cssi/SciSciGPT-SciSciNet huggingface dataset:
The impact of tumor receptor heterogeneity on the response to anti-angiogenic cancer treatment

Multiple promoters and inhibitors mediate angiogenesis, the formation of new blood vessels, and these factors represent potential targets for impeding vessel growth in tumors. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor targeted in anti-angiogenic cancer therapies. In addition, thrombospondin-1 (TSP1) is a major endogenous inhibitor of angiogenesis, and TSP1 mimetics are being developed as an alternative type of anti-angiogenic agent. The combination of bevacizumab, an anti-VEGF agent, and ABT-510, a TSP1 mimetic, has been tested in clinical trials to treat advanced solid tumors. However, the patients' responses are highly variable and show disappointing outcomes. To obtain mechanistic insight into the effects of this combination anti-angiogenic therapy, we have constructed a novel whole-body systems biology model including the VEGF and TSP1 reaction networks. Using this molecular-detailed model, we investigated how the combination anti-angiogenic therapy changes the amounts of pro-angiogenic and anti-angiogenic complexes in cancer patients. We particularly focus on answering the question of how the effect of the combination therapy is influenced by tumor receptor expression, one aspect of patient-to-patient variability. Overall, this model complements the clinical administration of combination anti-angiogenic therapy, highlights the role of tumor receptor variability in the heterogeneous responses to anti-angiogenic therapy, and identifies the tumor receptor profiles that correlate with a high likelihood of a positive response to the combination therapy. Our model provides novel understanding of the VEGF-TSP1 balance in cancer patients at the systems-level and could be further used to optimize combination anti-angiogenic therapy.
Synthesis of fused tricyclic amines from enolizable acyclic aldehydes by cyclization then dipolar cycloaddition cascade: synthesis of myrioxazine A.

A tandem one-pot reaction involving a condensation, then cyclization (N-alkylation), followed by an azomethine ylide or nitrone dipolar cycloaddition allows a synthesis of tricyclic amines from acy...
Facile synthesis of biologically active heterocycles by indium-induced reactions of aromatic nitro compounds in aqueous ethanol

Indium/ammonium chloride-induced reduction of aromatic nitro compounds to aromatic amines in aqueous ethanol was developed. Useful chemo-selectivity was observed in the reduction reaction. This method was extended to reductive cyclization and rearrangement toward the synthesis of various biologically active heterocycles, including quinoline, oxazines, quinalonones, and phenanthridine in excellent yield. The oxophilicity of indium metal influenced the reaction in aqueous ethanol. Metals like zinc and tin were not effective in promoting this kind of reactions under the present environmentally friendly conditions.
Improving Fraction Understanding in Sixth Graders with Mathematics Difficulties: Effects of a Number Line Approach Combined with Cognitive Learning Strategies.

The effectiveness of an experimental middle school fraction intervention was evaluated. The intervention was centered on the number line and incorporated key principles from the science of learning. Sixth graders (N = 51) who struggled with fraction concepts were randomly assigned at the student level to the experimental intervention (n = 28) or to a business-as-usual control who received their school’s intervention (n = 23). The experimental intervention occurred over 6 weeks (27 lessons). Fraction number line estimation, magnitude comparisons, concepts, and arithmetic were assessed at pretest, posttest, and delayed posttest. The experimental group demonstrated significantly more learning than the control group from pretest to posttest, with meaningful effect sizes on measures of fraction concepts (g = 1.09), number line estimation as measured by percent absolute error (g = −.85), and magnitude comparisons (g = .82). These improvements held at delayed posttest 7 weeks later. Exploratory analyses showed a significant interaction between classroom attentive behavior and intervention group on fraction concepts at posttest, suggesting a buffering effect of the experimental intervention on the normally negative impact of low attentive behavior on learning. A number line–centered approach to teaching fractions that also incorporates research-based learning strategies helps struggling learners to make durable gains in their conceptual understanding of fractions. (PsycINFO Database Record (c) 2020 APA, all rights reserved)
Instability analysis of the flow between two parallel plates where the bottom one coated with porous media

Abstract This study investigates the instability of pure Newtonian fluid flow between two parallel plates where the bottom one coated with various porous media with permeability K and porosity e. We have applied normal modes to perturb the coupled flow system. Specifically, the effects of some dimensionless parameters such as depth ratio, permeability parameter, and the porosity of the porous medium on the instability have been examined. We found these parameters play a critical role in the instability. Depending on these parameters, instability is initiated and dominated either by the fluid or by the porous region. In particular, we found that there are ranges of the depth ratio and the permeability parameter for each value of the porous media porosity that affect the instability of this coupled flow. We have also determined a new parameter which specifies the potential dominance and the stability margin of each mode. To validate our calculations, we have also compared our results with the Orr–Sommerfeld equation. In addition, we have examined three special extreme conditions to study the coupled flow system in more detail.
Improvements in the Synthesis of a Coumaromethacrylate Dye

Abstract A new method to prepare a coumaromethacrylate dye has been devised. The older three‐step route was shortened to a one‐pot, solvent‐free step.
Hydroflux synthesis and crystal structure of new lanthanide tungstate oxyhydroxides

