cssi/SciSciGPT-SciSciNet huggingface dataset:
The Missing Link? The Strategic Role of Procurement in Building Sustainable Supply Networks

The increasing number of scandals about supplier violations of environmental and social regulations has put multinational companies’ (MNCs) reputations at risk. Customers make MNCs accountable for such violations, regardless of whether the violations involve tier‐one or lower‐tier suppliers. To address this pressure, some MNCs require their tier‐one suppliers to comply with their sustainability requirements and ask them to “cascade” such requirements to their (lower‐tier) suppliers. This research investigates why this cascading effect often fails. I used inductive research to study three supply networks in the automotive, electronics, and pharmaceutical/consumer product industries. Three MNCs, 9 tier‐one suppliers, 22 lower‐tier suppliers, and 3 industry associations participated. This research (a) reveals that to cascade a buyer's sustainability requirements, the buyer's procurement unit needs to directly engage the supplier's procurement unit; (b) identifies three key interlinked procurement processes—assessing, training, and incentivizing—involving both suppliers and procurement personnel who are instrumental in building sustainable supply networks; and (c) shows how the lack of collaboration between procurement and internal (i.e., sustainability and R&D) and external stakeholders (i.e., industry associations) limits an MNC's effort to promote sustainability throughout the supply network. Thus, this study highlights procurement's strategic role in building sustainable supply networks and suggests important research directions for how to achieve sustainability throughout the supply networks.
Exclusionary Zoning and the Limits of Judicial Impact

Courts in the neighboring states of New Jersey, New York, and Pennsylvania have taken divergent approaches to local exclusionary zoning, which entails land use regulations restricting the developme...
Prevention of Heart Failure in Hypertension-Disentangling the Role of Evolving Left Ventricular Hypertrophy and Blood Pressure Lowering: The ALLHAT Study.

Background Hypertension is a known risk factor for heart failure (HF), possibly via the mechanism of cardiac remodeling and left ventricular hypertrophy (LVH). We studied the extent to which blood ...
Genetic architecture of laterality defects revealed by whole exome sequencing

Aberrant left-right patterning in the developing human embryo can lead to a broad spectrum of congenital malformations. The causes of most laterality defects are not known, with variants in established genes accounting for <20% of cases. We sought to characterize the genetic spectrum of these conditions by performing whole-exome sequencing of 323 unrelated laterality cases. We investigated the role of rare, predicted-damaging variation in 1726 putative laterality candidate genes derived from model organisms, pathway analyses, and human phenotypes. We also evaluated the contribution of homo/hemizygous exon deletions and gene-based burden of rare variation. A total of 28 candidate variants (26 rare predicted-damaging variants and 2 hemizygous deletions) were identified, including variants in genes known to cause heterotaxy and primary ciliary dyskinesia (ACVR2B, NODAL, ZIC3, DNAI1, DNAH5, HYDIN, MMP21), and genes without a human phenotype association, but with prior evidence for a role in embryonic laterality or cardiac development. Sanger validation of the latter variants in probands and their parents revealed no de novo variants, but apparent transmitted heterozygous (ROCK2, ISL1, SMAD2), and hemizygous (RAI2, RIPPLY1) variant patterns. Collectively, these variants account for 7.1% of our study subjects. We also observe evidence for an excess burden of rare, predicted loss-of-function variation in PXDNL and BMS1- two genes relevant to the broader laterality phenotype. These findings highlight potential new genes in the development of laterality defects, and suggest extensive locus heterogeneity and complex genetic models in this class of birth defects.
Pseudorandom Generators from the Second Fourier Level and Applications to AC0 with Parity Gates

A recent work of Chattopadhyay et al. (CCC 2018) introduced a new framework for the design of pseudorandom generators for Boolean functions. It works under the assumption that the Fourier tails of the Boolean functions are uniformly bounded for all levels by an exponential function. In this work, we design an alternative pseudorandom generator that only requires bounds on the second level of the Fourier tails. It is based on a derandomization of the work of Raz and Tal (ECCC 2018) who used the above framework to obtain an oracle separation between BQP and PH. As an application, we give a concrete conjecture for bounds on the second level of the Fourier tails for low degree polynomials over the finite field F_2. If true, it would imply an efficient pseudorandom generator for AC^0[oplus], a well-known open problem in complexity theory. As a stepping stone towards resolving this conjecture, we prove such bounds for the first level of the Fourier tails.
Locality Sensitive Imputation for Single Cell RNA-Seq Data.

