cssi/SciSciGPT-SciSciNet huggingface dataset:
The HyperKron Graph Model for Higher-Order Features

In this manuscript we present the HyperKron Graph model: an extension of the Kronecker Model, but with a distribution over hyperedges. We prove that we can efficiently generate graphs from this model in time proportional to the number of edges times a small log-factor, and find that in practice the runtime is linear with respect to the number of edges. We illustrate a number of useful features of the HyperKron model including non-trivial clustering and highly skewed degree distributions. Finally, we fit the HyperKron model to real-world networks, and demonstrate the model's flexibility with a complex application of the HyperKron model to networks with coherent feed-forward loops.
Geriatric Assessment for Primary Care Providers

Because of a growing, aging population and a shortage of geriatricians in the United States, the care of geriatric patients will mostly devolve to primary care providers. This article reviews the different aspects of a multidimensional, multidisciplinary geriatric assessment. Assessment tools and training of office staff to take on larger roles can help primary care providers reduce the burden of work associated with performing a comprehensive geriatric assessment.
Deriving enhanced geographical representations via similarity-based spectral analysis: predicting colorectal cancer survival curves in Iowa

Neural networks are capable of learning rich, nonlinear feature representations shown to be beneficial in many predictive tasks. In this work, we use such models to explore different geographical feature representations in the context of predicting colorectal cancer survival curves for patients in the state of Iowa, spanning the years 1989 to 2013. Specifically, we compare model performance using area between the curves (ABC) to assess (a) whether survival curves can be reasonably predicted for colorectal cancer patients in the state of Iowa, (b) whether geographical features improve predictive performance, (c) whether a simple binary representation, or a richer, spectral analysis-elicited representation perform better, and (d) whether spectral analysis-based representations can be improved upon by leveraging geographically-descriptive features. In exploring (d), we devise a similarity-based spectral analysis procedure, which allows for the combination of geographically relational and geographically descriptive features. Our findings suggest that survival curves can be reasonably estimated on average, with predictive performance deviating at the five-year survival mark among all models. We also find that geographical features improve predictive performance, and that better performance is obtained using richer, spectral analysis-elicited features. Furthermore, we find that similarity-based spectral analysis-elicited representations improve upon the original spectral analysis results by approximately 40%.
Location Order Recovery in Trails with Low Temporal Resolution

Researchers who study object movement problems related to topics like traffic flow analysis, patient monitoring, and software operation, need to know the correct order in which objects move. Here, we use the term trail to refer to a series of movements by an object. This paper introduces a new missing data problem that occurs when analyzing trails where there is inadequate temporal resolution on the events. The temporal resolution is inadequate when an object, which can only be in one place at one time, appears in the data to be in two or more locations at once. We refer to this lack of resolution as a broken point. Broken points prevent us from knowing the correct order of movement. We propose a three-phase framework for recovering the location order. Based on the Markov transition network, we are able to find the route with the highest probability. Our results show that this framework can efficiently find the correct location order in trails with low temporal resolution. We also demonstrate that by correcting the location order, the criticality of locations can change significantly.
MAKE IT BLUE: a controllable, color-changing dynamic costume

This work translates an inspiration derived from the Disney classic `Sleeping Beauty' to realize a smart child's costume with color-changing capabilities. The dress uses addressable multi-color NeoPixel LEDs to change its surface color based on input from two wand controllers, consistent with the animated sequence in which Princess Aurora's fairy godmothers argue over the best color for her gown. The garment's construction emphasizes diffusion of emitted light to achieve a more uniform color distribution, and explores benefits and drawbacks of two manufacturing methods for embedding LED pixels: a manual method based on hand-soldered wire connections consistent with typical electronic craft, and a more scalable surface-mount manufacturing method based on stitched traces and reflow soldering.
A look at classification and indexing practices for elementary school children: who are we really serving?

As indicated in the findings of a larger study investigating the information-seeking behavior of Grade 3 students it is asserted that traditional classification and indexing methods used in school ...
User equilibrium with a policy-based link transmission model for stochastic time-dependent traffic networks

Non-recurrent congestion is a major problem in traffic networks that causes unexpected delays during travels. In such a scenario, it is preferable to use adaptive paths or policies where next link decisions on reaching junctions are continuously adapted based on the information gained with time. In this paper, we study a traffic assignment problem in stochastic time-dependent networks. The problem is modeled as a fixed-point problem and existence of the equilibrium solution is discussed. We iteratively solve the problem using the method of successive averages (MSA). A novel network loading model inspired from Link transmission model is developed that accepts policies as inputs for solving the problem. This network loading model is different from the existing network loading models that take predefined paths for input flows. We demonstrate through numerical tests that solving traffic assignment problem with the proposed loading modeling scheme is more efficient as compared to solving the problem using path...
Palliative Care for Children with Central Nervous System Malignancies