Abstract Single crystals of Na5Ln(OH)6WO4 where Ln = Er, Tm, and Yb were grown out of a NaOH hydroflux. The crystals were characterized by single crystal X-ray diffraction and were found to crystallize in the monoclinic space group I2/a. The lattice parameter ranges for the three structures are a = 11.2024(7) A–11.2412(6) A, b = 16.1850(10) A–16.2220(10) A, and c = 11.9913(7) A–12.0323(7) A while the β angle range is 101.999(2)°–102.025(2)°.
Analysis of Copy Number Loss of the ErbB4 Receptor Tyrosine Kinase in Glioblastoma

Current treatments for glioblastoma multiforme (GBM)-an aggressive form of brain cancer-are minimally effective and yield a median survival of 14.6 months and a two-year survival rate of 30%. Given the severity of GBM and the limitations of its treatment, there is a need for the discovery of novel drug targets for GBM and more personalized treatment approaches based on the characteristics of an individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes, but publicly available data from the Cancer Cell Line Encyclopedia (CCLE) indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines, suggesting a potential tumor suppressor role. This loss is mutually exclusive with loss of its cognate ligand NRG1 in CCLE as well, more strongly suggesting a functional role. The availability of higher resolution copy number data from clinical GBM patients in The Cancer Genome Atlas (TCGA) revealed that a region in Intron 1 of the ERBB4 gene was deleted in 69.1% of tumor samples harboring ERBB4 copy number loss; however, it was also found to be deleted in the matched normal tissue samples from these GBM patients (n = 81). Using the DECIPHER Genome Browser, we also discovered that this mutation occurs at approximately the same frequency in the general population as it does in the disease population. We conclude from these results that this loss in Intron 1 of the ERBB4 gene is neither a de novo driver mutation nor a predisposing factor to GBM, despite the indications from CCLE. A biological role of this significantly occurring genetic alteration is still unknown. While this is a negative result, the broader conclusion is that while copy number data from large cell line-based data repositories may yield compelling hypotheses, careful follow up with higher resolution copy number assays, patient data, and general population analyses are essential to codify initial hypotheses prior to investing experimental resources.
The Hexacyanotitanate Ion: Synthesis and Crystal Structure of [NEt4]3[TiIII(CN)6]·4MeCN

The hexacyanotitanate salt, [Et4N]3[Ti(CN)6]·4MeCN, has been prepared by addition of tetraethylammonium cyanide to the titanium(III) triflate salt Ti(O3SCF3)3(MeCN)3. The orange crystalline product has been characterized by X-ray diffraction, and the d1 anion is only slightly distorted from ideal Oh symmetry. The anion resides on a center of symmetry and is characterized by the following parameters: Ti−C = 2.195(2), 2.197(3), and 2.213(3) A; C−N (av) = 1.141(4) A; C−Ti−C (cis) = 88.01(9), 88.02(9), 89.02(9), and 89.78(9)°; C−Ti−C (trans) = 180°. In addition to the crystallographic study, details of the IR (νCN = 2071 cm-1), EPR, and UV−vis spectra (Δo = 22800 cm-1) are given. Crystal data for [Et4N]3[Ti(CN)6]·4MeCN are as follows: monoclinic, space group I2/a, a = 18.171(6) A, b = 12.200(4) A, c = 20.989(5) A, β = 91.17(2)°, V = 4652(2) A3, Z = 4, wR2 = 0.2054 for 3831 data, 27 restraints, and 318 parameters.
A new route to the phosphazene polymerization precursors, Cl3P=NSiMe3 and (NPCl2)3

An improved synthesis of the phosphazene polymerization precursors, hexachlorocyclotriphosphazene, (NPCl2)3 (1), and Cl3PNSiMe3 (2) is reported. The addition of PCl5 to N(SiMe3)3 in methylene chloride at 40 °C produced a mixture of phosphazenes which contained 76% of 1. However, the addition of N(SiMe3)3 to PCl5 in methylene chloride at 0 °C, followed by the addition of hexane, provided 2 in 40% yield. The mechanism of the reaction is discussed.
iSeg: an efficient algorithm for segmentation of genomic and epigenomic data

Identification of functional elements of a genome often requires dividing a sequence of measurements along a genome into segments where adjacent segments have different properties, such as different mean values. Despite dozens of algorithms developed to address this problem in genomics research, methods with improved accuracy and speed are still needed to effectively tackle both existing and emerging genomic and epigenomic segmentation problems. We designed an efficient algorithm, called iSeg, for segmentation of genomic and epigenomic profiles. iSeg first utilizes dynamic programming to identify candidate segments and test for significance. It then uses a novel data structure based on two coupled balanced binary trees to detect overlapping significant segments and update them simultaneously during searching and refinement stages. Refinement and merging of significant segments are performed at the end to generate the final set of segments. By using an objective function based on the p-values of the segments, the algorithm can serve as a general computational framework to be combined with different assumptions on the distributions of the data. As a general segmentation method, it can segment different types of genomic and epigenomic data, such as DNA copy number variation, nucleosome occupancy, nuclease sensitivity, and differential nuclease sensitivity data. Using simple t-tests to compute p-values across multiple datasets of different types, we evaluate iSeg using both simulated and experimental datasets and show that it performs satisfactorily when compared with some other popular methods, which often employ more sophisticated statistical models. Implemented in C++, iSeg is also very computationally efficient, well suited for large numbers of input profiles and data with very long sequences. We have developed an efficient general-purpose segmentation tool and showed that it had comparable or more accurate results than many of the most popular segment-calling algorithms used in contemporary genomic data analysis. iSeg is capable of analyzing datasets that have both positive and negative values. Tunable parameters allow users to readily adjust the statistical stringency to best match the biological nature of individual datasets, including widely or sparsely mapped genomic datasets or those with non-normal distributions.
Bioinformatic analysis suggests potential mechanisms underlying parasitoid venom evolution and function