One of the most notable challenges in single cell RNA-Seq data analysis is the so called drop-out effect, where only a fraction of the transcriptome of each cell is captured. The random nature of drop-outs, however, makes it possible to consider imputation methods as means of correcting for drop-outs. In this paper we study some existing scRNA-Seq imputation methods and propose a novel iterative imputation approach based on efficiently computing highly similar cells. We then present the results of a comprehensive assessment of existing and proposed methods on real scRNA-Seq datasets with varying per cell sequencing depth.
Deflationary Pressures Today: The Chinese, Japanese and Spanish Cases Compared

This article considers the role of supply-side factors in the deflationary pressures seen in the aftermath of the global financial crisis. Although declines in consumer prices have been mild, much ...
Real-time multiprocessor locks with nesting: optimizing the common case

In prior work on multiprocessor real-time locking protocols, only protocols within the RNLP family support unrestricted lock nesting while guaranteeing asymptotically optimal priority-inversion blocking bounds. However, these protocols support nesting at the expense of increasing the cost of processing non-nested lock requests, which tend to be the common case in practice. To remedy this situation, a new fast-path mechanism is presented herein that extends prior RNLP variants by ensuring that non-nested requests are processed efficiently. This mechanism yields overhead and blocking costs for such requests that are nearly identical to those seen in the most efficient single-resource locking protocols. In experiments, the proposed fast-path mechanism enabled observed blocking times for non-nested requests that were up to 18 times lower than under an existing RNLP variant and improved schedulability over that variant and a simple group lock.
Maternal anemia and pregnancy outcomes: a population-based study.

This study aims to describe adverse maternal and neonatal outcomes in women diagnosed with anemia in pregnancy. This was a retrospective cohort study of California live births from 2007–2012, linked to maternal and infant hospital discharge records. Relative risks of adverse maternal and neonatal outcomes were calculated for women with and without anemia. Anemic mothers were more likely to be diagnosed with hypertension, diabetes, placental abruption, or chorioamnionitis, or require a blood transfusion or admission to the intensive care unit (aRRs 1.2–6.8). Infants born to anemic mothers were more likely to be born preterm (8.9% versus 6.5%), but not more likely to suffer morbidities associated with prematurity. In a population-based study, the diagnosis of anemia in pregnancy carries a higher risk of peri-partum, intra-partum, and post-partum complications for the mother, and a higher risk of preterm birth for the infant.
Optimal Interactive Coding for Insertions, Deletions, and Substitutions

Interactive coding, pioneered by Schulman (FOCS ’92, STOC ’93), is concerned with making communication protocols resilient to adversarial noise. The canonical model allows the adversary to alter a small constant fraction of symbols, chosen at the adversary’s discretion, as they pass through the communication channel. Braverman et al. proposed a far-reaching generalization of this model, whereby the adversary can additionally manipulate the channel by removing and inserting symbols. For any $\epsilon >0,$ they showed how to faithfully simulate any protocol in this model with corruption rate up to $1/18-\epsilon ,$ using a constant-size alphabet and a constant-factor overhead in communication. We give an optimal simulation of any protocol in this generalized model of substitutions, insertions, and deletions, tolerating a corruption rate up to $1/4-\epsilon $ , while keeping the alphabet to a constant size and the communication overhead to a constant factor. This resolves a question due to Gelles (2015). Our corruption tolerance matches an impossibility result for corruption rate 1/4 which holds even for substitutions alone (Braverman and Rao, STOC ‘11).
The associations between query-based and directed health information exchange with potentially avoidable use of health care services.

Objective To quantify the impact of two approaches (directed and query-based) to health information exchange (HIE) on potentially avoidable use of health care services. Data sources/study setting Data on ambulatory care providers' adoption of HIE were merged with Medicare fee-for-service claims from 2008 to 2014. Providers were from 13 counties in New York served by the Rochester Regional Health Information Organization (RHIO). Study design Linear regression models with provider and year fixed effects were used to estimate changes in the probability of utilization outcomes for Medicare beneficiaries attributed to providers adopting directed and/or query-based HIE compared with beneficiaries attributed to providers who had not adopted HIE. Data collection Providers' HIE adoption status was determined through Rochester RHIO registration records. RHIO and claims data were linked via National Provider Identifiers. Principal findings Query-based HIE adoption was associated with a 0.2 percentage point reduction in the probability of an ambulatory care sensitive hospitalization and a 1.1 percentage point decrease in the likelihood of an unplanned readmission. Directed HIE adoption was not associated with any outcome. Conclusions The Centers for Medicare & Medicaid Services' (CMS) EHR certification criteria includes requirements for directed HIE, but not query-based HIE. Pending further research, certification criteria should place equal weight on facilitating query-based and directed exchange.
Synthesis and antibacterial activity of 7-ethyl-3-methyl-4,7-dihydro-4-oxoisothiazolo[5,4-b]pyridine-5-carboxylic acid

The synthesis of the quinolone, 7-ethyl-3-methyl-4,7-dihydro-4-oxoisothiazolo[5,4-b]pyridine-5-carboxylic acid 4 was accomplished utilizing the Gould-Jacobs dependent route. The compound had very weak in vitro activity as compared to nalidixic acid versus E. coli, P. aeruginosa, K. pnuemoniae, S. aureus and P. mirabilis.
Approaches for synthesizing breathing MOFs by exploiting dimensional rigidity

Abstract A subclass of metal-organic frameworks (MOFs) undergoes a “breathing” phenomenon which is a reversible flexing of the framework as a function of adsorbed guest. The existence of multiple stable states in a single framework leads to the modification of the shape and size of the pores as a function of guest, and has encouraged researchers to consider innovative applications for these flexible materials. To assist in improving the designs of these breathing MOFs, a thorough understanding of the different mechanisms by which frameworks breathe, must be established. This review will classify current breathing mechanisms by designating which part of the framework will not flex. By classifying the dimensional rigidity within a framework, a more in-depth discussion of each breathing mechanism can be established. Additionally, strategies for the design and synthesis of the next generation of breathing MOFs based on the reviewed research are discussed.
Iron-sulfur cluster biosynthesis: toward an understanding of cellular machinery and molecular mechanism.

