cssi/SciSciGPT-SciSciNet huggingface dataset:
Prediction of severity and treatment outcome for ASD from fMRI.

Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome. Early diagnosis and precise treatment are essential for ASD patients. Although researchers have built many analytical models, there has been limited progress in accurate predictive models for early diagnosis. In this project, we aim to build an accurate model to predict treatment outcome and ASD severity from early stage functional magnetic resonance imaging (fMRI) scans. The difficulty in building large databases of patients who have received specific treatments and the high dimensionality of medical image analysis problems are challenges in this work. We propose a generic and accurate two-level approach for high-dimensional regression problems in medical image analysis. First, we perform region-level feature selection using a predefined brain parcellation. Based on the assumption that voxels within one region in the brain have similar values, for each region we use the bootstrapped mean of voxels within it as a feature. In this way, the dimension of data is reduced from number of voxels to number of regions. Then we detect predictive regions by various feature selection methods. Second, we extract voxels within selected regions, and perform voxel-level feature selection. To use this model in both linear and non-linear cases with limited training examples, we apply two-level elastic net regression and random forest (RF) models respectively. To validate accuracy and robustness of this approach, we perform experiments on both task-fMRI and resting state fMRI datasets. Furthermore, we visualize the influence of each region, and show that the results match well with other findings.
A Kinetic Analysis of Coupled (or Auxiliary) Enzyme Reactions

As a case study, we consider a coupled (or auxiliary) enzyme assay of two reactions obeying the Michaelis-Menten mechanism. The coupled reaction consists of a single-substrate, single-enzyme non-observable reaction followed by another single-substrate, single-enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction is the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the coupled reaction is described by a pair of interacting Michaelis-Menten equations. Moreover, we show that when the indicator reaction is fast, the quasi-steady-state dynamics are governed by three fast variables and one slow variable. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis-Menten equations, are derived. The theory can be extended to deal with more complex sequences of enzyme-catalyzed reactions.
Probiotics in Autoimmune and Inflammatory Disorders

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to impact the immune system, both in vivo and in vitro. This interaction is linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on mechanistic studies in animal models. Microbial–immune system crosstalk has been linked to: short-chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multiorgan inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.
Automated sequence and motion planning for robotic spatial extrusion of 3D trusses

While robotic spatial extrusion has demonstrated a new and efficient means to fabricate 3D truss structures in architectural scale, a major challenge remains in automatically planning extrusion sequence and robotic motion for trusses with unconstrained topologies. This paper presents the first attempt in the field to rigorously formulate the extrusion sequence and motion planning (SAMP) problem, using a CSP encoding. Furthermore, this research proposes a new hierarchical planning framework to solve the extrusion SAMP problems that usually have a long planning horizon and 3D configuration complexity. By decoupling sequence and motion planning, the planning framework is able to efficiently solve the extrusion sequence, end-effector poses, joint configurations, and transition trajectories for spatial trusses with nonstandard topologies. This paper also presents the first detailed computation data to reveal the runtime bottleneck on solving SAMP problems, which provides insight and comparing baseline for future algorithmic development. Together with the algorithmic results, this paper also presents an open-source and modularized software implementation called Choreo that is machine-agnostic. To demonstrate the power of this algorithmic framework, three case studies, including real fabrication and simulation results, are presented.
A Weighted Least-Squares Transport Equation Compatible with Source Iteration and Voids

AbstractSecond-order forms of the transport equation allow the use of continuous finite elements (CFEMs). This can be desired in multiphysics calculations where other physics require CFEM discretizations. Second-order transport operators are generally self-adjoint, yielding symmetric positive-definite (SPD) matrices, which allow the use of efficient linear algebra solvers with an enormous advantage in memory usage.Least-squares (LS) forms of the transport equation can circumvent the void problems of other second-order forms but are almost always nonconservative. Additionally, the standard LS form is not compatible with discrete ordinates method (SN) iterative solution techniques such as source iteration. A new form of the LS transport equation has recently been developed that is compatible with voids and standard SN iterative solution techniques. Performing nonlinear diffusion acceleration (NDA) using an independently differenced low-order equation enforces conservation for the whole system and makes this...
Summit: a scalable system for massive trajectory data management

MapReduce frameworks, e.g., Hadoop, have been used extensively in different applications that include machine learning, and spatial processing. In meantime, huge volumes of spatio-temporal trajectory data are coming from different sources over sometime, raised the demand to exploit the efficiency of Hadoop, coupled with the flexibility of the MapReduce framework, in trajectory data processing. This work describes Summit; a full-fledged MapReduce framework with native support for trajectory data.
Bayesian Model Selection in Survival Analysis

Bayesian model selection in survival analysis has become common practice with recent advances in computational technology and software. In this article, we review some Bayesian model selection techniques for the analysis of survival data. Keywords: Bayesian information criterion; conditional predictive ordinate; Gibbs sampling; L measure; posterior model probability; prior elicitation
Populist Antitrust and the 1927 Radio Act