Hymenopteran parasitoid wasps are a diverse collection of species that infect arthropod hosts and use factors found in their venoms to manipulate host immune responses, physiology, and behaviour. Whole parasitoid venoms have been profiled using proteomic approaches, and here we present a bioinformatic characterization of the venom protein content from Ganaspis sp. 1, a parasitoid that infects flies of the genus Drosophila. We find evidence that diverse evolutionary processes including multifunctionalization, co-option, gene duplication, and horizontal gene transfer may be acting in concert to drive venom gene evolution in Ganaspis sp.1. One major role of parasitoid wasp venom is host immune evasion. We previously demonstrated that Ganaspis sp. 1 venom inhibits immune cell activation in infected Drosophila melanogaster hosts, and our current analysis has uncovered additional predicted virulence functions. Overall, this analysis represents an important step towards understanding the composition and activity of parasitoid wasp venoms.
Nonstabilized N-unsubstituted azomethine ylides: a synthesis of indolizidine 239CD.

Treatment of a (2-azaallyl)stannane with HF·pyridine generated a nonstabilized N-unsubstituted azomethine ylide, which was found to undergo an efficient and stereoselective dipolar cycloaddition wi...
Alternative Vision of Living with IoT

My research examines the values, norms, and practices of subcultures formed as an "alternative" to the dominant way of life. In particular, I explore how technology relates to alternative forms of interaction or can be understood and reconstructed through alternative concepts or frameworks. For the past three years, I have conducted fieldwork with communities pursuing alternative lifestyles. This work considers how those alternative lifestyles may contribute to an understanding of objects and spaces in a home. Through my fieldwork and research through design (RtD), I hope to offer an alternative vision to living with IoT while imagining future domesticity in a unique and possibly groundbreaking way.
Advancements in oxazolidinone synthesis utilizing carbon dioxide as a C1 source

Abstract Carbon dioxide, a natural molecule, has been utilized in the synthesis of chemicals for several decades. Its innocuous chemical properties make it a favorable substance to incorporate in such synthetic processes. Recently, research is being conducted to include carbon dioxide in the production of a specific class of cyclic urethane molecules known as oxazolidinones. Oxazolidinones are important in synthetic and medicinal applications, which necessitate a greener method to produce them. In this review, various synthetic methods including catalytic processes that incorporate carbon dioxide to yield oxazolidinones have been discussed and the results of the research are presented. Emphasis is placed primarily on reactions of carbon dioxide with a variety of aziridines, propargylamines and 2-amino alcohols for the synthesis of oxazolidinones.
Network structural dependency in the human connectome across the life-span

Principles of network topology have been widely studied in the human connectome. Of particular interest is the modularity of the human brain, where the connectome is divided into subnetworks from w...
KNa3In9: A Zintl Network Phase Built of Layered Indium Icosahedra and Zigzag Chains. Synthesis, Structure, Bonding, and Properties

This phase was discovered following direct fusion of the elements in welded Nb tubes at 550 °C and equilibration at 300 °C for 1 week. Single-crystal X-ray diffraction analysis reveals that KNa3In9 crystallizes in an orthorhombic system (Cmca, Z = 8, a = 9.960(1) A, b =16.564(2) A, c = 17.530(2) A, 23 °C). The structure contains a three-dimensional indium network built of layers of empty In12 icosahedra that are each 12-bonded and interconnected by 4-bonded indium atoms that also form zigzag chains. All cations bridge between cluster faces or edges, and their mixed sizes appear critical to the stability of this particular structure, which does not occur in either binary system. Both empirical electron counting and EHTB band structure calculations on the macroanion indicate that the bonding in this structure is closed-shell, whereas resistivity and magnetic susceptibility measures show that the compound is a moderately poor metal.
Cyclization Reactions of Rhodium Carbene Complexes. Effect of Composition and Oxidation State of the Metal

Treatment of o-(1,7-octadiynyl)benzoyldiazoethane with rhodium(II) octanoate in pentane resulted in a double internal/internal alkyne insertion reaction producing a labile bicyclo[4.1.0]hept-1(7)-ene derivative which readily undergoes a Diels−Alder reaction with diphenylisobenzofuran. Changing the solvent from pentane to CH2Cl2 afforded a 2:1 mixture of cis- and trans-alkenyl-substituted indenones. Stepwise cyclization involving a set of dipolar intermediates occurs in CH2Cl2 whereas metallocyclobutenes are involved when pentane is used as the solvent. The rhodium(II) carboxylate catalyzed reaction of unsymmetrically substituted cyclopropenes gives substituted furans derived from cleavage of the less substituted β-bond. Thus, treatment of 3-benzoyl-3-methyl-1-(n-butyl)cyclopropene with Rh2OAc4 afforded a 26:1 mixture of 2-phenyl-3-methyl-4-(n-butyl)- and 2-phenyl-3-methyl-5-(n-butyl)furan. In contrast, the [ClRh(CO)2]2-catalyzed reaction resulted in cleavage of the more substituted σ-bond producing only 2...
Azithromycin Resistance through Interspecific Acquisition of an Epistasis-Dependent Efflux Pump Component and Transcriptional Regulator in Neisseria gonorrhoeae.

