bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer
Authors: Takane Kiyoko , Akagi Kiwamu , Fukuyo Masaki , Yagi Koichi , Takayama Tadatoshi , Kaneda Atsushi
Published: April 2017

Sporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome‐wide DNA methylation analysis to classify CRC into distinct subgroups: high‐, intermediate‐, and low‐methylation epigenotypes (HME, IME, and LME, respectively). HME CRC, also called CpG island methylator phenotype (CIMP)‐high CRC, shows methylation of both Group 1 markers (CIMP markers) and Group 2 markers, while IME/CIMP‐low CRC shows methylation of Group 2, but not of Group 1 markers, and LME CRC shows no methylation of either Group 1 or Group 2 markers. While BRAF‐ and KRAS‐mutation(+) CRC strongly correlated with HME and IME, respectively, clinicopathological features of NRAS‐mutation(+) CRC, including association with DNA methylation, remain unclear. To characterize NRAS‐mutation(+) CRC, the methylation levels of 19 methylation marker genes (6 Group 1 and 13 Group 2) were analyzed in 61 NRAS‐mutation(+) and 144 NRAS‐mutation(−) CRC cases by pyrosequencing, and their correlation with clinicopathological features was investigated. Different from KRAS‐mutation(+) CRC, NRAS‐mutation(+) CRC significantly correlated with LME. NRAS‐mutation(+) CRC showed significantly better prognosis than KRAS‐mutation(+) CRC (P = 3 × 10−4). NRAS‐mutation(+) CRC preferentially occurred in elder patients (P = 0.02) and at the distal colon (P = 0.006), showed significantly less lymph vessel invasion (P = 0.002), and correlated with LME (P = 8 × 10−5). DNA methylation significantly accumulated at the proximal colon. NRAS‐mutation(+) CRC may constitute a different subgroup from KRAS‐mutation(+) CRC, showing significant correlation with LME, older age, distal colon, and relatively better prognosis.
AzaGly‐Appended Peptidomimetics Structurally Related to PTR6154 as Potential PKB/Akt Inhibitors
Authors: Singh Shalini , Shrivastava Richa , Singh Gajendra , Ali Rafat , Sankar Ampapathi Ravi , Bhadhuria Smrati , Haq Wahajul
Published: April 2017

We report the synthesis and biological and physiochemical properties of a series of azaGly‐appended peptidomimetics. We have developed a simple and facile synthesis for azapeptides on solid support without any side reaction. The azaGly is inserted by in situ reaction of disuccinimidyl carbonate with free amine followed by treatment of hydrazine hydrate at room temperature. The new series of peptidomimetics was prepared by azaGly scanning of heptapeptide Arg‐Pro‐Arg‐Nle‐Tyr‐Dap‐Nle (Akt‐01), a GSK‐3β‐derived Akt inhibitor. The azaGly‐appended peptides showed significant improvement in biological activity and serum stability, with retention of conformation as evidenced by NMR and CD studies. The results clearly demonstrate that azaGly‐appended peptides are new peptidomimetics. Their synthesis makes this approach highly useful for the development of novel peptidomimetics of therapeutic potential.
AG490 suppresses interleukin‐34‐mediated osteoclastogenesis in mice bone marrow macrophages
Authors: Cheng Xin , Wan Qi‐Long , Li Zu‐Bing
Published: April 2017

Interleukin‐34 (IL‐34) has been recently identified as a novel cytokine, substituting for the function of macrophage colony‐stimulating factor (M‐CSF), a pivotal osteoclastogenic factor involved in bone‐related diseases (e.g., osteomyelitis of the jaws). However, the molecular mechanisms are not fully understood. This study aimed to explore the potential mechanism of IL‐34 in receptor activator of NF‐kB ligand (RANKL)‐induced osteoclast formation. We found that IL‐34 alone significantly maintained the survival of bone marrow macrophages (BMMs) and enhanced the expression of the osteoclast‐related genes TRAP, Ctsk, and NFATc1, as well as TRAP‐positive multinucleated cells combined with RANKL, which can be reversed by AG490. Conversely, AG490 did not affect the M‐CSF‐mediated osteoclastogenesis in the presence of RANKL. The protein expression of p‐STAT3 in BMMs was enhanced by IL‐34 combined with RANKL compared with RANKL alone, and AG490 inhibited the expression of p‐SATA3 at protein level in the IL‐34 plus RANKL group, resulting in significantly increased Smad7 expression. This study demonstrated for the first time that IL‐34 may play a crucial role in RANKL‐induced osteoclastogenesis by promoting the proliferation and differentiation of BMMs, stimulating p‐STAT3 expression, and inhibiting the expression of Smad7 in the absence of M‐CSF.
Surfer's ear
Authors: Okuyama Yumi , Baba Akira , Ojiri Hiroya , Nakajima Tsuneya
Published: April 2017

Key Clinical Message

Exostosis in external auditory canal is common among surfers. Common symptoms are decreased hearing or loss of hearing, ear infection, and/or plugging sensation. Repeated exposure to cold water is a key clinical history to suspect this condition. Based on symptoms and existence of infection, surgical removal of the exostosis is recommended.
The Influence of Operation Temperature and Variations of the Illumination on the Performance of Integrated Photoelectrochemical Water‐Splitting Devices
Authors: Welter Katharina , Smirnov Vladimir , Becker Jan‐Philipp , Borowski Patrick , Hoch Sascha , Maljusch Artjom , Jaegermann Wolfram , Finger Friedhelm
Published: April 2017

