bluuebunny/crossref_metadata_2025 huggingface dataset:
The new technology for increase goat cashmere yields
Authors: D Dorligsuren
Published: May 2018

As of 2016, the number of livestock has reached 61.5 million heads exceeding the pasture carrying capacity by 156 percent and over 9-10 times in some aimags and soums, which negatively affects the future sustainable growth and development of the livestock sector. One of the ways to reduce the pasture stocking rate and increase the income of herders is to increase the output per animal. A recent experiment in Mongolia demonstrates that herding Mongolian goats in specially designed dark shelter (darkness of the shelter is 0.1-0.5 lux) from 5 pm to 9 am in summer from May 15th to September 15th led to 50% reduction in grazing pressure and increase in cashmere yield and average cashmere length by 52% and 50-53% respectively, with cashmere diameter narrowed by 1.6%.
Effects of tourism on the herder’s lifestyle in Mongolia
Authors: B Shoshvandan , L Bayasgalan
Published: May 2018

The "Sustainable Development Complex Policy in Mongolia 2030" document represents the "Nomadic Culture" as a tourist hub, indicating that nomadic lifestyle is the main attraction in tourism. One of the main issues of concern for tourism in Mongolia is to focus on the herder lifestyle that differs from each other depending on natural zones. Therefore, we aim to study the different types of farming and lifestyle in such regions, as the Gobi, arid steppe, steppe, forest steppe and high mountain zone and determine which types of tourism are more convenient in each region.
Cuarenta años de Monarquía parlamentaria (Balance)
Authors: Torres del Moral Antonio
Published: May 2018

Resumen:En este artículo se ofrece una balance de la monarquía española durante 40 años, desde la sucesión de Franco Bahamonde por Juan Carlos I hasta la abdicación y la sucesión de Felipe VI. Por último se hace una propuesta dereforma constitucional en doce puntos.Abstract:In this article we offer a balance of the monarchy Spanish for 40 years, since the succession of Franco Bahamonde until the abdication of Juan Carlos I and the succession of Felipe VI. Finally, a proposal for a constitutional amendement is made in twelve points.Summary:1. Introduction. 2. From the Francoist Dictatorship to the establishment of the monarchy. 3. Monarchy and demolition of the Franco regime. 4. Monarchy and Constitution: 4.1. The Monarchy after the promulgation of the Constitution. 4.2. Succession system. Oath. 4.3. Monarchy and Armed Forces. 4.4. Inviolability and International Criminal Court. 5. Monarchy and public opinion. 6. Abdication of Juan Carlos I. 7. From Crown Prince to Felipe VI: 7.1. Apprenticeship. 7.2. A monarchy renewed for a new time. 8. Catalan crisis and message right. 8. Twelve touches to the Institution: 8.1. Approach. 8.2. No need for constitutional reform. 8.3. With mandatory constitutional reform.
La función de Gobierno en la Constitución española, cuarenta años después
Authors: Porras Nadales Antonio
Published: May 2018

Resumen:El modelo constitucional español expresa una apuesta por la gobernabilidad que nace del contexto histórico propio del parlamentarismo racionalizado y se fundamenta sobre un sistema electoral establecido desde 1977. Sin embargo tanto la configuración orgánica del ejecutivo como la puesta en práctica de la función de gobierno han tenido un desarrollo bastante limitado en la práctica, y algunas tareas centrales como la orientación estratégica, la programación de políticas públicas o la coordinación general del sistema se han reducido a puras inercias.Abstract:The Spanish constitutional model express a commitment to gobernability that is born from the historical context of «rationalized parlamentarism» and is based on an electoral system established since 1977. However, both the organic configuration of the executive and the implementation of the function of governing have had a rather limited development in practice, while some central tasks such as strategic orientation, public policy programing and overall system coordination, have been reduced to pure inertia.Summary:1. Introduction. 2. Government and governability: the starting point. 3. The function of government as a political function. 4. Government and governance: unfulfilled challenges. 5. A mediocre balance and its advantages. 6. Perspectives of historical change. 7. Final considerations.
La revocación de senadores de designación autonómica (la Ley valenciana 10/2016 y la STC 123/2017)
Authors: Navarro Marchante Vicente
Published: May 2018

Resumen:La Comunidad Autónoma Valenciana aprobó a finales del pasado año la Ley 10/2016 que modificaba varios aspectos de la ley territorial que regulaba diferentes aspectos en torno a la designación de senadores en representación de la Comunidad Autónoma. La nueva norma introduce, de forma novedosa en nuestro derecho, la posibilidad de revocación del senador designado por el parlamento autonómico, además de establecer la obligatoriedad del senador de comparecencia ante la cámara designante como forma de rendición de cuentas. La posibilidad de revocación del senador por pérdida de confianza de la cámara autonómica planteaba dudas de constitucionalidad por, entre otros, posible vulneración de la prohibición de mandato imperativo de los miembros de las Cortes Generales, ya resueltas por la STC 123/2017. El presente artículo, al hilo del análisis de la norma valenciana y su encaje constitucional, reflexiona sobre la naturaleza del mandato representativo y la peculiar función de la cámara derepresentación territorial.Abstract:The Valencian Autonomous Community approved at the end of last year the Law 10/2016 that modified several aspects of the territorial law that regulated different aspects about the appointment of senators in representation of the Autonomous Community. The new norm introduces, in a novel way in our right, the possibility of revocation of the senator appointed by the autonomic parliament, in addition to establishing the mandatory of the senator of appearance in the designating chamber as a form of accountability. The possibility of revocation of the senator due to loss of confidence of the autonomous chamber raises doubts of constitutionality by, among others, possible violation of the prohibition of imperative mandate of the members of the Cortes Generales, already resolved by STC 123/2017. This article, along the lines of the analysis of the Valencian norm and its constitutional reserve, reflects over the nature of the representative mandate and the peculiar function of the chamber of territorial representation.
El modelo de responsabilidad del Gobierno en la Constitución de 1978 o jugar a las siete y media
Authors: González Hernández Esther
Published: May 2018

