bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive, adaptive, and behavioral features in Joubert syndrome
Authors: Bulgheroni Sara , D'Arrigo Stefano , Signorini Sabrina , Briguglio Marilena , Di Sabato Maria Lucia , Casarano Manuela , Mancini Francesca , Romani Marta , Alfieri Paolo , Battini Roberta , Zoppello Marina , Tortorella Gaetano , Bertini Enrico , Leuzzi Vincenzo , Valente Enza Maria , Riva Daria
Published: August 2016

Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by a distinctive cerebellar and brainstem malformation recognizable on brain imaging, the so‐called molar tooth sign. The full spectrum of cognitive and behavioral phenotypes typical of JS is still far from being elucidated. The aim of this multicentric study was to define the clinical phenotype and neurobehavioral features of a large cohort of subjects with a neuroradiologically confirmed diagnosis of JS. Fifty‐four patients aged 10 months to 29 years were enrolled. Each patient underwent a neurological evaluation as well as psychiatric and neuropsychological assessments. Global cognitive functioning was remarkably variable with Full IQ/General Quotient ranging from 32 to 129. Communication skills appeared relatively preserved with respect to both Daily Living and Socialization abilities. The motor domain was the area of greatest vulnerability, with a negative impact on personal care, social, and academic skills. Most children did not show maladaptive behaviors consistent with a psychiatric diagnosis but approximately 40% of them presented emotional and behavioral problems. We conclude that intellectual disability remains a hallmark but cannot be considered a mandatory diagnostic criterion of JS. Despite the high variability in the phenotypic spectrum and the extent of multiorgan involvement, nearly one quarter of JS patients had a favorable long‐term outcome with borderline cognitive deficit or even normal cognition. Most of JS population also showed relatively preserved communication skills and overall discrete behavioral functioning in everyday life, independently from the presence and/or level of intellectual disability. © 2016 Wiley Periodicals, Inc.
ATXN2‐AS, a gene antisense to ATXN2, is associated with spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis
Authors: Li Pan P. , Sun Xin , Xia Guangbin , Arbez Nicolas , Paul Sharan , Zhu Shanshan , Peng H. Benjamin , Ross Christopher A. , Koeppen Arnulf H. , Margolis Russell L. , Pulst Stefan M. , Ashizawa Tetsuo , Rudnicki Dobrila D.
Published: August 2016

Objective

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by a CAG repeat expansion in the gene ataxin‐2 (ATXN2). ATXN2 intermediate‐length CAG expansions were identified as a risk factor for amyotrophic lateral sclerosis (ALS). The ATXN2 CAG repeat is translated into polyglutamine, and SCA2 pathogenesis has been thought to derive from ATXN2 protein containing an expanded polyglutamine tract. However, recent evidence of bidirectional transcription at multiple CAG/CTG disease loci has led us to test whether additional mechanisms of pathogenesis may contribute to SCA2.

Methods

In this work, using human postmortem tissue, various cell models, and animal models, we provide the first evidence that an antisense transcript at the SCA2 locus contributes to SCA2 pathogenesis.

Results

We demonstrate the expression of a transcript, containing the repeat as a CUG tract, derived from a gene (ATXN2‐AS) directly antisense to ATXN2. ATXN2‐AS transcripts with normal and expanded CUG repeats are expressed in human postmortem SCA2 brains, human SCA2 fibroblasts, induced SCA2 pluripotent stem cells, SCA2 neural stem cells, and lymphoblastoid lines containing an expanded ATXN2 allele associated with ALS. ATXN2‐AS transcripts with a CUG repeat expansion are toxic in an SCA2 cell model and form RNA foci in SCA2 cerebellar Purkinje cells. Finally, we detected missplicing of amyloid beta precursor protein and N‐methyl‐D‐aspartate receptor 1 in SCA2 brains, consistent with findings in other diseases characterized by RNA‐mediated pathogenesis.

Interpretation

These results suggest that ATXN2‐AS has a role in SCA2 and possibly ALS pathogenesis, and may therefore provide a novel therapeutic target for these diseases. Ann Neurol 2016;80:600–615
Organische Reaktionen in Mikrotröpfchen: Analyse von Reaktionsbeschleunigungen durch Massenspektrometrie
Authors: Yan Xin , Bain Ryan M. , Cooks R. Graham
Published: August 2016

Die bemerkenswerte Entdeckung, dass eine Reaktionsbeschleunigung in Lösungen mit begrenztem Volumen erfolgt, wirft ein augenscheinliches Rätsel auf. Durch Spray‐Ionisation gebildete Mikrotröpfchen können genutzt werden, um den Verlauf von Reaktionen in der Bulkphase zu verfolgen und außerdem Reaktionen zwischen den Reagentien in solch einer Reaktion zu beschleunigen. In diesem Kurzaufsatz werden Beschleunigungsphänomene in Tröpfchen und dünnen Filmen vorgestellt und moderne Methoden, die zur Untersuchung beschleunigter Reaktionen in Lösungen mit begrenztem Volumen und großer Oberfläche angewendet werden, zusammengefasst. Bedingungen, die entweder eine einfache Verfolgung oder eine Beschleunigung bestimmen, werden beim Auftreten von diskontinuierlicher und vollständiger Desolvatisierung als Endpunkt der Tropfenentwicklung abgestimmt. Die gegensätzlichen Merkmale von Reaktionen in Mikrotröpfchen und in Bulklösung werden in Verbindung mit möglichen Mechanismen, nach denen eine Reaktionsbeschleunigung in Mikrotröpfchen erfolgt, beschrieben. Derzeitige Anwendungen von Tröpfchen als Mikroreaktoren werden im Hinblick auf eine Reaktionsbeschleunigung in begrenzten Volumina und ein mögliches zukünftiges Scale‐up angeführt.
A Chemical Probe for the ATAD2 Bromodomain
Authors: Bamborough Paul , Chung Chun‐wa , Demont Emmanuel H. , Furze Rebecca C. , Bannister Andrew J. , Che Ka Hing , Diallo Hawa , Douault Clement , Grandi Paola , Kouzarides Tony , Michon Anne‐Marie , Mitchell Darren J. , Prinjha Rab K. , Rau Christina , Robson Samuel , Sheppard Robert J. , Upton Richard , Watson Robert J.
Published: August 2016

