cssi/SciSciGPT-SciSciNet huggingface dataset:
Cauchy combination test: a powerful test with analytic p-value calculation under arbitrary dependency structures.

Abstract–Combining individual p-values to aggregate multiple small effects has a long-standing interest in statistics, dating back to the classic Fisher’s combination test. In modern large-scale da...
Probabilistic Prediction of Interactive Driving Behavior via Hierarchical Inverse Reinforcement Learning

Autonomous vehicles (AVs) are on the road. To safely and efficiently interact with other road participants, AVs have to accurately predict the behavior of surrounding vehicles and plan accordingly. Such prediction should be probabilistic, to address the uncertainties in human behavior. Such prediction should also be interactive, since the distribution over all possible trajectories of the predicted vehicle depends not only on historical information, but also on future plans of other vehicles that interact with it. To achieve such interaction-aware predictions, we propose a probabilistic prediction approach based on hierarchical inverse reinforcement learning (IRL). First, we explicitly consider the hierarchical trajectory-generation process of human drivers involving both discrete and continuous driving decisions. Based on this, the distribution over all future trajectories of the predicted vehicle is formulated as a mixture of distributions partitioned by the discrete decisions. Then we apply IRL hierarchically to learn the distributions from real human demonstrations. A case study for the ramp-merging driving scenario is provided. The quantitative results show that the proposed approach can accurately predict both the discrete driving decisions such as yield or pass as well as the continuous trajectories.
Morphology of mitochondria in spatially restricted axons revealed by cryo-electron tomography

Neurons project axons to local and distal sites and can display heterogeneous morphologies with limited physical dimensions that may influence the structure of large organelles such as mitochondria. Using cryo-electron tomography (cryo-ET), we characterized native environments within axons and presynaptic varicosities to examine whether spatial restrictions within these compartments influence the morphology of mitochondria. Segmented tomographic reconstructions revealed distinctive morphological characteristics of mitochondria residing at the narrowed boundary between presynaptic varicosities and axons with limited physical dimensions (approximately 80 nm), compared to mitochondria in nonspatially restricted environments. Furthermore, segmentation of the tomograms revealed discrete organizations between the inner and outer membranes, suggesting possible independent remodeling of each membrane in mitochondria at spatially restricted axonal/varicosity boundaries. Thus, cryo-ET of mitochondria within axonal subcompartments reveals that spatial restrictions do not obstruct mitochondria from residing within them, but limited available space can influence their gross morphology and the organization of the inner and outer membranes. These findings offer new perspectives on the influence of physical and spatial characteristics of cellular environments on mitochondrial morphology and highlight the potential for remarkable structural plasticity of mitochondria to adapt to spatial restrictions within axons.
Discovery of highly insecticidal synthetic spinosyn mimics - CAMD enabled de novo design simplifying a complex natural product.

Simplifying complex natural products: Computer modeling-based design leads to highly insecticidal, chemically simpler synthetic mimics of the spinosyn natural products that are active in the field. © 2018 Society of Chemical Industry.
Asynchronous parallel primal–dual block coordinate update methods for affinely constrained convex programs

Recent several years have witnessed the surge of asynchronous (async-) parallel computing methods due to the extremely big data involved in many modern applications and also the advancement of multi-core machines and computer clusters. In optimization, most works about async-parallel methods are on unconstrained problems or those with block separable constraints. In this paper, we propose an async-parallel method based on block coordinate update (BCU) for solving convex problems with nonseparable linear constraint. Running on a single node, the method becomes a novel randomized primal–dual BCU for multi-block affinely constrained problems. For these problems, Gauss–Seidel cyclic primal–dual BCU is not guaranteed to converge to an optimal solution if no additional assumptions, such as strong convexity, are made. On the contrary, assuming convexity and existence of a primal–dual solution, we show that the objective value sequence generated by the proposed algorithm converges in probability to the optimal value and also the constraint residual to zero. In addition, we establish an ergodic O(1 / k) convergence result, where k is the number of iterations. Numerical experiments are performed to demonstrate the efficiency of the proposed method and significantly better speed-up performance than its sync-parallel counterpart.
The torsion function of convex domains of high eccentricity

The torsion function of a convex planar domain Ω has convex level sets, but explicit formulae are known only for rectangles and ellipses. Here we study the torsion function when the eccentricity of the domain is large. We obtain an approximation for the torsion function on any convex planar domain by viewing the domain as a perturbation of a rectangle in order to define an approximate Green’s function for the Laplacian. For a class of convex domains we use this approximation to establish sharp bounds on the Hessian and the infinitesimal shape of the level sets around its maximum. We also use these results to construct examples demonstrating contrasting behaviour of the torsion function and the first eigenfunction of the Dirichlet Laplacian around their respective maxima.
RANS-Based Aerodynamic Shape Optimization of a Strut-Braced Wing with Overset Meshes

The strut-braced wing aircraft configuration promises to reduce fuel burn by enabling higher spans that reduce lift-induced drag. A successful design for this configuration depends on a careful tra...
Analytical Modeling of Cache Behavior for Affine Programs

