bluuebunny/crossref_metadata_2025 huggingface dataset:
Migration of Resident Cardiac Stem Cells in Myocardial Infarction
Authors: Liang Simon X. , Phillips William D.
Published: December 2012

Ischemic heart disease is a major cause of morbidity and mortality worldwide. Stem cell‐based therapy, which aims to restore cardiac structure and function by regeneration of functional myocardium, has recently been proposed as a novel alternative treatment modality. Resident cardiac stem cells (CSCs) in adult hearts are a key cell type under investigation. CSCs have been shown to be able to repair damaged myocardium and improve myocardial function in both human and animal studies. This approach relies not only on the proliferation of the CSCs, but also upon their migration to the site of injury within the heart. Here, we briefly review reported CSC populations and discuss signaling factors and pathways required for the migration of CSCs. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.
Characteristics of Korean personal names
Authors: Kim Sungwon , Cho Seongyun
Published: December 2012

Korea, along with Asia at large, is producing more and more valuable academic materials. Furthermore, the demand for academic materials produced in non‐Western societies is increasing among English‐speaking users. In order to search among such material, users rely on keywords such as author names. However, Asian nations such as Korea and China have markedly different methods of writing personal names from Western naming traditions. Among these differences are name components, structure, writing customs, and distribution of surnames. These differences influence the Anglicization of Asian academic researchers' names, often leading to them being written in various fashions, unlike Western personal names. These inconsistent formats can often lead to difficulties in searching and finding academic materials for Western users unfamiliar with Korean and Asian personal names. This article presents methods for precisely understanding and categorizing Korean personal names in order to make academic materials by Korean authors easier to find for Westerners. As such, this article discusses characteristics particular to Korean personal names and furthermore analyzes how the personal names of Korean academic researchers are currently being written in English.
Reaction of Aromatic Peroxyl Radicals with Alkynes: A Mass Spectrometric and Computational Study Using the Distonic Radical Ion Approach
Authors: Li Cong H. , Khairallah George N. , Lam Adrian K. Y. , O'Hair Richard A. J. , Kirk Benjamin B. , Blanksby Stephen J. , da Silva Gabriel , Wille Uta
Published: December 2012

The reaction of the aromatic distonic peroxyl radical cations N‐methyl pyridinium‐4‐peroxyl (PyrOO.+) and 4‐(N,N,N‐trimethyl ammonium)‐phenyl peroxyl (AnOO.+), with symmetrical dialkyl alkynes 10a–c was studied in the gas phase by mass spectrometry. PyrOO.+ and AnOO.+ were produced through reaction of the respective distonic aryl radical cations Pyr.+ and An.+ with oxygen, O2. For the reaction of Pyr.+ with O2 an absolute rate coefficient of k1=7.1×10−12 cm3 molecule−1 s−1 and a collision efficiency of 1.2 % was determined at 298 K. The strongly electrophilic PyrOO.+ reacts with 3‐hexyne and 4‐octyne with absolute rate coefficients of khexyne=1.5×10−10 cm3 molecule−1 s−1 and koctyne=2.8×10−10 cm3 molecule−1 s−1, respectively, at 298 K. The reaction of both PyrOO.+ and AnOO.+ proceeds by radical addition to the alkyne, whereas propargylic hydrogen abstraction was observed as a very minor pathway only in the reactions involving PyrOO.+. A major reaction pathway of the vinyl radicals 11 formed upon PyrOO.+ addition to the alkynes involves γ‐fragmentation of the peroxy OO bond and formation of PyrO.+. The PyrO.+ is rapidly trapped by intermolecular hydrogen abstraction, presumably from a propargylic methylene group in the alkyne. The reaction of the less electrophilic AnOO.+ with alkynes is considerably slower and resulted in formation of AnO.+ as the only charged product. These findings suggest that electrophilic aromatic peroxyl radicals act as oxygen atom donors, which can be used to generate α‐oxo carbenes 13 (or isomeric species) from alkynes in a single step. Besides γ‐fragmentation, a number of competing unimolecular dissociative reactions also occur in vinyl radicals 11. The potential energy diagrams of these reactions were explored with density functional theory and ab initio methods, which enabled identification of the chemical structures of the most important products.
Phage survival: The biodegradability of M13 phage display library in vitro
Authors: Tóthová L'ubomíra , Bábíčková Janka , Celec Peter
Published: December 2012

Administration of bacteriophages is used for phage therapy modulation of gut microbiome or for in vivo phage display. The aim of the study was to analyze the survival of M13 phage in different body fluids and tissues in vitro. The survival of M13 phage was measured in vitro in human blood, saliva, urine, artificial gastric juice (AGJ), and mouse homogenates of stomach, jejunum, and colon after defined time points (5, 15, or 45 Min). The plates were inspected after overnight incubation and the plaques were counted. No phage was recovered after 5 Min of incubation with AGJ. In urine, the phage survival was decreased by 44% after 5 Min of incubation (P = 0.004). In saliva, the recovered titer was decreased by 33% and 88% (P < 0.05) after 15 and 45 Min, respectively. Phage coincubation with jejunum homogenate led to significant decrease of phage titer by 72% (P < 0.01) after 15 Min and by 99% (P < 0.001) after 45 Min. Decreased survival of M13 phage depending on time of incubation was proved under several in vitro conditions, with low pH in the AGJ having the most detrimental effect on phage survival. Phage pharmacokinetics described in vitro might have applications for the use of bacteriophages in vivo.
Analyse AKR‐induzierter Schädigungsprozesse in Beton
Authors: Weise Frank , Voland Katja , Pirskawetz Stephan , Meinel Dietmar
Published: December 2012

Zur Beurteilung der Alkaliempfindlichkeit der Gesteinskörnung finden normativ der Betonversuch mit Nebelkammerlagerung bei 40 °C und alternativ der 60 °C‐Betonversuch Anwendung. Als Beurteilungskriterium für den Schädigungsprozess wird bei beiden Verfahren die an Betonprismen diskontinuierlich ermittelte Dehnung herangezogen. Auch bei den zusätzlich in der Nebelkammer gelagerten Würfeln beschränkt sich die Schadensanalyse auf eine diskontinuierliche Verfolgung der maximalen Breite der Oberflächenrisse.

