bluuebunny/crossref_metadata_2025 huggingface dataset:
Composition of Muscle Fiber Types in Rat Rotator Cuff Muscles
Authors: Rui Yongjun , Pan Feng , Mi Jingyi
Published: June 2016

The rat is a suitable model to study human rotator cuff pathology owing to the similarities in morphological anatomy structure. However, few studies have reported the composition muscle fiber types of rotator cuff muscles in the rat. In this study, the myosin heavy chain (MyHC) isoforms were stained by immunofluorescence to show the muscle fiber types composition and distribution in rotator cuff muscles of the rat. It was found that rotator cuff muscles in the rat were of mixed fiber type composition. The majority of rotator cuff fibers labeled positively for MyHCII. Moreover, the rat rotator cuff muscles contained hybrid fibers. So, compared with human rotator cuff muscles composed partly of slow‐twitch fibers, the majority of fast‐twitch fibers in rat rotator cuff muscles should be considered when the rat model study focus on the pathological process of rotator cuff muscles after injury. Gaining greater insight into muscle fiber types in rotator cuff muscles of the rat may contribute to elucidate the mechanism of pathological change in rotator cuff muscles‐related diseases. Anat Rec, 299:1397–1401, 2016. © 2016 Wiley Periodicals, Inc.
The integration of an anatomy massive open online course (MOOC) into a medical anatomy curriculum
Authors: Swinnerton Bronwen J. , Morris Neil P. , Hotchkiss Stephanie , Pickering James D.
Published: June 2016

Massive open online courses (MOOCs) are designed as stand‐alone courses which can be accessed by any learner around the globe with only an internet‐enabled electronic device required. Although much research has focused on the enrolment and demographics of MOOCs, their impact on undergraduate campus‐based students is still unclear. This article explores the impact of integrating an anatomy MOOC in to the anatomy curriculum of a year 1 medical degree program at the University of Leeds, United Kingdom. The course did not replace any teaching that was already being delivered, and was used to supplement this teaching to support the students' consolidation and revision. Analysis of student feedback indicates a high level of usage, with evidence to suggest that female learners may have approached the course in a more personalized manner. Although the video based resources and quizzes were greatly appreciated as learning tools, significant evidence suggests the students did not engage, or were inclined to engage, with the discussion fora. Furthermore, a significant majority of students did not want the MOOC to replace the existing teaching they received. Given the feedback provided, this research suggests that although the student population believe there to be value in having access to MOOC material, their role as replacements to campus‐based teaching is not supported. Details regarding the enrolment and engagement of the general public with the MOOC during the two runs are also documented, with the suggestion that graduates employed in the healthcare sector were the primary users of the course. Anat Sci Educ 10: 53–67. © 2016 American Association of Anatomists.
Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: A case–control study
Authors: Noroozi Rezvan , Taheri Mohammad , Movafagh Abolfazl , Mirfakhraie Reza , Solgi Ghasem , Sayad Arezou , Mazdeh Mehrdokht , Darvish Hossein
Published: June 2016

Autism spectrum disorder (ASD) as a synaptopathy is revealed to be pertained to aberrant glutamatergic neurotransmission. Glutamate receptor, metabotropic 7 (GRM7), a receptor coding gene of this pathway, is a new candidate gene for autism. The aim of this study was to examine if there is a relationship between genetic variants rs779867 and rs6782011 of GRM7 with ASD. The present research was designed as a population‐based, case–control study including 518 ASD patients versus 472 control individuals. The results showed that the frequency of rs779867 G/G genotype was significantly higher in ASD patients compared to healthy controls (P = 0.0001). Also, the G allele of this SNP was found to be significantly more frequent in the patients than control group (P = 0.0001). Haplotype analysis exhibited significant association of two estimated block of rs6782011/rs779867 in ASD patients versus control group. We found higher significant frequency of GT haplotype and lower frequencies of AT and AC haplotypes in the patients group compared to healthy controls (P = 0.001, P = 0.006, and P = 0.05, respectively). Our study indicated that the rs779867 polymorphism is associated with ASD; thus, results of this study provide supportive evidence of association of the GRM7 gene with ASD. Autism Res 2016, 9: 1161–1168. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Molecular cloning and characterization of the promoter of aldehyde dehydrogenase gene from Artemisia annua
Authors: Wang Huanyan , Liu Wanhong , Qiu Fei , Chen Yupei , Zhang Fangyuan , Lan Xiaozhong , Chen Min , Zhang Haoxing , Liao Zhihua
Published: June 2016

In recent years, although several related genes had been cloned and characterized, the role of aldehyde dehydrogenase 1 (ALDH1), the newly cloned gene involved in artemisinin biosynthesis pathway, is still not clear. In this study, a 2,100‐bp ALDH1 promoter region fused with GUS reporter gene was stably transferred into Arabidopsis thaliana. Histochemical staining showed the methyl jasmonate (MeJA) and wounding treatment induced the GUS gene expression specifically in the trichomes of transgenic A. thaliana, consistent with the results that the expression level of ALDH1 gene was increased in the A. annua under MeJA and wounding treatments. Two RAA motifs (AP2/ERF binding site) but no W box (WRKY binding site) motif were identified in the ALDH1 promoter by the analysis through PLACE and plantCARE. Through the dual luciferase reporter assay, we revealed that both AaORA and AaERF2, rather than AaWRKY1, could activate the expression of ALDH1 promoter. Our study shed light on the in‐depth understanding of the role of ALDH1 in artemisinin biosynthesis.
Life cycle greenhouse gas emissions of bio‐oil from two‐step torrefaction and fast pyrolysis of pine
Authors: Winjobi Olumide , Shonnard David R , Bar‐Ziv Ezra , Zhou Wen
Published: June 2016

