cssi/SciSciGPT-SciSciNet huggingface dataset:
BRISC-V: An Open-Source Architecture Design Space Exploration Toolbox

In this work, we introduce the BRISC-V Toolbox, a register-transfer level (RTL) tool for architecture design space exploration. The BRISC-V Toolbox is an open-source, parameterized, synthesizable set of RTL modules for designing RISC-V based single and multi-core architecture systems. The toolbox is designed with a high degree of modularity. It provides highly parameterized, composable RTL modules for fast and accurate exploration of different RISC-V based core complexities, multi-level caching and memory organizations, system topologies, router architectures and routing schemes. BRISC-V can be used for both RTL simulation and FPGA based emulation. The hardware modules are implemented in synthesizable Verilog using no vendor-specific blocks. The toolbox includes a GCC RISC-V compiler tool-chain to assist in developing software for the cores and a web based system configuration graphical user interface (GUI). The BRISC-V Toolbox supports a myriad of RISC-V architectures, ranging from a simple single cycle processor to a multi-core SoC with a complex memory hierarchy and a network-on-chip. The modules are designed to support incremental additions and modifications. The module interfaces are carefully designed to enable an arbitrary pipeline depth and changes to a single module without impacting the rest of the system. The BRISC-V platform allows researchers to quickly instantiate complete working RISC-V multicore systems with synthesizable RTL correctness and make targeted modifications to fit their needs.
State-Space Space-Vector Model of the Induction Motor Including Magnetic Saturation and Iron Losses

This paper proposes a space-vector dynamic model of the rotating induction motor (RIM) taking into consideration both the magnetic saturation and the iron losses expressed in a state form. Such a model tries to improve some issues of the previously developed dynamic models. The main original aspects of the proposed model are the following: the magnetic saturation of the iron core has been described on the basis of both current versus flux and flux versus current functions; the model is based on the complete T space-vector electrical scheme of the RIM; two different state formulations have been proposed; it includes the iron losses, separating them in hysteresis and eddy current ones; and it includes the effect of the load on the magnetic saturation. The proposed model has been implemented in numerical simulation in MATLAB/Simulink environment and validated experimentally on a suitably developed test set-up based on a low-power RIM. The proposed model has been exploited also to simulate the behavior of a high-power RIM.
EU–Fatty Alcohols (Indonesia): Corporate Structure, Transfer Pricing, and Dumping

The EU–Fatty Alcohols decision of the Appellate Body addressed an important issue of the scope of permissible adjustments under Article 2.4 of the Agreement on Interpretation of Article VI of the GATT 1994, focusing on the ‘mark-up’ paid by an Indonesian exporter to a related company as a difference affecting price comparability between the export price and the normal value. The Appellate Body confirmed that the primary focus of the investigating authority's assessment is on whether the relationship between related companies can be demonstrated to be a factor that impacts the prices of the relevant transactions. This case raises the question of whether a harmonized approach to transfer pricing across different regulatory areas would be useful to bring greater consistency of treatment and certainty to international transactions.
Student–teacher relationships of children with autism spectrum disorder: Distinct contributions of language domains

Abstract Background and aims High quality student–teacher relationships (STR) are important for children's academic and social development. We explore how individual child language domains (semantics, syntax, pragmatics), teacher years of experience, and classroom placement (general or special education) relate to STR quality for children with autism spectrum disorder (ASD) across the school year. Methods and procedures 191 children with ASD (Mage = 5.6 years) completed a standardized language assessment and their teachers reported on STR quality twice during the school year. Outcome and results Pragmatics, but not semantics or syntax, had a direct effect on student–teacher closeness. The association between semantics and closeness was moderated by classroom type; for students with low semantics, teacher-reported closeness was lower in general versus special education. Teachers in special versus general education classrooms reported closer relationships. More experienced teachers reported closer and less conflictual relationships. None of the three language domains were associated with student–teacher conflict. Conclusions and implications Pragmatic and semantic language skills were associated with closer relationships. Language-focused therapies may be effective in carrying over to impact STR quality. Given the stability in relationship quality, targeted interventions should be delivered to teachers at the beginning of the school year to support positive relationship development.
Shelf Space Selection to Control Product Expiration

Product expiration is an important problem in the consumer-packaged-goods industry eroding profits and generating substantial waste. We propose that shelf space selection can be an operational lever to control expiration of perishable inventory. To this end, we first explain the conditions under which shelf space impacts expiration then develop a method to determine the appropriate level of shelf space which incorporates this impact. We formulate a shelf space selection problem for a single product using an infinite horizon Markov chain model. For the special case where demand is constant across periods, we find closed-form expressions for the average net profit, order levels, and expiration levels as a function of the product’s shelf space under different shelf rotation assumptions. We show that when inventory is not rotated, expiration increases quickly when shelf space exceeds the demand per period. In contrast, when inventory is rotated, the increase occurs when shelf space is larger than the product demand throughout its shelf life. Since computing the optimum shelf space is computationally-challenging for large shelf life values, we approximate the net profit function leveraging the constant demand analysis. Our approximation method is easy to implement and performs well with a median optimality gap of 0.41% across 160 scenarios. We compare our method with two alternative heuristics and find that it performs well. As a byproduct of this approximation, we develop several managerial insights for the shelf space decision at the tactical level. In addition, we extend our analysis to consider shelf space dependent demand.
Blockchain, adoption, and financial inclusion in India: Research opportunities