Iron-sulfur clusters are among the most complex metal-containing prosthetic centers in biology. Most if not all of the proteins involved in the biosynthesis of “simple” Fe-S clusters have been identified. The structural and functional chemistry of these proteins has been the subject of intense research efforts, and many of the key details are now understood in structural and mechanistic detail. The fact that Fe-S cluster-binding proteins can be reconstituted in vitro with no accessory proteins provides an important indicator of the intracellular roles for many proteins on the Fe-S cluster assembly pathway. Indeed, such proteins are more correctly viewed as carrier proteins, rather than as catalysts for the reaction, that both avoid the toxicity associated with free iron and sulfide and allow delivery at lower intracellular concentrations of these species. The IscU (or ISU) family of proteins serves a key role as scaffolding proteins on which [2Fe-2S] building blocks are assembled prior to transfer to final apo target proteins. IscU in particular exhibits highly unusual conformational flexibility that appears critical to its function.
Both DNA Polymerases δ and ε Contact Active and Stalled Replication Forks Differently.

Three DNA polymerases, polymerases α, δ, and e (Pol α, Pol δ, and Pol e), are responsible for eukaryotic genome duplication. When DNA replication stress is encountered, DNA synthesis stalls until the stress is ameliorated. However, it is not known whether there is a difference in the association of each polymerase with active and stalled replication forks. Here, we show that each DNA polymerase has a distinct pattern of association with active and stalled replication forks. Pol α is enriched at extending Okazaki fragments of active and stalled forks. In contrast, although Pol δ contacts the nascent lagging strands of active and stalled forks, it binds to only the matured (and not elongating) Okazaki fragments of stalled forks. Pol e has greater contact with the nascent single-stranded DNA (ssDNA) of the leading strand on active forks than on stalled forks. We propose that the configuration of DNA polymerases at stalled forks facilitates the resumption of DNA synthesis after stress removal.
Micro-UAV Detection with a Low-Grazing Angle Millimeter Wave Radar

Millimeter wave radars are popularly used in last-mile radar-based defense systems. Detection of low-altitude airborne target using these radars at low-grazing angles is an important problem in the field of electronic warfare, which becomes challenging due to the significant effects of clutters in the terrain. This paper provides both experimental and analytical investigation of micro unmanned aerial vehicle (UAV) detection in a rocky terrain using a low grazing angle, surface-sited 24 GHz dual polarized frequency modulated continuous wave (FMCW) radar. The radar backscatter signal from the UAV is polluted by land clutters which is modeled using a uniform Weibull distribution. A constant false alarm rate (CFAR) detector which employs adaptive thresholding is designed to detect the UAV in the rich clutter background. In order to further enhance the discrimination of the UAV from the clutter, the micro-Doppler signature of the rotating propellers and bulk trajectory of the UAV are extracted and plotted in the time-frequency domain.
The magic of the delta bonds: How to modulate electronic communication in pairs-of-pairs containing multiple bonded Mo2 species

Abstract An account is presented of the work done in our Laboratory at Texas A&M University on pairs-of-pairs whereby two multiple-bonded dimolybdenum units are joined by various types of linkers. These species that behave as Creutz–Taube analogs show that under appropriate conditions, electronic communication is facilitated by the electrons in delta bonds. The account shows how various experimental techniques such as electrochemical measurements, X-ray crystallography, near-infrared spectroscopy, EPR and NMR spectroscopies, magnetism and theoretical computations complement each other while interrogating these compounds.
Reactions of activated aryl sydnones with electrophiles

Electrophilic substitution on the aryl or sydnone ring of some ortho-substituted activated N-aryl-sydnones is reported.
Twenty-first Century Lattice Gauge Theory: Results from the QCD Lagrangian

Quantum chromodynamics (QCD) reduces the strong interactions, in all their variety, to an elegant nonabelian gauge theory. It clearly and elegantly explains hadrons at short distances, which has led to its universal acceptance. Since its advent, however, many of its long-distance, emergent properties have been believed to be true, without having been demonstrated to be true. This paper reviews a variety of results in this regime that have been established with lattice gauge theory, directly from the QCD Lagrangian. This body of work sheds light on the origin of hadron masses, its interplay with dynamical symmetry breaking, as well as on other intriguing features such as the phase structure of QCD. In addition, nonperturbative QCD is quantitatively important to many aspects of particle physics (especially the quark flavor sector), nuclear physics, and astrophysics. This review also surveys some of the most interesting connections to those subjects.
A base-catalyzed solution-phase parallel synthesis of substituted vinylic benzamides from 3-amino-2-cyclohexanones.