Resumen:El presente paper, analiza el régimen de responsabilidad del Gobierno contenido en la Constitución española de 29 de diciembre de 1978 desde una doble vertiente. Por un lado, explica las normas constitucionales que regulan el régimen de responsabilidad gubernamental tanto jurídica como política. Por otro, centra su atención en el desarrollo de las previsiones constitucionales en los cuarenta años de vigencia de nuestra Carta Magna, comentando los supuestos más sobresalientes de juicios penales en los que se ha visto inmersos ex-miembros del Consejo de Ministros y como las «cuestiones de confianza» o «mociones de censura» que han tenido lugar en sede parlamentaria. Por último, analiza, desde un punto de vista crítico, las insuficiencias del sistema y añade propuestas de futuro.Abstract:This paper analyzes the regime of government responsibility/responsiveness in the 1978 Spanish Constitution from a dual perspective. On one hand, it explains the constitutional rules that govern the regime of governmental responsibility/responsiveness, both legal and political. On the other hand, it focuses on the development of the constitutional provisions in the 40 years of our Constitution, commenting on the most outstanding cases of criminal trials in which former members of the Council of Ministers have been involved, such as «votes of confidence» or «motions of censorship» that have taken place in parliamentary seat. Finally, it analyzes, from a critical perspective, the inadequacies of the system and adding proposals for the future.SummaryI. 1978: A Constitution, without doubt, meritorious, II. From criminal responsibility to political responsibility. III. The Government’s responsibility in the 1978s Spanish Constitution: A. Art. 102 and criminal responsibility, B. Political responsibility through censure: a. A forgotten «vote of confidence», b. The «motion of censure»: three times and no resignation, IV. The future is coming. Bibliography.
La ejecución de las resoluciones del Tribunal Constitucional. ¿Un cambio de modelo de justicia constitucional?
Authors: Álvarez Conde Enrique
Published: May 2018

Resumen:La reforma, en 2015, de la LOTC ha supuesto importantes consecuencias jurídicas y políticas. En cuanto a las primeras se refiere, la reforma ha puesto en tela de juicio nuestro modelo de justicia constitucional así como la propia posición del Tribunal en relación con los demás poderes del Estado. Desde el punto de vista político, la reforma, aprobada precipitadamente y al final de la legislatura, esta concebida únicamente para resolver el problema soberanista catalán, situando en sede jurisdiccional decisiones políticas que nunca corresponden a un órgano de Justicia Constitucional. Como señaló la propia Comisión de Venecia, en su informe de marzo del 2017, y pese a haber sido declarada constitucional la reforma realizada, no es recomendable que estas competencias de ejecución sean atribuidas al Tribunal Constitucional.Abstract:The Spanish Constitutional Court Organization Act reform of 2015 has had significant legal and political repercussions. From a legal perspective, the reform has called into question both our constitutional justice model and the Court’s role in relation to other State powers. From a political point of view, the unwisely rush in adopting said reform at the end of the parliamentary term, was solely intended to resolve the Catalan sovereignty issue, thus placing political decisions at the hands of a Constitutional Court that should not be deciding on such matters. As pointed out by the Venice Commission itself, in its report of March 2017, and despite the reform´s constitutionality, attributing such enforcement powers to the Constitutional Court is not recommended. Summary:I. General remarks. II. Theoretical issues raised: A) The likely disruption of the Constitutional Justice model. B) The notion of Constitutional Review. C) Enforcement as a constituent element of the jurisdictional function. III. New measures for enforcing Constitutional Court decisions: A) The nature of the sentences. B) The default rules. C) The position of the Court in relation to the implementation of its decisions. D) The imposition of fines. E) Suspension of duties. F) Execution of alternative measures. G) Adoption of other necessary measures. IV. Implementation of the corresponding enforcement measures.
Topique et poétique du sublime. La leçon du laconisme quignardien
Authors: Declercq Gilles
Published: May 2018

Une affinité stellaire lie Pascal Quignard à l’auteur du Traité du sublime. Est donc ici étudiée la topique commune au sublime longinien et quignardien (energeia du transport pathétique ; court-circuit de la raison par le raptus esthétique ; emprise impérieuse du sensible sans logos). Ce sublime prend chez Quignard la forme verbale du laconisme, forme-sens qui confère au style le statut d’une arme de survie qui permet au lecteur, à l’écrivain et au penseur de tenir face aux forces prédatrices sous-jacentes au langage. Cette poïétique du style soustractif propre à la sentence foudroyante s’arrime au versant narratif de l’oeuvre par la ligature discrète de l’argumentation paradigmatique où l’assertion, thèse spéculative, trouve son argument dans l’essor même du récit.
Pascal Quignard : du monument à la ruine, de la ruine au vivant
Authors: Vuong Léa
Published: May 2018

