bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel role for flotillin‐1 in H‐Ras‐regulated breast cancer aggressiveness
Authors: Koh Minsoo , Yong Hae‐Young , Kim Eun‐Sook , Son Hwajin , Jeon You Rim , Hwang Jin‐Sun , Kim Myeong‐Ok , Cha Yujin , Choi Wahn Soo , Noh Dong‐Young , Lee Kyung‐Min , Kim Ki‐Bum , Lee Jae‐Seon , Kim Hyung Joon , Kim Haemin , Kim Hong‐Hee , Kim Eun Joo , Park So Yeon , Kim Hoe Suk , Moon Woo Kyung , Choi Kim Hyeong‐Reh , Moon Aree
Published: September 2015

Elevated expression and aberrant activation of Ras have been implicated in breast cancer aggressiveness. H‐Ras, but not N‐Ras, induces breast cell invasion. A crucial link between lipid rafts and H‐Ras function has been suggested. This study sought to identify the lipid raft protein(s) responsible for H‐Ras‐induced tumorigenicity and invasiveness of breast cancer. We conducted a comparative proteomic analysis of lipid raft proteins from invasive MCF10A human breast epithelial cells engineered to express active H‐Ras and non‐invasive cells expressing active N‐Ras. Here, we identified a lipid raft protein flotillin‐1 as an important regulator of H‐Ras activation and breast cell invasion. Flotillin‐1 was required for epidermal growth factor‐induced activation of H‐Ras, but not that of N‐Ras, in MDA‐MB‐231 triple‐negative breast cancer (TNBC) cells. Flotillin‐1 knockdown inhibited the invasiveness of MDA‐MB‐231 and Hs578T TNBC cells in vitro and in vivo. In xenograft mouse tumor models of these TNBC cell lines, we showed that flotillin‐1 played a critical role in tumor growth. Using human breast cancer samples, we provided clinical evidence for the metastatic potential of flotillin‐1. Membrane staining of flotillin‐1 was positively correlated with metastatic spread (p = 0.013) and inversely correlated with patient disease‐free survival rates (p = 0.005). Expression of flotillin‐1 was associated with H‐Ras in breast cancer, especially in TNBC (p < 0.001). Our findings provide insight into the molecular basis of Ras isoform‐specific interplay with flotillin‐1, leading to tumorigenicity and aggressiveness of breast cancer.
Erythrocytapheresis is a valid and safe therapeutic option in dysmetabolic iron overload syndrome
Authors: Vetro Calogero , Rosso Rosamaria , Palmucci Stefano , Russello Maurizio , Colletta Grazia , Romeo Maria Anna , Ximenes Benedetta , Romano Alessandra , Palumbo Giuseppe Alberto , Di Raimondo Francesco
Published: September 2015

Dysmetabolic iron overload syndrome is a rare event causing hepatic impairment with serious long‐term side effects. Here, we describe a case of metabolic syndrome‐related hepatic iron overload that showed a rapid, effective, and safe response to erythrocytapheresis. J. Clin. Apheresis 31:443–447, 2016. © 2015 Wiley Periodicals, Inc.
Bioreactors for heart valve tissue engineering: a review
Authors: Amrollahi Pouya , Tayebi Lobat
Published: September 2015

Bioreactors have great potential in the successful development of tissue‐engineered heart valve replacements, both at the research stage and in commercial platforms. Their ability to mimick the chemical and physiological conditions of the body has allowed researchers to study in vitro cellular responses, and this has helped in the fabrication of better and more efficient tissues in vivo. Use of different bioreactors, such as, rotating, dynamic flexure, cyclic stretch and pulsatile bioreactors, in tissue engineering of heart valves has been widely investigated. However, this research is still at its early stage, and many critical issues need to be resolved to make tissue engineered heart valves sufficiently reliable for clinical applications. In the following article, after a brief introduction to the structure and role of heart valves, the efforts of tissue engineers in designing heart valves using different bioreactors is described. © 2015 Society of Chemical Industry
When are overqualified employees creative? It depends on contextual factors
Authors: Luksyte Aleksandra , Spitzmueller Christiane
Published: September 2015

The research on perceived overqualification has mainly examined its negative consequences. Defined, employees who feel overqualified have surplus talent and thus can be excellent workers if managed properly; yet, empirical evidence in this domain is lacking. Building on person–environment fit theory, this research explored whether, when, and how employees who feel overqualified can engage in creative performance. The results of a multi‐source field study (N = 113 employees and 19 supervisors) supported theoretical predictions. Perceived overqualification was related positively to supervisor‐rated creative performance when these workers felt supported and appreciated and successfully negotiated developmental idiosyncratic deals. Opportunities to mentor others had an impact on the relationship between perceived overqualification and supervisor‐rated creativity, although the simple slopes were non‐significant. This study is novel in that it unpacked actionable steps that organizations can utilize to motivate this large segment of workforce to use their surplus qualifications constructively by, for example, engaging in creative performance. Copyright © 2015 John Wiley & Sons, Ltd.
Chronological variations in handaxes: patterns detected from fluvial archives in north‐west Europe
Authors: Bridgland David R. , White Mark J.
Published: September 2015

