bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐Compensated Insulating ZnO‐Based Piezoelectric Nanogenerators
Authors: Kim Dohwan , Lee Keun Young , Gupta Manoj Kumar , Majumder Subrata , Kim Sang‐Woo
Published: September 2014

Remarkable enhancement of piezoelectric power output from a nanogenerator (NG) based on a zinc oxide (ZnO) thin film is achieved via native defect control. A large number of unintentionally induced point defects that act as n‐type carriers in ZnO have a strong influence on screening the piezoelectric potential into a piezoelectric NG. Here, additional oxygen molecules bombarded into ZnO lead to oxygen‐rich conditions, and the n‐type conductivity of ZnO is decreased dramatically. The acceptor‐type point defects such as zinc vacancies created during the deposition process trap n‐type carriers occurring from donor‐type point defects through a self‐compensation mechanism. This unique insulating‐type ZnO thin film‐based NGs (IZ‐NGs) generates output voltage around 1.5 V that is over ten times higher than that of an n‐type ZnO thin film‐based NG (around 0.1 V). In addition, it is found that the power output performance of the IZ‐NG can be further increased by hybridizing with a p‐type polymer (poly(3‐hexylthiophene‐2,5‐diyl):phenyl‐C61‐butyric acid methyl ester) via surface free carrier neutralization.
Ultraviolet‐Light‐Induced Reversible and Stable Carrier Modulation in MoS2 Field‐Effect Transistors
Authors: Singh Arun Kumar , Andleeb Shaista , Singh Jai , Dung Hoang Tien , Seo Yongho , Eom Jonghwa
Published: September 2014

The tuning of charge carrier concentrations in semiconductor is necessary in order to approach high performance of the electronic and optoelectronic devices. It is demonstrated that the charge‐carrier density of single‐layer (SL), bilayer (BL), and few‐layer (FL) MoS2 nanosheets can be finely and reversibly tuned with N2 and O2 gas in the presence of deep‐ultraviolet (DUV) light. After exposure to N2 gas in the presence of DUV light, the threshold voltages of SL, BL, and FL MoS2 field‐effect transistors (FETs) shift towards negative gate voltages. The exposure to N2 gas in the presence of DUV light notably improves the drain‐to‐source current, carrier density, and charge‐carrier mobility for SL, BL, and FL MoS2 FETs. Subsequently, the same devices are exposed to O2 gas in the presence of DUV light for different periods and the electrical characteristics are completely recovered after a certain time. The doping by using the combination of N2 and O2 gas with DUV light provides a stable, effective, and facile approach for improving the performance of MoS2 electronic devices.
Adaptive Amphiphilic Dendrimer‐Based Nanoassemblies as Robust and Versatile siRNA Delivery Systems
Authors: Liu Xiaoxuan , Zhou Jiehua , Yu Tianzhu , Chen Chao , Cheng Qiang , Sengupta Kheya , Huang Yuanyu , Li Haitang , Liu Cheng , Wang Yang , Posocco Paola , Wang Menghua , Cui Qi , Giorgio Suzanne , Fermeglia Maurizio , Qu Fanqi , Pricl Sabrina , Shi Yanhong , Liang Zicai , Rocchi Palma , Rossi John J. , Peng Ling
Published: September 2014

siRNA delivery remains a major challenge in RNAi‐based therapy. Here, we report for the first time that an amphiphilic dendrimer is able to self‐assemble into adaptive supramolecular assemblies upon interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the currently available nonviral vectors. In addition, this amphiphilic dendrimer is able to harness the advantageous features of both polymer and lipid vectors and hence promotes effective siRNA delivery. Our study demonstrates for the first time that dendrimer‐based adaptive supramolecular assemblies represent novel and versatile means for functional siRNA delivery, heralding a new age of dendrimer‐based self‐assembled drug delivery in biomedical applications.
Proteasesonden, die Spaltung durch Excimeremission anzeigen
Authors: Fischbach Melanie , Resch‐Genger Ute , Seitz Oliver
Published: September 2014

Peptidbasierte Sonden, die nach einer proteolytischen Spaltung fluoreszieren, sind unschätzbare Hilfsmittel für Untersuchungen von Proteaseaktivitäten. Eine Signalerzeugung durch Pyrenexcimere ist vorteilhaft, da die große Stokes‐Verschiebung und die lange Lebensdauer der Excimeremission Messungen in autofluoreszierenden Medien wie Blutserum erleichtern. Die proteolytische Spaltung stört jedoch die Proximitätsbeziehungen, die für eine excimerbasierte Signalgebung notwendig sind. Wir stellen eine neue Sondenarchitektur vor, bei der die Pyrenexcimeremission durch Spaltung eingeschaltet wird. Die Methode beruht auf haarnadelförmigen Peptidnukleinsäure(PNA)‐Peptid‐Hybriden. Im PNA‐Stamm werden Pyreneinheiten und Anthrachinonlöscher reißverschlussartig positioniert. Die Excimer Hairpin Peptide Beacons erbringen eine bis zu 50‐fache Verstärkung der Pyrenexcimeremission. Zeitaufgelöste Messungen ermöglichen die Detektion der Matrixmetalloprotease 7 im humanen Blutserum.
Use of the Wilkinson Catalyst for the ortho‐CH Heteroarylation of Aromatic Amines: Facile Access to Highly Extended π‐Conjugated Heteroacenes for Organic Semiconductors
Authors: Huang Yumin , Wu Di , Huang Jingsheng , Guo Qiang , Li Juan , You Jingsong
Published: September 2014