Modern optimizing compiler design integrates program transformation strategies aimed at reducing data movement to/from main memory, exploiting the data cache hierarchy. But in reality, the effect of these transformations on the actual cache miss count is ignored in compilers, due to the lack of precise compile-time models of misses for hierarchical caches. Going a step further, when considering real-life systems, the data is vulnerable to hardware faults (e.g., bit flip) when it is stored in a cache without automatic error detection/correction. Determining the cache vulnerability of a program requires the computation of the lifetime of each data element in the cache, and the current state of practice for both cache miss analysis as well as vulnerability analysis is based on accurate simulation.
When Do Words Matter? Understanding the Impact of Lexical Choice on Audience Perception Using Individual Treatment Effect Estimation

Studies across many disciplines have shown that lexical choice can affect audience perception. For example, how users describe themselves in a social media profile can affect their perceived socio-economic status. However, we lack general methods for estimating the causal effect of lexical choice on the perception of a specific sentence. While randomized controlled trials may provide good estimates, they do not scale to the potentially millions of comparisons necessary to consider all lexical choices. Instead, in this paper, we first offer two classes of methods to estimate the effect on perception of changing one word to another in a given sentence. The first class of algorithms builds upon quasi-experimental designs to estimate individual treatment effects from observational data. The second class treats treatment effect estimation as a classification problem. We conduct experiments with three data sources (Yelp, Twitter, and Airbnb), finding that the algorithmic estimates align well with those produced by randomized-control trials. Additionally, we find that it is possible to transfer treatment effect classifiers across domains and still maintain high accuracy.
Generalizing causal inferences from individuals in randomized trials to all trial‐eligible individuals

We consider methods for causal inference in randomized trials nested within cohorts of trial-eligible individuals, including those who are not randomized. We show how baseline covariate data from the entire cohort, and treatment and outcome data only from randomized individuals, can be used to identify potential (counterfactual) outcome means and average treatment effects in the target population of all eligible individuals. We review identifiability conditions, propose estimators, and assess the estimators' finite-sample performance in simulation studies. As an illustration, we apply the estimators in a trial nested within a cohort of trial-eligible individuals to compare coronary artery bypass grafting surgery plus medical therapy vs. medical therapy alone for chronic coronary artery disease.
Race and Rights in the Digital Age

This essay discusses how, despite the liberatory potential of technology, racial bias pervades the digital space. This bias creates tension with both the formal, de jure equality notion of “colorblindness” (in U.S. constitutional law) as well as the broader, substantive, de facto equality idea (in international human rights law). The essay draws on the work of Osagie Obasogie to show how blind people perceive race in the same way as sighted people, despite not being able to see race. It then uses blindness as a metaphor to explore how race is seen and not seen online, and analyzes the implications of this for human rights.
New Constructions with Quadratic Separation between Sensitivity and Block Sensitivity

Nisan and Szegedy [Nisan and Szegedy, 1994] conjectured that block sensitivity is at most polynomial in sensitivity for any Boolean function. There is a huge gap between the best known upper bound on block sensitivity in terms of sensitivity - which is exponential, and the best known separating examples - which give only a quadratic separation between block sensitivity and sensitivity. In this paper we give various new constructions of families of Boolean functions that exhibit quadratic separation between sensitivity and block sensitivity. Our constructions have several novel aspects. For example, we give the first direct constructions of families of Boolean functions that have both 0-block sensitivity and 1-block sensitivity quadratically larger than sensitivity.
Adaptation of the proximal humerus to physical activity: a within-subject controlled study in baseball players

The proximal humerus is a common, yet understudied site for osteoporotic fracture. The current study explored the impact of prolonged physical activity on proximal humerus bone health by comparing bone properties between the throwing and nonthrowing arms within professional baseball players. The proximal humerus in throwing arms had 28.1% (95% CI, 17.8 to 38.3%) greater bone mass compared to nonthrowing arms, as assessed using dual-energy x-ray absorptiometry. At the level of the surgical neck, computed tomography revealed 12.0% (95% CI, 8.2 to 15.8%) greater total cross-sectional area and 31.0% (95% CI, 17.8 to 44.2%) greater cortical thickness within throwing arms, which contributed to 56.8% (95% CI, 44.9 to 68.8%) greater polar moment of inertia (i.e., estimated ability to resist torsional forces) compared to nonthrowing arms. Within the humeral head and greater tubercle regions, throwing arms had 3.1% (95% CI, 1.1 to 5.1%) more trabecular bone, as assessed using high-resolution magnetic resonance imaging. Three-dimensional mapping of voxel- and vertex-wise differences between arms using statistical parametric mapping techniques revealed throwing arms had adaptation within much of the proximal diaphysis, especially the posterolateral cortex. The pattern of proximal diaphysis adaptation approximated the pattern of strain energy distribution within the proximal humerus during a fastball pitch derived from a musculoskeletal and finite element model in a representative player. These data demonstrate the adaptive ability of the proximal humerus to physical activity-related mechanical loads. It remains to be established how they translate to exercise prescription to improve bone health within the proximal humerus; however, they provide unique insight into the relationship between prolonged loading and skeletal adaptation at a clinically relevant osteoporotic site.
Optimal Sensor Placement for Topology Identification in Smart Power Grids

