bluuebunny/crossref_metadata_2025 huggingface dataset:
Nickel‐Catalyzed Migratory Hydrocyanation of Internal Alkenes: Unexpected Diastereomeric‐Ligand‐Controlled Regiodivergence
Authors: Gao Jihui , Jiao Mingdong , Ni Jie , Yu Rongrong , Cheng Gui‐Juan , Fang Xianjie
Published: October 2020

A regiodivergent nickel‐catalyzed hydrocyanation of a broad range of internal alkenes involving a chain‐walking process is reported. When appropriate diastereomeric biaryl diphosphite ligands are applied, the same starting materials can be converted to either linear or branched nitriles with good yields and high regioselectivities. DFT calculations suggested that the catalyst architecture determines the regioselectivity by modulating electronic and steric interactions. In addition, moderate enantioselectivities were observed when branched nitriles were produced.
Fragment‐Bindung an die Kinase‐Scharnier‐Region: Wenn Ladungsverteilung und lokale pKa‐Verschiebungen etablierte Bioisosterie‐Konzepte fehlleiten
Authors: Oebbeke Matthias , Siefker Christof , Wagner Björn , Heine Andreas , Klebe Gerhard
Published: October 2020

Die medizinisch‐chemische Optimierung folgt einer Strategie, funktionelle Gruppen zu ersetzen und größere Substituenten an ein vielversprechendes Leitstrukturgerüst anzufügen. Wohl etablierte Bioisosterie‐Regeln werden berücksichtigt, dennoch ist es schwierig abzuschätzen, ob die durchgeführten Modifikationen auch wirklich den Anforderungen einer Bindestelle gerecht werden. Die Elektronendichteverteilung und die pKa‐Werte der Liganden werden moduliert und beeinflussen so Protonierungszustände und Bioverfügbarkeiten. Unter Berücksichtigung des benachbarten H‐Brücken‐Donor/Akzeptor‐Musters des Scharnierbindungsmotivs (“Hinge‐Region”) einer Kinase untersuchten wir kristallographisch eine Reihe von Fragmenten, um zu sehen, ob sie das erforderliche Interaktionsmuster erwidern können. Unerwarteterweise sind Benzoesäure und Benzamidin, mit den richtigen Substituenten dekoriert, ebenso wie ein Carboxamid oder eine phenolische OH‐Gruppe völlig bioisoster. Ein einzähniger Pyridinstickstoff übertrifft sogar zweizähnige Funktionalitäten am Liganden. Die Bedeutung der korrekten Einstellung von pKa‐Werten der angefügten funktionellen Gruppen am Liganden durch zusätzliche Substituenten am Molekülgerüst wird damit offensichtlich.
The Existence of a N→C Dative Bond in the C60–Piperidine Complex
Authors: Lamanec Maximilián , Lo Rabindranath , Nachtigallová Dana , Bakandritsos Aristides , Mohammadi Elmira , Dračínský Martin , Zbořil Radek , Hobza Pavel , Wang Weizhou
Published: October 2020

The complexes formed between carbon allotropes (C20, C60 fullerenes, graphene, and single‐wall carbon nanotubes) and piperidine have been investigated by means of computational quantum chemical and experimental IR and NMR techniques. Alongside hydrogen bonds, the C⋅⋅⋅N tetrel bond, and lone‐pair⋅⋅⋅π interactions, the unexpected N→C dative/covalent bond has been detected solely in complexes of fullerenes with piperidine. Non‐planarity and five‐member rings of carbon allotropes represent the key structural prerequisites for the unique formation of a dative N→C bond. The results of thermodynamics calculations, molecular dynamics simulations, and NMR and FTIR spectroscopy explain the specific interactions between C60 and piperidine. The differences in behavior of individual carbon allotropes in terms of dative bonding formation brings a new insight into their controllable organic functionalization.
Structure Based Design of Bicyclic Peptide Inhibitors of RbAp48
Authors: Hart Peter 't , Hommen Pascal , Noisier Anaïs , Krzyzanowski Adrian , Schüler Darijan , Porfetye Arthur T. , Akbarzadeh Mohammad , Vetter Ingrid R. , Adihou Hélène , Waldmann Herbert
Published: October 2020

The scaffolding protein RbAp48 is part of several epigenetic regulation complexes and is overexpressed in a variety of cancers. In order to develop tool compounds for the study of RbAp48 function, we have developed peptide inhibitors targeting the protein–protein interaction interface between RbAp48 and the scaffold protein MTA1. Based on a MTA1‐derived linear peptide with low micromolar affinity and informed by crystallographic analysis, a bicyclic peptide was developed that inhibits the RbAp48/MTA1 interaction with a very low nanomolar KD value of 8.56 nM, and which showed appreciable stability against cellular proteases. Design included exchange of a polar amide cyclization strategy to hydrophobic aromatic linkers enabling mono‐ and bicyclization by means of cysteine alkylation, which improved affinity by direct interaction of the linkers with a hydrophobic residue on RbAp48. Our results demonstrate that stepwise evolution of a structure‐based design is a suitable strategy for inhibitor development targeting PPIs.
A BN‐Doped Cycloparaphenylene Debuts
Authors: Chen Min , Unikela Kiran S. , Ramalakshmi Rongala , Li Bo , Darrigan Clovis , Chrostowska Anna , Liu Shih‐Yuan
Published: October 2020

