Complex Build-up Research Articles

Synthesis of Primary Amines via Hydrogen Atom Transfer-Initiated Cyclization/Reduction Cascade of Unsaturated Nitriles.

We report a hydrogen atom transfer-initiated cyclization/reduction cascade for the synthesis of primary amines from δ,ε- and ε,ζ-unsaturated nitriles. The HAT transformation employs Mn(acac)3 as a catalyst and utilizes air as an oxidant along with NaBH4 as a dual-purpose reductant toward the olefin and subsequently C═N. Aromatic and aliphatic nitriles incorporating mono-, di-, and trisubstituted olefins are substrates for the reaction. Starting materials bearing malonates are transformed into the corresponding bicyclic lactams, enabling the rapid buildup of structural complexity.

FAUST

Aims. Interstellar complex organic molecules (iCOMs) are species commonly found in the interstellar medium. They are believed to be crucial seed species for the build-up of chemical complexity in star forming regions as well as our own Solar System. Thus, understanding how their abundances evolve during the star formation process and whether it enriches the emerging planetary system is of paramount importance. Methods. We use data from the ALMA Large Program FAUST (Fifty AU STudy of the chemistry in the disk and envelope system of solar protostars) to study the compact line emission towards the [BHB2007] 11 proto-binary system (sources A and B), where a complex structure of filaments connecting the two sources with a larger circumbinary disk has previously been detected. More than 45 methyl formate (CH3OCHO) lines are clearly detected with upper energies in the [123, 366] K range, as well as 8 dimethyl ether transitions (CH3OCH3) in the [93, 191] K range, 1 ketene transition (H2CCO) and 4 formic acid transitions (t-HCOOH). We compute the abundance ratios with respect to CH3OH for CH3OCHO, CH3OCH3, H2CCO, t-HCOOH (as well as an upper limit for CH3CHO) through a radiative transfer analysis. We also report the upper limits on the column densities of nitrogen bearing iCOMs, N(C2H5CN) and N(C2H3CN). Results. The emission from the detected iCOMs and their precursors is compact and encompasses both protostars, which are separated by only 0.2″ (~28 au). The integrated intensities tend to align with the Southern filament, revealed by the high spatial resolution observations of the dust emission at 1.3 mm. A Position-Velocity and 2D analysis are performed on the strongest and uncontaminated CH3OCH3 transition and show three different spatial and velocity regions, two of them being close to 11B (Southern filament) and the third one near 11A. Conclusions. All our observations suggest that the detected methanol, as well as the other iCOMs, are generated by the shocked gas from the incoming filaments streaming towards [BHB2007] 11A and 11B, respectively, making this source one of the few where chemical enrichment of the gas caused by the streaming material is observed.

MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C.

Glycosylated mucin proteins contribute to the essential barrier function of the intestinal epithelium. The transmembrane mucin MUC13 is an abundant intestinal glycoprotein with important functions for mucosal maintenance that are not yet completely understood. We demonstrate that in human intestinal epithelial monolayers, MUC13 localized to both the apical surface and the tight junction (TJ) region on the lateral membrane. MUC13 deletion resulted in increased transepithelial resistance (TEER) and reduced translocation of small solutes. TEER buildup in ΔMUC13 cells could be prevented by addition of MLCK, ROCK or protein kinase C (PKC) inhibitors. The levels of TJ proteins including claudins and occludin were highly increased in membrane fractions of MUC13 knockout cells. Removal of the MUC13 cytoplasmic tail (CT) also altered TJ composition but did not affect TEER. The increased buildup of TJ complexes in ΔMUC13 and MUC13-ΔCT cells was dependent on PKC. The responsible PKC member might be PKCδ (or PRKCD) based on elevated protein levels in the absence of full-length MUC13. Our results demonstrate for the first time that a mucin protein can negatively regulate TJ function and stimulate intestinal barrier permeability.

STROMATOPOROID-ECHINODERM ECOLOGICAL SUCCESSIONS IN THE LATE ORDOVICIAN (KATIAN): REEF FACIES AND THE ROLE OF KEY BIOTA IN REEF ARCHITECTURE