The use of handaxe morphology as a cultural and temporal marker within the Quaternary Lower–Middle Palaeolithic record has had a very chequered history, and abuses in the past have led recent generations of archaeologist to reject it out of hand. In Britain, however, advances in dating Pleistocene sediments, setting their ages within a framework of ∼11 glacial–interglacial cycles over the past 1 Ma, has revealed several patterns in technology and morphology that must be related to changing practices and cultural preferences over time. These are not predictable, nor are they linear, but nevertheless they may aid understanding of the movements of different peoples in and out of Britain over the past 500 000 years. It is also clear that such patterns are to be expected over a much wider region of the nearby continent, although they might not be identical, or even similar, to those established for southern Britain. This paper extends from explanation of the British patterns to an exploration of the extent to which something comparable can be recognized in neighbouring areas of continental Europe: a baseline for a planned collaborative survey of data from the Acheulean of north‐west European river systems.
Aquaculture depredation by double‐crested cormorants breeding in Eastern North America
Authors: Craig Elizabeth C. , King D. Tommy , Sparks Jed P. , Curtis Paul D.
Published: September 2015

The double‐crested cormorant (Phalacrocorax auritus) has undergone population expansion throughout much of its historical range since the 1970s, resulting in increased pressure on foraging habitats including real and perceived competition with commercial and sport fisheries and impacts on the aquaculture industry. The specific objectives of this study were to determine the stable isotope ratios of birds wintering at aquaculture facilities and natural freshwater and marine habitats, and to determine what percent of birds at distinct breeding colonies wintered in each of these habitats. We exploited natural variation in isotopic ratios of carbon, nitrogen, and sulfur (from feathers) to determine the winter habitat use (i.e., aquaculture, natural freshwater, or marine) of birds collected on their summer breeding grounds in the eastern United States (from Minnesota to Vermont). The distribution of winter habitat use varied significantly across breeding colonies and between male and female cormorants. More specifically, use of aquaculture winter habitat was most prevalent in birds breeding in Lake Huron and Lake Erie. Overall, aquaculture habitats were used more by males, and marine habitats were used more by females. The stable isotope approach used in this study provided dietary confirmation of previously observed migratory patterns in the double‐crested cormorant. Because aquaculture was primarily used by males, and these males migrated to a broad range of breeding colonies, we suggest that targeting breeding birds to reduce aquaculture depredation is a less efficient strategy than managing birds at depredation sites on the wintering grounds. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
A multi‐laser flow cytometry method to measure single cell and population‐level relative fluorescence action spectra for the targeted study and isolation of phytoplankton in complex assemblages
Authors: Thompson Anne W. , van den Engh Ger
Published: September 2015

Discerning the diversity, abundance, and functional role of distinct phytoplankton groups is essential to ecological study of aquatic systems. Flow cytometry is a widely used method to rapidly identify and quantify individual phytoplankton cells. Here, we present a new flow cytometry method that uses up to five excitation colors to determine the relative fluorescence action spectra of phytoplankton within complex assemblages, thus leveraging the precise and high‐throughput capabilities of flow cytometry and the unique combinations of photosynthetic pigments in phylogenetically related groups of phytoplankton. First, we tested the method on cultivated Synechococcus of known pigment composition and genotype then we applied the method to a natural phytoplankton assemblage where we determined the relative fluorescence action spectra of numerous distinct populations. By coupling multi‐laser flow cytometry to cell sorting we demonstrated that natural phytoplankton populations with similar relative fluorescence action spectra belonged to the same taxonomic classes based on 18S rRNA gene phylogeny. This method will be instrumental in studying the ecology of distinct phytoplankton populations within complex microbial communities through spectral analysis of individual cells, identification of unique populations, and cell sorting for downstream applications such as enrichment for isolation, genome assembly, and linkage of chromatic and genetic information in a predictive fashion.
Acne scarring: A review of available therapeutic lasers
Authors: Cohen Brandon E. , Brauer Jeremy A. , Geronemus Roy G.
Published: September 2015

Background and Objective

The utilization of lasers in dermatology has greatly expanded in recent decades. Acne scarring is a common indication in which lasers play an important therapeutic role.

Study Design/Materials and Methods

Available lasers include traditional ablative lasers, such as carbon dioxide and erbium lasers, traditional non‐ablative lasers, such as neodymium, diode, alexandrite, pulsed dye lasers and intense pulse light, as well as both ablative, and non‐ablative fractional laser systems.

Conclusion

We sought to provide a framework for understanding the various types of lasers available to treat acne scars and review the primary literature pertaining to the efficacy, safety, and advantages of each laser discussed. Lasers Surg. Med. 48:95–115, 2016. © 2015 Wiley Periodicals, Inc.
Modeling corrosion‐induced damage of reinforced concrete elements with multiple‐arranged reinforcement bars
Authors: Ožbolt J. , Oršanić F. , Balabanić G.
Published: September 2015

Aggressive environmental conditions, such as exposure to the sea climate or use of de‐icing salts, have considerable influence on durability of reinforced concrete structures due to the reinforcement corrosion‐induced damage. Recently a coupled 3D chemo‐hygro‐thermo‐mechanical (CHTM) model for modeling of processes related to the chloride induced corrosion of steel reinforcement in concrete was developed. The model is briefly discussed and subsequently employed in the 3D finite element analysis of reinforced concrete (RC) beams exposed to aggressive environmental conditions, which were recently tested by Dong et al. . In the analysis, the corrosion‐induced damage is simulated by accounting for the interaction between several rebars. Moreover, the influence of the stirrups is also investigated. The numerical results are compared with experimental results and it is demonstrated that the numerical model realistically replicates corrosion‐induced damage of concrete. The same as in experimental tests, the beams without stirrups exhibits severe damage due to spalling of concrete cover and the presence of stirrups reduces the corrosion‐induced damage.
Brain contrasting ability of blood‐brain‐barrier–permeable nitroxyl contrast agents for magnetic resonance redox imaging
Authors: Matsumoto Ken‐ichiro , Yamasaki Toshihide , Nakamura Mizuki , Ishikawa Junji , Ueno Megumi , Nakanishi Ikuo , Sekita Aiko , Ozawa Yoshikazu , Kamada Tadashi , Aoki Ichio , Yamada Ken‐ichi
Published: September 2015