ABSTRACT Mosaic interspecifically acquired alleles of the multiple transferable resistance ( mtr ) efflux pump operon correlate with increased resistance to azithromycin in Neisseria gonorrhoeae in epidemiological studies. However, whether and how these alleles cause resistance is unclear. Here, we use population genomics, transformations, and transcriptional analyses to dissect the relationship between variant mtr alleles and azithromycin resistance. We find that the locus encompassing the mtrR transcriptional repressor and the mtrCDE pump is a hot spot of interspecific recombination introducing alleles from Neisseria meningitidis and Neisseria lactamica into N. gonorrhoeae, with multiple rare haplotypes in linkage disequilibrium at mtrD and the mtr promoter region. Transformations demonstrate that resistance to azithromycin, as well as to other antimicrobial compounds such as polymyxin B and crystal violet, is mediated through epistasis between these two loci and that the full-length mosaic mtrD allele is required. Gene expression profiling reveals the mechanism of resistance in mosaics couples novel mtrD alleles with promoter mutations that increase expression of the pump. Overall, our results demonstrate that epistatic interactions at mtr gained from multiple neisserial species has contributed to increased gonococcal resistance to diverse antimicrobial agents. IMPORTANCE Neisseria gonorrhoeae is the sexually transmitted bacterial pathogen responsible for more than 100 million cases of gonorrhea worldwide each year. The incidence of resistance to the macrolide azithromycin has increased in the past decade; however, a large proportion of the genetic basis of resistance remains unexplained. This study is the first to conclusively demonstrate the acquisition of macrolide resistance through mtr alleles from other Neisseria species, demonstrating that commensal Neisseria bacteria are a reservoir for antibiotic resistance to macrolides, extending the role of interspecies mosaicism in resistance beyond what has been previously described for cephalosporins. Ultimately, our results emphasize that future fine-mapping of genome-wide interspecies mosaicism may be valuable in understanding the pathways to antimicrobial resistance. Our results also have implications for diagnostics and public health surveillance and control, as they can be used to inform the development of sequence-based tools to monitor and control the spread of antibiotic-resistant gonorrhea.
The cation radical vinylcyclopropane→cyclopentene rearrangement: reaction mechanism and periselectivity

Abstract The vinylcyclopropane→cyclopentene rearrangement catalyzed by one-electron oxidation has been shown to be most consistent with a stepwise, cation radical mechanism. It was also discovered that the formal rearrangement periselectivity of vinylcyclopropanes with cis-alkyl substituents can be changed by one-electron oxidation.
Dipolar Cycloaddition Route to Diverse Analogues of Cocaine: The 6- and 7-Substituted 3-Phenyltropanes

In our quest for an antagonist or partial agonist of cocaine, access to certain 6- and 7-substituted 3-phenyltropanes of type I was required. Starting from 3-hydroxy-1-methyl-4-phenylpyridinium iodide, we disclose a pyridinium betaine-based dipolar cycloaddition route to tropenones of type II. In turn, we show how this intermediate can be transformed to type I products either through the copper-catalyzed conjugate addition reaction of Grignard reagents to the enones 7-9 or by the copper(I)-catalyzed cross coupling reaction of the allylic acetates 15a and 16a with Grignard reagents.
Vaccination has minimal impact on the intrahost diversity of H3N2 influenza viruses.

While influenza virus diversity and antigenic drift have been well characterized on a global scale, the factors that influence the virus’ rapid evolution within and between human hosts are less clear. Given the modest effectiveness of seasonal vaccination, vaccine-induced antibody responses could serve as a potent selective pressure for novel influenza variants at the individual or community level. We used next generation sequencing of patient-derived viruses from a randomized, placebo-controlled trial of vaccine efficacy to characterize the diversity of influenza A virus and to define the impact of vaccine-induced immunity on within-host populations. Importantly, this study design allowed us to isolate the impact of vaccination while still studying natural infection. We used pre-season hemagglutination inhibition and neuraminidase inhibition titers to quantify vaccine-induced immunity directly and to assess its impact on intrahost populations. We identified 166 cases of H3N2 influenza over 3 seasons and 5119 person-years. We obtained whole genome sequence data for 119 samples and used a stringent and empirically validated analysis pipeline to identify intrahost single nucleotide variants at ≥1% frequency. Phylogenetic analysis of consensus hemagglutinin and neuraminidase sequences showed no stratification by pre-season HAI and NAI titer, respectively. In our study population, we found that the vast majority of intrahost single nucleotide variants were rare and that very few were found in more than one individual. Most samples had fewer than 15 single nucleotide variants across the entire genome, and the level of diversity did not significantly vary with day of sampling, vaccination status, or pre-season antibody titer. Contrary to what has been suggested in experimental systems, our data indicate that seasonal influenza vaccination has little impact on intrahost diversity in natural infection and that vaccine-induced immunity may be only a minor contributor to antigenic drift at local scales.
A direct, highly convergent route to α-methylene-γ-lactones fused to medium and large rings