An improved method for the synthesis of benzamides from 3-amino-2-cyclohexenones is presented. Using sodium hydride, a base-catalyzed N-benzoylation provided significantly higher yields (71−79%) for the reported compounds. This novel protocol was applied in the solution-phase parallel synthesis of a 12-member library of vinylic benzamide derivatives of 3-amino-2-cyclohexenones in 63−90% yield, using a Radley's Carousel Reaction Station.
Non-Invasive Assays of Cochlear Synaptopathy – Candidates and Considerations

Abstract Studies in multiple species, including in post-mortem human tissue, have shown that normal aging and/or acoustic overexposure can lead to a significant loss of afferent synapses innervating the cochlea. Hypothetically, this cochlear synaptopathy can lead to perceptual deficits in challenging environments and can contribute to central neural effects such as tinnitus. However, because cochlear synaptopathy can occur without any measurable changes in audiometric thresholds, synaptopathy can remain hidden from standard clinical diagnostics. To understand the perceptual sequelae of synaptopathy and to evaluate the efficacy of emerging therapies, sensitive and specific non-invasive measures at the individual patient level need to be established. Pioneering experiments in specific mice strains have helped identify many candidate assays. These include auditory brainstem responses, the middle-ear muscle reflex, envelope-following responses, and extended high-frequency audiograms. Unfortunately, because these non-invasive measures can be also affected by extraneous factors other than synaptopathy, their application and interpretation in humans is not straightforward. Here, we systematically examine six extraneous factors through a series of interrelated human experiments aimed at understanding their effects. Using strategies that may help mitigate the effects of such extraneous factors, we then show that these suprathreshold physiological assays exhibit across-individual correlations with each other indicative of contributions from a common physiological source consistent with cochlear synaptopathy. Finally, we discuss the application of these assays to two key outstanding questions, and discuss some barriers that still remain. This article is part of a Special Issue entitled: Hearing Loss, Tinnitus, Hyperacusis, Central Gain.
Inhibition of Glyoxalase 1 reduces alcohol self-administration in dependent and nondependent rats.

Previous studies showed that the glyoxalase 1 (Glo1) gene modulates anxiety-like behavior, seizure susceptibility, depression-like behavior, and alcohol drinking in the drinking-in-the-dark paradigm in nondependent mice. Administration of the small-molecule GLO1 inhibitor S-bromobenzylglutathione cyclopentyl diester (pBBG) decreased alcohol drinking in nondependent mice, suggesting a possible therapeutic strategy. However, the preclinical therapeutic efficacy of pBBG in animal models of alcohol dependence remains to be demonstrated. We tested the effect of pBBG (7.5 and 25 mg/kg) on operant alcohol self-administration in alcohol-dependent and nondependent rats. Wistar rats were trained to self-administer 10% alcohol (v/v) and made dependent by chronic intermittent passive exposure to alcohol vapor for 5 weeks. Pretreatment with pBBG dose-dependently reduced alcohol self-administration in both nondependent and dependent animals, without affecting water self-administration. pBBG treatment was more effective in dependent rats than in nondependent rats. These data extend previous findings that implicated Glo1 in alcohol drinking in nondependent mice by showing even more profound effects in alcohol-dependent rats. These results suggest that the pharmacological inhibition of GLO1 is a relevant therapeutic target for the treatment of alcohol use disorders.
Low-Cost Concurrent Error Detection for GCM and CCM.

In many applications, encryption alone does not provide enough security. To enhance security, dedicated authenticated encryption (AE) mode are invented. Galios Counter Mode (GCM) and Counter with CBC-MAC mode (CCM) are the AE modes recommended by the National Institute of Standards and Technology. To support high data rates, AE modes are usually implemented in hardware. However, natural faults reduce its reliability and may undermine both its encryption and authentication capability. We present a low-cost concurrent error detection (CED) scheme for 7 AE architectures. The proposed technique explores idle cycles of the AE mode architectures. Experimental results shows that the performance overhead can be lower than 100% for all architectures depending on the workload. FPGA implementation results show that the hardware overhead in the 0.1-23.3% range and the power overhead is in the 0.2-23.2% range. ASIC implementation results show that the hardware overhead in the 0.1-22.8% range and the power overhead is in the 0.3-12.6% range. The underlying block cipher and hash module need not have CED built in. Thus, it allows system designers to integrate block cipher and hash function intellectual property from different vendors.
CscoreTool: fast Hi-C compartment analysis at high resolution.

Summary The genome-wide chromosome conformation capture (Hi-C) has revealed that the eukaryotic genome can be partitioned into A and B compartments that have distinctive chromatin and transcription features. Current Principle Component Analyses (PCA)-based method for the A/B compartment prediction based on Hi-C data requires substantial CPU time and memory. We report the development of a method, CscoreTool, which enables fast and memory-efficient determination of A/B compartments at high resolution even in datasets with low sequencing depth. Availability and implementation https://github.com/scoutzxb/CscoreTool. Contact xzheng@carnegiescience.edu. Supplementary information Supplementary data are available at Bioinformatics online.
THEORY OF NEUTRAL PARTICLES: MCLENNAN-CASE CONSTRUCT FOR NEUTRINO, ITS GENERALIZATION, AND A NEW WAVE EQUATION