Purpose

The detailed in vivo T1‐weighted contrasting abilities of nitroxyl contrast agents, which have been used as redox responsive contrast agents in several magnetic resonance‐based imaging modalities, in mouse brain were investigated.

Methods

Distribution and pharmacokinetics of five types of five‐membered‐ring nitroxyl radical compound were compared using T1‐weighted MRI.

Results

The blood–brain barrier (BBB) ‐impermeable 3‐carboxy‐2,2,5,5‐tetramethylpyrrolidine‐N‐oxyl (CxP) could not be distributed in the brain. The slightly lipophilic 3‐carbamoyl‐2,2,5,5‐tetramethylpyrrolidine‐N‐oxyl (CmP) showed slight distribution only in the ventricle, but not in the medulla and cortex. The amphiphilic 3‐methoxy‐carbonyl‐2,2,5,5‐tetramethyl‐pyrrolidine‐N‐oxyl (MCP) had good initial uniform distribution in the brain and showed typical 2‐phase signal decay profiles. A brain‐seeking nitroxyl probe, acetoxymethyl‐2,2,5,5‐tetramethyl‐pyrrolidine‐N‐oxyl‐3‐carboxylate (CxP‐AM), showed an accumulating phase, and then its accumulation was maintained in the medulla and ventricle regions, but not in the cortex. The lipophilic 4‐(N‐methyl piperidine)−2,2,5,5‐tetramethylpyrroline‐N‐oxyl (23c) was well distributed in the cortex and medulla, but slightly in the ventricle, and showed relatively rapid linear signal decay.

Conclusion

Nitroxyl contrast agents equipped with a suitable lipophilic substitution group could be BBB‐permeable functional contrast agents. MR redox imaging, which can estimate not only the redox characteristics but also the detailed distribution of the contrast agents, is a good candidate for a theranostic tool. Magn Reson Med 76:935–945, 2016. © 2015 Wiley Periodicals, Inc.
Quantitative susceptibility mapping using a superposed dipole inversion method: Application to intracranial hemorrhage
Authors: Sun Hongfu , Kate Mahesh , Gioia Laura C. , Emery Derek J. , Butcher Kenneth , Wilman Alan H.
Published: September 2015

Purpose

To investigate gradient‐echo phase errors caused by intracranial hemorrhage (ICH) of low signal magnitude, and propose methods to reduce artifacts from phase errors in quantitative susceptibility mapping (QSM) of ICH.

Methods

Two QSM methods are proposed: (1) mask‐inversion that masks the phase of low signal magnitude regions, and (2) ICH magnetic dipole field isolation followed by susceptibility superposition using multiple boundaries for background field removal. The reconstruction methods were tested in eight subjects with ICH using standard single‐echo susceptibility‐weighted imaging at 1.5 Tesla with 40 ms echo time. Different phase unwrapping algorithms were also compared.

Results

Significant phase errors were evident inside ICHs with low signal magnitude. The mask‐inversion method recovered susceptibility of ICH in numerical simulation and minimized phase error propagation in patients with ICH. The additional superposed dipole inversion process substantially suppressed and constrained streaking artifacts in all subjects. Using the proposed superposition method, ICH susceptibilities measured from long and short echo times were similar. Laplacian based phase unwrapping substantially underestimated the ICH dipole field as compared to a path‐based method.

Conclusion

The proposed methods of mask‐inversion as well as ICH isolation and superposition can substantially reduce artifacts in QSM of ICH. Magn Reson Med 76:781–791, 2016. © 2015 Wiley Periodicals, Inc.
A model‐based reconstruction technique for quantitative myocardial perfusion imaging
Authors: Tran‐Gia Johannes , Lohr David , Weng Andreas Max , Ritter Christian Oliver , Stäb Daniel , Bley Thorsten Alexander , Köstler Herbert
Published: September 2015

Purpose

To reduce saturation effects in the arterial input function (AIF) estimation of quantitative myocardial first‐pass saturation recovery perfusion imaging by employing a model‐based reconstruction.

Theory and Methods

Imaging was performed with a saturation recovery prepared radial FLASH sequence. A model‐based reconstruction was applied for reconstruction. By exploiting prior knowledge about the relaxation process, an image series with different saturation recovery times was reconstructed. By evaluating images with an effective saturation time of approximately 3 ms, saturation effects in the AIF determination were reduced. In a volunteer study, this approach was compared with a standard prebolus technique.

Results

In comparison to the low‐dose injection of a prebolus acquisition, saturation effects were further reduced in the AIFs determined using the model‐based approach. These effects, which were clearly visible for all six volunteers, were reflected in a statistically significant difference of up to 20% in the absolute perfusion values.