Abstract The economic development of rural India requires connecting remote villages to local and global supply chains. Yet, high rates of financial exclusion inhibit rural Indians from participating in these supply networks. We review the literature on financial inclusion, adoption, and blockchain in India, and posit that to resolve financial exclusion, the four challenges of geographical access, high cost, inappropriate banking products, and financial illiteracy need to be overcome. Next, we argue that blockchain technologies hold the potential to overcome most of these challenges. However, for blockchain technologies to become the cornerstone of financial inclusion initiatives, an understanding of technology adoption in India is needed. To guide the development of such understanding, we develop a research agenda on the antecedents of adoption, adoption patterns, and outcomes of adoption. Answering these research questions will lead to a nuanced understanding of adoption of blockchain-based technologies in rural India. The practical contribution of this paper is the discussion of how blockchain can alleviate the issue of financial exclusion in rural India, thereby providing a basis for a solution that could connect rural Indians to global supply chain networks. The theoretical contribution lies in the identification of knowledge gaps that should be answered to achieve financial inclusion of rural Indians.
The Two Margin Problem in Insurance Markets

Insurance markets often feature consumer sorting along both an extensive margin (whether to buy) and an intensive margin (which plan to buy). We present a new graphical theoretical framework that extends the workhorse model to incorporate both selection margins simultaneously. A key insight from our framework is that policies aimed at addressing one margin of selection often involve an economically meaningful trade-off on the other margin in terms of prices, enrollment, and welfare. For example, while a larger penalty for opting to remain uninsured reduces the uninsurance rate, it also tends to lead to unraveling of generous coverage because the newly insured are healthier and sort into less generous plans, driving down the relative prices of those plans. While risk adjustment transfers shift enrollment from lower- to higher-generosity plans, they also sometimes increase the uninsurance rate by raising the prices of less generous plans, which are the entry points into the market. We illustrate these trade-offs in an empirical sufficient statistics approach that is tightly linked to the graphical framework. Using data from Massachusetts, we show that in many policy environments these trade-offs can be empirically meaningful and can cause these policies to have unexpected consequences for overall social welfare.
Conjugate reduction of α,β-unsaturated ketones using an MnIII catalyst, phenylsilane and isopropyl alcohol

Abstract Treatment of a variety of α,β-unsaturated ketones with Mn(dpm) 3 (3 mol%)/PhSiH 3 (1.3 equiv.)/isopropyl alcohol with the exclusion of air resulted in the formation of the saturated ketone.
N-Acyl imine and enamide intermediates in the palladium-catalyzed amidocarbonylation reaction

Abstract N -Acyl imines and enamides have been synthesized and subjected to the reaction conditions for palladium-catalyzed amidocarbonylation of aldehydes. These compounds were competent substrates resulting in the formation of N -acyl amino acids; however, the presence of water was found to be necessary. Direct study of the same amidocarbonylation reaction revealed that enamides could be detected during the course of the reaction. A slight enhancement in the yield of the amidocarbonylation is observed in the presence of radical inhibitors ruling out a meaningful radical pathway. The results are most consistent with a mechanism involving complex equilibration of the starting materials to a number of intermediates which can converge to a haloamidal that subsequently undergoes a palladium insertion.
New lipophilic crown ethers with intraannular carboxylic acid groups: Synthesis and alkali metal cation extraction

A six-step synthetic route to four lipophilic crown ethers with intraannular carboxylic acid groups and ring sizes of 15-crown-4, 18-crown-5, 21-crown-6 and 24-crown-7 is described. Eight new polyether compounds that bear inward-facing bromo and formate ester substituents are prepared as synthetic intermediates. Selectivities and efficiencies of the four new lipophilic crown ether carboxylic acids in competitive alkali metal cation extraction from aqueous solutions into chloroform are evaluated.
Cleanliness in context: reconciling hygiene with a modern microbial perspective

The concept of hygiene is rooted in the relationship between cleanliness and the maintenance of good health. Since the widespread acceptance of the germ theory of disease, hygiene has become increasingly conflated with sterilization. In reviewing studies across the hygiene literature (most often hand hygiene), we found that nearly all studies of hand hygiene utilize bulk reduction in bacterial load as a proxy for reduced transmission of pathogenic organisms. This treatment of hygiene may be insufficient in light of recent microbial ecology research, which has demonstrated that humans have intimate and evolutionarily significant relationships with a diverse assemblage of microorganisms (our microbiota). The human skin is home to a diverse and specific community of microorganisms, which include members that exist across the ecological spectrum from pathogen through commensal to mutualist. Most evidence suggests that the skin microbiota is likely of direct benefit to the host and only rarely exhibits pathogenicity. This complex ecological context suggests that the conception of hygiene as a unilateral reduction or removal of microbes has outlived its usefulness. As such, we suggest the explicit definition of hygiene as “those actions and practices that reduce the spread or transmission of pathogenic microorganisms, and thus reduce the incidence of disease.”
New α-pyrone-containing metabolites from a marine-derived actinomycete

Abstract Four new α-pyrone-containing metabolites, wailupemycins A-C (1–3) and 3-epi-5-deoxyenterocin (4), were isolated together with known compounds enterocin (6) and 5-deoxyenterocin (5) from a Streptomyces sp. cultured from shallow water marine sediments. The structures of the new compounds were determined through the interpretation of spectral data. Compound 1 exhibited antimicrobial activity towards the Gram-negative bacterium Escherichia coli, while compound 4 inhibited the growth of Staphylococcus aureus.
Genomic evidence of genetic variation with pleiotropic effects on caterpillar fitness and plant traits in a model legume.