In policy circles of Washington DC, in academia, and among advocates and lobbyists, there has been growing attention to the role of antitrust enforcement versus regulation in today’s economy (see, e.g., Shapiro in Int J Ind Organ 61:714–748, 2017). Various populist arguments seek an expanded role for antitrust law, as proponents seek to control the perceived political and free speech dangers associated with market concentration. These new populists are particularly interested in large, content-laden companies such as Google, Facebook, and broadcast and cable firms. Strong interest in content companies is, of course, not new. This essay explores different political, economic, and philosophical regimes at play when the United States chose to enact the Radio Act of 1927 and regulate, rather than leave to antitrust controls, the emerging radio industry. By examining antitrust at the dawn of the Radio Act of 1927, there are lessons to be learned for the political treatment of today’s social media, broadcast, cable, and telecommunications industry. In particular the story of the Radio Act of 1927 highlights two historically recurring political themes: (1) a longstanding, near-universal political goal to control content and (2) the tension between selecting an ex post antitrust enforcement regime versus an ex ante regulatory regime to control economic concentration and power. It is this second theme that is primarily explored here.
On the Optimality of the Kautz-Singleton Construction in Probabilistic Group Testing

We consider the probabilistic group testing problem where $d$ random defective items in a large population of $N$ items are identified with high probability by applying binary tests. It is known that the $\Theta (d \log N)$ tests are necessary and sufficient to recover the defective set with vanishing probability of error when $d = O(N^{\alpha })$ for some $\alpha \in (0, 1)$ . However, to the best of our knowledge, there is no explicit (deterministic) construction achieving $\Theta (d \log N)$ tests in general. In this paper, we show that a famous construction introduced by Kautz and Singleton for the combinatorial group testing problem (which is known to be suboptimal for combinatorial group testing for moderate values of $d$ ) achieves the order optimal $\Theta (d \log N)$ tests in the probabilistic group testing problem when $d = \Omega (\log ^{2}\,\,N)$ . This provides a strongly explicit construction achieving the order optimal result in the probabilistic group testing setting for a wide range of values of $d$ . To prove the order-optimality of Kautz and Singleton’s construction in the probabilistic setting, we provide a novel analysis of the probability of a non-defective item being covered by a random defective set directly, rather than arguing from combinatorial properties of the underlying code, which has been the main approach in the literature. Furthermore, we use a recursive technique to convert this construction into one that can also be efficiently decoded with only a log-log factor increase in the number of tests.
Distance and Local Competition in Mobile Geofencing

The growing ubiquity of GPS-enabled smartphones has ushered in a new era of location-based services and online-to-offline commerce. Geofencing is one instance of this broader phenomenon, and it is ...
Cascaded collimator for atomic beams traveling in planar silicon devices

Micro- and increasingly, nano-fabrication have enabled the miniaturization of atomic devices, from vapor cells to atom chips for Bose-Einstein condensation. Here we present microfabricated planar devices for thermal atomic beams. Etched microchannels were used to create highly collimated, continuous rubidium atom beams traveling parallel to a silicon wafer surface. Precise, lithographic definition of the guiding channels allowed for shaping and tailoring the velocity distributions in ways not possible using conventional machining. Multiple miniature beams with individually prescribed geometries were created, including collimated, focusing and diverging outputs. A “cascaded” collimator was realized with 40 times greater purity than conventional collimators. These localized, miniature atom beam sources can be a valuable resource for a number of quantum technologies, including atom interferometers, clocks, Rydberg atoms, and hybrid atom-nanophotonic systems, as well as enabling controlled studies of atom-surface interactions at the nanometer scale. Bringing atomic beam technology to the chip scale is challenging due to the long distance required to filter the velocity distribution. Here, the authors report an engineering strategy for on-chip filtering of the velocity profile of atomic beams by fabricating planar, etched microchannel arrays.
How to Publish, but Most Importantly, Why

This essay responds to an invitation by the editors of Sociologica to write about publication strategy.
The political economy of the collaborative innovation bloc

In this issue, Elert and Henrekson offer an important and promising framework through which Austrian scholars to contribute to the study of entrepreneurship and innovation. I suggest a way to build upon their framework: incorporating insights from public choice. While Elert and Henrekson downplay self-interest in their institutional analysis, public choice offers important insights about the formation of public policies that affect innovation activity. Without this, a gap exists among the identification of institutional bottlenecks that hinder collaboration in the innovation bloc and the subsequent alleviation of those bottlenecks. Infusing public choice assumptions into the Collaborative Innovation Bloc framework reveals several promising areas for future research.
Management and Shocks to Worker Productivity

We study how managers mitigate the negative impacts of environmental shocks. Pairing productivity data from a garment firm with granular measures of air pollution, we show that productivity suffers...
Asymmetric Total Synthesis of (−)-VM55599: Establishment of the Absolute Stereochemistry and Biogenetic Implications

The first asymmetric biomimetic total synthesis of VM55599 (13) has been achieved utilizing an intramolecular Diels-Alder cycloaddition as a key step. The synthetic material was utilized to elucidate the absolute stereochemistry of the natural product. The results are discussed in terms of a unified biogenesis of the paraherquamides and VM55599.
How To Play Almost Any Mental Game Over The Net - Concurrent Composition via Super-Polynomial Simulation.

