bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Industrial Pt-Sn/Al2O3 Catalyst and Transient Product Formations during Propane Dehydrogenation
Authors: Ho Kah Sing , Chye Joanna Jo Ean , Chin Sim Yee , Cheng Chin Kui
Published: June 2013

The major problem plaguing propane dehydrogenation process is the coke formation on the Pt-Sn/Al2O3 catalyst which leads to catalyst deactivation. Due to information paucity, the physicochemical characteristics of the commercially obtained regenerated Pt-Sn/Al2O3 catalyst (operated in moving bed reactor) and coke formation at different temperatures of reaction were discussed. The physicochemical characterization of regenerated catalyst gave a BET surface area of 104.0 m2/g with graphitic carbon content of 8.0% indicative of incomplete carbon gasification during the industrial propylene production. Effect of temperatures on coke formation was identified by studying the product yield via temperature-programmed reaction carried out at 500oC, 600oC and 700oC. It was found that ethylene was precursor to carbon laydown while propylene tends to crack into methane. Post reaction, the spent catalyst possessed relatively lower surface area and pore radius whilst exhibited higher carbon content (31.80% at 700oC) compared to the regenerated catalyst. Significantly, current studies also found that higher reaction temperatures favoured the coke formation. Consequently, the propylene yield has decreased with reaction temperature. © 2013 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0)Corrigendum/Erratum of this article at: https://doi.org/10.9767/bcrec.9.2.7136.155
Model‐Independent and Model‐Based Methods to Assess Drug–Drug Interactions for Therapeutic Proteins
Authors: Wu Di , Barrett Jeffrey S.
Published: June 2013

Model‐independent and model‐dependent approaches are the two main methodsused to evaluate drug–drug interaction (DDI) between a therapeutic protein (TP) and a small‐molecule drug as well as between two TPs, and to predict DDI in different scenarios within model defined populations and scopes. This chapter provides an overview of these approaches.
The Cocktail Approach and Its Utility in Drug–Drug Interaction Assessments for Therapeutic Proteins
Authors: Jetter Alexander , Fuhr Uwe
Published: June 2013

This chapter demonstrates that the cocktail approach is suitable for the study of interactions between therapeutic proteins and drugs in humans—namely for the study of the effect of therapeutic proteins on cytochrome P450 enzyme activities.This is the area in which the FDA's current draft guideline on drug interaction studies recommends the use of cocktail phenotyping studies as an alternative to individual therapeutic protein–drug interaction studies.
Logistic Considerations in Study Design for Biologic Drug–Drug Interaction Assessments
Authors: Zhu Min , Sun Yu‐Nien (Tom)
Published: June 2013

Due to the unique characteristics of biologics in pharmacokinetics and immunogenicity, some design parameters of therapeutic protein (TP)–drug interaction studies are different from those for small molecules. A risk‐based drug–drug interaction assessment strategy for TPs should be implemented according to its risk factors, and appropriate study designs should be selected. The challenges and logistic considerations in study designs for TP–drug interactions are discussed in this chapter.
Monographs for Drug‐Drug Interactions of Therapeutics Biologics
Authors: Leu Jocelyn , Kasek Simone , Li Christine , Limothai Wararat , Madhura Dora Babu , Rathi Chetan , Rawal Sumit , Ryman Josiah , Thomson Margaret , Trivedi Ashit , Zhou Honghui , Meibohm Bernd
Published: June 2013

This article presents a compilation of drug‐drug interaction monographs involving therapeutic biologics. These include important “theoretical” drug‐drug interactions along with well‐established plausible mechanisms. These monographs are intended to provide for readers a guide to what might be encountered as potential therapeutic biologic‐drug interactions in clinical development programs and applied pharmacotherapy.
Chitosan‐Based Nanoparticles for Biomedical Applications
Authors: Koo Heebeom , Choi Kuiwon , Kwon Ick Chan , Kim Kwangmeyung
Published: June 2013

This chapter focuses on chitosan‐based nanoparticles for imaging and drug/gene delivery. Many studies on chitosan nanoparticles are introduced, which evaluate biological effects in living systems such as cultured cells or animal models. Furthermore, important considerations in developing chitosan‐based nanoparticles for diagnosis and therapy of diseases are discussed.
Nanocrystals Production, Characterization, and Application for Cancer Therapy
Authors: Hollis Christin P. , Li Tonglei
Published: June 2013

The delivery of synthesized drugs exhibiting poor solubility in water is extremely difficult, limiting bioavailability and causing adverse effects when solubilized. A need was determined for developing a formulation to deliver poorly water‐soluble drugs without indiscriminately reaching healthy organs and tissues. Therefore, nanocrystal formulations have been a significant focus for delivering poorly water‐soluble drugs via oral, paraenteral, and alternative routes. Using nanocrystal formulations avoids potential side effects and instability related to many existing delivery systems. Currently, few cancer therapy products are approved by the Food and Drug Administration (FDA) in which poorly soluble drugs are formulated by nanoparticles. In this chapter, the production of nanocrystals of pharmaceutical organic compounds is reviewed. Thereafter, the chapter will focus on the application of nanocrystals for cancer therapy.
Improved Graphitic Structure of Continuous Carbon Nanofibers via Graphene Oxide Templating
Authors: Papkov Dimitry , Goponenko Alexander , Compton Owen C. , An Zhi , Moravsky Alexander , Li Xing‐Zhong , Nguyen SonBinh T. , Dzenis Yuris A.
Published: June 2013