Life cycle assessment of bio‐oil from woody biomass through two pathways was carried out using a one‐step pathway that utilizes fast pyrolysis of pine and a two‐step pathway that incorporates a torrefaction step prior to fast pyrolysis. A two‐step pathway with torrefaction at a temperature of 330 °C and pyrolysis at 530 °C had a global warming potential of about 6 g CO2 equivalent per MJ of bio‐oil compared to about 39 g CO2 equivalent per MJ of bio‐oil for a one‐step pathway using an energy allocation‐based analysis. For a one‐step pathway, the size reduction step made the highest contribution of over 50% of the overall global warming potential. Greenhouse gas (GHG) savings of up to 80% compared to heavy fuel oil (HFO) were achieved for a two‐step pathway in comparison to a one‐step pathway due to savings in size reduction energy. The use of renewable energy sources produced internally to provide process heat either by first burning char and then condensables from torrefaction (oil) or vice versa resulted in similar global warming potential reduction in comparison to use of natural gas to provide process heat. The bio‐oil production pathways were found to be more sustainable in comparison to HFO due to relying chiefly on renewable biomass rather than fossil energy. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
Improving carbohydrate production of Chlorella sorokiniana NIES‐2168 through semi‐continuous process coupled with mixotrophic cultivation
Authors: Wang Yue , Chiu Sheng‐Yi , Ho Shih‐Hsin , Liu Zhuo , Hasunuma Tomohisa , Chang Ting‐Ting , Chang Kuan‐Fu , Chang Jo‐Shu , Ren Nan‐Qi , Kondo Akihiko
Published: June 2016

Biofuels from microalgae is now a hot issue of great potential. However, achieving high starch productivity with photoautotrophic microalgae is still challenging. A feasible approach to enhance the growth and target product of microalgae is to conduct mixotrophic cultivation. The appropriate acetate addition combined with CO2 supply as dual carbon sources (i.e., mixotrophic cultivation) could enhance the cell growth of some microalgae species, but the effect of acetate‐mediated mixotrophic culture mode on carbohydrate accumulation in microalgae remains unclear. Moreover, there is still lack of the information concerning how to increase the productivity of carbohydrates from microalgae under acetate‐amended mixotrophic cultivation and how to optimize the engineering strategies to achieve the goal. This study was undertaken to develop an optimal acetate‐contained mixotrophic cultivation system coupled with effective operation strategies to markedly improve the carbohydrate productivity of Chlorella sorokiniana NIES‐2168. The optimal carbohydrate productivity of 695 mg/L/d was obtained, which is the highest value ever reported. The monosaccharide in the accumulated carbohydrates is mainly glucose (i.e., 85–90%), which is very suitable for bio‐alcohols fermentation. Hence, by applying the optimal process developed in this study, C. sorokiniana NIES‐2168 has a high potential to serve as a feedstock for subsequent biofuels conversion.
Porting the synthetic D‐glucaric acid pathway from Escherichia coli to Saccharomyces cerevisiae
Authors: Gupta Amita , Hicks Michael A. , Manchester Shawn P. , Prather Kristala L. J.
Published: June 2016

D‐Glucaric acid can be produced as a value‐added chemical from biomass through a de novo pathway in Escherichia coli. However, previous studies have identified pH‐mediated toxicity at product concentrations of 5 g/L and have also found the eukaryotic myo‐inositol oxygenase (MIOX) enzyme to be rate‐limiting. We ported this pathway to Saccaromyces
cerevisiae, which is naturally acid‐tolerant and evaluate a codon‐optimized MIOX homologue. We constructed two engineered yeast strains that were distinguished solely by their MIOX gene – either the previous version from Mus musculus or a homologue from Arabidopsis thaliana codon‐optimized for expression in S. cerevisiae – in order to identify the rate‐limiting steps for D‐glucaric acid production both from a fermentative and non‐fermentative carbon source. myo‐Inositol availability was found to be rate‐limiting from glucose in both strains and demonstrated to be dependent on growth rate, whereas the previously used M. musculus MIOX activity was found to be rate‐limiting from glycerol. Maximum titers were 0.56 g/L from glucose in batch mode, 0.98 g/L from glucose in fed‐batch mode, and 1.6 g/L from glucose supplemented with myo‐inositol. Future work focusing on the MIOX enzyme, the interplay between growth and production modes, and promoting aerobic respiration should further improve this pathway.
Identifying and retargeting transcriptional hot spots in the human genome
Authors: Cheng Joseph K. , Lewis Amanda M. , Kim Do Soon , Dyess Timothy , Alper Hal S.
Published: June 2016

Mammalian cell line development requires streamlined methodologies that will reduce both the cost and time to identify candidate cell lines. Improvements in site‐specific genomic editing techniques can result in flexible, predictable, and robust cell line engineering. However, an outstanding question in the field is the specific site of integration. Here, we seek to identify productive loci within the human genome that will result in stable, high expression of heterologous DNA. Using an unbiased, random integration approach and a green fluorescent reporter construct, we identify ten single‐integrant, recombinant human cell lines that exhibit stable, high‐level expression. From these cell lines, eight unique corresponding integration loci were identified. These loci are concentrated in non‐protein coding regions or intronic regions of protein coding genes. Expression mapping of the surrounding genes reveals minimal disruption of endogenous gene expression. Finally, we demonstrate that targeted de novo integration at one of the identified loci, the 12th exon‐intron region of the GRIK1 gene on chromosome 21, results in superior expression and stability compared to the standard, illegitimate integration approach at levels approaching 4‐fold. The information identified here along with recent advances in site‐specific genomic editing techniques can lead to expedited cell line development.
Multiplexed Capillary Electrophoresis as Analytical Tool for Fast Optimization of Multi‐Enzyme Cascade Reactions – Synthesis of Nucleotide Sugars
Authors: Wahl Claudia , Hirtz Dennis , Elling Lothar
Published: June 2016