The first example of a BN‐doped cycloparaphenylene BN‐[10]CPP was synthesized and characterized. Its reactivity and photophysical properties were evaluated in direct comparison to its carbonaceous analogues Mes‐[10]CPP and [10]CPP. While the photophysical properties of BN‐[10]CPP remains similar to its carbonaceous analogues, the electronic structure changes associated with the introduction of a 1,2‐azaborine BN heterocycle into a CPP scaffold enables facile and selective late‐stage functionalizations that cannot be accomplished with carbonaceous CPPs. Specifically, Ir‐catalyzed hydrogenation of BN‐[10]CPP selectively reduces the BN heterocyclic ring, which upon hydrolysis produces a rare example of a macrocyclic paraphenylene 6 incorporating the versatile ketone functionality within the macrocyclic ring.
Magnetic‐Field‐Driven Extraction of Bioreceptors into Polymeric Membranes for Label‐Free Potentiometric Biosensing
Authors: Lv Enguang , Li Yanhong , Ding Jiawang , Qin Wei
Published: October 2020

We report here the concept of a magnetically controlled extraction of hydrophilic bioreceptors into polymeric membranes for bioassays. The potentiometric assay relies on the intrinsic charges of an antimicrobial peptide and its unique recognition abilities, which can eliminate the probe labeling and indicator addition. The target binding event could effectively prevent the extraction of the peptide into the polymeric membrane doped with an ion exchanger, thus resulting in a potential change. The potentiometric response properties of the peptide assembled on magnetic beads can be dynamically controlled and modulated by applying a magnetic field. Staphylococcus aureus, as a model of food‐borne pathogens, was measured at levels down to 10 CFU mL−1. Based on this sensing strategy, a potentiometric array was developed for the pattern recognition of bacteria. The proposed general platform can be used for potentiometric biosensing using other hydrophilic bioreceptors.
Nanoscale Anatomy of Iron‐Silica Self‐Organized Membranes: Implications for Prebiotic Chemistry
Authors: Kotopoulou Electra , Lopez‐Haro Miguel , Calvino Gamez Jose Juan , García‐Ruiz Juan Manuel
Published: October 2020

Iron‐silica self‐organized membranes, so‐called chemical gardens, behave as fuel cells and catalyze the formation of amino/carboxylic acids and RNA nucleobases from organics that were available on early Earth. Despite their relevance for prebiotic chemistry, little is known about their structure and mineralogy at the nanoscale. Studied here are focused ion beam milled sections of iron‐silica membranes, grown from synthetic and natural, alkaline, serpentinization‐derived fluids thought to be widespread on early Earth. Electron microscopy shows they comprise amorphous silica and iron nanoparticles of large surface areas and inter/intraparticle porosities. Their construction resembles that of a heterogeneous catalyst, but they can also exhibit a bilayer structure. Surface‐area measurements suggest that membranes grown from natural waters have even higher catalytic potential. Considering their geochemically plausible precipitation in the early hydrothermal systems where abiotic organics were produced, iron‐silica membranes might have assisted the generation and organization of the first biologically relevant organics.
A Radical Approach to Making Unnatural Amino Acids: Conversion of C−S Bonds in Cysteine Derivatives into C−C Bonds
Authors: Wang Yingwei , Deng Li‐Fan , Zhang Xia , Mou Ze‐Dong , Niu Dawen
Published: October 2020

Here we report a general approach to make unnatural amino acids from readily available cysteine derivatives. This method capitalizes on an intramolecular radical substitution process that generates alkyl radicals through C−S cleavage. The resulting alkyl radicals partook in diverse C−C bond forming events. These reactions proceed under mild, photocatalytic conditions at room temperature, and can be performed open to air. The utility of these transformations is further demonstrated in the straightforward synthesis of various unnatural amino acids and peptides that are difficult to access previously.
gem‐Difluoromethylene Alkyne‐Enabled Diverse C−H Functionalization and Application to the on‐DNA Synthesis of Difluorinated Isocoumarins
Authors: Gao Hui , Lin Shuang , Zhang Shuning , Chen Weijie , Liu Xiawen , Yang Guang , Lerner Richard A. , Xu Hongtao , Zhou Zhi , Yi Wei
Published: October 2020

Using gem‐difluoromethylene alkynes as effectors, unprecedented diverse C−H activation/[4+2] annulations of simple benzoic acids are reported. The chemodivergent reaction outcomes are well‐tuned by Rh/Ir‐catalyzed system; in the RhIII catalysis, 3‐alkenyl‐1H‐isochromen‐1‐one and 3,4‐dialkylideneisochroman‐1‐one skeletons are afforded in a solvent‐dependent manner whereas difluoromethylene‐substituted 1H‐isochromen‐1‐ones are generated under the IrIII‐catalyzed system. Mechanistic studies revealed that unusually double β‐F eliminations and fluorine effect‐induced regioselective reductive elimination are independently involved to enable distinct reaction modes for divergent product formations. Besides, synthetic application in both the derivatization of obtained diene products and the on‐DNA synthesis of DNA‐tagged difluorinated isocoumarin have been demonstrated, which manifested great potential for synthetic utility of the developed protocols.
Imaging Sodium Dendrite Growth in All‐Solid‐State Sodium Batteries Using 23Na T2‐Weighted Magnetic Resonance Imaging
Authors: Rees Gregory J. , Spencer Jolly Dominic , Ning Ziyang , Marrow T. James , Pavlovskaya Galina E. , Bruce Peter G.
Published: October 2020

Two‐dimensional, Knight‐shifted, T2‐contrasted 23Na magnetic resonance imaging (MRI) of an all‐solid‐state cell with a Na electrode and a ceramic electrolyte is employed to directly observe Na microstructural growth. A spalling dendritic morphology is observed and confirmed by more conventional post‐mortem analysis; X‐ray tomography and scanning electron microscopy. A significantly larger 23Na T2 for the dendritic growth, compared with the bulk metal electrode, is attributed to increased sodium ion mobility in the dendrite. 23Na T2‐contrast MRI of metallic sodium offers a clear, routine method for observing and isolating microstructural growths and can supplement the current suite of techniques utilised to analyse dendritic growth in all‐solid‐state cells.
Glycolic acid‐supported cobalt ferrite‐catalyzed one‐pot synthesis of pyrimido[4,5‐b]quinoline and indenopyrido[2,3‐d]pyrimidine derivatives
Authors: Gholami Ahmad , Mokhtary Masoud , Nikpassand Mohammad
Published: October 2020