Renewable and storable fuel hydrogen can be produced through light‐driven water splitting using photovoltaic‐biased electrosynthetic (PV‐EC) devices. The required voltage to drive the reaction is approximately 1.5 V, which can be provided using multi‐junction silicon solar cells. To generate these voltages at the operation point, the solar cells are electrically optimized with respect to the standard test conditions. However, if such devices were to be used outdoors, a wide range of different illumination conditions has to be considered. Herein, we discuss the dependence of the solar‐to‐hydrogen efficiency on the spectral quality, the incident illumination intensity and the operation temperature. It is found that in the case of high irradiation intensities (e. g. 1 sun), high operation temperatures reduce the PV performance, but the overall PV‐EC device performance remains almost unchanged due to improved kinetics in the EC part. In contrast, when the illumination intensity is reduced, the loss in PV performance cannot be compensated by improved EC performances due to higher temperatures.
Formation of Fe3O4 Nanoparticles Embedded in an Olive‐Shaped Carbon Skeleton as a High‐Performance Anode Material
Authors: Yao Xiufeng , Yang Zhanxu , Qi Chengyuan , Li Yue , Cai Tianfeng , Ren Tieqiang
Published: April 2017

Fe3O4 is a potential anode material for lithium‐ion batteries, because of its environmentally friendliness, high capacity, and inexpensive availability. However, Fe3O4 causes a severe capacity attenuation, owing to a large volume change, and it has a poor rate capability, owing to low conductivity. In this work, Fe3O4 nanoparticles embedded in an olive‐shaped carbon skeleton were prepared through the one‐step pyrolysis of metal‐organic framework (MOF) precursors in a nitrogen atmosphere. The Fe3O4 nanoparticles were evenly embedded in the olive‐shaped carbon skeleton and the Fe3O4 particle size was around 23 nm in width and 38 nm in length, which exhibits enhanced cycling and rate performance. The prepared Fe3O4/C material achieves a high initial charge and discharge capacity of 1423.0 mAhg−1 and 925.5 mAhg−1, respectively, and shows a remarkable cycle‐stable specific capacity of 877.0 mAhg−1 after 80 cycles at 0.5 C. High specific discharge capacities of 810, 720, 660, 585, 516, 486, and 460 mAhg−1 were obtained at 0.5, 1, 2, 6, 12, 15, and 20 C, respectively.
Anodic Chlorination of Selenophene‐Containing Polymers: Reaction Efficiency and Selective Reaction of Single Segment in Rod−Rod Diblockcopolymer
Authors: Shida Naoki , Okazaki Daichi , Kurioka Tomoyuki , Nishiyama Hiroki , Seferos Dwight S. , Tomita Ikuyoshi , Inagi Shinsuke
Published: April 2017

The post‐polymerization modification of selenophene‐containing (co)polymers is presented based on the electrochemical polymer reaction (ECPR). Selenophene‐ or thiophene‐containing (co)polymers, which are known to be promising materials in optoelectronic devices, were synthesized through Kumada catalyst transfer polymerization to give their homopolymers and block‐ or statistical copolymers with various side chains. Each of the series of polymers was subjected to post‐modification through the ECPR, and the reaction efficiencies were systematically compared. Selenophene‐containing polymers were successfully modified with better ECPR reaction efficiencies than their thiophene analogues. Moreover, the dramatic inhibiting effect of a branched side chain on the ECPR was observed and rationalized, which was very unexpected. Based on the basic tendency observed here, we have finally demonstrated the selective modification of a single segment of a rod−rod block copolymer for the first time.
An overview of large‐dimensional covariance and precision matrix estimators with applications in chemometrics
Authors: Engel Jasper , Buydens Lutgarde , Blanchet Lionel
Published: April 2017

The covariance matrix (or its inverse, the precision matrix) is central to many chemometric techniques. Traditional sample estimators perform poorly for high‐dimensional data such as metabolomics data. Because of this, many traditional inference techniques break down or produce unreliable results. In this paper, we selectively review several modern estimators of the covariance and precision matrix that improve upon the traditional sample estimator. We focus on 3 general techniques: eigenvalue‐shrinkage estimation, ridge‐type estimation, and structured estimation. These methods rely on different assumptions regarding the structure of the covariance or precision matrix. Various examples, in particular using metabolomics data, are used to compare these techniques and to demonstrate that in concert with, eg, principal component analysis, multivariate analysis of variance, and Gaussian graphical models, better results are obtained.
Improved Lithium‐Ion and Sodium‐Ion Storage Properties from Few‐Layered WS2 Nanosheets Embedded in a Mesoporous CMK‐3 Matrix
Authors: Pang Qiang , Gao Yu , Zhao Yingying , Ju Yanming , Qiu Hailong , Wei Yingjin , Liu Bingbing , Zou Bo , Du Fei , Chen Gang
Published: April 2017

An integrated WS2@CMK‐3 nanocomposite has been prepared by a one‐step hydrothermal method and then used as the anode material for lithium‐ion and sodium‐ion batteries. Ultrathin WS2 nanosheets have been successfully embedded into the ordered mesoporous carbon (CMK‐3) framework. Owing to the few‐layered nanostructure of WS2, as well as the high electronic conductivity and the volume confinement effect of CMK‐3, the material shows larger discharge capacity, better rate capability, and improved cycle stability than pristine WS2. When tested in lithium‐ion batteries, the material delivers a reversible capacity of 720 mA h g−1 after 100 cycles at a current density of 100 mA g−1. A large discharge capacity of 307 mA h g−1 is obtained at a current density of 2 A g−1. When used in sodium‐ion batteries, the material exhibits a capacity of 333 mA h g−1 at 100 mA g−1 without capacity fading after 70 cycles. A discharge capacity of 230 mA h g−1 is obtained at 2 A g−1. This excellent performance demonstrates that the WS2@CMK‐3 nanocomposite has great potential as a high‐performance anode material for next‐generation rechargeable batteries.
Solid‐State NMR Spectroscopy Proves the Presence of Penta‐coordinated Sc Sites in MIL‐100(Sc)
Authors: Giovine Raynald , Volkringer Christophe , Ashbrook Sharon E. , Trébosc Julien , McKay David , Loiseau Thierry , Amoureux Jean‐Paul , Lafon Olivier , Pourpoint Frédérique
Published: April 2017