ATAD2 is a cancer‐associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio‐isostere to exploit the unique properties of fluorine, and 2) using 1,3‐interactions to control the conformation of a piperidine ring. This resulted in the first reported low‐nanomolar, selective and cell permeable chemical probe for ATAD2.
A Microkinetic Model of Calcite Step Growth
Authors: Andersson M. P. , Dobberschütz S. , Sand K. K. , Tobler D. J. , De Yoreo J. J. , Stipp S. L. S.
Published: August 2016

In spite of decades of research, mineral growth models based on ion attachment and detachment rates fail to predict behavior beyond a narrow range of conditions. Here we present a microkinetic model that accurately reproduces calcite growth over a very wide range of published experimental data for solution composition, saturation index, pH and impurities. We demonstrate that polynuclear complexes play a central role in mineral growth at high supersaturation and that a classical complexation model is sufficient to reproduce measured rates. Dehydration of the attaching species, not the mineral surface, is rate limiting. Density functional theory supports our conclusions. The model provides new insights into the molecular mechanisms of mineral growth that control biomineralization, mineral scaling and industrial material synthesis.
Synthesis of Strophasterol A Guided by a Proposed Biosynthesis and Innate Reactivity
Authors: Heinze Robert C. , Lentz Dieter , Heretsch Philipp
Published: August 2016

The synthesis of strophasterol A, a moderator of endoplasmatic reticulum (ER) stress in Alzheimer's disease, and the first member of a structurally unprecedented class of secosterols, was achieved through the implementation of a key step of its proposed biosynthesis and two C−H oxidations. Analysis of the innate reactivity of the intermediates enabled the identification of a novel way to prepare an α‐chloro‐γ‐hydroxy‐δ‐keto enone, as well as its vinylogous α‐ketol rearrangement to a δ‐keto carboxylic acid.
A Parallel‐Displaced Directly Linked 21‐Carba‐23‐Thiaporphyrin Dimer Incorporating a Dihydrofulvalene Motif
Authors: Berlicka Anna , Białek Michał J. , Latos‐Grażyński Lechosław
Published: August 2016

In the search of porphyrin arrays with a unique geometry, the efficient synthesis of a directly linked 21‐carba‐23‐thiaporphyrin dimer with the distinctive dihydrofulvalene bridging motif has been developed. This compound acquires an uncommon parallel‐displaced arrangement of two carbaporphyrin planes. The dimer undergoes an acid‐triggered cleavage to create of the asymmetric carbathiaporphyrin–carbathiachlorin dyad or 2,3‐dihalo‐21‐carba‐23‐thiachlorin depending on choice of acid. A formation of a reactive carbocation intermediate is postulated to account for mechanism of cleavage.
Tunable molecular weights of poly(triphenylamine‐2,2′‐bithiophene) and their effects on photovoltaic performance as sensitizers for dye‐sensitized solar cells
Authors: Wang Haizhen , Ding Wenhui , Wang Gang , Pan Chunyue , Duan Meihong , Yu Guipeng
Published: August 2016

Despite the huge progress achieved over the past decade, the relationship between the molecular weights of dyes and the performance of dye‐sensitized solar cells (DSSCs) remains unclear. In this article, we report on the fine control of the number‐average molecular weight (Mn) of poly(triphenylamine‐2,2′‐bithiophene) (PPAT) dyes with cyanoacrylic acid moieties as acceptors. We found a correlation between the Mn and photovoltaic performance of these polymers when they were used for DSSC applications. In this study, three samples (PPAT‐01, PPAT‐02, and PPAT‐03) with different Mn values (Mns = 1700, 2800, and 3500 g/mol) were prepared through the control of the polymerization time and characterized by analytical gel permeation chromatography and NMR. Under the same experimental conditions, the overall cell efficiency of the oligomer dyes showed a nonmonotonic tendency with increasing molecular weight. The power‐conversion efficiencies were 2.81% for PPAT‐01, 4.72% for PPAT‐02, and 1.88% for PPAT‐03. UV absorption measurements proved that PPAT‐03 formed aggregation, whereas PPAT‐01 and PPAT‐02 were in the monolayer state adsorbed on TiO2. The larger aggregation decreased charge transfer; thus, poor photoelectric conversion performance was observed. Furthermore, a higher molecular weight reduced the amount of PPAT‐03 adsorbed on TiO2, and this had a crucial effect on the performance of the cells because of the reduced photocurrent. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44182.
Enhancing water swelling ability and mechanical properties of water‐swellable rubber by PAA/SBS nanofiber mats
Authors: Dehbari Nazila , Tavakoli Javad , Zhao Jinchao , Tang Youhong
Published: August 2016

Investigation of the potential use of nanofibers to reinforce composites has gained significance in many applications. In this article, the nanofiber mats of poly(acrylic acid) (PAA) and styrene–butadiene–styrene (SBS) triblock copolymer with composites structure were interweaved by double needle electrospinning process. The multiple nanofiber mats were added to conventional water‐swellable rubber (WSR). Improved mechanical and physical properties of WSR were obtained. Enhancement of the swellability of WSR + PAA/SBS nanofiber mats was derived from the PAA constituent absorbing water from the surface into the bulk and introducing random internal water channels between discontinuous superabsorbent polymers. The role of SBS nanofibers in the composite of WSR + PAA/SBS nanofiber mats was more related to the mechanical properties, where the breaking force of the composite increased to twice that of the conventional WSR. Interestingly, after immersion of the WSR + PAA/SBS nanofiber mats in water for 1 week, there was only a slight decrease in their mechanical properties of less than 5% compared to the dry state. The mechanisms and effects of the nanofiber mats in enhancing the mechanical and water swelling properties of WSR are also discussed. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44213.
Correlation study of damp heat and pressure cooker testing on backsheets
Authors: Ottersböck Bettina , Oreski Gernot , Pinter Gerald
Published: August 2016

