bluuebunny/crossref_metadata_2025 huggingface dataset:
Las capacidades dinámicas en la internacionalización de las empresas y cooperativas agroalimentarias integradas en clusters
Authors: Fayos-Gardó Teresa , Calderón-García Haydeé , Almanzar Marisela A.
Published: May 2017

El sector agroalimentario tiene ciertas características que dificultan su desarrollo internacional y que en parte pueden soslayarse con estrategias de cooperación a través de clusters de empresas. El presente trabajo tiene como principal aportación evidenciar que la pertenencia de una empresa del sector agroalimentario a un cluster provoca la aparición de capacidades dinámicas que la hacen más competitiva; a su vez, estas capacidades dinámicas pueden favorecer el desarrollo de capacidades dinámicas específicas de internacionalización en empresas, que de no pertenecer al cluster, difícilmente las hubiesen adquirido. Los resultados del estudio cualitativo realizado sobre los principales cluster agroalimentarios de la República Dominicana muestran que entre casi todas las capacidades dinámicas de cluster y de internacionalización hay una relación que será más intensa en aquellas capacidades propias de las primeras etapas del proceso de internacionalización.
El gasto público en discapacidad en la UE: estimación y análisis por culturas administrativas y modelos del Estado del bienestar
Authors: Dasí González Rosa María , Murgui Izquierdo Santiago
Published: May 2017

El objetivo de este trabajo es estimar y analizar el gasto público en materia de discapacidad en Europa, teniendo en cuenta que esta información no está disponible en las fuentes estadísticas accesibles de forma explícita. Las fuentes de datos utilizadas para estimar el gasto público en materia de discapacidad se definen en dos clasificaciones funcionales diferentes: el Sistema Europeo de Estadísticas Integradas de Protección Social (SEEPROS) y la Clasificación Funcional del Gasto de la Administración Pública (COFOG). El período analizado es 2005-2013, lo que nos permite estudiar la evolución desde los años previos a la crisis económica hasta los últimos datos disponibles. Se han identificado dos mediciones relativas para establecer un análisis comparativo de los recursos asignados por los diferentes países de la UE a la atención de la discapacidad. La primera considera el número de personas con discapacidad en cada país teniendo en cuenta que no existe una definición única de la discapacidad en toda la UE. La segunda considera el gasto público total para cada país en términos de contabilidad nacional (SEC 2010). La medición del gasto público en materia de discapacidad ofrece una mayor visibilidad de la atención pública de la discapacidad en Europa y permite la comparación entre los diferentes grupos de países que determinan las distintas culturas administrativas y modelos de bienestar.
La educación de postgrado en Economía Social en la universidad española ¿una asignatura pendiente?
Authors: Melián Navarro Amparo , Campos i Climent Vanessa , Sanchis Palacio Joan Ramon
Published: May 2017

El fomento de la Economía Social requiere del conocimiento de su relevancia y papel. Las empresas de participación y de Economía Social son las grandes desconocidas, y esa falta de información provoca que las iniciativas de creación de sociedades no vayan dirigidas hacia las empresas sociales, aunque en épocas de crisis, son buenas generadoras de rentas y de mantenimiento de los niveles de empleo. La formación es por lo tanto clave en esta tarea y la especifica en materia de Economía Social está escasamente desarrollada. El presente trabajo revela la todavía incipiente oferta formativa en estudios de máster que tienen como eje temático principal la Economía Social de mercado en la Universidad española (de acuerdo con las directrices del Espacio Europeo de Educación Superior (EEES)). Como características principales se destaca su promoción en las áreas geográficas en las que tradicionalmente el cooperativismo ha tenido y tiene un peso específico importante; su impartición mayoritaria en la modalidad presencial o semipresencial; los contenidos y materias que abogan por la formación jurídica y en el área de administración y dirección de empresas; y que responden a una promoción de las propias organizaciones de empresas de Economía Social.
The Geographic and Ethnic Affinities of Art (Élie Faure, 1935)
Authors: Flinn Margaret C.
Published: May 2017

This article traces what Élie Faure believed to be the racial, ethnic and geographic origins of art. Influenced by the writings of Gobineau and Taine, he asserts that the taxonomisation of species provides a model for the taxonomisation of artistic productions. The mixing of various races is evidenced in their artistic production, with the relative presence or absence of the rhythmic serving as an index for the presence or absence of certain types of blood, or racial/ethnic origins. Similarly, the qualities of the land where art is produced results in visible effects upon the (artistic) forms created by the people living in that geographic area. Métissage is considered a positive characteristic, and cinema the apogee of modern artistic production because of its integration of machine rhythms into the rhythms of human gesture.
Largest baleen whale mass mortality during strong El Niño event is likely related to harmful toxic algal bloom
Authors: Häussermann Verena , Gutstein Carolina S. , Beddington Michael , Cassis David , Olavarria Carlos , Dale Andrew C. , Valenzuela-Toro Ana M. , Perez-Alvarez Maria Jose , Sepúlveda Hector H. , McConnell Kaitlin M. , Horwitz Fanny E. , Försterra Günter
Published: May 2017