Continuous carbon nanofibers (CNF) present an attractive building block for a variety of multifunctional materials and devices. However, the carbonization of poly(acrylonitrile) (PAN) precursors usually results in CNFs with poor graphitic structure and, consequently, modest/non‐optimized properties. This paper reports that the graphitic structure of CNFs can be improved with an addition of a small amount of graphene oxide into PAN prior to processing. Continuous CNFs with 1.4 wt% of graphene oxide nanoparticles are prepared from PAN solutions by electrospinning, stabilized, and carbonized at 800 °C, 1200 °C, and 1850 °C. While the as‐prepared graphene oxide‐filled PAN nanofibers exhibit a considerable reduction in polymer crystallinity, Raman analysis of the carbonized nanofibers shows that both templating with graphene oxide and increasing the carbonization temperature significantly improve the graphitic order in CNFs. The effect of graphene oxide is more significant at higher carbonization temperatures. Selected area electron diffraction analysis of individual nanofibers reveals increased graphitic order and preferred orientation both in the vicinity of visible graphene oxide nanoparticles and in the regions where nanoparticles were not visible. These results indicate a possibility of global templating in CNFs, where the addition of a small amount of graphene oxide nanoparticles can template the formation of good, preferentially oriented graphitic crystallites in CNFs, leading to improved structure and mechanical and transport properties.
Behavior comparison for biomass observers in batch processes
Authors: Amicarelli Adriana , Quintero Olga , di Sciascio Fernando
Published: June 2013

On‐line estimation of biomass concentration in batch biotechnological processes is an active area of research because normally, the biomass is the desired process product output, and also because it is necessary for control purposes to replace the unavailable biomass concentration measurements with reliable and robust on‐line estimations. This work presents five different alternatives to face the problem of biomass estimation in a particular batch bioprocess (δ‐endotoxins production of Bacillus thuringiensis), namely: a phenomenological estimator based on dissolved oxygen balance, an extended Kalman filter estimator, a Gaussian process regression‐based estimator, an artificial neural networks‐based estimator, and finally, an estimator based on information fusion by a decentralized Kalman filter. Each proposed biomass estimation method has its own advantages and drawbacks according to their ability to take into account the model uncertainties and the measurement errors. First, the design techniques of these five biomass estimators are exposed, and finally, the behavior of each estimation method is compared. The availability of efficient biomass estimators is of great importance for engineers because, on the one hand, it allows developing new control strategies for other bioprocess variables such as for instance: the growth rate of the microorganism, the dissolved oxygen concentration, and so on. On the other hand, it is also important to improve the performance of the bioprocess optimization procedure. This work also aims to show the evolution on biomass estimation techniques from classical to more contemporary approaches, such as the design based on neural networks and Gaussian processes regression. © 2013 Curtin University of Technology and John Wiley & Sons, Ltd.
Two‐phase flow patterns in large diameter vertical pipes
Authors: Ali Shazia F. , Yeung Hoi
Published: June 2013

An experimental investigation of adiabatic upward co‐current air–water two‐phase flow has been carried out to determine the flow patterns in a 12.2=m‐high and 250=mm nominal diameter vertical pipe. The visual observations of flow patterns were supplemented by statistical analysis of the time‐averaged void fraction determined by pressure drop method. Four flow patterns were identified in the vertical test section, namely dispersed bubbly, bubbly, agitated bubblyand churn/forth flow within the experimental superficial velocity range ( ja = 0.18–2.2 m/s and jw = 0.18–1.2 m/s). Conventional slug flow consisting of smooth bullet‐shaped bubbles (Taylor bubble) and liquid slugs was never observed; instead, agitated bubbly flow was the most dominant flow pattern in relevant superficial velocity range. On the basis of the visual and statistically extracted information, a flow pattern map was developed and compared with the existing flow pattern maps. Available flow regime transition models compared against the present experimental data yielded poor agreement with none of the existing models predicting the transitions as a whole. A satisfactory agreement was obtained with other large diameter studies with inconsistencies mainly attributable to confusion in the identification of the flow patterns. © 2013 Curtin University of Technology and John Wiley & Sons, Ltd.
A Lipidomic Study of Phospholipid Classes and Species in Human Synovial Fluid
Authors: Kosinska Marta Krystyna , Liebisch Gerhard , Lochnit Guenter , Wilhelm Jochen , Klein Heiko , Kaesser Ulrich , Lasczkowski Gabriele , Rickert Markus , Schmitz Gerd , Steinmeyer Juergen
Published: June 2013

Objective

Membrane phospholipid species contribute to boundary lubrication that is provided by synovial fluid (SF). Altered levels of lubricants can be associated with increased friction, leading to articular cartilage damage. This study was undertaken to determine whether the composition of phospholipid species is altered in diseases of human knee joints.

Methods

The study was performed using SF from unaffected controls and patients with early osteoarthritis (OA), late OA, or rheumatoid arthritis (RA). Lipids were extracted from cell‐ and vesicle‐free SF from 9 control donors postmortem and from 17 patients with early OA, 13 patients with late OA, and 18 patients with RA. Phospholipid species were quantified by electrospray ionization tandem mass spectrometry.

Results

We conducted lipidomic analysis to provide the first detailed overview of phospholipid species in human SF. We identified 130 lipid species belonging to 8 lipid classes (phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, plasmalogens, phosphatidylserine, phosphatidylglycerol, sphingomyelin, and ceramide). Compared to SF from controls, SF from patients with early OA and those with late OA had higher levels of most phospholipid species. Moreover, the concentrations of 64 and 27 phospholipids differed between RA and early OA SF and between RA and late OA SF, respectively. Also, the levels of 66 phospholipid species were altered in early OA versus late OA.