Children with central nervous system (CNS) malignancies often suffer from high symptom burden and risk of death. Pediatric palliative care is a medical specialty, provided by an interdisciplinary team, which focuses on enhancing quality of life and minimizing suffering for children with life-threatening or life-limiting disease, and their families. Primary palliative care skills, which include basic symptom management, facilitation of goals-of-care discussions, and transition to hospice, can and should be developed by all providers of neuro-oncology care. This chapter will review the fundamentals of providing primary pediatric palliative care.
Earnings volatility, ambiguity, and crisis-period stock returns

Financial crises are marked by substantial increases in ambiguity where prices appear to decouple from fundamentals. Consistent with ambiguity‐based asset pricing theories, we find that ambiguity concerns are more severe for firms with higher earnings volatility, causing investors to demand a higher ambiguity premium for such firms. While there is no relation between earnings volatility and stock returns under normal conditions, there is a significant negative relation between crisis‐period stock returns and prior earnings volatility. The effect is stronger in firms with low institutional ownership and low analyst following, consistent with ambiguity concerns being greatest amongst firms with unsophisticated investors.
Europarties’ election pledges and European Commission legislative priorities: An assessment of their overlap:

Utilizing a newly compiled data set, this article demonstrates that some election pledges made by the transnational Europarties are included among the European Commission priorities issued during t...
An Analysis of Two-User Uplink Asynchronous Non-orthogonal Multiple Access Systems

Recent studies have numerically demonstrated the possible advantages of the asynchronous non-orthogonal multiple access (ANOMA) over the conventional synchronous non-orthogonal multiple access (NOMA). The ANOMA makes use of the oversampling technique by intentionally introducing a timing mismatch between symbols of different users. Focusing on a two-user uplink system, for the first time, we analytically prove that the ANOMA with a sufficiently large frame length can always outperform the NOMA in terms of the sum throughput. To this end, we derive the expression for the sum throughput of the ANOMA as a function of signal-to-noise ratio, frame length, and normalized timing mismatch. Based on the derived expression, we find that users should transmit at full powers to maximize the sum throughput. In addition, we obtain the optimal timing mismatch as the frame length goes to infinity. Moreover, we comprehensively study the impact of timing error on the ANOMA throughput performance. Two types of timing error, i.e., the synchronization timing error and the coordination timing error, are considered. We derive the throughput loss incurred by both types of timing error and find that the synchronization timing error has a greater impact on the throughput performance compared with the coordination timing error.
Annealed MAP

Maximum a Posteriori assignment (MAP) is the problem of finding the most probable instantiation of a set of variables given the partial evidence on the other variables in a Bayesian network. MAP has been shown to be a NP-hard problem [22], even for constrained networks, such as polytrees [18]. Hence, previous approaches often fail to yield any results for MAP problems in large complex Bayesian networks. To address this problem, we propose ANNEALEDMAP algorithm, a simulated annealing-based MAP algorithm. The ANNEALEDMAP algorithm simulates a non-homogeneous Markov chain whose invariant function is a probability density that concentrates itself on the modes of the target density. We tested this algorithm on several real Bayesian networks. The results show that, while maintaining good quality of the MAP solutions, the ANNEALEDMAP algorithm is also able to solve many problems that are beyond the reach of previous approaches.
Reconfigurable Multitask Audio Dynamics Processing Scheme

Automatic speech recognition (ASR), audio quality, and loudness are key performance indicators (KPIs) in smart speakers. To improve all these KPIs, audio dynamics processing is a crucial component in related systems. Unfortunately, single-band and existing multiband dynamics processing (MBDP) schemes fail to maximize bass and loudness but even produce unwanted peaks, distortions, and nonlinear echo so that an optimized ASR performance cannot be achieved. It has been a goal in both industry and academia to find a better audio dynamics processing for mitigating these problems. To provide such a desired solution, this paper proposes a novel reconfigurable multitask MBDP scheme through a global optimization framework. Through extensive testing, we show the accuracy and effectiveness of the proposed scheme in terms of bass and loudness maximization, distortion and nonlinear echo reduction, browning-out prevention, and significant ASR performance improvement.
Evolvability of Minimally Cognitive Agents

This work investigates evolvability of continuous-time recurrent neural networks to support the behavior of model-agents subject to fitness criteria that changes over the evolutionary timescale. A population of agents is alternatingly evolved to perform two tasks with inverted fitness awards. Evidence of evolvability is reported; it is shown that the population locates a region of "meta-fitness" in the landscape in which sub-regions of optimality for each task are easily accessible from one another.
Sub-3 Å apoferritin structure determined with full range of phase shifts using a single position of volta phase plate.