Advanced solid‐state NMR methods and first‐principles calculations demonstrate for the first time the formation of penta‐coordinated scandium sites. These coordinatively unsaturated sites were shown during the thermal activation of scandium‐based metal‐organic frameworks (MOFs). A 45Sc NMR experiment allows their specific observation in activated Sc3BTB2 (H3BTB=1,3,5‐tris(4‐carboxyphenyl)benzene) and MIL‐100(Sc) MOFs. The assignment of the ScO5 groups is supported by the DFT calculations of NMR parameters. The presence of ScO5 Lewis acid sites in MIL‐100(Sc) explains furthermore its catalytic activity. The first NMR experiment to probe 13C−45Sc distances is also introduced. This advanced solid‐state NMR pulse sequence allows the demonstration of the shrinkage of the MIL‐100(Sc) network when the activation temperature is raised.
Assessing How Correlated Molecular Orbital Calculations Can Perform versus Kohn–Sham DFT: Barrier Heights/Isomerizations
Authors: Varandas António J. C. , Martínez González Marco , Montero‐Cabrera Luis A. , Garcia de la Vega José M.
Published: April 2017

To assess the title issue, 38 hydrogen transfer barrier heights and 38 non‐hydrogen transfer barrier heights/isomerizations extracted from extensive databases have been considered, in addition to 4 2 p‐isomerization reactions and 6 others for large organic molecules. All Kohn–Sham DFT calculations have employed the popular M06‐2X functional, whereas the correlated molecular orbital (MO)‐based ones are from single‐reference MP2 and CCSD(T) methods. They have all utilized the same basis sets, with raw MO energies subsequently extrapolated to the complete basis set limit without additional cost. MP2 calculations are found to be as cost‐effective as DFT ones and often slightly more, while showing a satisfactory accuracy when compared with the reference data. Although the focus is on barrier heights, the results may bear broader implications, in that one may see successes and difficulties of DFT when compared with traditional MO theories for the same data.
Supramolecular Hydrogels Based on Minimalist Amphiphilic Squaramide–Squaramates for Controlled Release of Zwitterionic Biomolecules
Authors: López Carlos , Ximenis Marta , Orvay Francisca , Rotger Carmen , Costa Antonio
Published: April 2017

Supramolecular hydrogels with tunable properties have innovative applications in biomedicine, catalysis, and materials chemistry. Minimalist low‐molecular‐weight hydrogelators based on squaramide and squaramic acid motifs have been designed. This approach benefits from the high acidity of squaramic acids and the aromaticity of squaramides. Moreover, substituents on the aryl ring tune the π density of the arylsquaramide motif. Thus, materials featuring distinct thermal and mechanical properties have been successfully prepared. The hydrogel (G′≈400 Pa, G′′≈57 Pa; at 1.0 % w/v; 1 Hz) obtained from 4‐nitrophenylsquaramide motif 1 is thermoreversible (T=57 °C at 0.2 % w/v), thixotropic, self‐healable, and undergoes irreversible shrinking in response to saline stress. Furthermore, the hydrogel is injectable and can be loaded with substantial amounts (5:1 excess molar ratio) of zwitterionic biomolecules, such as l‐carnitine, γ‐aminobutyric acid (GABA), or d,l‐Ala‐d,l‐Ala, without any loss of structural integrity. Then, the release of these molecules can be modulated by saline solutions.
Vertically‐Oriented and Shape‐Tailored Electrocatalytic Metal Nanowire Arrays for Enzyme‐Free Galactosemia Rapid Diagnosis
Authors: García‐Carmona Laura , González María Cristina , Escarpa Alberto
Published: April 2017

Metallic catalytic nanowires such as nickel and copper nanowires (NWs) for electrochemical detection of carbohydrates involved in metabolic rare diseases are proposed. NWs were electrodeposited using a polycarbonate membrane template, which was cut with the desired shape, stuck in double‐sided adhesive tape, pasted into a non‐conductive substrate and in situ removed. This simple and versatile approach allowed to obtain NWs vertically oriented (v‐NWs), which are contained in the double‐sided adhesive tape, becoming highly versatile. The high specific surface of working electrode in which the transduction is supported exclusively by the nanomaterial yielded a high analytical performance [extremely low fouling for galactose (RSD<2 %; n=25)]. Likewise, v‐NWs exhibited a superior analytical performance with respect to commercial sputtered thick‐film electrodes showing also a clear advantage related with the price, as well as with non‐need clean room facilities. The analytical potency of the new approach was clearly demonstrated towards the fast and reliable diagnosis of galactosemia using precious newborn urine samples compared to standard clinical diagnosis. These results revealed new opportunities for future enzyme‐free diagnosis and development of future point‐of‐care applications.
Total Synthesis of (−)‐Morphine
Authors: Umihara Hirotatsu , Yokoshima Satoshi , Inoue Masayuki , Fukuyama Tohru
Published: April 2017