An unprecedented catalytic system composed of the Wilkinson catalyst [Rh(PPh3)3Cl] and CF3COOH enabled the highly regioselective cross‐coupling of aromatic amines with a variety of heteroarenes through dual CH bond cleavage. This protocol provided a facile and rapid route from readily available substrates to (2‐aminophenyl)heteroaryl compounds, which may be conveniently transformed into highly extended π‐conjugated heteroacenes. The experimental studies and calculations showed that thianaphtheno[3,2‐b]indoles have large HOMO–LUMO energy gaps and low‐lying HOMO levels, and could therefore potentially be high‐performance organic semiconductors. Herein we report the first use of a rhodium(I) catalyst for oxidative CH/CH coupling reactions. The current innovative catalyst system is much less expensive than [RhCp*Cl2]2/AgSbF6 and could open the door for the application of this approach to other types of CH activation processes.
Rhodium‐Catalyzed Cyclization of Diynes with Nitrones: A Formal [2+2+5] Approach to Bridged Eight‐Membered Heterocycles
Authors: Wang Chunxiang , Wang Dongping , Yan Hao , Wang Haolong , Pan Bin , Xin Xiaoyi , Li Xincheng , Wu Fan , Wan Boshun
Published: September 2014

N‐aryl‐substituted nitrones were employed as five‐atom coupling partners in the rhodium‐catalyzed cyclization with diynes. In this reaction, the nitrone moiety served as a directing group for the catalytic CH activation of the N‐aryl ring. This formal [2+2+5] approach allows rapid access to bridged eight‐membered heterocycles with broad substrate scope. The results of this study may provide new insight into the chemistry of nitrones and find applications in the synthesis of other heterocycles.
Visible‐Light‐Mediated 1,2‐Acyl Migration: The Reaction of Secondary Enamino Ketones with Singlet Oxygen
Authors: Fan Weigang , Li Pixu
Published: September 2014

Secondary enaminones were oxidized by photochemically generated singlet oxygen, followed by nucleophilic addition of alcohol and an unexpected 1,2‐acyl migration to afford quaternary amino acid derivatives. An ene‐type reaction pathway is proposed. It is distinctively different from the typical [2+2] addition of singlet oxygen to a CC bond pathway.
Synthesis and Antibacterial Activity of Some Novel 4‐Oxopyrido[2,3‐a]phenothiazines
Authors: Al‐Sinjilawi Hadeel T. , El‐Abadelah Mustafa M. , Mubarak Mohammad S. , Al‐Aboudi Amal , Abadleh Mohammed M. , Mahasneh Adel M. , Ahmad Asaad K. M. A.
Published: September 2014

A series of substituted 4‐oxopyrido[2,3‐a]phenothiazine‐3‐carboxylic acids (6a–d) were prepared via cyclization of the corresponding ethyl 7‐(arylthioxy)‐8‐nitro(or azido)‐4‐oxoquinoline‐3‐carboxylates (3a–d/4a–d), followed by hydrolysis of the resultant esters (5a–d). Among these tetracyclics, compound 6a with unsubstituted terminal benzo‐ring D was the most active against representative Gram‐positive and Gram‐negative bacterial strains. These compounds were also active against methicillin‐resistant Staphylococcus aureus (MRSA), with very low toxicity to normal cells. Virtual screening using ligand–protein docking modeling predicted that the compounds 6a–d are potential inhibitors of the topoisomerase IV enzyme and that hydrophobic interactions and hydrogen bonds are the major molecular interactions between these compounds and the residues of the active site of topoisomerase IV.
Restored Immunosuppressive Effect of Mesenchymal Stem Cells on B Cells After Olfactory 1/Early B Cell Factor–Associated Zinc‐Finger Protein Down‐Regulation in Patients With Systemic Lupus Erythematosus
Authors: Feng Xuebing , Che Nan , Liu Yan , Chen Haifeng , Wang Dandan , Li Xia , Chen Weiwei , Ma Xiaolei , Hua Bingzhu , Gao Xiang , Tsao Betty P. , Sun Lingyun
Published: September 2014

Objective

To evaluate whether olfactory 1/early B cell factor–associated zinc‐finger protein (OAZ), a candidate lupus susceptibility gene involved in antinuclear antibody (ANA) production, plays a role in the regulation of B cells by mesenchymal stem cells (MSCs).

Methods

MSCs derived from the bone marrow of patients with systemic lupus erythematosus (SLE) and healthy control subjects were expanded and incubated with small interfering RNAs specific for OAZ or a nontargeting sequence. Knockdown of messenger RNA levels of OAZ and its downstream genes was measured using real‐time polymerase chain reaction, and protein levels of chemokine/cytokine and immunoglobulins were determined by enzyme‐linked immunosorbent assay or Western blotting. The effects of modulating the OAZ levels in MSCs, by either silencing or overexpression, on B cell proliferation and terminal differentiation were assessed by coculturing MSCs with mouse spleen cells.

Results

OAZ gene expression was highly enriched in MSCs compared with peripheral blood leukocytes and was increased in patients with SLE compared with control subjects. After the silencing of OAZ expression, SLE MSCs could regain the ability to inhibit B cell proliferation and terminal differentiation, as indicated by decreased percentages of bromodeoxyuridine‐positive cells and CD138+ cells as well as decreased levels of IgG, IgM, and ANAs. The level of CCL2 was increased after OAZ knockdown, while anti‐CCL2 antibodies completely counteracted the effect of OAZ silencing. Umbilical cord–derived normal MSCs that overexpressed OAZ had a diminished ability to inhibit B cell proliferation and terminal differentiation.