Herein, one‐pot synthesis of pyrimido[4,5‐b]quinoline and indenopyrido[2,3‐d]pyrimidine derivatives was developed by the three‐component reaction of aldehydes, 6‐amino‐1,3‐dimethyluracil, and 1,3‐dicarbonyl compounds in the presence of glycolic acid‐supported cobalt ferrite CoFe2O4@SiO2@Si (CH2)3NHCOOCH2COOH as a novel magnetic catalyst in ethanol at reflux conditions. Glycolic acid‐supported cobalt ferrite was characterized via Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy‐dispersive X‐ray spectroscopy (EDX), and vibrating sample magnetometer (VSM). Moreover, the catalyst was easily recovered with magnetic separation and recycled at least for five times without significant loss of its catalytic activity. The products were formed in excellent yields over appropriate reaction times under environmentally friendly conditions. The high efficiency and easy isolation of catalyst from products with an external permanent magnet are some of the remarkable advantages of this method.
Comparative neuroanatomical study of the amygdala and fear conditioning in Nigerian breeds of Artiodactyla: Sheep (Uda) and goats (Red Sokoto)
Authors: George Itoro , Alawa Judith , Akpulu Peter , Alawa Clement
Published: October 2020

The aim of this study was to evaluate fear condition responses in sheep and goat and to relate this to the neuroarchitecture of their amygdala. Forty adult sheep (Uda breed) and 40 adult goats (Red Sokoto breed) were fear‐conditioned by associating the sound of a car horn (neutral stimuli) with water spray (aversive stimuli) and the fear response was determined by direct observation of the behavior of the sheep and goats and measuring their flight distances and escape time. Eight groups were studied, each comprising of 10 animals (five sheep and five goats). Goats and sheep were tested alternately in the morning of every day of the week for three consecutive weeks, in which 4 days was used for habituation and 3 days for testing. Histologically, neurons in the central and basolateral complex of the amygdala were studied and analyzed using Nissl and golgi staines. Behaviorally, goats elicited an active avoidance response expressed as flight with concomitant intense flight distances (p < .001) compared to sheep. Although, sheep had larger brain parameters, it showed attenuated basolateral amygdala cytoarchitecture consistent with reduced fear perception and response. Goats had significantly more densely distributed pyramidal and spiny stellate neurons in the basolateral amygdala while sheep showed more non‐pyramidal and aspiny neurons. These results provide interesting practical perspectives on how adaptions in the amygdala coincides with alterations in fear conditioning in domestic animals and may be the basis for the higher incidence of the sheep in automobile accidents than goats in developing countries especially Africa.
Mechanosensitive Control of Articular Cartilage and Subchondral Bone Homeostasis in Mice Requires Osteocytic Transforming Growth Factor β Signaling
Authors: Bailey Karsyn N. , Nguyen Jeffrey , Yee Cristal S. , Dole Neha S. , Dang Alexis , Alliston Tamara
Published: October 2020

Objective

Transforming growth factor β (TGFβ) signaling plays a complex tissue‐specific and nonlinear role in osteoarthritis (OA). This study was conducted to determine the osteocytic contributions of TGFβ signaling to OA.

Methods

To identify the role of osteocytic TGFβ signaling in joint homeostasis, we used 16‐week‐old male mice (n = 9–11 per group) and female mice (n = 7–11 per group) with an osteocyte‐intrinsic ablation of TGFβ receptor type II (TβRIIocy−/− mice) and assessed defects in cartilage degeneration, subchondral bone plate (SBP) thickness, and SBP sclerostin expression. To further investigate these mechanisms in 16‐week‐old male mice, we perturbed joint homeostasis by subjecting 8‐week‐old mice to medial meniscal/ligamentous injury (MLI), which preferentially disrupts the mechanical environment of the medial joint to induce OA.

Results

In all contexts, independent of sex, genotype, or medial or lateral joint compartment, increased SBP thickness and SBP sclerostin expression were spatially associated with cartilage degeneration. Male TβRIIocy−/− mice, but not female TβRIIocy−/− mice, had increased cartilage degeneration, increased SBP thickness, and higher levels of SBP sclerostin compared with control mice (all P < 0.05), demonstrating that the role of osteocytic TGFβ signaling on joint homeostasis is sexually dimorphic. With changes in joint mechanics following injury, control mice had increased SBP thickness, subchondral bone volume, and SBP sclerostin expression (all P < 0.05). TβRIIocy−/− mice, however, were insensitive to subchondral bone changes with injury, suggesting that mechanosensation at the SBP requires osteocytic TGFβ signaling.