Si la ruine est un motif omniprésent chez Pascal Quignard, l’auteur semble aussi poursuivre une ambition monumentale, celle du Dernier royaume, commencée en 2002 et qu’il poursuit toujours aujourd’hui. Cet article explore l’hésitation entre l’élaboration d’un monument littéraire et l’esthétique des ruines qui irrigue les textes de Quignard. Il donne une place privilégiée à des ouvrages récents, comme Sur l’idée d’une communauté de solitaires (2015), et aux dialogues avec d’autres arts tels que la musique, la danse et l’art visuel. Cette étude s’intéresse également aux fragments de textes et aux figures obscures, parfois dissimulées, qui nourrissent et influencent l’oeuvre : Roland Barthes, Walter Benjamin, mais aussi les artistes Carlotta Ikeda et Pierre Skira. Cet article montre d’abord les ruines comme des supports solides qui soutiennent la construction de monuments littéraires où Quignard commémore le souvenir d’êtres disparus. Puis, en s’appuyant sur la notion de « ruinophilie » développée par Svetlana Boym, cette étude expose la porosité des ruines quignardiennes, et s’intéresse à la manière dont elles laissent filtrer d’autres motifs, celui de la nature et du corps, à travers lesquels l’écrivain élabore, dans son écriture, de nouvelles manières de vivre dans le temps et dans l’espace.
Improving productivity while managing extensive molecular dynamics simulation data
Authors: Bandyopadhyay Avimanyu
Published: May 2018

This paper discusses the difficulties experienced by bioinformaticians while working with extensive data generated from extended molecular dynamics simulations. For better experimental analysis, it often becomes crucial to conduct simulations up to extended periods of time. When with limited resources, running a complete simulation up to a desired length of time can become quite difficult to be performed at one go. So, a new approach is proposed to simplify handling such data for better productivity.
A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells
Authors: Betleja Ewelina , Nanjundappa Rashmi , Cheng Tao , Mahjoub Moe R
Published: May 2018

The two centrioles of the centrosome in quiescent cells are inherently asymmetric structures that differ in age, morphology and function. How these asymmetric properties are established and maintained during quiescence remains unknown. Here, we show that a daughter centriole-associated ciliopathy protein, Cep120, plays a critical inhibitory role at daughter centrioles. Depletion of Cep120 in quiescent mouse and human cells causes accumulation of pericentriolar material (PCM) components including pericentrin, Cdk5Rap2, ninein and Cep170. The elevated PCM levels result in increased microtubule-nucleation activity at the centrosome. Consequently, loss of Cep120 leads to aberrant dynein-dependent trafficking of centrosomal proteins, dispersal of centriolar satellites, and defective ciliary assembly and signaling. Our results indicate that Cep120 helps to maintain centrosome homeostasis by inhibiting untimely maturation of the daughter centriole, and defines a potentially new molecular defect underlying the pathogenesis of ciliopathies such as Jeune Asphyxiating Thoracic Dystrophy and Joubert syndrome.
Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function
Authors: Geng Jie , Altman John D , Krishnakumar Sujatha , Raghavan Malini
Published: May 2018

When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8+ T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for HLA-I alleles such as HLA-B*35:01, peptide-deficient (empty) heterodimers are thermostable and detectable on the cell surface. Additionally, peptide-deficient HLA-B*35:01 tetramers preferentially bind CD8 and to a majority of blood-derived CD8+ T cells via a CD8-dependent binding mode. Further functional studies reveal that peptide-deficient conformers of HLA-B*35:01 do not directly activate CD8+ T cells, but accumulate at the immunological synapse in antigen-induced responses, and enhance cognate peptide-induced cell adhesion and CD8+ T cell activation. Together, these findings indicate that HLA-I peptide occupancy influences CD8 binding affinity, and reveal a new set of regulators of CD8+ T cell activation, mediated by the binding of empty HLA-I to CD8.
Robust control and data‐driven tuning of a hybrid integrator‐gain system with applications to wafer scanners
Authors: Heertjes M.F. , Irigoyen Perdiguero N. , Deenen D.A.
Published: May 2018

A hybrid integrator‐gain system is discussed that aims for improved low‐frequency disturbance rejection, while, at the same time, does not deteriorate overshoot and settling times when compared with a linear integrator. The hybrid integrator has similar phase advantages as the well‐known Clegg integrator but without inducing the discontinuous behavior resulting from resetting system state values. Optimal tuning of the controller parameters of the hybrid integrator is strongly influenced by machine‐specific properties and therefore favors a data‐driven optimization approach. However, as a time‐domain optimization algorithm can easily lead to nonrobust solutions in the sense of large peaking of the closed‐loop frequency response functions, frequency‐domain robustness constraints will be imposed. By means of an adaptive weighting filter design, the parameter updates are penalized upon violation of said robustness constraints. Posed in an unconstrained problem formulation, this is subsequently solved by applying a Gauss‐Newton–based parameter update scheme. Closed‐loop stability of the linear time‐invariant plant and controller in feedback connection with a hybrid integrator‐gain system element follows from a circle‐criterion‐like analysis, which is based on evaluating (measured) frequency response data. Measurement results obtained from an industrial wafer scanner demonstrate the effectiveness of the approach.
Microstructure, Phase Composition, and Thermal Stability of Two Zirconium Alloys Subjected to High‐Pressure Torsion at Different Temperatures
Authors: Rogachev Stanislav. O. , Nikulin Sergey A. , Rozhnov Andrey B. , Gorshenkov Mikhail V.
Published: May 2018