Conclusion

The application of model‐based reconstruction algorithms in quantitative myocardial perfusion imaging promises a significant improvement of the AIF determination. In addition to greatly reducing saturation effects that occur even for the prebolus methods, only a single bolus has to be applied. Magn Reson Med 76:880–887, 2016. © 2015 Wiley Periodicals, Inc.
Phased‐array combination for MR spectroscopic imaging using a water reference
Authors: Abdoli Abas , Maudsley Andrew A.
Published: September 2015

Purpose

To evaluate methods for multichannel combination of three‐dimensional MR spectroscopic imaging (MRSI) data with a focus on using information from a water‐reference spectroscopic image.

Methods

Volumetric MRSI data were acquired for a phantom and for human brain using 8‐ and 32‐channel detection. Acquisition included a water‐reference dataset that was used to determine the weights for several multichannel combination methods. Results were compared using the signal‐to‐noise ratio (SNR) of the N‐acetylaspartate resonance.

Results

Performance of all methods was very similar for the phantom study, with the whitened singular value decomposition (WSVD) and signal magnitude (S) weighting combination having a small advantage. For in vivo studies, the S weighting, SNR weighting and signal to noise squared (S/N2) weighting were the three best methods and performed similarly. Example spectra and SNR maps indicated that the SVD and WSVD methods tend to fail for voxels at the outer edges of the brain that include strong lipid signal contributions.

Conclusion

For data combination of MRSI data using water‐reference information, the S/N2 weighting, SNR and S weighting were the best methods in terms of spectral quality SNR. These methods are also computationally efficient and easy to implement. Magn Reson Med 76:733–741, 2016. © 2015 Wiley Periodicals, Inc.
Cocaine‐induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese‐enhanced MRI
Authors: Perrine Shane A. , Ghoddoussi Farhad , Desai Kirtan , Kohler Robert J. , Eapen Ajay T. , Lisieski Michael J. , Angoa‐Perez Mariana , Kuhn Donald M. , Bosse Kelly E. , Conti Alana C. , Bissig David , Berkowitz Bruce A.
Published: September 2015

A long‐standing goal of substance abuse research has been to link drug‐induced behavioral outcomes with the activity of specific brain regions to understand the neurobiology of addiction behaviors and to search for drug‐able targets. Here, we tested the hypothesis that cocaine produces locomotor (behavioral) sensitization that correlates with increased calcium channel‐mediated neuroactivity in brain regions linked with drug addiction, such as the nucleus accumbens (NAC), anterior striatum (AST) and hippocampus, as measured using manganese‐enhanced MRI (MEMRI). Rats were treated with cocaine for 5 days, followed by a 2‐day drug‐free period. The following day, locomotor sensitization was quantified as a metric of cocaine‐induced neuroplasticity in the presence of manganese. Immediately following behavioral testing, rats were examined for changes in calcium channel‐mediated neuronal activity in the NAC, AST, hippocampus and temporalis muscle, which was associated with behavioral sensitization using MEMRI. Cocaine significantly increased locomotor activity and produced behavioral sensitization compared with saline treatment of control rats. A significant increase in MEMRI signal intensity was determined in the NAC, but not AST or hippocampus, of cocaine‐treated rats compared with saline‐treated control rats. Cocaine did not increase signal intensity in the temporalis muscle. Notably, in support of our hypothesis, behavior was significantly and positively correlated with MEMRI signal intensity in the NAC. As neuronal uptake of manganese is regulated by calcium channels, these results indicate that MEMRI is a powerful research tool to study neuronal activity in freely behaving animals and to guide new calcium channel‐based therapies for the treatment of cocaine abuse and dependence. Copyright © 2015 John Wiley & Sons, Ltd.
Effect of Duodenal–Jejunal Bypass Surgery on Glycemic Control in Type 2 Diabetes: A Randomized Controlled Trial
Authors: Petry Tarissa Z. , Fabbrini Elisa , Otoch Jose P. , Carmona Murilo A. , Caravatto Pedro P. , Salles João E. , Sarian Thais , Correa Jose L. , Schiavon Carlos A. , Patterson Bruce W. , Cohen Ricardo , Klein Samuel
Published: September 2015

Objective

To determine whether upper gastrointestinal tract (UGI) bypass itself has beneficial effects on the factors involved in regulating glucose homeostasis in patients with type 2 diabetes (T2D).

Methods

A 12‐month randomized controlled trial was conducted in 17 overweight/obese subjects with T2D, who received standard medical care (SC, n = 7, BMI = 31.7 ± 3.5 kg/m2) or duodenal–jejunal bypass surgery with minimal gastric resection (DJBm) (n = 10; BMI = 29.7 ± 1.9 kg/m2). A 5‐h modified oral glucose tolerance test was performed at baseline and at 1, 6, and 12 months after surgery or starting SC.

Results

Body weight decreased progressively after DJBm (7.9 ± 4.1%, 9.6 ± 4.2%, and 10.2 ± 4.3% at 1, 6, and 12 months, respectively) but remained stable in the SC group (P < 0.001). DJBm, but not SC, improved: (1) oral glucose tolerance (decreased 2‐h glucose concentration, P = 0.039), (2) insulin sensitivity (decreased homeostasis model assessment of insulin resistance, P = 0.013), (3) early insulin response to a glucose load (increased insulinogenic index, P = 0.022), and (4) overall glycemic control (reduction in HbA1c with fewer diabetes medications).