Nucleotide sugars are considered as bottleneck and expensive substrates for enzymatic glycan synthesis using Leloir‐glycosyltransferases. Synthesis from cheap substrates such as monosaccharides is accomplished by multi‐enzyme cascade reactions. Optimization of product yields in such enzyme modules is dependent on the interplay of multiple parameters of the individual enzymes and governed by a considerable time effort when convential analytic methods like capillary electrophoresis (CE) or HPLC are applied. We here demonstrate for the first time multiplexed CE (MP‐CE) as fast analytical tool for the optimization of nucleotide sugar synthesis with multi‐enzyme cascade reactions. We introduce a universal separation method for nucleotides and nucleotide sugars enabling us to analyze the composition of six different enzyme modules in a high‐throughput format. Optimization of parameters (T, pH, inhibitors, kinetics, cofactors and enzyme amount) employing MP‐CE analysis is demonstrated for enzyme modules for the synthesis of UDP‐α‐D‐glucuronic acid (UDP‐GlcA) and UDP‐α‐D‐galactose (UDP‐Gal). In this way we achieve high space‐time‐yields: 1.8 g/L⋆h for UDP‐GlcA and 17 g/L⋆h for UDP‐Gal. The presented MP‐CE methodology has the impact to be used as general analytical tool for fast optimization of multi‐enzyme cascade reactions.
Dynamic interactions of the cortical networks during thought suppression
Authors: Aso Toshihiko , Nishimura Kazuo , Kiyonaka Takashi , Aoki Takaaki , Inagawa Michiyo , Matsuhashi Masao , Tobinaga Yoshikazu , Fukuyama Hidenao
Published: June 2016

Objectives

Thought suppression has spurred extensive research in clinical and preclinical fields, particularly with regard to the paradoxical aspects of this behavior. However, the involvement of the brain's inhibitory system in the dynamics underlying the continuous effort to suppress thoughts has yet to be clarified. This study aims to provide a unified perspective for the volitional suppression of internal events incorporating the current understanding of the brain's inhibitory system.

Materials and Methods

Twenty healthy volunteers underwent functional magnetic resonance imaging while they performed thought suppression blocks alternating with visual imagery blocks. The whole dataset was decomposed by group‐independent component analysis into 30 components. After discarding noise components, the 20 valid components were subjected to further analysis of their temporal properties including task‐relatedness and between‐component residual correlation.

Results

Combining a long task period and a data‐driven approach, we observed a right‐side‐dominant, lateral frontoparietal network to be strongly suppression related. This network exhibited increased fluctuation during suppression, which is compatible with the well‐known difficulty of suppression maintenance.

Conclusions

Between‐network correlation provided further insight into the coordinated engagement of the executive control and dorsal attention networks, as well as the reciprocal activation of imagery‐related components, thus revealing neural substrates associated with the rivalry between intrusive thoughts and the suppression process.
The ‘persuader’ rule dispute moves into crowded labor law field
Authors: Porter Michael
Published: June 2016

Labor‐union organizing efforts have become more visible on campuses during the past couple of years. Colleges and universities have seen organizing efforts involving a variety of participants, ranging from physical plant workers to faculty members and students.
Did a student win bid for reinstatement after a suspension?
Authors: Gelpi Aileen
Published: June 2016

Michael Marshall and a female student were in the honors tutorial program at Ohio University. That program had small class sizes, and the two lived in the same residence hall.
Production of a Novel Amide‐Containing Polyene by Activating a Cryptic Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08
Authors: Du Danyao , Katsuyama Yohei , Onaka Hiroyasu , Fujie Manabu , Satoh Noriyuki , Shin‐ya Kazuo , Ohnishi Yasuo
Published: June 2016

Streptomyces sp. MSC090213JE08 seems to have more than 20 cryptic biosynthetic gene clusters for secondary metabolites. We aimed to activate some of them by forced production of Streptomyces antibiotic regulatory protein (SARP) family transcriptional activators. We constructed seven recombinant strains, each of which contained a SARP gene under the control of a constitutive promoter, and subjected them to comparative metabolic profiling analysis. Four of the seven strains produced nine metabolites that were hardly detected in the control strains. We isolated a new metabolite (named ishigamide) from the SARP‐7‐expressing strain and determined its structure as 3‐((2E,4E,6E,8E)‐13‐hydroxytetradeca‐2,4,6,8‐tetraenamido)propanoic acid. Genome scanning and gene disruption studies identified the ishigamide biosynthetic gene cluster adjacent to the SARP‐7 gene. We think that a new subfamily of type II polyketide synthase is involved in the biosynthesis of the polyene structure of ishigamide.
Biosynthesis of Trehangelin in Polymorphospora rubra K07–0510: Identification of Metabolic Pathway to Angelyl‐CoA
Authors: Inahashi Yuki , Shiraishi Taro , Palm Kaia , Takahashi Yoko , Ōmura Satoshi , Kuzuyama Tomohisa , Nakashima Takuji
Published: June 2016