Conclusion

Our results provide new evidence that osteocytic TGFβ signaling is required for a mechanosensitive response to injury, and that osteocytes control SBP homeostasis to maintain cartilage health, identifying osteocytic TGFβ signaling as a novel therapeutic target for OA.
Tuning the Electronic Structure of Monoclinic Tungsten Oxide Nanoblocks by Indium Doping for Boosted Photoelectrochemical Performance
Authors: Kumar Mohanta Manoj , Kanta Sahu Tushar , Alam Suhaib , Qureshi Mohammad
Published: October 2020

Photoelectrochemical (PEC) water oxidation, a desirable strategy to meet future energy demands, has several bottle‐necks to resolve. One of the prominent issues is the availability of charge carriers at the surface reaction site to promote water oxidation. Of the several approaches, metal dopants to enhance the carrier density of the semiconductors, is an important one. In this work, we have studied the effect of In‐doping on monoclinic WO3 nanoblocks, growing vertically over fluorine‐doped tin oxide (FTO) without the aid of any seed layer. X‐ray photoelectron spectroscopy (XPS) data reveals that In3+ ions are partially occupying the W6+ ions in In‐doped WO3 photoanode. In3+ ions are offering better performance by adding additional charge carriers for amplifying the expression of the number of carriers. The maximum current density value of 2.18 mA/cm2 has been provided by the optimized In‐doped WO3 photoanode with 3 wt% indium doping at 1.23 V vs. RHE, which is ∼3 times higher than that of undoped monoclinic WO3 photoanode. Mott‐Schottky (MS) analysis reveals charge carrier density (ND) for In‐doped WO3 photoanode has been enhanced by a factor of 3. An average Faradic yield of ∼90 percent has been achieved which can serve as a model system using In3+ as a dopant for an inexpensive and attractive method for enhanced WO3 based PEC water oxidation.
Age‐specific prevalence and determinants of depression in long‐term breast cancer survivors compared to female population controls
Authors: Doege Daniela , Thong Melissa S. Y. , Koch‐Gallenkamp Lena , Jansen Lina , Bertram Heike , Eberle Andrea , Holleczek Bernd , Pritzkuleit Ron , Waldmann Annika , Zeissig Sylke R. , Brenner Hermann , Arndt Volker
Published: October 2020

Background

Depression is more prevalent in breast cancer (BC) survivors than in the general population. However, little is known about depression in long‐term survivors. Study objectives were: (1) to compare the age‐specific prevalence of depressive symptoms (a) in BC survivors vs female population controls, (b) in disease‐free BC survivors vs BC survivors with self‐reported recurrence vs controls, and (2) to explore determinants of depression in BC survivors.

Methods

About 3010 BC survivors (stage I‐III, 5‐16 years post‐diagnosis), and 1005 population controls were recruited in German multi‐regional population‐based studies. Depression was assessed by the Geriatric Depression Scale‐15. Prevalence of mild/severe and severe depression only were estimated via logistic regression, controlling for age and education. Multinomial logistic regression was used to explore determinants of mild and severe depression.

Results

Compared with population controls, BC survivors were more likely to report mild/severe depression (30.4% vs 23.8%, p = .0003), adjusted for age and education. At all age groups <80 years, prevalence of both mild/severe and severe depression only was significantly higher in BC survivors, while BC survivors ≥80 years reported severe depression less frequently than controls. BC survivors with recurrence reported significantly higher prevalence of mild/severe depression than disease‐free survivors and controls, but prevalence in disease‐free survivors and controls was comparable. Age, income, living independently, recurrence, and BMI were significant determinants of mild depression in BC survivors. Age, education, employment, income, recurrence, and BMI were significant determinants of severe depression.

Conclusions

Long‐term BC survivors <80 years report significantly higher prevalence of depressive symptoms than controls, which might be explained by recurrence and individual factors. The findings suggest that depression in BC survivors is common, and even more after BC recurrence. Clinicians should routinize screening and normalize referral to psychological care.
C‐Terminal Tag Location Hampers in Vitro Profiling of OGT Peptide Substrates by mRNA Display
Authors: Shi Jie , Sharif Suhela , Balsollier Cyril , Ruijtenbeek Rob , Pieters Roland J. , Jongkees Seino A. K.
Published: October 2020

O‐GlcNAc transferase (OGT) is the only enzyme that catalyzes the post‐translational modification of proteins at Ser/Thr with a single β‐N‐acetylglucosamine (O‐GlcNAcylation). Its activity has been associated with chronic diseases such as cancer, diabetes and neurodegenerative disease. Although numerous OGT substrates have been identified, its accepted substrate scope can still be refined. We report here an attempt to better define the peptide‐recognition requirements of the OGT active site by using mRNA display, taking advantage of its extremely high throughput to assess the substrate potential of a library of all possible nonamer peptides. An antibody‐based selection process is described here that is able to enrich an OGT substrate peptide from such a library, but with poor absolute recovery. Following four rounds of selection for O‐GlcNAcylated peptides, sequencing revealed 14 peptides containing Ser/Thr, but these were shown by luminescence‐coupled assays and peptide microarray not to be OGT substrates. By contrast, subsequent testing of an N‐terminal tag approach showed exemplary recovery. Our approach demonstrates the power of genetically encoded libraries for selection of peptide substrates, even from a very low initial starting abundance and under suboptimal conditions, and emphasizes the need to consider the binding biases of antibodies and both C‐ and N‐terminal tags in profiling peptide substrates by high‐throughput display.
Synthesis and Coordination Behavior of a New Hybrid Bidentate Ligand with Phosphine and Silylene Donors
Authors: Nazish Mohd , Siddiqui Mujahuddin M. , Kumar Sarkar Samir , Münch Annika , Legendre Christina M. , Herbst‐Irmer Regine , Stalke Dietmar , Roesky Herbert W.
Published: October 2020