The structure, phase composition, and thermal stability of the industrial zirconium alloys, namely, E110 (Zr–1% Nb) and E635 (Zr–1% Nb–0.3% Fe–1.2% Sn), which are subjected to high‐pressure torsion (HPT) at room temperature (RT), 200, and 400 °С have been studied. HPT of Zr‐alloys at RT (10 revolutions) leads to the formation of grain–subgrain nano‐sized structure and to increase the microhardness by 2.1…2.8 times. The increase in the HPT temperature to 200–400 °С leads to the increase in the structural‐element average size. The structural‐element size in the complexly alloyed E635 alloy in all cases is lower compared with the E110 alloy. The hardening of the alloys after HPT at RT and 200 °С is close, and at 400 °С is much less. HPT initiates the α‐Zr → (ω‐Zr + β‐Zr) transformation, which is the main factor for alloys hardening. The α‐Zr → (ω‐Zr + β‐Zr) transformation in the E635 alloy occurs less quickly. The maximum amount (ω‐Zr + β‐Zr) phase in the structure of the alloys is observed after HPT at RT and 200 °C, and the minimum − at 400 °C. During heating, the alloys undergo the reverse (ω‐Zr + β‐Zr) → α transformation which depends on both the alloy composition and HPT temperature.
Low‐Bandgap Polymers for High‐Performance Photodiodes with Maximal EQE near 1200 nm and Broad Spectral Response from 300 to 1700 nm
Authors: Han Jinfeng , Yang Dezhi , Ma Dongge , Qiao Wenqiang , Wang Zhi Yuan
Published: May 2018

Polymer photodiodes with broad spectral response above 1500 nm can be used for imaging in the near‐infrared window of the atmosphere. Three low‐bandgap polymers based on 3,6‐dithiophen‐2‐yl‐2,5‐dihydropyrrolo[3,4‐c]pyrrole‐1,4‐dione (DPP), [1,2,5]thiadiazolo[3,4‐g]quinoxaline (TQ), benzobisthiadiazole (BBT), and dithienopyrrole (DTP) are designed and synthesized. No‐gain and gain polymer photodiodes with polymers:PC71BM as active layer materials and with aluminum doped ZnO nanoparticles:2,9‐bis(3‐(dimethylamino)propyl)anthra[2,1,9‐def:6,5,10‐d′e′f′]diisoquinoline‐1,3,8,10(2H,9H)‐tetraone (AZO:PDIN), MoO3, and 2,9‐dimethyl‐4,7‐diphenyl‐1,10‐phenanthroline (BCP) as interlayer materials are prepared. No‐gain photodiodes based on polymer P1 exhibit the external quantum efficiency (EQE) of 7.8% at 1200 nm, which is among the best values of polymer photodiodes known to date. Gain photodiodes based on P1 and P3 also exhibit a maximal EQE near 1200 nm. In addition, gain photodiodes based on P1 have a specific detectivity over 1013 Jones in 300–1360 nm and spectral response in the region of 300–1700 nm.
Single Plasmonic Oligomer Chiral Spectroscopy
Authors: Karst Julian , Strohfeldt Nikolai , Schäferling Martin , Giessen Harald , Hentschel Mario
Published: May 2018

Chirality plays a crucial role in our everyday lives. Many biomolecules are handed and the associated biological processes rely on their handedness. Thus, chirality is investigated intensely, also because of the fundamental and inherent interest in the concept of chirality. However, virtually all studies are performed on large ensembles of chiral objects, which obstructs the contribution of the individual particle. Hence, it is highly desirable to study individual chiral objects. Here, it is shown how to measure chiroptical spectra in the visible spectral range of left‐ and right‐handed C4 symmetric single plasmonic nanoantenna ensembles, which are termed oligomers. The two‐layered oligomers are fabricated by top‐down electron beam lithography to offer a high degree of structural control. Dark‐field scattering spectroscopy as well as correlative scanning electron microscopy are utilized to study the influence of structural arrangement and individual shape on the optical properties of a single plasmonic oligomer. Even minute structural differences, which cannot be resolved in scanning electron microscopy, manifest themselves in clear differences in the chiroptical response. The results play an important role for further investigations and optimizations in design, fabrication, and measurements of single plasmonic enantiomers but also on the way toward single chiral object sensing.
Model Guided Development of a Simple Catalytic Method for the Synthesis of Unsymmetrical Stilbenes by Sequential Heck Reactions of Aryl Bromides with Ethylene
Authors: Barlow Helen , Buser Jonas Y. , Glauninger Hendrik , Luciani Carla V. , Martinelli Joseph R. , Oram Niall , Thompson‐Van Hook Nichole , Richardson Jeffery
Published: May 2018

Stilbenes are important and useful structural moieties, but methods for their preparation typically possess numerous inefficiencies. Presented here is a methodology for the two‐step, one pot preparation of unsymmetrical stilbenes via sequential Heck reactions. The first Heck reaction with ethylene gas was analysed as a function of temperature and pressure for electronically differentiated naphthyl bromides and model‐aided reaction optimization was utilized to define the system. In addition, reactNMR was utilized to determine ethylene solubility in common organic solvents useful for Heck reactions. Finally, an optimized sequential Heck reaction process was developed and applied to a range of substrates allowing for efficient preparation of unsymmetrical stilbenes, including the natural antioxidant, pterostilbene.