Abstract A general procedure for the synthesis of α-methylene lactones cis- or trans-fused to larger rings is described. The convenient approach originates with two ω-unsaturated aldehydes of the same or different chain length.
Correlations between Chemical Bonding and Magnetic Exchange Interactions: Synthesis, Crystal Structures, and Magnetic Properties of the New Family RE2AlGe2 (RE = Tb–Tm, Lu)

Six new rare-earth metal germanides with general formula RE2Al1–xGe2+x (RE = Tb–Tm, Lu; 0.13(2) ≤ x ≤ 0.37(2)) have been synthesized by direct fusion of the corresponding elements. Their structures have been established by single-crystal diffraction to crystallize with the orthorhombic space group Immm (no. 74), adopting the W2CoB2 structure type. The Al and Ge atoms are arranged in alternating planar layers, made of rhombic- and hexagonal-fragments. The rare-earth metal substructure consists of puckered four-connected nets. Electronic structure calculations support the coloring of the Ge and Al sites and account for the existence of a small homogeneity range. DC magnetization measurements for all specimens are also presented; based on the RKKY and mean-field theories for antiferromagnets, relationships between the chemical bonding and exchange interactions are discussed.
The microbial metagenome and bone tissue composition in mice with microbiome-induced reductions in bone strength.

Abstract The genetic components of microbial species that inhabit the body are known collectively as the microbiome. Modifications to the microbiome have been implicated in disease processes throughout the body and have recently been shown to influence bone. Prior work has associated changes in the microbial taxonomy (phyla, class, species, etc.) in the gut with bone phenotypes but has provided limited information regarding mechanisms. With the goal of achieving a more mechanistic understanding of the effects of the microbiome on bone, we perform a metagenomic analysis of the gut microbiome that provides information on the functional capacity of the microbes (all microbial genes present) rather than only characterizing the microbial taxa. Male C57Bl/6 mice were subjected to disruption of the gut microbiota (ΔMicrobiome) using oral antibiotics (from 4 to 16 weeks of age) or remained untreated (n = 6–7/group). Disruption of the gut microbiome in this manner has been shown to lead to reductions in tissue mechanical properties and whole bone strength in adulthood with only minor changes in bone geometry and density. ΔMicrobiome led to modifications in the abundance of microbial genes responsible for the synthesis of the bacterial cell wall and capsule; bacterially synthesized carbohydrates; and bacterially synthesized vitamins (B and K) (p
Repeated translocation of a gene cassette drives sex-chromosome turnover in strawberries

Turnovers of sex-determining systems represent important diversifying forces across eukaryotes. Shifts in sex chromosomes-but conservation of the master sex-determining genes-characterize distantly related animal lineages. Yet in plants, in which separate sexes have evolved repeatedly and sex chromosomes are typically homomorphic, we do not know whether such translocations drive sex-chromosome turnovers within closely related taxonomic groups. This phenomenon can only be demonstrated by identifying sex-associated nucleotide sequences, still largely unknown in plants. The wild North American octoploid strawberries (Fragaria) exhibit separate sexes (dioecy) with homomorphic, female heterogametic (ZW) inheritance, yet sex maps to three different chromosomes in different taxa. To characterize these turnovers, we identified sequences unique to females and assembled their reads into contigs. For most octoploid Fragaria taxa, a short (13 kb) sequence was observed in all females and never in males, implicating it as the sex-determining region (SDR). This female-specific "SDR cassette" contains both a gene with a known role in fruit and pollen production and a novel retrogene absent on Z and autosomal chromosomes. Phylogenetic comparison of SDR cassettes revealed three clades and a history of repeated translocation. Remarkably, the translocations can be ordered temporally due to the capture of adjacent sequence with each successive move. The accumulation of the "souvenir" sequence-and the resultant expansion of the hemizygous SDR over time-could have been adaptive by locking genes into linkage with sex. Terminal inverted repeats at the insertion borders suggest a means of movement. To our knowledge, this is the first plant SDR shown to be translocated, and it suggests a new mechanism ("move-lock-grow") for expansion and diversification of incipient sex chromosomes.
Enzymatic/Chemical Synthesis and Biological Evaluation of Seven-Membered Iminocyclitols

Several polyhydroxyperhydroazepines have been obtained either by chemoenzymatic or chemical synthesis. Condensation of (±)-3-azido-2-hydroxypropanaldehyde and dihydroxyacetone phosphate (DHAP) in the presence of a DHAP dependent aldolase followed by treatment with acid phosphatase and an isomerase gave a 6-azido-6-deoxyaldopyranose, which upon reductive amination afforded the title compound. The iminocyclitols can also be obtained by chemical manipulations of aldopyranoses, protected as benzyl glycosides or diisopropylidene ethers. Thus, d-galactose leads to a meso-3,4,5,6-tetrahydroxyperhydroazepine, d-mannose to a derivative with a C2 symmetry axis, and N-acetylglucosamine to a 6-acetamidoiminocyclitol. Asymmetrization of the meso azasugar was carried out by chemical means, to yield a 3-methoxy-4,5,6-trihydroxyazepane. An attempted enzymatic synthesis of the methoxy derivatives of these azasugars was unsuccessful, leading, however, to both enantiomers of 1-deoxy-2-O-methylmannojirimycin. Some of these c...
A Ru-catalyzed tandem alkyne-enone coupling/Michael addition: synthesis of 4-methylene-2,6-cis-tetrahydropyrans.

