bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Whole‐Exome Sequencing Revealing Somatic NLRP3 Mosaicism in a Patient With Chronic Infantile Neurologic, Cutaneous, Articular Syndrome
Authors: Omoyinmi Ebun , Melo Gomes Sónia , Standing Ariane , Rowczenio Dorota M. , Eleftheriou Despina , Klein Nigel , Aróstegui Juan I. , Lachmann Helen J. , Hawkins Philip N. , Brogan Paul A.
Published: December 2013

Objective

To identify the genetic cause of chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) using whole‐exome sequencing in a child who had typical clinical features but who was NLRP3 mutation negative based on conventional Sanger sequencing.

Methods

We performed whole‐exome sequencing on DNA from peripheral blood, using Illumina TruSeq Exome capture and the HiSeq sequencing platform. Exome data were analyzed in the Galaxy Web‐based suite. Whole‐exome sequencing findings were confirmed by massively parallel sequencing.

Results

Analysis of variants in known autoinflammatory genes led to the identification of the pathogenic p.F556L NLRP3 missense mutation in 17.7% of Illumina reads (25 of 141). No new candidate genes were identified. Massively parallel sequencing of DNA from peripheral blood (performed in duplicate) unequivocally confirmed the presence of this mutation in 14.5% of alleles. Reexamination of the original Sanger chromatograms revealed a small peak at nucleotide position c.1698 corresponding to the mutated allele. This had initially been regarded as background noise, but in retrospect is completely consistent with somatic mosaicism for the p.F556L NLRP3 mutation in this child with CINCA syndrome.

Conclusion

This is the first description of somatic NLRP3 mosaicism detected using whole‐exome sequencing in a “mutation‐negative” patient with CINCA syndrome. Our findings suggest that whole‐exome sequencing could be an important diagnostic tool for detecting somatic mosaicism, as well as for the discovery of novel causative gene mutations, in patients with clinical features of cryopyrin‐associated periodic syndromes who are NLRP3 mutation negative by conventional sequencing. This approach could also be applicable to patients with other autosomal‐dominant autoinflammatory diseases characterized by gain‐of‐function mutations who are mutation negative by conventional Sanger sequencing.
Combination of Tumor Necrosis Factor α and Interleukin‐6 Induces Mouse Osteoclast‐like Cells With Bone Resorption Activity Both In Vitro and In Vivo
Authors: Yokota Kazuhiro , Sato Kojiro , Miyazaki Takashi , Kitaura Hideki , Kayama Hisako , Miyoshi Fumihiko , Araki Yasuto , Akiyama Yuji , Takeda Kiyoshi , Mimura Toshihide
Published: December 2013

Objective

To clarify the function of osteoclast‐like multinuclear cells differentiated from bone marrow–derived macrophages (BMMs) by a combination of tumor necrosis factor α (TNFα) and interleukin‐6 (IL‐6), and to investigate the molecular mechanisms underlying the differentiation.

Methods

BMMs were stimulated by TNFα and/or IL‐6. The cells were then compared with conventional osteoclasts differentiated in vitro by RANKL. An in vitro pit formation assay on dentine slices and an in vivo resorption assay of calvarial bones were performed. We also evaluated the activities and expression levels of NF‐κB, c‐Fos, and NF‐ATc1, which are essential to the differentiation of conventional osteoclasts. Small interfering RNA was used to knock down c‐Fos. The effects of genetic ablation of STAT‐3 and pharmacologic inhibitors of NF‐AT, JAK, and ERK were also studied.

Results

Osteoclast‐like cell differentiation depended on TNFα and IL‐6 and was not inhibited by osteoprotegerin. These differentiated cells were associated with both in vitro and in vivo bone resorption activity. TNFα and IL‐6 had a synergistic effect on the activity and expression of c‐Fos. Knockdown of c‐Fos inhibited the expression of NF‐ATc1 and the differentiation of osteoclast‐like cells. All of these inhibitors blocked differentiation of the cells in vitro, but surprisingly, the conditional knockout of STAT‐3 did not. Tofacitinib also inhibited the bone destruction caused by TNFα and IL‐6 in vivo.

Conclusion

Our results demonstrate that a combination of the inflammatory cytokines TNFα and IL‐6 can induce osteoclast‐like cells that have in vitro and in vivo bone‐resorptive activity.
The importance of pyroglutamate in cellulase Cel7A
Authors: Dana Craig M. , Dotson‐Fagerstrom Alexandra , Roche Christine M. , Kal Sarala M. , Chokhawala Harshal A. , Blanch Harvey W. , Clark Douglas S.
Published: December 2013