Abstract Ecologically complex buildups within the Kimmswick Limestone of the Galena Group (Upper Ordovician, Katian) near St. Louis, Missouri, display unique communities of stromatoporoids, encrusting cyathocystid and edrioblastoid edrioasteroids, camerate and other crinoids, paracrinoids, bryozoans, tabulate, and rugose corals. Substrate stabilization and vertical ecological successions were influenced by labechiid stromatoporoids that transitioned from laminar to domal/pillar morphologies from the base of the reef to its terminus. Cyathocystid edrioasteroids occurred in dense aggregations within cryptic cavities, often inverted in life orientation. Surrounding facies consisted of bryozoan and chert-rich wackestones-packstones, cross-bedded abraded echinoderm grainstones, gastropod-bivalve grainstones, and echinoderm-bryozoan grainstone/rudstones, while reefal facies comprised stromatoporoid-echinoderm boundstones, and stromatoporoid-cyathocystid framestones. Reef geometry and facies distribution reflected both allogenic and autogenic controls fundamental to the initialization and stabilization of the Shady Valley reefs. Four distinct successional series, from initial stabilization of important binders to colonization and diversification of stemmed echinoderm groups and subsequent domination of labechiid stromatoporoid framebuilders, formed the vertical profile of the reefs. Laminar, domal and irregular frame-building stromatoporoids acted as sediment stabilizers and formed ideal substrates for encrusting hardground fauna, supporting the development of cryptic habitats exploited by diverse echinoderms at the acme of reef diversification. Similar Katian hardground ecological successions occur in coeval reefs elsewhere in North America, Europe, Baltica, and South China. However, the scale of the reef architecture, development of complete ecological successions, and the diversity and multiple ecological roles of labechiid stromatoporoids and echinoderms in the Kimmswick Limestone sets it apart.

Modelling deuterated isotopologues of methanol towards the pre-stellar core L1544

Context. In the extremely cold and dark environments of pre-stellar cores, methanol is formed on the surface of interstellar dust grains and released into the gas phase via non-thermal desorption mechanisms. Gaseous methanol constitutes the starting point for the formation of many massive complex organic molecules and is therefore of utmost importance for the build-up of chemical complexity. Aims. We aim to improve upon a previous model for the prediction of column densities and deuterium fractions of non-deuterated and singly deuterated methanol. Thereby, we try to identify crucial chemical and physical parameters for which the study of deuteration could provide valuable additional constraints. Methods. We employed a gas-grain chemical code to devise a model that is in agreement with the observed column density and deuterium fraction profiles of the innermost region of the pre-stellar core L1544. For that purpose, we developed a new treatment of reactive desorption, deriving an individual reactive desorption efficiency for every product species in a chemical reaction that depends on the reaction enthalpy and type of the underlying surface. Furthermore, we explored several options to promote the diffusion of hydrogen and deuterium atoms over the surface of interstellar dust grains in order to increase methanol formation. Results. Our fiducial model employs diffusion via the quantum tunnelling of hydrogen and deuterium atoms, resulting in CH3OH and CH2DOH column densities that are approximately an order of magnitude lower than the observed values, which is an improvement over the results of the previous model by a factor of 10. The N(CH2DOH)/N(CH3OH) ratio is reproduced within a factor of 1.2 for the centre and 1.8 for the position of the methanol peak. Given the large uncertainties that chemical models typically have, we consider our predictions to be in agreement with the observations. In general, we conclude that a diffusion process with a high diffusion rate needs to be employed to obtain methanol column densities that are in accordance with the observed values. Also, we find that the introduction of abstraction reactions into the methanol formation scheme suppresses deuteration when used in combination with a high diffusion rate.

Spectroscopic characterization and photochemistry of HC3N− and CH3C3N−: implications for ion chemistry in Titan's atmosphere

ABSTRACT Molecular ions are key intermediates in the build-up of chemical complexity in interstellar clouds. Among the more than 300 interstellar molecules, only eight negative ions, i.e. C2n+1N− (n = 0–3) and HC2n− (n = 2–5), have been astronomically observed. Understanding the formation mechanism of these ions under the interstellar conditions is essential for astrochemical modelling and establishing the astrochemical networks. Cyanopolyynes including the parent molecule HC3N are carbon-chain molecules that have been observed in a variety of astronomical objects such as the Titan's atmosphere. Herein, two cyanoacetylene anions HC3N‒ and CH3C3N‒ were generated in solid Ne matrix at 3 K and characterized with matrix-isolation infrared spectroscopy, as aided by isotopic substitutions and the ab initio calculations at the UCCSD(T)-F12a/cc-pVTZ-F12 level using second-order vibrational perturbation theory. Upon red-light irradiation at 625 nm, both ions undergo electron detachment by reformation of the neutral species. Importantly, the concomitant dehydrogenation of HC3N‒ has also been observed in the matrix, providing new insight into the intriguing mechanism for the formation of C3N‒ in the upper atmosphere of Titan.

Ligand-Enabled Carboamidation of Unactivated Alkenes through Enhanced Organonickel Electrophilicity.