For photovoltaic (PV) modules, high‐quality backsheets are essential. To verify these qualities, hot and humid tests of up to 1000 h are standard in the PV industry. Damp heat (DH) tests are useful for evaluating material quality and infant failures, especially for materials that are sensitive to hydrolysis. However, shorter test periods are needed. Hence, the objective of this study was to investigate and correlate the aging behavior of hydrolysis‐sensitive polyester [poly(ethylene terephthalate) (PET)] based backsheets after exposure to DH and pressure cooker conditions. The material properties, such as thermal and mechanical parameters, correlated well between the pressure cooker at 120 °C and the DH test, with the qualification that differences in the failure mechanism were seen after 96 and 2000 h, respectively. Nevertheless, it should be acceptable to use pressure cooker tests (PCTs) for fast material testing. The PCT is proposed to significantly reduce the testing time for infant failures and material quality to around 4 days for PET‐based backsheets. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44230.
Gelation performance of poly(ethylene imine) crosslinking polymer–layered silicate nanocomposite gel system for potential water‐shutoff use in high‐temperature reservoirs
Authors: Pu Wan‐Fen , Yang Yang , Yuan Cheng‐Dong
Published: August 2016

Polymer gels have been widely used for water shutoff in mature oil fields. In this paper, polyacrylamide (PAM)–montmorillonite (MMT) nanocomposites (NC) were prepared through in situ intercalative polymerization. Fourier transform infrared spectroscopy and X‐ray diffraction were conducted to characterize the prepared PAM/MMT nanocomposites. The gelation performance of poly(ethylene imine) (PEI) crosslinking PAM/MMT nanocomposite gel system (NC/PEI gel system) was systematically investigated by bottle testing and viscosity measurement methods. The results showed that the gelation performance of the NC/PEI gel system was greatly affected by the total dissolved solids, PAM/MMT nanocomposite concentration, and PEI concentration. The NC/PEI gel system exhibited much better thermal stability and gelation performance than the PAM/PEI gel system at the same conditions. The gelation performance after flowing through porous media of the NC/PEI gel system before injection and that of the subsequently injected gel system was different. The gel strength decreased and the gelation time was delayed after the gel system before injection was flowed through porous media. However, the gel strength of the subsequently injected gel system did not decrease, and only the gelation time was delayed after flowing through porous media. This study suggests that the NC/PEI gel system can be used as a potential water‐shutoff agent in high‐temperature reservoirs. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44243.
Controlling micro‐ and nanofibrillar morphology of polymer blends in low‐speed melt spinning process. Part II: Influences of extrusion rate on morphological changes of a PLA/PVA blend through a capillary die
Authors: Tran Nguyen Hoai An , Brünig Harald , Auf der Landwehr Maria , Vogel Roland , Pionteck Jürgen , Heinrich Gert
Published: August 2016

The effects of the extrusion rate on the morphological changes of poly(lactic acid) (PLA)/poly(vinyl alcohol) (PVA) blend through a capillary die were investigated. In this study, the extrusion rate or mass flow rate is altered from 0.5 g min−1 to 2 g min−1 with an increment of 0.5 g min−1. The PLA/PVA blend with a composition of 30/70 (wt %) exhibits a particle matrix morphology with dispersed PLA droplets within the PVA matrix. It is found that, the spherical or ellipsoidal dispersed PLA droplets are elongated and coalesced into rod‐like or longer ellipsoidal droplets when they pass through the capillary die. When the extrusion rate increases, the coalescence between the large PLA droplets occurs more intense. However, the changes of the extrusion rate have no strong effect on the coalescence of small droplets having diameter less than about 150 nm. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44257.
Fiber Arrangement in the Rat Tympanic Membrane
Authors: Liu Jian , Agrawal Sumit K. , Ladak Hanif M. , Wan Wankei
Published: August 2016

The fiber arrangement in the pars tensa of the rat tympanic membrane (TM) was observed using a high resolution scanning electron microscope. The entire pars tensa is composed of fibrils with diameter of approximately 25 nm. These fibrils can be grouped into radial, circular, parabolic, and oblique fibers as reported in other mammals. The radial fibrils interweave into a planar form rather than into discrete cylindrical fibers. Before attaching to the manubrium and tympanic ring, the radial fibrils bend and cross neighboring fibrils to form a random fibril network, and change their direction from perpendicular to somewhat parallel to the manubrium and tympanic ring. The circular fibrils form cylindrical fibers near the peripheral part of the TM while closer to the manubrium, they form planar bundles. The observed fiber morphology and arrangement may provide helpful information in improving numerical models for the TM's acoustical response and designing a fibrous graft for the repair of TM perforations. Anat Rec, 299:1531–1539, 2016. © 2016 Wiley Periodicals, Inc.
Adapting viral safety assurance strategies to continuous processing of biological products
Authors: Johnson Sarah A. , Brown Matthew R. , Lute Scott C. , Brorson Kurt A.
Published: August 2016

