bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanodiscs for INPHARMA NMR Characterization of GPCRs: Ligand Binding to the Human A2A Adenosine Receptor
Authors: Fredriksson Kai , Lottmann Philip , Hinz Sonja , Onila Iounut , Shymanets Aliaksei , Harteneck Christian , Müller Christa E. , Griesinger Christian , Exner Thomas E. 
Published: April 2017

AbstractG‐protein‐coupled‐receptors (GPCRs) are of fundamental importance for signal transduction through cell membranes. This makes them important drug targets, but structure‐based drug design (SBDD) is still hampered by the limitations for structure determination of unmodified GPCRs. We show that the interligand NOEs for pharmacophore mapping (INPHARMA) method can provide valuable information on ligand poses inside the binding site of the unmodified human A2A adenosine receptor reconstituted in nanodiscs. By comparing experimental INPHARMA spectra with back‐calculated spectra based on ligand poses obtained from molecular dynamics simulations, a complex structure for A2AR with the low‐affinity ligand 3‐pyrrolidin‐1‐ylquinoxalin‐2‐amine was determined based on the X‐ray structure of ligand ZM‐241,358 in complex with a modified A2AR.
A Method for the Late‐Stage Formation of Ketones, Acyloins, and Aldols from Alkenylstannanes: Application to the Total Synthesis of Paecilonic Acid A
Authors: Sommer Heiko , Hamilton James Y. , Fürstner Alois 
Published: April 2017

AbstractTreatment of alkenylstannanes with Cu(OAc)2/Et3N affords the corresponding enol esters or ketones under conditions that proved compatible with many common functionalities; these include groups that would neither survive under the standard Tamao–Fleming conditions for the oxidation of C
−SiR3 bonds nor under the conditions commonly used to oxidize C−B bonds. Chiral centers adjacent to the unveiled carbonyls are not racemized and competing protodestannation is marginal, even if the substrate carries unprotected −OH groups as internal proton sources. Therefore, the procedure is well suited for the preparation of acyloin and aldol derivatives. These enabling virtues are illustrated by a concise approach to the bicyclic lipid paecilonic acid A.
Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors
Authors: Gallier Florian , Martel Arnaud , Dujardin Gilles 
Published: April 2017

AbstractThe Robinson annulation is a reaction that has been useful for numerous syntheses since its discovery in 1935, especially in the field of steroid synthesis. The products are usually obtained after three consecutive steps: the formation of an enolate (or derivative), a conjugate addition, and an aldol reaction. Over the years, several methodological improvements have been made for each individual step or alternative routes have been devised to access the Robinson annulation products. The first part of this Review outlines the most relevant developments towards the formation of monocarbonyl‐derived Robinson annulation products (MRA products, MRAPs) and activated monocarbonyl‐derived Robinson annulation products (AMRA products, AMRAPs). The following sections are then devoted to the diastereoselective and enantioselective synthesis of these products, while the last section describes the enantiomeric resolution of racemic mixtures.
Characterizing the Evolution of Wide‐Gauge Features in Stylopodial Limb Elements of Titanosauriform Sauropods via Geometric Morphometrics
Authors: Ullmann Paul V. , Bonnan Matthew F. , Lacovara Kenneth J. 
Published: April 2017

ABSTRACTWide‐gauge posture of titanosauriform sauropods remains an enigmatic peculiarity among terrestrial vertebrates. Here, two‐dimensional geometric morphometrics and thin plate splines analyses were used to quantitatively analyze shape differences among sauropodomorph humeri and femora to identify how these elements may differ according to body gauge. Results demonstrate that titanosauriforms generally possess proportionately gracile humeri in comparison to other sauropods, with relatively more medially oriented humeral heads and proximally located deltopectoral crests. Myological repercussions of these features demonstrate a relative sacrificing of muscular torque for forelimb abduction/adduction in exchange for minimization of necessary muscle contraction to generate the same degree of limb excursion. Regarding femora, titanosauriforms possess significantly broader femora mediolaterally than other sauropods, with comparatively proximomedially placed fourth trochanters. Canonical variates results also identify a trend for titanosauriform femora to present distal condyles that are more frequently perpendicular to the long axis of the shaft or beveled medially. All of these femoral shape characteristics are expressed to the greatest degree by titanosaurians. Myologically, mediolateral femoral broadening increases relative mechanical advantages for hind limb abductor and adductor musculature. This supports previous hypotheses that suggested titanosauriforms were capable of a greater degree of hind limb abduction and adduction. This capability may have been necessary to maintain dynamic stability during wide‐gauge locomotion over uneven terrain. Overall, our results corroborate previous qualitative assessments of wide‐gauge attributes, afford new insights into statistically significant but obscure shape patterns, and add new clarity to aspects of the functional morphology of wide‐gauge posture. Anat Rec, 300:1618–1635, 2017. © 2017 Wiley Periodicals, Inc.
Production and characterization of active recombinant human factor II with consistent sialylation
Authors: Lee Jeong H. , Reier Jason , Heffner Kelley M. , Barton Christopher , Spencer David , Schmelzer Albert E. , Venkat Raghavan 
Published: April 2017