We construct a secure protocol for any multi-party functionality that remains secure (under a relaxed definition of security) when executed concurrently with multiple copies of itself and other protocols. We stress that we do not use any assumptions on existence of trusted parties, common reference string, honest majority or synchronicity of the network. The relaxation of security, introduced by Prabhakaran and Sahai (STOC ’04), is obtained by allowing the idealmodel simulator to run in quai-polynomial (as opposed to polynomial) time. Quasi-polynomial simulation suffices to ensure security for most applications of multi-party computation. Furthermore, Lindell (FOCS ’03, TCC’ 04) recently showed that such a protocol is impossible to obtain under the more standard definition of polynomial-time simulation by an ideal adversary. Our construction is the first such protocol under reasonably standard cryptographic assumptions. That is, existence of a hash function collection that is collision resistent with respect to circuits of subexponential size, and existence of trapdoor permutations that are secure with respect to circuits of quasi-polynomial size. We introduce a new technique: “protocol condensing”. That is, taking a protocol that has strong security properties but requires super-polynomial communication and computation, and then transforming it into a protocol with polynomial communication and computation, that still inherits the strong security properties of the original protocol. Our result is obtained by combining this technique with previous techniques of Canetti, Lindell, Ostrovsky, and Sahai (STOC ’02) and Pass (STOC ’04).
SYNTHESIS OF D, L-NORLABDANE OXIDE AND RELATED ODORANTS : AN INTRAMOLECULAR RADICAL APPROACH

A cascade radical approach to d,l-norlabdane oxide and related odorants is reported. Oxidative radical cyclization of polyene 4 with Mn(III) and Cu(II) afforded exclusively bicycle 3, which upon acid treatment gave tricycle 2 possessing the norlabdane oxide skeleton with a modified A-ring system. Tricycle 2 was ultimately converted to d,l-norlabdane oxide 1 and to several new A-ring labdane oxides as potential odorants.
Development of an end-game strategy towards apoptolidin: a sequential Suzuki coupling approach

Abstract An end-game strategy towards the synthesis of apoptolidin has been demonstrated in a model study, in which the C(1)–C(15) fragment was successfully assembled using three consecutive Suzuki coupling reactions.
Synthesis of 1,2,3-triazoles by cycloadditions of azides with enol ethers

1,2,3-Triazoles were prepared in good to modest yields by cycloaddition of alkyl azides onto enol ethers under solventless conditions. The reaction can access ring-fused triazoles that are unavailable by azide-alkyne cycloadditions and is easily scalable. The 1,2,3-triazole products bear functionality that may be readily derivatized.
Determination of the standard molar enthalpy of formation of Pd3P by direct-synthesis drop calorimetry

We have determined ΔfHδm(Pd3P, cr, 298.15 K) using direct-synthesis drop calorimetry. We measured ΔrHm which is the enthalpy of the reaction: 3Pd(cr) + P(red, am) = Pd3P(cr), at T = (298 ± 1) K. Our result for ΔrHm is −(203 ± 2) kJ·mol−1. Correcting for ΔfHδm(P, red, am, 298.15 K) yields a value for ΔfHδm(Pd3P, cr, 298.15 K) of −(198 ± 3) kJ·mol−1, where the reference state of phosphorus is P(black, orthorhombic). Calculated and experimental powder X-ray diffraction results were compared in order to confirm the identity of the product material as Pd3P.
A method for the parallel synthesis of multiply substituted oxazolidinones.

There are many examples of both naturally occurring and synthetic molecules containing a 2-oxazolidinone ring that have significant biological activity. The oxazolidinone ring potentially has three...
Synthesis of 2-aminoquinazolines from ortho-fluoroketones

The reactions of ten ortho-fluoroketones with guanidine carbonate in N,N-dimethylacetamide were investigated as a new synthetic approach to 2-amino-4-alkyl- and 2-amino-4-arylquinazolines. The yields obtained ranged from low to moderate and were highly dependent upon the nature of the substituents on the reactant. Eight new quinazolines were elaborated in this study.
Friedel−Crafts Acylation of Chromium-Carbene-Complex-Derived Ketenes

Photolysis of chromium alkoxycarbene complexes containing electron-rich aromatic systems on either the oxygen or carbon group of the carbene carbon resulted in intramolecular Friedel−Crafts acylation of the arene.
Meerwein’s Reagent Mediated, Significantly Enhanced Nucleophilic Fluorination on Alkoxysilanes

We developed a new facile method to fluorosilanes from alkoxysilanes using Meerwein’s reagent. Our protocol afforded fluo­rosilanes in excellent yields in various organic solvents including acetonitrile under mild reaction conditions at room temperature. We also proposed a reaction mechanism with the probable silyloxonium intermediates.
Nanocrystalline Y2O3:Eu phosphors prepared by alkalide reduction

(Y0.95Eu0.05)2O3 nanoparticles have been synthesized by subambient homogeneous reduction using alkalide solutions and subsequent oxidation. As synthesized, the material consists of free-flowing agg...
The relative contribution of color and material in object selection