Accurate network topology information is critical for secure operation of smart power distribution systems. Line outages can change the operational topology of a distribution network. As a result, topology identification by detecting outages is an important task to avoid mismatch between the topology that the operator believes is present and the actual topology. Power distribution systems are operated as radial trees and are recently adopting the integration of sensors to monitor the network in real time. In this paper, an optimal sensor placement solution is proposed that enables outage detection through statistical tests based on sensor measurements. Using two types of sensors, node sensors and line sensors, we propose a novel formulation for the optimal sensor placement as a cost optimization problem with binary decision variables, i.e., to place or not place a sensor at each bus/line. The advantage of the proposed placement strategy for outage detection is that it incorporates various types of sensors, is independent of load forecast statistics and is cost effective. Numerical results illustrating the placement solution are presented.
Emergent Coordination through Competition

We study the emergence of cooperative behaviors in reinforcement learning agents by introducing a challenging competitive multi-agent soccer environment with continuous simulated physics. We demonstrate that decentralized, population-based training with co-play can lead to a progression in agents' behaviors: from random, to simple ball chasing, and finally showing evidence of cooperation. Our study highlights several of the challenges encountered in large scale multi-agent training in continuous control. In particular, we demonstrate that the automatic optimization of simple shaping rewards, not themselves conducive to co-operative behavior, can lead to long-horizon team behavior. We further apply an evaluation scheme, grounded by game theoretic principals, that can assess agent performance in the absence of pre-defined evaluation tasks or human baselines.
Toward sensor-based sleep monitoring with electrodermal activity measures

We use self-report and electrodermal activity (EDA) wearable sensor data from 77 nights of sleep of six participants to test the efficacy of EDA data for sleep monitoring. We used factor analysis to find latent factors in the EDA data, and used causal model search to find the most probable graphical model accounting for self-reported sleep efficiency (SE), sleep quality (SQ), and the latent factors in the EDA data. Structural equation modeling was used to confirm fit of the extracted graph to the data. Based on the generated graph, logistic regression and naive Bayes models were used to test the efficacy of the EDA data in predicting SE and SQ. Six EDA features extracted from the total signal over a night’s sleep could be explained by two latent factors, EDA Magnitude and EDA Storms. EDA Magnitude performed as a strong predictor for SE to aid detection of substantial changes in time asleep. The performance of EDA Magnitude and SE in classifying SQ demonstrates promise for using a wearable sensor for sleep monitoring. However, our data suggest that obtaining a more accurate sensor-based measure of SE will be necessary before smaller changes in SQ can be detected from EDA sensor data alone.
Tournament minors

We say a digraph G is a minor of a digraph H if G can be obtained from a subdigraph of H by repeatedly contracting a strongly-connected subdigraph to a vertex. Here, we show that the class of all tournaments is a well-quasi-order under minor containment.
Replicability of Results

Because result replicability is important to researchers, and statistical significance does not evaluate replicability, both external and internal replicability analyses are important. Some researchers find true external replication studies impractical, and therefore turn to ‘internal’ methods. Three internal replicability analyses have been proposed: cross-validation, the jackknife, and the bootstrap. Keywords: statistical significance; replicability; bootstrap; jackknife; cross-validation; effect size
Posner’s Folly: The End of Legal Pragmatism and Coercion’s Clarity

Highly influential legal scholar and judge Richard Posner, newly retired from the bench, believes that law is irrelevant to most of his judicial decisions as well as to most constitutional decisions of the U.S. Supreme Court. His recent high-profile repudiation of the rule of law, made in statements for the general public, was consistent with what he and others have been saying to legal audiences for decades. Legal pragmatism has reached its end in abandoning all the restraints of law. Posner-endorsed “epistemological democracy” obscures a discretion that is much worse than the rule of law promoted by epistemological authoritarianism. I argue that a focus on conceptual essentialism and on the recognition of coercive intent as essential to the concept of law, both currently unpopular among legal theorists and many jurists, can clarify legal understandings and serve as starting points for the restoration of the rule of law. A much more precise, scientific approach to legal concepts is required in order to best ensure the rational and moral legitimacy of law and to combat eroding public confidence in political and legal institutions, especially in an increasingly diverse society. The rational regulation by some (lawmakers) of the real-world actions of others (ordinary citizens) requires that core or central instances of concepts have essential elements rather than be “democratic.” Although legal pragmatism has failed just as liberal theory generally has failed, the pragmatic value of different conceptual approaches is, in fact, the best measure of their worth. Without essentialism in concept formation and an emphasis on coercion, the abilities to understand and communicate effectively about the practical legal world are impaired. Non-essentialism grants too much unwarranted discretion to judges and other legal authorities, and thus undermines the rule of law. Non-essentialist or anti-essentialist conceptual approaches allow legal concepts to take on characteristics appropriate to religious and literary concepts, which leads to vague and self-contradictory legal concepts that incoherently and deceptively absorb disparate elements that are best kept independent in order to maximize law’s rationality and moral legitimacy. When made essentialist, the concept of political positive law shrinks, clarifies, and reveals its true features, including the physically-coercive nature of all laws and the valuable method of tracing the content of law by following its coercive intents and effects.
Education and training in clinical neuropsychology: Recent developments and documents from the clinical neuropsychology synarchy