ABSTRACTCoagulation factor II (prothrombin; FII) is the pre‐proteolyzed precursor to thrombin in the coagulation cascade. It has 10 sites of gamma‐carboxylation, which are required for its bioactivity, and is N‐glycosylated at three of four putative sites. Production of recombinant human FII (rhFII) using a platform fed‐batch process designed for monoclonal antibody production resulted in low levels of gamma‐carboxylation and sialylation. There have not been any prior reports of successful process development and clinical manufacture of rhFII with optimal, consistent gamma‐carboxylation and sialylation. In order to develop such a fed‐batch process, various process parameters were evaluated to determine their impact on product quality. Process temperature and temperature shift timing were important for both sialic acid level and gamma‐carboxyglutamate (Gla) level. In addition, vitamin K concentration and the type of surfactant used for preparation of vitamin K stock solution were also important for gamma carboxylation. A fed‐batch study performed with various medium additives known to be involved in the N‐glycosylation pathway, such as N‐acetyl‐d‐mannosamine (ManNAc), galactose (Gal), dexamethasone, and manganese sulfate, increased the level of sialylation and enabled the elucidation of some potential bottlenecks in the sialylation pathway. The optimized process based on these studies yielded a reduction in the level of missing Gla by 0.4 moles per mole of rhFII in cell culture and a nearly threefold increase in sialic acid level. The process was successfully implemented at the 2000 L scale where a high Gla level and sialylation levels were achieved in all GMP lots. Biotechnol. Bioeng. 2017;114: 1991–2000. © 2017 Wiley Periodicals, Inc.
Bio‐CoDa: A new analysis class to ensure accurate and precise monoclonal antibody CQA estimation and control
Authors: Lonardo Anthony , Saxena Parekh Babita , Srivastava Arvind 
Published: April 2017

ABSTRACTMonoclonal antibody production processes control critical quality attributes (CQAs), which are the measures that provide proof of a product's identity and quality. Critical decisions rely on the accuracy and precision of these measures, as well as their appropriate statistical treatment. Many measures require special attention. For example, the charge heterogeneity CQA measured by ionic exchange chromatography reports proportions or percentages of the total integrated peak area of known species. Since proportions sum to a constant (1 or 100%), they fall into a special class of data called compositional data that have a unit sum constraint and therefore an inherent correlation. However, these measures are often analyzed assuming independence which is incorrect. Estimating statistics with incorrect assumptions can lead to inferential failures (e.g., shelf life failures), or can lead to missing important structural patterns in the data. Presented here is a new class of analysis methods for CQAs compositional data called Biologic Compositional Data Analysis (Bio‐CoDa). The method is based on the elegant solution to analysis issues by Aitchison (1986). An introduction to the Bio‐CoDa methods with rational is presented as well as examples demonstrating its strengths. Biotechnol. Bioeng. 2017;114: 2001–2010. © 2017 Wiley Periodicals, Inc.
Characterization of the chondrocyte secretome in photoclickable poly(ethylene glycol) hydrogels
Authors: Schneider Margaret C. , Barnes Christopher A. , Bryant Stephanie J. 
Published: April 2017