Abstract Volta Phase Plate (VPP) has become an invaluable tool for cryo-EM structural determination of small protein complexes by increasing image contrast. Currently, the standard protocol of VPP usage periodically changes the VPP position to a fresh spot during data collection. Such a protocol was to target the phase shifts to a relatively narrow range (around 90°) based on the observations of increased phase shifts and image blur associated with more images taken with a single VPP position. Here, we report a 2.87 A resolution structure of apoferritin reconstructed from a dataset collected using only a single position of VPP. The reconstruction resolution and map density features are nearly identical to the reconstruction from the control dataset collected with periodic change of VPP positions. Further experiments have verified that similar results, including a 2.5 A resolution structure, could be obtained with a full range of phase shifts, different spots of variable phase shift increasing rates, and at different ages of the VPP post-installation. Furthermore, we have found that the phase shifts at low resolutions, probably related to the finite size of the Volta spots, could not be correctly modeled by current CTF model using a constant phase shift at all frequencies. In dataset III, severe beam tilt issue was identified but could be computationally corrected with iterative refinements. The observations in this study may provide new insights into further improvement of both the efficiency and robustness of VPP, and to help turn VPP into a plug-and-play device for high-resolution cryo-EM.
Text data analysis using Latent Dirichlet Allocation: an application to FOMC transcripts

This paper applies Latent Dirichlet Allocation (LDA), a machine learning algorithm, to analyse the transcripts of the U.S. Federal Open Market Committee (FOMC) covering the period 2003–2012, includ...
In situ 10-cell RNA sequencing in tissue and tumor biopsy samples

Single-cell transcriptomic methods classify new and existing cell types very effectively, but alternative approaches are needed to quantify the individual regulatory states of cells in their native tissue context. We combined the tissue preservation and single-cell resolution of laser capture with an improved preamplification procedure enabling RNA sequencing of 10 microdissected cells. This in situ 10-cell RNA sequencing (10cRNA-seq) can exploit fluorescent reporters of cell type in genetically engineered mice and is compatible with freshly cryoembedded clinical biopsies from patients. Through recombinant RNA spike-ins, we estimate dropout-free technical reliability as low as ~250 copies and a 50% detection sensitivity of ~45 copies per 10-cell reaction. By using small pools of microdissected cells, 10cRNA-seq improves technical per-cell reliability and sensitivity beyond existing approaches for single-cell RNA sequencing (scRNA-seq). Detection of low-abundance transcripts by 10cRNA-seq is comparable to random 10-cell groups of scRNA-seq data, suggesting no loss of gene recovery when cells are isolated in situ. Combined with existing approaches to deconvolve small pools of cells, 10cRNA-seq offers a reliable, unbiased, and sensitive way to measure cell-state heterogeneity in tissues and tumors.
Simple, efficient, high yield syntheses of substituted and unsubstituted 5‐benzoylbarbituric acids, and their corresponding schiff base phenylhydrazones

Preparation procedures for biologically important benzoylbarbiturates are presented. Several procedures are optimized to cover the preparations of a wide variety of substituted 5-benzoylbarbiturates. To further explore the biological importance of these compounds, multi- gram preparation procedures for nitrophenyl-hydrazones of benzoylbarbiturates and their corresponding salts with organic amines are discussed. It is demonstrated that these compounds can exist in several tautomeric forms and that the equilibrium in solution can be changed by temperature as well as by the pH of the solution. X-ray structural analysis performed on one of the nitrophenylhydrazones of benzoylbarbiturates fully agrees with the presented spectroscopic studies. AMI semi-empirical studies show that the enol form is preferred in the gas phase of benzoylbarbiturates over the keto form, which was also confirmed by NMR spectroscopic studies with chloroform as the solvent. Furthermore, AMI computed structural and electronic properties of the dinitrophenylhydrazone of 4-hydroxybenzoylbarbiturate compared favorably with the X-ray determined structure.
Synthesis of (−)-Haliclonadiamine

Diastereoselective and enantioselective hydrogenation of the racemic β-keto ester 5 to give the enantiomerically pure (96% ee) ester 8 is reported. The conversion of the derived vinylstannane 11 to the antibiotic marine alkaloid (−)-haliclonadiamine (1) is described.
Global existence of solutions to nonlinear Volterra integral equations

A new method is given for proving the global existence of the solution to nonlinear Volterra integral equations. A bound on the solution is derived. The results are based on a nonlinear inequality proved by the author earlier.
Synthesis of 1‐(benzotriazol‐1‐yl)alkyldiphenylphosphine oxides and their transformations to novel benzotriazol‐1‐yl‐substituted cyclopropanes