This work describes the synthesis and coordination behavior of a new mixed‐donor ligand PhC(NtBu)2SiC6H4PPh2 (1) containing both silylene and phosphine donor sites. Ligand 1 was synthesized from a reaction of ortho‐lithiated diphenylphosphinobenzene (LiC6H4PPh2) with chlorosilylene (PhC(NtBu)2SiCl). Treatment of 1 with Se and GeCl2 resulted in SiIV compounds 2 and 3 by selective oxidation of the silylene donor. This strong σ‐donor ligand induces dissociation of CuCl and PhBCl2 leading to formation of ionic complexes 4 and 5 respectively. The reaction of 1 with ZnCl2 and AlCl3 resulted in the formation of chelate complexes 5 and 7, respectively, while treatment with EtAlCl2 and GaCl3 forms monodentate complexes 8 and 9. X‐ray analysis of 4 showed that the copper is in the spiro center of the two five‐membered rings. Moreover, the copper(I)chloride has not been oxidized but dissociates to Cu+ and [CuCl2]−. All the compounds are well characterized by mass spectrometry, elemental analysis, NMR spectroscopy, and single‐crystal X‐ray diffraction studies.
Enhanced Stability and Emission Properties of Perylene Dyes by Surface Tethering: Preparation of Fluorescent Ru Nanoparticle Suspensions by Alkyne Linker Chemistry
Authors: Morais Eduardo , Moloney Cara , O'Modhrain Colin , McKiernan Eoin , Brougham Dermot F. , Sullivan James A.
Published: October 2020

Spherical ruthenium nanoparticles (NPs) with a narrow size distribution were synthesised in ethanol by a facile low‐temperature solvothermal process without the assistance of templates, structure‐directing agents or post annealing/reduction treatments. Surface passivation with a fluorescent perylene dye (EP), and with silane ligands (ETMS), both initially bearing alkyne groups and subsequently forming vinylidene linkages, provided stable suspensions of the marginally soluble free EP. Quantitative analysis of the suspension gave an estimated EP surface coverage of 15 %, corresponding to an EP/ETMS mole ratio of ≈1:6. Photophysical evaluation of the bound and free dye revealed similar absorption bands and extinction coefficients and improved properties for the bound state, including enhanced fluorescence in the visible range for the bound dye, an extended absorption range into the near‐UV providing strong emission in the visible, and significantly improved photostability. The physical basis of the enhanced photophysical properties, potential routes to further improvements and the implications for applications are discussed.
Excited State Dynamics of Isolated 6‐ and 8‐Hydroxyquinoline Molecules
Authors: Mestdagh Jean‐Michel , Poisson Lionel
Published: October 2020

The photoinduced dynamics of isolated n‐hydroxyquinoline (nHQ) molecules (n=6,8) was investigated in femtosecond pump‐probe experiments. A qualitative difference was found between 8HQ and 6HQ. After an initial rapid decay corresponding to the departure of the initial wavepacket out of the Franck‐Condon region of the excitation, the 8HQ probe signal decays to zero in 0.37 ps whereas a much longer time constant of 10.4 ps is observed in 6HQ. This interrogates on the role played by the intramolecular H‐bond N
HO which is at play the 8HQ molecule. Ab‐initio were performed at the MCSCF/aug‐cc‐pVDZ level on the 8HQ molecule to help the discussion. A complex energy landscape was found, which includes a conical intersection.
Individualized Dosing of Fluoropyrimidine‐Based Chemotherapy to Prevent Severe Fluoropyrimidine‐Related Toxicity: What Are the Options?
Authors: Knikman Jonathan E. , Gelderblom Hans , Beijnen Jos H. , Cats Annemieke , Guchelaar Henk‐Jan , Henricks Linda M.
Published: October 2020

Fluoropyrimidines are widely used in the treatment of several types of solid tumors. Although most often well tolerated, severe toxicity is encountered in ~ 20–30% of the patients. Individualized dosing for these patients can reduce the incidence of severe fluoropyrimidine‐related toxicity. However, no consensus has been achieved on which dosing strategy is preferred. The most established strategy for individualized dosing of fluoropyrimidines is upfront genotyping of theDPYDgene. Prospective research has shown thatDPYD‐guided dose‐individualization significantly reduces the incidence of severe toxicity and can be easily applied in routine daily practice. Furthermore, the measurement of the dihydropyrimidine dehydrogenase (DPD) enzyme activity has shown to accurately detect patients with a DPD deficiency. Yet, because this assay is time‐consuming and expensive, it is not widely implemented in routine clinical care. Other methods include the measurement of pretreatment endogenous serum uracil concentrations, the uracil/dihydrouracil‐ratio, and the 5‐fluorouracil (5‐FU) degradation rate. These methods have shown mixed results. Next to these methods to detect DPD deficiency, pharmacokinetically guided follow‐up of 5‐FU could potentially be used as an addition to dosing strategies to further improve the safety of fluoropyrimidines. Furthermore, baseline characteristics, such as sex, age, body composition, and renal function have shown to have a relationship with the development of severe toxicity. Therefore, these baseline characteristics should be considered as a dose‐individualization strategy. We present an overview of the current dose‐individualization strategies and provide perspectives for a future multiparametric approach.
Town mediation in Taiwan
Authors: Hera Gabor
Published: October 2020

The primary aim of this paper is to demonstrate the ways in which historical roots and social context have had an impact on mediation in Taiwan. During the investigation, the history, legal environment, and everyday practice of mediation were analyzed with particular attention to an out‐of‐court alternative dispute resolution method: town mediation. As the findings of a literature review and the qualitative field work confirm, town mediation only adheres to some principles of professionalism, and only to a limited extent. However, some specific features of town mediation that successfully contribute to peaceful conflict resolution are also discussed.
Organizational ambidexterity, green entrepreneurial orientation, and environmental performance in SMEs context: Examining the moderating role of perceived CSR
Authors: Shafique Imran , Kalyar Masood Nawaz , Mehwish Nadia
Published: October 2020