Conclusion

Our data indicate disease‐ and stage‐dependent differences in the relative composition and levels of phospholipid species in human SF. Such alterations might affect articular joint lubrication. Because certain phospholipids scavenge reactive oxygen species (ROS) and are pro‐ or antiinflammatory, any altered phospholipid level might influence ROS‐scavenging activity of SF and the inflammatory status of joints. Thus, phospholipids may be associated with the pathogenesis of OA.
Wnt Inhibitory Factor 1 Deficiency Uncouples Cartilage and Bone Destruction in Tumor Necrosis Factor α–Mediated Experimental Arthritis
Authors: Stock Michael , Böhm Christina , Scholtysek Carina , Englbrecht Matthias , Fürnrohr Barbara G. , Klinger Patricia , Gelse Kolja , Gayetskyy Svitlana , Engelke Klaus , Billmeier Ulrike , Wirtz Stefan , van den Berg Wim , Schett Georg
Published: June 2013

Objective

Wnt signaling plays a pivotal role in skeletal development and in the control of cartilage and bone turnover. We have recently shown that the secreted Wnt antagonist Wnt inhibitory factor 1 (WIF‐1) is mainly expressed in the upper layers of epiphyseal and articular cartilage and, to a lesser extent, in bone. Nevertheless, WIF‐1−/− mice develop normally. In light of these findings, we undertook this study to analyze the role of WIF‐1 in arthritis.

Methods

Expression analyses for WIF‐1 were performed by real‐time reverse transcription–polymerase chain reaction (RT‐PCR). WIF‐1−/− and tumor necrosis factor (TNF)–transgenic mice were crossbred, and the progression of arthritis in TNF‐transgenic WIF‐1−/− mice and littermate controls was evaluated. Structural joint damage was analyzed by histologic staining, histomorphometry, and micro–computed tomography. Wnt/β‐catenin signaling was investigated by real‐time RT‐PCR and immunofluorescence on primary chondrocytes.

Results

WIF‐1 expression was repressed by TNFα in chondrocytes and osteoblasts and down‐regulated in experimental arthritis and in articular cartilage from patients with rheumatoid arthritis. WIF‐1 deficiency partially protected TNF‐transgenic mice against bone erosion and loss of trabecular bone, probably as a result of less osteoclast activity. In contrast, arthritis‐related cartilage damage was aggravated by WIF‐1 deficiency, while overexpression of WIF‐1 attenuated cartilage degradation in TNF‐transgenic mice. In chondrocytes, TNFα stimulated canonical Wnt signaling, which could be blocked by WIF‐1, indicating a direct effect of TNFα and WIF‐1 on Wnt signaling in this system.

Conclusion

These data suggest that WIF‐1 may take part in the fine‐tuning of cartilage and bone turnover, promoting the balance of cartilage versus bone anabolism.
Topic‐based sentiment analysis for the social web: The role of mood and issue‐related words
Authors: Thelwall Mike , Buckley Kevan
Published: June 2013

General sentiment analysis for the social web has become increasingly useful for shedding light on the role of emotion in online communication and offline events in both academic research and data journalism. Nevertheless, existing general‐purpose social web sentiment analysis algorithms may not be optimal for texts focussed around specific topics. This article introduces 2 new methods, mood setting and lexicon extension, to improve the accuracy of topic‐specific lexical sentiment strength detection for the social web. Mood setting allows the topic mood to determine the default polarity for ostensibly neutral expressive text. Topic‐specific lexicon extension involves adding topic‐specific words to the default general sentiment lexicon. Experiments with 8 data sets show that both methods can improve sentiment analysis performance in corpora and are recommended when the topic focus is tightest.
Information‐based mitigation of intimate partner violence
Authors: Houston Ron , Westbrook Lynn
Published: June 2013

Compelled Nonuse of Information (CNI) is a model of information behavior developed by Houston (2009, 2011a). CNI posits the existence of nonvolitional mechanisms that force information behaviors beyond the control of the individual. The CNI model consists of six primary CNI types: intrinsic somatic barriers, socio‐environmental barriers, authoritarian barriers, threshold knowledge shortfall barriers, attention shortfall barriers, and filtering barriers. This typology of information interaction limitations functions across a full range of socio‐economic contexts and thus lends itself to analysis of intractable power‐based inequities such as intimate partner violence (IPV). IPV includes physical, mental, financial, and social attacks that, if known, generate socially sanctioned responses of both formal (e.g., law enforcement) and informal (e.g., pastoral) approaches. Using the CNI framework to analyze information factors in distinct facets of the IPV experience, as identified in the cross disciplinary research on this phenomenon, this article provides a practical application of CNI to a complicated, high‐risk phenomenon.
Scientific impact evaluation and the effect of self‐citations: Mitigating the bias by discounting the h‐index
Authors: Ferrara Emilio , Romero Alfonso E.
Published: June 2013

In this article, we propose a measure to assess scientific impact that discounts self‐citations and does not require any prior knowledge of their distribution among publications. This index can be applied to both researchers and journals. In particular, we show that it fills the gap of the h‐index and similar measures that do not take into account the effect of self‐citations for authors or journals impact evaluation. We provide 2 real‐world examples: First, we evaluate the research impact of the most productive scholars in computer science (according to DBLP Computer Science Bibliography, Universität Trier, Trier, Germany); then we revisit the impact of the journals ranked in the Computer Science Applications section of the SCImago Journal & Country Rank ranking service (Consejo Superior de Investigaciones Científicas, University of Granada, Extremadura, Madrid, Spain). We observe how self‐citations, in many cases, affect the rankings obtained according to different measures (including h‐index and ch‐index), and show how the proposed measure mitigates this effect.
Mechanistic Study of the Rhodium‐Catalyzed [3+2+2] Carbocyclization of Alkenylidenecyclopropanes with Alkynes
Authors: Yu Haizhu , Lu Qianqian , Dang Zhimin , Fu Yao
Published: June 2013