Diphenylphosphinous anion reacted with chloromethylbenzotriazole to give (benzotriazol-1-yl)methyldiphenylphosphine oxide, which, after lithiation, was alkylated to give 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides in good yield. Treatment of 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides with n-butyllithium followed by condensation with epoxides, afforded benzotriazol-1-yl-substituted cyclopropanes, which underwent further lithiation and subsequent reaction with numerous electrophiles to provide a variety of novel benzotriazol-1-yl-substituted cyclopropane derivatives.
Oxidative Cyclization of Unsaturated Ketene Dithioacetals with Ceric Ammonium Nitrate to Form Bicyclic Lactones

Abstract Ceric ammonium nitrate oxidizes unsaturated ketene dithioacetals in wet MeCN to give cation radicals that cyclize to trisubstituted double bonds and styrenes by cation-like cyclizations leading to cyclic cation radicals that are transformed by further oxidation, hydrolysis and cyclization to bicyclic lactones in moderate to good yield.
Breathing metals as a way of life: geobiology in action.

Many microbes have the ability to reduce transition metals, coupling this reduction to the oxidation of energy sources in a dissimilatory fashion. Because of their abundance, iron and manganese have been extensively studied, and it is well established that reduction of Mn and Fe account for significant turnover of organic carbon in many environments. In addition, many of the dissimilatory metal reducing bacteria (DMRB) also reduce other metals, including toxic metals like Cr(VI), and radioactive contaminants like U(VI), raising the expectations that these processes can be used for bioremediation. The processes involved in metal reduction remain mysterious, and often progress is slow, as nearly all iron and manganese oxides are solids, which offer particular challenges with regard to imaging and chemical measurements. In particular, the interactions that occur at the bacteria-mineral interfaces are not yet clearly elucidated. One DMRB, Shewanella oneidensis MR-1 offers the advantage that its genome has recently been sequenced, and with the availability of its genomic sequence, several aspects of its metal reducing abilities are now beginning to be seen. As these studies progress, it should be possible to separate several processes involved with metal reduction, including surface recognition, attachment, metal destabilization and reduction, and secondary mineral formation.
The Combination of TsNH2 and NCS as Nitrogen and Chlorine Sources for Direct Diamination of Enones

The regio-, stereo-, and chemoselective diamination of enones has been achieved without the observation of any haloamines. The reaction employs the readily available inexpensive combination of NCS and TsNH2 as an electrophilic nitrogen source, and three nitriles as nucleophilic nitrogen sources. A novel mechanism involving the formation of aziridinium intermediates from the reaction of TsNHCl with olefins and a new [2+3] cyclic addition for aziridinim ring opening has been proposed for the electrophilic diamination of olefins. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A new cationic, chiral catalyst for highly enantioselective Diels-Alder reactions.

The Diels−Alder reaction of cyclopentadiene and 2-methacrolein is catalyzed by a chiral Lewis acid to form the exo adduct in 96% yield and 96% ee.
The predictability of genomic changes underlying a recent host shift in Melissa blue butterflies

Despite accumulating evidence that evolution can be predictable, studies quantifying the predictability of evolution remain rare. Here, we measured the predictability of genome-wide evolutionary changes associated with a recent host shift in the Melissa blue butterfly (Lycaeides melissa). We asked whether and to what extent genome-wide patterns of evolutionary change in nature could be predicted (i) by comparisons among instances of repeated evolution and (ii) from SNP × performance associations in a laboratory experiment. We delineated the genetic loci (SNPs) most strongly associated with host use in two L. melissa lineages that colonized alfalfa. Whereas most SNPs were strongly associated with host use in none or one of these lineages, we detected a an approximately twofold excess of SNPs associated with host use in both lineages. Similarly, we found that host-associated SNPs in nature could also be partially predicted from SNP × performance (survival and weight) associations in a laboratory rearing experiment. But the extent of overlap, and thus degree of predictability, was somewhat reduced. Although we were able to predict (to a modest extent) the SNPs most strongly associated with host use in nature (in terms of parallelism and from the experiment), we had little to no ability to predict the direction of evolutionary change during the colonization of alfalfa. Our results show that different aspects of evolution associated with recent adaptation can be more or less predictable and highlight how stochastic and deterministic processes interact to drive patterns of genome-wide evolutionary change.
Latent variable model for aligning barcoded short-reads improves downstream analyses