The commercialization of lignocellulosic biofuels relies in part on the ability to engineer cellulase enzymes to have properties compatible with practical processing conditions. The cellulase Cel7A has been a common engineering target because it is present in very high concentrations in commercial cellulase cocktails. Significant effort has thus been focused on its recombinant expression. In particular, the yeast Saccharomyces cerevisiae has often been used both in the engineering and basic study of Cel7A. However, the expression titer and extent of glycosylation of Cel7A expressed in S. cerevisiae vary widely for Cel7A genes from different organisms, and the recombinant enzymes tend to be less active and less stable than their native counterparts. These observations motivate further study of recombinant expression of Cel7A in S. cerevisiae. Here, we compare the properties of Cel7A from Talaromyces emersonii expressed in both the budding yeast S. cerevisiae and the filamentous fungus Neurospora crassa. The Cel7A expressed in N. crassa had a higher melting temperature (by 10°C) and higher specific activity (twofold at 65°C) than the Cel7A expressed in S. cerevisiae. We examined several post‐translational modifications and found that the underlying cause of this disparity was the lack of N‐terminal glutamine cyclization in the Cel7A expressed in S. cerevisiae. Treating the enzyme in vitro with glutaminyl cyclase improved the properties of Cel7A expressed in S. cerevisiae to match those of Cel7A expressed in N. crassa. Biotechnol. Bioeng. 2014;111: 842–847. © 2013 Wiley Periodicals, Inc.
Promoting extracellular matrix remodeling via ascorbic acid enhances the survival of primary ovarian follicles encapsulated in alginate hydrogels
Authors: Tagler David , Makanji Yogeshwar , Tu Tao , Bernabé Beatriz Peñalver , Lee Raymond , Zhu Jie , Kniazeva Ekaterina , Hornick Jessica E. , Woodruff Teresa K. , Shea Lonnie D.
Published: December 2013

The in vitro growth of ovarian follicles is an emerging technology for fertility preservation. Various strategies support the culture of secondary and multilayer follicles from various species including mice, non‐human primate, and human; however, the culture of early stage (primary and primordial) follicles, which are more abundant in the ovary and survive cryopreservation, has been limited. Hydrogel‐encapsulating follicle culture systems that employed feeder cells, such as mouse embryonic fibroblasts (MEFs), stimulated the growth of primary follicles (70–80 µm); yet, survival was low and smaller follicles (<70 µm) rapidly lost structure and degenerated. These morphologic changes were associated with a breakdown of the follicular basement membrane; hence, this study investigated ascorbic acid based on its role in extracellular matrix (ECM) deposition/remodeling for other applications. The selection of ascorbic acid was further supported by a microarray analysis that suggested a decrease in mRNA levels of enzymes within the ascorbate pathway between primordial, primary, and secondary follicles. The supplementation of ascorbic acid (50 µg/mL) significantly enhanced the survival of primary follicles (<80 µm) cultured in alginate hydrogels, which coincided with improved structural integrity. Follicles developed antral cavities and increased to diameters exceeding 250 µm. Consistent with improved structural integrity, the gene/protein expression of ECM and cell adhesion molecules was significantly changed. This research supports the notion that modifying the culture environment (medium components) can substantially enhance the survival and growth of early stage follicles. Biotechnol. Bioeng. 2014;111: 1417–1429. © 2013 Wiley Periodicals, Inc.
Simultaneous uptake of lignocellulose‐based monosaccharides by Escherichia coli
Authors: Jarmander Johan , Hallström Björn M. , Larsson Gen
Published: December 2013

Lignocellulosic waste is a naturally abundant biomass and is therefore an attractive material to use in second generation biorefineries. Microbial growth on the monosaccharides present in hydrolyzed lignocellulose is however associated with several obstacles whereof one is the lack of simultaneous uptake of the sugars. We have studied the aerobic growth of Escherichia coli on D‐glucose, D‐xylose, and L‐arabinose and for simultaneous uptake to occur, both the carbon catabolite repression mechanism (CCR) and the AraC repression of xylose uptake and metabolism had to be removed. The strain AF1000 is a MC4100 derivative that is only able to assimilate arabinose after a considerable lag phase, which is unsuitable for commercial production. This strain was successfully adapted to growth on L‐arabinose and this led to simultaneous uptake of arabinose and xylose in a diauxic growth mode following glucose consumption. In this strain, a deletion in the phosphoenolpyruvate:phosphotransferase system (PTS) for glucose uptake, the ptsG mutation, was introduced. The resulting strain, PPA652ara simultaneously consumed all three monosaccharides at a maximum specific growth rate of 0.59 h−1, 55% higher than for the ptsG mutant alone. Also, no residual sugar was present in the cultivation medium. The potential of PPA652ara is further acknowledged by the performance of AF1000 during fed‐batch processing on a mixture of D‐glucose, D‐xylose, and L‐arabinose. The conclusion is that without the removal of both layers of carbon uptake control, this process results in accumulation of pentoses and leads to a reduction of the specific growth rate by 30%. Biotechnol. Bioeng. 2014;111: 1108–1115. © 2014 Wiley Periodicals, Inc.
Multi‐analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection
Authors: Huckans Marilyn , Fuller Bret E. , Olavarria Hannah , Sasaki Anna W. , Chang Michael , Flora Kenneth D. , Kolessar Michael , Kriz Daniel , Anderson Jeanne R. , Vandenbark Arthur A. , Loftis Jennifer M.
Published: December 2013

Background

The purpose of this study was to characterize hepatitis C virus (HCV)‐associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV‐associated neuropsychiatric symptoms—depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV.

Methods

Blood samples and neuropsychiatric symptom severity scales were collected from HCV‐infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV−, n = 40). Multi‐analyte profile analysis was used to evaluate plasma biomarkers.

Results

Compared with HCV− controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV− group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4–10 plasma immune factors; protein signatures significantly accounted for 19–40% of the variance in depression, anxiety, fatigue, and pain.

