bluuebunny/crossref_metadata_2025 huggingface dataset:
Interprofessional education: The magical mystery tour now less of a mystery
Authors: Harden Ronald M.
Published: June 2015

Interprofessional education (IPE) is on today's agenda in medical education as a response to advances in medicine, the changes that have taken place in healthcare delivery, and pressures from the public and the profession. Although attention has focused on IPE in the later stages of the education program, there are benefits to be gained from the introduction of IPE in the early years. Curriculum developments supporting this include the adoption of outcome‐based education and vertical integration. There is also a recognition that students’ attitudes and biases are formed early in their education and the appropriate learning environment in the early years is important. Interprofessional education in the early years can also be seen as a part of a more general trend to greater collaboration in the delivery of an education program in the healthcare professions. Anatomy by incorporating IPE can help shape the future of medical education as well as being shaped by it. The possibility of success or failure with IPE can be captured with the equation IPE = (V × I)/N, where V = the IPE vision, I = the implementation strategy and N = negative perceptions of the approach. Success is more likely where there is a well thought out and shared vision for what is to be achieved, an appropriate implementation strategy and a plan to counteract a negative mind‐set. Anat Sci Educ 8: 291–295. © 2015 American Association of Anatomists.
Aggregation of Beta‐Amyloid Peptides Proximal to Zwitterionic Lipid Bilayers
Authors: Yang Chien‐I , Tsai Brook N. F. , Huang Shing‐Jong , Wang Ting‐Yu , Tai Hwan‐Ching , Chan Jerry C. C.
Published: June 2015

One of the hallmarks of Alzheimers disease is the deposition of amyloid plaques, which consist of β‐amyloid (Aβ) peptides in fibrillar states. Nonfibrillar Aβ aggregates have been considered as an important intermediate in the pathway of fibrillization, but little is known about the formation mechanism. The on‐pathway β‐sheet intermediates of Aβ40 peptides can be trapped by incubating the peptides in liposomes formed by zwitterionic lipids. The aggregates of Aβ40 peptides have been prepared at a peptide concentration of less than 10 μm. Solid‐state NMR spectroscopy data show that the backbone conformation of the aggregates is almost identical to that of the fibrils formed in free solution. In contrast to anionic lipids, zwitterionic lipids, which are typical of neuronal soma, did not induce any significant conformational difference in Aβ40 fibrils. This liposome–Aβ system may serve as a useful model to study the fibril formation mechanism.
Transformations of Ferric Chloride‐Generated Stilbene Cation Radicals. The Effect of Aromatic Substitution and a Comparison with Anodic Oxidation
Authors: Hong Fong‐Jiao , Chong Kam‐Weng , Low Yun‐Yee , Thomas Noel F. , Kam Toh‐Seok
Published: June 2015

A systematic study on the FeCl3‐induced oxidation of 1,2‐diarylalkenes was carried out with the focus on the variation of product type as a function of aromatic substitution, as well as to compare the reactivity of stilbene cation radicals generated via FeIII oxidation with those generated by anodic oxidation. The aromatic substituents were found to fall into three main categories, namely those that give rise to tetralins and/or dehydrotetralins, those that give products possessing pallidol and ampelopsin F‐type carbon skeletons, and last, those that give rise to trimeric products, indanes, and dehydrotetralins/tetralins. The latter are those stilbenes with a para‐methoxy substituent in one ring and a para‐ or meta‐EWG (CF3, NO2, Cl, F) in the other, and represent the most prominent departure when compared with the behavior of the same stilbenes under the conditions of anodic oxidation. Reaction pathways to rationalize the formation of the different products are presented.
Palladium‐Catalyzed One‐Pot Carbonylative Sonogashira Reaction Employing Formic acid as the CO Source
Authors: Qi Xinxin , Jiang Li‐Bing , Li Chong‐Liang , Li Rui , Wu Xiao‐Feng
Published: June 2015

A convenient palladium‐catalyzed carbonylative coupling of aryl iodides and terminal alkynes with formic acid as the CO precursor has been developed. A variety of alkynones were obtained in good yields in a one‐pot manner for the first time.
Purification and characterization of the plastid‐localized NAD‐dependent malate dehydrogenase from Arabidopsis thaliana
Authors: An Yan , Cao Youzhi , Xu Yingwu
Published: June 2015

Malate dehydrogenase (MDH) ubiquitously exists in living organisms and has many isoforms in a single species. MDHs from some classes have been characterized for their catalytic properties, which show significant variations despite that they share high sequence identity for the active sites. One class MDH, the plastid‐localized NAD‐dependent MDH (plNAD‐MDH) is known to be important for plant survival in a dark environment, but its biochemical and enzymatic properties have not been well characterized. This study attempts to fill the gap. plNAD‐MDH was expressed in an Escherichia coli system and purified using nickel‐affinity chromatography followed by size exclusion chromatography. The N‐terminal fusion his‐tag was removed by protease cleavage. The gel filtration assay and glutaraldehyde cross‐linking results showed that the active enzyme was a homodimer in solution. Further assay indicated that plNAD‐MDH is most active at a neutral pH value. The Km values for oxaloacetate and NADH are found in the submillimolar order, a median range for most MDHs. The maximum reaction rate values, however, are dramatically different from other plant MDHs, indicating that plNAD‐MDH has different substrate specificity. Moreover, we obtained crystals for this enzyme, which laid the groundwork for further analysis of the enzymatic mechanism from structural stand point.
Ostracism Reduces Reliance on Poor Advice from Others during Decision Making
Authors: Byrne Kaileigh A. , Tibbett Thomas P. , Laserna Lauren N. , Carter‐Sowell Adrienne R. , Worthy Darrell A.
Published: June 2015