Recent years have seen the emergence of several "third-generation" sequencing platforms, each of which aims to address shortcomings of standard next-generation short-read sequencing by producing data that capture long-range information, thereby allowing us to access regions of the genome that are inaccessible with short-reads alone. These technologies either produce physically longer reads typically with higher error rates or instead capture long-range information at low error rates by virtue of read "barcodes" as in 10x Genomics9 Chromium platform. As with virtually all sequencing data, sequence alignment for third-generation sequencing data is the foundation on which all downstream analyses are based. Here we introduce a latent variable model for improving barcoded read alignment, thereby enabling improved downstream genotyping and phasing. We demonstrate the feasibility of this approach through developing EMerAld -- or EMA for short -- and testing it on the barcoded short-reads produced by 10x9s sequencing technologies. EMA not only produces more accurate alignments, but unlike other methods also assigns interpretable probabilities to the alignments it generates. We show that genotypes called from EMA9s alignments contain over 30% fewer false positives than those called from Lariat9s (the current 10x alignment tool), with a fewer number of false negatives, on datasets of NA12878 and NA24385 as compared to NIST GIAB gold standard variant calls. Moreover, we demonstrate that EMA is able to effectively resolve alignments in regions containing nearby homologous elements -- a particularly challenging problem in read mapping -- through the introduction of a novel statistical binning optimization framework, which allows us to find variants in the pharmacogenomically important CYP2D region that go undetected when using Lariat or BWA. Lastly, we show that EMA9s alignments improve phasing performance compared to Lariat9s in both NA12878 and NA24385, producing fewer switch/mismatch errors and larger phase blocks on average. EMA software and datasets used are available at http://ema.csail.mit.edu.
Modular synthesis of amine-functionalized oxazolines.

Substituted oxazoline amines have been prepared in high yield from β-amino alcohols and Fmoc-protected α-amino acids using CCl4, PPh3, and Hunig's base in a one-pot procedure followed by base-mediated deprotection.
Intellectual synthesis in mentorship determines success in academic careers

As academic careers become more competitive, junior scientists need to understand the value that mentorship brings to their success in academia. Previous research has found that, unsurprisingly, successful mentors tend to train successful students. But what characteristics of this relationship predict success, and how? We analyzed an open-access database of 18,856 researchers who have undergone both graduate and postdoctoral training, compiled across several fields of biomedical science with an emphasis on neuroscience. Our results show that postdoctoral mentors were more instrumental to trainees' success compared to graduate mentors. Trainees' success in academia was also predicted by the degree of intellectual synthesis between their graduate and postdoctoral mentors. Researchers were more likely to succeed if they trained under mentors with disparate expertise and integrated that expertise into their own work. This pattern has held up over at least 40 years, despite fluctuations in the number of students and availability of independent research positions.
Temporary Protection of H-Phosphinic Acids as a Synthetic Strategy.

H-Phosphinates obtained through various methodologies are protected directly by the reaction with triethyl orthoacetate. The resulting products can be manipulated easily, andvarious synthetic reactions are presented. For example, application to the synthesis of aspartate transcarbamoylase (ATCase) or kynureninase inhibitors are illustrated. Other reactions, such as Sharpless' asymmetric dihydroxylation, or Grubbs' olefin cross-metathesis are also demonstrated. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Knowledge-guided gene prioritization reveals new insights into the mechanisms of chemoresistance

Identification of genes whose basal mRNA expression predicts the sensitivity of tumor cells to cytotoxic treatments can play an important role in individualized cancer medicine. It enables detailed characterization of the mechanism of action of drugs. Furthermore, screening the expression of these genes in the tumor tissue may suggest the best course of chemotherapy or a combination of drugs to overcome drug resistance. We developed a computational method called ProGENI to identify genes most associated with the variation of drug response across different individuals, based on gene expression data. In contrast to existing methods, ProGENI also utilizes prior knowledge of protein–protein and genetic interactions, using random walk techniques. Analysis of two relatively new and large datasets including gene expression data on hundreds of cell lines and their cytotoxic responses to a large compendium of drugs reveals a significant improvement in prediction of drug sensitivity using genes identified by ProGENI compared to other methods. Our siRNA knockdown experiments on ProGENI-identified genes confirmed the role of many new genes in sensitivity to three chemotherapy drugs: cisplatin, docetaxel, and doxorubicin. Based on such experiments and extensive literature survey, we demonstrate that about 73% of our top predicted genes modulate drug response in selected cancer cell lines. In addition, global analysis of genes associated with groups of drugs uncovered pathways of cytotoxic response shared by each group. Our results suggest that knowledge-guided prioritization of genes using ProGENI gives new insight into mechanisms of drug resistance and identifies genes that may be targeted to overcome this phenomenon.
Ligand differentiated complementary Rh-catalyst systems for the enantioselective desymmetrization of meso-cyclic anhydrides

Two distinct systems for the rhodium-catalyzed enantioselective desymmetrization of meso-cyclic anhydrides have been developed. Each system has been optimized and are compatible with the use of in situ prepared organozinc reagents. Rhodium/PHOX species efficiently catalyze the addition of alkyl nucleophiles to glutaric anhydrides, while a rhodium/phosphoramidite system is effective in the enantioselective arylation of succinic and glutaric anhydrides.
Stereospecific, Enantiospecific Total Synthesis of the Sarpagine Indole Alkaloids (E)16-Epiaffinisine, (E)16-Epinormacusine B, and Dehydro-16-epiaffinisine