Asymmetric total synthesis of (−)‐morphine has been accomplished in 18 steps from commercially available 7‐methoxy‐2‐tetralone. Our synthesis features a simple transformation from a readily prepared chiral intermediate, construction of the E‐ring by acid‐mediated cyclization, and singlet oxygen‐mediated manipulation of the C‐ring. Transformation of the final stage involves construction of the morphinan skeleton by means of 1,6‐addition of in situ generated secondary amine.
Thermal Energy Storage Integration Based on Pinch Analysis – Methodology and Application
Authors: Olsen Donald , Liem Peter , Abdelouadoud Yasmina , Wellig Beat
Published: April 2017

Reducing thermal energy use in industry is an effective way to improve energy efficiency. Process integration methods tackle this challenge, of which pinch analysis is a popular approach for identifying direct heat recovery measures. Many processes are batch processes that can profit from indirect heat recovery using thermal energy storage (TES). This paper presents a systematic conceptual TES integration methodology. In addition, functionality to support this methodology has been implemented in the PinCH software and is presented in a case study.
MOSAIC – Enabling Large‐Scale Equation‐Based Flow Sheet Optimization
Authors: Esche Erik , Hoffmann Christian , Illner Markus , Müller David , Fillinger Sandra , Tolksdorf Gregor , Bonart Henning , Wozny Günter , Repke Jens‐Uwe
Published: April 2017

Dedicated software exists for both process simulation and optimization. Given the advantages of simultaneous optimization schemes, engineers are frequently tasked with reimplementing their simulation models in optimization languages or environments. In this contribution, a workflow is introduced to model chemical engineering models in MathML and to have an automatic code generation for both specialized simulation and optimization tools. Two examples are given to highlight the performance of this workflow implemented in the modeling, simulation, and optimization environment MOSAIC.
Facile Synthesis of Mo2C Nanocrystals Embedded in Nanoporous Carbon Network for Efficient Hydrogen Evolution
Authors: Chen Yuyun , Zhang Yun , Ma Yuling , Tang Tang , Dai Zhihui , Hu Jinsong , Wan Lijun
Published: April 2017

Exploring facile and easily‐scalable methods for synthesizing earth‐abundant, cost‐effective and efficient hydrogen evolution reaction (HER) electrocatalysts is essential for the mass production of hydrogen as a clean and sustainable energy carrier. We report here a simple strategy to produce Mo2C nanocrystals embedded in carbon network (Mo2C@C) by the direct pyrolysis of ammonium molybdate and polyvinylpyrrolidone (PVP). It is found that PVP can be effectively used as a single source to form carbides and carbon network. The long polymer chain and coordinating capability with transition metal of PVP make it possible to form connected porous carbon network and well‐dispersed Mo2C nanocrystals in several nanometers. The carbonization of PVP not only effectively in‐situ prevents the aggregation of Mo2C nanocrystals during their formation, but also provides conductive porous matrix. As a result, the Mo2C@C composite exhibits the superior electrocatalytic performance for HER, which can be ascribed to the large number of active sites from plenty of small Mo2C nanocrystals and the efficient mass and electron transport network from carbon matrix. This strategy may inspire the exploration of cost‐effective functional polymer as single source for both carbon precursor and nanostructure‐directed reagent to mass‐produce well‐defined metal carbides nanostructures embedded in porous carbon network for energy applications.
Depth‐weighted robust multivariate regression with application to sparse data
Authors: Dutta Subhajit , Genton Marc G.
Published: April 2017

A robust method for multivariate regression is developed based on robust estimators of the joint location and scatter matrix of the explanatory and response variables using the notion of data depth. The multivariate regression estimator possesses desirable affine equivariance properties, achieves the best breakdown point of any affine equivariant estimator, and has an influence function which is bounded in both the response as well as the predictor variable. To increase the efficiency of this estimator, a re‐weighted estimator based on robust Mahalanobis distances of the residual vectors is proposed. In practice, the method is more stable than existing methods that are constructed using subsamples of the data. The resulting multivariate regression technique is computationally feasible, and turns out to perform better than several popular robust multivariate regression methods when applied to various simulated data as well as a real benchmark data set. When the data dimension is quite high compared to the sample size it is still possible to use meaningful notions of data depth along with the corresponding depth values to construct a robust estimator in a sparse setting. The Canadian Journal of Statistics 45: 164–184; 2017 © 2017 Statistical Society of Canada
Tumor suppressor tropomyosin Tpm2.1 regulates sensitivity to apoptosis beyond anoikis characterized by changes in the levels of intrinsic apoptosis proteins
Authors: Desouza‐Armstrong Melissa , Gunning Peter W. , Stehn Justine R.
Published: April 2017