Decision making is rarely context‐free, and often, both social information and non‐social information are weighed into one's decisions. Incorporating information into a decision can be influenced by previous experiences. Ostracism has extensive effects, including taxing cognitive resources and increasing social monitoring. In decision making situations, individuals are often faced with both objective and social information and must choose which information to include or filter out. How will ostracism affect the reliance on objective and social information during decision making? Participants (N = 245) in Experiment 1 were randomly assigned to be included or ostracized in a standardized, group task. They then performed a dynamic decision making task that involved the presentation of either non‐social (i.e. biased reward feedback) or social (i.e., poor advice from a previous participant) misleading information. In Experiment 2, participants (N = 105) completed either the ostracism non‐social condition or social misleading information condition with explicit instructions stating that the advice given was from an individual who did not partake in the group task. Ostracized individuals relied more on non‐social misleading information and performed worse than included individuals. However, ostracized individuals discounted misleading social information and outperformed included individuals. Results of Experiment 2 replicated the findings of Experiment 1. Across two experiments, ostracized individuals were more critical of advice from others, both individuals who may have ostracized them and unrelated individuals. In other words, compared with included individuals, ostracized individuals underweighted advice from another individual but overweighed non‐social information during decision making. We conclude that when deceptive objective information is present, ostracism results in disadvantageous decision making. Copyright © 2015 John Wiley & Sons, Ltd.
A pedagogy of conceptual progression and the case for academic knowledge
Authors: Rata Elizabeth
Published: June 2015

The potential for academic knowledge to ‘interrupt’ inter‐generational reproduction in education is located in the structural contradictions that shape knowledge and democracy. Since the late 1990s research in the sociology of education, which theorises curriculum knowledge using the ideas of Durkheim, Vygotsky and Bernstein, suggests that academic knowledge, far from being the domain of conservative forces, contains the means by which the working‐class and marginalised groups may overcome class determinism. The paper argues for a pedagogy of conceptual progression to assist students across the ‘interruption’ or ‘discursive gap’ into academic knowledge. Such a pedagogy need not be confined to its central purpose—that of teaching abstract ideas drawn from their disciplinary systems of meaning and classified for teaching as academic subjects. It can also be the means to mediate the relationship between the context‐dependent knowledge of students’ experience and the context‐independent knowledge of the academic subject. This pedagogy might be the way to maintain the motivational intention of constructivism and ‘relevance’ approaches that emphasise students’ experience. However, it would use experience to illustrate the abstract ideas acquired in academic subjects, not serve as the source of knowledge itself, nor the knowledge focus.
High‐content imaging with micropatterned multiwell plates reveals influence of cell geometry and cytoskeleton on chromatin dynamics
Authors: Harkness Ty , McNulty Jason D. , Prestil Ryan , Seymour Stephanie K. , Klann Tyler , Murrell Michael , Ashton Randolph S. , Saha Krishanu
Published: June 2015

Understanding the mechanisms underpinning cellular responses to microenvironmental cues requires tight control not only of the complex milieu of soluble signaling factors, extracellular matrix (ECM) connections and cell‐cell contacts within cell culture, but also of the biophysics of human cells. Advances in biomaterial fabrication technologies have recently facilitated detailed examination of cellular biophysics and revealed that constraints on cell geometry arising from the cellular microenvironment influence a wide variety of human cell behaviors. Here, we create an in vitro platform capable of precise and independent control of biochemical and biophysical microenvironmental cues by adapting microcontact printing technology into the format of standard six‐ to 96‐well plates to create MicroContact Printed Well Plates (μCP Well Plates). Automated high‐content imaging of human cells seeded on μCP Well Plates revealed tight, highly consistent control of single‐cell geometry, cytoskeletal organization, and nuclear elongation. Detailed subcellular imaging of the actin cytoskeleton and chromatin within live human fibroblasts on μCP Well Plates was then used to describe a new relationship between cellular geometry and chromatin dynamics. In summary, the μCP Well Plate platform is an enabling high‐content screening technology for human cell biology and cellular engineering efforts that seek to identify key biochemical and biophysical cues in the cellular microenvironment.
Systematic review of high-intensity focused ultrasound ablation in the treatment of breast cancer
Authors: Peek M C L , Ahmed M , Napoli A , ten Haken B , McWilliams S , Usiskin S I , Pinder S E , van Hemelrijck M , Douek M
Published: June 2015

Background

A systematic review was undertaken to assess the clinical efficacy of non-invasive high-intensity focused ultrasound (HIFU) ablation in the treatment of breast cancer.

Methods

MEDLINE/PubMed library databases were used to identify all studies published up to December 2013 that evaluated the role of HIFU ablation in the treatment of breast cancer. Studies were eligible if they were performed on patients with breast cancer and objectively recorded at least one clinical outcome measure of response (imaging, histopathological or cosmetic) to HIFU treatment.

Results

Nine studies fulfilled the inclusion criteria. The absence of tumour or residual tumour after treatment was reported for 95·8 per cent of patients (160 of 167). No residual tumour was found in 46·2 per cent (55 of 119; range 17–100 per cent), less than 10 per cent residual tumour in 29·4 per cent (35 of 119; range 0–53 per cent), and between 10 and 90 per cent residual tumour in 22·7 per cent (27 of 119; range 0–60 per cent). The most common complication associated with HIFU ablation was pain (40·1 per cent) and less frequently oedema (16·8 per cent), skin burn (4·2 per cent) and pectoralis major injury (3·6 per cent). MRI showed an absence of contrast enhancement after treatment in 82 per cent of patients (31 of 38; range 50–100 per cent), indicative of coagulative necrosis. Correlation of contrast enhancement on pretreatment and post-treatment MRI successfully predicted the presence of residual disease.