Continuing our recent argument where we constructed a FNBWW type spin-1 boson having opposite relative intrinsic parity to that of the associated antiparticle, we now study eigenstates of the charge conjugation operator. Based on the observation that if ϕL(pμ) transforms as a (0, j) spinor under Lorentz boosts, then transforms as a (j, 0) spinor [with a similar relationship existing between ϕR(pμ) and where w ith Θ[j] the well-known Wigner matrix involved in the operation of time reversal] we introduce McLennan-Case type (j, 0)⊗(0, j) spinors. Relative phases between ϕR(pμ) and and and ϕL(pμ), turn out to have physical significance and are fixed by appropriate requirements. An explicit construction, and a series of physically relevant properties, for these spinors are obtained for spin-1/2 and spin-1 culminating in the construction of a new wave equation and the introduction of Dirac-like and Majorana-like quantum fields.
Analyzing Single Molecule Localization Microscopy Data Using Cubic Splines

The resolution of super-resolution microscopy based on single molecule localization is in part determined by the accuracy of the localization algorithm. In most published approaches to date this localization is done by fitting an analytical function that approximates the point spread function (PSF) of the microscope. However, particularly for localization in 3D, analytical functions such as a Gaussian, which are computationally inexpensive, may not accurately capture the PSF shape leading to reduced fitting accuracy. On the other hand, analytical functions that can accurately capture the PSF shape, such as those based on pupil functions, can be computationally expensive. Here we investigate the use of cubic splines as an alternative fitting approach. We demonstrate that cubic splines can capture the shape of any PSF with high accuracy and that they can be used for fitting the PSF with only a 2–3x increase in computation time as compared to Gaussian fitting. We provide an open-source software package that measures the PSF of any microscope and uses the measured PSF to perform 3D single molecule localization microscopy analysis with reasonable accuracy and speed.
Synthesis and Biological Evaluation of a "Natural" Insect Repellent

(11Z)-11,19-Icosadienyl acetate (1) has been shown to be an efficient repellent against the ant Myrmica rubra whereas its corresponding (11E) stereoisomer 2 does not exhibit any repellent activity at all. Several synthetic strategies for these two compounds have been evaluated.
The temporal evolution of conceptual object representations revealed through models of behavior, semantics and deep neural networks.

Abstract Visual object representations are commonly thought to emerge rapidly, yet it has remained unclear to what extent early brain responses reflect purely low-level visual features of these objects and how strongly those features contribute to later categorical or conceptual representations. Here, we aimed to estimate a lower temporal bound for the emergence of conceptual representations by defining two criteria that characterize such representations: 1) conceptual object representations should generalize across different exemplars of the same object, and 2) these representations should reflect high-level behavioral judgments. To test these criteria, we compared magnetoencephalography (MEG) recordings between two groups of participants (n = 16 per group) exposed to different exemplar images of the same object concepts. Further, we disentangled low-level from high-level MEG responses by estimating the unique and shared contribution of models of behavioral judgments, semantics, and different layers of deep neural networks of visual object processing. We find that 1) both generalization across exemplars as well as generalization of object-related signals across time increase after 150 ms, peaking around 230 ms; 2) representations specific to behavioral judgments emerged rapidly, peaking around 160 ms. Collectively, these results suggest a lower bound for the emergence of conceptual object representations around 150 ms following stimulus onset.
A solvent-free amidation of vinylogous esters via direct aziridination

Abstract A microwave-mediated aziridination of α,β-unsaturated ketones and esters through the decomposition of ethyl azidoformate has been developed. When the same atom-economical reaction conditions are applied to cyclic vinylogous esters, N-functionalization at the α-position occurs. Based on NMR analysis, these amidation products appear to be formed from the desired aziridine in moderate to good yields.
Complementary Information and Learning Traps

We develop a model of social learning from complementary information: short-lived agents sequentially choose from a large set of flexibly correlated information sources for prediction of an unknown state, and information is passed down across periods. Will the community collectively acquire the best kinds of information? Long-run outcomes fall into one of two cases: (i) efficient information aggregation, where the community eventually learns as fast as possible; (ii) “learning traps,” where the community gets stuck observing suboptimal sources and information aggregation is inefficient. Our main results identify a simple property of the underlying informational complementarities that determines which occurs. In both regimes, we characterize which sources are observed in the long run and how often.
Reclothing the Legal Emperor: Justice, Equity, and Governance in the Flat World.

In Rules for a Flat World , Hadfield delivers a paradigm-shifting wakeup call about law coming up short in today’s world and proposes creating markets for legal rules to enable the development of broad-based legal infrastructure that can meet current and future demand. I am less confident that markets are the preferred pattern for the emperor’s new wardrobe because law hearkens to non-market values. Aspirations to justice and equity lie at the heart of the enterprise of law, and they should be touchstones in transforming law for today’s flat world. Moreover, governance today – beyond the government-based governance generally acknowledged by lawyers – is more flat-world-friendly than we may initially realize, and our quest to transform law should be grounded in the robust and vibrant network of deliberation, policy-development and policy-implementation arrangements, and conflict engagement and resolution that already exists.
Accelerated simulation of evolutionary trajectories in origin-fixation models

