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Let |$p$| and |$q$| be anisotropic non-degenerate quadratic forms of dimension |$\geq 2$| over an arbitrary field |$F$|⁠ , let |$s$| be the unique non-negative integer for which |$2^s<{\textrm{dim}(p)} \leq 2^{s+1}$|⁠ , and let |$k$| be the dimension of the anisotropic part of |$q$| after extension to |$F(p)$|⁠. A recent conjecture of the author then asserts that |${\textrm{dim}(q)}$| must lie within |$k$| of an integer multiple of |$2^{s+1}$|⁠. This statement, which holds trivially if |$k \geq 2^s -1$|⁠ , represents a natural generalization of the well-known separation theorem of Hoffmann, bridging a gap between it and certain classical results on the Witt kernels of function fields of quadrics. In the present article, we prove the conjecture in the case where |$\textrm{char}(F) \neq 2$| and |${\textrm{dim}(p)}> 2k - 2^{s-1}$|⁠. This implies, in particular, that the conjecture holds if |$\textrm{char}(F) \neq 2$| and either |$k \leq 2^{s-1} + 2^{s-2}$| or |${\textrm{dim}(p)} \geq 2^s + 2^{s-1} - 4$|⁠. [ABSTRACT FROM AUTHOR]

Let R be a commutative and unital semi-local ring in which 2 is invertible. In this note, we show that anisotropic quadratic spaces over R remain anisotropic after base change to any odd-degree finite étale extension of R. This generalization of the classical Artin-Springer theorem (concerning the situation where R is a field) was previously established in the case where all residue fields of R are infinite by I. Panin and U. Rehmann. The more general result presented here permits one to extend a fundamental isotropy criterion of I. Panin and K. Pimenov for quadratic spaces over regular semi-local domains containing a field of characteristic ≠ 2 to the case where the ring has at least one residue field which is finite. [ABSTRACT FROM AUTHOR]

Using an analogue of Knebusch's generic splitting tower invariant in the theory of non-singular quadratic forms, we study the splitting behaviour of quasilinear (or Fermattype) forms of degree p over fields of characteristic p > 0. Several new applications of our main results to the theory of quasilinear quadratic forms are provided, including an analogue of a theorem of Vishik relating to the existence of outer excellent connections in the motives of smooth projective quadrics over fields of characteristic different from 2, partial results towards a quasilinear version of Karpenko's theorem on the possible values of the first higher Witt indices of non-singular quadratic forms in characteristic not 2, and a proof of a conjecture of Hoffmann concerning quadratic forms with maximal splitting in the quasilinear case. [ABSTRACT FROM AUTHOR]

We introduce Milnor–Witt K -groups of local rings and show that the n th Milnor–Witt K -group of a local ring R which contains an infinite field of characteristic not 2 is the pull-back of the n th power of the fundamental ideal in the Witt ring of R and the n th Milnor K -group of R over the n th Milnor K -group of R modulo 2. This generalizes the work of Morel–Hopkins on Milnor–Witt K -groups of a field. [ABSTRACT FROM AUTHOR]

Several benzoxazocenoneshave been found to exhibit novel cellularactivities. In the present study, we report a gold(I)-catalyzed 8-endo-dig hydroalkoxylation reaction of alkynamides to accessanalogous oxazocenone scaffolds. This methodology provided an advancedintermediate, which was elaborated to a des-benzo analog of a bioactivebenzoxazocenone. [ABSTRACT FROM AUTHOR]

Wepreviously reported the discovery of BRD0476 (1), a smallmolecule generated by diversity-oriented synthesis thatsuppresses cytokine-induced β-cell apoptosis. Herein, we reportthe synthesis and biological evaluation of 1and analogueswith improved aqueous solubility. By replacing naphthyl with quinolinemoieties, we prepared active analogues with up to a 1400-fold increasein solubility from 1. In addition, we demonstrated that 1and analogues inhibit STAT1 signal transduction inducedby IFN-γ. [ABSTRACT FROM AUTHOR]

We prove analogues of several well-known results concerning rational maps between quadrics for the class of so-called quasilinear p-hypersurfaces. These hypersurfaces are nowhere smooth over the base field, so many of the geometric methods which have been successfully applied to the study of projective homogeneous varieties over fields cannot be used. We are therefore forced to take an alternative approach, which is partly facilitated by the appearance of several non-traditional features in the study of these objects from an algebraic perspective. Our main results were previously known for the class of quasilinear quadrics. We provide new proofs here, because the original proofs do not immediately generalise for quasilinear hypersurfaces of higher degree. [ABSTRACT FROM AUTHOR]