Im Rahmen des Beitrags wird eine neuartige, bereits erfolgreich erprobte zerstörungsfreie Prüfmethodik vorgestellt. Diese ermöglicht durch eine gleichzeitige kontinuierliche Dehnungs‐, Schallemissions‐ und Ultraschallmessung eine kontinuierliche Verfolgung der inneren Gefügeveränderungen in den Betonprüfkörpern während der AKR‐provozierenden Lagerung. Dabei wurden drei zeitlich aufeinanderfolgende Phasen der inneren Gefügeveränderung mit einer Dominanz von Hydratation, Rissbildung sowie vermutlicher Rissverfüllung mit Reaktionsprodukten identifiziert. Die ablaufenden Rissbildungsprozesse wurden zusätzlich mit diskontinuierlich durchgeführten röntgentomografischen Untersuchungen zeitlich und räumlich visualisiert. Die CT‐Befunde wurden durch mikroskopische Untersuchungen bestätigt.

Analysis of ASR‐induced damage processes in concrete Application of innovative measurement techniques

The alkali‐reactive potential of aggregates is assessed according to the German guidelines by two different test methods. These are the 40 °C fog chamber storage and as an alternative method the 60 °C concrete prism test. In both tests, the discontinuously measured expansion of ASR‐generating stored concrete prisms is used as criterion for the internal damage process. The damage analysis of the cubes additionally stored in the 40 °C fog chamber is also restricted to the discontinuous measurement of the crack width on the cubes surfaces.

This paper describes an innovative, already successfully applied, non‐destructive measurement methodology. This methodology enables a continuous monitoring of the internal damage processes in ASR‐generating stored concrete specimens due to a continuous recording of expansion, acoustic emission and ultrasonic velocity. Thereby, three sequent phases of internal structural changes dominated by hydration, crack formation and filling of the cracks with ASR‐gel and/or other reaction products can be detected. The crack formation was temporally and spatially visualised by discontinuously applied X‐ray computed tomography measurements. Microscopic analyses confirm the findings of the X‐ray 3D‐CT.
Determination of sulpiride in pharmaceutical preparations and biological fluids using a Cr (III) enhanced chemiluminescence method
Authors: Khan Muhammad Naeem , Jan Muhammad Rasul , Shah Jasmin , Lee Sang Hak , Kim Young Ho
Published: December 2012

A highly sensitive and simple method for identifying sulpiride in pharmaceutical formulations and biological fluids is presented. The method is based on increased chemiluminescence (CL) intensity of a luminol–H2O2 system in response to the addition of Cr (III) under alkaline conditions. The CL intensity of the luminol–H2O2–Cr (III) system was greatly enhanced by the addition of sulpiride and the CL intensity was proportional to the concentration of sulpiride in a sample solution. Various parameters affecting the CL intensity were systematically investigated and optimized for determination of the sulpiride in a sample. Under the optimum conditions, the CL intensity was proportional to the concentration of sulpiride in the range of 0.068–4.0 µg/mL, with a good correlation coefficient of 0.997. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 8.50 × 10‐6 µg/mL and 2.83 × 10‐5 µg/mL, respectively. The method presented here produced good reproducibility with a relative standard deviation (RSD) of 2.70% (n = 7). The effects of common excipients and metal ions were studied for their interference effect. The method was validated statistically through recovery studies and successfully applied for the determination of sulpiride in pure form, pharmaceutical preparations and spiked human plasma samples. The percentage recoveries were found to range from 99.10 to 100.05% for pure form, 98.12 to 100.18% for pharmaceutical preparations and 97.9 to 101.4% for spiked human plasma. Copyright © 2012 John Wiley & Sons, Ltd.
Redox‐enzymes, cells and micro‐organisms acting on carbon nanostructures transformation: A mini‐review
Authors: Seabra Amedea B. , Paula Amauri J. , Durán Nelson
Published: December 2012

Carbon nanotubes, graphene and fullerenes are actual nanomaterials with many applications in different industrial areas, with increasing potentialities in the field of nanomedicine. Recently, different proactive approaches on toxicology and safety management have become the focus of intense interest once the industrial production of these materials had a significant growth in the last years, even though their short‐ and long‐term behaviors are not yet fully understood. The most important concerns involving these carbon‐based nanomaterials are their stability and potential effects of their life cycles on animals, humans, and environment. In this context, this mini review discuss the biodegradability of these materials, particularly through redox‐enzymes, micro‐organisms and cells, to contribute toward the design of biocompatible and biodegradable functionalized carbon nanostructures, in order to use these materials safely and with minimum impact on the environment. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2013
Synthesis of 2′‐Deoxy‐1′‐homo‐N‐nucleosides with Anti‐Influenza Activity by Catalytic Methyltrioxorhenium (MTO)/H2O2 Oxyfunctionalization
Authors: Saladino Raffaele , Neri Veronica , Checconi Paola , Celestino Ignacio , Nencioni Lucia , Palamara Anna Teresa , Crucianelli Marcello
Published: December 2012