While large mass mortality events (MMEs) are well known for toothed whales, they have been rare in baleen whales due to their less gregarious behavior. Although in most cases the cause of mortality has not been conclusively identified, some baleen whale mortality events have been linked to bio-oceanographic conditions, such as harmful algal blooms (HABs). In Southern Chile, HABs can be triggered by the ocean–atmosphere phenomenon El Niño. The frequency of the strongest El Niño events is increasing due to climate change. In March 2015, by far the largest reported mass mortality of baleen whales took place in a gulf in Southern Chile. Here, we show that the synchronous death of at least 343, primarily sei whales can be attributed to HABs during a building El Niño. Although considered an oceanic species, the sei whales died while feeding near to shore in previously unknown large aggregations. This provides evidence of new feeding grounds for the species. The combination of older and newer remains of whales in the same area indicate that MMEs have occurred more than once in recent years. Large HABs and reports of marine mammal MMEs along the Northeast Pacific coast may indicate similar processes in both hemispheres. Increasing MMEs through HABs may become a serious concern in the conservation of endangered whale species.
Cooperative effects of tropomyosin on the dynamics of the actin filament
Authors: Khaitlina Sofia , Tsaplina Olga , Hinssen Horst
Published: May 2017

Tropomyosin (Tpm) plays an important role in regulating the organisation and functions of the actin cytoskeleton. Here, we describe a new approach to analyse the effects of Tpm on actin dynamics. Using F‐actin proteolytically modified within the DNase‐binding loop (ECP‐actin), we show that Tpm binding almost completely suppresses the increased subunit exchange intrinsic for this F‐actin. The effect is both concentration‐dependent and cooperative, with half‐maximal inhibition observed at about a 1 : 50 Tpm : actin ratio. Tpm decreases not only the number concentration of ECP‐actin filaments, but also the rate of the filament subunit exchange. Our data suggest that Tpm regulates the dynamics of actin filaments by an allosteric strengthening of intermonomer contacts in the actin filament, and that this mechanism may be involved in the modulation of cytoskeletal dynamics.
Liver X receptors link lipid metabolism and inflammation
Authors: Schulman Ira G.
Published: May 2017

The response of immune cells to pathogens is often associated with changes in the flux through basic metabolic pathways. Indeed, in many cases changes in metabolism appear to be necessary for a robust immune response. The Liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that regulate gene networks controlling cholesterol and lipid metabolism. In immune cells, particularly in macrophages, LXRs also inhibit proinflammatory gene expression. This Review will highlight recent studies that connect LXR‐dependent control of lipid metabolism to regulation of the immune response.
EMT‐ and MET‐related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities
Authors: Kahlert Ulf D. , Joseph Justin V. , Kruyt Frank A. E.
Published: May 2017

The epithelial‐to mesenchymal (EMT) process is increasingly recognized for playing a key role in the progression, dissemination, and therapy resistance of epithelial tumors. Accumulating evidence suggests that EMT inducers also lead to a gain in mesenchymal properties and promote malignancy of nonepithelial tumors. In this review, we present and discuss current findings, illustrating the importance of EMT inducers in tumors originating from nonepithelial/mesenchymal tissues, including brain tumors, hematopoietic malignancies, and sarcomas. Among these tumors, the involvement of mesenchymal transition has been most extensively investigated in glioblastoma, providing proof for cell autonomous and microenvironment‐derived stimuli that provoke EMT‐like processes that regulate stem cell, invasive, and immunogenic properties as well as therapy resistance. The involvement of prominent EMT transcription factor families, such as TWIST, SNAI, and ZEB, in promoting therapy resistance and tumor aggressiveness has also been reported in lymphomas, leukemias, and sarcomas. A reverse process, resembling mesenchymal‐to‐epithelial transition (MET), seems particularly relevant for sarcomas, where (partial) epithelial differentiation is linked to less aggressive tumors and a better patient prognosis. Overall, a hybrid model in which more stable epithelial and mesenchymal intermediates exist likely extends to the biology of tumors originating from sources other than the epithelium. Deeper investigation and understanding of the EMT/MET machinery in nonepithelial tumors will shed light on the pathogenesis of these tumors, potentially paving the way toward the identification of clinically relevant biomarkers for prognosis and future therapeutic targets.
Submarine landslides triggered by destabilization of high‐saturation hydrate anomalies
Authors: Handwerger Alexander L. , Rempel Alan W. , Skarbek Rob M.
Published: May 2017

Submarine landslides occur along continental margins at depths that often intersect the gas hydrate stability zone, prompting suggestions that slope stability may be affected by perturbations that arise from changes in hydrate stability. Here we develop a numerical model to identify the conditions under which the destabilization of hydrates results in slope failure. Specifically, we focus on high‐saturation hydrate anomalies at fine‐grained to coarse‐grained stratigraphic boundaries that can transmit bridging stresses that decrease the effective stress at sediment contacts and disrupt normal sediment consolidation. We evaluate slope stability before and after hydrate destabilization. Hydrate anomalies act to significantly increase the overall slope stability due to large increases in effective cohesion. However, when hydrate anomalies destabilize there is a loss of cohesion and increase in effective stress that causes the sediment grains to rapidly consolidate and generate pore pressures that can either trigger immediate slope failure or weaken the surrounding sediment until the pore pressure diffuses away. In cases where failure does not occur, the sediment can remain weakened for months. In cases where failure does occur, we quantify landslide dynamics using a rate and state frictional model and find that landslides can display either slow or dynamic (i.e., catastrophic) motion depending on the rate‐dependent properties, size of the stress perturbation, and the size of the slip patch relative to a critical nucleation length scale. Our results illustrate the fundamental mechanisms through which the destabilization of gas hydrates can pose a significant geohazard.
Multianalytical provenance analysis of Eastern Ross Sea LGM till sediments (Antarctica): Petrography, geochronology, and thermochronology detrital data
Authors: Perotti Matteo , Andreucci Benedetta , Talarico Franco , Zattin Massimiliano , Langone Antonio
Published: May 2017