Plant-insect interactions are ubiquitous, and have been studied intensely because of their relevance to damage and pollination in agricultural plants, and to the ecology and evolution of biodiversity. Variation within species can affect the outcome of these interactions. Specific genes and chemicals that mediate these interactions have been identified, but genome- or metabolome-scale studies might be necessary to better understand the ecological and evolutionary consequences of intraspecific variation for plant-insect interactions. Here, we present such a study. Specifically, we assess the consequences of genome-wide genetic variation in the model plant Medicago truncatula for Lycaeides melissa caterpillar growth and survival (larval performance). Using a rearing experiment and a whole-genome SNP data set (>5 million SNPs), we found that polygenic variation in M. truncatula explains 9%-41% of the observed variation in caterpillar growth and survival. Genetic correlations among caterpillar performance and other plant traits, including structural defences and some anonymous chemical features, suggest that multiple M. truncatula alleles have pleiotropic effects on plant traits and caterpillar performance (or that substantial linkage disequilibrium exists among distinct loci affecting subsets of these traits). A moderate proportion of the genetic effect of M. truncatula alleles on L. melissa performance can be explained by the effect of these alleles on the plant traits we measured, especially leaf toughness. Taken together, our results show that intraspecific genetic variation in M. truncatula has a substantial effect on the successful development of L. melissa caterpillars (i.e., on a plant-insect interaction), and further point toward traits potentially mediating this genetic effect.
GLAST: physics goals and instrument status

The Gamma-ray Large Area Space Telescope (GLAST) is a space-based observatory scheduled to launch in October 2007 with two instruments: (1) the GLAST Burst Monitor (GBM), sensitive to photon energies between 8 keV and 25 MeV and optimized to detect gamma-ray bursts, and (2) the Large Area Telescope (LAT), sensitive to gamma rays between 20 MeV and 300 GeV and designed to survey the gamma-ray sky with unprecedented sensitivity. We describe the LAT and the GBM. We then focus on the LAT's capabilities for studying active galactic nuclei.
Profiling of Bacterial and Fungal Microbial Communities in Cystic Fibrosis Sputum Using RNA

Here, we report an approach to detect diverse bacterial and fungal taxa in complex samples by direct analysis of community RNA in one step using NanoString probe sets. We designed rRNA-targeting probe sets to detect 42 bacterial and fungal genera or species common in cystic fibrosis (CF) sputum and demonstrated the taxon specificity of these probes, as well as a linear response over more than 3 logs of input RNA. Culture-based analyses correlated qualitatively with relative abundance data on bacterial and fungal taxa obtained by NanoString, and the analysis of serial samples demonstrated the use of this method to simultaneously detect bacteria and fungi and to detect microbes at low abundance without an amplification step. Compared at the genus level, the relative abundances of bacterial taxa detected by analysis of RNA correlated with the relative abundances of the same taxa as measured by sequencing of the V4V5 region of the 16S rRNA gene amplified from community DNA from the same sample. We propose that this method may complement other methods designed to understand dynamic microbial communities, may provide information on bacteria and fungi in the same sample with a single assay, and with further development, may provide quick and easily interpreted diagnostic information on diverse bacteria and fungi at the genus or species level.IMPORTANCE Here we demonstrate the use of an RNA-based analysis of specific taxa of interest, including bacteria and fungi, within microbial communities. This multiplex method may be useful as a means to identify samples with specific combinations of taxa and to gain information on how specific populations vary over time and space or in response to perturbation. A rapid means to measure bacterial and fungal populations may aid in the study of host response to changes in microbial communities.
Interplay between small RNA pathways shapes chromatin landscapes in C. elegans.