Conclusions

DJBm causes moderate weight loss and improves metabolic function in T2D. However, our study cannot separate the benefits of moderate weight loss from the potential therapeutic effect of UGI tract bypass itself on the observed metabolic improvements.
Synthesis, characterization and cytotoxicity of polyethylene glycol coupled zinc oxide–chemically converted graphene nanocomposite on human OAW42 ovarian cancer cells
Authors: Naskar Atanu , Bera Susanta , Bhattacharya Rahul , Roy Sib Sankar , Jana Sunirmal
Published: September 2015

Present work reports for the first time on successful synthesis of polyethylene glycol (PEG) coupled ZnO–chemically converted graphene (CCG) nanocomposites (ZGP) as well as pristine nano ZnO (ZO), ZnO–CCG (ZG) and ZnO–PEG (ZP) by adopting facile solvothermal method using zinc acetate dihydrate, graphene oxide and PEG as precursor materials. X‐ray diffraction measurement of samples showed nanocrystalline hexagonal ZnO. Agglomeration of ZnO nanoparticles formed microspheres in ZG, and the agglomeration was found to be decreased in ZGP as revealed from field emission scanning and transmission electron microscopes. Raman and FTIR spectral studies evidenced the presence of chemically interacted CCG and polyethylene glycol in the nanocomposites. Content of the organics in ZGP was determined by thermogravimetric analysis. A mechanism was proposed on the formation of ZGP nanocomposite. From the measurement ofin vitrocytotoxicity, quantitative cell viability (CV) of human ovarian cancer cell line, OAW42, was obtained from control to a maximum of 200 µg/ml of sample concentrations. An excellent CV of the cancer cells was observed (nearly ~80% of viable cells at 50 µg/ml dose with respect to the control) for ZGP compared to ZO, ZG and ZP samples. The effective role of CCG and PEG in ZGP nanocomposite for enhancing the cell viability was explained. This simple strategy could be beneficial for synthesis of other metal oxide towards biomedical applications. Copyright © 2015 John Wiley & Sons, Ltd.
Preparation of antibacterial cellulose with a monochloro‐s‐triazine‐based N‐halamine biocide
Authors: Jiang Zhiming , Liu Yin , Li Rong , Ren Xuehong , Huang T. S.
Published: September 2015

A novel monochloro‐s‐triazine‐based N‐halamine precursor, 4‐(4‐(5,5‐dimethylhydantoin‐3‐ethylamino)‐6‐chloro‐1,3,5‐triazinylamino)‐benzenesulfonate (HB), was synthesized and characterized by proton nuclear magnetic resonance. The reactive dyes dyeing method was applied to bond HB onto cotton fabrics, and the treated fabrics were confirmed by Fourier transform infrared spectrometer and scanning electron microscope. The chlorinated HB‐treated fabrics showed excellent antibacterial efficacies against Staphylococcus aureus and Escherichia coli O157:H7 and inactivated all inoculated bacteria within 1 min of contact. Interestingly, it was found that the finishing process and following chlorination caused smaller tensile strength loss of cotton fabrics than the traditional pad‐dry‐cure method. Furthermore, the antimicrobial cotton fabrics exhibited good stability and regenerability. Copyright © 2015 John Wiley & Sons, Ltd.
Adenoma development in familial adenomatous polyposis and MUTYH‐associated polyposis: somatic landscape and driver genes
Authors: Rashid Mamunur , Fischer Andrej , Wilson Cathy H , Tiffen Jessamy , Rust Alistair G , Stevens Philip , Idziaszczyk Shelley , Maynard Julie , Williams Geraint T , Mustonen Ville , Sampson Julian R , Adams David J
Published: September 2015

Familial adenomatous polyposis (FAP) and MUTYH‐associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient, and a further 63 adenomas by capillary sequencing (41 FAP, 22 MAP). With these data we examined the profile of mutated genes, the mutational signatures and the somatic mutation rates, observing significant diversity in the constellations of mutated driver genes in different adenomas, and loss‐of‐function mutations in WTX (9%; p < 9.99e‐06), a gene implicated in regulation of the WNT pathway and p53 acetylation. These data extend our understanding of the early events in colorectal tumourigenesis in the polyposis syndromes. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Non‐ and semipolar AlInN one‐dimensionally lattice‐matched to GaN for realization of relaxed buffer layers for strain engineering in optically active GaN‐based devices
Authors: Buß E. R. , Horenburg P. , Rossow U. , Bremers H. , Meisch T. , Caliebe M. , Scholz F. , Hangleiter A.
Published: September 2015

In this contribution, we demonstrate that for non‐ and semipolar AlInN one‐dimensionally lattice‐matched to GaN, controlled relaxation in different in‐plane directions of the growth surface can be induced. All of our samples were grown on GaN templates on patterned r‐plane sapphire as well as on m‐oriented 6H‐SiC substrates and free‐standing pseudo‐bulk GaN substrates. The InN mole fraction of the AlInN is varied from 18% up to 28% corresponding to one‐dimensional lattice matching in various in‐plane directions of the growth surface. By controlling the composition as well as the thickness, we realized one‐dimensional relaxation of the AlInN layers along the nonlattice‐matched direction. This opens new perspectives for strain and polarization engineering in optically active layers grown subsequently and gives new possibilities to design high indium‐containing GaInN quantum well structures for efficient long wavelength light emitters.
Sample size planning for phase II trials based on success probabilities for phase III
Authors: Götte Heiko , Schüler Armin , Kirchner Marietta , Kieser Meinhard
Published: September 2015