Conclusions

Overall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in adults with or without HCV.
White matter integrity is associated with alcohol cue reactivity in heavy drinkers
Authors: Monnig Mollie A. , Thayer Rachel E. , Caprihan Arvind , Claus Eric D. , Yeo Ronald A. , Calhoun Vince D. , Hutchison Kent E.
Published: December 2013

Neuroimaging studies have shown that white matter damage accompanies excessive alcohol use, but the functional correlates of alcohol‐related white matter disruption remain unknown. This study applied tract‐based spatial statistics (TBSS) to diffusion tensor imaging (DTI) data from 332 heavy drinkers (mean age = 31.2 ± 9.4; 31% female) to obtain averaged fractional anisotropy (FA) values of 18 white matter tracts. Statistical analyses examined correlations ofFAvalues with blood‐oxygenation‐level‐dependent (BOLD) response to an alcohol taste cue, measured with functional magnetic resonance imaging (fMRI).FAvalues of nine white matter tracts (anterior corona radiata, body of corpus callosum, cingulate gyrus, external capsule, fornix, inferior frontooccipital fasciculus, posterior corona radiata, retrolenticular limb of internal capsule, and superior longitudinal fasciculus) were significantly, negatively correlated withBOLDactivation in medial frontal gyrus, parahippocampal gyrus, fusiform gyrus, cingulum, thalamus, caudate, putamen, insula, and cerebellum. The inverse relation between white matter integrity and functional activation during the alcohol taste cue provides support for the hypothesis that lower white matter integrity in frontoparietal and corticolimbic networks is a factor in loss of control over alcohol consumption.
Uniform Ag/AgCl Necklace‐Like Nano‐Heterostructures: Fabrication and Highly Efficient Plasmonic Photocatalysis
Authors: Jia Changchao , Yang Ping , Huang Baibiao
Published: December 2013

Ag/AgCl necklace‐like nano‐heterostructures with an average diameter of 55 nm were prepared by a facile in situ oxidation process. As a result of the presence of multiple crystalline Ag nanowires with lots of grain boundaries, uniform Ag/AgCl necklace‐like heterostructures can be successfully obtained in the presence of polyvinylpyrrolidone (PVP). Ag and AgCl are evenly distributed in the necklace‐like structures, which were divided into a number of tiny units that consisted of Ag and AgCl and enabled easy electron transfer. In contrast, a loose Ag/AgCl structure with large particles was prepared without the addition of PVP. A formation mechanism of the Ag/AgCl nano‐heterostructures was proposed. Furthermore, the molar ratio of Ag and AgCl plays an important role in the photocatalytic activity of the nano‐heterostructures, which can be tuned simply. The results of photocatalytic investigations demonstrate that the Ag/AgCl heterostructures with an 85 % AgCl component have an excellent activity for the decomposition of organic pollutants and water splitting to produce oxygen.
Pt3Co Concave Nanocubes: Synthesis, Formation Understanding, and Enhanced Catalytic Activity toward Hydrogenation of Styrene
Authors: Wang Chenyu , Lin Cuikun , Zhang Lihua , Quan Zewei , Sun Kai , Zhao Bo , Wang Feng , Porter Nathan , Wang Yuxuan , Fang Jiye
Published: December 2013

We report a facile synthesis route to prepare high‐quality Pt3Co nanocubes with a concave structure, and further demonstrate that these concave Pt3Co nanocubes are terminated with high‐index crystal facets. The success of this preparation is highly dependent on an appropriate nucleation process with a successively anisotropic overgrowth and a preservation of the resultant high‐index planes by control binding of oleyl‐amine/oleic acid with a fine‐tuned composition. Using a hydrogenation of styrene as a model reaction, these Pt3Co concave nanocubes as a new class of nanocatalysts with more open structure and active atomic sites located on their high‐index crystallographic planes exhibit an enhanced catalytic activity in comparison with low‐indexed surface terminated Pt3Co nanocubes in similar size.
Chiral Modification of Platinum by Co‐Adsorbed Cinchonidine and Trifluoroacetic Acid: Origin of Enhanced Stereocontrol in the Hydrogenation of Trifluoroacetophenone
Authors: Meemken Fabian , Baiker Alfons , Schenker Sebastian , Hungerbühler Konrad
Published: December 2013

Cinchonidine (CD) adsorbed onto a platinum metal catalyst leads to rate acceleration and induces strong stereocontrol in the asymmetric hydrogenation of trifluoroacetophenone. Addition of catalytic amounts of trifluoroacetic acid (TFA) significantly enhances the enantiomeric excess from 50 to 92 %. The origin of the enantioselectivity bestowed by co‐adsorbed CD and TFA is investigated by using in situ attenuated total reflection infrared spectroscopy and modulation excitation spectroscopy. Molecular interactions between the chiral modifier (CD), acid additive (TFA) and the trifluoro‐activated substrate at the solid–liquid interface are elucidated under conditions relevant to catalytic hydrogenations, that is, on a technical Pt/Al2O3 catalyst in the presence of H2 and solvent. Monitoring of the unmodified and modified surface during the hydrogenation provides an insight into the phenomenon of rate enhancement and the crucial interactions of CD with the ketone, corresponding product alcohol, and TFA. Comparison of the diastereomeric interactions occurring on the modified surface and in the liquid solution shows a striking difference for the chiral preferences of CD. The spectroscopic data, in combination with calculations of molecular structures and energies, sheds light on the reaction mechanism of the heterogeneous asymmetric hydrogenation of trifluoromethyl ketones and the involvement of TFA in the diastereomeric intermediate surface complex: the quinuclidine N atom of the adsorbed CD forms an NHO‐type hydrogen‐bonding interaction not only with the trifluoro‐activated ketone but also with the corresponding alcohol and the acid additive. Strong evidence is provided that it is a monodentate acid/base adduct in which the carboxylate of TFA resides at the quinuclidine N‐atom of CD, which imparts a better stereochemical control.
Controlling Protein Crystal Nucleation by Droplet‐Based Microfluidics
Authors: Maeki Masatoshi , Teshima Yuki , Yoshizuka Saori , Yamaguchi Hiroshi , Yamashita Kenichi , Miyazaki Masaya
Published: December 2013