Object perception is inherently multidimensional: information about color, material, texture and shape all guide how we interact with objects. We developed a paradigm that quantifies how two object properties (color and material) combine in object selection. On each experimental trial, observers viewed three blob-shaped objects-the target and two tests-and selected the test that was more similar to the target. Across trials, the target object was fixed, while the tests varied in color (across 7 levels) and material (also 7 levels, yielding 49 possible stimuli). We used an adaptive trial selection procedure (Quest+) to present, on each trial, the stimulus test pair that is most informative of underlying processes that drive selection. We present a novel computational model that allows us to describe observers' selection data in terms of (1) the underlying perceptual stimulus representation and (2) a color-material weight, which quantifies the relative importance of color vs. material in selection. We document large individual differences in the color-material weight across the 12 observers we tested. Furthermore, our analyses reveal limits on how precisely selection data simultaneously constrain perceptual representations and the color-material weight. These limits should guide future efforts towards understanding the multidimensional nature of object perception.
Addition of lithioimidazoles to isocyanates followed by Pd-coupling: access to 4-substituted imidazole-2,5-dicarboxamides

Facile access to 4-substituted N-butyl 2,5-dicarboxamides is achieved via direct lithiation of N-butyl imidazole and subsequent quenching with isocyanates followed by Pd-catalyzed coupling reactions.
Pd/C mediated synthesis of 2-substituted benzo[b]furans/nitrobenzo[b]furans in water

Abstract An efficient synthesis of 2-alkyl/aryl substituted benzo[b]furans/nitrobenzo[b]furans in water has been accomplished via Pd/C catalyzed reaction of o-iodophenols with terminal alkynes in the presence of PPh3, CuI and prolinol. This method can tolerate a variety of functional groups present in the alkynes as well as base labile nitro group in the o-iodophenols. The protocol does not require the use of a phase transfer catalyst or water-soluble phosphine ligands and is free from the use of any organic co-solvent.
Borylation of Arenes with Bis(hexylene glycolato)diboron

A series of diolate-substituted diboron compounds were investigated as reagents for iridium-catalyzed C–H borylations of arenes. These studies showed that commercially available bis(hex­ylene glycolato)diboron reacts with arenes in the presence of the catalyst generated from [Ir(COD)OMe]2 and di-tert-butylbipyridine. This reagent is prepared from a less expensive diol than the more commonly used bis(pinacolato)diboron reagent.
SYNTHESIS OF NOVEL D-2',3'-DIDEOXY-2',3'-ENDO-METHYLENE NUCLEOSIDES

Asymmetric synthesis of d-2′,3′-dideoxy-2′,3′-endo-methylene nucleosides was achieved via the intermediate 2,3-endo-methylene pentofuranoyl chloride 6, which was prepared from 1,2:5,6-Di-O-isopropylidene-D-mannitol 1 with high stereoselectivity (only α chlorosugar). The SN2 type condensation of 6 with sodium salt of adenine and silyated N4-benzoylcytosine gave the desired β-nucleosides as major isomers (β:α = 2.5:1 and 2:1, respectively).
Two novel Zintl compounds Na12Ge8Sn and Na15Ge8SnP: Single crystal and electronic structures

Abstract Two mixed anionic Zintl phases, Na12Ge8Sn and Na15Ge8SnP, have been synthesized and structurally characterized. Na12Ge8Sn crystallizes in the tetragonal space group P41212 (#92, a = 14.1172(2) A, c = 21.8483(7) A, V = 4354.3(2) A3, Z = 8, and R/wR = 0.0481/0.1213) and Na15Ge8SnP crystallizes in the orthorhombic space group Cmcm (#63, a = 17.517(4) A, b = 12.890(3) A, c = 11.111(2) A, V = 2508.7(9) A3, Z = 4, and R/wR = 0.0313/0.0669). Both compounds adopt new structure types and are made up of isolated Na+ cations, anionic (Ge4)4− tetrahedral clusters, and Sn4− or P3− anions. The structure of Na12Ge8Sn can be described as a square packing of two kinds of columns, highly distorted Sn centered Na icosahedra chains ( [ Na 9 Sn ] 5 + ∞ 1 ) and highly distorted Na(1) centered anti-rectangular prism (four (Ge4)4− and four Na, [ Na 3 ( Ge 4 ) 2 ] 5 − ∞ 1 ) chains. The structure of Na15Ge8SnP is composed of cationic [ Na 15 SnP ] 8 + ∞ 1 saw tooth-like chains, which are made up of Sn centered Na bicapped hexagonal prisms and P centered tricapped trigonal prisms, extending along the c axis with anionic (Ge4)4− tetrahedral clusters between the chains. The electronic structures have been studied using density functional theory.
Probing Supersymmetric Parameters With Astrophysical Observations

A wide range of techniques have been developed to search for particle dark matter, including direct detection, indirect detection, and collider searches. The prospects for the detection of neutralino dark matter is quite promising for each of these three very different methods. Looking ahead to a time in which these techniques have successfully detected neutralino dark matter, we explore the ability of these observations to determine the parameters of supersymmetry. In particular, we focus on the ability of direct and indirect detection techniques to measure the parameters μ and m A . We find that μ can be much more tightly constrained if astrophysical measurements are considered than by LHC data alone. In supersymmetric models within the A -funnel region of parameter space, we find that astrophysical measurements can determine m A to roughly ± 100 GeV precision.
Effect of water on Keck's catalytic asymmetric allylations of aldehydes

The complex generated from BINOL, Ti(i-PrO) 4 , and unactivated or a large amount of activated 4 A MS in toluene is very effective in catalytic allylations of aldehydes using allyltributyltin. Allylations with 2.5 mol% of the catalyst provide homoallylic alcohols with greater than 95% ee. Very high syn-selective allylations of protected b-hydroxyaldehydes are achieved with 5 mol% of the BINOL/Ti(i-PrO) 4 complex.
Describing the Local Structure of Sequence Graphs.