There has been a recent drive in commercial large‐scale production of biotechnology products to convert current batch mode processing to continuous processing manufacturing. There have been reports of model systems capable of adapting and linking upstream and downstream technologies into a continuous manufacturing pipeline. However, in many of these proposed continuous processing model systems, viral safety has not been comprehensively addressed. Viral safety and detection is a highly important and often expensive regulatory requirement for any new biological product. To ensure success in the adaption of continuous processing to large‐scale production, there is a need to consider the development of approaches that allow for seamless incorporation of viral testing and clearance/inactivation methods. In this review, we outline potential strategies to apply current viral testing and clearance/inactivation technologies to continuous processing, as well as modifications of existing unit operations to ensure the successful integration of viral clearance into the continuous processing of biological products. Biotechnol. Bioeng. 2017;114: 21–32. © 2016 Wiley Periodicals, Inc.
Modulation of human mesenchymal and pluripotent stem cell behavior using biophysical and biochemical cues: A review
Authors: Ding Sheryl , Kingshott Peter , Thissen Helmut , Pera Martin , Wang Peng‐Yuan
Published: August 2016

In vitro manipulation of human stem cells is a critical process in regenerative medicine and cellular therapies. Strategies and methods to maintain stem cells and direct them into specific lineages are ongoing challenges in these fields. To date, a number of studies have reported that besides biochemical stimulation, biophysical cues in the form of surface patterning and external stimulation also influence stem cell attachment, proliferation, and differentiation, and can be used in cell reprogramming and the maintenance of pluripotency. While biochemical cues are generally effective and easy to deliver, biophysical cues have many other advantages for scalability as they are cost efficient, have a longer lifetime, and can be easily defined. However, different protocols and cell sources utilized in a variety of studies have led to difficulties in obtaining clear conclusions about the effects of the biophysical environment on stem cells. In addition, the examination of different types of external stimulation is time consuming and limited by available fabrication techniques, resulting in a delay in commercialization and clinical applications. In this review, we aim to summarize the most important biophysical cues and methods for the culture of human stem cells, including mesenchymal and pluripotent stem cells, to facilitate their adoption in stem cell biology. The standard classical protocols of using biochemical cues will also be discussed for comparison. We believe that combining biochemical and biophysical stimulation has the greatest potential to generate functionally mature cells at a scalable and inexpensive rate for diverse applications in regenerative medicine and cell therapy. Biotechnol. Bioeng. 2017;114: 260–280. © 2016 Wiley Periodicals, Inc.
Efficient gene knockdown in Clostridium acetobutylicum by synthetic small regulatory RNAs
Authors: Cho Changhee , Lee Sang Yup
Published: August 2016

Clostridium is considered a promising microbial host for the production of valuable industrial chemicals. However, Clostridium is notorious for the difficulty of genetic manipulations, and consequently metabolic engineering. Thus, much effort has been exerted to develop novel tools for genetic and metabolic engineering of Clostridium strains. Here, we report the development of a synthetic small regulatory RNA (sRNA)‐based system for controlled gene expression in Clostridium acetobutylicum, consisting of a target recognition site, MicC sRNA scaffold, and an RNA chaperone Hfq. To examine the functional operation of sRNA system in C. acetobutylicum, expression control was first examined with the Evoglow fluorescent protein as a model protein. Initially, a C. acetobutylicum protein annotated as Hfq was combined with the synthetic sRNA based on the Escherichia coli MicC scaffold to knockdown Evoglow expression. However, C. acetobutylicum Hfq did not bind to E. coli MicC, while MicC scaffold‐based synthetic sRNA itself was able to knockdown the expression of Evoglow. When E. coli hfq gene was introduced, the knockdown efficiency assessed by measuring fluorescence intensity, could be much enhanced. Then, this E. coli MicC scaffold‐Hfq system was used to knock down adhE1 gene expression in C. acetobutylicum. Knocking down the adhE1 gene expression using the synthetic sRNA led to a 40% decrease in butanol production (2.5 g/L), compared to that (4.5 g/L) produced by the wild‐type strain harboring an empty vector. The sRNA system was further extended to knock down the pta gene expression in the buk mutant C. acetobutylicum strain PJC4BK for enhanced butanol production. The PJC4BK (pPta‐HfqEco) strain, which has the pta gene expression knocked down, was able to produce 16.9 g/L of butanol, which is higher than that (14.9 g/L) produced by the PJC4BK strain, mainly due to reduced acetic acid production. Fed‐batch culture of PJC4BK (pPta‐HfqEco) strain coupled with in situ gas stripping produced 105.5 g of total solvents (70.7 g butanol, 20.5 g acetone, and 14.3 g ethanol), demonstrating that the sRNA‐based engineered C. acetobutylicum strain can be cultured without instability. The synthetic sRNA system reported in this study will be useful for more efficient development of engineered C. acetobutylicum strains capable of producing valuable chemicals and fuels. Biotechnol. Bioeng. 2017;114: 374–383. © 2016 Wiley Periodicals, Inc.
Der Dornfinger – Deutschlands giftigste Spinne
Authors: Petrischak Hannes
Published: August 2016

Es gibt nur wenige Spinnenarten in Mitteleuropa, die in der Lage sind, mit ihren Cheliceren die menschliche Haut zu durchdringen. Ein Biss des Ammen‐Dornfingers (Cheiracanthium punctorium) kann durchaus unangenehme Folgen haben. Panik ist jedoch unangebracht, da Bisse selten und nicht wirklich gefährlich sind und sich bei umsichtigem Umgang mit den Tieren in der Regel vermeiden lassen.
Das Schaf: wolliges Herdentier mit Potenzial
Authors: Eitner Pascal
Published: August 2016

Die meisten Menschen verbinden Schafe (Ovis gmelini ssp. aries) zuerst mit ihrem flauschigen Äußeren: Schaf = Wolle. Dabei haben wir den Schafen noch viel mehr zu verdanken als nachwachsende Textilrohstoffe. Sie liefern uns wertvolles Leder und hochwertige Lebensmittel wie Fleisch und Milch. Außerdem halten sie Kulturlandschaften durch unermüdliche Beweidung offen, sodass dort eine einzigartige Tier‐ und Pflanzenwelt zu finden ist. Auch die Biotechnologie nutzt die genügsamen Wiederkäuer für moderne Produktionsverfahren.
Put disability‐discrimination claims to the ‘reasonableness’ test
Authors: Finnegan John F. , Hu Monvan
Published: August 2016