In recent years, high failure rates in phase III trials were observed. One of the main reasons is overoptimistic assumptions for the planning of phase III resulting from limited phase II information and/or unawareness of realistic success probabilities. We present an approach for planning a phase II trial in a time‐to‐event setting that considers the whole phase II/III clinical development programme. We derive stopping boundaries after phase II that minimise the number of events under side conditions for the conditional probabilities of correct go/no‐go decision after phase II as well as the conditional success probabilities for phase III. In addition, we give general recommendations for the choice of phase II sample size. Our simulations show that unconditional probabilities of go/no‐go decision as well as the unconditional success probabilities for phase III are influenced by the number of events observed in phase II. However, choosing more than 150 events in phase II seems not necessary as the impact on these probabilities then becomes quite small. We recommend considering aspects like the number of compounds in phase II and the resources available when determining the sample size. The lower the number of compounds and the lower the resources are for phase III, the higher the investment for phase II should be. Copyright © 2015 John Wiley & Sons, Ltd.
Idealized simulations of the effect of Taiwan topography on the tracks of tropical cyclones with different sizes
Authors: Tang Chi Kit , Chan Johnny C. L.
Published: September 2015

This is the third part of a study of the effect of topography on tropical cyclone (TC) tracks. In previous parts, idealized simulations were conducted using the Weather Research and Forecasting model to study the underlying mechanisms for the upstream northward deflection of a TC and the effects of local and remote topography. The initial TC size was the same in all these simulations. In this third part, the track deflections of TCs with different sizes are investigated. As in the two earlier parts, the simulations are made on a beta plane with no background flow.

For a TC approaching Taiwan, there is an apparent optimal TC size with the largest northward deflection. However, an appreciable track deflection is only found for smaller TCs approaching Taiwan directly. In addition, as might be expected, the onset location of the northward deflection is closer to Taiwan for smaller TCs. Moreover, the contribution from diabatic heating is opposite to that from horizontal advection (HA) in the potential vorticity tendency (PVT) calculation due to the vertical wind shear induced by the terrain‐induced gyres although HA is still the dominant term in the PVT equation.

A southward deflection on the eastern side of Taiwan is found in some smaller TC cases. A looping track occurs for a medium‐size TC approaching central Taiwan and a V‐shape track is found for a small‐size TC approaching northern Taiwan. Among the cases, some similarities can be found. First, the gyre flow becomes weak so that the TC is slowed down. Second, an individual cyclonic gyre is found on the southeastern side of Taiwan so that the TC is deflected westward and then southward. Third, another newly generated gyre pair pushes the TC northward after the southward deflection.
The Force Between Moving Charges
Authors: Bush V.
Published: September 2015

A theory of the force between moving charges, originally treated by Gauss and Weber, is developed. It involves a variant charge and an invariant mass, and is hence contrary to restricted relativity. It leads correctly to all our laws for electric circuits without the agency of a magnetic field. Some of the immediate objections to this scheme of attack are treated. It is considered in the light of the Kaufmann‐Bucherer results. Applied to atomistics it gives the same results as were obtained by Sommerfeld for fine structure by the use of restricted relativity. It gives, for an electron revolving about a nucleus, a critical diameter within which the electron may become imprisoned, and this diameter is computed to be of the order of magnitude believed experimentally to be the diameter of the atomic nucleus.
On the lnviscid Theory of Rotating Fluids
Authors: Greenspan H. P.
Published: September 2015

Conservation theorems for “energy” and mean circulation in an inviscid rotating fluid are stated in their most general forms (which do not presume the existence of inertial modes). The geostrophic motion that contains all the mean circulation of an initial velocity field is identified as the time average of the flow. A preliminary study of the in viscid motion inside a closed cone reveals many singular features and indicates that the inertial wave spectrum may be continuous.
On the Initial Value Problem for Rotating Stratified Flow
Authors: Howard Louis N. , Siegmann William L.
Published: September 2015

The time‐dependent properties of the flow generated by a small disturbance of a rigidly rotating, compressible, non‐dissipative fluid in a gravitational field are derived, without restricting the spacial dependence of the gravitational field or the shape of the rigid container. The conserved quantities are used to characterize in a new way the time‐independent portion of the flow in terms of data from the initial disturbance.
On the Ratio of Consecutive Eigenvalues in N‐Dimensions
Authors: Thompson Colin J.
Published: September 2015

It is proved that λ2 ≤ (1 + 4/N)λ1 where λ1 ≤ λ2 ≤ ··· are the eigenvalues of the N‐dimensional Laplace operator in a domain D with vanishing boundary conditions. This extends the N = 2 case of Payne, Pólya and Weinberger and the result is independent of the domain D.
Instability of a Vortex Sheet Leaving a Semi‐Infinite Plate
Authors: Orszag S. A. , Crow S. C.
Published: September 2015

The growth of undulations along an infinite vortex sheet is a classical problem of stability theory. Here we modify that problem by including the effects of a boundary: the vortex sheet is assumed to leave a rigid semi‐infinite plate and to undergo spatially growing undulations downstream. The usual solution for a doubly infinite sheet is corrected by the Wiener‐Hopf technique to account for the presence of the plate. The correction depends sensitively on whether a Kutta condition is enforced at the trailing edge. Two Kutta conditions, called rectified and full, are suggested to apply depending on conditions in the unperturbed flow. In either case, the correction due to the plate becomes negligible half a wavelength downstream from the trailing edge.
An Experimental Study of Inertial Waves in a Closed Cone
Authors: Beardsley R. C.
Published: September 2015