Conclusion

HIFU treatment can induce coagulative necrosis in breast cancers. Complete ablation has not been reported consistently on histopathology and no imaging modality has been able confidently to predict the percentage of complete ablation. Consistent tumour and margin necrosis with reliable follow-up imaging are required before HIFU ablation can be evaluated within large, prospective clinical trials.
Variations in survival and perioperative complications between hospitals based on data from two phase III clinical trials for oesophageal cancer
Authors: Kataoka K , Nakamura K , Mizusawa J , Fukuda H , Igaki H , Ozawa S , Hayashi K , Kato K , Kitagawa Y , Ando N
Published: June 2015

Background

Variations in institutional practice may contribute to different outcomes of cancer treatment. The impact of interinstitutional heterogeneity on outcomes between hospitals after oesophagectomy has not been examined previously using data from surgical clinical trials.

Methods

The data from two phase III trials for oesophageal cancer were used. Japan Clinical Oncology Group (JCOG) 9204 involved oesophagectomy (92-OP) versus oesophagectomy plus postoperative chemotherapy (92-POST), with accrual from 1992 to 1997. JCOG9907 involved postoperative chemotherapy (99-POST) versus preoperative chemotherapy (99-PRE), with accrual from 2000 to 2006. Hospitals contributing fewer than three patients were excluded. The influence of time and preoperative chemotherapy on interinstitutional heterogeneity related to postoperative complications and 5-year overall survival were evaluated by comparisons within and between these trial groups. Heterogeneity was estimated by a mixed-effects model after adjusting for age, sex, performance status, location of the primary tumour and clinical stage.

Results

Twelve hospitals in 92-OP (114 patients), 13 in 92-POST (114), 19 in 99-POST (158) and 18 in 99-PRE (154) were eligible. There was considerable heterogeneity in predicted postoperative complications in both groups in JCOG9204 (median 31·3 (range 15·0–68·2) per cent), and in 99-PRE (35·2 (22·6–46·6) per cent) but not in 99-POST (27·7 (27·7–27·7) per cent) from JCOG9907. A similar pattern was seen for predicted overall survival (92-POST: 66·4 (range 64·1–68·9) per cent; 99-PRE: 55·9 (54·0–59·7) per cent; 99-POST: 44·4 (44·4–44·4) per cent).

Conclusion

Interinstitutional heterogeneity regarding complications and survival after oesophagectomy is a problem that merits wider consideration.
Determinants of survival following pelvic exenteration for primary rectal cancer
Authors: Radwan R W , Jones H G , Rawat N , Davies M , Evans M D , Harris D A , Beynon J ,   Swansea Pelvic Oncology Group, McGregor A D , Morgan A R , Freites O , Patel B , Askill C , Rowley C , Pudney D , Hatcher O , Bose P , Fenn N , Lucas M G , Khot U , Chandrasekaran T V , Carr N D , Gwynne S , Drew P , Phan M D
Published: June 2015

Background

Pelvic exenteration is a potentially curative treatment for locally advanced primary rectal cancer. Previous studies have been limited by small sample sizes and heterogeneous data. A consecutive series of patients was studied to identify the clinicopathological determinants of survival.

Methods

All patients undergoing pelvic exenterative surgery for primary rectal cancer (1992–2014) at this hospital were analysed. The primary outcome measure was 5-year overall survival. Secondary endpoints included length of hospital stay, complication rate, 30-day mortality and disease recurrence rate. Statistical analysis was performed using Kaplan–Meier and Cox regression analysis.

Results

A total of 174 patients with a median age of 65 (range 31–90) years were included. Ninety-six patients underwent posterior pelvic exenteration and 78 had total pelvic exenteration. Median follow-up was 48 (range 1–229) months. Two patients (1·1 per cent) died within 30 days of surgery and 16·1 per cent returned to the operating theatre. The 5-year survival rate following complete resection (R0) was 59·3 per cent. In univariable analysis, adverse survival was associated with advanced age (P = 0·003), metastatic disease (P = 0·001), pathological node status (P = 0·001), circumferential resection margin (P = 0·001), local recurrence (P = 0·015) and the need for neoadjuvant therapy (P = 0·039).

Conclusion

Pelvic exenteration is an aggressive treatment option with a high morbidity rate that provides favourable long-term outcomes in patients with locally advanced primary rectal cancer.
Development and validation of TLC–densitometric method for simultaneous determination of two binary antihypertensive mixtures containing felodipine in fixed dose combinations
Authors: Mohamed Abdel‐Maaboud I. , Omar Mahmoud A. , Hammad Mohamed A. , Mohamed Abobakr A.
Published: June 2015