Higher education institutions are legally obligated to provide reasonable accommodations for students with disabilities.
Was university liable to student for failure to accommodate impairment?
Authors: Gelpi Aileen
Published: August 2016

The University of California, San Diego offered a Master Sports Program to the general public that consisted of group classes for triathlon training. When Anita Talevski enrolled in 2009, she told the program's coaches she was bipolar.
Characterization of the Aminotransferase ThdN from Thienodolin Biosynthesis in Streptomyces albogriseolus
Authors: Milbredt Daniela , Patallo Eugenio P. , van Pée Karl‐Heinz
Published: August 2016

In Streptomyces albogriseolus the indolethiophen alkaloid thienodolin is derived from tryptophan. The first step in thienodolin biosynthesis is the regioselective chlorination of tryptophan in the 6‐position of the indole ring. The second step is catalyzed by the aminotransferase ThdN. ThdN shows sequence homology (up to 69 % similarity) with known pyridoxal 5′‐phosphate‐dependent aminotransferases of the aspartate aminotransferase family from Gram‐positive bacteria. thdN was heterologously expressed in Pseudomonas fluorescens, and the enzyme was purified by nickel‐affinity chromatography. ThdN is a homodimeric enzyme with a mass of 90 600 kDa and catalyzes the conversion of l‐tryptophan and a number of chlorinated and brominated l‐tryptophans. The lowest KM values were found for 6‐bromo‐ and 6‐chlorotryptophan (40 and 66 μm, respectively). For l‐tryptophan it was 454 μm, which explains why thienodolin is the major product and dechlorothienodolin is only a minor component. The turnover number (kcat) for 7‐chlorotryptophan (128 min−1) was higher than that for the natural substrate 6‐chlorotryptophan (88 min−1).
Percutanous management of tricuspid regurgitation: The “Achilles tendon” of transcatheter valve interventions
Authors: Cilingiroglu Mehmet , Marmagkiolis Konstantinos
Published: August 2016

Key Points

Moderate‐to‐severe tricuspid insufficiency affects 1.6 million patients in the USA, resulting in increased morbidity and mortality and without safe and effective medical or surgical treatment options.

The unique tricuspid valve anatomy, the presence of immediate adjacent anatomic landmarks at risk and the decreased blood pressure of flow complicate the development of effective transcatheter strategies.

The HOVER trial will assess the safety and effectiveness of the CAVI approach with implantation of the Edwards, Sapien XT in the inferior vena cava.
Contrast‐induced nephropathy and peripheral intervention: Who's keeping track?
Authors: Lipinski Michael J. , Satler Lowell F.
Published: August 2016

Key Points

The incidence of contrast‐induced nephropathy is high at approximately 10% following peripheral angiography and intervention.

The same measures taken to protect against contrast‐induced nephropathy and acute kidney injury for coronary angiography and intervention should be applied for peripheral angiography and intervention.

Greater or mandatory reporting to the Peripheral Vascular Intervention (PVI) Registry of the NCDR may not only better ascertain the true incidence of CIN in general practice, but to also provide benchmarks for institutions to improve patient outcomes.
Boron‐Boron One‐Electron Sigma Bonds versus B‐X‐B Bridged Structures
Authors: Kusevska Elena , Montero‐Campillo M. Merced , Mó Otilia , Yáñez Manuel
Published: August 2016

The existence of one‐electron B−B σ bonds, for two different sets of compounds, was investigated by analyzing their electron density with different tools, namely QTAIM, ELF, NCIPLOT, and NBO approaches. Our results indicate that although the generic label “one‐electron sigma bond” is often used in the literature, the nature of these bonds varies considerably, or they even do not exist. The [B2X6]−radical anions give place to true covalent one‐electron σ bonds, the stronger the more electronegative is the X substituent. When both boron atoms are substituents in a rigid aromatic moiety, such as naphthalene, to yield 1,8‐disubstituted derivatives, two kinds of equilibrium structures are found, those also stabilized through a one‐electron σ bond (X=OH, F, Cl, CN) and those stabilized by the formation of B‐X‐B bridges (X=H, OMe). These 1,8‐BX2naphthalene derivatives can be considered as analogues of 1,8‐NX2naphthalene proton sponges. While the latter are able to stabilize a proton between the two basic sites, the former are able to stabilize an electron between the two electron‐deficient B atoms. Interestingly, when all the H atoms attached to B are substituted by phenyl groups no one‐electron σ bonds B−B bonds are formed, due to the dispersion of the unpaired electron in the aromatic substituents.
Anions as Triggers in Controlled Release Protocols from Mesoporous Silica Nanoparticles Functionalized with Macrocyclic Copper(II) Complexes
Authors: El Sayed Sameh , Milani Michele , Milanese Chiara , Licchelli Maurizio , Martínez‐Máñez Ramón , Sancenón Félix
Published: August 2016