Analysis of genetic variation using graph structures is an emerging paradigm of genomics. However, defining genetic sites on sequence graphs remains an open problem. Paten’s invention of the ultrabubble and snarl, special subgraphs of sequence graphs which can identified with efficient algorithms, represents important first step to segregating graphs into genetic sites. We extend the theory of ultrabubbles to a special subclass where every detail of the ultrabubble can be described in a series and parallel arrangement of genetic sites. We furthermore introduce the concept of bundle structures, which allows us to recognize the graph motifs created by additional combinations of variation in the graph, including but not limited to runs of abutting single nucleotide variants. We demonstrate linear-time identification of bundles in a bidirected graph. These two advances build on initial work on ultrabubbles in bidirected graphs, and define a more granular concept of genetic site.
Electrophilic amination of organozinc halides

Abstract The reaction of several functionalized primary, secondary and tertiary organozinc bromides, benzylzinc bromide, functionalized arylzinc halides and one heteroarylzinc bromide with di tert -butyl azodicarboxylate is described. The reaction products, N,N′ -di tert -butoxycarbonylhydrazino derivatives are obtained in excellent yields for most aliphatic substrates and good yields for aromatic substrates. These compounds are direct precursors of hydrazino and amino derivatives by deprotection. The process constitutes the first synthetically useful electrophilic amination of organozinc derivatives, and takes advantage of the broad functional group tolerance of the organozinc chemistry.
The [U2(μ-S2)2Cl8]4– Anion: Synthesis and Characterization of the Uranium Double Salt Cs5[U2(μ-S2)2Cl8]I

Red plates of Cs5[U2(μ-S2)2Cl8]I were obtained in good yield from the reaction at 1173 K of U, GeI2 or SnI4, and S, with CsCl flux. The compound crystallizes in space group D2h25-Immm of the orthorhombic system in the Cs5[Nb2(μ-S2)2Cl8]Cl structure type. The centrosymmetric [U2(μ-S2)2Cl8]4– anion in the structure has mmm symmetry with the two U4+ atoms separated by 3.747(1) A. Each U atom is coordinated to four Cl atoms and four S atoms from two S22– groups in a square-antiprismatic arrangement. The polarized absorbance spectra of Cs5[U2(μ-S2)2Cl8]I display prominent optical anisotropy. Magnetic measurements are consistent with the modified Curie–Weiss law at high temperatures. The low-temperature behavior may arise from antiferromagnetic coupling of the U4+ ions within the anion.
Holographic particle localization under multiple scattering

We introduce a computational framework that incorporates multiple scattering for large-scale three-dimensional (3-D) particle localization using single-shot in-line holography. Traditional holographic techniques rely on single-scattering models that become inaccurate under high particle densities and large refractive index contrasts. Existing multiple scattering solvers become computationally prohibitive for large-scale problems, which comprise millions of voxels within the scattering volume. Our approach overcomes the computational bottleneck by slicewise computation of multiple scattering under an efficient recursive framework. In the forward model, each recursion estimates the next higher-order multiple scattered field among the object slices. In the inverse model, each order of scattering is recursively estimated by a nonlinear optimization procedure. This nonlinear inverse model is further supplemented by a sparsity promoting procedure that is particularly effective in localizing 3-D distributed particles. We show that our multiple-scattering model leads to significant improvement in the quality of 3-D localization compared to traditional methods based on single scattering approximation. Our experiments demonstrate robust inverse multiple scattering, allowing reconstruction of 100 million voxels from a single 1-megapixel hologram with a sparsity prior. The performance bound of our approach is quantified in simulation and validated experimentally. Our work promises utilization of multiple scattering for versatile large-scale applications.
Synthesis and Characterization of a Nitroxide-Semiquinone Biradical.

The synthesis and characterization of an anion biradical, 1-••, composed of semiquinone and nitroxide functionalities is described. The biradical was prepared by reduction of the nitroxide−orthoquinone precursor using both electrochemical and chemical methods. The zero-field-splitting parameter, |D/hc|, for 1-•• is consistent with the proposed electronic structure, based on a comparison to |D/hc| of related biradicals. Finally, the results of variable-temperature EPR spectroscopy are in agreement with ferromagnetic (high-spin) coupling of the two unpaired electrons through the m-phenylene group.
A simple route to tetrahydro-1,4-benzodiazepin-3-ones bearing diverse N1, N4, and C10 functionalization

Abstract We describe an efficient synthesis of enantiopure tetrahydro-1,4-benzodiazepine-3-ones derived from l -alanine. Diverse substitution at N1, N4, and C10 can be achieved by coupling various N-alkyl derivatives of l -alanine and N-allyl-(2-fluoro-5-nitro)benzylamine. Cyclization of this intermediate proceeds in high yield and without racemization, providing diversity at N1. The NO2 group was easily transformed into other functional groups or removed, providing diversity at C10. Finally, oxidative deallylation allows diverse substitution to be installed at N4.
Synthesis of the diazonamide A macrocyclic core via a Dieckmann-type cyclization.