An experimental study of inertial waves in a closed cone is presented in which the inertial waves are excited by a slight periodic oscillation superimposed on the cone's basic rotation rate. The dynamic pressure field is measured along the cone's rotation axis; no standing modal structure is observed, confirming Greenspan's (1969) argument that the closed cone appears open to inertial oscillations and the inertial wave spectrum is continuous. Similar pressure measurements made in the frustum of a right circular cone show that removal of the singular apex of the cone leads to standing wave modes.
The Evolution of Multi‐Phase Modes for Nonlinear Dispersive Waves
Authors: Ablowitz M. J. , Benney D. J.
Published: September 2015

A method is devised to study the evolution of a system of waves which locally have a multiply periodic structure. The present theory generalizes the results obtained by Whitham for the development of a single periodic wave train subject to large scale variations. The interactions are fully nonlinear.
The Rotation of a Gravitating Sphere in a Monatomic Gas, II
Authors: Foster M. R.
Published: September 2015

The purpose of this work is to study the fluid motion caused by the high speed rotation of a gravitating sphere in a monatomic gas. It has been possible to find a stable steady solution only for very small Prandtl number, which can be interpreted to mean an optically thick gas. The flow is characterized by a flat radial jet in the equatorial plane and a viscous boundary layer on the spherical surface which, in some cases, lies beneath a thermal boundary layer. That the outer region must be hydrostatic puts very stringent constraints on the associated velocity field which necessitate still another boundary layer on the sphere. This last layer is shown to be unstable to small disturbances in certain temperature ranges. Finally, a similar solution that exists for order one Prandtl number must be disregarded because this last boundary layer is always unstable.
The Nonlinear Critical Layer in a Slightly Stratified Shear Flow
Authors: Kelly R. E. , Maslowe S. A.
Published: September 2015

An attempt is made in this paper to extend the nonlinear critical layer analysis, as developed for homogeneous shear flows by Benney and Bergeron [1] and Davis [2], to the case of a stratified shear flow. Although the analysis is restricted to small values of the Richardson number evaluated at the edge of the critical layer, it is definitely shown that buoyancy leads to the formation within the critical layer region of thin velocity and thermal boundary layers which tend to reduce the local Richardson number. We suggest that this result has considerable relevance to the phenomenon of clear air turbulence. As in the homogeneous case, no phase change of the disturbance takes place across the nonlinear critical layer.
A Proof of the Griffiths Inequalities for the X‐Y Model
Authors: Gallavotti G.
Published: September 2015

We present a simple generalization of the Griffiths inequalities to the X ‐ Y model.
Configurations Maximizing the Number of Pairs of Hamming‐Adjacent Lattice Points
Authors: Kleitman D. J. , Krieger M. M. , Rothschild B. L.
Published: September 2015

The following question is considered: Which sets of k lattice points among the nd points in a d‐dimensional cube of length n maximize the number of pairs of points differing in only one coordinate? It is shown that maximal configurations for any (d, n, k) are obtained by choosing the first k points in a lexicographic ordering of the points by coordinates. Some possible generalizations of the problem are discussed.
Dynamics of a Local Perturbation in the XY Model. I—Approach to Equilibrium
Authors: Abraham D. B. , Barouch E. , Gallavotti G. , Martin‐Löf A.
Published: September 2015

The magnetisation and spin correlation functions of the X–Y model are analysed exactly when the system is subjected to a local perturbation of the magnetic field in the z‐direction. When such a perturbation is removed, these quantities approach their equilibrium values asymptotically as (time)−1.
Approximation of the vth Root of N
Authors: Everett C. J. , Metropolis N.
Published: September 2015

We present a class of functions gK(w), K ≥ 2, for which the recursive sequences wn + 1 = gK(wn) converge to N1/v with relative error
. Newton's method results when K = 2. The coefficients of the gK(w) form a triangle, which is Pascal's for v = 2. In this case, if w1 = x1/y1, where x1, y1 is the first positive solution of Pell's equation x2 − Ny2 = 1, then wn + 1 = xn + 1/yn + 1 is the Knpth or 2Knpth convergent of the continued fraction for
, its period p being even or odd.
Numerical Simulation of Incompressible Flows Within Simple Boundaries. I. Galerkin (Spectral) Representations
Authors: Orszag Steven A.
Published: September 2015

Galerkin (spectral) methods are explored for the numerical simulation of incompressible flows within simple boundaries. A major part of the paper is devoted to the development of transform methods for efficient simulation of flows in box geometries with periodic and free‐slip boundary conditions. Techniques for incorporating known symmetries and invariances into transform methods are illustrated for the Taylor‐Green vortex. Galerkin methods for accurate and efficient representation of rigid no‐slip boundary conditions are also explained. A class of pseudospectral approximations is introduced in order to handle more complicated dynamical interactions in more complicated geometries. Later papers in this series will demonstrate the important advantages of spectral methods over finite‐difference methods for simulation of many of the flows of current interest and will present specific numerical results for various transition and turbulent flows.
Applications of Slowly Varying Nonlinear Dispersive Wave Theories
Authors: Ablowitz M. J.
Published: September 2015