Conclusion

OAZ down‐regulation could restore the impaired function of SLE MSCs in the immune regulation of B cells, contributing to a reduction in ANA levels. OAZ might represent a new target for therapy in patients with SLE.
Heuristic Dynamic Programming Using Echo State Network For Multivariable Tracking Control Of Wastewater Treatment Process
Authors: Ying‐Chun Bo , Jun‐Fei Qiao
Published: September 2014

This paper proposes a heuristic dynamic programming (HDP) scheme to simultaneously control the dissolved oxygen concentration and the nitrate level in wastewater treatment processes (WWTP). Unlike traditional HDP schemes, the optimal control values are calculated in an analytical way by the proposed HDP controller. It can reduce the learning burden of the HDP controller to a great extent. The system model and the evaluation indexJare approximated by two echo state networks (ESNs). Gradient‐based learning algorithms are employed to train both ESNs online, and the convergence of the training algorithm is investigated based on Lyapunov theory. The performance of the proposed ESN‐based HDP (E‐HDP) controller is tested and evaluated on a WWTP benchmark. Experimental results demonstrate that the proposed approach can achieve effective performance.
Impact of heavy vehicles on surrounding traffic characteristics
Authors: Moridpour Sara , Mazloumi Ehsan , Mesbah Mahmoud
Published: September 2014

This work examines the impact of heavy vehicle movements on measured traffic characteristics in detail. Although the number of heavy vehicles within the traffic stream is only a small percentage, their impact is prominent. Heavy vehicles impose physical and psychological effects on surrounding traffic flow because of their length and size (physical) and acceleration/deceleration (operational) characteristics. The objective of this work is to investigate the differences in traffic characteristics in the vicinity of heavy vehicles and passenger cars. The analysis focuses on heavy traffic conditions (level of service E) using a trajectory data of highway I‐80 in California. The results show that larger front and rear space gaps exist for heavy vehicles compared with passenger cars. This may be because of the limitations in manoeuvrability of heavy vehicles and the safety concerns of the rear vehicle drivers, respectively. In addition, heavy vehicle drivers mainly keep a constant speed and do not change their speed frequently. This work also examines the impact of heavy vehicles on their surrounding traffic in terms of average travel time and number of lane changing manoeuvres using Advanced Interactive Microscopic Simulator for Urban and Non‐Urban Networks (AIMSUN) microscopic traffic simulation package. According to the results, the average travel time increases when proportion of heavy vehicles rises in each lane. To reflect the impact of heavy vehicles on average travel time, a term related to heavy vehicle percentage is introduced into two different travel time equations, Bureau of Public Roads and Akçelik's travel time equations. The results show that using an exclusive term for heavy vehicles can better estimate the travel times for more than 10%. Finally, number of passenger car lane changing manoeuvres per lane will be more frequent when more heavy vehicles exist in that lane. The influence of heavy vehicles on the number of passenger car lane changing is intensified in higher traffic densities and higher percentage of heavy vehicles. Large numbers of lane changing manoeuvres can increase the number of traffic accidents and potentially reduce traffic safety. The results show an increase of 5% in the likelihood of accidents, when percentage of heavy vehicles increases to 30% of total traffic. Copyright © 2014 John Wiley & Sons, Ltd.
Behrings Nachlässe – Behrings Biographien
Authors: Enke Ulrike
Published: September 2014

Behring’s Personal Papers – Behring’s Lives. The article wants to show the connection between the enriched personal papers of Emil von Behring (1854–1917) in the Behring archives in Marburg (established in 1927) and the history of the first biography of the scientist, which was published by Heinz Zeiss and Richard Bieling during Nazi era in 1940. One focus is placed on Behring’s widow Else von Behring (1876–1936), who was active in arranging Behring’s papers in proper order and in searching a biographer of her husband’s life. The paper also presents new discoveries from the Behring Works archives in Marburg which show Behring – founder of the serum therapy and first winner of the Nobel Prize for medicine in 1901 – as an entrepreneur who was fighting for control and influence in the field of science and of business: maybe another narration of Behring’s life.
Deborah R. Coen
Authors: Hochadel Oliver
Published: September 2014

The Earthquake Observers: Disaster Science from Lisbon to Richter, Chicago/London: University of Chicago Press 2013. 348 S., geb., $ 35,00. ISBN 978‐0‐226‐11181‐0.
The evolution of down‐scale virus filtration equipment for virus clearance studies
Authors: Wieser Andreas , Berting Andreas , Medek Christian , Poelsler Gerhard , Kreil Thomas R.
Published: September 2014

The role of virus filtration in assuring the safety of biopharmaceutical products has gained importance in recent years. This is due to the fundamental advantages of virus filtration, which conceptually can remove all pathogens as long as their size is larger than the biomolecule of commercial interest, while at the same time being neutral to the biological activity of biopharmaceutical compound(s). Major progress has been made in the development of adequate filtration membranes that can remove even smaller viruses, or possibly even all.

Establishing down‐scaled models for virus clearance studies that are fully equivalent with respect to operating parameters at manufacturing scale is a continuing challenge. This is especially true for virus filtration procedures where virus clearance studies at small‐scale determine the operating parameters, which can be used at manufacturing scale. This has limited volume‐to‐filter‐area‐ratios, with significant impact on process economics.

An advanced small‐scale model of virus filtration, which allows the investigation of the full complexity of these processes, is described here. It includes the automated monitoring and control of all process parameters, as well as an electronic data acquisition system, which is fully compliant with current regulatory requirements for electronic records in a pharmaceutical environment. Biotechnol. Bioeng. 2015;112: 633–637. © 2014 Wiley Periodicals, Inc.
Phosphodiesterase DosP increases persistence by reducing cAMP which reduces the signal indole
Authors: Kwan Brian W. , Osbourne Devon O. , Hu Ying , Benedik Michael J. , Wood Thomas K.
Published: September 2014