Suzuki coupling of 18 and 30 affords 9 as an interconverting mixture of two atropisomers. Treatment with LDA at −23 °C affords the macrocyclic ketone 8 in 57% yield.
Direct Observation of Topoisomerase IA Gate Dynamics

Type IA topoisomerases cleave single-stranded DNA and relieve negative supercoils in discrete steps corresponding to the passage of the intact DNA strand through the cleaved strand. Although type IA topoisomerases are assumed to accomplish this strand passage via a protein-mediated DNA gate, opening of this gate has never been observed. We developed a single-molecule assay to directly measure gate opening of the Escherichia coli type IA topoisomerases I and III. We found that after cleavage of single-stranded DNA, the protein gate opens by as much as 6.6 nm and can close against forces in excess of 16 pN. Key differences in the cleavage, ligation, and gate dynamics of these two enzymes provide insights into their different cellular functions. The single-molecule results are broadly consistent with conformational changes obtained from molecular dynamics simulations. These results allowed us to develop a mechanistic model of interactions between type IA topoisomerases and single-stranded DNA. Single-molecule magnetic tweezers analyses and supporting MD simulations provide evidence for protein-gate opening of type IA topoisomerases.
Polycomb-mediated chromatin loops revealed by a subkilobase-resolution chromatin interaction map

The locations of chromatin loops in Drosophila were determined by Hi-C (chemical cross-linking, restriction digestion, ligation, and high-throughput DNA sequencing). Whereas most loop boundaries or “anchors” are associated with CTCF protein in mammals, loop anchors in Drosophila were found most often in association with the polycomb group (PcG) protein Polycomb (Pc), a subunit of polycomb repressive complex 1 (PRC1). Loops were frequently located within domains of PcG-repressed chromatin. Promoters located at PRC1 loop anchors regulate some of the most important developmental genes and are less likely to be expressed than those not at PRC1 loop anchors. Although DNA looping has most commonly been associated with enhancer–promoter communication, our results indicate that loops are also associated with gene repression.
Learning from Longitudinal Data in Electronic Health Record and Genetic Data to Improve Cardiovascular Event Prediction.

Current approaches to predicting a cardiovascular disease (CVD) event rely on conventional risk factors and cross-sectional data. In this study, we applied machine learning and deep learning models to 10-year CVD event prediction by using longitudinal electronic health record (EHR) and genetic data. Our study cohort included 109, 490 individuals. In the first experiment, we extracted aggregated and longitudinal features from EHR. We applied logistic regression, random forests, gradient boosting trees, convolutional neural networks (CNN) and recurrent neural networks with long short-term memory (LSTM) units. In the second experiment, we applied a late-fusion approach to incorporate genetic features. We compared the performance with approaches currently utilized in routine clinical practice – American College of Cardiology and the American Heart Association (ACC/AHA) Pooled Cohort Risk Equation. Our results indicated that incorporating longitudinal feature lead to better event prediction. Combining genetic features through a late-fusion approach can further improve CVD prediction, underscoring the importance of integrating relevant genetic data whenever available.
An analysis of the electronic states of aceanthrylene

The electronic spectrum of aceanthrylene (AA) is examined experimentally and theoretically by use of simple perturbational molecular orbital theory and by use of a semiempirical PPP SCF CI calculation. The long-wavelength transition near 540 nm is assigned to a new state characteristic of a 4N annulene perimeter called a S transition that is not present in the precursor analogue anthracene. Stretched polyethylene sheet spectra are used to verify the calculated polarization assignments. The excited states contain extensive configuration interaction. The lowest triplet state is characterized by MNDO calculation and its electron density is used partially to explain the triplet-state photodimerization of AA. The emission behavior of 2-methylaceanthrylene is characterized by a weak fluorescence near 460 nm. This is an upper excited state emission or anomalous fluorescence.
Rearrangements of Cyclobutenones. Synthesis of N-Methyl-7,8-dihydrobenzophenanthridine-9,12-diols and Related Compounds

A useful synthetic route to benzophenanthridines and annulated derivatives is reported. These arise from the thermolysis (refluxing chlorobenzene) of squaric acid-derived 4-(3-N-methyl-N-arylpropynyl)-cyclobutenones via a mechanism which involves an electrocyclic ring opening of the cyclobutenone to the corresponding enynylketenes. Subsequent ring closure to a diradical intermediate followed by radical arylation gives the benzophenanthridines.
One-pot conversion of benzyl carbamates into fluorenylmethyl carbamates