Previous theories for the slow dispersion of singly periodic and multiply periodic nonlinear wavetrains are applied to various examples. Stability of the solution with respect to large scale variations and possible shocks in the wave properties (frequency, wavenumber, and amplitude) are discussed. The general approach is also used to analyze certain aperiodic waves.
The Generation of Clear Air Turbulence by Nonlinear Waves
Authors: Maslowe S. A.
Published: September 2015

The structure of the critical layer in a stratified shear flow is investigated for finite‐amplitude waves at high Reynolds numbers. Under such conditions, which are characteristic of the Clear Air Turbulence environment, nonlinear effects will dominate over diffusive effects. Nevertheless, it is shown that viscosity and heat‐conduction still play a significant role in the evolution of such waves. The reason is that buoyancy leads to the formation of thin diffusive shear layers within the critical layer. The local Richardson number is greatly reduced in these layers and they are, therefore, likely to break down into turbulence. A nonlinear mechanism is thus revealed for producing localized instabilities in flows that are stable on a linear basis. The analysis is developed for arbitrary values of the mean flow Richardson number and results are obtained numerically.
Approximate Methods for Obtaining Multi‐Phase Modes in Nonlinear Dispersive Wave Problems
Authors: Ablowitz M. J.
Published: September 2015

Perturbation and numerical methods are used to find singly periodic and multiply periodic solutions to equations which arise in the study of nonlinear wave propagation. Approximation techniques such as these are essential in those cases where exact representations of the modes are not feasible.
On the Evaluation of Iteration Parameters for the Boundary Vorticity
Authors: Israeli M.
Published: September 2015

A method suggested for computing iteration parameters for the boundary vorticity of slightly viscous fluids (Israeli 1970) is reconsidered. A more general model is constructed which is applicable to rotating and non‐rotating flows in several coordinate systems, and each coordinate can be independently stretched. The iteration parameters can be used with either the time centered implicit (Crank‐Nicholson) or with the alternating direction implicit (Peaceman‐Rachford) time differencing approximation.
The Motion of a Vortex Pair in a Stratified Atmosphere
Authors: Saffman P. G.
Published: September 2015

The movement of a horizontal vortex pair through an inhomogeneous fluid is considered. The problem is formulated first for the case when the ambient fluid is uniform, the fluid moving with the vortex pair has a different density, and the motion is supposed laminar and inviscid. An approximate solution is obtained, which predicts that the distance between the vortices stays constant and the vortices accelerate at a constant rate. This solution is then applied to motion in a stratified atmosphere and it is found that the vortices oscillate vertically with a frequency and amplitude depending on the initial conditions and the stratification. Finally, approximate equations are constructed to describe the effects of turbulent entrainment into the fluid moving with the vortex pair, and an estimate of the damping is obtained.
Critical Layers m Parallel Flows
Authors: Haberman Richard
Published: September 2015

Finite amplitude neutrally stable two‐dimensional disturbances in parallel flows are determined for large Reynolds numbers when both nonlinearity and viscosity are important in the critical layer. The phase shift across the critical layer depends on the local vertical Reynolds number in the critical layer, and it varies monotonically between the value zero of the nonlinear theory and — π of the viscous theory. An O(ɛ½) distortion of both the mean and fundamental harmonic is shown to be necessary. The eigenvalue problem is solved for long waves yielding neutral modes which link the two previous theories. In particular certain difficulties of the nonlinear theory are resolved.
On Trapped Modes of Rotating Fluids in Spherical Shells
Authors: Israeli Moshe
Published: September 2015

The question of existence of axisymmetric, equatorially trapped modes in rotating spherical shells (Stern, 1963; Stewartson and Rickard, 1969) is approached by means of a numerical simulation. The existence of one trapped mode is confirmed, and the dependence of its frequency on the thickness of the shell is investigated. The ray theoretical approach of Bretherton (1964) is also reconsidered, and it is found that in a shell of given thickness there are only a limited number of closed ray patterns which are confined to the vicinity of the equator. A continuous band of frequencies is associated with each one of these rays. It is found that the frequencies derived by the numerical simulation for thin shells agree with the maximum frequency in the first of these bands. It is conjectured that this fact may be associated with the viscous boundary conditions driving the forced oscillations inside the shell.
Boundary Value Problems with a Turning Point
Authors: Lakin W. D.
Published: September 2015

A boundary value problem involving a second order differential equation on an interval containing a single turning point is considered. Asymptotic approximations to solutions of the differential equation are obtained by the comparison equation method. An essential feature of the work is that domains of validity are restricted so that all approximations are “complete” in the sense of Olver. Asymptotic solutions of the boundary value problem are studied in the special cases where resonance is possible.
A Forcing Mechanism for Spiral Density Waves in Galaxies
Authors: Feldman S. I. , Lin C. C.
Published: September 2015

In this paper, we consider gas dynamical models of spiral galaxies in which there is a rigidly rotating, weakly barlike structure in the central regions. It is found that, in the neighborhood of the corotation circle, this barlike structure forces a trailing spiral wave. Such a driven wave could then propagate inwards to the bar and complete a feedback loop to maintain the spiral structure. For basic distributions typical of our Galaxy, if a ten‐per‐cent oval distortion is assumed, the strength of the induced spiral field is found to be of the order of a few per cent of the axisymmetric field, in agreement with observational data.