A new densitometric thin‐layer chromatographic method has been developed for simultaneous determination of two binary mixtures containing felodipine in combination with either metoprolol (mixture I) or ramipril (mixture II). The two mixtures were quantitatively separated on 60 F254 silica gel plates using toluene–ethyl acetate–methanol–ammonia as mobile phase with UV detection at 233 and 229 nm for mixtures I and II, respectively. The studied drugs were satisfactorily resolved with retention factor (Rf) values of 0.34 ± 0.03 and 0.65 ± 0.03 for metoprolol and felodipine, respectively, in mixture I and 0.35 ± 0.03 and 0.74 ± 0.03 for ramipril and felodipine, respectively, in mixture II. Linearity ranges were 2000–7000 and 200–700 ng/band for metoprolol and felodipine, respectively, in mixture I and 1500–4000 ng/band for both ramipril and felodipine in mixture II. Correlation coefficient (r) values were 0.9968 for both metoprolol and felodipine in mixture I and 0.9993 for ramipril and 0.9989 for felodipine in mixture II. The method has been validated according to International Conference on Harmonization guidelines and has been successfully applied for determination of the studied drugs in their dosage forms without interference from commonly encountered excipients. Copyright © 2015 John Wiley & Sons, Ltd.
Investigation of chemical diversity in different parts and origins of ethnomedicine Gentiana rigescens Franch using targeted metabolite profiling and multivariate statistical analysis
Authors: Pan Yu , Zhang Ji , Shen Tao , Zhao Yan‐Li , Zuo Zhi‐Tian , Wang Yuan‐Zhong , Li Wan‐Yi
Published: June 2015

Gentiana rigescens, an ethnomedicine, is widely cultivated in Yunnan province of China. Although a wide range of metabolites including iridoid glycosides, flavonoids and triterpenoids have been reported in this ethnomedicine, the data on accumulation and distribution of metabolites in certain parts are limited. In this study, targeted metabolic fingerprinting of iridoid glycosides based on liquid chromatography–ultraviolet detection–tandem mass spectrometry (LC‐UV‐MS/MS) was developed to investigate the metabolic similarities and differences in different parts and origins. Thirty‐one compounds, including iridoid glycosides and flavonoids, were detected from targeted metabolite profiling and plausibly assigned to the different parts of G. rigescens. Multivariate statistical analysis was designed to reveal close chemical similarities between all the selected samples and to identify key metabolites characteristic of the standard. The results suggested that accumulation and distribution of metabolites in aerial and underground parts were different. Moreover, root samples tended to be grouped on the basis of the geographical closeness of region. Five metabolites can be considered as potential markers for the classification of underground parts from different regions. These results provided chemical information on the potential pharmaceutical value for further research, making G. rigescens ideal for the rational usage of different parts and exploitation of the source. Copyright © 2015 John Wiley & Sons, Ltd.
Blunted responses to reward in remitted post‐traumatic stress disorder
Authors: Kalebasi Nilufer , Kuelen Eveline , Schnyder Ulrich , Schumacher Sonja , Mueller‐Pfeiffer Christoph , Wilhelm Frank H. , Athilingam Jegath , Moergeli Hanspeter , Martin‐Soelch Chantal
Published: June 2015

Background

Recent evidence suggests blunted responses to rewarding stimuli in patients with post‐traumatic stress disorder (PTSD). However, it is not clear whether these alterations in reward processing normalize in remitted PTSD patients.

Methods

We tested behavioral and physiological responses to monetary reward in a spatial memory task in 13 accident survivors with remitted PTSD, 14 accident survivors who never had PTSD, and 16 nontrauma‐exposed subjects. All accident survivors were recruited from two samples of severely physically injured patients, who had participated in previous prospective studies on the incidence of PTSD after accidental injury approximately 10 years ago. Reaction time, accuracy, skin conductance responses, and self‐reported mood were assessed during the task.

Results

Accident survivors who never had PTSD and nontrauma exposed controls reported significantly higher positive mood in the reinforced versus nonreinforced condition (P < 0.045 and P < 0.001, respectively), while there was no effect of reinforcement in remitted PTSD subjects.

Conclusions

Our findings suggest an alteration of the reward system in remitted PTSD. Further research is needed to investigate whether altered reward processing is a residual characteristic in PTSD after remission of symptoms or, alternatively, a preexisting risk factor for the development of PTSD after a traumatic event.
Investigation of Structural Determinants for the Substrate Specificity in the Zinc‐Dependent Alcohol Dehydrogenase CPCR2 from Candida parapsilosis
Authors: Loderer Christoph , Dhoke Gaurao V. , Davari Mehdi D. , Kroutil Wolfgang , Schwaneberg Ulrich , Bocola Marco , Ansorge‐Schumacher Marion B.
Published: June 2015

Zinc‐dependent alcohol dehydrogenases (ADHs) are a class of enzymes applied in different biocatalytic processes ranging from lab to industrial scale. However, one drawback is the limited substrate range, necessitating a whole array of different ADHs for the relevant substrate classes. In this study, we investigated structural determinants of the substrate spectrum in the zinc‐dependent ADH carbonyl reductase 2 from Candida parapsilosis (CPCR2), combining methods of mutational analysis with in silico substrate docking. Assigned active site residues were genetically randomized, and the resulting mutant libraries were screened with a selection of challenging carbonyl substrates. Three variants (C57A, W116K, and L119M) with improved activities toward different substrates were detected at neighboring positions in the active site. Thus, all possible combinations of the mutations were generated and characterized for their substrate specificity, yielding several improved variants. The most interesting were a C57A variant, with a 27‐fold increase in specific activity for 4′‐acetamidoacetophenone, and the double mutant CPCR2 B16‐(C57A, L119M), with a 45‐fold improvement in the kcat⋅KM−1 value. The obtained variants were further investigated by in silico docking experiments. The results indicate that the mentioned residues are structural determinants of the substrate specificity of CPCR2, being major players in the definition of the active site. Comparison of these results with closely related enzymes suggests that these might even be transferred to other ADHs.
A Light‐Controlled TLR4 Agonist and Selectable Activation of Cell Subpopulations
Authors: Stutts Lalisa , Esser‐Kahn Aaron P.
Published: June 2015