Abstract A simple one-pot procedure smoothly converted N -benzyloxycarbonyl groups into N -fluorenylmethoxycarbonyl groups via hydrogenation with a poisoned catalyst in the presence of Fmoc-OSu. Functional groups such as t -butyl esters, t -butyl ethers, and N -Boc were stable under the reaction conditions.
An intramolecular Diels-Alder route to novel tetracyclic benzo[b]thiophene derivatives

Abstract A one-pot route to 3-benzo[b]thiophen-2-yl-acrylates ( 2 ) from the corresponding thiophenols ( 1 ) is reported. Ester reduction and subsequent hydroxyl esterification deliver psuedo trienoates ( II ) which undergo an intramolecular Diels–Alder (IMDA) reaction to give two 2-oxa-9-thiacyclopenta[b]fluoren-3-one products ( I )—the major Diels–Alder product rearomatizes to 7 .
Homonuclear correlated spectroscopy (COSY): The basics of two‐dimensional NMR

The basic principles of homonuclear correlated spectroscopy, the COSY experiment, are presented. The underlying theory is given for a single pair of coupled spins. The differences between magnitude-mode and phase-sensitive experiments are discussed. Features of the cross peaks are described, and the procedure for carrying out experiments is given. Examples of both magnitude and phase-sensitive COSY experiments are shown.
Development of new hypervalent iodine reagents with improved properties and reactivity by redirecting secondary bonds at iodine center

Abstract Hypervalent iodine reagents have found wide application in organic synthesis as versatile, efficient, and environmentally sustainable reagents. Particularly important hypervalent iodine reagents used as atom and group transfer reagents include: iodosylbenzene, (PhIO)n, (tosylimino)iodobenzene, (PhINTs)n, and iodonium ylide, PhI = C(CO2CH3)2. Despite the significant interest in these reagents as primary sources of “O”, “NR” and “CR2” units in transition metal catalyzed processes, their practical application is hampered. In particular, their tightly aggregated and polymeric structures in the solid state render these polyvalent iodine species insoluble in all nonreactive media and prevent their use in chemical reactions under homogenous conditions, which can be undesirable for many synthetic and mechanistic studies. In this review we describe our work on the rational design and development of new soluble, thermally stable, and highly reactive hypervalent iodine reagents based on structural modifications that lead to redirection of secondary bonding from intermolecular to intramolecular modes. Specifically, the introduction of a coordinating donor in the ortho-position of the phenyliodine (III) moiety leads to a significant improvement of solubility of a hypervalent iodine reagent. Based on this approach, we have developed a series of new hypervalent iodine reagents, which can be used as selective oxidants, nitrene or carbene precursors, and atom transfer reagents. Specific examples of these new reagents are represented by iodosylarenes and iminophenyliodanes bearing tert-butylsulfonyl group in the ortho-position of the phenyl ring and by the ortho-alkoxy substituted iodonium imides and ylides. These new pseudocyclic (and cyclic) reagents have excellent solubility in organic solvents and can be used as efficient reagents for catalytic formation of new C O, C N and C C bonds, as well as to enable the generation and detection of highly reactive metal species involved in catalysis and biomimetic reactions.
Transcriptomic characterization of signaling pathways associated with osteoblastic differentiation of MC-3T3E1 cells

Bone remodeling involves the coordinated actions of osteoclasts, which resorb the calcified bony matrix, and osteoblasts, which refill erosion pits created by osteoclasts to restore skeletal integrity and adapt to changes in mechanical load. Osteoblasts are derived from pluripotent mesenchymal stem cell precursors, which undergo differentiation under the influence of a host of local and environmental cues. To characterize the autocrine/paracrine signaling networks associated with osteoblast maturation and function, we performed gene network analysis using complementary “agnostic” DNA microarray and “targeted” NanoString nCounter datasets derived from murine MC3T3-E1 cells induced to undergo synchronized osteoblastic differentiation in vitro. Pairwise datasets representing changes in gene expression associated with growth arrest (day 2 to 5 in culture), differentiation (day 5 to 10 in culture), and osteoblast maturation (day 10 to 28 in culture) were analyzed using Ingenuity Systems Pathways Analysis to generate predictions about signaling pathway activity based on the temporal sequence of changes in target gene expression. Our data indicate that some pathways involved in osteoblast differentiation, e.g. Wnt/β-catenin signaling, are most active early in the process, while others, e.g. TGFβ/BMP, cytokine/JAK-STAT and TNFα/RANKL signaling, increase in activity as differentiation progresses. Collectively, these pathways contribute to the sequential expression of genes involved in the synthesis and mineralization of extracellular matrix. These results provide insight into the temporal coordination and complex interplay between signaling networks controlling gene expression during osteoblast differentiation. A more complete understanding of these processes may aid the discovery of novel methods to promote osteoblast development for the treatment of conditions characterized by low bone mineral density.
Juvenile hormone, but not nutrition or social cues, affects reproductive maturation in solitary alkali bees (Nomia melanderi)