In order to reveal provenance of detrital sediments supplied by West Antarctic Ice Sheet (WAIS), 19 glaciomarine cores of Last Glacial Maximum age were analyzed from Eastern Ross Sea and Sulzberger Bay. Analytical techniques included petrographic analysis of gravel‐sized clasts, geochronology (zircon U‐Pb: Zrn‐UPb) and thermochronology (apatite fission track: AFT) of sand‐sized fractions. Petrographic analysis revealed a similarity with the lithologies presently exposed in western Marie Byrd Land (MBL), with major roles played by low‐grade metamorphic rocks and granitoids. Furthermore Zrn‐UPb and AFT data allowed to identify the ages of formation and cooling of sedimentary source area, consisting of Cambrian‐Precambrian basement (i.e., Swanson Formation in western MBL) which underwent at least two episodes of magma intrusion, migmatization and cooling during Devonian‐Carboniferous and Cretaceous‐Paleocene times. Scarcity of volcanic clasts in the region of Ross Sea along the front of West Antarctica Ice Streams in association with the occurrence of AFT Oligocene‐Pliocene dates suggests a localized tectonic exhumation of portions of MBL, as already documented for the opposite side of West Antarctic Rift System in the Transantarctic Mountains. Furthermore, a Zrn‐UPb and AFT population of Late Triassic‐Jurassic age indicates the presence of unexposed rocks that formed or metamorphosed at that time in the sedimentary source area, which could be identified in McAyeal Ice Stream and Bindschadler Ice Stream catchment areas.
Well‐preserved low thermal inertia ejecta deposits surrounding young secondary impact craters on Mars
Authors: Hill J. R. , Christensen P. R.
Published: May 2017

Following the most recent updates to the Mars Odyssey Thermal Emission Imaging System daytime and nighttime infrared global mosaics, a colorized global map was produced that combines the thermophysical information from the nighttime infrared global mosaic with the morphologic context of the daytime infrared global mosaic. During the validation of this map, large numbers of low thermal inertia ejecta deposits surrounding small young impact craters were observed. A near‐global survey (60°N–60°S) identified 4024 of these low thermal inertia ejecta deposits, which were then categorized based on their apparent state of degradation. Mapping their locations revealed that they occur almost exclusively in regions with intermediate‐to‐high thermal inertias, with distinct clusters in northern Terra Sirenum, Solis Planum, and southwestern Daedalia Planum. High‐Resolution Imaging Science Experiment images show that the thermophysically distinct facies of the deposits are well correlated with the estimated average ejecta grain sizes, which decrease with radial distance from the crater. Comparisons with recent primary impact craters and secondary impact craters surrounding Zunil Crater show that the low thermal inertia ejecta deposits very closely resemble the secondary craters, but not the primary craters. We conclude that the low thermal inertia ejecta deposits are secondary impact crater ejecta deposits, many of which originated from the rayed crater primary impact events, and are both well preserved and easily identifiable due to the absence of dust cover and aeolian modification that would otherwise reduce the thermal contrast between the ejecta facies and the surrounding terrain.
Observed radiative cooling over the Tibetan Plateau for the past three decades driven by snow cover‐induced surface albedo anomaly
Authors: Chen Xiaona , Long Di , Hong Yang , Liang Shunlin , Hou Aizhong
Published: May 2017

Seasonal snow cover on the Tibetan Plateau (TP) is a sensitive indicator of climate change. Unlike the decreasing snow cover extent and associated weakening of radiative cooling effects for the Northern Hemisphere during recent decades reported by previous studies, snow cover variability over the TP and its impact on the energy budget remain largely unknown. We defined the snow cover‐induced radiative forcing (SnRF) as the instantaneous perturbation to Earth's shortwave radiation at the top of the atmosphere (TOA) induced by the presence of snow cover. Here using satellite observations and a radiative kernel approach, we found slightly enhanced SnRF, i.e., a radiative cooling effect on the TP during the past three decades (1982–2014). However, this cooling effect weakened during 2001–2014 because of reduced snow cover at a rate of −0.61% decade−1 and land surface albedo at a rate of −0.72% decade−1. Changes in snow cover fraction are highly correlated with anomalies in land surface albedo (as) over the TP both spatially and temporally. Moreover, the SnRF is closely related to the direct observation of TOA shortwave flux anomalies (R2 = 0.54, p = 0.004) over the TP during 2001–2014. Despite the insignificant interannual variability in SnRF, its intra‐annual variability has intensified driven mostly by enhanced SnRF during the snow accumulation season but weakened SnRF during the melt season, indicating greater energy release during the transition between accumulation and melt seasons. This may pose a great challenge to snow meltwater use and flood prediction for transboundary rivers originating from the TP, such as the Brahmaputra River basin.
B
ook of
C
ommon
P
rayer, The
Authors: Rosendale Timothy
Published: May 2017

The Book of Common Prayer, first published in 1549, was and technically still is the official liturgy of the Church of England, and is arguably one of the most important texts in English history. It is primarily the work of archbishop of Canterbury Thomas Cranmer, assisted by a range of scholars, bishops, and theologians, and its purpose was to provide nationally standardized forms of worship, in English, and with generally (if sometimes ambiguously) Protestant commitments.
T
aylor,
J
ohn
Authors: Mardock James
Published: May 2017