This paper describes a new route for the synthesis of 1′‐homo‐N‐nucleoside derivatives by means of either methyltrioxorhenium (MTO) or supported MTO catalysts, with H2O2 as the primary oxidant. Under these selective conditions, the oxyfunctionalization of the heterocyclic ring and the N heteroatom oxidation were operative processes, regardless of the type of substrate used, that is, purine or pyrimidine derivatives. In addition, the oxidation of 1′‐homo‐N‐thionucleosides, showed the occurrence of site‐specific oxidative nucleophilic substitutions of the heterocyclic ring. The MTO/H2O2 system showed, in general, high reactivity under both homogeneous and heterogeneous conditions, affording the final products with high conversion values of substrates and from medium to high yields. Many of the novel 1′‐homo‐N‐nucleoside analogues were active against the influenza A virus, without any cytotoxic effects, retaining their activity in both protected and unprotected forms.
Auf dem Weg zu Quantencomputern und neuem Zeitstandard
Authors: Harrer Roswitha
Published: December 2012

Der Nobelpreis für Physik 2012 geht dieses Jahr an zwei Forscher aus der Quantenoptik. Sie haben durch bahnbrechende Experimente den Grundstein für die Entwicklung von Quantencomputern und extrem genauen Uhren gelegt.
Ein erster Zugang zum Diazirinon N2CO
Authors: Beckers Helmut , Zeng Xiaoqing , Willner Helge
Published: December 2012

Mit der Synthese und umfassenden Charakterisierung des zyklischen Diazirinons wurde kürzlich ein überraschend langlebiges Dimer der beiden stabilsten zweiatomigen Moleküle N2 und CO beschrieben.
Kinetics of Methyldiethanolamine Mineralization by Using UV/H2O2 Process
Authors: Harimurti Sabtanti , Rahmah Anisa Ur , Omar Abdul Aziz , Thanapalan Murugesan
Published: December 2012

The UV/H2O2 is one of the popular techniques in the advanced oxidation processes (AOPs) and has been applied in the wastewater treatment during recent two decades. UV exposure on the H2O2 generate highly reactive hydroxyl radicals (OH•), which are used to degrade organic contaminants through oxidation processes in wastewater. This present study involves the estimation of hydroxyl radical rate constants of methyldiethanolamine (MDEA) mineralization at different temperatures by using UV/H2O2 in aqueous solution. Laboratory experiments have been conducted and the profile of MDEA mineralization has been established. The hydroxyl radical rate constants and the activation energy of mineralization process have been calculated. The estimated hydroxyl rate constants and the activation energy are in good agreement with those reported in the literature.
Vermicomposting: An Eco‐Friendly Option for Fermentation and Dye Decolourization Waste Disposal
Authors: Kaushik Prachi , Malik Anushree , Sharma Satyawati
Published: December 2012

By‐products of various industrial fermentations can be good adsorbents for removing hazardous dyes from wastewater. However, after biosorption, regeneration of biomass is essential to minimize the solid waste generation or else the dye laden biomass should be suitably disposed off. In the present work, experiments were conducted on the Acid Navy Blue and Methylene Blue dyes which were biosorbed to the fungal biomass (strain closely related to Aspergillus lentulus) produced on corncob as the substrate through solid state fermentation. In order to dispose the dye laden biomass, it was vermicomposted along with cow dung (CD) employing Eisenia fetida. Results indicated that the dye laden biomass was not lethal toward the earthworms as no mortality was observed. However, as compared with control experiments (where dye laden biomass was absent), the reproductive potential of the earthworms was affected. Nevertheless, further investigations on optimization of biomass and CD ratios can facilitate vermicomposting as a potential route for disposing dye laden biomass.
Benchmarking the Lithium–Thiophene Complex
Authors: Harding Michael E. , Klopper Wim
Published: December 2012

The equilibrium geometry and the binding energy of the lithium–thiophene complex are determined by means of an accurate composite scheme. The scheme is based on approximate explicitly correlated coupled‐cluster theory with single and double excitations extended by higher‐level excitations. Core correlation effects as well as relativistic, diagonal Born–Oppenheimer, and counterpoise corrections are also taken into account. The best estimate of the binding energy amounts to De=41.2 kJ mol−1, with a 95 % confidence interval of ±1.0 kJ mol−1.
Personality Disorder Traits and Self‐Reported Target Problems in a Treatment‐Seeking Sample
Authors: Huband Nick , Evans Chris , Duggan Conor , Khan Omer
Published: December 2012

Background

Assessments of personality disorder (PD) by clinicians or researchers are not always congruent with the problems that clients view as most salient. This can result in disagreement over areas for change, leading to dissatisfaction and the risk of treatment attrition.

Method

The sample comprised 141 treatment‐seeking adults with PD. Each described the five things they most wanted to change about themselves. These target problems were compared with PD diagnoses obtained from the International Personality Disorder Examination.

Results

The congruence between the clients' target problems and PD traits identified by the professionals was generally weak. Disagreement arose where a client's target problem was not a PD trait and, less frequently, where the client and the professional agreed on the presence of a trait but not on its importance. Surprisingly, doubting the trustworthiness of others was the most commonly reported target problem in this treatment‐seeking sample even though many such participants did not qualify for that particular paranoid trait.