Catalytic carboamination of alkenes is a powerful synthetic tool to access valuable amine scaffolds from abundant and readily available alkenes. Although a number of synthetic approaches have been developed to achieve the rapid buildup of molecular complexity in this realm, the installation of diverse carbon and nitrogen functionalities onto unactivated alkenes remains underdeveloped. Here we present a ligand design approach to enable nickel-catalyzed three-component carboamidation that is applicable to a wide range of alkenyl amine derivatives via a tandem process involving alkyl migratory insertion and inner-sphere metal-nitrenoid transfer. With this method, various nitrogen functionalities can be installed into both internal and terminal unactivated alkenes, leading to differentially substituted diamines that would otherwise be difficult to access. Mechanistic investigations reveal that the tailored Ni(cod)(BQiPr) precatalyst modulates the electronic properties of the presumed π-alkene-nickel intermediate via the quinone ligand, leading to enhanced carbonickelation efficiency across the unactivated C═C bond. These findings establish nickel's ability to catalyze multicomponent carboamidation with a high efficiency and exquisite selectivity.

Site-selective methylene C-H oxidation of an alkyl diamine enabled by supramolecular recognition using a bioinspired manganese catalyst.

Site-selective oxidation of aliphatic C-H bonds is a powerful synthetic tool because it enables rapid build-up of product complexity and diversity from simple precursors. Besides the poor reactivity of alkyl C-H bonds, the main challenge in this reaction consists in differentiating between the multiple similar sites present in most organic molecules. Herein, a manganese oxidation catalyst equipped with two 18-benzo-6-crown ether receptors has been employed in the oxidation of the long chain tetradecane-1,14-diamine. 1H-NMR studies evidence simultaneous binding of the two protonated amine moieties to the crown ether receptors. This recognition has been used to pursue site-selective oxidation of a methylenic site, using hydrogen peroxide as oxidant in the presence of carboxylic acids as co-ligands. Excellent site-selectivity towards the central methylenic sites (C6 and C7) is observed, overcoming selectivity parameters derived from polar deactivation by simple amine protonation and selectivity observed in the oxidation of related monoprotonated amines.

Common demanding conditions among professional high-level military and sport leaders: a cross-contextual qualitative reflexive thematic analysis

Military and sport have attracted increased research interest separately as two distinctly demanding performance- and leadership-driven contexts. However, cross-contextual psychological research in leadership is lacking. Such research has potential to expose unique cross-fertilising insights into resemblances in leadership challenges among military and sport leaders, transferable to a broader range of contexts. Thus, the current study simultaneously explored high-level military and sport leaders’ real-life experiences of similarities in demanding conditions and their psychological manifestations. Sixteen participants - eight Swedish high-level military leaders and eight Swedish high-level sport leaders, participated in the study. Using a qualitative inductive cross-contextual design enabled in-depth knowledge and transferability. A reflexive thematic analysis (RTA) of sixteen interview transcripts generated four common themes of demanding conditions: (1) Developing organisations: Leading under an extensive workload and responsibility, (2) Managing destructive superiors and subordinates: Standing up for oneself, (3) Taking care of the minds and moods of others: Leading deliberated difficult conversations, and (4) Periods of extreme concentration: Leading critical coordination, decisions, and timing. The findings tie high-level military and sports leaders together into a high-stress and high-stakes leader role invoked to manoeuvre a complex buildup of demanding conditions. Implications are presented. Keywords: High-level leaders, military, sport, demanding conditions.

FAUST

Aims. Methanol is a ubiquitous species commonly found in the molecular interstellar medium. It is also a crucial seed species for the build-up of chemical complexity in star forming regions. Thus, understanding how its abundance evolves during the star formation process and whether it enriches the emerging planetary system is of paramount importance. Methods. We used new data from the ALMA Large Program FAUST (Fifty AU STudy of the chemistry in the disc/envelope system of solar protostars) to study the methanol line emission towards the [BHB2007] 11 protobinary system (sources A and B), where a complex structure of filaments connecting the two sources with a larger circumbinary disc has previously been detected. Results. Twelve methanol lines have been detected with upper energies in the [45–537] K range along with one 13CH3OH transition and one methyl formate (CH3OCHO) line blended with one of the methanol transitions. The methanol emission is compact (FWHM ~ 0.5″) and encompasses both protostars, which are separated by only 0.2″ (28 au). In addition, the overall methanol line emission presents three velocity components, which are not spatially resolved by our observations. Nonetheless, a detailed analysis of the spatial origin of these three components suggests that they are associated with three different spatial regions, with two of them close to 11B and the third one associated with 11A. A radiative transfer analysis of the methanol lines gives a kinetic temperature of [100–140] K, an H2 volume density of 106–107 cm−3 and column density of a few 1018 cm−2 in all three components with a source size of ~0.15″. Thus, this hot and dense gas is highly enriched in methanol with an abundance as high as 10−5. Using previous continuum data, we show that dust opacity can potentially completely absorb the methanol line emission from the two binary objects. Conclusions. Although we cannot firmly exclude other possibilities, we suggest that the detected hot methanol is resulting from the shocked gas from the incoming filaments streaming towards [BHB2007] 11A and B, respectively. Higher spatial resolution observations are necessary to confirm this hypothesis.