John Taylor (1578–1653) is best known to literary historians by his self‐given title ‘the Water‐Poet’, taken from his trade as a London waterman – that is, a hired rower, the early modern equivalent of a taxi driver. Taylor's popularity during his 50‐year literary career as a self‐educated poet, journalist, pamphleteer, and propagandist – which stands in stark contrast to his relative obscurity today – is mainly due to his successful lifelong campaign of self‐promotion and cultivation of celebrity. By virtue of his trade, he became acquainted with the courtiers, wits, lawyers, and poets drawn to the Bankside theatres, and he eventually achieved royal patronage. During Taylor's Jacobean heyday, Ben Jonson claimed that King James himself preferred ‘the sculler's’ verses to Philip Sidney's.
W
eever,
J
ohn
Authors: Darcy Robert
Published: May 2017

John Weever (1575/76–1632), satirist, poet, epigrammist, and antiquarian, is primarily remembered for
Ancient funerall monuments
(1631), an 871‐page work cataloguing ancient, medieval, and contemporary epitaphs. Since many of these physical epitaphs have been lost, Weever's transcriptions and commentaries have proved invaluable to scholars. Weever is also known for his satirical verses: he published five books of epigrams and satires, and attempted to follow the model of his lauded mentor Ben Jonson, although his efforts in this regard were ridiculed by his contemporaries.
B
rooks,
C
leanth
Authors: Wastal Carrie K.
Published: May 2017

Cleanth Brooks (1906–94) was one of the most influential and innovative writers in what has come to be known as the “new criticism.” Though he is best known for his collection of essays,
The Well‐Wrought Urn
(1947), in which the new critical emphasis on irony and paradox find eloquent expression, he was also a scholar of southern US writing, particularly the work of William Faulkner, and his
William Faulkner: The Yoknapatawpha Country
(1963) is still widely read today.
Point of View/Focalization
Authors: Steffen Heather M.
Published: May 2017

Point of view, in literary studies, describes the position from which a narrative is told; it is the vantage point from which its events, situations, and characters are presented to the reader. Always a concern for fiction writers, point of view has been a major topic for literary critics since the early twentieth century when Henry James wrote about it in a series of prefaces to his novels (later collected as
The Art of the Novel
[1934]) and Percy Lubbock elaborated on it in
The Craft of Fiction
(1921). Lubbock, following James, called point of view the “relation in which the narrator stands to the story” (1955 [1921]: 251). Point of view remained a popular and vital element of criticism through the 1970s, in no small measure due to the centrality of the concept in Wayne Booth's
Rhetoric of Fiction
(1961). By the late 1960s, in his
Figures
, Gerard Genette had introduced the concept of focalization, which is related to point of view, but makes a clear distinction between the position of the narrator (the point from which the story is told) and the position from which events of the narrative can be viewed. A single text may contain several points of view or kinds of focalization at different moments in the narrative.
A Strategy to Design High‐Density Nanoscale Devices utilizing Vapor Deposition of Metal Halide Perovskite Materials
Authors: Hwang Bohee , Lee Jang‐Sik
Published: May 2017

The demand for high memory density has increased due to increasing needs of information storage, such as big data processing and the Internet of Things. Organic–inorganic perovskite materials that show nonvolatile resistive switching memory properties have potential applications as the resistive switching layer for next‐generation memory devices, but, for practical applications, these materials should be utilized in high‐density data‐storage devices. Here, nanoscale memory devices are fabricated by sequential vapor deposition of organolead halide perovskite (OHP) CH3NH3PbI3 layers on wafers perforated with 250 nm via‐holes. These devices have bipolar resistive switching properties, and show low‐voltage operation, fast switching speed (200 ns), good endurance, and data‐retention time >105 s. Moreover, the use of sequential vapor deposition is extended to deposit CH3NH3PbI3 as the memory element in a cross‐point array structure. This method to fabricate high‐density memory devices could be used for memory cells that occupy large areas, and to overcome the scaling limit of existing methods; it also presents a way to use OHPs to increase memory storage capacity.
Salicylic Acid‐Catalyzed One‐Pot Hydrodeamination of Aromatic Amines by tert‐Butyl Nitrite in Tetrahydrofuran
Authors: Felipe‐Blanco Diego , Alonso Francisco , Gonzalez‐Gomez Jose C.
Published: May 2017

A significant acceleration in the hydrodeamination of in situ formed diazonium salts (from aromatic amines) has been observed in the presence of 10‐mol% salicylic acid, using tetrahydrofuran as the hydrogen donor. The reaction proceeds efficiently at 20 °C for a wide range of substituted anilines, even at 10‐mmol scale, without any other additive. The same protocol has been adapted to the selective deuterodeamination of some aromatic amines. Control experiments clearly show that aryl radicals are involved in the reaction mechanism.

magnified image
Disorders of sex development (DSD): Clinical service delivery in the United States
Authors: Rolston Aimee M. , Gardner Melissa , van Leeuwen Kathleen , Mohnach Lauren , Keegan Catherine , Délot Emmanuèle , Vilain Eric , Sandberg David E. ,   members of the DSD‐TRN Advocacy,   Advisory Network Accord Alliance
Published: May 2017