Conclusion

Personality disorder diagnoses were generally poor indicators of the problems these clients cited as most important. This lack of correspondence may explain some of the lack of effectiveness of interventions for PD. Copyright © 2012 John Wiley & Sons, Ltd.

Key Practitioner Message:

The problem that a client with personality disorder (PD) views as most important may only be weakly identified in a formal diagnostic assessment.

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PD traits are insufficient to describe fully the things clients most want to change about themselves.

Many clients with PD consider difficulty trusting others to be their most important problem, despite not qualifying for that particular paranoid trait.

Risk of disagreement between the clinician and the client might be reduced if both parties can engage in a discussion about the results of any formal diagnostic assessment.
Relationship Between Patient Pre‐treatment Object Relations Functioning and Psychodynamic Techniques Early in Treatment
Authors: Mullin Anthony S. J. , Hilsenroth Mark J.
Published: December 2012

This study explored the relationship between patient pre‐treatment object relations (OR) functioning and psychodynamic techniques employed during two early sessions (third and ninth). The sample consisted of 76 outpatients engaged in short‐term psychodynamic psychotherapy. Results showed that lower levels of patient pre‐treatment OR functioning, particularly in the identity and affective domains, were related to a greater use of psychodynamic–interpersonal techniques in sessions. Patients who had more adaptive management of aggressive impulses were related to a greater use of cognitive–behavioural techniques by therapists. In addition, exploratory analyses between OR functioning and specific psychodynamic–interpersonal and cognitive–behavioural techniques showed that lower OR functioning in terms of affect, self‐esteem, identity coherence, social causality, emotional investment in relationships as well as Global OR were significantly related to therapist focus on avoidance of important topics and affective changes during the session. Implications for clinical practice and Q1 future research are discussed. Copyright © 2012 John Wiley & Sons, Ltd.

Key Practitioner Message:

Consider more frequent use of psychodynamic techniques early in treatment with patients expressing more pathological object representations, particularly when these deficits are in the affective and identity domains.

Lower patient object relations functioning may necessitate an in session focus on issues that are avoided or uncomfortable early in treatment.

Lower patient object relations functioning may necessitate the need to address and explore labile affective expressions in session as they occur early in treatment.

When patients are able to more adaptively express or manage aggressive impulses early within psychodynamic psychotherapy consider the integration of problem solving, goal oriented, future focused (i.e., CB) techniques.
Synthesis and characterization of strontium chloroborate whiskers
Authors: Zhu Donghai , Yun Shan , Nai Xueying , Zhao Dongmei , Liu Xin , Li Wu
Published: December 2012

Single crystalline strontium chloroborate (Sr2B5O9Cl) whiskers with uniform diameter have been synthesized by a facile route based on the calcination of precursor. The precursor was prepared by the sedimentation reaction between SrCl2 and Na2B4O7 aqueous solution. The products were characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectrum (FT‐IR). An optimal synthesis temperature for preparing Sr2B5O9Cl whiskers was obtained, and the possible formation process was also presented.
Climate and landscape drivers of tree decline in a Mediterranean ecoregion
Authors: Brouwers Niels C. , Mercer Jack , Lyons Tom , Poot Pieter , Veneklaas Erik , Hardy Giles
Published: December 2012

Climate change and anthropogenic land use are increasingly affecting the resilience of natural ecosystems. In Mediterranean ecoregions, forests and woodlands have shown progressive declines in health. This study focuses on the decline of an endemic woodland tree species,Eucalyptus wandoo(wandoo), occurring in the biodiversity hotspot of southwest Western Australia. We determined the change in health of wandoo stands between 2002 and 2008 across its geographic and climatic range, and associated this change in health with non‐biotic variables focusing on: (1) fragment metrics; (2) topography; (3) soil characteristics; and (4) climate. Only fragment metrics and climate variables were found to be significantly related to the observed change in health. Stands that were small with high perimeter/area ratios were found to be most sensitive to health declines. Recent increases in autumn temperatures and decreases in annual rainfall were negatively affecting health of wandoo most prominently in the low rainfall zone of its climatic range. Together, these results suggest the onset of range contraction for this ecologically important species, which is likely to be exacerbated by projected future changes in climate. Our results emphasize the importance of establishing monitoring programs to identify changes in health and decline trends early to inform management strategies, particularly in the sensitive Mediterranean ecoregions.
Recirculating bone marrow B cells in C57BL/6 mice are more tolerant of highly hydrophobic and highly charged CDR‐H3s than those in BALB/c mice
Authors: Khass Mohamed , Buckley Kevin , Kapoor Pratibha , Schelonka Robert L. , Watkins Leticia S. , Zhuang Yingxin , Schroeder Harry W.
Published: December 2012

To test whether mechanisms controlling the range of diversity of the developing antibody repertoire in C57BL/6 mice (IgHb) operate similarly to those identified in BALB/c mice (IgHa), we compared the sequences of VH7183‐containing H‐chain transcripts from sorted adult bone marrow C57BL/6 B‐cell subsets with those previously obtained from BALB/c mice. Patterns of VDJ gene segment utilization and CDR‐H3 amino acid composition, charge, and average length in C57BL/6 pro‐B cells were similar, although not identical, to BALB/c pro‐B cells. However, C57BL/6 mature, recirculating B cells failed to demonstrate the reduction in the use of VH81X and the narrowing in the range of variance of CDR‐H3 hydrophobicity that characterizes B‐cell maturation in BALB/c mice. To further test the ability of the C57BL/6 strain to discard B cells expressing highly charged CDR‐H3s, we introduced a mutant IgHa DH allele that forces use of arginine, asparagine, and histidine. Unlike BALB/c mice, C57BL/6 mice congenic for the charged DH maintained normal numbers of mature, recirculating B cells that were enriched for charged CDR‐H3s. Together these findings indicate that the mature C57BL/6 B‐cell pool permits expression of immunoglobulins with antigen‐binding sites that are typically discarded during late‐stage bone marrow B‐cell development in BALB/c mice.
The Glaser–Hay Reaction: Optimization and Scope Based on 13C NMR Kinetics Experiments
Authors: Vilhelmsen Mie H. , Jensen Jonas , Tortzen Christian G. , Nielsen Mogens B.
Published: December 2012