This study aims to investigate the effects of organizational ambidexterity and green entrepreneurial orientation (GEO) on the environmental performance of small‐ and medium‐sized enterprises (SMEs). Drawing upon social capital theory (SCT), this study suggests corporate social responsibility (CSR) as an important context that moderates the organizational ambidexterity–GEO nexus. Data were collected from 307 Pakistani manufacturing SMEs and analyzed through partial least squares (PLS)‐based structural equation modeling (SEM). The results provided empirical evidence in support of the study's hypotheses. The findings imply that the complexity and difficulty firms face in achieving environmental performance can be reduced through simultaneous exploration and exploitation of innovation as well as and through GEO. Furthermore, the effectiveness of ambidexterity in prompting GEO and subsequent environmental performance can be optimized as long as firms are capable of creating a suitable context, that is, CSR.
Keggin‐type Heteropolyacids‐Catalyzed Selective Hydrothermal Oxidation of Microalgae for Low Nitrogen Biofuel Production
Authors: Shen Zhensheng , Long Feiping , Ma Tian , Li Huan , Li An , Feng Qian , Liu Jiuyi , Sun Yingqiang
Published: October 2020

Hydrothermal liquefaction (HTL) of microalgae for biofuel production is suffering from low bio‐oil yield and high heteroatomic compositions owing to their low efficiency and selectivity to hydrolysis of cellular compounds. Hereby we report Keggin‐type (Mo−V−P) heteropolyacids (HPAs)‐catalyzed HTL of microalgae for efficient low‐nitrogen biocrude production. The increases of reaction temperature, reaction time, and vanadium substitution degrees of HPAs are favorable to biocrude yield initially, whereas a significant decrease of biocrude yield is observed owing to the enhanced oxidation of carbohydrates above the optimum reaction conditions. The maximum biocrude yield of HPAs‐catalyzed HTL of microalgae is 29.95 % at reaction temperature of 300 °C, reaction time of 2 h, and 5 wt% of HPA‐4, which is about 19.66 % higher than that of control with 71.17 % less N‐containing compounds, including 1,3‐propanediamine, 1‐pentanamine, and 2, 2’‐heptamethylene‐di‐2‐imidazoline than that of control. This work reveals that HPAs with Brønsted acidity and reversible redox properties are capable of both enhancing biocrude production via catalyzing the hydrolysis of cellular compounds and reducing their nitrogen content through avoiding the Maillard reactions between the intermediates of hydrolysis of carbohydrates and proteins. HPAs‐catalyzed HTL is an efficient strategy to produce low N‐containing biofuels, possibly paving the way of their direct use in modern motors.
Unlocking the Potential of Substrate‐Directed CO2 Activation and Conversion: Pushing the Boundaries of Catalytic Cyclic Carbonate and Carbamate Formation
Authors: Limburg Bart , Cristòfol Àlex , Della Monica Francesco , Kleij Arjan W.
Published: October 2020

The unparalleled potential of substrate‐induced reactivity modes in the catalytic conversion of carbon dioxide and alcohol or amine functionalized epoxides is discussed in relation to more conventional epoxide/CO2 coupling strategies. This conceptually new approach allows for a substantial extension of the substitution degree and functionality of cyclic carbonate/carbamate products, which are predominant products in the area of nonreductive CO2 transformations. Apart from the creation of an advanced library of CO2‐based heterocyclic products and intermediates, also the underlying mechanistic reasons for this novel reactivity profile are debated with a prominent role for the design and structure of the involved catalysts.
Genetic differentiation underlies seasonal variation in thermal tolerance, body size, and plasticity in a short‐lived copepod
Authors: Sasaki Matthew C. , Dam Hans G.
Published: October 2020

Organisms experience variation in the thermal environment on several different temporal scales, with seasonality being particularly prominent in temperate regions. For organisms with short generation times, seasonal variation is experienced across, rather than within, generations. How this affects the seasonal evolution of thermal tolerance and phenotypic plasticity is understudied, but has direct implications for the thermal ecology of these organisms. Here we document intra‐annual patterns of thermal tolerance in two species of Acartia copepods (Crustacea) from a highly seasonal estuary, showing strong variation across the annual temperature cycle. Common garden, split‐brood experiments indicate that this seasonal variation in thermal tolerance, along with seasonal variation in body size and phenotypic plasticity, is likely affected by genetic polymorphism. Our results show that adaptation to seasonal variation is important to consider when predicting how populations may respond to ongoing climate change.
Critical appraisal of the instantaneous end‐diastolic pulmonary arterial wedge pressures
Authors: Manouras Aristomenis , Lund Lars H. , Gellér László , Nagy Anikó Ilona , Johnson Jonas
Published: October 2020

Aims

A substantial shift in the field of pulmonary hypertension (PH) is ongoing, as the previous practice of mean pulmonary arterial wedge pressure (PAWPM) is no longer supported. Instead, aiming for a better estimate of end‐diastolic pressures (EDP), instantaneous PAWP at mid‐A‐wave (PAWPmid‐A) or, in the absence of an A‐wave, at 130–160 ms following QRS onset has recently been recommended. Electrocardiogram‐gated PAWP (PAWPQRS) has also been proposed. The quantitative differences as well as the diagnostic and prognostic utility of these novel PAWP measurements have not been evaluated. We set out to address these issues.