The nematode Caenorhabditis elegans contains several types of endogenous small interfering RNAs (endo-siRNAs) produced by RNA-dependent RNA polymerase (RdRP) complexes. Both ‘silencing’ siRNAs bound by Worm-specific Argonautes (WAGO) and ‘activating’ siRNAs bound by the CSR-1 Argonaute require the DRH-3 helicase, an RdRP component. Here, we show that, in the drh-3(ne4253) mutant deficient in RdRP-produced secondary endo-siRNAs, the silencing histone mark H3K9me3 is largely depleted, whereas in the csr-1 partially rescued null mutant strain (WM193), this mark is ectopically deposited on CSR-1 target genes. Moreover, we observe ectopic H3K9me3 at enhancer elements and an increased number of small RNAs that match enhancers in both drh-3 and csr-1 mutants. Finally, we detect accumulation of H3K27me3 at highly expressed genes in the drh-3(ne4253) mutant, which correlates with their reduced transcription. Our study shows that when abundant RdRP-produced siRNAs are depleted, there is ectopic elevation of noncoding RNAs linked to sites with increased silencing chromatin marks. Moreover, our results suggest that enhancer small RNAs may guide local H3K9 methylation.
Synthesis directed towards putative advanced intermediates in sarubicin A biosynthesis

Abstract 3,6-Dihydroxyanthranilamide, 5, and its 5-propyl derivative, 15, were synthesized. The former was found to be very unstable, but the later was stable and could be reversibly oxidized to the analogous quinone. 3,6-Dimethoxyanthranilamide was protected as an acetone acetaminal and formylated at C-5 to give 18. A hetero-Diels-Alder reaction with Danishefsky's diene and 18 was effected with the aid of sonication and ZnCl2, yielding a model, 20, for a putative C-glycoside intermediate in the biosynthesis of sarubicin A, 1. However, when 18 and the triethylsiloxydiene derived from 3-penten-2-one were treated under the same conditions no reaction occurred, while p-dimethylaminobenzaldehyde only gave an aldol product 23.
Benzylic C–H activation and C–O bond formation via aryl to benzylic 1,4-palladium migrations

Abstract A procedure for benzylic C–H activation has been developed using a palladium 1,4-aryl to benzylic migration as a key step. Carboxylates and phenoxides readily trap the resulting benzylic palladium intermediates obtained from palladium ‘through space’ migration. Aryl bromides and iodides have been successfully employed in this reaction, furnishing moderate to good yields. The mechanism of this reaction has been studied by deuterium-labeling experiments, which suggest that the migration of palladium from an aryl to a benzylic position occurs reversibly. The reaction conditions developed for the migration process also oxidize the neighboring benzylic alcohols to the corresponding aldehydes and ketones.
Studies of fragment assembly aldol reactions of chiral aldehydes and chiral methyl ketones: stereoselective synthesis of the C(13)–C(25) segment of scytophycin C

Abstract A highly stereoselective synthesis of the C(13)–C(25) fragment of scytophycin C is described, along with stereochemical studies of the key fragment assembly methyl ketone aldol reaction.
Validation of Twitter opinion trends with national polling aggregates: Hillary Clinton vs Donald Trump

Measuring and forecasting opinion trends from real-time social media is a long-standing goal of big-data analytics. Despite the large amount of work addressing this question, there has been no clear validation of online social media opinion trend with traditional surveys. Here we develop a method to infer the opinion of Twitter users by using a combination of statistical physics of complex networks and machine learning based on hashtags co-occurrence to build an in-domain training set of the order of a million tweets. We validate our method in the context of 2016 US Presidential Election by comparing the Twitter opinion trend with the New York Times National Polling Average, representing an aggregate of hundreds of independent traditional polls. The Twitter opinion trend follows the aggregated NYT polls with remarkable accuracy. We investigate the dynamics of the social network formed by the interactions among millions of Twitter supporters and infer the support of each user to the presidential candidates. Our analytics unleash the power of Twitter to uncover social trends from elections, brands to political movements, and at a fraction of the cost of traditional surveys.
Preclinical modeling of exposure to a global marine bio-contaminant: Effects of in utero Domoic acid exposure on neonatal behavior and infant memory.

Abstract Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis prior to breeding and throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate development during early infancy, offspring were administered a Neonatal Assessment modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems using the novelty paradigm. Results indicated that prenatal DA exposure did not impact early survival reflexes or responsivity to the environment. Findings from the recognition memory assessment, given between 1 and 2 months of age, showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. Performance was not diminished by the introduction of delay periods. However, when more difficult recognition problems were introduced, the looking behavior of the 0.15 mg/kg DA group was random and infants failed to show differential visual attention to novel test stimuli. This finding suggests subtle but significant impairment in recognition memory and demonstrates that chronic fetal exposure to DA may impact developing cognitive processes.
The microprotein Minion controls cell fusion and muscle formation

Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, their function remains to be determined. Skeletal muscle development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process. Here we report the identification of Minion (microprotein inducer of fusion), a smORF encoding an essential skeletal muscle specific microprotein. Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally and demonstrate a marked reduction in fused muscle fibres. The fusogenic activity of Minion is conserved in the human orthologue, and co-expression of Minion and the transmembrane protein Myomaker is sufficient to induce cellular fusion accompanied by rapid cytoskeletal rearrangement, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component programme for the induction of mammalian cell fusion. Moreover, these data also significantly expand the known functions of smORF-encoded microproteins.
An efficient method for the cleavage of p-methoxybenzylidene (PMP), tetrahydropyranyl (THP) and 1,3-dithiane protecting groups by Selectfluor™

Abstract A new and efficient method for the cleavage of the PMP, THP and 1,3-dithiane protecting groups with Selectfluor™ has been developed.
Reaction of benzohydroximinoyl chlorides and β‐(trifluoromethyl)‐acetylenic esters: Synthesis of regioisomeric (trifluoromethyl)‐isoxazolecarboxylate esters and oxime addition products