Three different mesoporous silica nano‐sized materials (SC1, SC2, and SC3), loaded with [Ru(bipy)3]2+ dye (bipy=bipyridine) and functionalized on the external surface with three macrocyclic copper(II) complexes (C1, C2, and C3), were synthesized and characterized. When SC1, SC2, and SC3 were suspended in water, the entrapped [Ru(bipy)3]2+ dye was free to diffuse from the inner pores to the solution. However, addition of anions induced certain degrees of pore blockage, with subsequent dye release inhibition. Small monovalent and divalent anions were unable to induce complete pore blockage, whereas bulky and highly charged anions induced marked reductions in [Ru(bipy)3]2+ delivery. The best [Ru(bipy)3]2+ delivery inhibitors were ATP and hexametaphosphate anions. Inhibition was ascribed to the interaction of the anions with the grafted CuII complexes on the surface of the SC1, SC2, and SC3 supports. The hexametaphosphate anion was selected to prepare two capped materials (SC1‐mPh and SC3‐mPh). Studies of the [Ru(bipy)3]2+ dye release from solids SC1‐mPh and SC3‐mPh alone and in the presence of a collection of selected anions (HS−, F−, Br−, Cl−, I−, CN−, HPO42−, AcO−, citrate, NO32−, HCO3−, SO42−, and S2O82−), amino acids (alanine and histidine), thiol‐containing biomolecules (cysteine, methylcysteine, homocysteine, and glutathione (GSH)), and oxidants (H2O2) were performed. None of the chemicals tested, except hydrogen sulphide, was able to induce remarkable cargo delivery in both solids. The observed dye release was ascribed to a demetalation reaction of the C1 and C3 complexes induced by the hydrogen sulphide anion.
Construction of Alkynylplatinum(II) Bzimpy‐Functionalized Metallacycles and Their Hierarchical Self‐Assembly Behavior in Solution Promoted by Pt⋅⋅⋅Pt and π–π Interactions
Authors: Jiang Bo , Zhang Jing , Zheng Wei , Chen Li‐Jun , Yin Guang‐Qiang , Wang Yu‐Xuan , Sun Bin , Li Xiaopeng , Yang Hai‐Bo
Published: August 2016

A family of new alkynylplatinum(II) 2,6‐bis(benzimidazol‐2′‐yl)pyridine (bzimpy)‐functionalized supramolecular metallacycles with different shapes and sizes have been successfully prepared by coordination‐driven self‐assembly. The obtained metallacycles showed switchable emission and a strong tendency to form intermolecular Pt⋅⋅⋅Pt and π–π stacking interactions in solution that were not displayed by their individual precursors. Further investigation revealed that the existence of the metallacyclic scaffold at the core could facilitate the formation of intermolecular Pt⋅⋅⋅Pt and π–π stacking interactions of peripheral alkynylplatinum(II) bzimpy units. Moreover, the shapes and sizes of the metallacyclic scaffold have a significant influence on the hierarchical self‐assembly behavior. Among the three metallacycles, hexagonal metallacycle A, with a relatively small size, could spontaneously self‐assemble into an aromatic guest stimuli‐responsive metallogel at room temperature without a heating–cooling process.
Localized Mixed‐Valence and Redox Activity within a Triazole‐Bridged Dinucleating Ligand upon Coordination to Palladium
Authors: Broere Daniël L. J. , Plessius Raoul , Tory Joanne , Demeshko Serhiy , de Bruin Bas , Siegler Maxime A. , Hartl Frantisek , van der Vlugt Jarl Ivar
Published: August 2016

The new dinucleating redox‐active ligand (LH4), bearing two redox‐active NNO‐binding pockets linked by a 1,2,3‐triazole unit, is synthetically readily accessible. Coordination to two equivalents of PdII resulted in the formation of paramagnetic (S=
) dinuclear Pd complexes with a κ2‐N,N′‐bridging triazole and a single bridging chlorido or azido ligand. A combined spectroscopic, spectroelectrochemical, and computational study confirmed Robin–Day Class II mixed‐valence within the redox‐active ligand, with little influence of the secondary bridging anionic ligand. Intervalence charge transfer was observed between the two ligand binding pockets. Selective one‐electron oxidation allowed for isolation of the corresponding cationic ligand‐based diradical species. SQUID (super‐conducting quantum interference device) measurements of these compounds revealed weak anti‐ferromagnetic spin coupling between the two ligand‐centered radicals and an overall singlet ground state in the solid state, which is supported by DFT calculations. The rigid and conjugated dinucleating redox‐active ligand framework thus allows for efficient electronic communication between the two binding pockets.
Photocatalyzed Hydrogen Evolution from Water by a Composite Catalyst of NH2‐MIL‐125(Ti) and Surface Nickel(II) Species
Authors: Meyer Kim , Bashir Shahid , Llorca Jordi , Idriss Hicham , Ranocchiari Marco , van Bokhoven Jeroen A.
Published: August 2016

A composite of the metal–organic framework (MOF) NH2‐MIL‐125(Ti) and molecular and ionic nickel(II) species, catalyzed hydrogen evolution from water under UV light. In 95 v/v % aqueous conditions the composite produced hydrogen in quantities two orders of magnitude higher than that of the virgin framework and an order of magnitude greater than that of the molecular catalyst. In a 2 v/v % water and acetonitrile mixture, the composite demonstrated a TOF of 28 mol H2 g(Ni)−1 h−1 and remained active for up to 50 h, sustaining catalysis for three times longer and yielding 20‐fold the amount of hydrogen. Appraisal of physical mixtures of the MOF and each of the nickel species under identical photocatalytic conditions suggest that similar surface localized light sensitization and proton reduction processes operate in the composite catalyst. Both nickel species contribute to catalytic conversion, although different activation behaviors are observed.
Recent Advances in Gold‐Catalyzed Intermolecular Aryl C−H Functionalization
Authors: Kramer Søren
Published: August 2016

The direct and selective functionalization of C−H bonds offers a powerful opportunity for greener and shorter routes to valuable chemicals. While still in its infancy, research exploiting the unique features of gold catalysis for the functionalization of aryl C−H bonds has demonstrated great potential for facile regioselective decoration of (hetero)arenes. Particularly within the last five years, a more general strategy for utilizing oxidative gold catalysis has emanated including an improved understanding of the underlying mechanistic pathways. To encourage and facilitate further research in intermolecular C−H functionalization of arenes with homogeneous gold catalysis, this Minireview critically presents the transformations and mechanistic data available within this field.
One‐Step SnO2 Nanotree Growth
Authors: Schönherr Piet , Hesjedal Thorsten
Published: August 2016