A Ru-catalyzed tandem alkyne−enone coupling/Michael addition reaction is reported. It provides an efficient, atom-economic entry to 4-methylene-2,6-cis-tetrahydropyrans from simple, readily available homopropargylic alcohols and β,γ-unsaturated enones in good yields. Further functionalization of the resultant vinylsilane leads to the synthesis of either geometrically defined trisubstituted alkene exocyclic to the 2,6-cis-dihydropyran.
Model-Based Clustering of Nonparametric Weighted Networks with Application to Water Pollution Analysis

Water pollution is a major global environmental problem, and it poses a great environmental risk to public health and biological diversity. This work is motivated by assessing the potential environ...
Pressure dependence of peroxynitrite reactions. Support for a radical mechanism.

Activation volumes (ΔV⧧) have been determined for several reactions of peroxynitrite using the stopped-flow technique. Spontaneous decomposition of ONOOH to NO3- in 0.15 M phosphate, pH 4.5, gave Δ...
Simulation of visual perception and learning with a retinal prosthesis.

Objective The nature of artificial vision with a retinal prosthesis, and the degree to which the brain can adapt to the unnatural input from such a device, are poorly understood. Therefore, the development of current and future devices may be aided by theory and simulations that help to infer and understand what prosthesis patients see. Approach A biologically-informed, extensible computational framework is presented here to predict visual perception and the potential effect of learning with a subretinal prosthesis. The framework relies on optimal linear reconstruction of the stimulus from retinal responses to infer the visual information available to the patient. A simulation of the physiological optics of the eye and light responses of the major retinal neurons was used to calculate the optimal linear transformation for reconstructing natural images from retinal activity. The result was then used to reconstruct the visual stimulus during the artificial activation expected from a subretinal prosthesis in a degenerated retina, as a proxy for inferred visual perception. Main results Several simple observations reveal the potential utility of such a simulation framework. The inferred perception obtained with prosthesis activation was substantially degraded compared to the inferred perception obtained with normal retinal responses, as expected given the limited resolution and lack of cell type specificity of the prosthesis. Consistent with clinical findings and the importance of cell type specificity, reconstruction using only ON cells, and not OFF cells, was substantially more accurate. Finally, when reconstruction was re-optimized for prosthesis stimulation, simulating the greatest potential for learning by the patient, the accuracy of inferred perception was much closer to that of healthy vision. Significance The reconstruction approach thus provides a more complete method for exploring the potential for treating blindness with retinal prostheses than has been available previously. It may also be useful for interpreting patient data in clinical trials, and for improving prosthesis design.
Synthesis and photochemistry of spiro[2.5]octa-1,4-dien-3-ones. Reversible biradical formation and biradical-olefin cycloaddition

Abstract Photolysis of the spiro[2.5]octa-1,4-dien-3-one 9a results in photoisomerization via the nitrile-stabilized biradical 10 . Photolysis of dienone 9b in the presence of tetramethylethylene gave spiro[4.5]deca-1,4-dien-3-one 12 by cycloaddition of the intermediate biradical 11 to tetramethylethylene.
Bioinformatic analysis of long-lasting transcriptional and translational changes in the basolateral amygdala following acute stress

Stress profoundly impacts the brain and increases the risk of developing a psychiatric disorder. The brain's response to stress is mediated by a number of pathways that affect gene expression and protein function throughout the cell. Understanding how stress achieves such dramatic effects on the brain requires an understanding of the brain's stress response pathways. The majority of studies focused on molecular changes have employed repeated or chronic stress paradigms to assess the long-term consequences of stress and have not taken an integrative genomic and/or proteomic approach. Here, we determined the lasting impact of a single stressful event (restraint) on the broad molecular profile of the basolateral amygdala complex (BLC), a key brain region mediating emotion, memory and stress. Molecular profiling performed thirty days post-restraint consisted of small RNA sequencing, RNA sequencing and quantitative mass spectrometry and identified long-lasting changes in microRNA (miRNA), messenger RNA (mRNA) and proteins. Alignment of the three datasets further delineated the regulation of stress-specific pathways which were validated by qPCR and Western Blot analysis. From this analysis, mir-29a-5p was identified as a putative regulator of stress-induced adaptations in the BLC. Further, a number of predicted mir-29a-5p targets are regulated at the mRNA and protein level. The concerted and long-lasting disruption of multiple molecular pathways in the amygdala by a single stress event is expected to be sufficient to alter behavioral responses to a wide array of future experiences, including exposure to additional stressors.
The use of sulfur ylides in the synthesis of substituted indoles.

This letter describes the insertion of rhodium carbenoids into thioindoles. C-10 thioindoles undergo fragmentation−coupling reactions when exposed to rhodium carbenoids. In an analogous fashion, ketoester- and malonate-substituted carbenoids have been found to insert into C-2 thioindoles. In contrast, vinylogous carbenoids were found to alkylate C-2 thioindoles at C-3.
UpSetR: an R package for the visualization of intersecting sets and their properties

Motivation Venn and Euler diagrams are a popular yet inadequate solution for quantitative visualization of set intersections. A scalable alternative to Venn and Euler diagrams for visualizing intersecting sets and their properties is needed. Results We developed UpSetR, an open source R package that employs a scalable matrix-based visualization to show intersections of sets, their size, and other properties. Availability and implementation UpSetR is available at https://github.com/hms-dbmi/UpSetR/ and released under the MIT License. A Shiny app is available at https://gehlenborglab.shinyapps.io/upsetr/ . Contact nils@hms.harvard.edu. Supplementary information Supplementary data are available at Bioinformatics online.
Synthesis of 1-Oxadecalones via the Lewis Acid Catalyzed Dihydropyrone Diels−Alder Reaction