Persisters are bacteria that are highly tolerant to antibiotics due to their dormant state and are of clinical significance owing to their role in infections. Given that the population of persisters increases in biofilms and that cyclic diguanylate (c‐di‐GMP) is an intracellular signal that increases biofilm formation, we sought to determine whether c‐di‐GMP has a role in bacterial persistence. By examining the effect of 30 genes from Escherichia coli, including diguanylate cyclases that synthesize c‐di‐GMP and phosphodiesterases that breakdown c‐di‐GMP, we determined that DosP (direct oxygen sensing phosphodiesterase) increases persistence by over a thousand fold. Using both transcriptomic and proteomic approaches, we determined that DosP increases persistence by decreasing tryptophanase activity and thus indole. Corroborating this effect, addition of indole reduced persistence. Despite the role of DosP as a c‐di‐GMP phosphodiesterase, the decrease in tryptophanase activity was found to be a result of cyclic adenosine monophosphate (cAMP) phosphodiesterase activity. Corroborating this result, the reduction of cAMP via CpdA, a cAMP‐specific phosphodiesterase, increased persistence and reduced indole levels similarly to DosP. Therefore, phosphodiesterase DosP increases persistence by reducing the interkingdom signal indole via reduction of the global regulator cAMP. Biotechnol. Bioeng. 2015;112: 588–600. © 2014 Wiley Periodicals, Inc.
On the model‐based optimization of secreting mammalian cell (GS‐NS0) cultures
Authors: Kiparissides A. , Pistikopoulos E. N. , Mantalaris A.
Published: September 2014

The global bio‐manufacturing industry requires improved process efficiency to satisfy the increasing demands for biochemicals, biofuels, and biologics. The use of model‐based techniques can facilitate the reduction of unnecessary experimentation and reduce labor and operating costs by identifying the most informative experiments and providing strategies to optimize the bioprocess at hand. Herein, we investigate the potential of a research methodology that combines model development, parameter estimation, global sensitivity analysis, and selection of optimal feeding policies via dynamic optimization methods to improve the efficiency of an industrially relevant bioprocess. Data from a set of batch experiments was used to estimate values for the parameters of an unstructured model describing monoclonal antibody (mAb) production in GS‐NS0 cell cultures. Global Sensitivity Analysis (GSA) highlighted parameters with a strong effect on the model output and data from a fed‐batch experiment were used to refine their estimated values. Model‐based optimization was used to identify a feeding regime that maximized final mAb titer. An independent fed‐batch experiment was conducted to validate both the results of the optimization and the predictive capabilities of the developed model. The successful integration of wet‐lab experimentation and mathematical model development, analysis, and optimization represents a unique, novel, and interdisciplinary approach that addresses the complicated research and industrial problem of model‐based optimization of cell based processes. Biotechnol. Bioeng. 2015;112: 536–548. © 2014 Wiley Periodicals, Inc.
The persuasive effectiveness of mini‐films: Narrative transportation and fantasy proneness
Authors: Chen Tsai
Published: September 2014

Little empirical investigation has been made on mini‐films, an innovative online marketing technique of branded entertainment. This study intends to gain a deeper understanding of the advertising effectiveness of mini‐films. Employing a narrative persuasion research approach, an online survey with hyperlinks to a variety of real mini‐films was conducted to test the aggregate persuasive effectiveness of this marketing innovation. The results demonstrated that narrative transportation has a major influence on the attitude toward the mini‐film; the mini‐film attitude fully mediates the effect of narrative transportation to brand attitude, and subsequently to purchase intention. Furthermore, conceptualized as a normal consumer characteristic, the influence of fantasy proneness on the persuasive mechanism of this online advertising genre has also been under study. Empirical evidence showed that fantasy proneness has a positive influence on narrative transportation. This study has made a contribution to academics and practitioners alike for future research into branded entertainment. Copyright © 2014 John Wiley & Sons, Ltd.
Redesigning Arithmetic for Student Success: Supporting Faculty to Teach in New Ways
Authors: Bickerstaff Susan , Lontz Barbara , Cormier Maria Scott , Xu Di
Published: September 2014

This chapter describes a promising new approach to teaching developmental arithmetic and prealgebra, and presents research findings that demonstrate how a faculty support network helped instructors adopt new teaching strategies and gain confidence in teaching the reformed course.
Strategies for Integrating Student Supports and Academics
Authors: Dadgar Mina , Nodine Thad , Bracco Kathy Reeves , Venezia Andrea
Published: September 2014

This chapter defines the integration of academics and student support services and offers examples of models and strategies from colleges nationally.
What We've Learned About Supporting Faculty, Administrator, and Staff Engagement
Authors: Kadlec Alison , Rowlett Isaac
Published: September 2014

This chapter focuses on how colleges can increase faculty, administrator, and staff engagement in reform processes, with the message that large‐scale change is not merely technical work; there is a powerful human dimension that can make or break a reform.
Putting the Pieces Together: Lessons Learned for Future Reforms
Authors: Venezia Andrea , Hughes Katherine L.
Published: September 2014

This chapter summarizes the main lessons learned throughout the volume and highlights common needs with any large‐scale reform along with common strategies.
Catalysis via Sol–Gel Acid Silicas: An Important Chemical Technology for 2nd Generation Biorefineries
Authors: Ciriminna Rosaria , Demma Carà Piera , Lopez‐Sanchez Jose A. , Pagliaro Mario
Published: September 2014

Heterogeneously catalyzed processes using mesoporous acid silicas selectively afford many valued products from biomass components. The versatile nanochemistry of the sol–gel process allows to shape materials with catalytically attractive morphologies, as well as to further functionalize the inner mesoporosity with other active species affording nanocomposites suitable for consecutive reactions in one‐pot. Using selected examples from recent chemical research, we identify an approach that will likely produce catalysts of enhanced performance, suitable for practical application.
Homogeneous Photocatalytic Reduction of CO2 to CO Using Iron(0) Porphyrin Catalysts: Mechanism and Intrinsic Limitations
Authors: Bonin Julien , Chaussemier Marie , Robert Marc , Routier Mathilde
Published: September 2014