Herein, we demonstrate the potential of droplet‐based microfluidics for controlling protein crystallization and generating single‐protein crystals. We estimated the critical droplet size for obtaining a single crystal within a microdroplet and investigated the crystallization of four model proteins to confirm the effect of protein molecular diffusion on crystallization. A single crystal was obtained in microdroplets smaller than the critical size by using droplet‐based microfluidics. In the case of thaumatin crystallization, a single thaumatin crystal was obtained in a 200 μm droplet even with high supersaturation. In the case of ferritin crystallization, the nucleation profile of ferritin crystals had a wider distribution than the nucleation profiles of lysozyme, thaumatin, and glucose isomerase crystallization. We found that the droplet‐based microfluidic approach was able to control the nucleation of a protein by providing control over the crystallization conditions and the droplet size, and that the diffusion of protein molecules is a significant factor in controlling the nucleation of protein crystals in droplet‐based microfluidics.
Sequence‐Specific DNA Alkylation Targeting for Kras Codon 13 Mutation by Pyrrole–Imidazole Polyamide seco‐CBI Conjugates
Authors: Taylor Rhys Dylan , Asamitsu Sefan , Takenaka Tomohiro , Yamamoto Makoto , Hashiya Kaori , Kawamoto Yusuke , Bando Toshikazu , Nagase Hiroki , Sugiyama Hiroshi
Published: December 2013

Hairpin N‐methylpyrrole‐N‐methylimidazole polyamide seco‐CBI conjugates 2–6 were designed for synthesis by Fmoc solid‐phase synthesis, and their DNA‐alkylating activities against the Kras codon 13 mutation were compared by high‐resolution denaturing gel electrophoresis with 225 base pair (bp) DNA fragments. Conjugate 5 had high reactivity towards the Kras codon 13 mutation site, with alkylation occurring at the A of the sequence 5′‐ACGTCACCA‐3′ (site 2), including minor 1 bp‐mismatch alkylation against wild type 5′‐ACGCCACCA‐3′ (site 3). Conjugate 6, which differs from conjugate 5 by exchanging one Py unit with a β unit, showed high selectivity but only weakly alkylated the A of 5′‐ACGTCACCA‐3′ (site 2). The hairpin polyamide seco‐CBI conjugate 5 thus alkylates according to Dervan′s pairing rule with the pairing recognition which β/β pair targets T–A and A–T pairs. SPR and a computer‐minimized model suggest that 5 binds to the target sequence with high affinity in a hairpin conformation, allowing for efficient DNA alkylation.
Equilibrium Shift in Solution: Molecular Shape Recognition and Precipitation of a Synthetic Double Helix Using Helicene‐Grafted Silica Nanoparticles
Authors: Miyagawa Masamichi , Ichinose Wataru , Yamaguchi Masahiko
Published: December 2013

Chiral silica nanoparticles (70 nm) grafted with (P)‐helicene recognized the molecular shape of double helix and random coil (P)‐ethynylhelicene oligomers in solution. A mixture of the (P)‐nanoparticles and double helix precipitated much faster than a mixture of the (P)‐nanoparticles and random coil, and the precipitate contained only the double helix. The mixture of the (P)‐nanoparticles and (P)‐ethynylhelicene pentamer reversibly dispersed in trifluoromethylbenzene upon heating at 70 °C and precipitated upon cooling at 25 °C. When a 10:90 equilibrium mixture of the double helix and random coil in solution was treated with the (P)‐nanoparticles, the double helix was precipitated in 53 % yield and was accompanied by equilibrium shift.
Janus Microspheres for Visual Assessment of Molecular Interconnects
Authors: Fliedel Christophe , Faramarzi Vina , Rosa Vitor , Doudin Bernard , Braunstein Pierre
Published: December 2013

A rigid S‐functionalized metalloligand is used to pair Janus Au‐coated silica microspheres and the resulting assemblies are assessed with optical microscopy. New Pd complexes provide stable molecular interconnects, and the metal centre controls the structure of the linker and provides the desired rigidity, by virtue of its well‐established coordination chemistry.
NAD(P)H‐Independent Asymmetric CC Bond Reduction Catalyzed by Ene Reductases by Using Artificial Co‐substrates as the Hydrogen Donor
Authors: Winkler Christoph K. , Clay Dorina , Entner Marcello , Plank Markus , Faber Kurt
Published: December 2013