ABSTRACTPoly(ethylene glycol) (PEG) hydrogels are highly tunable platforms that are promising cell delivery vehicles for chondrocytes and cartilage tissue engineering. In addition to characterizing the type of extracellular matrix (ECM) that forms, understanding the types of proteins that are secreted by encapsulated cells may be important. Thus, the objectives for this study were to characterize the secretome of chondrocytes encapsulated in PEG hydrogels and determine whether the secretome varies as a function of hydrogel stiffness and culture condition. Bovine chondrocytes were encapsulated in photoclickable PEG hydrogels with a compressive modulus of 8 and 46 kPa and cultured under free swelling or dynamic compressive loading conditions. Cartilage ECM deposition was assessed by biochemical assays and immunohistochemistry. The conditioned medium was analyzed by liquid chromatography‐tandem mass spectrometry. Chondrocytes maintained their phenotype within the hydrogels and deposited cartilage‐specific ECM that increased over time and included aggrecan and collagens II and VI. Analysis of the secretome revealed a total of 64 proteins, which were largely similar among all experimental conditions. The identified proteins have diverse functions such as biological regulation, response to stress, and collagen fibril organization. Notably, many of the proteins important to the assembly of a collagen‐rich cartilage ECM were identified and included collagen types II(α1), VI (α1, α2, and α3), IX (α1), XI (α1 and α2), and biglycan. In addition, many of the other identified proteins have been reported to be present within cell‐secreted exosomes. In summary, chondrocytes encapsulated within photoclickable PEG hydrogels secrete many types of proteins that diffuse out of the hydrogel and which have diverse functions, but which are largely preserved across different hydrogel culture environments. Biotechnol. Bioeng. 2017;114: 2096–2108. © 2017 Wiley Periodicals, Inc.
Galapagos – noch immer Trauminseln im Pazifik
Authors: Petrischak Hannes 
Published: April 2017

ZusammenfassungDas günstige Zusammentreffen mehrerer bedeutsamer Meeresströmungen hat ideale Voraussetzungen geschaffen, dass sich auf Galapagos eine Tier‐ und Pflanzenwelt etablieren konnte, die einem einzigartigen Laboratorium der Evolution gleicht. Im Gegensatz zu manch anderen Regionen der Erde haben fast alle Arten, die sich hier entwickelt haben, den Einfluss des Menschen bis heute überlebt. So können noch immer einzigartige Erlebnisse mit Pinguinen am Äquator, Flugunfähigen Kormoranen, Seelöwen und Seebären, einer Vielzahl von Meeresvögeln, Meeres‐ und Riesenschildkröten, Meerechsen und Landleguanen, Spottdrosseln und Darwinfinken gelingen. Intensive Schutzbemühungen müssen weiterhin den Einfluss invasiver Arten, insbesondere verwilderter Haustiere, minimieren und außerdem dafür sorgen, dass der boomende Tourismus in möglichst sanften Bahnen bleibt.
Nachrichten des Verbandes Biologie, Biowissenschaften & Biomedizin in Deutschland
Authors: von Essen Liesa‐Marlena 
Published: April 2017

Ausbildung & KarriereAkkreditierungAuszeichnung für exzellente HochschullehreWissenschaft & GesellschaftInvasive ArtenVBIOStartESCH 2016 – 1st Emerging Science Convention in HamburgLandesverbändeNordrhein‐Westfalen
A novel mass spectrometry‐based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l‐arginine and l‐citrulline optimized for LC‐MS‐TOF and LC‐MS/MS
Authors: Wiśniewski Jerzy , Fleszar Mariusz G. , Piechowicz Joanna , Krzystek‐Korpacka Małgorzata , Chachaj Angelika , Szuba Andrzej , Lorenc‐Kukula Katarzyna , Masłowski Leszek , Witkiewicz Wojciech , Gamian Andrzej 
Published: April 2017

AbstractNitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of l‐arginine to l‐citrulline. l‐Arginine methylated derivatives, asymmetric and symmetric dimethylarginines (asymmetric dimethylarginine, ADMA, and symmetric dimethylarginine, SDMA), regulate l‐arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of l‐arginine, l‐citrulline, ADMA and SDMA. Compounds are measured as stable 2,3,4,5,6‐pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse‐phase column. Serum aliquots (100 μL) were spiked with isotope‐labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25°C for 10 minu using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R2 = 0.9966–0.9986) for all derivatized compounds. Good accuracy (94.67–99.91%) and precision (1.92–11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower l‐arginine and l‐citrulline in angiologic patients. This robust and fast LC‐ESI‐MS method may be a useful tool in quantitative analysis of l‐arginine, ADMA, SDMA and l‐citrulline.
Autonomous social gaze model for an interactive virtual character in real‐life settings
Authors: Yumak Zerrin , van den Brink Bram , Egges Arjan 
Published: April 2017