The spatial and temporal aspects of immune cell signaling are key parameters in defining the magnitude of an immune response. Toll‐like receptors (TLRs) on innate immune cells are important in the early detection of pathogens and initiation of an immune response. Controlling the spatial and temporal signaling of TLRs would enable further study of immune synergies and assist in the development of new vaccines. Here, we show a light‐based method for the spatial control of TLR4 signaling. A TLR4 agonist, pyrimido[5,4‐b]indole, was protected with a cage at a position critical for receptor binding. This afforded a photocontrollable agonist that was inactive while caged, yet effected NF‐κB activity in cells following UV photocontrolled deprotection. We demonstrated spatial control of NF‐κB activation within a population of cells by treating all cells with the caged TLR4 agonist and constraining light exposure and consequent activation to a region of interest.
Super‐Resolution Imaging and Quantitative Analysis of Membrane Protein/Lipid Raft Clustering Mediated by Cell‐Surface Self‐Assembly of Hybrid Nanoconjugates
Authors: Hartley Jonathan M. , Chu Te‐Wei , Peterson Eric M. , Zhang Rui , Yang Jiyuan , Harris Joel , Kopeček Jindřich
Published: June 2015

Super‐resolution imaging was used to quantify organizational changes in the plasma membrane after treatment with hybrid nanoconjugates. The nanoconjugates crosslinked CD20 on the surface of malignant B cells, thereby inducing apoptosis. Super‐resolution images were analyzed by using pair‐correlation analysis to determine cluster size and to count the average number of molecules in the clusters. The role of lipid rafts was investigated by pre‐treating cells with a cholesterol chelator and actin destabilizer to prevent lipid raft formation. Lipid raft cluster size correlated with apoptosis induction after treatment with the nanoconjugates. Lipid raft clusters had radii of ∼200 nm in cells treated with the hybrid nanoconjugates. Super‐resolution images provided precise molecule location coordinates that could be used to determine density of bound conjugates, cluster size, and number of molecules per cluster.
Low‐dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson's disease symptoms without side effects
Authors: Wakade Chandramohan , Chong Raymond , Bradley Eric , Morgan John C.
Published: June 2015

Key Clinical Message

A 65‐year‐old male, Parkinson's disease patient, was evaluated for GPR109A expression, niacin index, UPDRS scale, handwriting test, and quality of sleep with and without niacin treatment. The evaluation was repeated 3 months after niacin was stopped. Niacin modulated the abovementioned parameters and showed the overall improvement without side effects.
Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report
Authors: Annaloro Claudio , Costa Antonella , Fracchiolla Nicola S , Mometto Gabriella , Artuso Silvia , Saporiti Giorgia , Tagliaferri Elena , Grifoni Federica , Onida Francesco , Cortelezzi Agostino
Published: June 2015

Key Clinical Message

We present a case of severe, irreversible neurotoxicity in a 55‐year‐old‐patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory‐motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity.
Divergent Multicomponent Tandem Palladium‐Catalyzed Aminocarbonylation‐Cyclization Approaches to Functionalized Imidazothiazinones and Imidazothiazoles
Authors: Veltri Lucia , Mancuso Raffaella , Altomare Angela , Gabriele Bartolo
Published: June 2015

The reactivity of 2‐(prop‐2‐ynylthio)imidazoles under PdI2/KI‐catalyzed oxidative aminocarbonylation conditions has been studied. Under relatively mild conditions, 0.33–1 mol % of catalyst at 100 °C in MeCN and under 20 atm (at 25 °C) of a 4:1 mixture of CO/air, and in the presence of an equimolar amount of a secondary nucleophilic amine, substrates that are unsubstituted or bear a single substituent on the imidazole ring were converted directly in a multicomponent fashion into functionalized imidazothiazinones. This transformation occurred through a new auto‐tandem catalysis process that involves two concatenated catalytic cycles both catalyzed by PdI2: oxidative aminocarbonylation of the terminal triple bond/cyclocarbonylation. However, in the presence of an excess of secondary amine, 4,5‐disubstituted substrates led selectively to functionalized imidazothiazoles through an oxidative aminocarbonylation/conjugate addition process.
Silver–Cobalt Oxides Derived from Silver Nanoparticles Deposited on Layered Double Hydroxides for Methane Combustion
Authors: Zhao Shen , Li Junhua
Published: June 2015

Ag nanoparticles (Ag NPs) have been deposited successfully on CoAl‐layered double hydroxide (CoAl‐LDH) layers through a simple and facile self‐redox process to give Ag‐CoAl‐LDHs. Furthermore, the CoAl‐LDHs and the Ag‐CoAl‐LDHs are calcined in air at different temperatures (500, 600, and 700 °C) to give CoAlO‐X and Ag‐CoAlO‐X catalysts for methane combustion (X=500, 600, and 700). The catalytic and characterization results reveal that Ag‐CoAlO‐600 has the highest catalytic activity as it has the highest low‐temperature reducibility and the most abundant surface Co3+ and surface adsorbed oxygen species. In addition, the Ag NP sizes on Ag‐CoAlO and the morphology changes of the CoAlO nanosheet supports affect the catalytic activity of methane combustion.
A Comprehensive Computational Fluid Dynamics Study of Droplet‐Film Impact and Heat Transfer
Authors: Jiang Fan , Wang Yijun , Xiang Jianhua , Liu Zhenzhang
Published: June 2015