Following the principles of care recommended in the 2006 Consensus Statement on Disorders of Sex Development (DSD), along with input from representatives of peer support and advocacy groups, this study surveyed DSD clinical management practices at healthcare facilities in the United States. DSD are congenital conditions in which development of chromosomal, gonadal, or anatomic sex is atypical. Facilities providing care for patients with DSD were targeted for participation. Specialty providers completed a survey with questions in six broad categories: Institution Information, Nomenclature and Care Guidelines, Interdisciplinary Services, Staff and Community Education, DSD Management, and Research. Twenty‐two of 36 targeted sites (61%) participated. Differences were observed between sites with regard to what conditions were considered to be DSD. All sites reported some degree of involvement of pediatric urology and/or surgery and pediatric endocrinology in the care of DSD patients. Gynecology and neonatology were most frequently not represented. Wide variation was observed across sites in continuing education standards, obtaining informed consent for clinical procedures, and in specific clinical management practices. This survey is the first to assess DSD clinical management practices in the United States. The findings establish a baseline of current practices against which providers delivering care to these patients and their families can benchmark their efforts. Such surveys also provide a practical framework for collaboration in identifying opportunities for change that enhance health and quality of life outcomes for patients and families affected by DSD.
Asymmetric Synthesis of Functionalized Nitrophenols via a Copper(II)‐Mediated Bromination/Debromination Aromatization Sequence
Authors: Liu Xue‐Li , Zhang Xiao‐Long , Guo Yan‐Jun , Meng Chen‐Hong , Xia Ai‐Bao , Xu Dan‐Qian
Published: May 2017

A stereospecific copper(II)‐mediated bromination/debromination aromatization sequence leading to functionalized nitrophenols from corresponding γ‐nitroketones is described. It provided a simple methodology for the construction of nitrophenols in moderate to good yields and moderate to high enantioselectivities.
Elektronische Struktur und magnetische Anisotropie eines ungesättigten Cyclopentadienyleisen(I)‐Komplexes mit 15 Valenzelektronen
Authors: Chakraborty Uttam , Demeshko Serhiy , Meyer Franc , Rebreyend Christophe , de Bruin Bas , Atanasov Mihail , Neese Frank , Mühldorf Bernd , Wolf Robert
Published: May 2017

Der 15‐Valenzelektronen‐Komplex [CpArFe(IiPr2Me2)] (1, CpAr=C5(C6H4‐4‐Et)5; IiPr2Me2=1,3‐Diisopropyl‐4,5‐dimethylimidazolin‐2‐yliden) ist ausgehend von der Eisen(II)‐Vorstufe [CpArFe(μ‐Br)]2 in hohen Ausbeuten zugänglich. 57Fe‐Mößbauer‐ und EPR‐Daten, magnetische Messungen und Ab‐initio‐Ligandenfeldrechnungen deuten auf einen S=3/2‐Grundzustand mit einer großen negativen Nullfeldaufspaltung hin. Infolgedessen weist 1 magnetische Anisotropie mit einer effektiven Spinumkehrbarriere von Ueff=64 cm−1 auf. Zudem katalysiert 1 die Dehydrierung von Dimethylamin‐Boran unter Bildung von Tetramethyl‐1,3‐diaza‐2,4‐diboretan unter milden Bedingungen.
Privilegierte Strukturen neu betrachtet
Authors: Schneider Petra , Schneider Gisbert
Published: May 2017

Privilegierte Strukturen inspirieren den Entwurf von Substanzbibliotheken für die medizinische Chemie. Wir haben 1.4 Millionen bioaktive Substanzen hinsichtlich der Dominanz bestimmter chemischer Grundgerüste (“frameworks”) untersucht. Dabei diente die Shannon‐Entropie als ein quantitatives Maß für deren Promiskuität bezüglich der verschiedenen Targetfamilien. Diese Analyse offenbarte eine inverse Beziehung zwischen der Zahl an Wasserstoffbrückenakzeptoren und der beobachteten Promiskuität des Grundgerüsts. Des Weiteren scheinen sich strukturell einfache Gerüste besonders für Substanzbibliotheken mit unterschiedlichem Promiskuitätsgrad zu eignen, wohingegen sp3‐reiche heterozyklische Grundgerüste den Entwurf von Target‐fokussierten Bibliotheken ermöglichen. Die Resultate unserer Studie erlauben ein kritisches Hinterfragen von oft nur vermuteten besonderen Eigenschaften so genannter privilegierter Strukturen und weisen einen Weg zu deren systematischer Nutzung in der medizinischen Chemie.
Dearomative Intramolecular (4+3) Cycloadditions of Arenes with Epoxy and Aziridinyl Enolsilanes
Authors: Ling Jesse , Lam Sarah , Low Kam‐Hung , Chiu Pauline
Published: May 2017

An intramolecular (4+3) cycloaddition of epoxy and aziridinyl enolsilanes with benzene, naphthalene, and anthracene derivatives is reported. Highly functionalized polycyclic alcohols and amines are generated under relatively mild reaction conditions with yields up to 89 %. Optically enriched cycloadducts are obtained from cycloadditions of enantiomerically pure epoxides and aziridines.
Polynitro‐Functionalized Dipyrazolo‐1,3,5‐triazinanes: Energetic Polycyclization toward High Density and Excellent Molecular Stability
Authors: Yin Ping , Zhang Jiaheng , Imler Gregory H. , Parrish Damon A. , Shreeve Jean'ne M.
Published: May 2017