Trehangelins are trehalose angelates discovered from endophytic actinomycete Polymorphospora rubra K07‐0510. We identified the trehangelin biosynthetic gene cluster, including genes that encode a glycoside hydrolase‐like protein (thgC), α‐amylase (thgD), 3‐ketoacyl‐ACP synthase III (thgI), 3‐ketoacyl‐ACP reductase (thgK), enoyl‐CoA hydratase (thgH) and acyl transferase (thgJ). Heterologous expression of thgH, thgI, thgJ and thgK confirmed the importance of these genes in the biosynthesis of trehangelin A. Enzymatic activity studies showed that ThgI catalyses the condensation of acetyl‐CoA and methylmalonyl‐CoA to 2‐methylacetoacetyl‐CoA (MAA‐CoA), ThgK catalyses NADPH‐dependent reduction of MAA‐CoA to 3‐hydroxy‐2‐methylbutyryl‐CoA (HMB‐CoA) and ThgH catalyses the dehydration of HMB‐CoA to angelyl‐CoA (AN‐CoA). This is the first report on the elucidation of the enzymatic formation of AN‐CoA.
Transcatheter aortic valve‐in‐valve treatment of degenerative stentless supra‐annular Freedom Solo valves: A single centre experience
Authors: Cockburn James , Dooley Maureen , Parker Jessica , Hill Andrew , Hutchinson Nevil , de Belder Adam , Trivedi Uday , Hildick‐Smith David
Published: June 2016

Background

Redo surgery for degenerative bioprosthetic aortic valves is associated with significant morbidity and mortality. Report results of valve‐in‐valve therapy (ViV‐TAVI) in failed supra‐annular stentless Freedom Solo (FS) bioprostheses, which are the highest risk for coronary occlusion.

Methods

Six patients with FS valves (mean age 78.5 years, 50% males). Five had valvular restenosis (peak gradient 87.2 mm Hg, valve area 0.63 cm2), one had severe regurgitation (AR). Median time to failure was 7 years.

Results

Patients were high risk (mean STS/Logistic EuroScore 10.6 15.8, respectively). FS valves ranged from 21 to 25 mm. Successful ViV‐TAVI was achieved in 4/6 patients (67%). Of the unsuccessful cases, (patient 1 and 2 of series) patient 1 underwent BAV with simultaneous aortography which revealed left main stem occlusion. The procedure was stopped and the patient went forward for repeat surgery. Patient 2 underwent successful ViV‐TAVI with a 26‐mm CoreValve with a guide catheter in the left main, but on removal coronary obstruction occurred, necessitating valve snaring into the aorta. Among the successful cases, (patients 3, 4, 5, 6) the TAVIs used were CoreValve Evolut R 23 mm (n = 3), and Lotus 23 mm (n = 1). In the successful cases the peak gradient fell from 83.0 to 38.3 mm Hg. No patient was left with >1+ AR. One patient had a stroke on Day 2, with full neurological recovery. Two patients underwent semi‐elective pacing for LBBB and PR >280 ms.

Conclusions

ViV‐TAVI in stentless Freedom Solo valves is high risk. The risk of coronary occlusion is high. The smallest possible prosthesis (1:1 sizing) should be used, and strategies to protect the coronary vessels must be considered. © 2016 Wiley Periodicals, Inc.
Contemporary practice patterns related to the risk of acute kidney injury in the catheterization laboratory: Results from a survey of Society of Cardiovascular Angiography and Intervention (SCAI) cardiologists
Authors: Prasad Anand , Sohn Aaron , Morales Jonathan , Williams Ken , Bailey Steven R. , Levin Daniel , McCullough Peter A. , Mehran Roxana , Lopez‐Cruz Georgina , Harder Joel
Published: June 2016

Objectives

The goal of the present study was to survey the Society of Cardiovascular Angiography and Intervention (SCAI) member cardiologists to evaluate contemporary practice patterns with regards to contrast use, acute kidney injury (AKI) risk assessment, and prevention in patients undergoing invasive angiography. We sought to compare the physician responses against guideline statements and evidence‐based data from clinical studies.

Methods

A 20‐question online survey based on a modified Likert scale was sent out via email to the Society of Cardiovascular Angiography and Intervention (SCAI) member cardiologists. The survey questions focused on prophylaxis methods, medication management, risk assessment, contrast agent use, and postprocedure care. A scoring system was developed which examined the individual responses to analyze the 10 questions with the greatest strength of evidence in the literature and guidelines.

Results

The survey was completed by 506 individuals. Selected responses of note included the use of standardized volume expansion protocols: 64.8%, use of iso‐osmolar contrast (iodixanol) in the majority of patients at risk of AKI: 55%, and 27% of individuals reported diluting contrast with saline for patients at risk of AKI during coronary angiography. For questions with support from guideline documents, 56.9% of the responses were scored as concordant with evidence‐based data. Individuals who reported that the risk of AKI was often or always important in planning angiography for “at risk patients” were more likely to closely monitor renal function (76.7% vs. 40.0%, P = 0.003), obtain nephrology consultation (45.2% vs. 13.3%, P = 0.016) and use iso‐osmolar contrast agents (56.0% vs. 26.7%, P = 0.033).

Conclusions

The majority of cardiologists participating in this survey, reported practice patterns consistent with guideline and evidence‐based recommendations. However, over 40% of responses to questions were inconsistent with these recommendations, suggesting continued opportunities for education and quality improvement concerning AKI prevention. © 2016 Wiley Periodicals, Inc.
Impact of imaging approach on radiation dose and associated cancer risk in children undergoing cardiac catheterization
Authors: Hill Kevin D. , Wang Chu , Einstein Andrew J. , Januzis Natalie , Nguyen Giao , Li Jennifer S. , Fleming Gregory A. , Yoshizumi Terry K.
Published: June 2016

Objectives

To quantify the impact of image optimization on absorbed radiation dose and associated risk in children undergoing cardiac catheterization.