The Clinical Neuropsychology Synarchy (CNS) interfaces with the American Psychological Association and affiliated organizations to address issues and advances in specialty training. The past several years have seen the development and dissemination of several initiatives pertinent to specialty training. Among these initiatives was the creation of a taxonomy for education and training in clinical neuropsychology. In additional there has been a movement toward competency-based education that has become codified in the APA's new Standards for Accreditation. Calls for competency-based education have also influenced the expectations of the APA's Committee on Recognition of Specialties and Proficiencies in Professional Psychology. As the convener of national clinical neuropsychology organizations, the CNS has overseen the development of relevant documents for our specialty. This paper presents three documents critical to training in our field that were developed through the CNS and approved by its member organizations. The first is the Taxonomy for Education and Training in Clinical Neuropsychology. The second is Entry Level Competencies for Clinical Neuropsychology and the third is a distillation of the entry-level competency document for the purpose of identifying competencies to be addressed at the post-doctoral residency level.
Reactions to Intravenous Administration of Solutions

Despite the fact that many articles have appeared concerning the cause and elimination of pyrexial reactions after the administrations of solutions by vein, there still remains much lack of knowledge on the part of physicians and hospital personnel, so that these reactions still occur with a frequency inexcusable in the light of present day knowledge. Since most of the articles have appeared in technical or surgical journals they have escaped the eye of most of those responsible for the production of solutions and the care of tubing and needles, and therefore the application of the known successful methods of avoiding reactions has not become widespread. Commercial houses have, in general, attempted to correct the situation, but too often contact is made only with a purchasing agent who looks at the increased cost of material presented and refuses to buy it until forced to by the medical staff's complaints about reactions.
Weighted Reservoir Sampling from Distributed Streams

We consider message-efficient continuous random sampling from a distributed stream, where the probability of inclusion of an item in the sample is proportional to a weight associated with the item. The unweighted version, where all weights are equal, is well studied, and admits tight upper and lower bounds on message complexity. For weighted sampling with replacement, there is a simple reduction to unweighted sampling with replacement. However, in many applications the stream may have only a few heavy items which may dominate a random sample when chosen with replacement. Weighted samplingwithout replacement (weighted SWOR) eludes this issue, since such heavy items can be sampled at most once. In this work, we present the first message-optimal algorithm for weighted SWOR from a distributed stream. Our algorithm also has optimal space and time complexity. As an application of our algorithm for weighted SWOR, we derive the first distributed streaming algorithms for trackingheavy hitters with residual error. Here the goal is to identify stream items that contribute significantly to the residual stream, once the heaviest items are removed. Residual heavy hitters generalize the notion of $\ell_1$ heavy hitters and are important in streams that have a skewed distribution of weights. In addition to the upper bound, we also provide a lower bound on the message complexity that is nearly tight up to a $log(1/\eps)$ factor. Finally, we use our weighted sampling algorithm to improve the message complexity of distributed $L_1$ tracking, also known as count tracking, which is a widely studied problem in distributed streaming. We also derive a tight message lower bound, which closes the message complexity of this fundamental problem.
Establishing a common metric for self‐reported anxiety in patients with prostate cancer: Linking the Memorial Anxiety Scale for Prostate Cancer with PROMIS Anxiety

Background Anxiety is a common patient concern and clinical endpoint in prostate cancer outcomes research. It is measured using different self-report instruments that are not directly comparable, thereby making clinical trials, clinical performance measurement, and comparative effectiveness research challenging when anxiety is the outcome of interest. The objective of the current study was to enable a common reporting metric of anxiety so that scores on commonly used anxiety measures could be converted into Patient-Reported Outcomes Measurement Information System (PROMIS) scores for ease of application, interpretation, and comparability. Methods Using an internet health panel, a total of 806 men with clinically localized prostate cancer completed items from the National Institutes of Health PROMIS Anxiety Short Form (version 7a) and the 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC). A common metric was created using analyses based on item response theory, producing score crosswalk tables. The linking relationships were evaluated by resampling small subsets and estimating confidence intervals for the differences between the observed and linked PROMIS scores. Results Results of factor analysis and item response theory model fit supported the hypothesis that both scales measure essentially the same concept. Therefore, crosswalk tables appear to be justified and increasingly robust with increasing sample sizes. Conclusions MAX-PC Anxiety results can be expressed on the PROMIS Anxiety metric for the purposes of clinical performance measurement, clinical trial outcomes, comparative effectiveness research, and other efforts to compare anxiety results across studies that use any one of these measures.
Discovery and in vitro evaluation of potent kinase inhibitors: Pyrido[1',2':1,5]pyrazolo[3,4-d]pyrimidines