A photochemical catalytic reduction of CO2 was performed in an organic solvent with iron(0) porphyrins as homogeneous molecular catalysts under visible light irradiation. With modified tetraphenylporphyrins consisting of internal phenolic groups, the photochemical process led to the production of CO, with H2 as a minor product. High catalytic selectivity for CO formation and turnover numbers up to 30 were obtained. Degradation of the catalyst occurred at longer irradiation times, along with decreased selectivity. Furthermore, addition of a weak acid, which increased the reduction efficiency under electrochemical conditions, led to rapid deactivation of the catalyst. With the unmodified tetraphenylporphyrin as catalyst, we observed lower performance and higher proportion of H2, which highlighted differences in the reduction pathways followed. A combination of a spectroscopic study and product analysis performed under various conditions led to detailed reduction mechanisms and helped pave the way for designing durable photocatalytic systems.
Combined Experimental and Theoretical Study on the Reactivity of Compounds I and II in Horseradish Peroxidase Biomimetics
Authors: Ji Li , Franke Alicja , Brindell Małgorzata , Oszajca Maria , Zahl Achim , van Eldik Rudi
Published: September 2014

For the exploration of the intrinsic reactivity of two key active species in the catalytic cycle of horseradish peroxidase (HRP), Compound I (HRP‐I) and Compound II (HRP‐II), we generated in situ [FeIVO(TMP+.)(2‐MeIm)]+ and [FeIVO(TMP)(2‐MeIm)]0 (TMP=5,10,15,20‐tetramesitylporphyrin; 2‐MeIm=2‐methylimidazole) as biomimetics for HRP‐I and HRP‐II, respectively. Their catalytic activities in epoxidation, hydrogen abstraction, and heteroatom oxidation reactions were studied in acetonitrile at −15 °C by utilizing rapid‐scan UV/Vis spectroscopy. Comparison of the second‐order rate constants measured for the direct reactions of the HRP‐I and HRP‐II mimics with the selected substrates clearly confirmed the outstanding oxidizing capability of the HRP‐I mimic, which is significantly higher than that of HRP‐II. The experimental study was supported by computational modeling (DFT calculations) of the oxidation mechanism of the selected substrates with the involvement of quartet and doublet HRP‐I mimics (2,4Cpd I) and the closed‐shell triplet spin HRP‐II model (3Cpd II) as oxidizing species. The significantly lower activation barriers calculated for the oxidation systems involving 2,4Cpd I than those found for 3Cpd II are in line with the much higher oxidizing efficiency of the HRP‐I mimic proven in the experimental part of the study. In addition, the DFT calculations show that all three reaction types catalyzed by HRP‐I occur on the doublet spin surface in an effectively concerted manner, whereas these reactions may proceed in a stepwise mechanism with the HRP‐II mimic as oxidant. However, the high desaturation or oxygen rebound barriers during CH bond activation processes by the HRP‐II mimic predict a sufficient lifetime for the substrate radical formed through hydrogen abstraction. Thus, the theoretical calculations suggest that the dissociation of the substrate radical may be a more favorable pathway than desaturation or oxygen rebound processes. Importantly, depending on the electronic nature of the oxidizing species, that is, 2,4Cpd I or 3Cpd II, an interesting region‐selective conversion phenomenon between sulfoxidation and H‐atom abstraction was revealed in the course of the oxidation reaction of dimethylsulfide. The combined experimental and theoretical study on the elucidation of the intrinsic reactivity patterns of the HRP‐I and HRP‐II mimics provides a valuable tool for evaluating the particular role of the HRP active species in biological systems.
Rational Design of Heat‐Set and Specific‐Ion‐Responsive Supramolecular Hydrogels Based on the Hofmeister Effect
Authors: Nebot Vicent J. , Ojeda‐Flores Juan J. , Smets Johan , Fernández‐Prieto Susana , Escuder Beatriu , Miravet Juan F.
Published: September 2014

Smart supramolecular hydrogels have been prepared from a bolaamphiphilic L‐valine derivative in aqueous solutions of different salts. The hydrogels respond selectively to different ions and are either reinforced or weakened. In one case, in contrast to conventional systems, the hydrogels are formed upon heating of the system. The use of the hydrogels in the controlled release of an entrapped dye is described as a proof of the potential applications of these systems. The responsive hydrogels were rationally designed by taking into account the noticeable effect of different ions from the Hofmeister series in the solubility of the hydrogelator, which was assessed by using NMR experiments. On the one hand, kosmotropic anions such as sulfate produce a remarkable solubility decrease in the gelator, which is associated with gel reinforcement, as measured by rheological experiments. On the other hand, chaotropic species such as perchlorate weaken the gel. A dramatic effect was observed in the presence of guanidinium chloride, which boosted the solubility of the gelator, in accordance with its chaotropic behaviour reported in protein science. In this case, a direct interaction of the guanidinium species with the carbonyl groups of the hydrogelator is detected by 13C NMR spectroscopy. The weakening of this interaction upon a temperature increase allows for the preparation of heat‐set hydrogelating systems.
Discovery of Methyl 4′‐Methyl‐5‐(7‐nitrobenzo[c][1,2,5]oxadiazol‐4‐yl)‐[1,1′‐biphenyl]‐3‐carboxylate, an Improved Small‐Molecule Inhibitor of c‐Myc–Max Dimerization
Authors: Chauhan Jay , Wang Huabo , Yap Jeremy L. , Sabato Philip E. , Hu Angela , Prochownik Edward V. , Fletcher Steven
Published: September 2014