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De novo gain‐of‐function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy
Authors: Ambrosino Paolo , Soldovieri Maria Virginia , Bast Thomas , Turnpenny Peter D. , Uhrig Sabine , Biskup Saskia , Döcker Miriam , Fleck Thilo , Mosca Ilaria , Manocchio Laura , Iraci Nunzio , Taglialatela Maurizio , Lemke Johannes R.
Published: May 2018

Variants in several potassium channel genes have been found in developmental and epileptic encephalopathies (DEE). We report on 2 females with de novo variants in KCNT2 with West syndrome followed by Lennox‐Gastaut syndrome or with DEE with migrating focal seizures. After in vitro analysis suggested quinidine‐responsive gain‐of‐function effects, we treated 1 of the girls with quinidine add‐on therapy and achieved marked clinical improvements. This suggests that the new spectrum of KCNT2‐related disorders do not only share similar phenotypic and in vitro functional and pharmacological features with previously known KCNT1‐related disorders, but also represents a further example for possible precision medicine approaches. Ann Neurol 2018;83:1198–1204
Neue Methoden und Designprinzipien für zellgängige Peptide
Authors: Peraro Leila , Kritzer Joshua A.
Published: May 2018

Biomoleküle, wie Antikörper, Proteine und Peptide, sind wichtige Werkzeuge in der chemischen Biologie und Ansatzpunkte für die Wirkstoffentwicklung. Sie wurden erfolgreich verwendet, um eine Reihe von extrazellulären Proteinen zu inhibieren, allerdings stellt die Interaktion mit intrazellulären Proteinen eine weit größere Herausforderung dar. In dieser Aufsatz diskutieren wir unterschiedliche chemische Ansätze, die zu zellgängigen Peptiden geführt haben, und identifizieren drei eigenständige Vorgehensweisen: die Maskierung von Rückgratamiden, die Strukturierung von Guanidingruppen und die amphipathische Strukturierung. Wir fassen zusammen, wie anhand großer Datensätze, die in steigendem Maße entstehen, spezifischere Designprinzipien für jede dieser Strategien abgeleitet werden können. Wir beschreiben außerdem Vor‐ und Nachteile gängiger Methoden zur Quantifizierung der Zellpenetration. Abschließend geben wir eine Übersicht über die vielversprechendsten Ansätze für die Anwendung dieser neuen Methoden und Designprinzipien zur Optimierung der zytosolischen Penetration eines bioaktiven Peptids.
Dipole Effects on Electron Transfer are Enormous
Authors: Krzeszewski Maciej , Espinoza Eli M. , Červinka Ctirad , Derr James B. , Clark John A. , Borchardt Dan , Beran Gregory J. O. , Gryko Daniel T. , Vullev Valentine I.
Published: May 2018

Molecular dipoles present important, but underutilized, methods for guiding electron transfer (ET) processes. While dipoles generate fields of Gigavolts per meter in their vicinity, reported differences between rates of ET along versus against dipoles are often small or undetectable. Herein we show unprecedentedly large dipole effects on ET. Depending on their orientation, dipoles either ensure picosecond ET, or turn ET completely off. Furthermore, favorable dipole orientation makes ET possible even in lipophilic medium, which appears counterintuitive for non‐charged donor–acceptor systems. Our analysis reveals that dipoles can substantially alter the ET driving force for low solvent polarity, which accounts for these unique trends. This discovery opens doors for guiding forward ET processes while suppressing undesired backward electron transduction, which is one of the holy grails of photophysics and energy science.
Electro‐Oxidative S−H/S−H Cross‐Coupling with Hydrogen Evolution: Facile Access to Unsymmetrical Disulfides
Authors: Huang Pengfei , Wang Pan , Tang Shan , Fu Zhuangjiong , Lei Aiwen
Published: May 2018

Sulfur is an essential element because it exists widely in proteins. The disulfide bond is an important moiety in many different types of significant organic molecules. A new approach for oxidant‐ and catalyst‐free S−H/S−H cross‐coupling, with hydrogen evolution, to construct unsymmetrical disulfides was developed. Under the conditions of an undivided cell at room temperature, a series of unsymmetrical disulfides were prepared with up to 87 % yield from the direct coupling of an aryl mercaptan and alkyl mercaptan. Gram‐scale synthesis also highlights the synthetic utility of this electrochemical strategy.
Effective Assignment of α2,3/α2,6‐Sialic Acid Isomers by LC‐MS/MS‐Based Glycoproteomics
Authors: Pett Christian , Nasir Waqas , Sihlbom Carina , Olsson Britt‐Marie , Caixeta Vanessa , Schorlemer Manuel , Zahedi René P. , Larson Göran , Nilsson Jonas , Westerlind Ulrika
Published: May 2018

Distinct structural changes of the α2,3/α2,6‐sialic acid glycosidic linkages on glycoproteins are of importance in cancer biology, inflammatory diseases, and virus tropism. Current glycoproteomic methodologies are, however, not amenable toward high‐throughput characterization of sialic acid isomers. To enable such assignments, a mass spectrometry method utilizing synthetic model glycopeptides for the analysis of oxonium ion intensity ratios was developed. This method was successfully applied in large‐scale glycoproteomics, thus allowing the site‐specific structural characterization of sialic acid isomers.
Highly Productive Oxidative Biocatalysis in Continuous Flow by Enhancing the Aqueous Equilibrium Solubility of Oxygen
Authors: Chapman Michael R. , Cosgrove Sebastian C. , Turner Nicholas J. , Kapur Nikil , Blacker A. John
Published: May 2018