A comparison between Au, TiO2 and self‐catalysed growth of SnO2 nanostructures using chemical vapour deposition is reported. TiO2 enables growth of a nanonetwork of SnO2, whereas self‐catalysed growth results in nanoclusters. Using Au catalyst, single‐crystalline SnO2 nanowire trees can be grown in a one‐step process. Two types of trees are identified that differ in size, presence of a catalytic tip, and degree of branching. The growth mechanism of these nanotrees is based on branch‐splitting and self‐seeding by the catalytic tip, facilitating at least three levels of branching, namely trunk, branch and leaf.
Peptide‐Based Molecular Hydrogels as Supramolecular Protein Mimics
Authors: Singh Nishant , Kumar Mohit , Miravet Juan F. , Ulijn Rein V. , Escuder Beatriu
Published: August 2016

This Minireview concerns recent advances in the design, synthesis, and application of low molecular‐weight peptidic hydrogelators. The sequence‐specific combinations of amino acid side chain functionalities combined with hydrogen bonding of amide backbones and hydrophobic (aromatic) capping groups give these peptidic molecules the intrinsic tendency to self‐assemble. The most prevalent designs include N‐capped amino acid residues, bolamphiphilic peptides, and amphipathic peptides. Factors such as hydrophobic effects, the Hofmeister effect, and tunable ionization influence their aggregation properties. The self‐assembly of simple bio‐inspired building blocks into higher organized structures allows comparisons to be drawn with proteins and their complex functionalities, providing preliminary insights into complex biological functions and also enabling their application in a wide range of fields including catalysis, biomedical applications, and mimicry of natural dissipative systems. The Minireview is concluded by a short summary and outlook, highlighting the advances and steps required to bridge the gaps in the understanding of such systems.
Fluorescence‐Tuned Polyhedral Oligomeric Silsesquioxane‐Based Porous Polymers
Authors: Wang Dengxu , Feng Shengyu , Liu Hongzhi
Published: August 2016

Two series of new polyhedral oligomeric silsesquioxane (POSS)‐based fluorescent hybrid porous polymers, HPP‐1 and HPP‐2, have been prepared by the Heck reaction of octavinylsilsesquioxane with 2,2′,7,7′‐tetrabromo‐9,9′‐spirobifluorene and 1,3,6,8‐tetrabromopyrene, respectively. Three sets of reaction conditions were employed to assess their effect on fluorescence. These materials exhibit tunable fluorescence from nearly no fluorescence to bright fluorescence both in the solid state and dispersed in ethanol under UV light irradiation by simply altering the reaction conditions. We speculated that the difference may be attributable to the fluorescence quenching induced by Et3N, P(o‐CH3Ph)3, and their hydrogen bromide salts employed in the reactions. This finding could give valuable suggestions for the construction of porous polymers with tunable/controllable fluorescence, especially those prepared by Heck and Sonogashira reactions in which these quenchers are used as organic bases or co‐catalysts. In addition, the porosities can also be tuned, but different trends in porosity have been found in these two series of polymers, which suggests that various factors should be carefully considered in the preparation of porous polymers with tunable/controllable porosity. Furthermore, HPP‐1 c showed moderate CO2 uptake and fluorescence that was efficiently quenched by nitroaromatic explosives, thereby indicating that these materials could be utilized as solid absorbents for the capture and storage of CO2 and as sensing agents for the detection of explosives.
Chiral HPLC Separation and Modeling of Four Stereomers of DL‐Leucine‐DL‐Tryptophan Dipeptide on Amylose Chiral Column
Authors: Alajmi Mohammed F. , Hussain Afzal , Suhail Mohd. , Mukhtar Sofi Danish , Sahoo Dibya Ranjan , Asnin Leonid , Ali Imran
Published: August 2016

Chiral high‐performance liquid chromatography (HPLC) separation and modeling of four stereomers of DL‐leucine‐tryptophan DL‐dipeptide on AmyCoat‐RP column are described. The mobile phase applied was ammonium acetate (10 mM)‐methanol‐acetonitrile (50:5:45, v/v). The flow rate of the mobile phases was 0.8 mL/min with UV detection at 230 nm. The values of retention factors for LL‐, DD‐, DL‐, and LD‐ stereomers were 2.25, 3.60, 5.00, and 6.50, respectively. The values of separation and resolution factors were 1.60, 1.39, and 1.30 and 7.76, 8.05, and 7.19. The limits of detection and quantitation were ranging from 1.0–2.3 and 5.6–14.0 μg/mL. The simulation studies established the elution orders and the mechanism of chiral recognition. It was seen that π–π connections and hydrogen bondings were the main forces for enantiomeric resolution. The reported chiral HPLC method may be applied for the enantiomeric separation of DL‐leucine‐DL‐tryptophan in unknown matrices.Chirality 28:642–648, 2016. © 2016 Wiley Periodicals, Inc.
The influence of personal and social identity on the clothing consumption of adolescents
Authors: Badaoui Khafid , Lebrun Anne‐Marie , Su Che‐Jen , Bouchet Patrick
Published: August 2016

We consider the influence of personal and social identity among adolescents on the importance they attach to clothing products and brands. The conceptual framework includes more conventional variables such as socialization (family, peers, media, and celebrities) and individual characteristics (gender and grade level). Based on a sample of 1,596 French high school adolescents, our results highlight: (i) the influence of identity on the importance attached to product and brand; (ii) the mediating effects of personal and social identities; and (iii) the moderating effects of gender and grade level. We conclude with an analysis of theoretical contributions, practical implications, and future research directions. Copyright © 2016 ASAC. Published by John Wiley & Sons, Ltd.
Oxidative desulphurization of model fuel by in situ produced hydrogen peroxide on palladium/active carbon
Authors: Wang Qing , Wang Shengqiang , Yu Hongbing
Published: August 2016