c‐Myc is a basic helix‐loop‐helix‐leucine zipper (bHLH‐ZIP) transcription factor that is responsible for the transcription of a wide range of target genes involved in many cancer‐related cellular processes. Over‐expression of c‐Myc has been observed in, and directly contributes to, a variety of human cancers including those of the hematopoietic system, lung, prostate and colon. To become transcriptionally active, c‐Myc must first dimerize with Myc‐associated factor X (Max) via its own bHLH‐ZIP domain. A proven strategy towards the inhibition of c‐Myc oncogenic activity is to interfere with the structural integrity of the c‐Myc–Max heterodimer. The small molecule 10074‐G5 is an inhibitor of c‐Myc–Max dimerization (IC50=146 μM) that operates by binding and stabilizing c‐Myc in its monomeric form. We have identified a congener of 10074‐G5, termed 3jc48‐3 (methyl 4′‐methyl‐5‐(7‐nitrobenzo[c][1,2,5]oxadiazol‐4‐yl)‐[1,1′‐biphenyl]‐3‐carboxylate), that is about five times as potent (IC50=34 μM) at inhibiting c‐Myc–Max dimerization as the parent compound. 3jc48‐3 exhibited an approximate twofold selectivity for c‐Myc–Max heterodimers over Max–Max homodimers, suggesting that its mode of action is through binding c‐Myc. 3jc48‐3 inhibited the proliferation of c‐Myc‐over‐expressing HL60 and Daudi cells with single‐digit micromolar IC50 values by causing growth arrest at the G0/G1 phase. Co‐immunoprecipitation studies indicated that 3jc48‐3 inhibits c‐Myc–Max dimerization in cells, which was further substantiated by the specific silencing of a c‐Myc‐driven luciferase reporter gene. Finally, 3jc48‐3′s intracellular half‐life was >17 h. Collectively, these data demonstrate 3jc48‐3 to be one of the most potent, cellularly active and stable c‐Myc inhibitors reported to date.
CCRL1 marks heterogeneity in cortical and medullary thymic epithelial cells
Authors: Ohigashi Izumi , Takahama Yousuke
Published: September 2014

Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs), which play essential roles in the establishment of a functionally competent and self‐tolerant repertoire of T cells, are derived from common thymic epithelial progenitor cells (pTECs). Recent findings indicate that mTECs are derived from cells that express molecules that are abundant in cTECs rather than mTECs, and provide fresh insight into the characteristics of pTECs and their diversification pathways into TEC subpopulations. In this issue of the European Journal of Immunology, Ribeiro et al. [Eur. J. Immunol. 2014. 44: 2918–2924] focus on CCRL1, an atypical chemokine receptor that is highly expressed by cTECs rather than mTECs, and show that CCRL1‐expressing embryonic TECs can give rise to mTECs. Interestingly, Ribeiro et al. further report that a fraction of postnatal mTECs express CCRL1 at a low level, suggesting novel complexity in mTECs.
Arylsulfonyl Groups: The Best Cyclization Auxiliaries for the Preparation of ATRC γ‐Lactams can be Acidolytically Removed
Authors: Clark Andrew J. , Cornia Andrea , Felluga Fulvia , Gennaro Armando , Ghelfi Franco , Isse Abdirisak A. , Menziani Maria Cristina , Muniz‐Miranda Francesco , Roncaglia Fabrizio , Spinelli Domenico
Published: September 2014

The N‐arylsulfonyl group, which is the best and most useful cyclization auxiliary for the transition‐metal‐catalyzed atom transfer radical cyclization (ATRC) of N‐allyl‐α‐polychloroamides, can be effectively removed from the target γ‐lactams by using H2SO4–HOAc, without impairing the halogen functions. The reaction involves H+ attack on the aromatic moiety, and is strongly responsive to the electronic properties of the substituent bound to the aromatic ring: electron‐donating groups, such as methyl or methoxy are, in fact, required for efficient “deprotection”. The N‐p‐nitrophenylsulfonyl cyclization auxiliary, in contrast to all the other sulfonyl groups tested, proved to be unsuitable for the ATRC, owing to a side reductive transposition that halts the redox cycle.
Use of grape pomaces to produce biomass of a Komagataella pastoris strain expressing a bovine chymosin activity
Authors: Kingston Diego , Novelli Guido F. , Cerrutti Patricia , Recupero Matias N. , Blasco Martin , Galvagno Miguel A.
Published: September 2014

The use of agroindustrial wastes not only decreases bioprocesses and disposal costs but also contributes to the upgrading of the residues. An active recombinant methanol‐inducible bovine chymosin has been expressed in our laboratory in the yeast Komagataella pastoris, and grape pomace extracts (GRE) were proposed as a convenient C‐energy source for the biomass production of the genetically engineered strain. Carbon and nitrogen sources, growth factors, and initial pH conditions were selected by classical methodology; thereafter, growth conditions optimization was performed using statistical designed experiments (DoEs). In the presence of (in g·L−1) 67.0 monosaccharides (glucose and fructose) from GRE, 5.0 (NH4)2SO4, and 10.0 sugar cane molasses (CMz), a yield of 20.0 g·L−1 cell dry weight (CDW) was obtained aerobically after 60 h incubation at 28°C and pH 4.0. Applying a fed‐batch strategy with methanol:sorbitol as the enzyme inducers, a chymosin production of 8.53 International Milk Clotting Units (IMCU) per mg protein was obtained in the supernatant. The results presented show that through a statistical design, a simple, cheap, and easy to prepare culture medium could be developed using two agroindustrial derivatives (GRE and CMz) to obtain a higher value added product.
Understanding and Improving Campus Climates for Activists
Authors: Martin Georgianna L.
Published: September 2014

This chapter synthesizes the common themes across chapters in this volume and argues that campus activists are an integral part of the higher education landscape.
Management of the compromised airway and role of tracheotomy in anaplastic thyroid carcinoma
Authors: Mani Navin , McNamara Katherine , Lowe Natalie , Loughran Sean , Yap Beng K.
Published: September 2014

Background

Anaplastic thyroid carcinoma (ATC) is an uncommon thyroid malignancy with a poor prognosis. American Thyroid Association (ATA) guidelines acknowledge the complexity of airway management in these patients. We studied our local experience with the aim of providing guidance in airway management in ATC.