The 1-oxadecalin unit serves as the structural core for a diverse variety of natural products, including the PAF antagonist phomactin A (1, Figure 1).1 Our interest in this area led us to consider an expedient method for the preparation of the 1-oxadecalone framework (e.g., 2) as part of a synthetic effort geared toward this natural product.2 Toward this end, we recently reported the facile preparation of highly functionalized 1-oxadecalone derivatives via the Diels-Alder reaction of 5-substituted 2,3-dihydro-4H-pyran-4-ones (4).3 Though this work demonstrated for the first time that dihydropyrones could be used effectively as dienophiles in this application, in practice, the thermal reaction is limited to the use of dienes that contain two or more electron-donating groups due to the relatively low reactivity of the dihydropyrone dienophile. We now report an extension of the dihydropyrone Diels-Alder reaction via the use of Lewis acid catalysis.4 In this way, the scope of this method can be expanded to include the synthesis of 1-oxadecalone derivatives that were previously inaccessible under thermal conditions.
Synthesis of carboalkoxychloro- and bromodiazirines

The first known 3H-diazirines bearing a carbonyl group and a halogen atom on C-3 have been prepared by a novel synthetic method. Carboalkoxychloro- and bromodiazirines 1a-d are formed in up to 45% yields by reductive dechlorination of carboalkoxy-N,N,N'-trichloroformamidines 9a,b using chloride or bromide ion. This method constitutes the first example of the use of N,N,N'-trichloroamidines as starting materials in organic synthesis.
CRYSTAL STRUCTURE AND RAMAN SPECTROSCOPY OF FEVMOO7 AND CRVMOO7 WITH MO=O DOUBLE BONDS

Single crystals of FeVMoO7 and CrVMoO7 were grown by a flux method from Fe2O3−V2O5−MoO3 and Cr2O3−V2O5−MoO3 melts, respectively. Single-crystal X-ray diffraction revealed that FeVMoO7 and CrVMoO7 are isostructural, in which V5+ and Mo6+ ions in the [VMoO7]3- units are crystallographically distinct, and one type of oxygen is bonded only to molybdenum, forming a MoO double bond. These rare structural features were also studied by infrared and Raman spectroscopy. Raman MoO stretching frequencies are consistent with the assignments made in previous surface studies of molybdate catalysts. Crystal data for FeVMoO7: triclinic, space group P1 (No. 2), with a = 5.564(1) A, b = 6.669(1) A, c = 7.909(1) A, α = 97.65(1)°, β = 90.33(1)°, γ = 101.32(2)° and Z = 2. Crystal data for CrVMoO7: triclinic, space group P1 (No. 2), with a = 5.5273(9) A, b = 6.582(1) A, c = 7.8650(9) A, α = 96.19(1)°, β = 89.87(1)°, γ = 102.01(1)°, and Z = 2.
A Diastereo- and Enantioselective Synthesis of α-Substituted syn-α,β-Diamino Acids

Highly diastereo- and enantioselective additions of substituted alpha-nitroesters to imines have been developed. High diastereoselection relies on the finding that the combination of chiral proton catalyst 2b and alpha-nitro aryl esters bearing 2,6-disubstitution combine to raise substrate-controlled diastereoselection to >20:1 in favor of the syn diastereomer. Furthermore, the chiral catalyst provides enantioselection to the 99% level through control of the addition step in which the azomethine pi-faces are differentiated. The bifunctional chiral protic acid catalyst enables these reactions to proceed without separate preactivation of either substrate, leading to a straightforward synthetic protocol for the formation of alpha,beta-diamino phenyl alanine derivatives.
Structure-Bonding Relationships in the Laves Phases†

The Laves phase structures (MgCu2 MgZn2 and MgNi2 types) are adopted by a large number of binary intermetallic compounds of composition AB2. These phases belong to the class of tetrahedrally closepacked alloys. Two of the structural features of the Laves phases which have aroused interest are, firstly the dependence of the structure adopted (especially the choice between the cubic MgCu2 and hexagonal MgZn2 types) on the number of valence electrons of the constituent metal atoms and, secondly the structural distortions observed in a number of the hexagonal MgZn2 type phases. By performing extended Huckel band calculations on model AB2 compounds with both the cubic and hexagonal structures and on the B sub-nets alone, structure electron-count and deformation-electron count correlations are derived. These correlations depend on the highly peaked nature of the density of states of the Laves phases, primarily due to the B network.
Enantioselective synthesis of propargylamines through Zr-catalyzed addition of mixed alkynylzinc reagents to arylimines.