Background

Various imaging and fluoroscopy system technical parameters including camera magnification, source‐to‐image distance, collimation, antiscatter grids, beam quality, and pulse rates, all affect radiation dose but have not been well studied in younger children.

Methods

We used anthropomorphic phantoms (ages: newborn and 5 years old) to measure surface radiation exposure from various imaging approaches and estimated absorbed organ doses and effective doses (ED) using Monte Carlo simulations. Models developed in the National Academies' Biological Effects of Ionizing Radiation VII report were used to compare an imaging protocol optimized for dose reduction versus suboptimal imaging (+20 cm source‐to‐image‐distance, +1 magnification setting, no collimation) on lifetime attributable risk (LAR) of cancer.

Results

For the newborn and 5‐year‐old phantoms, respectively ED changes were as follows: +157% and +232% for an increase from 6‐inch to 10‐inch camera magnification; +61% and +59% for a 20 cm increase in source‐to‐image‐distance; −42% and −48% with addition of 1‐inch periphery collimation; −31% and −46% with removal of the antiscatter grid. Compared with an optimized protocol, suboptimal imaging increased ED by 2.75‐fold (newborn) and fourfold (5 years old). Estimated cancer LAR from 30‐min of posteroanterior fluoroscopy using optimized versus suboptimal imaging, respectively was 0.42% versus 1.23% (newborn female), 0.20% versus 0.53% (newborn male), 0.47% versus 1.70% (5‐year‐old female) and 0.16% versus 0.69% (5‐year‐old male).

Conclusions

Radiation‐related risks to children undergoing cardiac catheterization can be substantial but are markedly reduced with an optimized imaging approach. © 2016 Wiley Periodicals, Inc.
Specific Electrocatalytic Oxidation of Cellulose at Carbon Electrodes Modified by Gold Nanoparticles
Authors: Sugano Yasuhito , Kumar Narendra , Peurla Markus , Roine Jorma , Aho Atte , Bobacka Johan , Mikkola Jyri‐Pekka
Published: June 2016

The influence of the size and oxidation state of Au nanoparticles (AuNPs) as electrocatalysts for the electro‐oxidation of cellulose was studied. Carbon paper electrodes modified with AuNPs were used as the electrocatalysts for the electro‐oxidation of cellulose dissolved in 1.3 m NaOH. The size and oxidation state of the AuNPs were determined by using SEM, TEM, and X‐ray photoelectron spectroscopy. Both the size and the oxidation state of the AuNPs were found to influence the electrocatalytic properties of the electrode, as studied by using cyclic voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy. The carbon paper electrodes decorated with AuNPs (less than 25 nm) that consist of metallic Au gave rise to a significantly higher electrocatalytic activity than a bare polycrystalline Au electrode.
Reactivity Study of Pyridyl‐Substituted 1‐Metalla‐2,5‐diaza‐cyclopenta‐2,4‐dienes of Group 4 Metallocenes
Authors: Becker Lisanne , Reiß Fabian , Altenburger Kai , Spannenberg Anke , Arndt Perdita , Jiao Haijun , Rosenthal Uwe
Published: June 2016

In this work the reactivity of 1‐metalla‐2,5‐diaza‐cyclopenta‐2,4‐dienes of group 4 metallocenes, especially of the pyridyl‐substituted examples, towards small molecules is investigated. The addition of H2, CO2, Ph−C≡N, 2‐py−C≡N, 1,3‐dicyanobenzene or 2,6‐dicyanopyridine results in exchange reactions, which are accompanied by the elimination of a nitrile. For CO2, a coordination to the five‐membered cycle occurs in case of Cp*2Zr(N=C(2‐py)−C(2‐py)=N). A 1,4‐diaza‐buta‐1,3‐diene complex is formed by H‐transfer in the conversion of the analogous titanocene compound with CH3−C≡N, PhCH2−C≡N or acetone. For CH3−C≡N a coupling product of three acetonitrile molecules is established additionally. In order to split off the metallocene from the coupled nitriles, we examined reactions with HCl, PhPCl2, PhPSCl2 and SOCl2. In the last case, the respective thiadiazole oxides and the metallocene dichlorides were obtained. A subsequent reaction produced thiadiazoles.
Enantioselective Alkynylation of 2‐Trifluoroacetyl Imidazoles Catalyzed by Bis‐Cyclometalated Rhodium(III) Complexes Containing Pinene‐Derived Ligands
Authors: Zheng Yu , Harms Klaus , Zhang Lilu , Meggers Eric
Published: June 2016

Chiral rhodium(III) complexes containing two cyclometalating 2‐phenyl‐5,6‐(S,S)‐pinenopyridine ligands and two additional acetonitriles are introduced as excellent catalysts for the highly enantioselective alkynylation of 2‐trifluoroacetyl imidazoles. Whereas the ligand‐based chirality permits the straightforward synthesis of the complexes in a diastereomerically and enantiomerically pure fashion, the metal‐centered chirality is responsible for the asymmetric induction over the course of the catalysis. For comparison, the analogous iridium congeners provide only low enantioselectivity, and previously reported benzoxazole‐ and benzothiazole‐based catalysts do not show any catalytic activity for this reaction under standard reaction conditions.
Adsorption mechanism of the simulated red mud from diaspore with high levels of silicon and iron
Authors: Liu Jinwei , Hu Huiping , Wang Meng , Chen Qiyuan , Dai Kuan
Published: June 2016