A systematic theoretical study has been performed on the recently reported RhI‐catalyzed [3+2+2] carbocyclization reactions between alkenylidenecyclopropanes (ACPs) and alkynes. With the aid of theoretical calculations, two possible mechanisms, that is, alkene‐carbometalation‐first and alkyne‐carbometalation‐first mechanisms, are examined in this study. In the oxidative addition step, the possibility of reaction on either the distal or proximal CC bond of the cyclopropane group has been evaluated. The calculations indicate that the alkene‐activation‐first mechanism is more favored for the overall catalytic cycle. This mechanism involves four steps, that is, oxidative addition of the distal (rather than the proximal) CC bond of cyclopropane group, alkene carbometalation, alkyne carbometalation, and reductive elimination. The rate‐determining step in the overall catalytic cycle is the carbometalation of the alkyne (i.e., the alkyne‐insertion step) and this step also determines the regioselectivity. Finally, the origin of the regioselectivity is determined by the steric effect (i.e., the steric crowding between the electron‐withdrawing group on alkyne and other ligands on the rhodium center) in the alkyne‐insertion step.
Discrimination between two rice metallothionein isoforms belonging to type 1 and type 4 in metal‐binding ability
Authors: Nezhad Rezvan Mohammadi , Shahpiri Azar , Mirlohi Aghafakhr
Published: June 2013

Metallothioneins (MTs) are a superfamily of low‐molecular‐weight, cysteine (Cys)‐rich proteins that are believed to play important roles in protection against metal toxicity and oxidative stress. Plants have several MT isoforms, which are classified into four types based on the arrangement of Cys residues. In this study, two rice (Oryza sativa) MT isoforms, OsMTI‐1b and OsMTII‐1a from type 1 and type 4, respectively, were heterologously expressed in Escherichia coli as carboxy‐terminal extensions of glutathione‐S‐transferase (GST). Transformed cells expressing GST–OsMTI‐1b showed increased tolerance to Ni2+, Cd2+, and Zn2+ and accumulated more metal ions compared with cells expressing GST alone. However, heterologous expression of GST–OsMTII‐1a had no significant effects on metal tolerance or ion accumulation. The UV absorption spectra and competitive reactions of in vitro Cd‐incubated proteins with 5‐5′‐dithiobis(2‐nitrobenzoic) acid revealed that GST–OsMTI‐1b, but not GST–OsMTII‐1a, is able to form Cd‐thiolate clusters. Furthermore, heterologous expression of both GST–OsMTI‐1b and GST–OsMTII‐1a conferred H2O2 tolerance to E. coli cells. Taken together, the results presented here show that two different rice MT isoforms belonging to type 1 and type 4 differ in Ni2+, Cd2+, and Zn2+ binding abilities, but they may have overlapping function in protection of cells against oxidative stress.
The combination of DHEA, histamine, and insulin increases adipogenic differentiation and enhances tissue transplantation outcome in mice
Authors: Park Yoorim , Jung Min Kyung , Yoon Sun Young , Lee Ha‐Reum , Hur Dae Young , Kim Daejin , Yang Yoolhee , Kim Tae Sung , Kim Seonghan , Yoon Suk Ran , Park Hyun Jeong , Bang Sa Ik , Cho Dae Ho
Published: June 2013

Adipose stem cells (ASCs) are pluripotent cells that can generate pure fat tissue for regeneration. Differentiated adipose cells have been generated by a common inducer cocktail composed of dexamethasone, insulin, and isobutylmethylxanthine (DIM). The major drawbacks of adipose cells are their tendency to float on the culture media and their cost. To overcome some of these disadvantages, a new inducer cocktail that includes insulin, dehydroepiandrosterone, and histamine (DHIH) was tested. As a result, lipid accumulation was elevated more than twofold with DHIH than with DIM. Cell adhesion and viability, which are important factors for stable differentiation, were increased with DHIH and were proven through measurement of mRNA expression levels of adhesion marker genes, N‐cadherin and vascular cell adhesion molecule, as well as through an alamar blue assay. The expression of adipogenesis‐related genes, adiponectin, and glucose transporter type 4 lasted for a long time. To improve the efficiency of grafting, cell adhesion and neovascularization need to be increased. Neovascularization was observed around the transplanted adipose cells, which showed a higher number of vessel formation in DHIH than in DIM. The above results suggest that DHIH can produce pure differentiated adipose cells effectively and enhance their adhesion onto the target location when these differentiated adipose cells were applied as a clinical resource.
Collagen functionalized with unsaturated cyclic anhydrides—interactions in solution and solid state
Authors: Potorac S. , Popa M. , Picton L. , Dulong V. , Verestiuc L. , Cerf D. Le
Published: June 2013