The actin cytoskeleton is a polymer system that acts both as a sensor and mediator of apoptosis. Tropomyosins (Tpm) are a family of actin binding proteins that form co‐polymers with actin and diversify actin filament function. Previous studies have shown that elevated expression of the tropomyosin isoform Tpm2.1 sensitized cells to apoptosis induced by cell detachment (anoikis) via an unknown mechanism. It is not yet known whether Tpm2.1 or other tropomyosin isoforms regulate sensitivity to apoptosis beyond anoikis. In this study, rat neuroepithelial cells overexpressing specific tropomyosin isoforms (Tpm1.7, Tpm2.1, Tpm3.1, and Tpm4.2) were screened for sensitivity to different classes of apoptotic stimuli, including both cytoskeletal and non‐cytoskeletal targeting compounds. Results showed that elevated expression of tropomyosins in general inhibited apoptosis sensitivity to different stimuli. However, Tpm2.1 overexpression consistently enhanced sensitivity to anoikis as well as apoptosis induced by the actin targeting drug jasplakinolide (JASP). In contrast the cancer‐associated isoform Tpm3.1 inhibited the induction of apoptosis by a range of agents. Treatment of Tpm2.1 overexpressing cells with JASP was accompanied by enhanced sensitivity to mitochondrial depolarization, a hallmark of intrinsic apoptosis. Moreover, Tpm2.1 overexpressing cells showed elevated levels of the apoptosis proteins Bak (proapoptotic), Mcl‐1 (prosurvival), Bcl‐2 (prosurvival) and phosphorylated p53 (Ser392). Finally, JASP treatment of Tpm2.1 cells caused significantly reduced Mcl‐1, Bcl‐2 and p53 (Ser392) levels relative to control cells. We therefore propose that Tpm2.1 regulates sensitivity to apoptosis beyond the scope of anoikis by modulating the expression of key intrinsic apoptosis proteins which primes the cell for death.
Serum 25‐hydroxyvitamin D, vitamin D binding protein, and prostate cancer risk in black men
Authors: Layne Tracy M. , Weinstein Stephanie J. , Graubard Barry I. , Ma Xiaomei , Mayne Susan T. , Albanes Demetrius
Published: April 2017

BACKGROUND

Few studies have prospectively examined the relationship between vitamin D status and prostate cancer risk in black men, a group at high risk for both low vitamin D status and prostate cancer.

METHODS

Among black men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we identified 226 prostate cancer cases and 452 controls matched on age at randomization (±5 years), date of blood draw (±30 days), calendar year of cohort entry, and time since baseline prostate cancer screening (±1 year). Conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between serum 25‐hydroxyvitamin D [25(OH)D], vitamin D binding protein (DBP), the 25(OH)D:DBP molar ratio, and prostate cancer risk.

RESULTS

Serum 25(OH)D was not associated with overall prostate cancer (Q4 vs Q1: OR, 0.73; 95% CI, 0.40‐1.33; P for trend = .25), although there were apparent inverse associations for nonaggressive disease (global P = .03, clinical stage I/II, and Gleason score <7) and among men ≥62 years old (P for interaction = .04) that were restricted to Q3. Interestingly, serum DBP was significantly inversely associated with prostate cancer risk (Q4 vs Q1: OR, 0.45; 95% CI, 0.20‐1.00; P for trend = .03), whereas the 25(OH)D:DBP molar ratio was not. Results were similar when we mutually adjusted for 25(OH)D and DBP, and we found no evidence of interaction between the two.

CONCLUSION

Our study suggests higher (versus lower) circulating DBP may be independently associated with a decreased prostate cancer risk in black men independent of 25(OH)D status. Cancer 2017;123:2698‐704. © 2017 American Cancer Society.
Alternative lengthening of telomeres and ATRX/DAXX loss can be reliably detected in FNAs of pancreatic neuroendocrine tumors
Authors: VandenBussche Christopher J. , Allison Derek B. , Graham Mindy K. , Charu Vivek , Lennon Anne Marie , Wolfgang Christopher L. , Hruban Ralph H. , Heaphy Christopher M.
Published: April 2017

BACKGROUND

Pancreatic neuroendocrine tumors (PanNETs) frequently use the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT is strongly correlated with α thalassemia‐mental retardation, X linked (ATRX), and death domain‐associated protein 6 (DAXX) alterations and a poor prognosis in patients with primary PanNET. Because fine‐needle aspiration (FNA) is a noninvasive way to sample tumors, the authors evaluated whether they could accurately detect ALT and loss of ATRX/DAXX in a primary PanNET cohort of FNAs.

METHODS

All preoperative FNA cytology cases (2005‐2016) with adequate remnant FNA cell block material were assessed for ALT by telomere‐specific fluorescence in situ hybridization and for ATRX and DAXX protein expression by immunohistochemistry. For 21 patients who underwent tumor resection, the resected specimen also was assessed to determine the concordance between the FNA and surgical specimens.

RESULTS

In the primary PanNET cohort of 65 FNAs, ALT was detected in 15 specimens (23%). Although all ATRX‐negative and DAXX‐negative tumors were ALT‐positive, 3 of 14 (21%) ALT‐positive tumors did not exhibit nuclear loss of either ATRX or DAXX. The ALT‐positive tumors were associated with larger radiographic size (4.9 vs 2.4 cm, on average; P < .05) and higher grade (P < .05). Overall, there was 100% concordance in ALT status and ATRX/DAXX immunohistochemistry results between the FNA and surgical specimens.

CONCLUSIONS

Both ALT and loss of ATRX/DAXX can be accurately performed on FNA specimens with adequate material. Because ALT is a fundamental mechanism of pathogenesis, the ability to determine ALT in small biospecimens has implications for the design of clinical trials. Cancer Cytopathol 2017;125:544–51. © 2017 American Cancer Society.
Performance of CuII‐, PbII‐, and HgII‐Exchanged Mordenite in the Adsorption of I2, ICH3, H2O, CO, ClCH3, and Cl2: A Density Functional Study
Authors: Chibani Siwar , Medlej Israa , Lebègue Sébastien , Ángyán János G. , Cantrel Laurent , Badawi Michael
Published: April 2017