Addition of mixed alkynylzinc reagents to various arylimines is catalyzed by chiral amino acid-based ligand 1 and Zr(Oi-Pr)4·HOi-Pr to afford chiral propargylamines in up to 90% ee. Oxidative removal of the o-anisidyl group affords the free amine, which can then be acylated.
Chiral auxiliary mediated stereoselective allylation of electron deficient radicals

Abstract Electron deficient radicals bearing oxazolidine chiral auxiliaries undergo efficient addition to allyltributyltin with moderate to excellent stereoselectivities.
Individual differences in relational reasoning

Various forms of relational processing have been linked to cognitive capacity measures, such as working memory and fluid intelligence. However, previous work has not established the extent to which different forms of relational processing reflect common factors, nor whether individual differences in cognitive style also contribute to variations in relational reasoning. The current study took an individual-differences approach to investigate the prerequisites for relational processing. In two studies, college students completed a battery of standardized tests of individual differences related to fluid intelligence and cognitive style, as well as a series of experimental tasks that require relational reasoning. Moderate correlations were obtained between relational processing and measures of cognitive capacity. Questionnaire measures of cognitive style generally did not improve predictions of relational processing beyond the influence of measures of cognitive capacity.
A Tensor-Train accelerated solver for integral equations in complex geometries

Abstract We present a framework using the Quantized Tensor Train ( qtt ) decomposition to accurately and efficiently solve volume and boundary integral equations in three dimensions. We describe how the qtt decomposition can be used as a hierarchical compression and inversion scheme for matrices arising from the discretization of integral equations. For a broad range of problems, computational and storage costs of the inversion scheme are extremely modest O ( log ⁡ N ) and once the inverse is computed, it can be applied in O ( N log ⁡ N ) . We analyze the qtt ranks for hierarchically low rank matrices and discuss its relationship to commonly used hierarchical compression techniques such as fmm and hss . We prove that the qtt ranks are bounded for translation-invariant systems and argue that this behavior extends to non-translation invariant volume and boundary integrals. For volume integrals, the qtt decomposition provides an efficient direct solver requiring significantly less memory compared to other fast direct solvers. We present results demonstrating the remarkable performance of the qtt -based solver when applied to both translation and non-translation invariant volume integrals in 3d . For boundary integral equations, we demonstrate that using a qtt decomposition to construct preconditioners for a Krylov subspace method leads to an efficient and robust solver with a small memory footprint. We test the qtt preconditioners in the iterative solution of an exterior elliptic boundary value problem (Laplace) formulated as a boundary integral equation in complex, multiply connected geometries.
Control Energy of Lattice Graphs

The control of complex networks has generated considerable interest in a variety of fields from traffic management to neural systems. A commonly used metric to compare two particular control strategies that accomplish the same task is the control energy, the time-integral of the sum of squares of all control inputs. The minimum control energy problem determines the control input that lower bounds all other control inputs with respect to their control energies. Here, we focus on the infinite lattice graph with linear dynamics and analytically derive the expression for the minimum control energy in terms of the modified Bessel function. We then demonstrate that the control energy of the infinite lattice graph accurately predicts the control energy of finite lattice graphs.
A Light-Weight Vibrational Motor Powered Recoil Robot That Hops Rapidly Across Granular Media

A 1 cm coin vibrational motor fixed to the center of a 4 cm square foam platform moves rapidly across granular media (poppy seeds, millet, corn meal) at a speed of up to 30 cm/s, or about 5 body lengths/s. Fast speeds are achieved with dimensionless acceleration number, similar to a Froude number, up to 50, allowing the light-weight 1.4 g mechanism to remain above the substrate, levitated and propelled by its kicks off the surface. The mechanism is low cost and moves without any external moving parts. With 2 s exposures we photograph the trajectory of the mechanism using an LED blocked except for a pin-hole and fixed to the mechanism. Trajectories can exhibit period doubling phenomena similar to a ball bouncing on a vibrating table top. A two dimensional numerical model gives similar trajectories, though a vertical drag force is required to keep the mechanism height low. We attribute the vertical drag force to aerodynamic suction from air flow below the mechanism base and through the granular substrate. Our numerical model suggests that speed is maximized when the mechanism is prevented from jumping high off the surface. In this way the mechanism resembles a galloping or jumping animal whose body remains nearly at the same height above the ground during its gait.
Predicting with Distributions

We consider a new learning model in which a joint distribution over vector pairs $(x,y)$ is determined by an unknown function $c(x)$ that maps input vectors $x$ not to individual outputs, but to entire {\em distributions\/} over output vectors $y$. Our main results take the form of rather general reductions from our model to algorithms for PAC learning the function class and the distribution class separately, and show that virtually every such combination yields an efficient algorithm in our model. Our methods include a randomized reduction to classification noise and an application of Le Cam's method to obtain robust learning algorithms.
Generalized Bilinear Deep Convolutional Neural Networks for Multimodal Biometric Identification

In this paper, we propose to employ a bank of modality-dedicated Convolutional Neural Networks (CNNs), fuse, train, and optimize them together for person classification tasks. A modality-dedicated CNN is used for each modality to extract modality-specific features. We demonstrate that, rather than spatial fusion at the convolutional layers, the fusion can be performed on the outputs of the fully-connected layers of the modality-specific CNNs without any loss of performance and with significant reduction in the number of parameters. We show that, using multiple CNNs with multimodal fusion at the feature-level, we significantly outperform systems that use unimodal representation. We study weighted feature, bilinear, and compact bilinear feature-level fusion algorithms for multimodal biometric person identification. Finally, We propose generalized compact bilinear fusion algorithm to deploy both the weighted feature fusion and compact bilinear schemes. We provide the results for the proposed algorithms on three challenging databases: CMU Multi-PIE, BioCop, and BIOMDATA.