The oxidative Glaser–Hay coupling of two terminal alkynes to furnish a butadiyne is a key reaction for acetylenic scaffolding. Although the reaction is performed under rather simple conditions [CuCl/TMEDA/O2 (air)], the mechanism is still under debate. Herein we present detailed studies on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl‐substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found to be zero‐order with respect to the terminal alkyne reactant under standard preparative conditions. Moreover, as the reaction proceeded, a clear change to slower reaction kinetics was observed, but it was still apparently zero‐order. The onset of this change was found to depend on the catalyst loading. This unfavorable change in reaction profile could be avoided by adding molecular sieves to the reaction mixture, thereby removing the water that is accumulated from the air and produced in the reaction in which dioxygen acts as the oxidizing agent. Not unexpectedly, the stirring rate, and hence uptake of air (O2), was found to have a significant effect on the rate of the reaction: The percentage of alkyne remaining after a certain time decreased linearly with the rate of stirring. On the basis of systematic studies, the optimized conditions for the coupling reaction using CuCl/TMEDA as the catalyst system are presented. Finally, we investigated the effect of different ligands and found that piperidine can also be conveniently employed as a ligand, albeit monodentate, in accord with related studies.
4‐Alkenyl‐2‐aminothiazoles: Smart Dienes for Polar [4 + 2] Cycloadditions
Authors: Alajarin Mateo , Cabrera Jose , Sanchez‐Andrada Pilar , Orenes Raul‐Angel , Pastor Aurelia
Published: December 2012

An exhaustive investigation into the [4 + 2] cycloadditions of 4‐alkenyl‐2‐aminothiazoles with a wide range of dienophiles has been carried out. 4‐Alkenyl‐2‐aminothiazoles act as good in‐out dienes, reacting with dienophiles bearing electron‐withdrawing groups. The heteroannulations, typically conducted under mild conditions, were endo‐selective when cyclic dienophiles were used, and regioselective when the reactions are conducted with unsymmetrical dienophiles. The endo‐selective processes presumably take place by concerted but highly asynchronous mechanisms. In contrast, the low levels of endo selectivity and the lack of stereospecificity in the reactions with certain acyclic dienophiles indicate a stepwise mechanism with a zwitterion as the most plausible intermediate. The course of the reaction changes when the highly reactive PTAD and TCNE are used as dienophiles, since in these cases, only addition products were obtained. Calculations of the HOMO and LUMO energy values of representative 4‐alkenyl‐2‐aminothiazoles, and the results of π‐facial diastereoselective processes by using chiral substrates are also disclosed.
Synthetic Progress in cMyc‐Max Oncoprotein Miniaturization: Semi‐Online Monitoring Gives Solid‐Phase Access to Hydrophobic b(‐HLH‐)ZIP Peptidosteroid Tweezers
Authors: Verzele Dieter , Madder Annemieke
Published: December 2012

Miniature versions of basic leucine zipper (bZIP) and basic helix–loop–helix zipper (b‐HLH‐ZIP) transcription factors are promising tools for molecular dissection of the genetic information in a post‐genomic context. Despite the opportunities of genome interfering agents based on certain oncogenic zipper proteins, structural mimicry of transcription factors is a delicate undertaking, and experimental fine‐tuning through bottom‐up organic chemistry could benefit from solid‐phase/library approaches. Involved in a variety of human pathologies, we became interested in the miniaturization of the cMyc‐Max b‐HLH‐ZIP oncoprotein, and herein elaborate on our synthetic progress in that direction. A bile acid scaffold was successfully employed as artificial dimerization interface in this new type of transcription factor model. Orthogonality of the applied Alloc/Boc/Fmoc chemistries allowed the synthesis of both homo‐ and heterodimeric peptidosteroid conjugates, covalently restricted with defined geometrical properties. Recognition peptides were assembled through standard Fmoc/tBu solid‐phase peptide synthesis (SPPS) chemistry, assisted by automated procedures for consecutive chain elongation on solid support. Invaluable to monitor present strategy, a photocleavable linker allowed rapid, yet detailed analysis of side chain protected peptide intermediates, liberated from the sampled resin, by reverse‐phase HPLC and MALDI‐TOF‐MS. By decorating each scaffold position with two basic region peptides in a 2 × 2 design, a first generation of unprecedented b(‐HLH‐)ZIP peptidosteroids was efficiently obtained. As such, a versatile methodology amenable to library generation is presented.
Synthesis of Functionalized, Sterically Congested Calix[4]phyrin Macrocycles Using Donor–Acceptor‐Substituted Cyclopropanes – First Example of a Mono‐meso‐spirolactone Incorporated into a Calix[4]phyrin
Authors: Beyzavi M. Hassan , Lentz Dieter , Reissig Hans‐Ulrich , Wiehe Arno
Published: December 2012