The discovery, synthesis, potential binding mode, and in vitro kinase profile of several pyrido[1',2':1,5]pyrazolo[3,4-d]pyrimidines as potent kinase inhibitors are discussed.
An enantioselective synthesis of the C2–C16 segment of antitumor macrolide laulimalide

An enantioselective synthesis of the C2-C16 segment of the novel antitumor agent laulimalide is described. The key steps involve a highly diastereoselective allylation, ring-closing olefin metathesis of a homoallylic alcohol derived acrylate ester, a stereoselective anomeric alkylation and an elaboration of an exo-methylene unit by a Julia olefination reaction.
GAUGE FIELDS AND SPACE-TIME

In this article I attempt to collect some ideas, opinions and formulae which may be useful in solving the problem of gauge/string/space-time correspondence. This includes the validity of D-brane representation, counting of gauge-invariant words, relations between the null states and the Yang-Mills equations and the discussion of the strong coupling limit of the string sigma model. The article is based on the talk given at the "Odyssey 2001" conference.
Mononuclear heterocyclic rearrangement: Synthesis of [5:5] bicyclic [c]-fused 3-aminopyrazoles via the N-N bond formation strategy

The formation of [5:5] bicyclic heterocyclic ring systems containing [c]pyrazoles, i.e. imidazo[4,5-c]pyrazole, pyrazolo[3,4-c]pyrazole, pyrrolo-[2,3-c]pyrazole, and pyrazolo[3,4-d][1,2,3]triazole, was accomplished by mononuclear heterocyclic rearrangement (MHR). The core pyrazole ring was formed based on a N-N bond formation strategy. The ring transformation of 5-substituted 3-(2-aminoaryl)-1,2,4-oxadiazoles (14, 15a-b, 16b and 33) under thermal conditions to the corresponding [5:5] bicyclic [c]-fused 3-aminopyrazole ring systems (17a, 18a-b, 20 and 34 respectively) was promoted by sodium hydride in DMF or DMSO. The ring transformation by MHR has provided a practical and general synthetic method for the derivatives of 3-aminoimidazo-[4,5-c]pyrazole (4), 3-aminopyrazolo[3,4-c]pyrazole (5), 3-aminopyrrolo[2,3-c]-pyrazole (6) and 6-aminopyrazolo[3,4-d][1,2,3]triazole (7).
Simulation of P2X-mediated calcium signalling in microglia.

Key points A computational model of P2X channel activation in microglia was developed that includes downfield Ca2+ -dependent signalling pathways. This model provides quantitative insights into how diverse signalling pathways in microglia converge to control microglial function. Abstract Microglia function is orchestrated through highly coupled signalling pathways that depend on calcium (Ca2+ ). In response to extracellular ATP, transient increases in intracellular Ca2+ driven through the activation of purinergic receptors, P2X and P2Y, are sufficient to promote cytokine synthesis. Although the steps comprising the pathways bridging purinergic receptor activation with transcriptional responses have been probed in great detail, a quantitative model for how these steps collectively control cytokine production has not been established. Here we developed a minimal computational model that quantitatively links extracellular stimulation of two prominent ionotropic purinergic receptors, P2X4 and P2X7, with the graded production of a gene product, namely the tumour necrosis factor α (TNFα) cytokine. In addition to Ca2+ handling mechanisms common to eukaryotic cells, our model includes microglia-specific processes including ATP-dependent P2X4 and P2X7 activation, activation of nuclear factor of activated T-cells (NFAT) transcription factors, and TNFα production. Parameters for this model were optimized to reproduce published data for these processes, where available. With this model, we determined the propensity for TNFα production in microglia, subject to a wide range of ATP exposure amplitudes, frequencies and durations that the cells could encounter in vivo. Furthermore, we have investigated the extent to which modulation of the signal transduction pathways influence TNFα production. Our results suggest that pulsatile stimulation of P2X4 via micromolar ATP may be sufficient to promote TNFα production, whereas high-amplitude ATP exposure is necessary for production via P2X7. Furthermore, under conditions that increase P2X4 expression, for instance, following activation by pathogen-associated molecular factors, P2X4-associated TNFα production is greatly enhanced. Given that Ca2+ homeostasis in microglia is profoundly important to its function, this computational model provides a quantitative framework to explore hypotheses pertaining to microglial physiology.
Power Analysis Attack on Hardware Implementation of MAC-Keccak on FPGAs.

Keccak is the hash function selected by NIST as the new SHA-3 standard. Keccak is built on Sponge construction and it provides a new MAC function called MAC-Keccak. These new algorithms have raised questions with regards to side-channel leakage and analysis attacks of MAC-Keccak. So far there exists prior work on attacks of software implementations of MACKeccak, but there has been no comprehensive side-channel vulnerability assessment of its hardware implementation. In this paper we describe an attack on the θ step of the first round of MACKeccak implemented on an FPGA. We construct several different side-channel leakage models and implement attacks based on them. Our work shows that an unmasked hardware implementation of SHA-3 is vulnerable to power-based side-channel attacks.
VCPA: genomic variant calling pipeline and data management tool for Alzheimer's Disease Sequencing Project.