Periodic dispersion‐corrected DFT is used to investigate the adsorption of I2 and ICH3, which may be released during a severe nuclear accident, for three divalent cation (Cu2+, Pb2+ and Hg2+)‐exchanged mordenites with an Si/Al ratio of 23. Gases such as H2O, CO, ClCH3, and Cl2 present in the containment atmosphere can inhibit the selective adsorption of iodine species. To identify the most promising adsorbents, a systematic study is performed in which all the possible cationic sites in the main channel of the mordenite structure are considered. For the energetically most stable sites, the divalent cation is located in the small rings (five‐ or six‐membered) containing two Al atoms, while in the energetically less stable configurations, the two Al atoms are far apart (>7 Å) and the cation is close to only one Al atom. Upon adsorption of the various molecules, the coordination number of the cation decreases with increasing interaction energy, as the molecules can attract the divalent cations from the framework. Finally, the computed interaction energies show that Hg‐mordenite (MOR) could be a suitable material for selective adsorption of volatile iodine species, contrary to Cu‐MOR and Pb‐MOR.
Characterization and Functional Analysis of Mouse Semi‐invariant Natural T Cells
Authors: Kumar Amrendra , Bezbradica Jelena S. , Stanic Aleksandar K. , Joyce Sebastian
Published: April 2017

Semi‐invariant natural killer T (iNKT) cells are CD1d‐restricted innate‐like lymphocytes that recognize lipid agonists. Activated iNKT cells have immunoregulatory properties. Human and mouse iNKT cell functions elicited by different glycolipid agonists are highly conserved, making the mouse an excellent animal model for understanding iNKT cell biology in vivo. This unit describes basic methods for the characterization and quantification (see Basic Protocol 1) and functional analysis of mouse iNKT cells in vivo or in vitro. This unit also contains protocols that describe enrichment and purification of iNKT cells, generation of CD1d tetramer, and lipid antigen loading onto cell‐bound and soluble CD1d for activation of NKT cell hybridomas. © 2017 by John Wiley & Sons, Inc.
Basic Multicolor Flow Cytometry
Authors: Maciorowski Zofia , Chattopadhyay Pratip K. , Jain Paresh
Published: April 2017

Multicolor flow cytometry is a rapidly evolving technology that uses multiple fluorescent markers to identify and characterize cellular subpopulations of interest, allowing rapid analysis on tens of thousands of cells per second, with the possibility of isolating pure, viable populations by cell sorting for further experimentation. This unit covers the tools needed by the beginning immunologist to plan and run multicolor experiments, with information on fluorochromes and their characteristics, spectral spillover, compensation and spread, instrument and reagent variables, and the basic elements of multicolor panel design. Protocols to quantify and maximize sensitivity by titration of reagents and optimization of instrument settings, as well as basic surface and intracellular cell staining, are included. © 2017 by John Wiley & Sons, Inc.
Self‐Assembly of Manganese(II)–Phytate Coordination Polymers: Synthesis, Crystal Structure, and Physicochemical Properties
Authors: Quiñone Delfina , Veiga Nicolás , Torres Julia , Bazzicalupi Carla , Bianchi Antonio , Kremer Carlos
Published: April 2017

myo‐Inositol phosphates are an important group of biomolecules that are present in all eukaryotic cells. The most abundant member of this family in nature is InsP6(phytate, L12−in its fully deprotonated form). Phytate interacts strongly with inorganic and organic cations, and this interaction is essential for determining the possible functions of this biomolecule. Herein, the chemical, thermodynamic, and structural characterization of phytate–MnIIspecies is presented in a study aimed at understanding how the interaction of the two components modulates their biological roles and their bioavailability. Polynuclear complexes Mn5(H2L)⋅16 H2O (1) and (H2terpy)2[Mn(H6L)(terpy)(H2O)]⋅17 H2O (terpy=terpyridine) (2) were prepared and characterized by different techniques. The isolation of1and the determination of its solubility, together with potentiometric titrations of the MnII–phytate system, allow the full description of this binary system. The preparation and crystal structure of2show a novel coordination mode of phytate, that is, the formation of infinite polymeric chains through equatorial phosphate groups.
Self‐Assembled Liquid‐Crystalline Ion Conductors in Dye‐Sensitized Solar Cells: Effects of Molecular Sensitizers on Their Performance
Authors: Högberg Daniel , Soberats Bartolome , Yoshio Masafumi , Mizumura Yurika , Uchida Satoshi , Kloo Lars , Segawa Hiroshi , Kato Takashi
Published: April 2017

Dye‐sensitized solar cells employing nonvolatile liquid‐crystalline (LC) electrolytes that form nanostructures capable of efficient ion transport are reported. The LC electrolyte consists of a cyclic carbonate‐functionalized mesogen and an iodide‐based ionic liquid that nanosegregates into lamellar structures exhibiting over four times higher ion conductivities parallel to the layers than perpendicular to the layers. The self‐assembled ion pathways allow efficient ion transport in the semi‐solid LC state. When used together with organic dyes, DSSCs employing these LC electrolytes show higher power conversion efficiency (PCE) than metal–organic dyes. This behavior is not observed for devices containing standard liquid electrolytes. The higher PCEs of the LC‐based devices can be attributed to longer electron lifetimes (τ) and higher electron densities in the photoelectrodes. The high concentration of iodide ions in the nanostructured pathways of the LC electrolyte is thought to induce reductive quenching of the ruthenium‐based sensitizer, which competes with the electron injection process and lowers the τ and electron densities of the TiO2.
Transcriptome‐wide Identification of RNA‐binding Protein Binding Sites Using Photoactivatable‐Ribonucleoside‐Enhanced Crosslinking Immunoprecipitation (PAR‐CLIP)
Authors: Maatz Henrike , Kolinski Marcin , Hubner Norbert , Landthaler Markus
Published: April 2017