The triethylamine induced reaction of benzohydroximinoyl chlorides, precursors of nitrile oxides, with β-trifluoromethylacetylenic esters gives rise to three products: 5-trifluoromethyl-4-isoxozolecarboxylate esters, regioisomeric 4-trifluoromethyl-5-isoxazolecarboxylate esters and an unexpected oxime 1,4-addition adduct. Product distribution is rationalized in terms of two competing reaction modes, either 1,4 addition of the oxime anion to the acetylenic ester or formation of the nitrile oxide followed by 1,3-dipolar cycloaddi-tion. Anionic 1,4-addition of the oximinoyl chloride to the acetylenic ester is preferred at low temperatures, while nitrile oxide formation followed by cycloaddition is preferred at temperatures above 0 °C. Regioisomeric products from addition of nitrile oxides to various perfluoroalkylacetylenes are compared and assigned by 13C NMR.
Wolbachia effects on Rift Valley fever virus infection in Culex tarsalis mosquitoes

Innovative tools are needed to alleviate the burden of mosquito-borne diseases, and strategies that target the pathogen are being considered. A possible tactic is the use of Wolbachia, a maternally inherited, endosymbiotic bacterium that can (but does not always) suppress diverse pathogens when introduced to naive mosquito species. We investigated effects of somatic Wolbachia (strain wAlbB) infection on Rift Valley fever virus (RVFV) in Culex tarsalis mosquitoes. When compared to Wolbachia-uninfected mosquitoes, there was no significant effect of Wolbachia infection on RVFV infection, dissemination, or transmission frequencies, nor on viral body or saliva titers. Within Wolbachia-infected mosquitoes, there was a modest negative correlation between RVFV body titers and Wolbachia density, suggesting that Wolbachia may slightly suppress RVFV in a density-dependent manner in this mosquito species. These results are contrary to previous work in the same mosquito species, showing Wolbachia-induced enhancement of West Nile virus infection rates. Taken together, these results highlight the importance of exploring the breadth of pathogen modulations induced by Wolbachia.
Support for the Dominance Theory in Drosophila Transcriptomes

Interactions among divergent elements of transcriptional networks from different species can lead to misexpression in hybrids through regulatory incompatibilities, some with the potential to generate sterility. While the possible contribution of faster-male evolution to this misexpression has been explored, the role of the hemizygous X chromosome (i.e., the dominance theory for transcriptomes) remains yet to be determined. Here, we study genome-wide patterns of gene expression in females and males of Drosophila yakuba, Drosophila santomea and their hybrids. We used attached-X stocks to specifically test the dominance theory, and we uncovered a significant contribution of recessive alleles on the X chromosome to hybrid misexpression. Our analyses also suggest a contribution of weakly deleterious regulatory mutations to gene expression divergence in genes with sex-biased expression, but only in the sex toward which the expression is biased (e.g., genes with female-biased expression when analyzed in females). In the opposite sex, we found stronger selective constraints on gene expression divergence. Although genes with a high degree of male-biased expression show a clear signal of faster-X evolution of gene expression, we also detected slower-X evolution in other gene classes (e.g., female-biased genes). This slower-X effect is mediated by significant decreases in cis- and trans-regulatory divergence. The distinct behavior of X-linked genes with a high degree of male-biased expression is consistent with these genes experiencing a higher incidence of positively selected regulatory mutations than their autosomal counterparts.
Synthesis of 2,2′-bipyrrole-5-carboxaldehydes and their application in the synthesis of B-ring functionalized prodiginines and tambjamines

Abstract Facile, versatile, and cost-effective synthetic routes for the preparation of a range of new 3-alkyl-, 4-alkyl-, 3,4-dialkyl-, and 3-halo-4-alkyl-2,2′-bipyrrole-5-carboxaldehydes have been developed. These 2,2′-bipyrrole-5-carboxaldehydes offer interesting potential as building blocks for making bioactive natural and unnatural products, as demonstrated by the synthesis of B-ring functionalized prodiginines (PGs) and tambjamines.
Synthesis and anticonvulsant activity of 3H-imidazo[4,5-c]-pyridazine, 1H-imidazo[4,5-d]pyridazine and 1H-benzimidazole analogues of 9-(2-fluorobenzyl)-6-methylamino-9H-purine

The 3H-imidazo[4,5-c]pyridazine, 1H-imidazo[4,5-d]pyridazine, and 1H-benzimidazole analogues of the potent anticonvulsant purine 9-(2-fluorobenzyl)-6-methylamino-9H-purine (1, 78U79) were synthesized and tested for anticonvulsant activity. The 3H-imidazo[4,5-c]pyridazines 8 and 9 were prepared in five stages from 3,4,5-trichloropyridazine (2). The 1H-imidazolo[4,5-d]pyridazine 15 was synthesized in four stages from 5-[(benzyloxy)methyl]-1,5-dihydro-4H-imidazo[4,5-d] pyridazin-4-one (10a). The benz-imidazole analogues 18 and 20 were prepared from 2,6-dinitroaniline in three stages. These compounds were one-tenth or less as active as 1 in protecting rats against maximal electroshock-induced seizures.
Copper-Catalyzed C−P Bond Construction via Direct Coupling of Secondary Phosphines and Phosphites with Aryl and Vinyl Halides