Summary We report VCPA, our SNP/Indel Variant Calling Pipeline and data management tool used for the analysis of whole genome and exome sequencing (WGS/WES) for the Alzheimer's Disease Sequencing Project. VCPA consists of two independent but linkable components: pipeline and tracking database. The pipeline, implemented using the Workflow Description Language and fully optimized for the Amazon elastic compute cloud environment, includes steps from aligning raw sequence reads to variant calling using GATK. The tracking database allows users to view job running status in real time and visualize >100 quality metrics per genome. VCPA is functionally equivalent to the CCDG/TOPMed pipeline. Users can use the pipeline and the dockerized database to process large WGS/WES datasets on Amazon cloud with minimal configuration. Availability and implementation VCPA is released under the MIT license and is available for academic and nonprofit use for free. The pipeline source code and step-by-step instructions are available from the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (http://www.niagads.org/VCPA). Supplementary information Supplementary data are available at Bioinformatics online.
The stereochemical outcome from mitsunobu couplings of vicinal, N-protected acyclic amino alcohols

Abstract Contrary to results expected in Mitsunobu reactions of amides derived from acyclic vic-amino alcohols (i.e., double inversion and hence, retention), urethane derivatives afford products solely of inversion.
Rhodium(III)-Catalyzed C-H Activation Mediated Synthesis of Isoquinolones from Amides and Cyclopropenes.

We have developed a synthesis of 4-substituted isoquinolones from the rhodium(III)-catalyzed, C–H activation mediated coupling of O-pivaloyl benzhydroxamic acids and 3,3-disubstituted cyclopropenes. Experiments suggest the formation of a [4.1.0] bicyclic system, which can open under acidic conditions to generate the desired isoquinolone.
Surface Acoustic Wave Chemical Sensor Arrays: New Chemically Sensitive Interfaces Combined with Novel Cluster Analysis To Detect Volatile Organic Compounds and Mixtures

Three approaches confer chemical selectivity upon a sensor-based system.1 The “traditional” approach uses a single sensor functionalized with a chemically sensitive material selective for the analyte. This works well when interferences are few, or chemically unlike the analyte, or when highly specific materialsse.g., suitable biological or molecular-recognition complexessare available. Even with exquisite selectivity, the transducer platform often must include a physical selectivity mechanism as well, so that nonspecific adsorption does not defeat a carefully crafted interface. An example is wavelength-specific optical detection that can differentiate between analytes physisorbed on the surfaces of a molecular cage and those residing inside. In contrast, a “nonspecific” transducer such as the mass-sensitive surface acoustic wave (SAW) device cannot differentiate between physisorbed and molecularly complexed mass on the surface of a device, unless a secondary perturbation such as a change in mechanical or electrical properties accompanies the mass change.2 Recent advances in both miniaturized and “micro” versions of traditional analytical techniques drive a second approach to chemical selectivity, that of separating analytes in time, space, or the spectral domain.3-5 Typified by electrophoretic separations in microfabricated channels on glass chips, the micro-total-analytical system (μ-TAS) approach can diminish the role of the sensor to that of a nonspecific detector that responds to any impinging compound. The elapsed time from sample introduction to detection, rather than detector selectivity, identifies the analyte. We focus in this Account on chemical sensor arrays as a means to obviate the difficult, costly process of developing a new material with high chemical specificity for each analyte: one array can provide distinct responses for tens of chemicals and mixtures. We emphasize that many of the subsections of this Account are, to varying degree, “platform independent”, so that arrays of optical fibers, electrochemical sensors, chemiresistors, metal oxides, or thermal devices can be conceptually substituted for the SAW platforms that we discuss in detail. The moderate selectivity requirements for arrays allow consideration of a much wider range of materialsseverything from common organic polymers to porous ceramicssthan for molecularly specific sensors. Furthermore, arrays retain some of the “passive sampling” features of discrete sensors that μ-TAS must relinquish due to its reliance upon addition of reagents, pumping, mixing, and the like.
Montmorillonite K10 Clay Catalyzed Synthesis of 4-Aryltetrahydropyrans: A One-Pot, Multicomponent, Environmentally Friendly Prins–Friedel–Crafts-Type Reaction

The Montmorillonite K10 clay catalyzed synthesis of 4-aryltetrahydropyrans is presented as a one-pot, multicomponent, environmentally friendly Prins–Friedel–Crafts-type reaction.
Synthesis of highly epimerizable N-protected α-amino aldehydes of high enantiomeric excess

Abstract The Dess–Martin periodinane was found to be a superior oxidant for the efficient, epimerization-free synthesis of optically active N -protected α-amino aldehydes from the corresponding N -protected β-amino alcohols. Highly racemization-prone products, including N -Fmoc phenylglycinal and N -trifluoroacetyl α-amino aldehydes, were prepared in ≥95% yield with ≤1% epimerization.
Diastereoselectivity in the lateral metalation and electrophilic quenching of isoxazolyloxazolines