The first stereospecific total synthesis of the sarpagine indole alkaloids (E)16-epiaffinisine (1), (E)16-epinormacusine B (2), and dehydro-16-epiaffinisine (4) has been completed; this method has also resulted in the synthesis of dehydro-16-epinormacusine B (5). The formation of the required ether in both 4 and 5 was realized with complete control from the top face on treatment of the corresponding alcohols with DDQ/THF in 98% and 95% yields, respectively.
Feynman-Schwinger technique in field theories

In these lectures we introduce the Feynman-Schwinger representation method for solying nonperturbative problems in field theory. As an introduction we first give a brief overview of integral equations and path integral methods for solving nonperturbative problems. Then we discuss the Feynman-Schwinger (FSR) representation method with applications to scalar interactions. The FSR approach is a continuum path integral integral approach in terms of covariant trajectories of particles. Using the exact results provided by the FSR approach we test the reliability of commonly used approximations for nonperturbative summation of interactions for few body systems.
A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain

Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more effective than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as in neurons, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network.
Neural Coding of Leg Proprioception in Drosophila

Summary Animals rely on an internal sense of body position and movement to effectively control motor behavior. This sense of proprioception is mediated by diverse populations of mechanosensory neurons distributed throughout the body. Here, we investigate neural coding of leg proprioception in Drosophila, using in vivo two-photon calcium imaging of proprioceptive sensory neurons during controlled movements of the fly tibia. We found that the axons of leg proprioceptors are organized into distinct functional projections that contain topographic representations of specific kinematic features. Using subclass-specific genetic driver lines, we show that one group of axons encodes tibia position (flexion/extension), another encodes movement direction, and a third encodes bidirectional movement and vibration frequency. Overall, our findings reveal how proprioceptive stimuli from a single leg joint are encoded by a diverse population of sensory neurons, and provide a framework for understanding how proprioceptive feedback signals are used by motor circuits to coordinate the body.
POCl3-mediated synthesis of hydrolysis-prone 2-trifluoroethylbenzimidazoles

Abstract Loss of a trifluoromethyl group has been observed as an unproductive side reaction in the formation of 2-trifluoroethylbenzimidazoles. A hydrolytic mechanism for this transformation is proposed that is consistent with evidence for the identity of reaction intermediates. Cyclodehydration with POCl 3 suppresses hydrolysis of the trifluoromethyl group and provides 2-trifluoroethylbenzimidazoles in good yields.
SV-plaudit: A cloud-based framework for manually curating thousands of structural variants.

SV-plaudit is a framework for rapidly curating structural variant (SV) predictions. For each SV, we generate an image that visualizes the coverage and alignment signals from a set of samples. Images are uploaded to our cloud framework where users assess the quality of each image using a client-side web application. Reports can then be generated as a tab-delimited file or annotated Variant Call Format (VCF) file. As a proof of principle, nine researchers collaborated for 1 hour to evaluate 1,350 SVs each. We anticipate that SV-plaudit will become a standard step in variant calling pipelines and the crowd-sourced curation of other biological results. Code available at https://github.com/jbelyeu/SV-plaudit Demonstration video available at https://www.youtube.com/watch?v=ono8kHMKxDs
Push–pull alkenes from cyclic ketene-N,N′-acetals: a wide span of double bond lengths and twist angles

Abstract Push–pull alkenes can be quickly accessed by cyclic ketene-N,N′-acetal chemistry. A number of push–pull structures with a wide span of double bond lengths and twist angles were synthesized from the reactions of (1) N,N′-dimethyl cyclic ketene-N,N′-acetals with isocyanates, (2) the products from (1) with isocyanates, (3) 2-methylimidazoline and 2-methyl-1,4,5,6-tetrahydropyrimidine with diacid chlorides, (4) 2-methylimidazoline, and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine with benzoyl chlorides, and (5) 1,2-dimethylimidazoline and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine with aryl isocyanates. These reactions proceed under very mild conditions and give moderate to excellent yields. X-ray crystallographic analysis of eight pxush–pull alkenes indicates that the central double bond lengths and twists are sensitive to the ring sizes (5 or 6), ring structures (fused or non-fused), electron donating and withdrawing strengths of pushing and pulling portions, respectively, number of electron pushing or pulling groups and substituent steric effects.
An alternate preparation of thioester resin linkers for solid-phase synthesis of peptide C-terminal thioacids

Abstract An alternative preparation of thioester resin linkers for solid-phase synthesis of peptide C-terminal thioacids is presented.
The Infectious Bronchitis Coronavirus Envelope Protein Alters Golgi pH To Protect the Spike Protein and Promote the Release of Infectious Virus

Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro The E protein from avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which require residues in the HD. Mutation of the HD of IBV E in a recombinant virus background results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV spike (S) protein on the plasma membrane compared to wild-type (WT) IBV-infected cells, and aberrant cleavage of IBV S on virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with an increased Golgi luminal pH. Infection with IBV or expression of IBV E induces neutralization of Golgi pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cell factors, protecting IBV S from premature cleavage and leading to the efficient release of infectious virus from the cells. This is the first demonstration of a coronavirus-induced alteration in the microenvironment of the secretory pathway.IMPORTANCE Coronaviruses are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including the use of attenuated viruses that lack the CoV E protein or express E mutants. However, no approved vaccines or antiviral therapeutics exist. Understanding the role of the CoV E protein in virus assembly and release is thus an important prerequisite for potential vaccines as well as in identifying novel antiviral therapeutics.
Synthesis of (-)-laulimalide: an agent for microtubule stabilization

Abstract An enantioselective synthesis of (−)-laulimalide is described. Key reactions include a convergent allylation coupling reaction, asymmetric conjugate addition, the allenylstannane Ferrier reaction and a chelation-controlled alkenylzinc addition as the basis for stereocontrol in critical elements of chirality.
New uranium chalcoantimonates, RbU2SbS8 and KU2SbSe8, with a polar noncentrosymmetric structure

The new compounds, RbU2SbS8 and KU2SbSe8, were prepared as golden-black, blocklike crystals by the polychalcogenide molten flux method. RbU2SbS8 crystallizes in the monoclinic space group Cm with a = 7.9543(9) A, b = 11.0987(13) A, c = 7.2794(10) A, β = 106.030(2)°, and Z = 2. The compound has a two-dimensional character with layers running perpendicular to the c-axis. The coordination geometry around the U4+ atoms is best described as a bicapped trigonal prism. The trigonal prisms share triangular faces with neighboring prisms, forming one-dimensional columns along the a-axis. The columns are then joined to construct sheets by sharing capping S atoms. Sb3+ ions are sitting at the center of a slightly distorted seesaw coordination environment (CN = 4). Rb+ ions are stabilized in 8-coordinate bicapped trigonal prismatic sites. KU2SbSe8 crystallizes in the monoclinic space group Cm with a = 11.5763(2) A, b = 8.2033(1) A, c = 15.2742(1) A, β = 112.22(2)°, and Z = 4. KU2SbSe8 has essentially the same structur...
Polyhydroxylated aziridinylcyclopentanes as glycomimetics: a new competitive inhibitor of α-mannosidase

Abstract The synthesis of 6 , a new competitive inhibitor of jackbean α-mannosidase, was achieved in three steps from pyridine, illustrating the promising potential of substituted 6-azabicyclo[3.1.0]hexanes as glycomimetics.
Recent developments in high frequency/high magnetic field CW EPR. Applications in chemistry and biology

A recent review of developments in high magnetic field/high frequency continuous wave electron paramagnetic resonance (EPR) spectroscopy is presented. The main motivations to develop instrumentation beyond “conventional” spectrometers are the desire to increase the spectral resolution and the need for high frequencies in the case of large zero field splitting systems. The potential of high frequency EPR is illustrated with the study of a Mn based spin cluster, which also confirms the need for multifrequency measurements. Examples of high field/high frequency EPR applications to chemistry and biology demonstrate that additional structural information can be obtained with the resolution achieved at 245 GHz.
Beyond modularity: Fine-scale mechanisms and rules for brain network reconfiguration

The human brain is in constant flux, as distinct areas engage in transient communication to support basic behaviors as well as complex cognition. The collection of interactions between cortical and subcortical areas forms a functional brain network whose topology evolves with time. Despite the nontrivial dynamics that are germane to this networked system, experimental evidence demonstrates that functional interactions organize into putative brain systems that facilitate different facets of cognitive computation. We hypothesize that such dynamic functional networks are organized around a set of rules that constrain their spatial architecture - which brain regions may functionally interact - and their temporal architecture - how these interactions fluctuate over time. To objectively uncover these organizing principles, we apply an unsupervised machine learning approach called non-negative matrix factorization to time-evolving, resting state functional networks in 20 healthy subjects. This machine learning approach automatically groups temporally co-varying functional interactions into subgraphs that represent putative topological modes of dynamic functional architecture. We find that subgraphs are stratified based on both the underlying modular organization and the topographical distance of their strongest interactions: while many subgraphs are largely contained within modules, others span between modules and are expressed differently over time. The relationship between dynamic subgraphs and modular architecture is further highlighted by the ability of time-varying subgraph expression to explain inter-individual differences in module reorganization. Collectively, these results point to the critical role that subgraphs play in constraining the topography and topology of functional brain networks. More broadly, this machine learning approach opens a new door for understanding the architecture of dynamic functional networks during both task and rest states, and for probing alterations of that architecture in disease.
Recent Studies of Group 14 Derivatives of Small nido‐Boranes