AbstractThis paper presents a gaze behavior model for an interactive virtual character situated in the real world. We are interested in estimating which user has an intention to interact, in other words which user is engaged with the virtual character. The model takes into account behavioral cues such as proximity, velocity, posture, and sound; estimates an engagement score; and drives the gaze behavior of the virtual character. Initially, we assign equal weights to these features. Using data collected in a real setting, we analyze which features have higher importance. We found that the model with weighted features correlates better with the ground‐truth data.
Compulsive buying behavior: Re‐evaluating its dimensions and screening
Authors: Maccarrone‐Eaglen Agata , Schofield Peter 
Published: April 2017

AbstractDespite the significant research in the consumer behavior literature on compulsive buying behavior (CBB), there is still no general agreement about the dimensionality or diagnostic screening of the disorder. Previous studies have identified two principal dimensions: compulsivity and impulsivity, although more recent strands of theory characterize CBB with reference to loss of self‐control and behavioral addiction. This study challenges the impulsive–compulsive paradigm by validating a new model with compulsive and self‐control impaired spending dimensions. The model more closely reflects the disorder's ego‐dystonic character, routed in an anxiety‐based reactive mechanism with uncontrollable buying and an inability to rationalize the behavior and its consequences. The study also develops and cross‐validates a new seven‐item CBB screening tool, using a comparative analysis with three existing screeners and an independent sample. The findings indicate that compulsive buying results from both compulsive and self‐control impaired impulsive elements, which are characteristic of behavioral addiction.
Twisting of Alkynes towards a Carbon Double Helix
Authors: Adam Abdulselam , Haberhauer Gebhard 
Published: April 2017

AbstractThe carbon allotrope exhibiting only one‐dimensional sp‐hybridized carbon atoms is called carbyne. However, its existence is very controversial. Studies on model compounds for carbyne revealed that many oligoalkynes show not a straight, but a bent structure of the carbon chain. Here, we question whether it would also be possible to obtain a more complex structure from carbyne, such as a dimeric double helix. Based on quantum chemical calculations, we show that only a small energetic expense is needed for the formation of a double helix starting from oligoalkyne chains. In some cases, the double helix‐like conformation is more stable than the corresponding conformation with a parallel arrangement of the acetylene chains. Furthermore, model systems were synthesized in which two diphenyl oligoalkyne chains are fixed and twisted by a chiral imidazole‐containing clamp. A structural investigation of these model systems was performed based on UV and CD spectroscopy and quantum chemical calculations. The observed twisting in these model systems can be regarded as the first small step towards an imaginable carbon double helix.
Extending Unique 1D Borate Chains to 3D Frameworks by Introducing Metallic Nodes
Authors: Wei Qi , Sun Shi‐Jia , Zhang Jie , Yang Guo‐Yu 
Published: April 2017

AbstractTwo novel alkali/alkaline‐earth borates, Ba6[B6O9(OH)6]2(H3BO3) (1) and Li7MAlB12O24 (M=Ba, Sr, Ca) (2 a–c), with 1D and 3D structures have been made hydrothermally and characterized. 1 features a rare 1D anionic chain built by hexaborate clusters of B6O11(OH)6; each made of six BO4/BO2(OH)2 tetrahedra. The anionic chains are embedded in the channels of a Ba6‐based wheel‐cluster open‐framework. On the basis of the structural analyses of 1, by incorporating Al atoms as the linkers and tuning the reaction conditions, the novel anhydrous 3D aluminoborates (ABOs) 2 a–c have been successfully obtained, constructed from B6O14‐based cluster chains and AlO6 octahedra. The 3D ABO framework and 3D Ba‐O‐Li network are interpenetrated to give a final dense structure. The study not only realized the expansion of the structure from the 1D chain of 1 to the 3D dense ABOs 2 a–c, but also obtained the first 3D AlO6‐containing ABOs made under hydrothermal conditions. Different from the previously known 4‐connected zeolite‐type ABOs, alternately arranged from AlO4 tetrahedra and oxo‐boron clusters, the AlO6 octahedra in 2 a–c as the linkers join to six 1D B6O14‐based cluster chains to produce 3D ABOs. The optical diffuse reflectance spectra reveal that 2 a–c have wide range transparency. In addition, the thermal property analysis proves that 2 a–c are congruently melting compounds and possess high thermostability.
Ultrahigh Average Thermoelectric Figure of Merit, Low Lattice Thermal Conductivity and Enhanced Microhardness in Nanostructured (GeTe)x(AgSbSe2)100−x
Authors: Samanta Manisha , Roychowdhury Subhajit , Ghatak Jay , Perumal Suresh , Biswas Kanishka 
Published: April 2017