Metalation and electrophilic quenching of chiral isoxazolyloxazolines at the C-5 position of the isoxazole gives rise to modest diastereoselectivity in most cases. In general, the 4(S)-(methoxymethyl)-5(S)-phenyl-2-oxazoline auxilliary (Meyer's reagent) produces the S absolute configuration at the C-5 isoxazole position of the major diastereomer, for priorities isoxazole>El>R>H. The enantiomerically pure isoxazolyloxazolines 3 can be obtained by preparative HPLC
Eukaryotic association module in phage WO genomes from Wolbachia

Viruses are trifurcated into eukaryotic, archaeal and bacterial categories. This domain-specific ecology underscores why eukaryotic viruses typically co-opt eukaryotic genes and bacteriophages commonly harbour bacterial genes. However, the presence of bacteriophages in obligate intracellular bacteria of eukaryotes may promote DNA transfers between eukaryotes and bacteriophages. Here we report a metagenomic analysis of purified bacteriophage WO particles of Wolbachia and uncover a eukaryotic association module in the complete WO genome. It harbours predicted domains, such as the black widow latrotoxin C-terminal domain, that are uninterrupted in bacteriophage genomes, enriched with eukaryotic protease cleavage sites and combined with additional domains to forge one of the largest bacteriophage genes to date (14,256 bp). To the best of our knowledge, these eukaryotic-like domains have never before been reported in packaged bacteriophages and their phylogeny, distribution and sequence diversity imply lateral transfers between bacteriophage/prophage and animal genomes. Finally, the WO genome sequences and identification of attachment sites will potentially advance genetic manipulation of Wolbachia. Viruses commonly exchange genetic material with their hosts, but not with species from other domains of life. Here, the authors find that the bacteriophage WO of Wolbachiacontains eukaryotic-like genes, implicating lateral genetic transfer between eukaryotes and viruses infecting bacteria.
Spatial variation of the native colon microbiota in healthy adults

The microbiome has been implicated in the development of colorectal cancer and inflammatory bowel diseases. The specific traits of these diseases vary along the axis of the digestive tract. Further, variation in the structure of the gut microbiota has been associated with both diseases. We profiled the microbiota of the healthy proximal and distal mucosa and lumen to better understand how bacterial populations vary along the colon. We used a two-colonoscope approach to sample proximal and distal mucosal and luminal contents from the colons of 20 healthy subjects that had not undergone any bowel preparation procedure. The biopsies and home-collected stool were subjected to 16S rRNA gene sequencing, and random forest classification models were built using taxa abundance and location to identify microbiota specific to each site. The right mucosa and lumen had the most similar community structures of the five sites we considered from each subject. The distal mucosa had higher relative abundance of Finegoldia, Murdochiella, Peptoniphilus, Porphyromonas, and Anaerococcus The proximal mucosa had more of the genera Enterobacteriaceae, Bacteroides, and Pseudomonas The classification model performed well when classifying mucosal samples into proximal or distal sides (AUC = 0.808). Separating proximal and distal luminal samples proved more challenging (AUC = 0.599), and specific microbiota that differentiated the two were hard to identify. By sampling the unprepped colon, we identified distinct bacterial populations native to the proximal and distal sides. Further investigation of these bacteria may elucidate if and how these groups contribute to different disease processes on their respective sides of the colon. Cancer Prev Res; 11(7); 393-402. ©2018 AACR.
Fluorinated stannanes ☆: Part 2. The stereospecific synthesis of fluorinated stannanes via a Barbier-type reaction between fluorinated halides and tributyltin chloride mediated by zinc or cadmium

Abstract Fluorinated stannanes are valuable synthons in synthetic organofluorine chemistry. Fluorinated vinyl, alkyl and aryl halides reacted efficiently with tri- n -butyltin chloride in the presence of zinc or cadmium to yield the corresponding stannanes in good yields. In some cases, yield of the stannanes showed a dramatic improvement over the transmetalation method. In all other cases, comparable yields were obtained.
Anti-phage islands force their target phage to directly mediate island excision and spread

Vibrio cholerae, the causative agent of the diarrheal disease cholera, is antagonized by the lytic phage ICP1 in the aquatic environment and in human hosts. Mobile genetic elements called PLEs (phage-inducible chromosomal island-like elements) protect V. cholerae from ICP1 infection and initiate their anti-phage response by excising from the chromosome. Here, we show that PLE 1 encodes a large serine recombinase, Int, that exploits an ICP1-specific protein as a recombination directionality factor (RDF) to excise PLE 1 in response to phage infection. We show that this phage-encoded protein is sufficient to direct Int-mediated recombination in vitro and that it is highly conserved in all sequenced ICP1 genomes. Our results uncover an aspect of the molecular specificity underlying the conflict between a single predatory phage and V. cholerae PLE and contribute to our understanding of long-term evolution between phage and their bacterial hosts.
Synthesis of 2-amino-4-oxo-5-substitutedbenzylthiopyrrolo[2,3-d]-pyrimidines as potential inhibitors of thymidylate synthase †