To develop a nicotinamide‐independent single flavoenzyme system for the asymmetric bioreduction of CC bonds, four types of hydrogen donor, encompassing more than 50 candidates, were investigated. Six highly potent, cheap, and commercially available co‐substrates were identified that (under the optimized conditions) resulted in conversions and enantioselectivities comparable with, or even superior to, those obtained with traditional two‐enzyme nicotinamide adenine dinucleotide phosphate (NAD(P)H)‐recycling systems.
Tuning the Photophysical Properties of BODIPY Molecules by π‐Conjugation with Fischer Carbene Complexes
Authors: Chu Gong Ming , Guerrero‐Martínez Andrés , Fernández Israel , Sierra Miguel Ángel
Published: December 2013

The synthesis, structure, and photophysical properties of novel BODIPY–Fischer alkoxy‐, thio‐, and aminocarbene dyads are reported. The BODIPY chromophore is directly attached to the carbene ligand by an ethylenic spacer, thus forming donor–bridge–acceptor π‐extended systems. The extension of the π‐conjugation is decisive in the equilibrium geometries of the dyads and is clearly reflected in the corresponding absorption and emission spectra. Whereas the BODIPY fragment is mainly isolated in aminocarbene complexes, it is fully conjugated in alkoxycarbene derivatives. The former thus exhibit the characteristic photophysical properties of BODIPY units, whereas complete suppression of the BODIPY fluorescence emission is observed in the latter, as a direct consequence of the strong electron‐accepting character of the (CO)5MC moiety. As the π‐acceptor character of the metal–carbene group can be modified, the electronic properties of the conjugated BODIPY can be tuned. Density functional calculations have been carried out to gain insight into the photophysical properties.
FeCl3‐Mediated Three‐Component Cascade Reaction: An Effective Approach to the Construction of Highly Functionalized Pyrrolo[1,2‐c]quinazolinones
Authors: Zheng Hu‐Fei , Yu Zhi‐Hua , Yuan Wei , Tang Zi‐Long , Clough John , Gu Yu‐Cheng , Shi De‐Qing
Published: December 2013

An unexpected FeCl3‐mediated three‐component cascade reaction has been used to construct structurally diverse pyrrolo[1,2‐c]quinazolinone derivatives with potential biological activities. This method has advantages of mild conditions, simple work‐up, as well as wide substrate scope, which makes it a powerful approach to the synthesis of diverse pyrrolo[1,2‐c]quinazolinones. This cascade reaction involves 1,3‐dipolar cycloaddition between azomethine ylides and allenoates, followed by intramolecular nucleophilic addition in the presence of FeCl3. The obtained products could be easily transformed into derivatives with the pyrrolo[2,3‐c]quinazoline alkaloid skeleton.
Investigation of the Thermal Stability of the Carbon Framework of Graphene Oxide
Authors: Eigler Siegfried , Grimm Stefan , Hirsch Andreas
Published: December 2013

In this study, we use our recently prepared graphene oxide (GO) with an almost intact σ‐framework of carbon atoms (ai‐GO) to probe the thermal stability of the carbon framework for the first time. Ai‐GO exhibits few defects because CO2 formation is prevented during synthesis. Ai‐GO was thermally treated before chemical reduction and the resulting defect density in graphene was subsequently determined by statistical Raman microscopy. Surprisingly, the carbon framework of ai‐GO is stable in thin films up to 100 °C. Furthermore, we find evidence for an increase in the quality of ai‐GO upon annealing at 50 °C before reduction. The carbon framework of GO prepared according to the popular Hummers’ method (GO‐c) appears to be less stable and decomposition starts at 50 °C, which is qualitatively indicated by CO2‐trapping experiments in μm‐thin films. Information about the stability of GO is important for storing, processing, and using GO in many applications.
Gold(III)‐Mediated Contraction of Benzene to Cyclopentadiene: From p‐Benziporphyrin to Gold(III) True Tetraarylcarbaporphyrin
Authors: Szyszko Bartosz , Kupietz Kamil , Szterenberg Ludmiła , Latos‐Grażyński Lechosław
Published: December 2013

The reaction of p‐benziporphyrin, sodium tetrachloroaurate(III) dihydrate, and potassium carbonate in dichloromethane yielded gold(III) 5,10,15,20‐tetraaryl‐21‐carbaporphyrin owing to the contraction of p‐phenylene to cyclopentadiene. This molecule is the very first representative of a true 5,10,15,20‐tetraaryl‐21‐carbaporphyrin complex where four trigonal donor atoms are involved in equatorial coordination. The contraction adds an unprecedented route to numerous organic transformations of aromatic compounds catalyzed by simple gold(III) compounds. p‐Benziporphyrin provided the unique environment to alter the fundamental reactivity of the benzene unit facilitating its contraction to cyclopentadiene.
Is prostate cancer changing?: Evolving patterns of metastatic castration‐resistant prostate cancer
Authors: Doctor Stephanie M. , Tsao Che‐Kai , Godbold James H. , Galsky Matthew D. , Oh William K.
Published: December 2013

BACKGROUND

Metastatic castration‐resistant prostate cancer (mCRPC) most commonly metastasizes to the bone, and less commonly to nonosseous sites (eg, lymph nodes, liver, lung). With new therapies extending survival in mCRPC, it was hypothesized that the pattern of metastases is changing over time. The pattern of metastatic disease was evaluated in men with mCRPC, as reported in baseline characteristics of prospective clinical trials over 2 decades.