AbstractWaste heat sources are generally diffused and provide a range of temperatures rather than a particular temperature. Thus, thermoelectric waste heat to electricity conversion requires a high average thermoelectric figure of merit (ZTavg) of materials over the entire working temperature along with a high peak thermoelectric figure of merit (ZTmax). Herein an ultrahigh ZTavg of 1.4 for (GeTe)80(AgSbSe2)20 [TAGSSe‐80, T=tellurium, A=antimony, G=germanium, S=silver, Se=selenium] is reported in the temperature range of 300–700 K, which is one of the highest values measured amongst the state‐of‐the‐art Pb‐free polycrystalline thermoelectric materials. Moreover, TAGSSe‐80 exhibits a high ZTmax of 1.9 at 660 K, which is reversible and reproducible with respect to several heating–cooling cycles. The high thermoelectric performance of TAGSSe‐x is attributed to extremely low lattice thermal conductivity (κlat), which mainly arises due to extensive phonon scattering by hierarchical nano/meso‐structures in the TAGSSe‐x matrix. Addition of AgSbSe2 in GeTe results in κlat of ≈0.4 W mK−1 in the 300–700 K range, approaching to the theoretical minimum limit of lattice thermal conductivity (κmin) of GeTe. Additionally, (GeTe)80(AgSbSe2)20 exhibits a higher Vickers microhardness (mechanical stability) value of ≈209 kgf mm−2 compared to the other state‐of‐the‐art metal chalcogenides, making it an important material for thermoelectrics.
Determination of the enantiomeric purity of the selective dopamine transporter inhibitor (+)‐R,R‐4‐(2‐benzhydryloxyethyl)‐1‐(4‐fluorobenzyl)piperidin‐3‐ol
Authors: Neiens Patrick , Höfner Georg , Wanner Klaus T. 
Published: April 2017

Abstract(+)‐R,R‐D‐84 ((+)‐R,R‐4‐(2‐benzhydryloxyethyl)‐1‐(4‐fluorobenzyl)piperidin‐3‐ol) is a promising pharmacological tool for the dopamine transporter (DAT), due to its high affinity and selectivity for this target. In this study, an analytical method to ascertain the enantiomeric purity of this compound was established. For this purpose, a high‐performance liquid chromatographic (HPLC) method, based on a cellulose derived chiral stationary phase (CSP) was developed. The method was characterized concerning its specificity, linearity, and range. It was shown that the method is suitable to determine an enantiomeric excess of up to 99.8%. With only a few adjustments, this analytical CSP‐HPLC method is also well suited to separate (+)‐R,R‐D‐84 from its enantiomer in a semipreparative scale.
Enantioselective potential of polysaccharide‐based chiral stationary phases in supercritical fluid chromatography
Authors: Kucerova Gabriela , Kalikova Kveta , Tesarova Eva 
Published: April 2017

AbstractThe enantioselective potential of two polysaccharide‐based chiral stationary phases for analysis of chiral structurally diverse biologically active compounds was evaluated in supercritical fluid chromatography using a set of 52 analytes. The chiral selectors immobilized on 2.5 μm silica particles were tris‐(3,5‐dimethylphenylcarmabate) derivatives of cellulose or amylose. The influence of the polysaccharide backbone, different organic modifiers, and different mobile phase additives on retention and enantioseparation was monitored. Conditions for fast baseline enantioseparation were found for the majority of the compounds. The success rate of baseline and partial enantioseparation with cellulose‐based chiral stationary phase was 51.9% and 15.4%, respectively. Using amylose‐based chiral stationary phase we obtained 76.9% of baseline enantioseparations and 9.6% of partial enantioseparations of the tested compounds. The best results on cellulose‐based chiral stationary phase were achieved particularly with propane‐2‐ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO2, respectively. Methanol and basic additive isopropylamine were preferred on amylose‐based chiral stationary phase. The complementary enantioselectivity of the cellulose‐ and amylose‐based chiral stationary phases allows separation of the majority of the tested structurally different compounds. Separation systems were found to be directly applicable for analyses of biologically active compounds of interest.