The flocculation effect of Hx‐600 on the simulated red mud of the Bayer process from diaspore with high levels of silicon and iron was investigated, and a flocculant with high content of hydroxamate groups (HCPAM) and sodium polyacrylate (PAAS) was chosen as the model compound of Hx‐600. The typical silicon‐containing and iron‐containing monominerals in red mud, hydration grossular and hematite, were correspondingly synthesized, and the adsorption mechanism with HCPAM or PAAS was investigated using FTIR and XPS, respectively. The results reveal physical adsorption of HCPAM or PAAS on the surfaces of hydration grossular and chemisorption of HCPAM or PAAS on the surfaces of hematite. The atomic Mulliken populations of the model compounds of HCPAM and PAAS were calculated by quantum chemical calculation. The results show that a five‐membered ring may be formed on the surfaces of HCPAM‐treated hematite and a four‐membered ring may be formed on the surfaces of PAAS‐treated hematite. A stronger adsorption of the flocculant with hydroxamate groups on the hematite surfaces can be estimated, compared to carboxyl groups. Therefore, the improvement of settling performance achieved by Hx‐600 could be attributed to the high content of hydroxamate groups and high molecular weight (mass) of Hx‐600. A chemisorption with a bridging flocculation between the iron‐containing component in red mud and Hx‐600, and a physical adsorption with a bridging flocculation between the silicon‐containing component in red mud and Hx‐600 can enhance the settling performance of the simulated red mud of the Bayer process from diaspore with high levels of silicon and iron.
Actin filaments—A target for redox regulation
Authors: Wilson Carlos , Terman Jonathan R. , González‐Billault Christian , Ahmed Giasuddin
Published: June 2016

Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through noncovalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation‐reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function. Here, we review work implicating Redox intermediates in post‐translationally altering actin and discuss what is known regarding how these alterations affect the properties of actin. We also focus on two of the best characterized enzymatic sources of these Redox intermediates—the NADPH oxidase NOX and the flavoprotein monooxygenase MICAL—and detail how they have both been identified as altering actin, but share little similarity and employ different means to regulate actin dynamics. Finally, we discuss the role of these enzymes and redox signaling in regulating the actin cytoskeleton in vivo and highlight their importance for neuronal form and function in health and disease. © 2016 Wiley Periodicals, Inc.
A theoretical analysis of chemical exchange saturation transfer echo planar imaging (CEST‐EPI) steady state solution and the CEST sensitivity efficiency‐based optimization approach
Authors: Jiang Weiping , Zhou Iris Yuwen , Wen Lingyi , Zhou Xin , Sun Phillip Zhe
Published: June 2016

Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute labile protons and microenvironmental properties, augmenting routine relaxation‐based MRI. Recent developments of quantitative CEST (qCEST) analysis such as omega plots and RF‐power based ratiometric calculation have extended our ability to elucidate the underlying CEST system beyond the simplistic apparent CEST measurement. CEST MRI strongly varies with experimental factors, including the RF irradiation level and duration as well as repetition time and flip angle. In addition, the CEST MRI effect is typically small, and experimental optimization strategies have to be carefully evaluated in order to enhance the CEST imaging sensitivity. Although routine CEST MRI has been optimized largely based on maximizing the magnitude of the CEST effect, the CEST signal‐to‐noise (SNR) efficiency provides a more suitable optimization index, particularly when the scan time is constrained. Herein, we derive an analytical solution of the CEST effect that takes into account key experimental parameters including repetition time, imaging flip angle and RF irradiation level, and solve its SNR efficiency. The solution expedites CEST imaging sensitivity calculation, substantially faster than the Bloch–McConnell equation‐based numerical simulation approach. In addition, the analytical solution‐based SNR formula enables the exhaustive optimization of CEST MRI, which simultaneously predicts multiple optimal parameters such as repetition time, flip angle and RF saturation level based on the chemical shift and exchange rate. The sensitivity efficiency‐based optimization approach could simplify and guide imaging of CEST agents, including glycogen, glucose, creatine, gamma‐aminobutyric acid and glutamate. Copyright © 2016 John Wiley & Sons, Ltd.
Breast intraductal papillomas without atypia in radiologic‐pathologic concordant core‐needle biopsies: Rate of upgrade to carcinoma at excision
Authors: Pareja Fresia , Corben Adriana D. , Brennan Sandra B. , Murray Melissa P. , Bowser Zenica L. , Jakate Kiran , Sebastiano Christopher , Morrow Monica , Morris Elizabeth A. , Brogi Edi
Published: June 2016

BACKGROUND

The surgical management of mammary intraductal papilloma without atypia (IDP) identified at core‐needle biopsy (CNB) is controversial. This study assessed the rate of upgrade to carcinoma at surgical excision (EXC).

METHODS

This study identified women with a CNB diagnosis of intraductal papilloma without atypia or carcinoma at a cancer center between 2003 and 2013. Radiologic‐pathologic concordance was assessed for all cases, and discordant cases were excluded. The radiologic and clinicopathologic features of patients with a CNB diagnosis of IDP were correlated with an upgrade to carcinoma at EXC.

RESULTS

The study population consists of 189 women with 196 IDPs; 166 women (171 IDPs) underwent EXC. The upgrade rate was 2.3% (4 of 171). The upgraded lesions were 2 invasive lobular carcinomas and 2 cases of ductal carcinoma in situ (DCIS). One case of DCIS involved the residual IDP, whereas the other 3 carcinomas were ≥ 8 mm away. Twenty‐four women (25 IDPs) did not undergo EXC and had stable imaging on follow‐up (median, 23.5 months).

