental context reinstatement enables better retrieval of memories from the same context, at the expense of memories from other contexts. To test this hypothesis, we had participants study lists of words, interleaved with task-irrelevant images from one category (e.g., scenes). Following encoding, participants were cued to mentally reinstate the context associated with a particular list, by thinking about the images that had appeared between the words. We measured context reinstatement by applying multivariate pattern classifiers to fMRI, and related this to performance on a free recall test that followed immediately afterwards. To increase sensitivity, we used a closed-loop neurofeedback procedure, whereby higher classifier evidence for the cued category elicited increased visibility of the images from the studied context onscreen. Our goal was to create a positive feedback loop that amplified small fluctuations in mental context reinstatement, making it easier to experimentally detect a relationship between context reinstatement and recall. As predicted, we found that greater amounts of classifier evidence were associated with better recall of words from the reinstated context, and worse recall of words from a different context. In a second experiment, we assessed the role of neurofeedback in identifying this brain-behavior relationship by presenting context images again and manipulating whether their visibility depended on classifier evidence. When neurofeedback was removed, the relationship between classifier evidence and memory retrieval disappeared. Together, these findings demonstrate a clear effect of context reinstatement on memory recall and suggest that neurofeedback can be a useful tool for characterizing brain-behavior relationships.
Synthesis and chemistry of bridgehead allylsilanes. Stereoselective reactions with aldehydes.

A type II intramolecular Diels−Alder reaction provides access to bicyclo[5.3.1] ring systems with an imbedded bridgehead allylsilane. The Lewis acid catalyzed reactions of these compounds with aldehydes proceed efficiently and with control of stereochemistry.
Cryptographic Agility and its Relation to Circular Encryption.

We initiate a provable-security treatment of cryptographic agility. A primitive (for example PRFs, authenticated encryption schemes or digital signatures) is agile when multiple, individually secure schemes can securely share the same key. We provide a surprising connection between two seemingly unrelated but challenging questions. The first, new to this paper, is whether wPRFs (weak-PRFs) are agile. The second, already posed several times in the literature, is whether every secure (IND-R) encryption scheme is secure when encrypting cycles. We resolve the second question in the negative and thereby the first as well. We go on to provide a comprehensive treatment of agility, with definitions for various different primitives. We explain the practical motivations for agility. We provide foundational results that show to what extent it is achievable and practical constructions to achieve it to the best extent possible. On the theoretical side our work uncovers new notions and relations and settles stated open questions, and on the practical side it serves to guide developers.
Chiral Phosphoric Acid Catalyzed Stereoselective Spiroketalizations

The spiroketal functionality is an important structural motif present in numerous natural products. The synthesis of chiral spiroketals is typically achieved under equilibrating conditions and only few asymmetric approaches are known. We have demonstrated that chiral phosphoric acids (CPAs) could serve as effective catalysts for enantioselective spiroketalizations as well as control the course of the corresponding diastereoselective reactions.
Tandem 1,3-dipolar cycloaddition of mesoionic 2,4-diphenyl-1,3-oxathiolium-5-olate with cycloocta-1,5-diene. A new synthesis of the tetracyclo[6.2.0.04,10.05,9]decane ring system

Abstract The mesoionic heterocycle 2,4-diphenyl-1,3-oxathiolium-5-olate ( 5 ) undergoes a tandem 1,3-dipolar cycloaddition reaction with cycloocta-1,5-diene ( 6 ) to give cycloadduct sulfide 7 in modest yield. Oxidation to sulfone 8 and photochemical extrusion of SO 2 affords 9,10-diphenyltetracyclo[6.2.0.0 4,10 .0 5,9 ]decane ( 9 ) in high yield.
Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling

Toll-like receptor 4 interactor with leucine-rich repeats (Tril) functions as a coreceptor for Toll-like receptors (Tlrs) to mediate innate immune responses in adults. In embryos, Tril signals to promote degradation of the Bmp inhibitor, Smad7, to allow for blood formation. It is not known whether this function requires, or is independent of, Tlrs. In the current studies, we performed a structure-function analysis, which indicated that the fibronectin type III (FN) domain and the intracellular domain of Tril are required to trigger Smad7 degradation in Xenopus embryos. Furthermore, we found evidence suggesting that a Tril deletion mutant lacking the FN domain (Tril∆FN) can dominantly inhibit signaling by endogenous Tril when overexpressed. This finding raises the possibility that the FN domain functions to bind endogenous Tril ligands. We also show that Tril cycles between the cell surface and endosomes and that the Tril extracellular domain, as well as cadherin based cell-cell adhesion, are required for cell surface retention, while the intracellular domain is required for internalization in Xenopus ectodermal explants. Using a CHO cell aggregation assay, we show that, unlike other transmembrane proteins that contain leucine-rich repeats, Tril is not sufficient to mediate homophilic adhesion.
Improved solubility and stability of trialkylammonium selenocarboxylate in organic solvents for efficient amidation with azides

Trialkylammonium selenocarboxylate, formed in situ from the reaction of diacyl diselenide with piperidine in the presence of diisopropylethylamine, was found to react readily at room temperature with electron-deficient azides to form amides in excellent yields. The trialkylammonium selenocarboxylate salt formed has good solubility and stability in organic solvents. The enhanced stability allowed mild heating to improve the amidation yields with electron-rich azides.
CRISPRs for Strain Tracking and Their Application to Microbiota Transplantation Data Analysis