Methods and results

Pressure tracings of 141 patients with PH due to left heart disease (PH‐LHD) and 43 with primary pulmonary arterial hypertension (PAH) were analysed. PAWP was measured as follows: (i) mean pressure (PAWPM); (ii) per the latest consensus approach [PAWPmid‐A, or in atrial fibrillation 130, 140, 150, and 160 ms following QRS onset (PAWP130–160)]; (iii) at QRS onset (PAWPQRS); and (iv) Z‐point (PAWPZ). For each PAWP, the corresponding pulmonary vascular resistance (PVR) and diastolic pressure gradient were calculated. The cohort comprised 45% female. Mean age was 66 ± 15. PAWPmid‐A was in good agreement with PAWPZ (17.3 [14.5 to 21.2] vs. 17.6 [14.2 to 21.6] mmHg, P = 0.63), whereas PAWPQRS provided significantly lower values (15.3 [12.5 to 19.2] mmHg, P < 0.001). In atrial fibrillation, PAWP130 and PAWPQRS yielded the optimal temporal and quantitative analyses of EDPs. The ability to differentiate PAH from PH‐LHD was similar for the various PAWP measurements [PAWPM: area under the curve (AUC) 0.98, confidence interval (CI) 0.96–0.99; PAWPmid‐A/130: AUC 0.94, CI 0.91–0.98; PAWPQRS: AUC 0.96, CI 0.94–0.99, P < 0.001 for all]. PVR based on instantaneous PAWP measurements failed to provide superior prognostic information in PH‐LHD as compared with conventional PVR.

Conclusions

Although instantaneous PAWP measurement might better represent EDP, they nevertheless fail to yield incremental diagnostic or prognostic information in PH‐LHD as compared with conventional measurements.
Capillary zone electrophoresis of proteins applying ionic liquids for dynamic coating and as background electrolyte component
Authors: Mező Emerencia , Páger Csilla , Makszin Lilla , Kilár Ferenc
Published: October 2020

The use of ionic liquids in capillary electrophoresis, either as coating material or as components of the background electrolyte needs systematic standardization to set up optimal conditions. Excellent separation of the proteins was achieved using 1‐ethyl‐3‐methylimidazolium tetrafluoroborate ([emim][BF4]) or 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([bmim][BF4]) ionic liquids using the properly made ionic‐liquid–water binary mixtures for the experiments. The binary mixture has a distinctly stable and well perceptible low pH, which depends on the concentration of the ionic liquid, and on the preparation time of the mixture. Optimal conditions for the electrophoretic separation were obtained upon a multivariate analysis of the experimental parameters (applied voltage, migration time, concentration, and type of the ionic liquid). The standardized condition provides a low electroendosmotic flow toward the anode, which, however, did not hinder the proteins to migrate toward the cathode. The migration of cytochrome c, lysozyme, myoglobin, trypsin, and apo‐transferrin at a pH around 2, far below the isoelectric points of the proteins, showed RSD values of the migration times less than 7.5% and less than 6.5% when using [emim][BF4] or [bmim][BF4], respectively, either in run‐to‐run or day‐to‐day experiments. The determination of the extent of the EOF is not possible with the commonly used EOF markers, due to interaction with the ionic‐liquid constituents. The interaction of the ionic liquids with the proteins influences the migration order in zone electrophoresis. This method has been applied successfully for the analyses of real biological samples such as proteins from egg whites and human tears.
Fine‐grained gravity flow deposits and their depositional processes: A case study from the Cretaceous Nenjiang Formation, Songliao Basin, NE China
Authors: Tian Xing , Gao Yuan , Li Zhiyang , Carlos Zavala , Chen Zongyang , Huang Yongjian , Yu Enxiao , Wang Chengshan
Published: October 2020

The Songliao Basin in NE China is a large rift basin filled with Cretaceous terrestrial sediments. Lacustrine mudstones of the Nenjiang Formation form an important source rock in the Cretaceous Songliao Basin. These shales are commonly thought to have been deposited in deep, quiet, and anoxic environments. Samples obtained from the core of the SK‐2 scientific borehole provide critical insights to understand the hydrodynamic and hydroclimatic environments, which are, however, different from the traditional views regarding the deposition of these rocks. By following a mudstone description guide, five different mudstone lithofacies (LF) transported and deposited by muddy hyperpycnal flows and muddy debris flows were recognized. They are laminated fine mudstone (LF1), laminated medium mudstone (LF2), and laminated coarse mudstone (LF3) showing pairs of inverse grading (Ha) and normal grading (Hb) under the microscope, graded coarse mudstone (LF4) and massive coarse mudstone (LF5). We found that mudstones of the First Member of the Nenjiang Formation are dominated by siliciclastic detritus and argillaceous components and show frequent variations in grain size. Because large‐scale sub‐lacustrine channels travelling long distance (>80 km) were widely distributed in the Songliao palaeolake during the deposition of the Nenjiang Formation, fluctuations in mudstone grain size might have been caused by velocity fluctuations in flows. Sedimentary structures and textures preserved in mudstones of the First Member of the Nenjiang Formation indicate that the majority of these lithofacies were accumulated by muddy hyperpycnal flows and muddy debris flows. Therefore, a depositional model dominantly influenced by muddy hyperpycnal flows and debris flows is proposed. This work not only provides a new view for the depositional process of mudstones of the Songliao Basin, NE China, but also give insights to understand lacustrine palaeoenvironment and terrestrial palaeoclimate.
Cortical reorganization following auditory deprivation predicts cochlear implant performance in postlingually deaf adults
Authors: Sun Zhe , Seo Ji Won , Park Hong Ju , Lee Jee Yeon , Kwak Min Young , Kim Yehree , Lee Je Yeon , Park Jun Woo , Kang Woo Seok , Ahn Joong Ho , Chung Jong Woo , Kim Hosung
Published: October 2020