Calix[4]phyrins are an important class of hybrid macrocyclic systems at the interface between porphyrins and calixpyrroles (porphyrinogens). A new stepwise synthesis of oxidation‐resistant meso‐hydrogenated calix[4]phyrins is reported, which allows variable substitution in the residues of their sp2‐meso‐centers without the need for a porphyrin intermediate. It relies on the acid‐catalyzed condensation of a sterically hindered donor–acceptor‐substituted cyclopropane precursor with pyrrole to form a sterically congested dipyrromethane. This was subsequently condensed with a wide range of alkyl and aryl aldehydes bearing electron‐donating or electron‐withdrawing substituents followed by an oxidation step to form stable calix[4]phyrin(1.1.1.1)s with bridging meso‐CH hydrogen atoms through an acid‐promoted dehydrative condensation. The methodology avoids any need for premetallation of the macrocycle and/or the use of organometallic catalysts or reagents and allows the incorporation of the bulky cyclopropane‐derived substituents specifically into the 5,15‐meso‐like positions. The resulting regioisomerically pure products display conformational features that reflect their mixed nature between porphyrins and calixpyrroles and they were assessed by X‐ray diffraction analysis, NMR techniques and UV/Vis spectroscopy. The possibility to introduce key functional groups enables subsequent modification of these calix[4]phyrins and allows their connection to other groups such as biologically active moieties. Of special interest is an unprecedented example of an acid‐driven lactonization that results in the incorporation of a mono‐meso‐spirolactone into a calix[4]phyrin(1.1.1.1). Moreover, it is demonstrated that this approach to calix[4]phyrins is also applicable to other sterically congested dipyrromethanes.
A novel anonymous authentication scheme without cryptography
Authors: Shi Run‐hua , Zhong Hong , Huang Liu‐sheng
Published: December 2012

In this paper, we present a novel anonymous authentication scheme without employing any symmetric or asymmetric cryptosystem. The security of our scheme is guaranteed by the basic theories for solving linear equations, which can ensure it is unconditionally secure. The proposed scheme is adaptable for resource‐constrained devices or wireless networks well, because it only needs to perform several scalar multiplications instead of complex cryptographic operations and takes only one round of message exchange (challenge–response) between the verification centre and the legal user. Copyright © 2012 John Wiley & Sons, Ltd.
Antitumor effects of combining metronomic chemotherapy with the antivascular action of ultrasound stimulated microbubbles
Authors: Todorova Margarita , Agache Vlad , Mortazavi Omid , Chen Branson , Karshafian Raffi , Hynynen Kullervo , Man Shan , Kerbel Robert S. , Goertz David E.
Published: December 2012

Considerable effort is being directed toward investigating the use of ultrasound (US) stimulated microbubbles (MB) to promote the uptake of anticancer agents in tumors. In this study we propose and investigate a new method for combining therapeutic ultrasound with anticancer agents, which is to induce antivascular effects and combine these with an antiangiogenic treatment strategy, in this case metronomic chemotherapy. This is effectively a vascular targeting rather than a drug delivery approach. Experiments were conducted on MDA‐MB‐231 breast cancer tumors implanted in athymic mice. Metronomic cyclophosphamide (MCTX) was employed as an antiangiogenic therapy and was administered through the drinking water. Ultrasound stimulated microbubble treatments (USMB) were conducted at 1 MHz employing short bursts (0.00024 duty cycle) at 1.6 MPa in combination with the commercial microbubble agent Definity. USMB treatments were performed on a weekly basis for 4 weeks and MCTX was administered for 10 weeks. The USMB induced an acute reduction of blood flow as confirmed with US contrast imaging and DiOC7 perfusion staining. Longitudinal experiments demonstrated that significant growth inhibition occurred in MCTX‐only and USMB‐only treatment groups relative to control tumors. The combined USMB and MCTX treatment group showed significant growth inhibition and survival prolongation relative to the USMB‐only (p < 0.01) and MCTX‐only treatment groups (p < 0.01). These results indicate the feasibility of a new approach to combining therapeutic ultrasound with an anticancer agent.
Meta‐analysis of microRNA expression in lung cancer
Authors: Võsa Urmo , Vooder Tõnu , Kolde Raivo , Vilo Jaak , Metspalu Andres , Annilo Tarmo
Published: December 2012

The prognostic and diagnostic value of microRNA (miRNA) expression aberrations in lung cancer has been studied intensely in recent years. However, due to the application of different technological platforms and small sample size, the miRNA expression profiling efforts have led to inconsistent results between the studies. We performed a comprehensive meta‐analysis of 20 published miRNA expression studies in lung cancer, including a total of 598 tumor and 528 non‐cancerous control samples. Using a recently published robust rank aggregation method, we identified a statistically significant miRNA meta‐signature of seven upregulated (miR‐21, miR‐210, miR‐182, miR‐31, miR‐200b, miR‐205 and miR‐183) and eight downregulated (miR‐126‐3p, miR‐30a, miR‐30d, miR‐486‐5p, miR‐451a, miR‐126‐5p, miR‐143 and miR‐145) miRNAs. We conducted a gene set enrichment analysis to identify pathways that are most strongly affected by altered expression of these miRNAs. We found that meta‐signature miRNAs cooperatively target functionally related and biologically relevant genes in signaling and developmental pathways. We have shown that such meta‐analysis approach is suitable and effective solution for identification of statistically significant miRNA meta‐signature by combining several miRNA expression studies. This method allows the analysis of data produced by different technological platforms that cannot be otherwise directly compared or in the case when raw data are unavailable.
Knockdown of prolyl‐4‐hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA‐MB‐231 cells by affecting TGF‐β1 processing
Authors: Wottawa Marieke , Leisering Pia , Ahlen Melanie von , Schnelle Moritz , Vogel Sabine , Malz Cordula , Bordoli Mattia Renato , Camenisch Gieri , Hesse Amke , Napp Joanna , Alves Frauke , Kristiansen Glen , Farhat Katja , Katschinski Dörthe Magdalena
Published: December 2012