Photo-Friedel–Crafts acylation of a naphthoquinone was attempted in an effort to access a diazobenzofluorenone en route to the epoxykinamycin natural product FL-120B′. Photoirradiation of the naphthoquinone substrate which resulted in the unexpected formation of a tetracyclic naphthofuran viaa decarbonylative photocyclization process is described. [ABSTRACT FROM AUTHOR]

Abstract: Aniline along with the substituted anilines, 2-methylaniline, 2-ethylaniline, 2-propylaniline, have been polymerized and intercalated into FeOCl via an in situ polymerization/intercalation process. Powder X-ray diffraction provides evidence for the intercalation of the polymers. FTIR and thermo gravimetric analysis (TGA) also support the inclusion of the polyanilines between the layers of FeOCl. The electrical resistivity of the intercalation compounds was measured as a function of temperature, and is consistent, in most cases, with the variable-range hopping (Mott law) model. [Copyright &y& Elsevier]

Abstract: Poly (ethylene oxide) (PEO), polyvinylpyrrolidone (PVP), methyl cellulose (Mcel), poly [oligo(ethylene glycol)-oxalate] (POEGO), poly[oxymethylene-(oxyethylene)] (POMOE), and poly[bis-(methoxyethoxyethoxy)phosphazene] (MEEP) were intercalated into hectorite. The intercalated hectorites were characterized by powder X-ray diffraction (XRD), thermogravimetric analysis (TGA) and infra-red spectroscopy. The interlayer expansion depended on the amount of polymer added as well as on its dimension. The polymer-intercalated materials exhibited higher thermal stability when compared to the bulk polymers. [Copyright &y& Elsevier]

Abstract: In this paper we report on the synthesis of a nanomaterial consisting of polyaniline sandwiched between the sheets of layered titanate. This was achieved by first intercalating aniline into the titanate, followed by heat treatment in air. The resulting intercalate was characterized by powder X-ray diffraction, thermogravimetric analysis and FTIR spectroscopy. [Copyright &y& Elsevier]

Abstract: The highly ionically conducting polymer poly[bis(methoxyethoxyethoxy)phosphazene] (MEEP) has been complexed with lithium triflate and intercalated between the layers of graphite oxide (GO). The resulting composite was characterized by powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, and ionic conductivity measurements. [Copyright &y& Elsevier]

Abstract: Intercalation compounds of polyethylene oxide, polyvinylpyrrolidone, methyl cellulose, poly[oxymethylene-(oxyethylene)] and poly[oligo(ethylene glycol oxalate)] into graphite oxide (GO) have been synthesized. The forces of attraction between the polymers and GO are primarily dipole–dipole and/or hydrogen bonding arising from the polar groups in the polymers and the functional groups (COC, COOH, COH and C GO. Addition of a small amount of dilute NaOH resulted in deprotonation of the acidic functionalities which caused exfoliation of the layered structure. Mixing with polymer solutions, followed by addition of a small amount of HCl induced flocculation of the graphite oxide with the polymers trapped in the gallery space. The resulting composites were characterized by powder X-ray diffraction and thermogravimetric analysis. [Copyright &y& Elsevier]

Abstract: From the first recorded accounts, over 7000 years ago, various forms of natural products have been utilized to treat pain disorders. Prototypical examples of such natural products are the opium poppy (Papaver soniferum) and the bark of the willow tree (Salix spp.). It was not until the 19th century when individual compounds were isolated from these substances and were determined to posses the desired effects. The known sources of these substances have been thoroughly investigated. Over the last several decades, more analgesic substances have been purified from natural products resulting in novel structural classes and mechanisms of actions. Plants and other natural products described in historical ethnobotanical and ethnopharmacological literature have become of more recent interest in drug discovery efforts. These manuscripts and reports are being utilized to aid in the identification of natural products that have been historically employed in the alleviation of pain. A large factor that has highlighted the importance of discovering novel compounds to treat pain has been in the fundamental understanding of the complex mechanisms of pain transmission in the nervous system. Nociceptive processing involves many receptor classes, enzymes and signaling pathways. The identification of novel classes of compounds from natural sources may lead to advancing the understanding of these underlying pharmacological mechanisms. With the potential of uncovering new compounds with idealistic pharmacological profiles (i.e., no side effects, no addictive potential), natural products still hold great promise for the future of drug discovery especially in the treatment of pain disorders and potentially drug addictions. [Copyright &y& Elsevier]