This article briefly reviews this area, describes some of our own recent work and also presents some new data. The preparation and characterization of a series of triphenyltin-substituted penta- and hexaboranes is described. The species 1-(SnPh 3 )B 5 H 8 (1) and 2,3-μ-(SnPh 3 )B 5 H 8 (3) are prepared from SnPh 3 Cl and K[B 5 H 8 ] by careful selection of solvent and conditions, and the intermediacy of 2-(SnPh 3 )B 5 H 8 (2), in the formation of 1 from 3, was demonstrated by NMR spectroscopy. The species 1, 2 and 3 were characterized by 11 B, 1 H and 119 Sn NMR spectra and 11 B- 119 Sn coupling was observed for the first time in a polyhedral borane. Crystal structures were determined for 3 and the chloro-derivative of 1, 1-(SnClPh 2 )B 5 H 8 (4). Using similar techniques, three of the six possible linkage isomers of SnPh 2 (B 5 H 8 ) 2 namely μ,μ'-SnPh 2 (B 5 H 8 ) 2 (10), μ,2'-SnPh 2 (B 5 H 8 ) 2 (11) and μ,1'-SnPh 2 (B 5 H 8 ) 2 (12) were isolated and completely characterized including crystal structure determinations. The use of non-basic solvents such as CH 2 Cl 2 allows the isolation of the bridging species 3 and 10 whereas basic solvents such as Et 2 O or THF catalyse the rearrangement to species with the substituent in the 1-position, namely the 1 and 12 isomers. Isomer 11 is prepared by carrying out reactions in EtO 2 and 12 is also prepared by the reaction between 4 and K[B 5 H 8 ] in CH 2 Cl 2 . The hexaborane derivatives 2,3-μ-(SnPh 3 )B 6 H 9 , 2,3-μ-(SnMe 3 )B 6 H 9 and 2,3-μ-(SiPh 3 )B 6 H 9 were also prepared and characterized although all three species were too unstable to afford crystals suitable for X-ray analysis. Finally, attempts to prepare pentaboranyl derivatives containing two SnPh 3 substituents provided evidence for the formation of μ,1-(SnPh 3 ) 2 B 5 H 7 and 1,2-(SnPh 3 ) 2 B 5 H 7
Synthesis and photophysical properties of fluorescent 2,5-dibenzoxazolylphenols and related compounds with excited state proton-transfer

A series of new 2,5-dibenzoxazolylphenols and related compounds was prepared by condensation of hydroxy- and methanesulfonamidoterephthalic acids with 2-aminophenols. These displayed excited state intramolecular proton-transfer fluorescence at room temperature and above with quantum yields as high as 0.48 and emission peaks of 492-517 nm. The methanesulfonamido group was found about as effective a proton donor as the phenolic hydroxyl group. Incorporation of substituents onto the benzoxazole moieties increased solubility of the fluors in hydrocarbon solvents in some cases, but reduced quantum yields. These fluors are of interest as wavelength shifters in a scintillating detecting medium for ionizing radiation.
Lytic transglycosylases RlpA and MltC assist in Vibrio cholerae daughter cell separation

The cell wall is a crucial structural feature in the vast majority of bacteria and comprises a covalently closed network of peptidoglycan (PG) strands. While PG synthesis is important for survival under many conditions, the cell wall is also a dynamic structure, undergoing degradation and remodeling by 'autolysins', enzymes that break down PG. Cell division, for example, requires extensive PG remodeling, especially during separation of daughter cells, which depends heavily upon the activity of amidases. However, in Vibrio cholerae, we demonstrate that amidase activity alone is insufficient for daughter cell separation and that lytic transglycosylases RlpA and MltC both contribute to this process. MltC and RlpA both localize to the septum and are functionally redundant under normal laboratory conditions; however, only RlpA can support normal cell separation in low-salt media. The division-specific activity of lytic transglycosylases has implications for the local structure of septal PG, suggesting that there may be glycan bridges between daughter cells that cannot be resolved by amidases. We propose that lytic transglycosylases at the septum cleave PG strands that are crosslinked beyond the reach of the highly regulated activity of the amidase and clear PG debris that may block the completion of outer membrane invagination.
Applications of cutoff resolvent estimates to the wave equation

We consider solutions to the linear wave equation on non-compact Riemannian manifolds without boundary when the geodesic flow admits a filamentary hyperbolic trapped set. We obtain a polynomial rate of local energy decay with exponent depending only on the dimension.