A new fused N‐heterocyclic framework, dipyrazolo‐1,3,5‐triazinane, was synthesized and the physiochemical properties of its derivatives were investigated to evaluate the integrated energetic performance. In contrast to 1,3,5‐trinitro‐1,3,5‐triazinane (RDX) featuring a distorted chair confirmation, polynitro‐functionalized dipyrazolo‐1,3,5‐triazinanes have nearly planar backbones, thereby enhancing the density and thermal stability. Among these new energetic tricyclic compounds, 5 a and 12 show favorable crystal densities of 1.937 g cm−3 and 1.990 g cm−3 at 150 K, respectively, which rank highest in triazinane‐based energetic compounds. Additionally, this synthetic approach was carried out to form seven‐membered and eight‐membered rings, giving rise to tetranitro dipyrazolo‐1,3,5‐triazepane (5 b) and tetranitro dipyrazolo‐1,3,5‐triazocane (5 c), respectively.
Privileged Structures Revisited
Authors: Schneider Petra , Schneider Gisbert
Published: May 2017

Privileged structures inspire compound library design in medicinal chemistry. We performed a comprehensive analysis of 1.4 million bioactive compounds, with the aim of assessing the prevalence of certain molecular frameworks. We used the Shannon entropy formalism to quantify the promiscuity of the most frequently observed atom scaffolds across the annotated target families. This analysis revealed an apparent inverse relationship between hydrogen‐bond‐acceptor count of a scaffold and its potential promiscuity. The results further suggest that chemically easily accessible scaffolds can serve as templates for the generation of bespoke compound libraries with differing degrees of multiple target engagement, and heterocyclic, sp3‐rich frameworks are particularly suited for target‐focused library design. The outcome of our study enables us to place some of the many narratives surrounding the concept of privileged structures into a critical context.
Controlling the α/γ‐Reactivity of Vinylogous Ketone Enolates in Organocatalytic Enantioselective Michael Reactions
Authors: Iriarte Igor , Olaizola Olatz , Vera Silvia , Gamboa Iñaki , Oiarbide Mikel , Palomo Claudio
Published: May 2017

The first regio‐, diastereo‐, and enantioselective direct Michael reaction of β,γ‐unsaturated ketones with nitroolefins is enabled by Brønsted base/hydrogen‐bonding bifunctional catalysis. A squaramide‐substituted tertiary amine catalyzes the reaction of a broad range of β,γ‐unsaturated ketones to proceed at the α‐site exclusively, giving rise to adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90–98 % ee range.
Direct Zinc(II)‐Catalyzed Enantioconvergent Additions of Terminal Alkynes to α‐Keto Esters
Authors: Zavesky Blane P. , Johnson Jeffrey S.
Published: May 2017

The addition of terminal alkynes to racemic β‐stereogenic α‐keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by a non‐toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition.
Aromatic‐Imide‐Based Thermally Activated Delayed Fluorescence Materials for Highly Efficient Organic Light‐Emitting Diodes
Authors: Li Meng , Liu Yanwei , Duan Ruihong , Wei Xiaofang , Yi Yuanping , Wang Ying , Chen Chuan‐Feng
Published: May 2017

Aromatic‐imide‐based thermally activated delayed fluorescence (TADF) materials with a twisted donor–acceptor–donor skeleton were efficiently synthesized and exhibited excellent thermal stability and high photoluminescence quantum yields. The small ΔEST value (<0.1 eV) along with the clear temperature‐dependent delayed component of their transient photoluminescence (PL) spectra demonstrated their excellent TADF properties. Moreover, the performance of organic light‐emitting diodes in which TADF materials AI‐Cz and AI‐TBCz were used as dopants were outstanding, with external quantum efficiencies up to 23.2 and 21.1 %, respectively.
Quaternary ammonium‐functionalized polymers in biodegradable matrices: Physicochemical properties, morphology, and biodegradability
Authors: Belkhir Kedafi , Jegat Corinne , Prochazka Frédéric , Taha Mohamed
Published: May 2017

Quaternary ammonium‐functionalized polymers (QAFPs) based on branched structures of poly(lactic acid) (PLA) and polycaprolactone (PCL) were blended with neat matrices of PLA and PCL to improve their processability in the melt phase at 160 °C. Different formulations were prepared by varying the proportions of the components of the blends (0, 10, 20, 50, and 60 wt % of QAFP). The rheological behavior of each component and their blends was studied at 160 °C and dynamic mechanical analyses were carried out. The thermal properties of the matrices were also investigated by thermogravimetric analyses and differential scanning calorimetry; they were found to be affected by the presence of QAFPs within them. All the studied blends had a dispersed morphology, highlighted by scanning electron microscopy. The water contact angle of the blends was studied and showed that the hydrophilicity of the surfaces of the blends increased by increasing their QAFP content. The biodegradability of both the components and the blends was investigated: a decrease of the biodegradation kinetics was observed due to the presence of the quaternary ammonium groups, but the materials remain biodegradable. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45261.
Simultaneous determination of ginsenoside Rb1, ginsenoside Rg1, paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma by liquid chromatography–tandem mass spectrometry: Application to a pharmacokinetic study of wen‐Yang‐Huo‐Xue soft capsule
Authors: Wu Xiujun , You Yang , Qu Gonglin , Ma Ran , Zhang Mingxue
Published: May 2017