Abstract CRISPR-Cas systems are adaptive immune systems naturally found in bacteria and archaea. Prokaryotes use these immune systems to defend against invaders, which include phages, plasmids, and...
Pore Surface Functionalization of MCM-48 Mesoporous Silica with Tungsten and Molybdenum Metal Centers: Perspectives on Catalytic Peroxide Activation

The pore surface of MCM-48 mesoporous silica was functionalized with tungsten and molybdenum metal centers by the anhydrous reaction of metal alkoxides with surface silanol groups. Resulting metal−oxo species were attached via covalent M−O−Si bonds as confirmed with photoacoustic (PAS)-FTIR. Diffuse reflectance UV−visible spectroscopy indicates that the metal oxo groups are predominantly comprised of tetrahedral and octahedral coordinated monomers. MCM-48 grafted with Mo and W is active for brominating phenol red with hydrogen peroxide at neutral pH in a manner similar to Ti−MCM-48, as we reported earlier. The rates of bromination for Mo, W, and four other metals, after normalization for metal concentration, measured as absorption peak intensities of the resultant bromophenol blue, are as follows: 50:46:16:2.8:1:0 W:Mo:Ti:Zr:V:Re. The different rates of reactivity, and hence the general degree of metal−peroxo activation, can be explained on the basis of size, charge, coordination sphere, and electronegat...
First Cubane-like Polysulfidomolybdate: Synthesis and Crystal Structure of Cs6[Mo4S23.6]

The first cubane-like polysulfidomolybdate, Cs6[Mo4S23.6], has been synthesized by the reaction of Mo6Br12 with Cs2S3 in water. The structure comprises a [Mo4S4]6+ tetrahedral core with a combinati...
MORE Chemistry for Less Pollution: Applications for Process Development

Microwave-assisted rapid organic reactions constitute an emerging technology that could make industrially important organic syntheses more eco-friendly than conventional reactions. In our laboratory Microwave-Induced Organic Reaction Enhancement (MORE) chemistry techniques have been developed that are safe since all reactions are conducted in open systems to avoid any chance of explosions that have been observed in sealed systems. MORE chemistry can be conducted without an added solvent if one or more of the reactants is a liquid that absorbs microwaves efficiently. When it is necessary to add a dipolar solvent for transferring microwave energy to the reactants, it is adequate to add just enough solvent to form a slurry at room temperature. The growing concern about the effect of organic solvents and chemical wastes on the environment is attracting attention to non-traditional synthetic approaches that might 'reduce pollution at the source'. In this context MORE chemistry techniques are potentially valuable as they reduce the need for organic solvents and also increase 'atom economy' by improving product selectivity and chemical yield.
A novel synthesis of 3,4-disubstituted cinnolines from o-trifluorophenyl hydrazones

Abstract An efficient synthesis of 3-aryl-4-aminocinnolines from ortho-trifluoromethylphenyl hydrazones is described. The mechanism of the described transformation is likely to involve the formation of the quinone methide intermediate. The described procedure is easily adaptable to automated solid phase synthesis leading to analytically pure heterocycles.
Gold(I)-catalyzed double migration cascades toward (1E,3E)-dienes and naphthalenes

Abstract A novel gold(I)-catalyzed cascade cycloisomerization of a variety of propargylic esters leading to unsymmetrically substituted naphthalenes has been developed. This domino process involves an unprecedented tandem sequence of 1,3- and 1,2-migrations of two substantially different migrating groups. It is believed that this transformation proceeds via formation of 1,3-diene intermediate or its equivalent, which, upon carbocyclization and aromatization steps, transforms into the naphthalene skeleton. In addition, it was also demonstrated that a variety of 1,3-dienes can be accessed stereoselectively via the 1,3-migration–proton transfer cascade.
Synthesis and Investigation of Tin(II) Pyrophosphate Sn2P2O7

The structural investigation of Sn2P2O7 was carried out for the first time by means of single crystal and powder X-ray diffraction. The crystal structure of β-Sn2P2O7 pyrophosphate was solved using...
BAYESIAN LARGE-SCALE MULTIPLE REGRESSION WITH SUMMARY STATISTICS FROM GENOME-WIDE ASSOCIATION STUDIES

Bayesian methods for large-scale multiple regression provide attractive approaches to the analysis of genome-wide association studies (GWAS). For example, they can estimate heritability of complex traits, allowing for both polygenic and sparse models; and by incorporating external genomic data into the priors, they can increase power and yield new biological insights. However, these methods require access to individual genotypes and phenotypes, which are often not easily available. Here we provide a framework for performing these analyses without individual-level data. Specifically, we introduce a "Regression with Summary Statistics" (RSS) likelihood, which relates the multiple regression coefficients to univariate regression results that are often easily available. The RSS likelihood requires estimates of correlations among covariates (SNPs), which also can be obtained from public databases. We perform Bayesian multiple regression analysis by combining the RSS likelihood with previously proposed prior distributions, sampling posteriors by Markov chain Monte Carlo. In a wide range of simulations RSS performs similarly to analyses using the individual data, both for estimating heritability and detecting associations. We apply RSS to a GWAS of human height that contains 253,288 individuals typed at 1.06 million SNPs, for which analyses of individual-level data are practically impossible. Estimates of heritability (52%) are consistent with, but more precise, than previous results using subsets of these data. We also identify many previously unreported loci that show evidence for association with height in our analyses. Software is available at https://github.com/stephenslab/rss.