We report a simple, mild, and synthetically clean approach to accelerate the rate of enzymatic oxidation reactions by a factor of up to 100 when compared to conventional batch gas/liquid systems. Biocatalytic decomposition of H2O2 is used to produce a soluble source of O2 directly in reaction media, thereby enabling the concentration of aqueous O2 to be increased beyond equilibrium solubility under safe and practical conditions. To best exploit this method, a novel flow reactor was developed to maximize productivity (g product L−1 h−1). This scalable benchtop method provides a distinct advantage over conventional bio‐oxidation in that no pressurized gas or specialist equipment is employed. The method is general across different oxidase enzymes and compatible with a variety of functional groups. These results culminate in record space‐time yields for bio‐oxidation.
Shadow Mask Templates for Site‐Selective Metal Exchange in Magnesium Porphyrin Nanorings
Authors: Bols Pernille S. , Anderson Harry L.
Published: May 2018

Molecular templates can be used in many different ways to control the outcome of chemical reactions. Herein, we present a new type of template‐directed synthesis. We show that templates can be used as shadow masks: The shape of the template becomes imprinted on the product because reactions only occur at sites not masked by the template. We demonstrate this effect by using oligopyridine templates to dictate the sites of demetalation when a magnesium porphyrin nanoring is treated with acid. Magnesium centers that are coordinated to the template are protected whereas uncoordinated magnesium centers are removed. After site‐selective demetalation, the template can be removed, and other cations, such as zinc(II) and copper(II), can be inserted into the free‐base porphyrin centers. This strategy provides a simple route to a wide range of heterometalated porphyrin arrays.
Electrophilic Formylation of Arenes by Silylium Ion Mediated Activation of Carbon Monoxide
Authors: Omann Lukas , Qu Zheng‐Wang , Irran Elisabeth , Klare Hendrik F. T. , Grimme Stefan , Oestreich Martin
Published: May 2018

Arene‐stabilized silylium ions react with carbon monoxide rather than carbon monoxide adducts of silylium ions reacting with arenes. This mechanism is supported by quantum‐chemical calculations. Even sterically hindered mesitylene and electronically deactivated chlorobenzene engage in this electrophilic aromatic substitution. The silylium ion mediated formylation corresponds to Gattermann–Koch reactions promoted by strong Brønsted acids. The resulting silylcarboxonium ion of the arenecarbaldehyde was crystallographically characterized, for the first time revealing the molecular structure of this synthetically important intermediate.
From Metal–Organic Frameworks to Single‐Atom Fe Implanted N‐doped Porous Carbons: Efficient Oxygen Reduction in Both Alkaline and Acidic Media
Authors: Jiao Long , Wan Gang , Zhang Rui , Zhou Hua , Yu Shu‐Hong , Jiang Hai‐Long
Published: May 2018

It remains highly desired but a great challenge to achieve atomically dispersed metals in high loadings for efficient catalysis. Now porphyrinic metal–organic frameworks (MOFs) have been synthesized based on a novel mixed‐ligand strategy to afford high‐content (1.76 wt %) single‐atom (SA) iron‐implanted N‐doped porous carbon (FeSA‐N‐C) via pyrolysis. Thanks to the single‐atom Fe sites, hierarchical pores, oriented mesochannels and high conductivity, the optimized FeSA‐N‐C exhibits excellent oxygen reduction activity and stability, surpassing almost all non‐noble‐metal catalysts and state‐of‐the‐art Pt/C, in both alkaline and more challenging acidic media. More far‐reaching, this MOF‐based mixed‐ligand strategy opens a novel avenue to the precise fabrication of efficient single‐atom catalysts.
Catalytic Enantioselective Cloke–Wilson Rearrangement
Authors: Ortega Alesandere , Manzano Rubén , Uria Uxue , Carrillo Luisa , Reyes Efraim , Tejero Tomas , Merino Pedro , Vicario Jose L.
Published: May 2018

Racemic cyclopropyl ketones undergo enantioselective rearrangement to deliver the corresponding dihydrofurans in the presence of a chiral phosphoric acid as the catalyst. The reaction involves activation of the donor‐acceptor cyclopropane substrate by the chiral Brønsted acid catalyst to promote the ring‐opening event, thus generating a carbocationic intermediate that subsequently undergoes cyclization. Computational studies and control experiments support this mechanistic pathway.
Synthesis, characterization and theoretical and fluorescence emission microscopy studies of new Pd/Pt–cyclopropa[60]fullerene complexes: Application of Taguchi method for optimization of parameters in Suzuki–Miyaura reaction
Authors: Sabounchei Seyyed Javad , Badpa Khadijeh , Hashemi Ali , Salehzadeh Sadegh , Maleki Farahnaz , Hosseinzadeh Leila
Published: May 2018

The reactions of unsymmetric phosphorus ylides of the type [Ph2P(CH2)nPPh2C(H)C(O)C6H4‐p‐CN] (n = 1 (Y1); n = 2 (Y2)) with C60 and M(dba)2 (M = Pd or Pt; dba = dibenzylideneacetone) are reported. Based on the various coordination modes of these ylides in complexation, the following new Pd/Pt–cyclopropa[60]fullerene complexes were obtained: P,C‐coordinated [(η2‐C60)Pd(κ2‐Y1)] (1) and [(η2‐C60)Pt(κ2‐Y1)] (2) complexes and P‐coordinated [(η2‐C60)Pd(Y2)2] (3) and [(η2‐C60)Pt(Y2)2] (4) complexes. These compounds were characterized using Fourier transform infrared, UV–visible and NMR (1H, 13C and 31P) spectroscopies and scanning electron microscopy. Furthermore, cytotoxicity studies showed that nanoparticles of these complexes can be used as non‐toxic labels for cellular imaging application. Also energy decomposition analysis results revealed that the percentage contribution of ΔEelec in total interaction energy is considerably larger than that of ΔEorb. Thus, in all complexes the (η2‐C60)M(Y1) bond is considerably more electrostatic in nature than the (η2‐C60)M(Y1) bond. Finally, by application of the Taguchi method for optimization of parameters in Suzuki–Miyaura reaction, the catalytic activity of Pd complexes 1 and 3 was investigated in the cross‐coupling reaction of various aryl chlorides with phenylboronic acid. According to analysis of variance results, solvent has the highest F value and it has high contribution percentage (36.75%) to the yield of Suzuki–Miyaura reaction.
Prediction for regularized clusterwise multiblock regression
Authors: Bougeard S. , Cariou V. , Saporta G. , Niang N.
Published: May 2018