Long‐term hearing loss in postlingually deaf (PD) adults may lead to brain structural changes that affect the outcomes of cochlear implantation. We studied 94 PD patients who underwent cochlear implantation and 37 patients who were MRI‐scanned within 2 weeks after the onset of sudden hearing loss and expected with minimal brain structural changes in relation to deafness. Compared with those with sudden hearing loss, we found lower gray matter (GM) probabilities in bilateral thalami, superior, middle, inferior temporal cortices as well as the central cortical regions corresponding to the movement and sensation of the lips, tongue, and larynx in the PD group. Among these brain areas, the GM in the middle temporal cortex showed negative correlation with disease duration, whereas the other areas displayed positive correlations. Left superior, middle temporal cortical, and bilateral thalamic GMs were the most accurate predictors of post‐cochlear implantation word recognition scores (mean absolute error [MAE] = 10.1, r = .82), which was superior to clinical variables used (MAE: 12.1, p < .05). Using the combined brain morphological and clinical features, we achieved the best prediction of the outcome (MAE: 8.51, r = .90). Our findings suggest that the cross‐modal plasticity allowing the superior temporal cortex and thalamus to process other modal sensory inputs reverses the initially lower volume when deafness becomes persistent. The middle temporal cortex processing higher‐level language comprehension shows persistent negative correlations with disease duration, suggesting this area's association with degraded speech comprehensions due to long‐term deafness. Morphological features combined with clinical variables might play a key role in predicting outcomes of cochlear implantation.
Total Synthesis of (−)‐Rotundone and (−)‐epi‐Rotundone from Monoterpene Precursors
Authors: Rüthi Fabian , Schröder Fridtjof
Published: October 2020

The first total synthesis of (−)‐rotundone has been accomplished from (+)‐(R)‐limonene and therefore for the first time from an unrelated monoterpene instead of modifying structurally closely related sesquiterpene precursors such as α‐guaiene. Challenges such as intermediates with stereocenters prone to epimerization by enolization were overcome by designing a β‐methyl‐keto route starting from (+)‐(R)‐limonene which finally gave (−)‐rotundone by Nazarov cyclization of a precursor 13a. Diastereomer (−)‐epi‐rotundone was separated from (−)‐rotundone chromatographically. An alternative route from rac‐citronellal provided a diastereomer mixture of racemic Nazarov precursor 13 through a TRIP‐catalyzed intramolecular aldolization, thus indicating that the Nazarov cyclization precursor 13a is in principle accessible from (−)‐(S)‐citronellal. The 11‐step synthesis from (+)‐(R)‐limonene with ca. 1 % overall yield confirmed the absolute configuration of (−)‐rotundone and provided samples of good olfactory quality.
Does global value chain participation enhance domestic value‐added in exports? Evidence from emerging market economies
Authors: Jangam Bhushan Praveen , Rath Badri Narayan
Published: October 2020

This study aims to examine whether the participation of 24 emerging market economies (EMEs) in global value chains (GVCs) enhance the economic upgrading in the form of improvements in domestic value‐added exports over the period 1995–2011. To do so, first, the study explores the forward and backward participation in GVCs which shows an increasing level of GVCs participation. Second, this study empirically investigates the impact of GVCs on the domestic value‐added exports using panel feasible generalised least squares technique. The results reveal that both forward and backward participation has significantly improved the economic upgrading in case of EMEs. Further, the results show similar findings across several subgroups based on incomes, regions and others. Policies to foster greater GVC participation can help EMEs to tap the potential benefits associated.
Small business investment: The importance of financing strategies and social networks
Authors: Nguyen Bach
Published: October 2020

This study examines the association between financing strategies and firm investments. Employing theory of financing constraints and literature on formal/informal financing of small businesses to investigate a set of 15,851 observations of Vietnamese small businesses in 11 years, we suggest a pecking order of financing strategies in terms of firm investments, in ascending order as follows: (a) firms using no external finance, (b) firms using informal finance only, (c) firms using both formal and informal finance and (d) firms using formal finance only. In addition, we incorporate the theory of social capital to explore the moderating effect of networking on the relationship between financing and investment. Empirical results show that networks may enhance the relationship between informal finance and firm investments but not formal finance.
Detecting the athlete's abnormal emotions before competition via support vector data description
Authors: Gao Yue , Ma Ziyin
Published: October 2020

The athlete's emotions directly affect the quality of sport competition, which is an important factor that affects the action and competition effect. Therefore, it is very important to discover the athlete's abnormal emotions before competition in time. In this paper, we utilize the electromyography signal to monitor athlete emotions. First, we collect massive electromyography signal data from VICON system. Then, we remove the noises from collected electromyography signal data by using discrete wavelet transform. Lastly, we learn a support vector data description (SVDD) model from the clean data offline. The SVDD is a classical anomaly detection method which is widely used in finding abnormal events. The trained SVDD model is used to monitor the abnormal athlete's emotion automatically. The accuracy of monitoring athlete's abnormal emotions achieves 87.34%.
Immunobiology and immunotherapy of COVID‐19: A clinically updated overview
Authors: Esmaeilzadeh Abdolreza , Elahi Reza
Published: October 2020

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a new member of the coronavirus family that can cause coronavirus disease 2019 (COVID‐19). COVID‐9 has become a global pandemic with severe health issues around the world. Identifying the accurate immunopathogenesis of the COVID‐19 and the immune response against SARS‐CoV‐2 is necessary for the development of therapeutic approaches and rational drug design. This paper aims to overview the updated clinical data on the immunopathogenesis of the COVID‐19 and review the innate and adaptive immune response to SARS‐CoV‐2. Also, challenges of the immune response to SARS‐CoV‐2 leading to dysfunctional immune response and their contribution to the progression of the disease have been discussed. To achieve a more efficient immune response, multiple methods could be applied, including regulation of the immune response, augmentation of the immune system against the virus, inhibition of the dysfunctional immune checkpoints, and inhibition of the viral replication/infection. Based on the immune response against SARS‐CoV‐2 and its dysfunction, we introduce potential immunotherapies as well as reviewing recruiting/completed clinical trials of COVID‐19.