A simple and sensitive HPLC–MS/MS method was developed and fully validated for simultaneous determination of ginsenoside Rb1, ginsenoside Rg1, paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma. Plasma samples were pretreated with protein precipitation using acetonitrile. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). All analytes and digoxin (internal stand, IS) were quantitated through electrospray ionization in negative ion multiple reaction monitoring mode. All calibration curves exhibited good linearity (r > 0.9960) over a wide concentration range for all components. The intra‐day and inter‐day precisions (RSD) at three different levels were all <12.0% and the accuracies (RE) ranging from −6.1 to 6.2%. The extraction recoveries of the five compounds ranged from 89.2 to 97.1%. The validated method was successfully applied in a comparative pharmacokinetic study of Wen‐Yang‐Huo‐Xue soft capsule (WYHXSC) in rats. Compared with single pure component, the exposure of the investigated components, except for oxypaeoniflorin, increased after oral administration of WYHXSC in rats, which suggested a synergistic effects between the herbs in the WYHXSC preparations.
Duration of dual antiplatelet therapy following drug‐eluting stent implantation: A systemic review and meta‐analysis of randomized controlled trials with longer follow up
Authors: Sharma Abhishek , Agrawal Sahil , Garg Aakash , Vallakati Ajay , Lavie Carl J. , Helft Gerald
Published: May 2017

Objective

To evaluate the long term efficacy and safety of long duration DAPT (L‐DAPT) compared to short duration DAPT (S‐DAPT) after drug‐eluting stent (DES) implantation.

Methods

We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) assessing the clinical impact of L‐DAPT versus S‐DAPT after DES and have mean follow up period of at least 2 years or longer. Primary end point was stent thrombosis (ST). Secondary endpoints were all‐cause mortality, cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR), thrombolysis in myocardial infarction (TIMI) major bleeding and stroke. Event rates were compared using a random effects model.

Results

We identified five RCTs in which 19,760 patients were randomized to S‐DAPT (N = 9,810) and L‐DAPT (n = 9,950), respectively. Compared with L‐DAPT, S‐DAPT was associated with higher rate of MI (odds ratio [OR] 1.48, 95% confidence interval [CI] [1.04, 2.10]). There were no significant differences between S‐DAPT and L‐DAPT in terms of all cause mortality, cardiac mortality, ST, TVR or stroke (OR 0.90, 95% CI [0.73, 1.12]; OR 1.02, 95% CI [0.80, 1.30]; OR 1.59, 95% CI [0.77, 3.27]; OR 0.87 95% CI [0.67, 1.14]; and OR 1.08 95% CI [0.81, 1.46], respectively). However, rate of TIMI major bleeding was significantly lower with S‐DAPT compared to L‐DAPT (OR 0.64, 95% CI [0.41, 0.99]).

Conclusions

In the present analysis of RCTs with longer follow up (2 years or longer), S‐DAPT compared with L‐DAPT, was associated with higher rate of MI and lower rate of major bleeding without any significant difference in the rates of all cause mortality, cardiac mortality, ST, TVR, and stroke.
Transseptal transcatheter mitral valve‐in‐valve: A step by step guide from preprocedural planning to postprocedural care
Authors: Guerrero Mayra , Salinger Michael , Pursnani Amit , Pearson Paul , Lampert Mark , Levisay Justin , Russell Hyde , Feldman Ted
Published: May 2017

Transcatheter mitral valve replacement has been successfully performed with the use of aortic transcatheter heart valves in hundreds of patients worldwide with severe dysfunction of a degenerated mitral bioprosthesis and high surgical risk for repeat operation. The delivery approach in the vast majority of the mitral valve‐in‐valve procedures has been transapical. Although the transseptal approach may be more technically challenging, it is less invasive and may be preferred by patients. Data from case series and a large international registry suggest that patients treated with transseptal mitral valve‐in‐valve have faster recovery, more improvement in left ventricular ejection fraction and possibly lower mortality compared with patients treated with transapical approach. A prospective clinical trial, the MITRAL trial (Mitral Implantation of TRAnscatheter vaLves) is evaluating the safety and feasibility of transvenous transseptal mitral valve‐in‐valve. The experience from this trial has allowed us to improve our procedural approach. In anticipation of a wider adoption of the transseptal approach for mitral valve‐in‐valve, we describe our current method step‐by‐step from planning the procedure through postprocedural management. This is an evolving technique that has changed with experience and the transition to newer generation transcatheter heart valve devices. We discuss the use of cardiac computed tomography for planning the procedure including transseptal puncture and valve size selection, provide procedural and technical tips, and discuss postprocedural care.
Efficacy of radiation dose reduction due to real‐time monitoring and visualization of peak skin dose during coronary angiography and percutaneous coronary intervention
Authors: Ichimoto Eiji , Kadohira Tadayuki , Nakayama Takashi , De Gregorio Joseph
Published: May 2017

Objectives

This study assessed that the use of real‐time monitoring and visualization of peak skin dose could reduce radiation dose during coronary angiography (CAG) and percutaneous coronary intervention (PCI).

Background

Exposure to ionizing radiation has dose related effects including skin damage. Reducing the radiation exposure is important during CAG and PCI. The skin dose‐tracking system (DTS) has a real‐time monitor of radiation peak skin dose.

Methods

A total of 323 consecutive patients who underwent CAG and PCI between September 2014 and June 2015 were enrolled. Patients were classified into with DTS group (CAG alone in 104 and PCI in 57 patients) or without DTS group (CAG alone in 106 and PCI in 56 patients).

Results

There was no significant difference in reference air kerma between CAG alone with and without DTS groups. Reference air kerma with DTS group during PCI was lower than without DTS group (204.6 ± 141.1 mGy vs. 294.2 ± 237.4 mGy, P = 0.016). Moreover, kerma area product (17.8 ± 13.0 Gycm2 vs. 25.2 ± 19.3 Gycm2, P = 0.019) and number of cine runs (12.8 ± 5.0 vs. 15.5 ± 6.5, P = 0.013) with DTS group were lower than without DTS group. Multiple regression analysis showed increased reference air kerma was associated with male gender, body mass index and type B2/C lesion. Conversely, DTS correlated with decreased reference air kerma.