Dearomatization [4+2] Cycloaddition of Nonactivated Benzene Derivatives.

Dearomatization reactions have recently emerged as a powerful tool for the rapid buildup of molecular complexity. Here, an unparalleled thermal dearomatization [4+2] cycloaddition reaction between benzene derivatives and a 2H-phosphindole tungsten complex was reported. The unique reactivity of the in situ-generated 2H-phosphindole complex toward benzene was revealed by density functional theory calculations. We thus provide new insights into the dearomatization of nonactivated arenes and pave the way for the manipulation of the dearomatization for further applications.

Synthesis of complex bicyclic scaffolds by intermolecular photosensitized dearomative cycloadditions of activated alkenes and naphthalenes.

The rapid buildup of molecular complexity from simple precursors is a key goal in organic chemistry. One strategy to achieve this is through a dearomative cycloaddition wherein a 2D arene and alkene is converted to a 3D structure. In many cases this type of reactivity has been achieved with photochemistry. Despite the prospect of such a reaction, most known variants are intramolecular, which greatly limits the scope of chemical space that can be accessed. Intermolecular variants are known but are generally limited to heterocyclic systems such as indoles or quinolines. Herein, a method for intermolecular dearomative cycloaddition of simple naphthalenes with alkenes is presented. The reactions operate by a photoinduced sensitization of the arene. The bridged bicyclic products are generated with control of regiochemistry and function for a range of alkenes. In addition, the products can serve as useful intermediates as demonstrated in the synthesis of a biologically active benzazapine analog. Mechanistic studies are also included, which support reaction via a triplet excited state and that the selectivity can be rationalized by spin-density calculations.

Hybrid deep learning model using recurrent neural network and gated recurrent unit for heart disease prediction

<span>This paper proposes a new hybrid deep learning model for heart disease prediction using recurrent neural network (RNN) with the combination of multiple gated recurrent units (GRU), long short-term memory (LSTM) and Adam optimizer. This proposed model resulted in an outstanding accuracy of 98.6876% which is the highest in the existing model of RNN. The model was developed in Python 3.7 by integrating RNN in multiple GRU that operates in Keras and Tensorflow as the backend for deep learning process, supported by various Python libraries. The recent existing models using RNN have reached an accuracy of 98.23% and deep neural network (DNN) has reached 98.5%. The common drawbacks of the existing models are low accuracy due to the complex build-up of the neural network, high number of neurons with redundancy in the neural network model and imbalance datasets of Cleveland. Experiments were conducted with various customized model, where results showed that the proposed model using RNN and multiple GRU with synthetic minority oversampling technique (SMOTe) has reached the best performance level. This is the highest accuracy result for RNN using Cleveland datasets and much promising for making an early heart disease prediction for the patients.</span>

Im Sog des Untergangs

Drawn into Doom. On the Conception of Narrative Suspense in the Nibelungenlied This paper examines the potential and the structure of narrative suspense in the Nibelungenlied, as it specifically evolves in the final part of the Middle High German epic, beginning with Kriemhild’s treacherous invitation. Due to the inevitabi­lity of the catastrophe, the expectations of the reader or listener are directed at those details of the plot which are part of the text’s distinct interpretation of the traditional story, so that possible anticipations reside in the questions of ›how‹ and ›when‹, while not completely disregarding the question of ›what‹. The complex and extensive build-up of suspense towards the end can be regarded as a genuine pro­duct of the literarization of oral lore.

Small rings in the bigger picture: ring expansion of three- and four-membered rings to access larger all-carbon cyclic systems.

The release of the inherent ring strain of cyclobutane and cyclopropane derivatives allows a rapid build-up of molecular complexity. This review highlights the state-of-the-art of the ring expansions of three- and four-membered cycles and is organised by types of reactions with emphasis on the reaction mechanisms. Selected examples are discussed to illustrate the synthetic potential of this elegant synthetic tool.