We present an accelerated algorithm to forward-simulate origin-fixation models. Our algorithm requires, on average, only about two fitness evaluations per fixed mutation, whereas traditional algorithms require, per one fixed mutation, a number of fitness evaluations of the order of the effective population size, Ne Our accelerated algorithm yields the exact same steady state as the original algorithm but produces a different order of fixed mutations. By comparing several relevant evolutionary metrics, such as the distribution of fixed selection coefficients and the probability of reversion, we find that the two algorithms behave equivalently in many respects. However, the accelerated algorithm yields less variance in fixed selection coefficients. Notably, we are able to recover the expected amount of variance by rescaling population size, and we find a linear relationship between the rescaled population size and the population size used by the original algorithm. Considering the widespread usage of origin-fixation simulations across many areas of evolutionary biology, we introduce our accelerated algorithm as a useful tool for increasing the computational complexity of fitness functions without sacrificing much in terms of accuracy of the evolutionary simulation.
An Efficient Synthesis Of 6-Substituted 2-(2H-[1,2,4]Triazol-3-Ylmethyl)-1,2,3,4-Tetrahydro-Isoquinolines

Abstract A synthesis of 6-nitro and 6-amino 2-(2H-[1,2,4]triazol-3-ylmethyl)-1,2,3,4-tetrahydro-isoquinolines using a bis-alkylation process is described. 5-(Aminomethyl)-1-(p-methoxybenzyl)-triazole was prepared by a regioselective route from 1,2,4-triazole.
APPLES: Fast Distance-Based Phylogenetic Placement.

Abstract Phylogenetic placement consists of adding a query species onto an existing phylogeny and has increasing relevance as sequence datasets continue to grow in size and diversity. Placement is useful for updating existing phylogenies and for identifying samples taxonomically using (meta-)barcoding or metagenomics. Maximum likelihood (ML) methods of phylogenetic placement exist, but these methods are not scalable to trees with many thousands of leaves. They also rely on assembled and aligned sequences for the reference tree and the query and thus cannot analyze unassembled reads used recently in applications such as genome skimming. Here, we introduce APPLES, a distance-based method of phylogenetic placement that improves on ML by more than an order of magnitude in speed and memory and comes very close to ML in accuracy. APPLES has better accuracy than ML for placing on trees with thousands of species and can place on trees with a hundred thousands species where ML cannot run. Finally, APPLES can accurately identify samples without assembled sequences for the reference or the query using k-mer-based distances, a scenario that ML cannot handle.
Independent Synthesis, Solution Behavior, and Studies on the Mechanism of Formation of a Primary Amine-Derived Fluorophore Representing Cross-linking of Proteins by (E)-4-Hydroxy-2-nonenal

Lipid peroxidation in aging and degenerative disease results in the production of 4-hydroxy-2-alkenals that modify proteins and give rise to both protein cross-linking and fluorophore generation. Recent model studies demonstrated that the major ex/em 360/430 fluorophore formed from (E)-4-hydroxy-2-nonenal (HNE) or (E)-4-hydroxy-2-hexenal (HHE) and protein lysine-based amine is a 2-alkyl-2-hydroxy-1,2-dihydropyrrol-3-one iminium 1:2 cross-link (1), a structure that is further confirmed here using 15N-labeling, and which has pH stability characteristics the same as those of lipofuscin pigments isolated from human tissues. Fluorophore generation represents an overall four-electron oxidation, requires dioxygen, and is enhanced by the presence of Cu(II). The HNE−propylamine-derived fluorophore 1a was independently synthesized from either 3,4-dioxononanal (8) or (E)-4-oxo-2-nonenal (13), providing further evidence for its assigned structure and clues to how it forms from HNE. Mechanistic studies on HNE-derived ...
Preparation and Reduction of Hexahydro[2.2]paracyclophane.

Hexahydro[2.2]paracyclophane (6) and related compounds were prepared from the extrusion of sulfur dioxide from 2,11-dithia-4,5,6,7,8,9-hexahydro[3.3]paracyclophane 2,2,11,11-tetraoxide (9) by either the Ramberg−Backlund reaction or a flash pyrolysis. Compound 6 is the first cyclophane to contain both a benzene ring and a cyclohexane ring. Birch reduction of compound 6 gave a diene containing two double bonds in the same ring, which is different from the dienes obtained from the catalytic hydrogenation of [2.2]paracyclophane.
Synthesis and structure of the subnitrides Ba2GeGaN and (BaxSr1−x)3Ge2N2; x≈0.7

Abstract We report the structure of the new subnitride Ba2GeGaN synthesized as crystals from the elements in a sealed Nb tube at 760°C using a Na Ba melt as the growth medium. Shiny black prisms of Ba2GeGaN crystallize in P21/m (No. 11) with a = 7.249(1) A , b = 4.210(1) A , c = 9.314(1) A , β = 108.87(1)° and Z = 2 . It contains infinite zigzag chains, x1[GeGaN4−], composed of alternating Ge2− and GaN2− units joined by GeGa bonds. The structure is related to that of BaGe with alternate Ge atoms replaced by the isoelectronic GaN2− fragment. Such GaN2− fragments occur in CaGaN. We also report the occurrence of a solid solution between the previously reported subnitrides Ba3Ge2N2 and Sr3Ge2N2 which contain infinite chains, x1[Ge2−], and GeN24− units. We have characterized one member of this solid solution with composition (Ba0.79(1)Sr0.21(1))3Ge2N2 and crystallizing in P21/m (No. 11) with a = 9.5109(9) A , b = 4.0201(3) A , c = 10.0412(9) A , β = 113.06(1)° and Z = 2 .
Convergent allostery in ribonucleotide reductase.