The Eulerian multiphase model and continuum surface force (CSF) are employed to simulate the liquid droplet impinging onto a solid wall with a pre‐existing thin film of the same liquid. The numerical results are compared with the experimental data reported in the literature, indicating a reasonable matching. The flow field and splashing behavior of a droplet impinging onto a liquid film are analyzed. The reason for the edge of the crown to eject into secondary drops is found. The splashing behavior can be influenced by the impacting velocity and fluid properties. The effects of impact velocity, droplet diameter, depth of film, liquid property, and droplet and wall temperature on the heat removal are investigated. Numerical results demonstrate that an increase in impact velocity, droplet diameter, film depth, cooling droplet, and wall temperature enhances the dissipated heat. These results can provide a reference for designing spray‐cooling systems.
Power Requirement for Mixing Shear‐Thinning Fluids with a Planetary Mixer
Authors: Auger Frederic , André Christophe , Bouvier Laurent , Redl Andreas , Morel Marie‐Hélène , Delaplace Guillaume
Published: June 2015

The optimal control of processes dealing with non‐Newtonian liquids requires the knowledge and control of the power demand of the mixing equipment. In this context, an extension of the Metzner and Otto concept to planetary mixers is proposed to adapt this concept to planetary mixers. The theoretical part of this work defines modified expressions of Reynolds and power numbers. These definitions introduce a characteristic velocity uch that is used to define the parameter Ks. A planetary mixer is employed to experimentally ascertain this guideline. Power consumption measurements carried out by mixing shear‐thinning fluids permit to determine the Ks factor. This factor varies only slightly with the flow behavior index and may be regarded as a defined constant for this geometry. Finally, experiments with an additional shear‐thickening fluid confirm the validity of this approach.
Kinetic Modeling of Sunflower Oil Methanolysis Catalyzed by Calcium‐Based Catalysts
Authors: Tasić Marija B. , Miladinović Marija R. , Stamenković Olivera S. , Veljković Vlada B. , Skala Dejan U.
Published: June 2015

The kinetic model originally developed for quicklime‐catalyzed methanolysis of sunflower oil was tested for another three calcium‐based catalysts, namely, neat CaO, Ca(OH)2, and CaO·ZnO. This model includes the changing reaction mechanism and the triacylglycerol (TAG) mass transfer. The applicability and generalization capability of this model for heterogeneous methanolysis reaction catalyzed by calcium‐based catalysts was evaluated. As indicated by the high coefficient of determination and the relatively small mean relative percentage deviation, the model was a reliable predictor of the time variation of TAG conversion degree in the sunflower oil methanolysis over all four calcium‐based catalysts within the ranges of the reaction conditions applied. This model is recommended in general for describing the kinetics of sunflower oil methanolysis over calcium‐based catalysts.
One‐Pot Synthesis of Allylic Sulfones, Ketosulfones, and Triflyl Allylic Alcohols from Domino Reactions of Allylic Alcohols with Sulfinic Acid under Metal‐Free Conditions
Authors: Chu Xue‐Qiang , Meng Hua , Xu Xiao‐Ping , Ji Shun‐Jun
Published: June 2015

A metal‐free tandem procedure by using a sulfonylation reaction of aryl allylic alcohols followed by an iodobenzenediacetate (PIDA)‐promoted oxidative functionalization has been established. Allylic sulfones, γ‐ketosulfones, and triflyl allylic alcohols have been constructed in a single operation. The methodology incorporates the sulfonyl (both aryl and triflyl) functionality with a simple work‐up procedure.
Pyrrolo‐dC Metal‐Mediated Base Pairs in the Reverse Watson–Crick Double Helix: Enhanced Stability of Parallel DNA and Impact of 6‐Pyridinyl Residues on Fluorescence and Silver‐Ion Binding
Authors: Yang Haozhe , Mei Hui , Seela Frank
Published: June 2015

Reverse Watson–Crick DNA with parallel‐strand orientation (ps DNA) has been constructed. Pyrrolo‐dC (PyrdC) nucleosides with phenyl and pyridinyl residues linked to the 6 position of the pyrrolo[2,3‐d]pyrimidine base have been incorporated in 12‐ and 25‐mer oligonucleotide duplexes and utilized as silver‐ion binding sites. Thermal‐stability studies on the parallel DNA strands demonstrated extremely strong silver‐ion binding and strongly enhanced duplex stability. Stoichiometric UV and fluorescence titration experiments verified that a single 2pyPyrdC–2pyPyrdC pair captures two silver ions in ps DNA. A structure for the PyrdC silver‐ion base pair that aligns 7‐deazapurine bases head‐to‐tail instead of head‐to‐head, as suggested for canonical DNA, is proposed. The silver DNA double helix represents the first example of a ps DNA structure built up of bidentate and tridentate reverse Watson–Crick base pairs stabilized by a dinuclear silver‐mediated PyrdC pair.
Diversity in Gold‐Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H‐Azirines: [3+2] versus [4+3] Cycloadditions
Authors: Pawar Samir Kundlik , Sahani Rajkumar Lalji , Liu Rai‐Shung
Published: June 2015

Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole products with two regioselectivities when the Cβ‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H‐benzo[d]azepine products instead.
Cysteine‐Mediated Intracellular Building of Luciferin to Enhance Probe Retention and Fluorescence Turn‐On
Authors: Zheng Mengmeng , Huang Haixiao , Zhou Mi , Wang Yuqi , Zhang Yan , Ye Deju , Chen Hong‐Yuan
Published: June 2015