Bank Complexity, Governance, and Risk

Bank holding companies (BHCs) can be complex organizations, conducting multiple lines of business through many distinct legal entities and across a range of geographies. While such complexity raises the the costs of bank resolution when organizations fail, the effect of complexity on BHCs' broader risk profiles is less well understood. Business, organizational, and geographic complexity can engender explicit trade-offs between the agency problems that increase risk and the diversification, liquidity management, and synergy improvements that reduce risk. The outcomes of such trade-offs may depend on bank governance arrangements. We test these conjectures using data on large U.S. BHCs for the 1996-2018 period. Organizational complexity and geographic scope tend to provide diversification gains and reduce idiosyncratic and liquidity risks while also increasing BHCs' exposure to systematic and systemic risks. Regulatory changes focused on organizational complexity have significantly reduced this type of complexity, leading to a decrease in systemic risk and an increase in liquidity risk among BHCs. While bank governance structures have, in some cases, significantly affected the buildup of BHC complexity, better governance arrangements have not moderated the effects of complexity on risk outcomes.

High-MYC Cells Depend on NUAK1 to Prevent Stalled Transcription

NUAK1 inhibition caused buildup of nonproductive stalled transcription complexes in high-MYC cells.

Recent Advances in Nickel-Catalyzed Three-Component Difunctionalization of Unactivated Alkenes

Catalytic, intermolecular difunctionalization of alkenes represents an efficient and diverse protocol for the buildup of molecular complexity from abundant materials by forging two chemical bonds in a single operation. Despite important progress in this area, transition-metal-catalyzed three-component difunctionalization of unactivated alkenes remains underdeveloped, mainly because of the low reactivity, reduced polarization, and high tendency toward β-hydride elimination of these compounds. In this context, nickel-catalyzed, selective, intermolecular difunctionalization methods that generally proceed via two distinct reaction pathways, migratory insertion of nickel species into alkenes and radical addition to alkenes, have been developed. This short review highlights recent advances in this area.1 Introduction2 Nickel-Catalyzed Three-Component Difunctionalization of Unactivated­ Alkenes via Migratory Insertion Processes3 Nickel-Catalyzed Three-Component Difunctionalization of Unactivated­ Alkenes via Radical Processes4 Conclusions and Perspectives

Chiral phosphoric acid catalyzed aminative dearomatization of \u03b1-naphthols/Michael addition sequence

Asymmetric dearomatization reactions have recently emerged as a powerful tool for the rapid build-up of the molecular complexity. Chiral three-dimensional polycyclic molecules bearing contiguous stereogenic centers can be synthesized from readily available planar aromatic feedstocks. Here we report that an intermolecular asymmetric dearomatization reaction of α-naphthols bearing a tethered nucleophile at the C4 position of the naphthol ring is achieved by a chiral phosphoric acid. The reaction proceeds via a highly chemo- and regioselective aminative dearomatization/Michael addition sequence, affording a wide array of functionalized cyclic ketones in good yields (up to 93%) with excellent enantioselectivity (up to >99% ee). The catalyst loading can be reduced to 0.1 mol%. Preliminary mechanistic investigations identify that the enantioselectivity is established in the dearomatization step, while the Michael addition is the rate-limiting step. A working model accounting for the origin of the stereochemistry is proposed based on DFT calculations.

Sleep-like bistability, loss of causality and complexity in the cerebral cortex of unresponsive wakefulness syndrome patients

Unresponsiveness Wakefulness Syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and responsive to sensory stimuli. In most of these patients, Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) shows that structurally preserved cortical areas react to TMS, but fail to engage complex patterns of effective interactions, as assessed by the perturbational complexity index (PCI). Another condition during which thalamocortical circuits are intact, active and reactive, yet unable to generate complex responses, is non-rapid eye movement (NREM) sleep, in which cortical neurons become bistable and tend to fall into a silent state (OFF-period) upon receiving an input. Here we tested whether a pathological form of bistability may be responsible for the loss of cortical complexity in UWS patients. In eyes-open UWS patients (n=16) TMS evoked a slow wave-like EEG response that was associated with a suppression of high-frequency (above 20Hz) oscillations suggesting the occurrence of OFF-periods similar to the ones observed in healthy subjects (n=8) during NREM sleep. Crucially, this phenomenon was never detected in healthy awake subjects (n=20). In all targeted cortical areas (Brodmann areas 6 and 7, bilaterally) of UWS patients, pathological OFF-periods significantly impaired local causal interactions (as measured by the phase-locking factor) and prevented the build-up of global complexity (as measured by PCI). Our results draw a first link between neuronal events (OFF-periods) and global brain dynamics (complexity) in UWS patients. Detecting the presence of sleep-like bistability and tracking its evolution over time, may offer a valuable read-out to devise, guide and titrate therapeutic strategies aimed at restoring consciousness.