Ribonucleotide reductases (RNRs) use a conserved radical-based mechanism to catalyze the conversion of ribonucleotides to deoxyribonucleotides. Within the RNR family, class Ib RNRs are notable for being largely restricted to bacteria, including many pathogens, and for lacking an evolutionarily mobile ATP-cone domain that allosterically controls overall activity. In this study, we report the emergence of a distinct and unexpected mechanism of activity regulation in the sole RNR of the model organism Bacillus subtilis. Using a hypothesis-driven structural approach that combines the strengths of small-angle X-ray scattering (SAXS), crystallography, and cryo-electron microscopy (cryo-EM), we describe the reversible interconversion of six unique structures, including a flexible active tetramer and two inhibited helical filaments. These structures reveal the conformational gymnastics necessary for RNR activity and the molecular basis for its control via an evolutionarily convergent form of allostery. Ribonucleotide reductase (RNR) catalyzes the conversion of ribonucleotides to deoxyribonucleotides, which is an essential step in DNA synthesis. Here the authors use small-angle X-ray scattering, X-ray crystallography, and cryo-electron microscopy to capture active and inactive forms of the Bacillus subtilis RNR and provide mechanistic insights into a convergent form of allosteric regulation.
A ring-closing olefin metathesis approach to bridged azabicyclic structures

A facile and general entry to functionalized bridged bicyclic nitrogen heterocycles has been developed that involves the ring-closing metathesis (RCM) of cis-2,6-dialkenyl-N-acyl piperidines that were readily prepared from glutarimide or 4-methoxypyridine.
ARGON: fast, whole-genome simulation of the discrete time Wright-Fisher process

Motivation Simulation under the coalescent model is ubiquitous in the analysis of genetic data. The rapid growth of real data sets from multiple human populations led to increasing interest in simulating very large sample sizes at whole-chromosome scales. When the sample size is large, the coalescent model becomes an increasingly inaccurate approximation of the discrete time Wright-Fisher model (DTWF). Analytical and computational treatment of the DTWF, however, is generally harder. Results We present a simulator (ARGON) for the DTWF process that scales up to hundreds of thousands of samples and whole-chromosome lengths, with a time/memory performance comparable or superior to currently available methods for coalescent simulation. The simulator supports arbitrary demographic history, migration, Newick tree output, variable mutation/recombination rates and gene conversion, and efficiently outputs pairwise identical-by-descent sharing data. Availability ARGON (version 0.1) is written in Java, open source, and freely available at https://github.com/pierpal/ARGON CONTACT: ppalama@hsph.harvard.edu Supplementary information Supplementary data are available at Bioinformatics online.
What makes an N12 cage stable

Much recent attention has been given to molecules containing only nitrogen atoms. Such molecules Nx can undergo the reaction Nx → (x/2)N2, which is very exothermic. These molecules are potential candidates for high energy density materials (HEDM). However, many all-nitrogen molecules dissociate too easily to be stable, practical energy sources. It is important to know which nitrogen molecules will be stable and which will not. In the current study, a variety of N12 cages with all single bonds are examined by theoretical calculations to determine which ones are the most thermodynamically stable. Calculations are carried out using Hartree−Fock (HF) theory, gradient-corrected density functional theory (DFT), and Moller−Plesset perturbation theory (MP2 and MP4). Relative energies among the various isomers are calculated and trends are examined in order to determine which structural features lead to the most energetically favorable molecules.
Synthesis of 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

The reaction of methyl 2-bromo-6-(trifluoromethyl)-3-pyridinecarboxylate (1) with methanesulfonamide gave methyl 2-[(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridine-carboxylate (2). Alkylation of compound 2 with methyl iodide followed by cyclization of the resulting methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate (3) yielded 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide (4). The reaction of compound 4 with α,2,4-trichlorotoluene, methyl bromopropionate, methyl iodide, 3-trifluoromethylphenyl isocyanate, phenyl isocyanate and 2,4-dichloro-5-(2-propynyloxy)phenyl isothiocyanate gave, respectively, 4-[(2,4-dichlorophenyl)methoxy]-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazine 2,2-dioxide (5), methyl 2-[[1-methyl-2,2-dioxido-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4-yl]oxy]propanoate (6), 1,3,3-trimethyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide (7), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide (8), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-phenyl-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide (9) and N-[2,4-dichloro-5-(2-propynyloxy)phenyl]-4-hydroxy-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2] thiazine-3-carboxamide 2,2-dioxide (10).
Chemically Accurate Relative Folding Stability of RNA Hairpins from Molecular Simulations

To benchmark RNA force fields, we compared the folding stabilities of three 12-nucleotide hairpin stem loops estimated by simulation to stabilities determined by experiment. We used umbrella sampling and a reaction coordinate of end-to-end (5' to 3' hydroxyl oxygen) distance to estimate the free energy change of the transition from the native conformation to a fully extended conformation with no hydrogen bonds between non-neighboring bases. Each simulation was performed four times using the AMBER FF99+bsc0+χOL3 force field, and each window, spaced at 1 A intervals, was sampled for 1 μs, for a total of 552 μs of simulation. We compared differences in the simulated free energy changes to analogous differences in free energies from optical melting experiments using thermodynamic cycles where the free energy change between stretched and random coil sequences is assumed to be sequence-independent. The differences between experimental and simulated ΔΔ G° are, on average, 0.98 ± 0.66 kcal/mol, which is chemically accurate and suggests that analogous simulations could be used predictively. We also report a novel method to identify where replica free energies diverge along a reaction coordinate, thus indicating where additional sampling would most improve convergence. We conclude by discussing methods to more economically perform these simulations.
Three new phases in the K/Cu/Th/S system: KCuThS3, K2Cu2ThS4, and K3Cu3Th2S7.