Methods

Patients with histologically confirmed ATC from January 2004 to December 2011 were identified from our institutional database. The data were retrospectively analyzed using hospital case notes.

Results

Twenty‐six patients were identified with ATC, 25 of who died from the disease. Five of 26 patients (19%) had stridor at presentation. A further 6 of 26 patients (23%) developed stridor during or soon after radiotherapy. Nine patients (36%) died of airway obstruction.

Conclusion

Tracheotomy can facilitate completion of palliative treatment in those patients with ATC and stridor. Given the short life expectancy of these patients, a balanced decision must be made regarding the role and timing of tracheotomy. © 2015 Wiley Periodicals, Inc. Head Neck 38: 85–88, 2016
Predicting backbone Cα angles and dihedrals from protein sequences by stacked sparse auto‐encoder deep neural network
Authors: Lyons James , Dehzangi Abdollah , Heffernan Rhys , Sharma Alok , Paliwal Kuldip , Sattar Abdul , Zhou Yaoqi , Yang Yuedong
Published: September 2014

Because a nearly constant distance between two neighbouring Cα atoms, local backbone structure of proteins can be represented accurately by the angle between Cαi−1CαiCαi+1 (θ) and a dihedral angle rotated about the CαiCαi+1 bond (τ). θ and τ angles, as the representative of structural properties of three to four amino‐acid residues, offer a description of backbone conformations that is complementary to φ and ψ angles (single residue) and secondary structures (>3 residues). Here, we report the first machine‐learning technique for sequence‐based prediction of θ and τ angles. Predicted angles based on an independent test have a mean absolute error of 9° for θ and 34° for τ with a distribution on the θ‐τ plane close to that of native values. The average root‐mean‐square distance of 10‐residue fragment structures constructed from predicted θ and τ angles is only 1.9Å from their corresponding native structures. Predicted θ and τ angles are expected to be complementary to predicted ϕ and ψ angles and secondary structures for using in model validation and template‐based as well as template‐free structure prediction. The deep neural network learning technique is available as an on‐line server called Structural Property prediction with Integrated DEep neuRal network (SPIDER) at http://sparks‐lab.org. © 2014 Wiley Periodicals, Inc.
Bi‐channel Surface Acoustic Wave Gas Sensor for Carbon Disulfide and Methanol Vapors in Polymer Plants
Authors: Chou Yu‐Chen , Shih Jeng‐Shong
Published: September 2014

A C60‐polyphenylacetylene (C60‐PPA) and polyvinylpyrrolidone (PVP) coated two‐channel surface acoustic wave (SAW) crystal gas sensor with a homemade computer interface for data acquisition and data processing was developed and employed to detect carbon disulfide (CS2) and methanol (CH3OH) vapors in polymer plants. The frequency of surface acoustic wave oscillator decreases due to the adsorption of gas molecules on the coated materials of the SAW sensor. Six coating materials (C60‐PPA, nafion, PPA, crytand [2,2], polyethene glycol and PVP) were used to adsorb and detect carbon disulfide and methanol gases. Adsorption of all the six coating materials to CS2 and CH3OH was found to be physical adsorption. The C60‐PPA coated SAW detector exhibited more sensitive to CS2 than the other coating materials. In contrast, the PVP coated SAW detector was more sensitive to CH3OH than the other coating materials. With the two‐channel SAW sensor, the C60‐PPA coated SAW showed a good detection limit of 0.4 ppm and good reproducibility with RSD of 3.37 % (n=10) for CS2. Similarly, the PVP coated SAW also showed a good detection limit of 0.05 ppm and good reproducibility, with RSD of 0.86 % (n=10) for CH3OH. The interference effect of other organic molecules on the SAW detection system was negligible, except for the irreversible adsorption of C60‐PPA to propylamine. The frequency signals from the two‐channel SAW sensor array C60‐PPA and PVP coatings were processed by a back‐propagation artificial neural network (BPN) and multiple regression analysis (MRA). Thus a two‐channel SAW sensor array with BPN and MRA has been successfully applied for the qualitative and quantitative analyses of CS2 and CH3OH in mixtures.
ZnO: An Ecofriendly, Green Nano‐catalyst for the Synthesis of Pyrazole Derivatives under Aqueous Media
Authors: Girish Yarabally R. , Kumar Kothanahally S. Sharath , Manasa Heggadihalli S. , Shashikanth Sheena
Published: September 2014

An efficient nano ZnO catalyzed green protocol for the synthesis of pyrazol derivatives by condensation of different substituted phenyl hydrazines/semicarbazide/thiosemicarbazide with 1,3‐diketone/ketoester at ambient temperature has been achieved. ZnO nanocatalyst was prepared by low temperature solution combustion method. From the Scherrer method the crystallite size of ZnO was estimated and found to be in the range of 30–50 nm. The main advantage of this protocol is an excellent yield, short reaction time and easy work up procedure. The catalyst was found to be reusable up to five catalytic cycles without any appreciable loss in activity of the catalyst.
Involvement of Intracellular Signaling in the IL‐1β Inhibitory Effect on Fructose Intestinal Absorption
Authors: Rodríguez‐Yoldi María J. , Gascón Sonia , Barranquero Cristina , García‐Barrios Alberto , Osada Jesús
Published: September 2014