A general method for the coupling of aryl and vinyl halides with diaryl and dialkyl phosphines, as well as with dibutyl phosphite, is reported. This highly efficient transformation is realized through the use of copper(I) iodide as a catalyst, N,N‘-dimethylethylenediamine as a ligand, and Cs2CO3 as a base. A variety of sterically hindered and/or functionalized substrates were found to react under these reaction conditions to provide products in good to excellent yields.
Synthesis and Characterization of Two Quaternary Uranium Tellurides, RbTiU3Te9 and CsTiU3Te9

Black crystals of RbTiU₃Te₉ and CsTiU₃Te₉ have been synthesized at 1223 and 1173 K, respectively, by high-temperature solid-state routes. These compounds crystallize in a new structure type in space group C(2h)²-P2₁/m of the monoclinic system. The structure, which is similar to that of CsTiUTe₅, consists of UTe₂ layers connected into a three-dimensional framework by TiTe₆ octahedra. The expanded UTe₂ layers leave channels that are filled by Rb or Cs atoms. Single-crystal resistivity measurements on CsTiU₃Te₉ are consistent with semiconducting behavior; the calculated activation energy is 0.30(1) eV. X-ray photoelectron spectroscopic measurements on CsTiU₃Te₉ indicate that the compound contains U⁴⁺. From single-crystal magnetic measurements, CsTiU₃Te₉ is consistent with antiferromagnetic coupling between magnetic U atoms. The very low value of the effective magnetic moment of 0.56(2) μ(B) is believed to arise from a coexistence of magnetic and nonmagnetic U atoms.
A two-step, one-pot procedure using acid chlorides and propargyl amines to form tri-substituted oxazoles via gold-catalyzed cyclization

2,4-Disubstituted-5-methyl oxazoles were prepared from a 2-step, 1-pot procedure using acid chlorides and propargyl amines. These conditions lead to the formation of propargyl amides in situ followed by AuCl3 catalyzed cyclization. We were interested in this novel formation of tri-substituted oxazoles and exploring the scope of the reaction using these mild conditions. A variety of aryl and aliphatic amides containing sensitive functional groups were tolerated giving good yields.
Regioselective Synthesis of Indoles via Reductive Annulation of Nitrosoaromatics with Alkynes

[reaction: see text] Indoles are produced regioselectively and in moderate yields by two new processes: (a) from the [CpRu(CO)2]2-catalyzed reaction of nitrosoaromatics (ArNO) with alkynes under carbon monoxide and (b) in a two-step sequence involving the (uncatalyzed) reaction of ArNO with alkynes, followed by reduction of the intermediate adduct.
Intercellular Communication via the comX-Inducing Peptide (XIP) of Streptococcus mutans.

Gram-positive bacteria utilize exported peptides to coordinate genetic and physiological processes required for biofilm formation, stress responses, and ecological competitiveness. One example is activation of natural genetic competence by ComR and the com X - i nducing p eptide (XIP) in Streptococcus mutans Although the competence pathway can be activated by the addition of synthetic XIP in defined medium, the hypothesis that XIP is able to function as an intercellular signaling molecule has not been rigorously tested. Coculture model systems were developed that included a "sender" strain that overexpressed the XIP precursor (ComS) and a "responder" strain harboring a green fluorescent protein (GFP) reporter fused to a ComR-activated gene (comX) promoter. The ability of the sender strain to provide a signal to activate GFP expression was monitored at the individual cell and population levels using (i) planktonic culture systems, (ii) cells suspended in an agarose matrix, or (iii) cells growing in biofilms. XIP was shown to be freely diffusible, and XIP signaling between the S. mutans sender and responder strains did not require cell-to-cell contact. The presence of a sucrose-derived exopolysaccharide matrix diminished the efficiency of XIP signaling in biofilms, possibly by affecting the spatial distribution of XIP senders and potential responders. Intercellular signaling was greatly impaired in a strain lacking the primary autolysin, AtlA, and was substantially greater when the sender strain underwent lysis. Collectively, these data provide evidence that S. mutans XIP can indeed function as a peptide signal between cells and highlight the importance of studying signaling with an endogenously produced peptide(s) in populations in various environments and physiologic states.IMPORTANCE The comX-inducing peptide (XIP) of Streptococcus mutans is a key regulatory element in the activation of genetic competence, which allows cells to take up extracellular DNA. XIP has been found in cell culture fluids, and the addition of synthetic XIP to physiologically receptive cells can robustly induce competence gene expression. However, there is a lack of consensus as to whether XIP can function as an intercellular communication signal. Here, we show that XIP indeed signals between cells in S. mutans, but that cell lysis may be a critical factor, as opposed to a dedicated secretion/processing system, in allowing for release of XIP into the environment. The results have important implications in the context of the ecology, virulence, and evolution of a ubiquitous human pathogen and related organisms.
Studies directed toward the synthesis of viridenomycin. Route 1: assembly of three advanced intermediates

Abstract Three enantiomerically and geometrically pure building blocks representing fragments of the antifungal antibiotic viridenomycin have been prepared.
Evolutionary rate covariation analysis of E-cadherin identifies Raskol as a regulator of cell adhesion and actin dynamics in Drosophila.