CONCLUSIONS

The upgrade rate at EXC for IDPs diagnosed at CNB with radiologic‐pathologic concordance was 2.3%. These findings suggest that observation is appropriate for patients with radiologic‐pathologic concordant CNB yielding IDP, regardless of its size. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2819–2827. © 2016 American Cancer Society
Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A Center for International Blood and Marrow Transplant Research (CIBMTR) analysis
Authors: Deol Abhinav , Sengsayadeth Salyka , Ahn Kwang Woo , Wang Hai‐Lin , Aljurf Mahmoud , Antin Joseph Harry , Battiwalla Minoo , Bornhauser Martin , Cahn Jean‐Yves , Camitta Bruce , Chen Yi‐Bin , Cutler Corey S. , Gale Robert Peter , Ganguly Siddhartha , Hamadani Mehdi , Inamoto Yoshihiro , Jagasia Madan , Kamble Rammurti , Koreth John , Lazarus Hillard M. , Liesveld Jane , Litzow Mark R. , Marks David I. , Nishihori Taiga , Olsson Richard F. , Reshef Ran , Rowe Jacob M. , Saad Ayman A. , Sabloff Mitchell , Schouten Harry C. , Shea Thomas C. , Soiffer Robert J. , Uy Geoffrey L. , Waller Edmond K. , Wiernik Peter H. , Wirk Baldeep , Woolfrey Ann E. , Bunjes Donald , Devine Steven , de Lima Marcos , Sandmaier Brenda M. , Weisdorf Dan , Khoury Hanna Jean , Saber Wael
Published: June 2016

BACKGROUND

Patients with FMS like tyrosine kinase 3 (FLT3)‐mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT).

METHODS

Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes.

RESULTS

In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild‐type (WT) group (38% [95% confidence interval (CI), 30%‐45%] vs 28% [95% CI, 24%‐33%]; P = .04; relative risk, 1.60 [95% CI, 1.15‐2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia‐free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3‐year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%‐57%; WT group: 55%, 95% CI, 50%‐60%; P = .20).

CONCLUSIONS

The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long‐term survivors. Cancer 2016;122:3005‐3014. © 2016 American Cancer Society.
A randomized phase 2 study exploring the role of bevacizumab and a chemotherapy‐free approach in HER2‐positive metastatic breast cancer: The HAT study (BOOG 2008‐2003), a Dutch Breast Cancer Research Group trial
Authors: Drooger Jan C. , van Tinteren Harm , de Groot Steffen M. , ten Tije Albert J. , de Graaf Hiltje , Portielje Johanneke E. A. , Jager Agnes , Honkoop Aafke , Linn Sabine C. , Kroep Judith R. , Erdkamp Frans L. G. , Hamberg Paul , Imholz Alex L. T. , van Rossum‐Schornagel Quirine C. , Heijns Joan B. , van Leeuwen‐Stok A. Elise , Sleijfer Stefan
Published: June 2016

BACKGROUND

To explore the role of bevacizumab and a chemotherapy‐free approach, the authors evaluated the combination of bevacizumab, trastuzumab, and paclitaxel (HAT) and the regimen of trastuzumab and bevacizumab (HA) with the addition of paclitaxel after progression (HA‐HAT) as first‐line treatment for patients with human epidermal growth factor receptor 2 (HER2)‐positive metastatic breast cancer.

METHODS

In a noncomparative phase 2 trial, patients were randomized between HAT and HA‐HAT. The primary endpoint was the progression‐free rate at 1 year (1‐year PFR). In the HA‐HAT group, progression‐free survival (PFS) was separately established for HA (PFS1) and HAT (PFS2).

RESULTS

Eighty‐four patients received HAT (n = 39) or HA‐HAT (n = 45). The 1‐year PFR was 74.4% (95% confidence interval [CI], 61.8%‐89.4%) and 62.2% (95% CI, 49.6%‐89.4%) in the HAT and HA‐HAT arms, respectively. The median PFS was 19.8 months (95% CI, 14.9‐25.6 months) in the HAT arm and 19.6 months (95% CI, 12.0‐32.0 months) in the HA‐HAT arm. In the HA‐HAT arm, the median PFS1 was 10.4 months (95% CI, 6.2‐15.0 months), and the median PFS2 was 8.2 months (95% CI, 7.0‐12.6 months). The number and severity of adverse events were comparable between the arms.

CONCLUSIONS

Both HAT and HA‐HAT have promising activity in patients with HER2‐positive metastatic breast cancer. In particular, starting with only targeted agents and delaying chemotherapy is worth further exploration. Cancer 2016;122:2961‐2970. © 2016 American Cancer Society.
Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression in breast cancer FNA cell blocks and paired histologic specimens: A large retrospective study
Authors: Vohra Poonam , Buelow Benjamin , Chen Yunn‐Yi , Serrano Maria , Vohra Manjiv Singh , Berry Anna , Ljung Britt‐Marie
Published: June 2016

BACKGROUND

Molecular analysis represents an increasingly important component of the pathologic examination of tumor specimens. Notably, the characterization of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression in breast cancer specimens provides critical prognostic and predictive information. The objective of the current study was to compare the concordance of these markers as determined on fine‐needle aspiration (FNA) cell blocks compared with tissue blocks prepared from surgical specimens.

METHODS

A total of 134 cases of breast carcinoma were identified from 2002 through 2014 with both FNA cell blocks (fixed in 10% formalin) and corresponding available tissue blocks and ER, PR, and HER2 were characterized in both specimens. Negative and positive concordances were determined for ER and PR in cell blocks compared with tissue blocks, and for HER2 immunohistochemistry on cell blocks and tissue blocks versus the corresponding reference method, fluorescence in situ hybridization (FISH).