Maleic anhydride (CMA) and itaconic anhydride modified collagen (CITA) were prepared as precursors for production of interpenetrated polymer networks (IPN). Calculated values for Huggins coefficient in aqueous diluted and semi‐diluted solutions of modified collagen indicated a slightly tendency of aggregation for itaconic anhydride‐modified collagen. In semi‐diluted solution collagen (Coll) and CMA present slightly differences in the thixotropic behavior, while CITA has a pronounced thixotropic behavior. Flow and oscillatory measurements revealed an elastic behavior of the collagen solutions, pure and modified with MA or ITA, as the storage modulus (G′) has always a superior value compared with the loss modulus (G″). The denaturation temperature (Td) of unmodified collagen increased from 34oC to 40oC for CMA and to 39oC for CITA respectively, by formation of covalent bonds that stabilize the triple helix. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 228–236, 2014.
Fast analysis of triterpenoids in Ganoderma lucidum spores by ultra‐performance liquid chromatography coupled with triple quadrupole mass spectrometry
Authors: Yan Zhou , Xia Bing , Qiu Ming Hua , Li Sheng Ding , Xu Hong Xi
Published: June 2013

A rapid and reliable method was established for simultaneous determination of main triterpenoids in Ganoderma lucidum spores using ultra‐high‐performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC‐TQ‐MS). The established method was validated in terms of linearity, sensitivity, precision, accuracy and stability, and was successfully applied to determine the contents of 10 main triterpenoids in different batches of G. lucidum spores. The analysis results showed that moderate levels of triterpenoids were found in G. lucidum spores. In addition, a MS full scan with a daughter ion scan experiment was performed to identify the potential derivatives of triterpenoids present in G. lucidum spores. As a result, a total of 22 triterpenoids from different G. lucidum spores were unequivocally or tentatively identified via comparisons with authentic standards and literatures. This method provides both qualitative and quantitative results without the need for repetitive UPLC‐MS analyses, thereby increasing efficiency and productivity, making it suitable for high‐throughput applications. Copyright © 2013 John Wiley & Sons, Ltd.
Fluorescent THF‐Based Fructose Analogue Exhibits Fructose‐Dependent Uptake
Authors: Tanasova Marina , Plutschack Matthew , Muroski Megan E. , Sturla Shana J. , Strouse Geoffrey F. , McQuade D. Tyler
Published: June 2013

Recent publications suggest that high dietary fructose might play a significant role in cancer metabolism and can exacerbate a number of aspects of metabolic syndrome. Addressing the role that fructose plays in human health is a controversial question and requires a detailed understanding of many factors including the mechanism of fructose transport into healthy and diseased cells. Fructose transport into cells is thought to be largely mediated by the passive hexose transporters Glut2 and Glut5. To date, no probes that can be selectively transported by one of these enzymes but not by the other have been identified. The data presented here indicate that, in MCF‐7 cells, a 1‐amino‐2,5‐anhydro‐D‐mannitol‐based fluorescent NBDM probe is transported twice as efficiently as fructose and that this takes place with the aid of Glut5. Its Glut5 specificity and differential uptake in cancer cells and in normal cells suggest this NBDM probe as a potentially useful tool for cross‐cell‐line correlation of Glut5 transport activity.
Dual Activators of Protein Kinase R (PKR) and Protein Kinase R‐Like Kinase (PERK) Identify Common and Divergent Catalytic Targets
Authors: Bai Huijun , Chen Ting , Ming Jie , Sun Hong , Cao Peng , Fusco Dahlene N. , Chung Raymond T. , Chorev Michael , Jin Qi , Aktas Bertal H.
Published: June 2013

Chemical genetics has evolved into a powerful tool for studying gene function in normal and pathobiology. PKR and PERK, two eukaryotic translation initiation factor 2 alpha (eIF2α) kinases, play critical roles in the maintenance of cellular hemostasis, metabolic stability, and anti‐viral defenses. Both kinases interact with and phosphorylate additional substrates including tumor suppressor p53 and nuclear protein 90. Loss of function of both kinases has been studied by reverse genetics and with recently identified inhibitors. In contrast, no activating probes for studying the catalytic activity of these kinases are available. We identified 3‐(2,3‐dihydrobenzo[b][1,4]dioxin‐6‐yl)‐5,7‐dihydroxy‐4H‐chromen‐4‐one (DHBDC) as a specific dual activator of PKR and PERK by screening a chemical library of 20 000 small molecules in a dual luciferase surrogate eIF2α phosphorylation assay. We present here extensive biological characterization and a preliminary structure–activity relationship of DHBDC, which phosphorylates eIF2α by activating PKR and PERK but no other eIF2α kinases. These agents also activate downstream effectors of eIF2α phosphorylation by inducing CEBP homologue protein, suppressing cyclin D1 expression, and inhibiting cancer cell proliferation, all in a manner dependent on PKR and PERK. Consistent with the role of eIF2α phosphorylation in viral infection, DHBDC inhibits the proliferation of human hepatitis C virus. Finally, DHBDC induces the phosphorylation of IκBα and activates the NF‐κB pathway. Surprisingly, activation of the NF‐κB pathway is dependent on PERK but independent of PKR activity. These data indicate that DHBDC is an invaluable probe for elucidating the role of PKR and PERK in normal and pathobiology.
Failing left ventricle to ascending aorta conduit—Hybrid implantation of a melody valve and NuMed covered stent
Authors: Gössl Mario , Johnson Jonathan N. , Hagler Donald J.
Published: June 2013