METHODS

This study identified all phase 2 and 3 therapeutic studies in men with mCRPC in PubMed and American Society of Clinical Oncology abstracts from 1990 to 2012. Studies were excluded if they did not report demographic data and sites of metastasis, or excluded patients with a specific site of metastatic disease (except brain). For each type of metastasis, weighted least squares linear regression models were used to evaluate temporal trends.

RESULTS

A total of 290 eligible studies (270 phase 2 studies and 20 phase 3 studies) involving 19,110 patients were identified. Between 1990 and 2012, the rate of nonosseous metastasis increased significantly at 1.6% per year (P < .0001), whereas the rate of osseous metastasis decreased at 0.5% per year (P < .0001). The rate of lymph node metastasis increased at 1.4% per year (P < .0001), but the rate of liver and lung metastasis remained relatively stable.

CONCLUSIONS

A notable change was found in the pattern of metastasis in patients with mCRPC. Because these evolving patterns may have important implications in treatment selection and prognosis, it is crucial that future clinical trials of patients with mCRPC define patients with a uniform reporting of nonosseous metastasis. Cancer 2014;120:833–839. © 2013 American Cancer Society.
Drug resistance and BCR‐ABL kinase domain mutations in Philadelphia chromosome–positive acute lymphoblastic leukemia from the imatinib to the second‐generation tyrosine kinase inhibitor era: The main changes are in the type of mutations, but not in the frequency of mutation involvement
Authors: Soverini Simona , De Benedittis Caterina , Papayannidis Cristina , Paolini Stefania , Venturi Claudia , Iacobucci Ilaria , Luppi Mario , Bresciani Paola , Salvucci Marzia , Russo Domenico , Sica Simona , Orlandi Ester , Intermesoli Tamara , Gozzini Antonella , Bonifacio Massimiliano , Rigolin Gian Matteo , Pane Fabrizio , Baccarani Michele , Cavo Michele , Martinelli Giovanni
Published: December 2013

BACKGROUND

Patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) frequently relapse on imatinib with acquisition of BCR‐ABL kinase domain (KD) mutations. To analyze the changes that second‐generation tyrosine kinase inhibitors (TKIs) have brought in mutation frequency and type, a database review was undertaken of the results of all the BCR‐ABL KD mutation analyses performed in the authors' laboratory from January 2004 to January 2013.

METHODS

Interrogation of the database retrieved 450 mutation analyses in 272 patients with Ph+ ALL. Prescreening of samples was performed with denaturing high‐performance liquid chromatography (D‐HPLC), followed by direct sequencing of D‐HPLC–positive cases.

RESULTS

BCR‐ABL KD mutations were detected in 70% of imatinib‐resistant patients, with T315I, E255K, and Y253H mutations accounting for 75% of cases. Seventy‐eight percent of the patients reported to be resistant to second‐generation TKIs after imatinib failure were positive for mutations, and 58% of them had multiple mutations. Analysis of patients relapsing on dasatinib revealed a newly acquired T315I mutation in almost two‐thirds of the cases. Direct sequencing detected no mutations at diagnosis, even in patients who relapsed after a few months.

CONCLUSIONS

Second‐generation TKIs ensure a more rapid debulking of the leukemic clone and have much fewer insensitive mutations, but long‐term disease control remains a problem, and the T315I mutation is revealed to be an even more frequent enemy. BCR‐ABL KD mutation screening of patients with Ph+ ALL who are receiving imatinib or second‐generation TKIs would be a precious ally for timely treatment optimization. In contrast, the clinical usefulness of conventional direct sequencing at diagnosis seems to be very low. Cancer 2014;120:1002–1009. © 2013 American Cancer Society.
Genomics of racial and ethnic disparities in childhood acute lymphoblastic leukemia
Authors: Lim Joshua Yew‐Suang , Bhatia Smita , Robison Leslie L. , Yang Jun J.
Published: December 2013

Although the cure rates of childhood acute lymphoblastic leukemia (ALL) have improved dramatically in the past 40 years, not all children have benefited equally from this impressive progress. Racial and ethnic disparities in the incidence and treatment outcome of childhood ALL persist, with Hispanic children having an elevated risk of developing ALL and one of the lowest survival rates after ALL therapy. A critical barrier to progress is the lack of an understanding of the causes of ALL disparities, particularly racial and ethnic differences in ALL biology. In this review, the authors summarize the current knowledge on population variation in childhood ALL incidence and treatment outcome, discuss the contributing genetic and nongenetic variables, and highlight possible therapeutic interventions to mitigate disparities in ALL. Cancer 2014;120:955–962. © 2013 American Cancer Society.
Elevated intrinsic cancer stem cell population in human papillomavirus‐associated head and neck squamous cell carcinoma
Authors: Zhang Manchao , Kumar Bhavna , Piao Longzhu , Xie Xiujie , Schmitt Alessandra , Arradaza Nicole , Cippola Michael , Old Matthew , Agrawal Amit , Ozer Enver , Schuller David E. , Teknos Theodoros N. , Pan Quintin
Published: December 2013

BACKGROUND

Human papillomavirus 16 (HPV16) is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), particularly the development of oropharyngeal squamous cell carcinoma (OPSCC). Cancer stem cells (CSCs) are resistant to conventional therapies, and it is postulated that they are responsible for disease recurrence and/or progression. Because the prognoses of patients with HPV16‐positive and HPV‐negative HNSCC are distinct, the authors sought to determine whether differences in the number of CSCs could account for this clinical observation.