A series of ten novel 2-amino-4-oxo-5-[(substitutedbenzyl)thio]pyrrolo[2,3-d]pyrimidines 2-11 were synthesized as potential inhibitors of thymidylate synthase and as antitumor agents. The analogues contain various electron withdrawing and electron donating substituents on the benzylsulfanyl ring of the side chains and were synthesized from the key intermediate 2-amino-4-oxo-6-methylpyrrolo[2,3-d]pyrimidine, 14. Appropriately substituted benzyl mercaptans were appended to the 5-position of 14 via an oxidative addition reaction using iodine, ethanol and water. The compounds were evaluated against human, Escherichia coli and Toxoplasma gondii thymidylate synthase and against human, Escherichia coli and Toxoplasma gondii dihydrofolate reductase. The most potent inhibitor, (6) which has a 4′-methoxy substituent on the side chain, has an IC50=25 μM against human thymidylate synthase. Contrary to analogues of general structure 1, electron donating or electron withdrawing substituents on the side chain of 2-11 had little or no influence on the human thymidylate synthase inhibitory activity.
Synthesis of 4'-epi-iodo-4'-deoxy-daunorubicin, a potential cancer radiotherapeutic agent.

Abstract We have prepared 4′- epi -iodo-4′-deoxy-daunorubicin (IDDNR)( 1 ), a doxorubicin analog, via a 5-step synthesis involving a protected daunorubicin triflate derivative ( 4 ). This triflate derivative will allow the facile and regiospecific nucleophilic preparation of I-125 or Br-80m labelled analogs of IDDNR. Auger electron-emitting I-125- or Br-80m-labelled analogs of IDDNR may have potential as cancer radiotherapeutic agents.
Developing an automated iterative near-term forecasting system for an ecological study

Most forecasts for the future state of ecological systems are conducted once and never updated or assessed. As a result, many available ecological forecasts are not based on the most up-to-date data, and the scientific progress of ecological forecasting models is slowed by a lack of feedback on how well the forecasts perform. Iterative near-term ecological forecasting involves repeated daily to annual scale forecasts of an ecological system as new data becomes available and regular assessment of the resulting forecasts. We demonstrate how automated iterative near-term forecasting systems for ecology can be constructed by building one to conduct monthly forecasts of rodent abundances at the Portal Project, a long-term study with over 40 years of monthly data. This system automates most aspects of the six stages of converting raw data into new forecasts: data collection, data sharing, data manipulation, modeling and forecasting, archiving, and presentation of the forecasts. The forecasting system uses R code for working with data, fitting models, making forecasts, and archiving and presenting these forecasts. The resulting pipeline is automated using continuous integration (a software development tool) to run the entire pipeline once a week. The cyberinfrastructure is designed for long-term maintainability and to allow the easy addition of new models. Constructing this forecasting system required a team with expertise ranging from field site experience to software development. Automated near-term iterative forecasting systems will allow the science of ecological forecasting to advance more rapidly and provide the most up-to-date forecasts possible for conservation and management. These forecasting systems will also accelerate basic science by allowing new models of natural systems to be quickly implemented and compared to existing models. Using existing technology, and teams with diverse skill sets, it is possible for ecologists to build these systems and use them to advance our understanding of natural systems.
Preparation and evaluation of a cyclic acyl nitrone as a synthon for stereospecific α-amino acid synthesis

Abstract The preparation and characterization of cyclic optically active (5R)-3,4,5,6-tetrahydro-5-phenyl-2H-1,4-oxazin-2-one-N-oxide (2) is described. This nitrone, which is viewed as a template for the synthesis of γ-oxygenated α-amino acids, reacts with alkenes efficiently and with high stereospecificity.
From Arene Oxides to Diol Epoxides and DNA

Abstract Although the polycyclic aromatic hydrocarbons (PAH) are structurally less complex compared to many other compounds with high biological activity, their metabolism, the chemical reactivity of their metabolites, and the mutagenicity and tumorigenicity of these metabolites have stimulated intensive research into their mechanisms of action. The present report focuses on our contributions to the identification of bay-region and fjord-region diol epoxides as ultimate carcinogens of the PAH and describes some of the remarkable stereochemical control involved in their synthesis, metabolic formation, and expression of tumorigenic activity.
Superresolution microscopy of the β-carboxysome reveals a homogeneous matrix

Application of 3D-structured illumination microscopy to study the protein organization of the β-carboxysome in Synechococcus elongatus reveals new structural details of this bacterial microcompartm...
Efficient and selective N-alkylation of carbamates in the presence of Cs2CO3 and TBAI

Abstract Mild and selective N -alkylation of carbamates was carried out in the presence of cesium carbonate, tetrabutylammonium iodide (TBAI), and a halide. This protocol was highly selective and efficient, offering aliphatic and aromatic N -alkyl carbamates exclusively in high yields.