Thiophenic compounds are considered one of the major obstacles in deep desulphurization of transportation gasoil. In this paper, a single‐stage reactor, in which the induction of hydrogen peroxide, oxidation of thiophenes, and adsorption of sulphones from model fuel was demonstrated in one single step at mild temperatures. In our proposed mechanism, the removal of thiophenes from model fuel undergoes three stages: 2‐propanol dehydrogenation and in situ generation of hydrogen peroxide, oxidative desulphurization, and the adsorption of sulphones on active carbon. Palladium/active carbon (Pd/C) was not only used to catalyze the production of hydrogen peroxide, but also guarantees efficiency in the adsorption of sulphones from the oil phase and aqueous phase owing to its large specific surface area and pore volume. Thus, the goal to get ultra‐low sulphur fuel was well achieved under optimal conditions after almost all the sulphones had entered into the pores of active carbon and stayed in the adsorbent. Accumulation of sulphur in active carbon inhibits further desulphurization operation. Washing with excessive anhydrous ethanol, the efficiency of Pd/C was almost fully recovered.
2‐Amino[1,2,4]triazolo[1,5‐c]quinazolines and Derived Novel Heterocycles: Syntheses and Structure–Activity Relationships of Potent Adenosine Receptor Antagonists
Authors: Burbiel Joachim C. , Ghattas Wadih , Küppers Petra , Köse Meryem , Lacher Svenja , Herzner Anna‐Maria , Kombu Rajan Subramanian , Akkinepally Raghuram Rao , Hockemeyer Jörg , Müller Christa E.
Published: August 2016

2‐Amino[1,2,4]triazolo[1,5‐c]quinazolines were identified as potent adenosine receptor (AR) antagonists. Synthetic strategies were devised to gain access to a broad range of derivatives including novel polyheterocyclic compounds. Potent and selective A3AR antagonists were discovered, including 3,5‐diphenyl[1,2,4]triazolo[4,3‐c]quinazoline (17, Ki human A3AR 1.16 nm) and 5′‐phenyl‐1,2‐dihydro‐3′H‐spiro[indole‐3,2′‐[1,2,4]triazolo[1,5‐c]quinazolin]‐2‐one (20, Ki human A3AR 6.94 nm). In addition, multitarget antagonists were obtained, such as the dual A1/A3 antagonist 2,5‐diphenyl[1,2,4]triazolo[1,5‐c]quinazoline (13 b, Ki human A1AR 51.6 nm, human A3AR 11.1 nm), and the balanced pan‐AR antagonists 5‐(2‐thienyl)[1,2,4]triazolo[1,5‐c]quinazolin‐2‐amine (11 c, Ki human A1AR 131 nm, A2AAR 32.7 nm, A2BAR 150 nm, A3AR 47.5 nm) and 9‐bromo‐5‐phenyl[1,2,4]triazolo[1,5‐c]quinazolin‐2‐amine (11 q, Ki human A1AR 67.7 nm, A2AAR 13.6 nm, A2BAR 75.0 nm, A3AR 703 nm). In many cases, significantly different affinities for human and rat receptors were observed, which emphasizes the need for caution in extrapolating conclusions between different species.
Clinical outcomes in metastatic uveal melanoma treated with PD‐1 and PD‐L1 antibodies
Authors: Algazi Alain P. , Tsai Katy K. , Shoushtari Alexander N. , Munhoz Rodrigo R. , Eroglu Zeynep , Piulats Josep M. , Ott Patrick A. , Johnson Douglas B. , Hwang Jimmy , Daud Adil I. , Sosman Jeffrey A. , Carvajal Richard D. , Chmielowski Bartosz , Postow Michael A. , Weber Jeffrey S. , Sullivan Ryan J.
Published: August 2016

BACKGROUND

Antibodies inhibiting the programmed death receptor 1 (PD‐1) have demonstrated significant activity in the treatment of advanced cutaneous melanoma. The efficacy and safety of PD‐1 blockade in patients with uveal melanoma has not been well characterized.

METHODS

Fifty‐eight patients with stage IV uveal melanoma received PD‐1 or PD‐1 ligand (PD‐L1) antibodies between 2009 and 2015 at 9 academic centers. Patients who were evaluable for response were eligible for the analysis. Imaging was performed every 12 weeks and at the investigators' discretion. Safety and clinical efficacy outcomes, including the best overall response, progression‐free survival (PFS), and overall survival (OS), were retrospectively determined.

RESULTS

Of 56 eligible patients, 48 (86%) had received prior therapy, and 35 (63%) had received treatment with ipilimumab. Three patients had an objective response to ipilimumab, and 8 had stable disease as their best response. Thirty‐eight patients (68%) received pembrolizumab, 16 (29%) received nivolumab, and 2 (4%) received atezolizumab. Objective tumor responses were observed in 2 patients for an overall response rate of 3.6% (95% confidence interval [CI], 1.8%‐22.5%). Stable disease (≥6 months) was observed in 5 patients (9%). The median PFS was 2.6 months (95% CI, 2.4‐2.8 months), and the median OS was 7.6 months (95% CI, 0.7‐14.6 months). There was no association between prior treatment with ipilimumab or liver‐directed therapy and PFS or OS. Treatment was well tolerated, and only 1 patient discontinued treatment because of toxicity.

CONCLUSIONS

PD‐1 and PD‐L1 antibodies rarely confer durable remissions in patients with metastatic uveal melanoma. Clinical trial enrollment should be prioritized in this population. Cancer 2016;122:3344–3353. © 2016 American Cancer Society.