METHODS

CSC populations in HPV16‐positive and HPV‐negative HNSCC were assessed using a proprietary assay based on expression of the enzyme aldehyde dehydrogenase (ALDH), an in vitro tumorsphere formation assay, and an in vivo limiting cell dilution in nonobese diabetic/severe combined immunodeficiency mice. A high‐density tissue microarray was stained with ALDH1, a CSC marker, to determine the association between CSCs and HPV16‐positive/HPV‐negative OPSCC.

RESULTS

HPV16‐positive HNSCC had a greater intrinsic CSC pool than HPV‐negative HNSCC. Inactivation of p53 has been identified as a major mechanism for the elevated CSC population in HPV16‐positive HNSCC. In vivo limiting cell dilution experiments using tumors from patients with HPV16‐positive and HPV‐negative OPSCC indicated that the CSC frequency was 62.5‐fold greater in an HPV16‐positive OPSCC tumor than in an HPV‐negative OPSCC tumor. Primary tumors from patients with HPV16‐positive OPSCC were associated with elevated tumor ALDH1 staining, further extending the association between HPV16 and CSCs.

CONCLUSIONS

The current data and the clinical observation that patients with HPV16‐positive HNSCC respond more favorably to current treatment paradigms than patients with HPV‐negative HNSCC support the suggestion that CSC phenotype is not homogeneous. Therefore, the reliance on the CSC number may be insufficient to accurately assess the potential of a particular tumor for disease recurrence and/or progression. Cancer 2014;120:992–1001. © 2014 American Cancer Society.
Invariant Measures and the Soliton Resolution Conjecture
Authors: Chatterjee Sourav
Published: December 2013

The soliton resolution conjecture for the focusing nonlinear Schrödinger equation (NLS) is the vaguely worded claim that a global solution of the NLS, for generic initial data, will eventually resolve into a radiation component that disperses like a linear solution, plus a localized component that behaves like a soliton or multisoliton solution. Considered to be one of the fundamental open problems in the area of nonlinear dispersive equations, this conjecture has eluded a proof or even a precise formulation to date.

This paper proves a “statistical version” of this conjecture at mass‐subcritical nonlinearity, in the following sense: The uniform probability distribution on the set of all functions with a given mass and energy, if such a thing existed, would be a natural invariant measure for the NLS flow and would reflect the long‐term behavior for “generic initial data” with that mass and energy. Unfortunately, such a probability measure does not exist. We circumvent this problem by constructing a sequence of discrete measures that, in principle, approximate this fictitious probability distribution as the grid size goes to 0. We then show that a continuum limit of this sequence of probability measures does exist in a certain sense, and in agreement with the soliton resolution conjecture, the limit measure concentrates on the unique ground state soliton. Combining this with results from ergodic theory, we present a tentative formulation and proof of the soliton resolution conjecture in the discrete setting.

The above results, following in the footsteps of a program of studying the long‐term behavior of nonlinear dispersive equations through their natural invariant measures initiated by Lebowitz, Rose, and Speer and carried forward by Bourgain, McKean, Tzvetkov, Oh, and others, are proved using a combination of techniques from large deviations, PDEs, harmonic analysis, and bare‐hands probability theory. It is valid in any dimension. © 2014 Wiley Periodicals, Inc.
The Role of Molecular Dipole Orientation in Single‐Molecule Fluorescence Microscopy and Implications for Super‐Resolution Imaging
Authors: Backlund Mikael P. , Lew Matthew D. , Backer Adam S. , Sahl Steffen J. , Moerner W. E.
Published: December 2013

Numerous methods for determining the orientation of single‐molecule transition dipole moments from microscopic images of the molecular fluorescence have been developed in recent years. At the same time, techniques that rely on nanometer‐level accuracy in the determination of molecular position, such as single‐molecule super‐resolution imaging, have proven immensely successful in their ability to access unprecedented levels of detail and resolution previously hidden by the optical diffraction limit. However, the level of accuracy in the determination of position is threatened by insufficient treatment of molecular orientation. Here we review a number of methods for measuring molecular orientation using fluorescence microscopy, focusing on approaches that are most compatible with position estimation and single‐molecule super‐resolution imaging. We highlight recent methods based on quadrated pupil imaging and on double‐helix point spread function microscopy and apply them to the study of fluorophore mobility on immunolabeled microtubules.
Hollow Porous Carbon Fiber from Cotton with Nitrogen Doping
Authors: Shen Wenzhong , Hu Tuoping , Wang Peiyu , Sun Haizhen , Fan Weibin
Published: December 2013

Porous carbon fiber with hollow structure and hydrophilic groups was successfully prepared from cotton. The structures and surface chemical properties of the porous carbon fiber were characterized by nitrogen adsorption isotherms, thermogravimetry, FTIR spectroscopy, and scanning electron microscopy. The morphologies of porous carbons prepared under different conditions were observed and compared. The resulting porous carbons had a microporous structure with a pore size distribution around 0.7–2.0 nm. The pyrolysis and decomposition of cotton to form a condensation cross‐linked ring structure took place from 230 to 350 °C. Nitrogen‐containing groups could be incorporated into the carbon matrix by urea decomposition during the carbonization process. The porous carbon contained more hydrophilic groups and its fiber structure was kept; the carbon yield was improved in the presence of KOH/urea. The porous carbon fiber showed high adsorption capacities of CO2 as a result of its surface hydrophilic groups and developed pore structure.
Influence of Chromophore Length and Acceptor Groups on the Optical Properties of Rigidified Merocyanine Dyes
Authors: Kreß Katharina Christina , Fischer Thomas , Stumpe Joachim , Frey Wolfgang , Raith Melanie , Beiraghi Omid , Eichhorn S. Holger , Tussetschläger Stefan , Laschat Sabine
Published: December 2013