A variety of bacteria and their excreted/secreted products having direct effects on epithelial ion transport and permeability and the release of cytokines during bacterial infection may impact directly on epithelial function. Interleukin‐1β (IL‐1β) is a pleiotropic cytokine that affects the intestinal absorption of nutrients. The aim of this work was to study the intracellular signaling pathways involved in the inhibitory effect of IL‐1β on D‐fructose intestinal transport in rabbit jejunum and Caco‐2 cells. The results show that the cytokine inhibitory effect was completely reversed in presence of proteasome or PKC selective inhibitors in IL‐1β treated rabbits. In addition, the activation of PI3K abolished the IL‐1β effect. Likewise, these results were confirmed in Caco‐2 cells. In addition, p‐PI3K expression was increased by IL‐1β‐treatment whereas the expression of p‐PKCα was not significantly affected. In summary, the results suggest that IL‐1β could regulate the activation of pPKCα 73, pPI3K 55, and NF‐kB proteins. These events could exert an inhibitory effect on fructose intestinal absorption by a modification of GLUT5 insertion to brush‐border membrane and/or the functional transporter activity. This effect is independent of hormonal milieu and nervous stimuli. J. Cell. Physiol. 230: 896–902, 2015. © 2014 Wiley Periodicals, Inc.
MicroRNA‐302a Stimulates Osteoblastic Differentiation by Repressing COUP‐TFII Expression
Authors: Kang In‐Hong , Jeong Byung‐Chul , Hur Sung‐Woong , Choi Hyuck , Choi Seung‐Ho , Ryu Je‐Hwang , Hwang Yun‐Chan , Koh Jeong‐Tae
Published: September 2014

Chicken ovalbumin upstream promoter transcription factor II (COUP‐TFII) is a potent transcription factor that represses osteoblast differentiation and bone formation. Previously, we observed that stimuli for osteoblast differentiation, such as bone morphogenetic protein 2 (BMP2), inhibits COUP‐TFII expression. This study was undertaken to identify BMP2‐regulated and COUP‐TFII‐targeting microRNAs (miRNAs), and to explore their regulatory roles in osteoblast differentiation. Based on in silico analysis, 12 miRNAs were selected and their expression in BMP2‐treated MC3T3‐E1 cells was examined. BMP2 induced miR‐302a expression in dose‐ and time‐dependent manners with the decrease in COUP‐TFII expression. Runx2, a BMP2‐downstream transcription factor, specifically regulated miR‐302a expression and its promoter activity. A computer‐based prediction algorithm led to the identification of two miR‐302a binding sites on the 3′‐untranslational region of COUP‐TFII mRNA (S1: 620–626 bp, S2: 1,016–1,022 bp), and a luciferase assay showed that miR‐302a directly targeted S1 and S2. Transfection of miR‐302a precursor significantly enhanced expression of osteogenic marker genes with decreasing COUP‐TFII mRNA and protein level, alkaline phosphatase activity and matrix mineralization. On the other hand, inhibition of miR‐302a significantly attenuated BMP2‐induced osteoblast specific gene expression, alkaline phosphatase activity, and matrix mineralization with increasing COUP‐TFII mRNA and protein level. These results indicate that miR‐302a is induced by osteogenic stimuli and promotes osteoblast differentiation by targeting COUP‐TFII. MiR‐302a could be a positive regulator for osteoblast differentiation. J. Cell. Physiol. 230: 911–921, 2015. © 2014 Wiley Periodicals, Inc.
Liver transplantation for intrahepatic cholangiocarcinoma
Authors: Hashimoto Koji , Miller Charles M.
Published: September 2014

The indication of liver transplantation for intrahepatic cholangiocarcinoma (ICC) is highly controversial. Initially, liver transplantation was embraced as a promising treatment for ICC, providing both a wider surgical margin and a potential cure for the underlying liver disease. However, the majority of transplant centers have abandoned liver transplantation for ICC due to poor long‐term survival and high recurrence rates. Interestingly, these decisions were based on studies with highly inconsistent outcomes due to a limited number of patients, various patient selection criteria, and the use of nonstandardized adjunctive therapy protocols. Indeed, recent studies have revealed that ICC patients with small solitary tumors have excellent long‐term survival after liver transplantation. Moreover, as seen in early‐stage hilar cholangiocarcinoma, neoadjuvant and adjuvant therapy hold promise for improved long‐term survival in patients with locally advanced ICC. As we work to expand treatment options for ICC, further evidence of success in this area is needed in order to justify the use of limited organ resources to treat ICC. Continued efforts to improve diagnosis of ICC, hone patient selection criteria, and implement standardized treatment protocols could provide certain patients with ICC access to potentially life‐saving liver transplantation.
Glycans of myelin proteins
Authors: Sedzik Jan , Jastrzebski Jan Pawel , Grandis Marina
Published: September 2014

Human P0 is the main myelin glycoprotein of the peripheral nervous system. It can bind six different glycans, all linked to Asn93, the unique glycosylation site. Other myelin glycoproteins, also with a single glycosylation site (PMP22 at Asn36, MOG at Asn31), bind only one glycan. The MAG has 10 glycosylation sites; the glycoprotein OMgp has 11 glycosylation sites. Aside from P0, no comprehensive data are available on other myelin glycoproteins. Here we review and analyze all published data on the physicochemical structure of the glycans linked to P0, PMP22, MOG, and MAG. Most data concern bovine P0, whose glycan moieties have an MW ranging from 1,294.56 Da (GP3) to 2,279.94 Da (GP5). The pI of glycosylated P0 protein varies from pH 9.32 to 9.46. The most charged glycan is MS2 containing three sulfate groups and one glucuronic acid; whereas the least charged one is the BA2 residue. All glycans contain one fucose and one galactose. The most mannose rich are the glycans MS2 and GP4, each of them has four mannoses; OPPE1 contains five N‐acetylglucosamines and one sulfated glucuronic acid; GP4 contains one sialic acid. Furthermore, human P0 variants causing both gain and loss of glycosylation have been described and cause peripheral neuropathies with variable clinical severity. In particular, the substitution T95→M is a very common in Europe and is associated with a late‐onset axonal neuropathy. Although peripheral myelin is made up largely of glycoproteins, mutations altering glycosylation have been described only in P0. This attractive avenue of research requires further study. © 2014 Wiley Periodicals, Inc.