RNA‐binding proteins (RBPs) mediate important co‐ and post‐transcriptional gene regulation by binding pre‐mRNA in a sequence‐ and/or structure‐specific manner. For a comprehensive understanding of RBP function, transcriptome‐wide mapping of the RNA‐binding sites is essential, and CLIP‐seq methods have been developed to elucidate protein/RNA interactions at high resolution. CLIP‐seq combines protein/RNA UV‐crosslinking with immunoprecipitation (CLIP) followed by high‐throughput sequencing of crosslinked RNA fragments. To overcome the limitations of low RNA‐protein crosslinking efficiency in standard CLIP‐seq, photoactivatable‐ribonucleoside‐enhanced CLIP (PAR‐CLIP) has been developed. Here, living cells or whole organisms are fed photo‐activatable nucleoside analogs that are incorporated into nascent RNA transcripts before UV treatment. This allows greater crosslinking efficiency at comparable radiation doses for enhanced RNA recovery and separation of crosslinked target RNA fragments from background RNA degradation products. Moreover, it facilitates the generation of specific UV‐induced mutations that mark the crosslinking nucleotide and allow transcriptome‐wide identification of RBP binding sites at single‐nucleotide resolution. © by 2017 John Wiley & Sons, Inc.
Preparing Viable Single Cells from Human Tissue and Tumors for Cytomic Analysis
Authors: Leelatian Nalin , Doxie Deon B. , Greenplate Allison R. , Sinnaeve Justine , Ihrie Rebecca A. , Irish Jonathan M.
Published: April 2017

Mass cytometry is a single‐cell biology technique that samples >500 cells per second, measures >35 features per cell, and is sensitive across a dynamic range of >104 relative intensity units per feature. This combination of technical assets has powered a series of recent cytomic studies where investigators used mass cytometry to measure protein and phospho‐protein expression in millions of cells, characterize rare cell types in healthy and diseased tissues, and reveal novel, unexpected cells. However, these advances largely occurred in studies of blood, lymphoid tissues, and bone marrow, since the cells in these tissues are readily obtained in single‐cell suspensions. This unit establishes a primer for single‐cell analysis of solid tumors and tissues, and has been tested with mass cytometry. The cells obtained from these protocols can be fixed for study, cryopreserved for long‐term storage, or perturbed ex vivo to dissect responses to stimuli and inhibitors. © 2017 by John Wiley & Sons, Inc.
Pharmacokinetics and Pharmacodynamics of Intravenous Immunoglobulin G Maintenance Therapy in Chronic Immune‐mediated Neuropathies
Authors: Fokkink WJR , Koch BCP , Ramakers CRB , van Doorn PA , van Gelder T , Jacobs BC
Published: April 2017

The regimen for IVIg maintenance treatment varies considerably between patients with chronic immune‐mediated neuropathies. Although it is widely recognized that treatment regimens should be improved, detailed pharmacokinetics (PK) of IVIg have not yet been established. We aimed to determine the PK of IVIg maintenance treatment in patients with clinically stable, treatment‐dependent, chronic immune‐mediated neuropathy. Patients received a median IVIg dose of 30 g (range, 15–70 g) every 14 days (range, 7–28 days) resulting in high IgG peak levels (median, 25.9 g/L; range, 16.7–41.0 g/L) and trough levels (median, 16.1 g/L; range, 9.7–23.6 g/L). IgG PK parameters, including half‐life (median, 23.1 days; range, 11–60 days), were constant during subsequent courses in the same patients, but varied considerably between patients. The IgG levels at 1 week after infusion correlated with grip strength. These results provide insight into the PK of IVIg maintenance treatment in patients with chronic immune‐mediated neuropathies.
On‐pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens
Authors: Cavalca V , Rocca B , Veglia F , Petrucci G , Porro B , Myasoedova V , De Cristofaro R , Turnu L , Bonomi A , Songia P , Cavallotti L , Zanobini M , Camera M , Alamanni F , Parolari A , Patrono C , Tremoli E
Published: April 2017

On‐pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase‐1 renewal, thereby modifying low‐dose aspirin pharmacodynamics. Thirty‐seven patients on standard aspirin 100 mg once‐daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once‐daily, 100 mg twice‐daily, or 200 mg once‐daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C‐reactive protein, and interleukin‐6 significantly increased. Interleukin‐6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once‐daily showed a significant increase in serum thromboxane (TX)B2 within the 24‐hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100 mg twice‐daily lowered serum TXB2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once‐daily dose, rescues the impaired antiplatelet effect of low‐dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.
Synthesis of erythrocyte like MnCo2O4 as anode for high performance lithium ion batteries
Authors: Li Guihua , Zhai Qinghe , Liu Qian , Jin Rencheng
Published: April 2017

Erythrocyte like MnCo2O4 has been synthesized using a facile solvothermal method and sintering treatment. The obtained sample is constructed by many smaller nanocrystals and possesses high surface area, which can efficiently increase the contact area for electrode/electrolyte, shorten the pathway for Li+ diffusion and buffer the volume variation during electrochemical cycling. Electrochemical investigations demonstrate that the erythrocyte like MnCo2O4 exhibits good electrochemical performance. A specific capacity of 960 mAh g−1 can be achieved after 100 cycles at the current density of 200 mA g−1.
Zeolites as sustainable catalysts for the selective synthesis of renewable bisphenols from lignin‐derived monomers
Authors: Ferrini Paola , Koelewijn Steven‐Friso , Van Aelst Joost , Nuttens Nicolas , Sels Bert F.
Published: April 2017