Invited for this month’s cover are the three collaborating groups from the University of Stuttgart and the Fraunhofer Institute for Applied Polymer Research in Potsdam, both from Germany as well as the University of Windsor, Canada. The cover picture shows the shift of frontier orbital energies and symmetries upon excitation with light for three different chromophore lengths. Read the full text of the article at 10.1002/cplu.201300308
Mesostructured Platinum‐Free Anode and Carbon‐Free Cathode Catalysts for Durable Proton Exchange Membrane Fuel Cells
Authors: Cui Xiangzhi , Shi Jianlin , Wang Yongxia , Chen Yu , Zhang Lingxia , Hua Zile
Published: December 2013

As one of the most important clean energy sources, proton exchange membrane fuel cells (PEMFCs) have been a topic of extensive research focus for decades. Unfortunately, several critical technique obstacles, such as the high cost of platinum electrode catalysts, performance degradation due to the CO poisoning of the platinum anode, and carbon corrosion by oxygen in the cathode, have greatly impeded its commercial development. A prototype of a single PEMFC catalyzed by a mesostructured platinum‐free WO3/C anode and a mesostructured carbon‐free Pt/WC cathode catalysts is reported herein. The prototype cell exhibited 93 % power output of a standard PEMFC using commercial Pt/C catalysts at 50 and 70 °C, and more importantly, CO poisoning‐free and carbon corrosion‐resistant characters of the anode and cathode, respectively. Consequently, the prototype cell demonstrated considerably enhanced cell operation durability. The mesostructured electrode catalysts are therefore highly promising in the future development and application of PEMFCs.
Upward appearance comparison and the development of eating pathology in college women
Authors: Arigo Danielle , Schumacher Leah , Martin Lindsay M.
Published: December 2013

Objective

Body dissatisfaction and disordered eating behaviors are common among college women, yet only a subset of this population develops clinically significant disordered eating symptoms during college. Appearance‐based social comparisons, particularly those made to others with “better” bodies (i.e., upward appearance comparisons), have demonstrated concurrent relationships with body dissatisfaction and disordered eating. Little is known about the value of these comparisons for predicting the development of eating pathology, however.

Method

The present study examined the predictive value of upward appearance comparisons, as well as established risk factors (e.g., body dissatisfaction, negative affect), for the onset of clinically significant eating pathology over one college semester. College women (N = 454) completed validated self‐report measures at the beginning of one semester, and again nine weeks later.

Results

Women who were newly above the clinical threshold for eating pathology at follow‐up (n = 31) exhibited stronger baseline tendencies toward upward appearance comparisons than women who were below the threshold at both time points. In contrast, women who were already above the clinical threshold at baseline scored higher on established risk factors.

Discussion

These findings suggest that the extent of upward appearance comparison may be useful for identifying college women at particular risk for developing clinically significant disordered eating symptoms. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:467–470)
On the evolution of omnivory in a community context
Authors: Chubaty Alex M. , Ma Brian O. , Stein Robert W. , Gillespie David R. , Henry Lee M. , Phelan Conan , Palsson Eirikur , Simon Franz W. , Roitberg Bernard D.
Published: December 2013

Omnivory is extremely common in animals, yet theory predicts that when given a choice of resources specialization should be favored over being generalist. The evolution of a feeding phenotype involves complex interactions with many factors other than resource choice alone, including environmental heterogeneity, resource quality, availability, and interactions with other organisms. We applied an evolutionary simulation model to examine how ecological conditions shape evolution of feeding phenotypes (e.g., omnivory), by varying the quality and availability (absolute and relative) of plant and animal (prey) resources. Resulting feeding phenotypes were defined by the relative contribution of plants and prey to diets of individuals. We characterized organisms using seven traits that were allowed to evolve freely in different simulated environments, and we asked which traits are important for different feeding phenotypes to evolve among interacting organisms. Carnivores, herbivores, and omnivores all coexisted without any requirement in the model for a synergistic effect of eating plant and animal prey. Omnivores were most prevalent when ratio of plants and animal prey was low, and to a lesser degree, when habitat productivity was high. A key result of the model is that omnivores evolved through many different combinations of trait values and environmental contexts. Specific combinations of traits tended to form emergent trait complexes, and under certain environmental conditions, are expressed as omnivorous feeding phenotypes. The results indicate that relative availabilities of plants and prey (over the quality of resources) determine an individual's feeding class and that feeding phenotypes are often the product of convergent evolution of emergent trait complexes under specific environmental conditions. Foraging outcomes appear to be consequences of degree and type of phenotypic specialization for plant and animal prey, navigation and exploitation of the habitat, reproduction, and interactions with other individuals in a heterogeneous environment. Omnivory should not be treated as a fixed strategy, but instead a pattern of phenotypic expression, emerging from diverse genetic sources and coevolving across a range of ecological contexts.