Synthetic exploration of K/Cu/Th/S quaternary phase space has yielded three new compounds: KCuThS 3 (I), K 2 -Cu 2 ThS 4 (II), and K 3 Cu 3 Th 2 S 7 (III). All three phases are semiconductors with optical band gaps of 2.95, 2.17, and 2.49 eV(I-III). Compound I crystallizes in the orthorhombic space group Cmcm with a = 4.076(1) A, b = 13.864-(4) A, and c = 10.541(3) A. Compound II crystallizes in the monoclinic space group C2/m with a = 14.522(1) A, b = 4.026(3) A, and c = 7.566(6) A; p = 109.949(1)°. Compound III crystallizes in orthorhombic space group Pbcn with a = 4.051(2) A, b = 14.023(8) A, and c = 24.633(13) A. The compounds are all layered materials, with each layer composed of threads of edge-sharing ThS 6 octahedra bridged by CuS 4 tetrahedral threads of varying dimension. The layers are separated by well-ordered potassium ions. The relatively wide range of optical band gaps is attributed to the extent of the CuS 4 motifs. As the dimension of the CuS 4 chains increases, band gaps decrease in the series. All materials were characterized by single-crystal X-ray diffraction, microprobe chemical analysis, and diffuse reflectance spectroscopy (NIR-UV).
Predictability and persistence of prebiotic dietary supplementation in a healthy human cohort.

Dietary interventions to manipulate the human gut microbiome for improved health have received increasing attention. However, their design has been limited by a lack of understanding of the quantitative impact of diet on a host’s microbiota. We present a highly controlled diet perturbation experiment in a healthy, human cohort in which individual micronutrients are spiked in against a standardized background. We identify strong and predictable responses of specific microbes across participants consuming prebiotic spike-ins, at the level of both strains and functional genes, suggesting fine-scale resource partitioning in the human gut. No predictable responses to non-prebiotic micronutrients were found. Surprisingly, we did not observe decreases in day-to-day variability of the microbiota compared to a complex, varying diet, and instead found evidence of diet-induced stress and an associated loss of biodiversity. Our data offer insights into the effect of a low complexity diet on the gut microbiome, and suggest that effective personalized dietary interventions will rely on functional, strain-level characterization of a patient’s microbiota.
Individual differences in response precision correlate with adaptation bias.

The internal representation of stimuli is imperfect and subject to bias. Noise introduced at initial encoding and during maintenance degrades the precision of representation. Stimulus estimation is also biased away from recently encountered stimuli, a phenomenon known as adaptation. Within a Bayesian framework, greater biases are predicted to result from poor precision. We tested for this effect in individual difference measures. 202 subjects contributed data through an on-line experiment. During separate face and color blocks, subjects performed three different tasks: an immediate stimulus-match, a 5 seconds delayed match, and 5 seconds of adaptation followed by a delayed match. The stimulus spaces were circular and subjects entered their responses on a color/face wheel. Bias and precision of responses were extracted while accounting for the probability of random guesses. We found that the adaptation manipulation induced the expected bias in responses, and the magnitude of this bias varied reliably and substantially between subjects. Across subjects, there was a negative correlation between mean precision and bias. This relationship was replicated in a new experiment with 192 subjects. This result is consistent with a Bayesian observer model, in which the precision of perceptual representation influences the magnitude of perceptual bias.
Disorder–Order Structural Transformation in Electron-Poor Sr3Au8Sn3 Driven by Chemical Bonding Optimization

Sr3Au8Sn3 was synthesized through fusion of a stoichiometric amount of pure metals at 800 °C and annealing treatments at lower temperatures. Single-crystal X-ray diffraction analyses revealed that Sr3Au8Sn3 has a La3Al11-type Immm structure (a = 4.6767(8) A, b = 9.646(2) A, c = 14.170(2) A, Z = 2) if annealed at 550 °C and above but a Ca3Au8Ge3-type structure (Pnnm, a = 9.6082(8) A, b = 14.171(1) A, c = 4.6719(4) A, Z = 2) if annealed at 400 °C. The transition occurs at about 454 °C according to DTA data. Both structures feature columns of Sr-centered pentagonal and hexagonal prisms of Au and Sn stacked along the respective longest axial directions, but different “colorings” of the polyhedra are evident. In the high-temperature phase (Immm) all sites shared between the two prisms adopt 50:50 mixtures of Au/Sn atoms, whereas in the low-temperature phase (Pnnm) Au or Sn are completely ordered. A Klassengleiche group–subgroup relationship was established between these two structures. LMTO-ASA calculations re...