The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization. The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link actin to intercellular adhesions. Over time, evolutionary pressures have shaped the signaling and mechanical functions of the adherens junction to meet specific developmental and physiological demands. Evolutionary rate covariation (ERC) identifies proteins with correlated fluctuations in evolutionary rate that can reflect shared selective pressures and functions. Here we use ERC to identify proteins with evolutionary histories similar to the Drosophila E-cadherin (DE-cad) ortholog. Core adherens junction components α-catenin and p120-catenin displayed positive ERC correlations with DE-cad, indicating that they evolved under similar selective pressures during evolution between Drosophila species. Further analysis of the DE-cad ERC profile revealed a collection of proteins not previously associated with DE-cad function or cadherin-mediated adhesion. We then analyzed the function of a subset of ERC-identified candidates by RNAi during border cell (BC) migration and identified novel genes that function to regulate DE-cad. Among these, we found that the gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates BC migration and adhesion. We named CG42684 raskol (“to split” in Russian) and show that it regulates DE-cad levels and actin protrusions in BCs. We propose that Raskol functions with DE-cad to restrict Ras/Rho signaling and help guide BC migration. Our results demonstrate that a coordinated selective pressure has shaped the adherens junction and this can be leveraged to identify novel components of the complexes and signaling pathways that regulate cadherin-mediated adhesion.
Genetic Architecture and Molecular Networks Underlying Leaf Thickness in Desert-Adapted Tomato Solanum pennellii

Thicker leaves allow plants to grow in water-limited conditions. However, our understanding of the genetic underpinnings of this highly functional leaf shape trait is poor. We used a custom-built confocal profilometer to directly measure leaf thickness in a set of introgression lines (ILs) derived from the desert tomato Solanum pennellii and identified quantitative trait loci. We report evidence of a complex genetic architecture of this trait and roles for both genetic and environmental factors. Several ILs with thick leaves have dramatically elongated palisade mesophyll cells and, in some cases, increased leaf ploidy. We characterized the thick IL2-5 and IL4-3 in detail and found increased mesophyll cell size and leaf ploidy levels, suggesting that endoreduplication underpins leaf thickness in tomato. Next, we queried the transcriptomes and inferred dynamic Bayesian networks of gene expression across early leaf ontogeny in these lines to compare the molecular networks that pattern leaf thickness. We show that thick ILs share S. pennellii-like expression profiles for putative regulators of cell shape and meristem determinacy as well as a general signature of cell cycle-related gene expression. However, our network data suggest that leaf thickness in these two lines is patterned at least partially by distinct mechanisms. Consistent with this hypothesis, double homozygote lines combining introgression segments from these two ILs show additive phenotypes, including thick leaves, higher ploidy levels, and larger palisade mesophyll cells. Collectively, these data establish a framework of genetic, anatomical, and molecular mechanisms that pattern leaf thickness in desert-adapted tomato.
Discrete and continuous coupled nonlinear integrable systems via the dressing method

A discrete analogue of the dressing method is presented and used to derive integrable nonlinear evolution equations, including two infinite families of novel continuous and discrete coupled integrable systems of equations of nonlinear Schrodinger type. First, a demonstration is given of how discrete nonlinear integrable equations can be derived starting from their linear counterparts. Then, starting from two uncoupled, discrete one-directional linear wave equations, an appropriate matrix Riemann-Hilbert problem is constructed, and a discrete matrix nonlinear Schrodinger system of equations is derived, together with its Lax pair. The corresponding compatible vector reductions admitted by these systems are also discussed, as well as their continuum limits. Finally, by increasing the size of the problem, three-component discrete and continuous integrable discrete systems are derived, as well as their generalizations to systems with an arbitrary number of components.
The synthesis of 3-pyrazinyl-imidazo[1,2-a]pyridines from a vinyl ether

Abstract A new method has been developed for the synthesis of 3-pyrazinyl-imidazo[1,2-a]pyridines. 2-Chloro-6-[(Z)-2-ethoxyethenyl]pyrazine was treated with N-bromosuccinimide in dioxane–water to generate the 2-bromo-2-(6-chloropyrazin-2-yl)-1-ethoxyethanol intermediate. In a subsequent one-pot step, optional treatment with various 2-aminopyridines provided the cyclized 3-pyrazinyl-imidazo[1,2-a]pyridines in 31–76% yields.
Synthesis of trans‐7‐hydroxymethyl‐2‐(2‐benz[d]isoxazol‐3‐yl)octahydro‐2H‐pyrido[1,2‐a]pyrazine

An efficient synthesis of trans-7-hydroxymethyl-2-(2-benz[d]isoxazol-3-yl)octahydro-2H-pyrido[1,2-a]-pyrazine 2 is presented which relies on the equilibration of cis-dimethyl piperidinedicarboxylate followed by alkylation with phthalimidoethyl triflate.
Novel Zinc (II)-Mediated Epimerization of 2‘-Carbonylalkyl-α-C-glycopyranosides to Their β-Anomers