The prolyl‐4‐hydroxylase domain 1–3 (PHD1–3) enzymes are regulating the protein stability of the α‐subunit of the hypoxia‐inducible factor‐1 (HIF‐1), which mediates oxygen‐dependent gene expression. PHD2 is the main isoform regulating HIF‐1α hydroxylation and thus stability in normoxia. In human cancers, HIF‐1α is overexpressed as a result of intratumoral hypoxia which in turn promotes tumor progression. The role of PHD2 for tumor progression is in contrast far from being thoroughly understood. Therefore, we established PHD2 knockdown clones of MDA‐MB‐231 breast cancer cells and analyzed their tumor‐forming potential in a SCID mouse model. Tumor progression was significantly impaired in the PHD2 knockdown MDA‐MB‐231 cells, which could be partially rescued by re‐establishing PHD2 expression. In a RNA profile screen, we identified the secreted phosphoprotein 1 (SPP1) as one target, which is differentially regulated as a consequence of the PHD2 knockdown. Knockdown of PHD2 drastically reduced the SPP1 expression in MDA‐MB‐231 cells. A correlation of SPP1 and PHD2 expression was additionally verified in 294 invasive breast cancer biopsies. In subsequent analyses, we identified that PHD2 alters the processing of transforming growth factor (TGF)‐β1, which is highly involved in SPP1 expression. The altered processing capacity was associated with a dislocation of the pro‐protein convertase furin. Thus, our data demonstrate that in MDA‐MB‐231 cells PHD2 might affect tumor‐relevant TGF‐β1 target gene expression by altering the TGF‐β1 processing capacity.
Productivity increment of biodegradable and biorenewable copolymer containing 3‐hydroxyvalerate monomer initiated by alcohols as precursor substrates
Authors: Shantini K. , Bhubalan Kesaven , Yahya Ahmad Ramli Mohd , Amirul A.A.
Published: December 2012

Background

The production cost and the material properties of polyhydroxyalkanoate (PHA), a biodegradable plastic are common issues of debate. It has become a constant challenge for researchers to find suitable and relatively cheap carbon substrates. This study has investigated the production of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) [P(3HB‐co‐3HV)], using a combination of fatty acids and alcohols. The fermentation process described in this study also highlights the potential use of 1‐pentanol for the generation of 3HV monomer, in contrast to odd carbon numbered volatile fatty acids, which are known to exert some levels of toxicity towards the cells.

Results

Among the various mixtures of fatty acids and 3HV precursors, the mixture of 0.50 wt% C oleic acid and 0.06 wt% C 1‐pentanol was found suitable for the production of this copolymer. It was found that Cupriavidus sp. USMAA2‐4 could produce up to 56 wt% of P(3HB‐co‐3HV) with 8 mol% 3HV monomer units. The 3HV monomer composition was also successfully regulated in the range 3–66 mol% by manipulating the culture conditions. The number average molecular weight of the copolymer produced was in the range 217–351 kDa.

Conclusion

The findings of this study might be used as a platform for scale‐up production of 3HV copolymers with different monomer compositions using mixtures of oleic acid and alcohols, namely 1‐pentanol for a sustainable production process.© 2012 Society of Chemical Industry
The structural and biochemical basis for cellulose biodegradation
Authors: Wang Mingyu , Liu Kai , Dai Li , Zhang Jie , Fang Xu
Published: December 2012

The increasing petroleum price and the foreseeable depletion of fossil fuels has prompted research on bioenergy, particularly bioethanol and biobutanol from renewable lignocellulosic biomass, the primary component of which is cellulose. One key requirement of lignocellulose degradation is to improve the efficiency of a group of enzymes with general name cellulase, the collaboration of which degrades cellulose to glucose. Significant progress has been made in the last decade on understanding the structural and chemical properties of the substrate cellulose, the structural and biochemical properties of cellulases, their enzymatic mechanisms and the mechanism of synergistic catalysis by cellulases. This manuscript reviews the progress in the aforementioned fields, particularly the structural basis and enzymatic mechanisms of reactions leading to the degradation of cellulose. Based on these discoveries, popular models of enzymatic cellulose degradation are discussed, in the hope of benefiting further in‐depth investigations of this complex, multi‐component enzymatic reaction.© 2012 Society of Chemical Industry
Development of an AdEasy‐based system to produce first‐ and second‐generation adenoviral vectors with tropism for CAR‐ or CD46‐positive cells
Authors: Janssen Josephine M. , Liu Jin , Skokan Jaroslav , Gonçalves Manuel A. F. V. , de Vries Antoine A. F.
Published: December 2012

Background

The AdEasy system has acquired preeminence amongst the various methods for producing first‐generation, early region 1 (E1)‐deleted human adenovirus (HAdV) vectors (AdVs) as a result of the fast and reproducible recovery of full‐length AdV genomes via homologous recombination in Escherichia coli.