RESULTS

Concordance for ER expression evaluated on a cell block compared with the corresponding tissue block was 96.2%. Concordance for PR expression was 77.5%. Overall agreement of HER2 FISH testing between cell blocks and tissue blocks was 96.7%. For both cell blocks and tissue blocks, HER2 expression by immunohistochemistry demonstrated ≥98% positive and negative concordance with the FISH reference method.

CONCLUSIONS

ER, PR, and HER2 determination on FNA‐acquired cell block (fixed exclusively in 10% formalin) showed excellent agreement for ER and HER2 and moderate agreement for PR with the corresponding tissue block. These findings support the equivalency of ER and HER2 evaluation performed on FNA cell blocks compared with surgical tissue blocks. Cancer Cytopathol 2016;124:828‐35. © 2016 American Cancer Society.
Comparison of genome sequencing and clinical genotyping for pharmacogenes
Authors: Yang W , Wu G , Broeckel U , Smith CA , Turner V , Haidar CE , Wang S , Carter R , Karol SE , Neale G , Crews KR , Yang JJ , Mullighan CG , Downing JR , Evans WE , Relling MV
Published: June 2016

We compared whole exome sequencing (WES, n = 176 patients) and whole genome sequencing (WGS, n = 68) and clinical genotyping (DMET array‐based approach) for interrogating 13 genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. We focused on 127 CPIC important variants: 103 single nucleotide variations (SNV), 21 insertion/deletions (Indel), HLA‐B alleles, and two CYP2D6 structural variations. WES and WGS provided interrogation of nonoverlapping sets of 115 SNV/Indels with call rate >98%. Among 68 loci interrogated by both WES and DMET, 64 loci (94.1%, confidence interval [CI]: 85.6–98.4%) showed no discrepant genotyping calls. Among 66 loci interrogated by both WGS and DMET, 63 loci (95.5%, CI: 87.2–99.0%) showed no discrepant genotyping calls. In conclusion, even without optimization to interrogate pharmacogenetic variants, WES and WGS displayed potential to provide reliable interrogation of most pharmacogenes and further validation of genome sequencing in a clinical lab setting is warranted.
Preparation of Novel Li4SiO4 Sorbents with Superior Performance at Low CO2 Concentration
Authors: Yang Xinwei , Liu Wenqiang , Sun Jian , Hu Yingchao , Wang Wenyu , Chen Hongqiang , Zhang Yang , Li Xian , Xu Minghou
Published: June 2016

This work produced Li4SiO4 sorbents through an impregnated‐suspension method to overcome its typical poor performance at low CO2 concentrations. A SiO2 colloidal solution and two different organic lithium precursors were selected. A bulgy surface morphology (and thus, the significantly enlarged reacting surface area) was obtained for Li4SiO4, which contributed to the high absorption capacity. As a result, the capacity in cyclic tests at 15 vol % CO2 was approximately 8 times higher than conventional Li4SiO4 prepared through a solid‐state reaction. The phenomenon of a progressively increasing capacity (i.e., sustainable usage) was observed over the 40 cycles investigated, and this increasing trend continued to the last cycle. Correspondingly, over the course of the multicycle absorption/ desorption processes, the sorbents evolve from lacking porosity to having a high number of micron‐sized pores.
A Comparative Study on the Reactivity of Various Ketohexoses to Furanics in Methanol
Authors: van Putten Robert‐Jan , van der Waal Jan C. , Harmse Martin , van de Bovenkamp Henk H. , de Jong Ed , Heeres Hero J.
Published: June 2016

The acid‐catalysed dehydration of the four 2‐ketohexoses (fructose, sorbose, tagatose and psicose) to furanics was studied in methanol (65 g L−1 substrate concentration, 17 and 34 mm sulfuric acid, 100 °C) with Avantium high‐throughput technology. Significant differences in the reactivities of the hexoses and yields of 5‐hydroxymethylfurfural (HMF) and its methyl ether (MMF) were observed. Psicose and tagatose were the most reactive, and psicose also afforded the highest combined yield of MMF and HMF of approximately 55 % at 96 % sugar conversion. Hydroxyacetylfuran and its corresponding methyl ether were formed as byproducts, particularly for sorbose and tagatose, with a maximum combined yield of 8 % for sorbose. The formation of hydroxyacetylfuran was studied through 13C NMR spectroscopy with labelled sorbose, which provided new insights into the reaction mechanism.
Comparing Bilingual to Monolingual Learners on English Spelling: A Meta‐analytic Review
Authors: Zhao Jing , Quiroz Blanca , Dixon L. Quentin , Joshi R. Malatesha
Published: June 2016

This study reports on a meta‐analysis to examine how bilingual learners compare with English monolingual learners on two English spelling outcomes: real‐word spelling and pseudo‐word spelling. Eighteen studies published in peer‐reviewed journals between 1990 and 2014 were retrieved. The study‐level variables and characteristics (e.g. sample size, study design and research instruments) were coded, and 29 independent effect sizes across the 18 retrieved studies were analysed. We found that bilinguals outperformed monolinguals on real‐word spelling overall and more so in early grades, but monolinguals outperformed bilinguals on pseudo‐word spelling. Further, bilinguals at risk for reading difficulties did better on real‐word spelling than monolinguals at risk for reading difficulties. Having investigated systematic sources of variability in effect sizes, we conclude that in comparison with their monolingual peers, bilingual learners, especially those from alphabetic L1 backgrounds, are able to master constrained skills, such as English spelling, in the current instructional context. Copyright © 2016 John Wiley & Sons, Ltd.