We present the case of a 36‐year‐old woman with increasing shortness of breath, a new 3/4 diastolic murmur, and a complex history of LV outflow tract obstruction. She has undergone multiple surgeries including the replacement of her old LV apex to ascending aorta conduit with a 20‐mm Gore‐Tex tube graft, addition of a 24‐mm homograft sutured between the conduit and the LV apex, and insertion of a 21‐mm Freestyle porcine valve conduit between the Gore‐Tex tube graft and allograft at age 23. The current assessment showed a failing Freestyle conduit prosthesis leading to left heart decompensation. Due to substantial surgical risk, the patient underwent successful implantation of a Melody valve into the Gore‐Tex tube and exclusion of the failing Freestyle bioprosthesis with a NuMed CP stent in a hybrid procedure. The case nicely illustrates the collaborative potential of cardiovascular surgeons and interventional cardiologists in the new arena of a hybrid operating room. Complex hybrid procedures like the current one, especially those including percutaneous placements of valves, offer therapeutic options for patients that are otherwise too high risk for conventional open heart surgery. © 2013 Wiley Periodicals, Inc.
Radial artery spasm associated with transradial cardiovascular procedures: Results from the RAS registry
Authors: Goldsmit Alejandro , Kiemeneij Ferdinand , Gilchrist Ian C , Kantor Pablo , Kedev Sasko , Kwan Tak , Dharma Surya , Valdivieso Leon , Wenstemberg Bernard , Patel Tejas
Published: June 2013

Objectives

To report the incidence and predictors of moderate/severe radial artery spasm (RAS) in patients undergoing cardiovascular percutaneous procedures through a transradial approach (TRA) in centers with TRA expertise.

Background

Data regarding the actual rate of clinically meaningful RAS are limited due to difference in study designs and operator expertise.

Methods

The RAS registry, an international (14 centers from Argentina, Chile, India, Indonesia, Macedonia, The Netherlands and United States of America) registry that included 1,868 patients undergoing TRA cardiovascular procedures (63.5% diagnostic and 56.5% therapeutic).All selected centers used TRA as default strategy in the cardiac catheterization laboratory. Throughout 2012, each center included all consecutive TRA cases (during a 2‐month period) into a dedicated database covering clinical characteristics as well as procedural topics related to TRA patterns and RAS occurrence.

Results

The incidence of moderate/severe RAS was 2.7%. Only 0.7% of patients required crossover (8 to transfemoral and 5 to contralateral TRA). Patients with moderately/severe spasm were more frequently females, had a history of dyslipidemia, received more often a 7F sheath and more puncture attempts than patients without spasm. By multivariate analysis, the need for more than one attempt and the use of a 7 F sheath were independent predictors of the development of moderate/severe RAS.

Conclusions

The incidence of moderate/severe RAS is low in centers with a default TRA. Its development appears to be strongly related to the numbers of puncture attempts and the use of large sheaths. © 2013 Wiley Periodicals, Inc.
MF Interactions and Heterobimetallics: Furthering the Understanding of Heterobimetallic Stabilization
Authors: Buchanan William D. , Ruhlandt‐Senge Karin
Published: June 2013

Heterobimetallic complexes containing alkali, alkaline‐earth, and divalent europium metals utilizing the perfluoro‐tert‐butoxide (PFTB) ligand following the general formula, [AM(PFTB)3(co‐ligand)x] (A=Na, K; M=Mg, Sr, Ba, Eu; co‐ligand=THF, toluene), have been isolated. These compounds sublime at low temperatures with low residual weight indicating their potential as metal–organic chemical‐vapor deposition (MOCVD) precursors. The complexes have unique molecular architectures that are strongly influenced by MF interactions, as was verified in the solid state by using X‐ray crystallography. The significance of these interactions were further reinforced by bond‐valence sums analysis and 19F VT‐NMR spectroscopy, in which rotational energies of 18.75 and 19.08 kcal mol−1 were measured.
Towards Dynamic Control of Wettability by Using Functionalized Altitudinal Molecular Motors on Solid Surfaces
Authors: London Gábor , Chen Kuang‐Yen , Carroll Gregory T. , Feringa Ben L.
Published: June 2013

We report the synthesis of altitudinal molecular motors that contain functional groups in their rotor part. In an approach to achieve dynamic control over the properties of solid surfaces, a hydrophobic perfluorobutyl chain and a relatively hydrophilic cyano group were introduced to the rotor part of the motors. Molecular motors were attached to quartz surfaces by using interfacial 1,3‐dipolar cycloadditions. To test the effect of the functional groups on the rotary motion, photochemical and thermal isomerization studies of the motors were performed both in solution and when attached to the surface. We found that the substituents have no significant effect on the thermal and photochemical processes, and the functionalized motors preserved their rotary function both in solution and on a quartz surface. Preliminary results on the influence of the functional groups on surface wettability are also described.
Peripheral Arylation of Subporphyrazines
Authors: Higashino Tomohiro , Rodríguez‐Morgade M. Salomé , Osuka Atsuhiro , Torres Tomás
Published: June 2013

Peripherally hexaarylated subporphyrazines (SubPzs) have been prepared through a Pd‐catalyzed, CuTC‐mediated coupling of a hexaethylsulfanylated subporphyrazine with arylboronic acids. The introduced aryl substituents strongly influence the electronic properties of the subporphyrazine through effective conjugative interaction. Aryl rings endowed with π‐electron‐donating groups at the para positions produce a remarkable perturbation of the electron density of the SubPz macrocycle. This is reflected through significant redshifts of the SubPz CT and Q‐bands, together with increase of the molar absorptivity of the former, with respect to those exhibited by the hexaphenyl‐SubPz 2 a. Moreover, the trend in the first SubPz reduction potentials correlates with the Hammett constants (σp) corresponding to the para substituents of the aryl. The domed, extended SubPz π‐system self‐assembles in the solid state to form a dimeric capsule that houses a solvent molecule.
Synthesis and Radiopharmacological Characterisation of a Fluorine‐18‐Labelled Azadipeptide Nitrile as a Potential PET Tracer for in vivo Imaging of Cysteine Cathepsins
Authors: Löser Reik , Bergmann Ralf , Frizler Maxim , Mosch Birgit , Dombrowski Lilli , Kuchar Manuela , Steinbach Jörg , Gütschow Michael , Pietzsch Jens
Published: June 2013