Methods

From the classical AdEasy system, a new production platform was derived to assemble first‐ and second‐generation [i.e. E1‐ plus early region 2A (E2A)‐deleted] AdVs displaying on their surface HAdV serotype 5 (HAdV5) fibers (F5) or chimeric fibers (F5/50) comprising the tail of F5 and the fiber shaft and knob of HAdV serotype 50 (HAdV50). The CD46‐interacting chimeric fibers allow for the high‐level transduction of various human primary cell types of clinical interest with low or no surface expression of the Coxsackievirus and adenovirus receptor.

Results

A new set of pAdEasy plasmid ‘backbones’ with or without E2A and encoding F5 or F5/50 was constructed and recombined in E. coli strain BJ5183 with a ‘shuttle’ plasmid coding for β‐galactosidase. The resulting clones yielded AdV preparations with similar high titers following their rescue and propagation in producer cells. The AdVs with F5/50 were superior to those carrying F5 with respect to transducing human skeletal myocytes and mesenchymal stem cells.

Conclusions

In the present study, an AdEasy system tailored for the production of not only first‐, but also second‐generation AdVs equipped with the receptor‐interacting fiber domains of the prototypic species C HAdV5 or of the species B member HAdV50 is presented. This system expands the range of applications for this robust and versatile AdV production platform. Copyright © 2012 John Wiley & Sons, Ltd.
Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N‐oxide in plasma by LC‐MS/MS: application for a pharmacokinetic study
Authors: Thappali Satheeshmanikandan RS , Varanasi Kanthikiran VS , Veeraraghavan Sridhar , Vakkalanka Swaroop Kumar VS , K Mukkanti
Published: December 2012

A sensitive and reliable high‐performance liquid chromatography–mass spectrometry (LC–MS/MS) was developed and validated for simultaneous quantification IC87114, roflumilast (RFM), and its active metabolite roflumilast N‐oxide (RFN) using tolbutamide as an internal standard. The analytes were extracted by using liquid–liquid extraction and separated on a reverse phase C18 column (50 mm × 3 mm i.d., 4.6 µ) using methanol: 2 mM ammonium acetate buffer, pH 4.0 as mobile phase at a flow rate 1 mL/min in gradient mode. Selective reaction monitoring was performed using the transitions m/z 398.3 > 145.9, 403.1 >186.9, 419.1 > 187.0 and 271.1 > 155.0 to quantify quantification IC87114, RFM, RFN and tolbutamide, respectively. The method was validated over the concentration range of 0.1–60 ng.mL−1 for RFM and RFN and 6 to 2980 ng.mL−1 for IC87114. Intra‐ and inter‐day accuracy and precision of validated method were within the acceptable limits of <15% at all concentrations. Coefficients of correlation (r2) for the calibration curves were >0.99 for all analytes. The quantitation method was successfully applied for simultaneous estimation of IC87114, RFM and RFN in a pharmacokinetic drug–drug interaction study in Wistar rats. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of the photodegradation products of metolachlor: structural elucidation, potential toxicity and persistence
Authors: Coffinet Sarah , Rifai Ahmad , Genty Christophe , Souissi Yasmine , Bourcier Sophie , Sablier Michel , Bouchonnet Stéphane
Published: December 2012

Aqueous solutions of metolachlor and metolachlor‐d6 were photolyzed with UV‐visible radiations. The structures of 15 by‐products of metolachlor were determined through gas chromatography‐mass spectrometry analyses using electron and chemical ionization combined with multistage mass spectrometry. The photolysis by‐products of metolachlor resulted mainly from dehalogenation and hydroxylation, in some cases accompanied by cyclization. In silico tests for toxicity prediction showed that the toxicity of some photolysis products is expected to be greater than that of metolachlor. Persistence studies showed that the by‐product relative abundances vary in large amounts with the irradiation time. The post‐photolysis evolution of the solution was also studied, in order to determine the persistence of the main by‐products. It allowed to establish that most of the by‐products can be found more than 12 h after the end of the photolysis, which is of a great concern as treated water is generally available for consumption only a few hours after treatment in most of industrial processes. Copyright © 2012 John Wiley & Sons, Ltd.
Pulsed hydrogen/deuterium exchange mass spectrometry for time‐resolved membrane protein folding studies
Authors: Khanal Anil , Pan Yan , Brown Leonid S. , Konermann Lars
Published: December 2012

Kinetic folding experiments by pulsed hydrogen/deuterium exchange (HDX) mass spectrometry (MS) are a well‐established tool for water‐soluble proteins. To the best of our knowledge, the current study is the first that applies this approach to an integral membrane protein. The native state of bacteriorhodopsin (BR) comprises seven transmembrane helices and a covalently bound retinal cofactor. BR exposure to sodium dodecyl sulfate (SDS) induces partial unfolding and retinal loss. We employ a custom‐built three‐stage mixing device for pulsed‐HDX/MS investigations of BR refolding. The reaction is triggered by mixing SDS‐denatured protein with bicelles. After a variable folding time (10 ms to 24 h), the protein is exposed to excess D2O buffer under rapid exchange conditions. The HDX pulse is terminated by acid quenching after 24 ms. Subsequent off‐line analysis is performed by size exclusion chromatography and electrospray MS. These measurements yield the number of protected backbone N–H sites as a function of folding time, reflecting the recovery of secondary structure. Our results indicate that much of the BR secondary structure is formed quite late during the reaction, on a time scale of 10 s and beyond. It is hoped that in the future it will be possible to extend the pulsed‐HDX/MS approach employed here to membrane proteins other than BR. Copyright © 2012 John Wiley & Sons, Ltd.