The development of sensitive and selective small molecular probes that enable real‐time detection of endogenous cysteine (Cys) has become an attractive topic because of the essential roles played by Cys in controlling the cellular nitrogen balance and in maintaining biological redox homeostasis. Herein, we report a Cys‐specific probe, 2‐cyanobenzothiazol‐6‐yl acrylate (CBTOA), that shows not only fluorescence turn‐on for sensitive detection of endogenous Cys but also enhanced probe retention inside cells for real‐time monitoring of Cys levels upon external stimulation. Cys‐mediated intracellular formation of luciferin from CBTOA was the key strategy leading to this new type of fluorogenic probe. CBTOA showed fast response to Cys in living cells and liver tissue slices with high sensitivity and selectivity. By using CBTOA as a real‐time probe, we were able to monitor the change in Cys levels in living HeLa cells under ROS‐induced oxidative stress as well as in human mesenchymal stem cells during adipogenic differentiation.
Conformational Plasticity in Glycomimetics: Fluorocarbamethyl‐L‐idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings
Authors: Unione Luca , Xu Bixue , Díaz Dolores , Martín‐Santamaría Sonsoles , Poveda Ana , Sardinha João , Rauter Amelia Pilar , Blériot Yves , Zhang Yongmin , Cañada F. Javier , Sollogoub Matthieu , Jiménez‐Barbero Jesus
Published: June 2015

Sugar function, structure and dynamics are intricately correlated. Ring flexibility is intrinsically related to biological activity; actually plasticity in L‐iduronic rings modulates their interactions with biological receptors. However, the access to the experimental values of the energy barriers and free‐energy difference for conformer interconversion in water solution has been elusive. Here, a new generation of fluorine‐containing glycomimetics is presented. We have applied a combination of organic synthesis, NMR spectroscopy and computational methods to investigate the conformational behaviour of idose‐ and glucose‐like rings. We have used low‐temperature NMR spectroscopic experiments to slow down the conformational exchange of the idose‐like rings. Under these conditions, the exchange rate becomes slow in the 19F NMR spectroscopic chemical shift timescale and allows shedding light on the thermodynamic and kinetic features of the equilibrium. Despite the minimal structural differences between these compounds, a remarkable difference in their dynamic behaviour indeed occurs. The importance of introducing fluorine atoms in these sugars mimics is also highlighted. Only the use of 19F NMR spectroscopic experiments has permitted the unveiling of key features of the conformational equilibrium that would have otherwise remained unobserved.
Dendrimers with Oligospiroketal (OSK) Building Blocks: Synthesis and Properties
Authors: Wessig Pablo , Budach Dennis , Thünemann Andreas F.
Published: June 2015

The development of novel dendrimers containing oligospiroketal (OSK) rods as building blocks is described. The linkage between the core unit (CU), branching units (BU), and OSK rods relies on the CuAAC reaction between terminal alkynes and azides. Two different strategies of dendrimer synthesis were investigated and it was found that the convergent approach is clearly superior to the divergent one. SAXS measurements and MD simulations indicate that the obtained dendrimer features a globular structure with very low density. Obviously, the OSK rods stabilize a rather loose mass‐fractal structure.
Total Synthesis, Stereochemical Revision, and Biological Reassessment of Mandelalide A: Chemical Mimicry of Intrafamily Relationships
Authors: Willwacher Jens , Heggen Berit , Wirtz Conny , Thiel Walter , Fürstner Alois
Published: June 2015

Mandelalide A and three congeners had recently been isolated as the supposedly highly cytotoxic principles of an ascidian collected off the South African coastline. Since these compounds are hardly available from the natural source, a concise synthesis route was developed, targeting structure 1 as the purported representation of mandelalide A. The sequence involves an iridium‐catalyzed two‐directional Krische allylation and a cobalt‐catalyzed carbonylative epoxide opening as entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal acetylene metathesis into natural product total synthesis, which is remarkable in that this class of substrates had been beyond the reach of alkyne metathesis for decades. Synthetic 1, however, proved not to be identical with the natural product. In an attempt to clarify this issue, NMR spectra were simulated for 20 conceivable diastereomers by using DFT followed by DP4 analysis; however, this did not provide a reliable assignment either. The puzzle was ultimately solved by the preparation of three diastereomers, of which compound 6 proved identical with mandelalide A in all analytical and spectroscopic regards. As the entire “northern sector” about the tetrahydrofuran ring in 6 shows the opposite configuration of what had originally been assigned, it is highly likely that the stereostructures of the sister compounds mandelalides B–D must be corrected analogously; we propose that these natural products are accurately represented by structures 68–70. In an attempt to prove this reassignment, an entry into mandelalides C and D was sought by subjecting an advanced intermediate of the synthesis of 6 to a largely unprecedented intramolecular Morita–Baylis–Hillman reaction, which furnished the γ‐lactone derivative 74 as a mixture of diastereomers. Whereas (24R)‐74 was amenable to a hydroxyl‐directed dihydroxylation by using OsO4/TMEDA as the reagent, the sister compound (24S)‐74 did not follow a directed path but simply obeyed Kishi’s rule; only this unexpected escape precluded the preparation of mandelalides C and D by this route. A combined spectroscopic and computational (DFT) study showed that the reasons for this strikingly different behavior of the two diastereomers of 74 are rooted in their conformational peculiarities. This aspect apart, our results show that the OsO4/TMEDA complex reacts preferentially with electron deficient double bonds even if other alkenes are present that are more electron rich and less encumbered. Finally, in a brief biological survey authentic mandelalide A (6) was found to exhibit appreciable cytotoxicity only against one out of three tested human cancer cell lines and all synthetic congeners were hardly active. No significant fungicidal properties were observed.
ChemInform Abstract: Nickel‐Rich Layered Lithium Transition‐Metal Oxide for High‐Energy Lithium‐Ion Batteries
Authors: Liu Wen , Oh Pilgun , Liu Xien , Lee Min‐Joon , Cho Woongrae , Chae Sujong , Kim Youngsik , Cho Jaephil
Published: June 2015