Alternative biobased bisphenols from lignocellulosic biomass are not only favorable to reduce the environmental impact of current petroleum‐derived plastics, but they can be simultaneously beneficial for health issues related to bisphenol A (BPA). Additionally, conventional BPA synthesis entails a large excess of unrecoverable homogeneous acid catalyst (e.g., HCl) or unrecyclable thermolabile sulfonated resins. In this report, zeolites are proposed as recoverable and thermally stable solid acids for the Brønsted‐acid‐catalyzed condensation between 4‐methylguaiacol and formaldehyde to selectively produce renewable bisphenols. It is found that the Brønsted‐acid‐site density plays a pivotal role for catalyst performance. In particular, the cheap and environmentally friendly FAU 40 exhibits outstanding activity (turnover frequency of 496 h−1) and selectivity (>95 %), outperforming even the best benchmark catalyst. Additionally, the zeolite can be easily recycled without activity loss after regeneration by coke burn‐off. The catalytic zeolite system also seems very promising for other lignin‐derived alkylphenols, alkylguaiacols, and alkylsyringols.
Metal‐Free Synthesis of N‐Aryl Amides using Organocatalytic Ring‐Opening Aminolysis of Lactones
Authors: Guo Wusheng , Gómez José Enrique , Martínez‐Rodríguez Luis , Bandeira Nuno A. G. , Bo Carles , Kleij Arjan W.
Published: April 2017

Catalytic ring‐opening of bio‐sourced non‐strained lactones with aromatic amines can offer a straightforward, 100 % atom‐economical, and sustainable pathway towards relevant N‐aryl amide scaffolds. Herein, the first general, metal‐free, and highly efficient N‐aryl amide formation is reported from poorly reactive aromatic amines and non‐strained lactones under mild operating conditions using an organic bicyclic guanidine catalyst. This protocol has high application potential as exemplified by the formal syntheses of drug‐relevant molecules.
Glycidol, a Valuable Substrate for the Synthesis of Monoalkyl Glyceryl Ethers: A Simplified Life Cycle Approach
Authors: Ricciardi Maria , Passarini Fabrizio , Vassura Ivano , Proto Antonio , Capacchione Carmine , Cucciniello Raffaele , Cespi Daniele
Published: April 2017

The disposal of any waste by recovering it within the production plant represents the ultimate goal of every biorefinery. In this scenario, the selective preparation of monoalkyl glyceryl ethers (MAGEs) starting from glycidol, obtained as byproduct in the epichlorohydrin production plant, represents a very promising strategy. Here, we report the synthesis of MAGEs through the reaction of glycidol with alcohols catalyzed by a green homogeneous Lewis acids catalyst, such as BiIII triflate, under very mild reaction conditions. To evaluate the green potential of the proposed alternative, a simplified life cycle assessment (LCA) approach was followed by comparing the environmental performance of the proposed innovative route to prepare MAGEs with that of the most investigated pathway from glycerol. A considerable reduction of all impact categories considered was observed in our experimental conditions, suggesting that the glycidol‐to‐MAGEs route can be a valuable integration to the glycerol‐to‐MAGEs chain. Thanks to the use of primary data within the LCA model, the results achieved are a very good approximation of the real case.
Threshold voltage extraction techniques adaptable from sub‐micron CMOS to large‐area oxide TFT technologies
Authors: Samanta Smrutilekha , Tiwari Bhawna , Bahubalindruni Pydi Ganga , Barquinha Pedro , Goes Joao
Published: April 2017

This paper proposed simple and accurate threshold voltage (VTH) extraction techniques, which can be directly adaptable to various semiconductor technologies ranging from deep sub‐micron complementary metal–oxide–semiconductor to large‐area thin‐film transistor devices. These techniques are developed using multiple circuits, namely, a dynamic source follower, an inverter with a diode‐connected load and a current mirror topology, which allow a direct determination of VTH. As the proposed techniques are experimented with large‐area emerging technologies, which have a stable single type (n‐type) transistor, all the designs employed in this work are confined to only n‐type transistors for a fair comparison. The semiconductor technologies under consideration are standard complementary metal–oxide–semiconductor (65 and 130 nm) and oxide (indium–gallium–zinc–oxide and zinc–tin–oxide) thin‐film transistors. In order to validate the accuracy of the proposed techniques, extracted VTH from these methods are compared against the value from linear transfer characteristics. The resulting relative error is within 5%, reinforcing proposed techniques suitability to different semiconductor technologies ranging from deep sub‐micron to large‐area transistors. Copyright © 2017 John Wiley & Sons, Ltd.
Fine social aspiration: Twitter as a voice for cytopathology
Authors: Lepe M. , Gardner J. M.
Published: April 2017

Social media is an influential tool that has the power to transform cytopathology. Twitter is being used more and more to share cutting‐edge updates from pathology meetings (“live‐tweeting”). Modern smartphones can now take high resolution microscopic photographs and easily transmit them worldwide via Twitter, Facebook, and other social media, allowing cytopathologists to share educational pearls and discuss difficult cases on a global scale like never before. Social media also allows cytopathologists to share a behind‐the‐scenes look at their subspecialty with other physicians and even the non‐medical public, helping them to better understand the crucial importance of cytopathology in modern medicine. This could positively impact rapport with other specialties, influence policy making, and possibly even improve delivery of patient care. Rare disease patient communities are being formed by patients on Facebook. By joining and volunteering with these patient groups, cytopathologists would have further opportunity to interact directly with patients and their family members, explaining the role of cytopathology in patient care and helping patients to better understand their own diseases. Social media enables cytopathologists and their colleagues in other pathology subspecialties to easily and rapidly form a broad and diverse worldwide network with one another. The authors believe that this is the key to a bright future for our specialty, a strong unified global community of pathologists all working together for education, patient advocacy, and outstanding patient care. Social media can allow us to build that community, strengthen its bonds, and harness its power like never before in history. Diagn. Cytopathol. 2017;45:705–713. © 2017 Wiley Periodicals, Inc.