In a large variety of fields such as epidemiology, process monitoring, chemometrics, marketing, and social sciences among others, many research questions pertain to regression analysis from large data sets. Although in some cases standard regression will suffice, modeling is sometimes more challenging for various reasons (i) explain several variables; (ii) with a large number of explanatory variables organized into meaningful, usually ill‐conditioned, multidimensional matrices; (iii) where observations come from different subpopulations; and (iv) with the opportunity to predict new observations. Although some developed methods partially meet these challenges, none of them covers all these aspects. To fill this gap, a new method, called regularized clusterwise multiblock regression (CW.rMBREG), is proposed. The method CW.rMBREG combines clustering and a component‐based (multiblock) model associated with a well‐defined criterion to optimize. It provides simultaneously a partition of the observations into clusters along with the regression coefficients associated with each cluster. To go further, we propose to investigate a key feature generally neglected in clusterwise regression, ie, the prediction of new observations. The usefulness of CW.rMBREG is illustrated on the basis of both a simulation study and a real example in the field of indoor air quality. It results that CW.rMBREG improves the quality of the prediction and facilitates the interpretation of complex ill‐conditioned data. The proposed method is available for users through the R package mbclusterwise.
Synaptotagmin XIII expression and peritoneal metastasis in gastric cancer
Authors: Kanda M , Shimizu D , Tanaka H , Tanaka C , Kobayashi D , Hayashi M , Takami H , Niwa Y , Yamada S , Fujii T , Sugimoto H , Kodera Y
Published: May 2018

Background

Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The aim of this study was to identify molecules responsible for mediating peritoneal metastasis of gastric cancer.

Methods

Transcriptome and bioinformatics analyses were conducted to identify molecules associated with peritoneal metastasis. The therapeutic effects of intraperitoneally administered small interfering (si) RNA were evaluated using mouse xenograft models. Expression of mRNA and protein was determined in gastric tissues from patients with gastric cancer.

Results

Synaptotagmin XIII (SYT13) was expressed at significantly higher levels in patients with peritoneal recurrence, but not in those with hepatic or distant lymph node recurrence. Inhibition of SYT13 expression in a gastric cancer cell line transfected with SYT13-specific siRNA (siSYT13) was associated with decreased invasion and migration ability of the cells, but not with proliferation and apoptosis. Intraperitoneal administration of siSYT13 significantly inhibited the growth of peritoneal nodules and prolonged survival in mice. In an analysis of 200 patients with gastric cancer, SYT13 expression in primary gastric cancer tissues was significantly greater in patients with peritoneal recurrence or metastasis. A high level of SYT13 expression in primary gastric cancer tissues was an independent risk factor for peritoneal recurrence.

Conclusion

SYT13 expression in gastric cancer is associated with perioneal metatases and is a potential target for treatment.
Control of the Near Infrared Photoluminescence of Locally Functionalized Single‐Walled Carbon Nanotubes via Doping by Azacrown‐Ether Modification
Authors: Onitsuka Hisashi , Fujigaya Tsuyohiko , Nakashima Naotoshi , Shiraki Tomohiro
Published: May 2018

Doped semiconducting single‐walled carbon nanotubes (SWNTs) through local chemical functionalization (lf‐SWNTs) show fascinating photoluminescence (PL) that appears with a longer wavelength and enhanced quantum yield compared to the original PL of non‐modified SWNTs. In this study, we introduce an azacrown ether moiety at the doped sites of lf‐SWNTs (CR‐lf‐SWNTs), and observe selective PL wavelength shifts depending on different interaction modes of silver ion inclusion and protonation of the amino group in the ring. Interestingly, their different values of the wavelength shifts show a clear correlation with calculated electron density of the nitrogen atom in the azacrown moiety in case of the inclusion form and the protonated form. This newly‐observed responsiveness based on molecular interactions is expected to create doped sites that can versatilely control the PL functions based on molecular systems.
An Engineered Lithocholate‐Based Facial Amphiphile Stabilizes Membrane Proteins: Assessing the Impact of Detergent Customizability on Protein Stability
Authors: Das Manabendra , Du Yang , Mortensen Jonas S. , Bae Hyoung Eun , Byrne Bernadette , Loland Claus J. , Kobilka Brian K. , Chae Pil Seok
Published: May 2018