Review: [structure, cathode material performance enhancement, solid electrolyte interface engineering, safety; 89 refs.
Enhanced Anticancer Cells Effects of Optimized Suspension Stable As2O3‐Loaded Poly(lactic‐co‐glycolic acid) Nanocapsules
Authors: Song Xiaoli , You Juan , Xu Chunlan , Zhu Aiping , Yan Caifeng , Guo Rong
Published: June 2015

This study is to prepare a nanosuspension based on poly(lactic‐co‐glycolic acid) (PLGA) for delivery, controlled release and enhanced anti‐solid tumor effects of As2O3. As2O3‐loaded PLGA nanocapsules (As2O3‐PLGA NCs) were prepared by double emulsion‐solvent evaporation method and were optimized by univariate analysis in combination with orthogonal experimental according to several factors. The optimized As2O3‐PLGA NCs presented suitable physical stability, favorable size of (200.2±10.6) nm (PDI=0.117±0.008), spherical shape, and high encapsulation efficiency (92.48%±2.14%). The in vitro suspension stability of the NCs was excellent. The release of As2O3 from the NCs showed pH responsive release characteristics. The NCs can be efficiently taken up by SMMC‐7721 cell and showed excellent antitumor efficacy against SMMC‐7721 cell line. Then, As2O3‐PLGA NCs could be considered as a promising formulation for the pH dependent release of As2O3 in cancer cells and enhance the anti‐solid tumor effects of As2O3.
A Silole‐Based Efficient Electroluminescent Material with Good Electron‐Transporting Potential
Authors: Quan Changyun , Nie Han , Hu Rongrong , Qin Anjun , Zhao Zujin , Tang Ben Zhong
Published: June 2015

A new silole derivative, 2,5‐bis(7‐(dimesitylboranyl)‐9,9‐dimethylfluoren‐2‐yl)‐1‐methyl‐1,3,4‐triphenylsilole ((MesBF)2MTPS), is synthesized and characterized. (MesBF)2MTPS shows a good fluorescence efficiency of 15% in THF solution and a higher efficiency of 86% in solid film, presenting an aggregation‐enhanced emission characteristic. It is thermally and morphologically stable, with high decomposition and glass‐transition temperatures of 257 and 171°C, respectively. The LUMO energy level (−2.96 eV) of (MesBF)2MTPS is lower than that of TPBi, revealing its electron‐transporting potential. Efficient organic light‐emitting diodes (OLEDs) are fabricated using (MesBF)2MTPS as emitter, which radiates yellow light at 554 nm, and affords high maximum luminance, current efficiency, and external quantum efficiency of 48348 cd·m−2, 12.3 cd·A−1, and 4.1%, respectively.
2DB0 mapping of micro solenoids with and without FC‐84 and SU‐8 at 9.4 T
Authors: Mohammadzadeh Mohammad
Published: June 2015

This work addresses the effect of susceptibility matching improvement of micro‐solenoid coil materials on decreasing the B0 deviation in MR imaging of mass‐limited samples at high Tesla animal scanners. For this purpose, I investigated the effect of improving the solenoids of 1 and 0.5 mm diameters “susceptibility matching” by surrounding them in FC‐84 and SU‐8. Comparing 2D B0 maps of solenoids of 1 mm show that the mean value of B0 deviation has decreased by factors of 15.6 and 4.72 for the coils embedded with FC‐84 and SU‐8 respectively. Likewise, the mean of B0 deviation has decreased by factors of 13.15 and 5.27 for the solenoids of 0.5 mm diameter embedded in FC‐84 and SU‐8, respectively. MR images acquired by the solenoids 0.5 and 1 mm are clearly verifying the role of using susceptible materials in the coil structure in reducing the geometrical artifacts due to B0 deviation. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 45B: 69–77, 2015
Acoustic analysis for a split MRI system using FE method
Authors: Wang Yaohui , Liu Feng , Weber Ewald , Tang Fangfang , Jin Jin , Tesiram Yas , Crozier Stuart
Published: June 2015

In some MRI‐LINAC (Magnetic Resonance Imaging and Linear Accelerator) hybrid systems, the MRI scanner is split into two parts to form a central gap for the accommodation of the patient or a LINAC. Little is known about the acoustic characteristics of the split gradient coil structure needed for this system; however, it is believed to be very different from its typical configurations. It is important to develop dedicated numerical methods for the characterization of the unique acoustic properties, to provide engineering solutions for the noise attenuation for such a new system. In this article, we modeled the acoustic fields of a split MRI system and traditional gradient structures using the finite element method. The models were validated against acoustic experimental results obtained from a conventional MRI scanner. The acoustic field distribution analysis showed that the average sound pressure levels in the central gap were lower than those in the cylindrical tunnels of the split MRI system at most frequencies. This was also true when both the x coils or z coils were energized independently. Thus, if the patient bed is placed perpendicular to the axis of the main magnet of the split MRI system, the patient will be subjected to relatively lower acoustic intensities compared with that if the patient bed is placed parallel to the axis of the main magnet. Further work is planned to reduce the sound level in the central gap where the patient bed may be placed for this split system. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 45B: 85–96, 2015