Eusocial insect colonies are defined by extreme variation in reproductive activity among castes, but the ancestral conditions from which this variation arose are unknown. Investigating the factors that contribute to variation in reproductive physiology among solitary insects that are closely related to social species can help to fill this gap. We experimentally tested the role of nutrition, juvenile hormone (JH) and social cues on reproductive maturation in solitary alkali bees (Halictidae: Nomia melanderi). We found that alkali bee females emerge from overwintering with small Dufour's glands and small ovaries, containing oocytes in the early stages of development. Oocyte maturation occurs rapidly, and is staggered between the two ovaries. Lab-reared females reached reproductive maturity without access to mates or nesting opportunities, and many had resorbed oocytes. Initial activation of these reproductive structures does not depend on pollen consumption, though dietary protein or lipids may be necessary for long-term reproductive activity. JH is likely to be a limiting factor in alkali bee reproductive activation, as females treated with JH were more likely to develop mature oocytes and Dufour's glands. Unlike for related social bees, the effects of JH were not suppressed by the presence of older, reproductive females. These results provide valuable insight into the factors that influence reproductive activity in an important native pollinator, and those that may have been particularly influential in the evolution of reproductive castes.
Hierarchical Discrete Distribution Decomposition for Match Density Estimation

Explicit representations of the global match distributions of pixel-wise correspondences between pairs of images are desirable for uncertainty estimation and downstream applications. However, the computation of the match density for each pixel may be prohibitively expensive due to the large number of candidates. In this paper, we propose Hierarchical Discrete Distribution Decomposition (HD^3), a framework suitable for learning probabilistic pixel correspondences in both optical flow and stereo matching. We decompose the full match density into multiple scales hierarchically, and estimate the local matching distributions at each scale conditioned on the matching and warping at coarser scales. The local distributions can then be composed together to form the global match density. Despite its simplicity, our probabilistic method achieves state-of-the-art results for both optical flow and stereo matching on established benchmarks. We also find the estimated uncertainty is a good indication of the reliability of the predicted correspondences.
The preparation of 2-iodoamides from glucals and their further transformations into oxazolines

Abstract 2-Deoxy-2-iodo-glycosylamides have been prepared from a variety of protected d -glucals by their reaction with N-iodosuccinimide and amides. Benzyl protected 2-iodoamides, when treated with sodium hydride and 15-crown-5, gave stable C1 N-linked 2-glycooxazolines as the major products. Silyl protected 2-iodoamides afforded the C1 O-linked 2-glycooxazolines; presumably by the rearrangement of unstable N-acylaziridine intermediates.
Di(methylimidazole)prolinol Silyl Ether Catalyzed Highly Michael Addition of Aldehydes to Nitroolefins in Water

A new pyrrolidine-based organocatalyst for asymmetric reactions has been developed and shown to be a very effective catalyst for the Michael reaction involving various nitroolefins and aldehydes in water. This design is based on the introduction of a hydrophilic group into the pyrrolidine side chain. This catalyst, di(methylimidazole)prolinol silyl ether in combination with sodium bicarbonate as additive effectively catalyzed the Michael addition of aldehydes to nitroolefins in water as solvent in high yields and excellent enantioselectivities.
Synthesis of 2,4-diamino-5,10-dideaza nonclassical antifolates

Condensation of 2,4,6-triaminopyrimidine (8) with bromomalonaldehyde (9) afforded, after pivaloylation, 2,4-dipivaloyl-6-bromopyrido[2,3-d]pyrimidine (11). This 6-bromo derivative served as a key intermediate for the synthesis of 2,4-diamino-6-[2-(3′,4′-dimethoxyphenyl)ethenyl]pyrido[2,3-d]pyrimidine (5) via a palladium catalyzed carbon-carbon coupling with 3,4-dimethoxystyrene (12). Compound 5, its 9,10-dihydro analogue 6 and the 5,6,7,8,9,10-hexahydro analogue 7 were of interest as potential inhibitors of dihydrofolate reductase. Compounds 6 and 7 were synthesized from 5 by catalytic hydrogenation over 5% Pd-C.
Otteliones A and B: Potently cytotoxic 4-methylene-2-cyclohexenones from Ottelia alismoides

Two diastereomeric 4-methylene-2-cyclohexenones, otteliones A and B (1A and 1B), have been isolated from the freshwater plant Ottelia alismoides collected in the Nile Delta, Egypt. These natural products show remarkable in vitro cytotoxicity against various cancer cell lines. Ottelione B proved to have a constitution identical to that of the known (constitution only) ottelione A. The relative configurations of both 1A and 1B were studied by NOE and by the combination of molecular modeling and 1H NMR coupling constant analysis. A unique relative configurational assignment (1α,3β,3aβ,7aα) was deduced for 1B; 1A was assigned one of two alternative diastereomers (1α,3α,3aα,7aα or 1α,3α,3aβ,7aβ).
A general route to 4-imidazolyl-containing multidentate ligands for biomimetic studies.

4-Iodo-1-tritylimidazole undergoes magnesium−iodine exchange with a Grignard reagent to give selectively the 4-magnesioimidazole derivative, which reacts with esters to form a variety of poly-4-imidazolyl carbinol compounds in 40−79% yields. A wide range of bi-, tri-, and pentadentate ligands featuring 4-substituted imidazole units have been efficiently synthesized.