Conclusions

The use of DTS could reduce radiation dose during PCI. Real‐time radiation monitoring and visualization of peak skin dose was effective for the patients with PCI.
Low‐Temperature CO Methanation in Oil‐Tempered Plate Reactors by Optimization of Catalyst Activation Conditions
Authors: Schlüter Michael , Albrecht Matthias , Sündermann Madeleine , Rönsch Stefan
Published: May 2017

Ni‐catalyzed methanation has been discovered more than 100 years ago. Since then, many applications based on syngas – from coal or biomass – for the production of synthetic natural gas (SNG) have been established. Nevertheless, methanation still bears great potential for optimization. Especially for decentralized, biomass‐based applications, decreased methanation temperatures and pressures are expected to lower the costs of the overall process. Consequently, it is necessary to obtain a catalyst that is highly active under such reduced reaction conditions. This objective was successfully reached by a systematic variation of reduction temperature, pressure, and hydrogen concentration under the aspects of the design of experiment within the catalyst activation process.
Stereochemical Alignment in Triphospha[3]ferrocenophanes
Authors: Borucki Stefan , Kelemen Zsolt , Maurer Martin , Bruhn Clemens , Nyulászi László , Pietschnig Rudolf
Published: May 2017

A series of triphospha[3]ferrocenophanes of the type Fe(C5H4‐PtBu)2PX with X=H, F, Cl, Br, I, NEt2, tBu has been prepared and characterized by heteronuclear NMR spectroscopy and X‐ray crystallography. Despite having three stereogenic centers, the selective formation of a reduced number of diastereomers (either one or two) has been observed for these ferrocenophanes. Theoretical calculations revealed that the inversion of the central stereogenic center inverts the frontier orbital sequence leading to either an iron or a phosphorus centered HOMO depending on the respective diastereomer. CV measurements supported these results. For the all‐tert‐butyl substituted [3]ferrocenophane Fe(C5H4)2(PtBu)3 a chiral staggered conformation has been found in the solid state which differs substantially from the only other all‐organo substituted [3]ferrocenophane, Fe(C5H4)2(PPh)3.
Helical Oligonaphthodioxepins Showing Intense Circularly Polarized Luminescence (CPL) in Solution and in the Solid State
Authors: Takaishi Kazuto , Yamamoto Takahiro , Hinoide Sakiko , Ema Tadashi
Published: May 2017

A series of oligonaphthodioxepins was synthesized, revealing a helically arranged octamer, (R,R,R,R,R,R,R)‐3, which showed intense circularly polarized luminescence (CPL) both in solution and in the solid state. The fluorescence quantum yields (ΦFL) in solution and in the solid state were 0.90 and 0.22, respectively, and the glum values in solution and in the solid state were +2.2×10−3 and +7.0×10−3, respectively. This is one of the highest solid‐state CPL glum values yet reported. The high ΦFL and glum values were due to the rigidity, as well as to the fact that (R,R,R,R,R,R,R)‐3 was a non‐planar molecule. Moreover, (R,R,R,R,R,R,R)‐3 was highly stable both chemically and stereochemically.
Probing Bis‐FeIV MauG: Isolation of Highly Reactive Radical Intermediates
Authors: Guchhait Tapas , Sarkar Sabyasachi , Pandit Younis Ahmad , Rath Sankar Prasad
Published: May 2017

MauG is a diheme enzyme that utilizes two covalently bound c‐type heme centers. We report here step‐wise oxidations of a synthetic analogue of MauG in which two heme centers are bridged covalently through a flexible linker containing a pyrrole moiety. One‐ and two‐electron oxidations produce monocation radical and dication diradical intermediates, respectively, which, being highly reactive, undergo spontaneous intramolecular rearrangement involving the pyrrole bridge itself to form indolizinium‐fused chlorin–porphyrin and spiro–porphyrinato heterodimers. Unlike in MauG, where the two oxidizing equivalents produce the bis‐FeIV redox state, the synthetic analogue of the same, however, stabilizes two ferric hemes, each coupled with a porphyrin π‐cation radical. The present study highlights the possible role played by the bridge in the electronic communication.
N‐Heterocyclic Vinylidene‐Stabilized Phosphorus Biradicaloid
Authors: Rottschäfer Dennis , Neumann Beate , Stammler Hans‐Georg , Ghadwal Rajendra S.
Published: May 2017

Four‐membered biradicaloid compounds containing a N2E2 (E=main group element) framework have been thoroughly investigated; however, the synthesis of stable analogues with a C2P2 skeleton remains a challenge. Base‐mediated double C−H functionalization of IPr=CH2 (1) (IPr=C[N(2,6‐iPr2‐C6H3)CH]2) with PCl3 affords [{(IPr)CP}2Cl]Cl (2) as a royal blue solid. Treatment of 2 with KC8 yields the stable phosphorus biradicaloid [(IPr)CP]2 (3) featuring a four‐membered C2P2 ring. Compound 3 is diamagnetic and shows sharp and temperature‐independent NMR resonances, revealing its singlet biradicaloid nature. The stability of 3 is attributed to the σ‐ and π‐electron‐donating property of the N‐heterocyclic vinylidene [(IPr)C] group.