A fluorinated cathepsin inhibitor based on the azadipeptide nitrile chemotype was prepared and selected for positron emission tomography (PET) tracer development owing to its high affinity for the oncologically relevant cathepsins L, S, K and B. Labelling with fluorine‐18 was accomplished in an efficient and reliable two‐step, one‐pot radiosynthesis by using 2‐[18F]fluoroethylnosylate as a prosthetic agent. The pharmacokinetic properties of the resulting radiotracer compound were studied in vitro, ex vivo and in vivo in normal rats by radiometabolite analysis and small‐animal positron emission tomography. These investigations revealed rapid conjugate formation of the tracer with glutathione in the blood, which is associated with slow blood clearance. The potential of the developed 18F‐labelled probe to image tumour‐associated cathepsin activity was investigated by dynamic small‐animal PET imaging in nude mice bearing tumours derived from the human NCI‐H292 lung carcinoma cell line. Computational analysis of the obtained image data indicated the time‐dependent accumulation of the radiotracer in the tumours. The expression of the target enzymes in the tumours was confirmed by immunohistochemistry with specific antibodies. This indicates that azadipeptide nitriles have the potential to target thiol‐dependent cathepsins in vivo despite their disadvantageous pharmacokinetics.
Design of a Highly Selective and Potent Class of Non‐planar Estrogen Receptor β Agonists
Authors: Sundén Henrik , Ma Jian‐Nong , Hansen Lars K. , Gustavsson Anna‐Lena , Burstein Ethan S. , Olsson Roger
Published: June 2013

Selective activation of the estrogen receptor β (ERβ) could be a safe approach to hormone replacement therapy for both women and men, in contrast to the estrogens currently used for women which activate both ERβ and ERα, occasionally causing severe side effects. The selective ERβ agonist AC‐131 has shown efficacy in animal models of Parkinson’s disease and neuropathic pain. With the use of AC‐131 as template, herein we report the discovery, synthesis, and structure–activity relationship (SAR) study of a new class of dihydrobenzofurans as potent and selective ERβ agonists. The SAR was established by enantioselective synthesis, molecular modeling, and whole‐cell‐based functional assays. The most potent diastereomer, cis‐10‐SR, was shown to have an EC50 value of <1 nM, potency 100‐fold higher than that of AC‐131. Even more interestingly, compound trans‐10‐SS exhibited 1000‐fold ERβ/ERα selectivity while still maintaining good potency (∼10 nM). In addition, trans‐10‐SS showed only partial agonist activity (30–60 % Eff.) toward ERα at 10 μM. This unprecedented selectivity could be rationalized by molecular modeling. Compound trans‐10‐SS appears to be the first molecule to take advantage of both conservative amino acid differences found in the α‐ and β‐faces of the binding cavities of ERα and ERβ.
Diverse neuronal lineages make stereotyped contributions to the Drosophila locomotor control center, the central complex
Authors: Yang Jacob S. , Awasaki Takeshi , Yu Hung‐Hsiang , He Yisheng , Ding Peng , Kao Jui‐Chun , Lee Tzumin
Published: June 2013

The Drosophila central brain develops from a fixed number of neuroblasts. Each neuroblast makes a clone of neurons that exhibit common trajectories. Here we identified 15 distinct clones that carry larval‐born neurons innervating the Drosophila central complex (CX), which consists of four midline structures including the protocerebral bridge (PB), fan‐shaped body (FB), ellipsoid body (EB), and noduli (NO). Clonal analysis revealed that the small‐field CX neurons, which establish intricate projections across different CX substructures, exist in four isomorphic groups that respectively derive from four complex posterior asense‐negative lineages. In terms of the region‐characteristic large‐field CX neurons, we found that two lineages make PB neurons, 10 lineages produce FB neurons, three lineages generate EB neurons, and two lineages yield NO neurons. The diverse FB developmental origins reflect the discrete input pathways for different FB subcompartments. Clonal analysis enlightens both development and anatomy of the insect locomotor control center. J. Comp. Neurol. 521:6245–2662, 2013. © 2013 Wiley Periodicals, Inc.
Engineering‐aided treatment of chest deformities to improve the process of breathing
Authors: Gzik‐Zroska Bożena , Wolański Wojciech , Gzik Marek
Published: June 2013

In this paper, the application of new visualization technologies in correction of funnel chest is presented. Often, such defects cause problems with breathing, and therefore, to improve the cardiorespiratory efficiency, a correction is required. The virtual model of chest was formulated to determine the strains and stresses after correction of deformation with using the stabilizing plate. From biomechanical point of view, the knowledge of the load‐affecting stabilizer is necessary to select optimal parameters of the plate. The force‐affecting plate that was used in the correction of chest deformation by Nuss method was determined on the basis of finite element model of funnel chest. The main aim of this work was to select the optimal thickness of plate. Calculations were conducted for three alternative constraints. Copyright © 2013 John Wiley & Sons, Ltd.
Harnessing Light with Photonic Nanowires: Fundamentals and Applications to Quantum Optics
Authors: Claudon Julien , Gregersen Niels , Lalanne Philippe , Gérard Jean‐Michel
Published: June 2013