The method is applicable to chiral, highly complex compounds of type (VII) and the thus obtained oxazocenone (VIII) serves as the substrate for the preparation of the quinoline derivative (IX). [ABSTRACT FROM AUTHOR]

This paper focuses on with the cyclic plasticity modelling of welded, ex-service P91 material. A multi-material model is developed for high temperature cyclic plasticity, including the effects of the three different material zones in the vicinity of the weld: parent metal, weld metal and heat-affected zone. The cyclic plasticity behaviour of the three zones is identified from previously-published high temperature, low cycle fatigue experimental tests on uniaxial parent metal, weld metal and cross-weld (repair weld) specimens on ex-service P91 material. The heat-affected zone is shown to be significantly softer than the parent and weld metals and to act as a focus for concentration of plastic strain, leading to significantly inhomogeneous distributions of stress and strain in the weldment. The multi-material cyclic plasticity model is applied, via a three-dimensional finite element analysis of a welded T-piece header-branch connection, to predict the effects of cyclic internal pressure and small amplitude thermal fluctuations. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we report on the insertion of polypyrrole into layered graphite oxide. This was achieved by using the exfoliating and re-stacking properties of the host. The resulting intercalated product was characterized by powder X-ray diffraction, FT-IR spectroscopy, thermogravimetric analysis and scanning electron microscopy. [Copyright &y& Elsevier]

Phenotypic cell-based screening is a powerful approach to small-molecule discovery, but a major challenge of this strategy lies in determining the intracellular target and mechanism of action (MoA) for validated hits. Here, we show that the small-molecule BRD0476, a novel suppressor of pancreatic β-cell apoptosis, inhibits interferon-gamma (IFN-γ)-induced Janus kinase 2 (JAK2) and signal transducer and activation of transcription 1 (STAT1) signaling to promote β-cell survival. However, unlike common JAK-STAT pathway inhibitors, BRD0476 inhibits JAK-STAT signaling without suppressing the kinase activity of any JAK. Rather, we identified the deubiquitinase ubiquitin-specific peptidase 9X (USP9X) as an intracellular target, using a quantitative proteomic analysis in rat β cells. RNAi-mediated and CRISPR/Cas9 knockdown mimicked the effects of BRD0476, and reverse chemical genetics using a known inhibitor of USP9X blocked JAK-STAT signaling without suppressing JAK activity. Site-directed mutagenesis of a putative ubiquitination site on JAK2 mitigated BRD0476 activity, suggesting a competition between phosphorylation and ubiquitination to explain small-molecule MoA. These results demonstrate that phenotypic screening, followed by comprehensive MoA efforts, can provide novel mechanistic insights into ostensibly well-understood cell signaling pathways. Furthermore, these results uncover USP9X as a potential target for regulating JAK2 activity in cellular inflammation. [ABSTRACT FROM AUTHOR]

Oil sands-influenced process waters have been observed to cause reproductive effects and to induced CYP1A activity in fishes; however, little progress has been made in determining causative agents. Naphthenic acids (NAs) are the predominant organic compounds in process-affected waters, but due to the complexity of the mixture, it has been difficult to examine causal linkages in fishes. The aim of this study was to use in vitro assays specific to reproductive and CYP1A mechanisms to determine if specific add extractable fractions of NAs obtained from oil sands-influenced water are active toward reproductive processes or interact with the Ah receptor responsible for CYP1A activity. NAs were extracted from aged oil sands-influenced waters by use of acid precipitation, and the mixture was fractionated into three acidic and one neutral fraction. The four fractions were examined for Ah receptor-mediated potency by use of the H4IIE-luc bioassay, effects on production of steroid hormones by use of the H295R steroidogenesis assay, and sex steroid receptor binding activity using the yeast estrogen screen and yeast androgen screen. The mixtures were characterized by high resolution mass spectrometry, 1H nuclear magnetic resonance, and attenuated total reflectance infrared spectroscopy. The neutral fraction elicited Ah-receptor mediated activity after 24 h but not after 48 or 72 h. None of the fractions contained measurable levels of estrogen or androgen receptor agonists nor did they cause reductions in steroidogenesis. A number of fractions showed antiestrogenic or antiandrogenicity potency, with the neutral and main acidic fractions being the most potent. Neutral aromatic compounds are likely responsible for the CYP1A activity observed. Direct estrogenic, androgenic, or steroidogenic mechanisms are unlikely for NAs based on these results, but NAs act as potent antiandrogen or antiestrogens. [ABSTRACT FROM AUTHOR]