2‘-Aldehydes and 2‘-ketones of α-C-glycosides, including the gluco-, galacto-, and manno- series, were epimerized exclusively to their β-anomers in good-to-excellent yields under basic conditions and in the presence of zinc acetate. The β-stereoselectivity is independent of the neighboring group at 2-O-substitution of sugar substrates. Therefore, this provides a particularly useful method for the preparation of manno-β-C-glycosides. The epimerization is likely initiated by the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chair-boat structure. Due to the activation generated by the Zn−O coordination, fission of the C1−O bond occurs, leading to opening of the pyranose ring, which is spontaneously followed by a change in conformation. The more stable anti chair-boat transition state is favored, and the subsequent hetero-intramolecular Michael addition results in the formation of β-C-glycoside in a ring-closure step.
Efficient Synthesis of Peptides by Extension at the N-and C-Terminii of Arginine

l-Nω-Nitroarginine and l-arginine were coupled with N-(Cbz-α-aminoacyl)benzotriazoles and N-Cbz-dipeptidoylbenzotriazoles to provide arginine ll-dipeptides 9a−e, 11a−d; lll-tripeptides 18a−c, 20; and diastereomeric mixtures (9b+9b′), (9c+9c′), (11b+11b′) and (18c+18c′) [compound numbers written within parentheses represent a diastereomeric mixture or racemate; compound numbers without parentheses represent an achiral compound or a single enantiomer] by extension at the N-terminus of arginine, in isolated yields of 66−95% with complete retention of chirality as evidenced by NMR and HPLC analysis. Arginine ll-dipeptides 15a−d were synthesized by extension at the C-terminus of arginine in isolated yield of 66−80%, using benzotriazole activated arginine l-ωNO2-Arg-Bt, 13. Our methodology has also been used to synthesize the protected RGD peptide (Cbzα-l-ωNO2-Arg-Gly-l-Asp-(OH)2) 21.
Synthesis of the Antitumor Agent Aglycon (±)-Calicheamicinone Using an o-Quinone Monoketal Strategy

Commercially available 5-methoxysalicylic acid 16 was converted into the o-quinone monoketal 21, which was attached to the enediyne 22, resulting in 23. After protection of the tert-alcohol 24 and conversion of the ester 25 to aldehyde 28, treatment with LiN(TMS)2 gave a 1:4 mixture of the 12α- and 12β-ols 29 and 30, respectively. Oxidation of the mixture 29/30 followed by DIBAL-H reduction resulted in exclusive formation of 29. Deprotection of 29 gave 34, which on treatment with Ph2SNH gave the 2-amino adduct 35. Protection of 35 as the tris-Boc derivative 37 followed by intermolecular Wadsworth−Emmons reaction gave the lactone 38. The lactone 38 was converted into the bis-methyl carbamate derivative 52, which was reduced with NaBH4/CeCl3 to give 55. Conversion of the allylic alcohol 55 into the thiol acetate 58 and then to the trisulfide 61 followed previous precedent. Finally, removal of the enol Boc protecting group and the alcohol protecting groups gave (±)-calicheamicinone (2).
Catalytic and selective conversion of (Z)-2-en-4-ynoic acids to either 2H-pyran-2-ones in the presence of ZnBr2 or (Z)-5-alkylidenefuran-2(5H)-ones in the presence of Ag2CO3

Abstract Treatment of (Z)-5-alkyl-2-en-4-ynoic acids ( 1 ), prepared by the Pd-catalyzed alkynylzinc–β-haloacrylic acid coupling, with 5–10 mol% of ZnBr2 can produce 6-alkyl-2H-pyran-2-ones ( 2 ) along with minor amounts of (Z)-5-alkylidenefuran-2(5H)-ones ( 3 ) in >90% combined yields, with often very high (≈95/5) pyranone/furanone ratios. On the other hand, lactonization of 1 catalyzed by Ag2CO3 provides a selective synthesis of (Z)-5-alkylidenefuran-2(5H)-ones ( 3 ) in >90% yields along with minor amounts (≤5%) of 2 .
Rearrangement of 3-amido-1-hydroxyazetidin-2-ones

Abstract Reactions of 3-amido-1-hydroxyazetidin-2-ones with p -toluenesulfonyl chloride in the presence of triethylamine or diisopropylethylamine provided 4-imidazolin-2-ones in moderate yields.
Total synthesis of γ-hydroxy-α,β-unsaturated aldehydic esters of cholesterol and 2-lysophosphatidylcholine

Free radical-induced oxidation of polyunsaturated fatty esters in low-density lipoproteins (LDLs) generates 2-lysophosphatidylcholine (PC) and cholesterol esters of γ-hydroxy-α,β-unsaturated aldehy...
NUCLEOPHILE-ASSISTED CLEAVAGE OF BENZYLTRIALKYLSILANE CATION RADICALS

The cation radicals of benzyltrialkylsilanes have been generated using photoinduced electron transfer and characterized using transient absorption spectroscopy. Absolute rate constants for nucleoph...