Amphiphiles are critical tools for the structural and functional study of membrane proteins. Membrane proteins encapsulated by conventional head‐to‐tail detergents tend to undergo structural degradation, necessitating the development of structurally novel agents with improved efficacy. In recent years, facial amphiphiles have yielded encouraging results in terms of membrane protein stability. Herein, we report a new facial detergent (i.e., LFA‐C4) that confers greater stability to tested membrane proteins than the bola form analogue. Owing to the increased facial property and the adaptability of the detergent micelles in complex with different membrane proteins, LFA‐C4 yields increased stability compared to n‐dodecyl‐β‐d‐maltoside (DDM). Thus, this study not only describes a novel maltoside detergent with enhanced protein‐stabilizing properties, but also shows that the customizable nature of a detergent plays an important role in the stabilization of membrane proteins. Owing to both synthetic convenience and enhanced stabilization efficacy for a range of membrane proteins, the new agent has major potential in membrane protein research.
Rational Design and Synthesis of Modified Teixobactin Analogues: In Vitro Antibacterial Activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa
Authors: Ng Vivian , Kuehne Sarah A. , Chan Weng C.
Published: May 2018

Teixobactin, a recently discovered depsipeptide that binds to bacterial lipid II and lipid III, provides a promising molecular scaffold for the design of new antimicrobials. Herein, we describe the synthesis and antimicrobial evaluation of systematically modified teixobactin analogues. The replacement of the Ile11 residue with aliphatic isosteres, the modification of the guanidino group at residue 10 and the introduction of a rigidifying residue, that is, dehydroamino acid, into the macrocyclic ring generated useful structure–activity information. Extensive antimicrobial susceptibility assessment against a panel of clinically relevant Staphylococcus aureus and Propionibacterium acnes strains led to the identification of the new lead compound, [Arg(Me)10,Nle11]teixobactin, with an excellent bactericidal activity (minimum inhibitory concentration (MIC)=2–4 μg mL−1). Significantly, the antimicrobial activity of several of the teixobactin analogues against the pathogenic Gram‐negative Pseudomonas aeruginosa was “restored” when combined with the sub‐MIC concentration of the outer membrane‐disruptive antibiotic colistin. The antimicrobial effectiveness of a [Tfn10,Nle11]teixobactin (32 μg mL−1)–colistin (2 μg mL−1; 0.5×MIC) combination against P. aeruginosa PAO1 reveals, for the first time, an alternative therapeutic option in the treatment of Gram‐negative infections.
Multivalent Metallosupramolecular Assemblies as Effective DNA Binding Agents
Authors: Drożdż Wojciech , Walczak Anna , Bessin Yannick , Gervais Virginie , Cao Xiao‐Yu , Lehn Jean‐Marie , Ulrich Sébastien , Stefankiewicz Artur R.
Published: May 2018

We report the implementation of coordination chemistry onto the generation of new types of metallosupramolecular complexes with laterally appended cationic moieties for DNA binding in buffered aqueous media. Utilization of an N,N,O‐type coordination pocket along with an octahedral zinc(II) metal ion allowed us to obtain mono‐ and tetranuclear complexes in both solution and solid state, as confirmed by NMR spectroscopy and single‐crystal X‐ray diffraction, respectively. By using isothermal titration calorimetry and gel electrophoresis, multiply charged cationic assemblies were observed to effectively bind to DNA through multivalent electrostatic interactions. Furthermore, we observed a correlation between the multivalency of the compounds employed and the effectiveness of DNA binding.
Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease
Authors: Goyal Deepti , Kaur Amandeep , Goyal Bhupesh
Published: May 2018

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The Food and Drug Administration has approved drugs (e.g., rivastigmine, donepezil, galantamine, and memantine) that at best provide marginal benefits, thus emphasizing the urgent need to explore other molecular entities as future drug candidates for AD. Looking at the wide pharmaceutical applications of heterocyclic compounds and particularly those containing benzofuran and indole ring systems, these molecular frameworks have drawn special attention from medicinal chemists for further evaluation in numerous diseases. This article focuses on the history and recent advances of benzofuran‐ and indole‐based compounds as inhibitors of butyrylcholinesterase, acetylcholinesterase, γ‐secretase, β‐secretase, tau misfolding, and β‐amyloid aggregation.
Timing of palliative care needs reporting and aggressiveness of care near the end of life in metastatic lung cancer: A national registry‐based study
Authors: Goldwasser François , Vinant Pascale , Aubry Régis , Rochigneux Philippe , Beaussant Yvan , Huillard Olivier , Morin Lucas
Published: May 2018

BACKGROUND

Early integration of palliative care for patients with metastatic lung cancer improves their quality of life and survival and reduces the aggressiveness of care near the end of life. This study examined the association between the timing of palliative care needs reporting and the aggressiveness of end‐of‐life care.

METHODS

This retrospective cohort study used the French National Hospital Registry to identify all hospitalized adults (≥20 years old) who died of metastatic lung cancer in France between 2010 and 2013. It compared the use of care and treatments near the end of life as a function of the timing of the first reporting of palliative care needs. The use of chemotherapy and the use of invasive ventilation were defined as primary outcomes. Propensity score weighting was used to control for potential confounders.

RESULTS

Among a total of 64,950 deceased patients with metastatic lung cancer, the reporting of palliative care needs was characterized as timely (from 91 to 31 days before death) for 26.3%, late (from 30 to 8 days before death) for 31.5%, and very late (from 7 to 0 days before death) for 12.8%. Palliative care needs were not reported for 19,106 patients (29.4%). Patients with timely reporting of palliative care needs had the earliest and most progressive decrease in the use of anticancer therapy. The use of invasive ventilation also increased with a delay in palliative care needs reporting.

CONCLUSIONS

There is a clear association between the timing of palliative care needs reporting and the aggressiveness of care near the end of life. Cancer 2018;124:3044‐51. © 2018 American Cancer Society.