The efficient feeding of spontaneous emission (SE) into a controlled optical mode lies at the heart of a new generation of advanced optoelectronic devices, such as low‐threshold microlasers and bright sources of quantum light. In the solid state, single‐mode emission was first demonstrated by using the Purcell effect that arises in a resonant microcavity. Recently, the need to relax the constraints inherent to such a narrow‐band approach has motivated large effort to develop structures ensuring broadband and efficient SE control. This minireview deals with fiber‐like photonic nanowires, a class of high‐index waveguides that features key assets in this context. Combining theoretical predictions and experimental results, the paper details the SE dynamics in such tiny wires. In addition, it shows how the far‐field emission of a single wire can be tailored through proper engineering of the two wire ends. As an application in the field of quantum optics, we review the realization of an ultrabright single‐photon source. This first device was based on a self‐assembled quantum dot embedded in a wire antenna realized with a top‐down fabrication process. Considering recent advances in the direct growth of tapered photonic wires, we also propose a bottom‐up fabrication route to realize a complete device. In particular, this proposal ensures the optimal 3D positioning of a single emitter inside the antenna. Finally, future research and application prospects are also reviewed.
Characterization of Thermally Stable Brønsted Acid Sites on Alumina‐Supported Niobium Oxide after Calcination at High Temperatures
Authors: Kitano Tomoyuki , Shishido Tetsuya , Teramura Kentaro , Tanaka Tsunehiro
Published: June 2013

Thermally stable Brønsted acid sites were generated on alumina‐supported niobium oxide (Nb2O5/Al2O3) by calcination at high temperatures, such as 1123 K. The results of structural characterization by using Fourier‐transform infrared (FTIR) spectroscopy, TEM, scanning transmission electron microscopy (STEM), and energy‐dispersive X‐ray (EDX) analysis indicated that the Nb2O5 monolayer domains were highly dispersed over alumina at low Nb2O5 loadings, such as 5 wt %, and no Brønsted acid sites were presents. The coverage of Nb2O5 monolayer domains over Al2O3 increased with increasing Nb2O5 loading and almost‐full coverage was obtained at a loading of 16 wt %. A sharp increase in the number of hydroxy groups, which acted as Brønsted acid sites, was observed at this loading level. The relationship between the acidic properties and the structure of the material suggested that the bridging hydroxy groups (NbO(H)Nb), which were formed at the boundaries between the domains of the Nb2O5 monolayer, acted as thermally stable Brønsted acid sites.
Lithium‐Functionalized Metal–Organic Frameworks that Show >10 wt % H2 Uptake at Ambient Temperature
Authors: Han Sang Soo , Jung Dong Hyun , Choi Seung‐Hoon , Heo Jiyoung
Published: June 2013

We have used grand canonical Monte Carlo simulations with a first‐principles‐based force field to show that metal–organic frameworks (MOFs) with Li functional groups (i.e. CLi bonds) allow for exceptional H2 uptake at ambient temperature. For example, at 298 K and 100 bar, IRMOF‐1‐4Li shows a total H2 uptake of 5.54 wt % and MOF‐200‐27Li exhibits a total H2 uptake of 10.30 wt %, which are much higher than the corresponding values with pristine MOFs. Li‐functionalized MOF‐200 (MOF‐200‐27Li) shows 11.84 wt % H2 binding at 243 K and 100 bar. These hydrogen‐storage capacities exceed the 2015 DOE target of 5.5 wt % H2. Moreover, the incorporation of Li functional groups into MOFs provides more benefits, such as higher delivery amount, for H2 uptake than previously reported Li‐doped MOFs.
Thermal Activation of Ammonia by Transition‐Metal Hydroxide Cations
Authors: Kretschmer Robert , Schlangen Maria , Schwarz Helmut
Published: June 2013

With the exception of [Cu(OH)]+, the thermal reactions of the first‐row transition‐metal hydroxide cations, [Sc(OH)]+–[Zn(OH)]+, with ammonia have been studied by means of gas‐phase experiments and by computational methods for the whole series. The primary reaction channels involve NH bond activation, forming [M(NH2)]+ concomitantly with the elimination of water, and adduct formation, leading to [M(OH)(NH3)]+. Furthermore, [Ti(OH)]+ and [V(OH)]+ react with ammonia under dehydrogenation conditions, leading to [M,O,N,H2]+ (M=Ti, V), and for [Ni(OH)]+ ligand exchange is observed. Computations of the main reaction channels have been performed for the [M(OH)]+/NH3 couples (M=Sc–Zn) to uncover the underlying reaction mechanism and periodic trends across the first row. For NH bond activation, σ‐bond metathesis was found to be the underlying mechanism.
Assembly of Tin Oxide/Graphene Nanosheets into 3D Hierarchical Frameworks for High‐Performance Lithium Storage
Authors: Huang Yanshan , Wu Dongqing , Han Sheng , Li Shuang , Xiao Li , Zhang Fan , Feng Xinliang
Published: June 2013

3D hierarchical tin oxide/graphene frameworks (SnO2/GFs) were built up by the in situ synthesis of 2D SnO2/graphene nanosheets followed by hydrothermal assembly. These SnO2/GFs exhibited a 3D hierarchical porous architecture with mesopores (≈3 nm), macropores (3–6 μm), and a large surface area (244 m2 g−1), which not only effectively prevented the agglomeration of SnO2 nanoparticles, but also facilitated fast ion and electron transport in 3D pathways. As a consequence, the SnO2/GFs exhibited a high capacity of 830 mAh g−1 for up to 70 charge–discharge cycles at 100 mA g−1. Even at a high current density of 500 mA g−1, a reversible capacity of 621 mAh g−1 could be maintained for SnO2/GFs with excellent cycling stability. Such performance is superior to that of previously reported SnO2/graphene and other SnO2/carbon composites with similar weight contents of SnO2.