bluuebunny/crossref_metadata_2025 huggingface dataset:
The prognostic impact of high Nijmegen breakage syndrome (NBS1) gene expression in ERG‐negative prostate cancers lacking PTEN deletion is driven by KPNA2 expression
Authors: Grupp Katharina , Boumesli Rebecca , Tsourlakis Maria Christina , Koop Christina , Wilczak Waldemar , Adam Meike , Sauter Guido , Simon Ronald , Izbicki Jakob Robert , Graefen Markus , Huland Hartwig , Steurer Stefan , Schlomm Thorsten , Minner Sarah , Quaas Alexander
Published: February 2014

The Nijmegen breakage syndrome (NBS1) gene was suggested as a prostate cancer susceptibility gene. This study was undertaken to determine, whether NBS1 expression is linked to clinically or molecularly relevant subgroups of prostate cancer. NBS1 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancer specimens. NBS1 expression was absent or only weakly detectable in benign prostate. In prostate cancers, NBS1 expression was found in 81.3% of interpretable tumors and was considered strong in 41.3% of cases. NBS1 upregulation was tightly linked to ERG‐positive cancers (p < 0.0001). Within ERG‐negative cancers, strong NBS1 immunostaining was linked to advanced pathological tumor stage, high Gleason grade, and positive nodal status (p < 0.0001 each), while high NBS1 immunostaining was only weakly associated with advanced pathological tumor stage in ERG‐positive cancers (p = 0.0099). A comparison with chromosomal deletions revealed a strong NBS1 upregulation in PTEN‐deleted cancers, while deletions of 3p13, 5q21 and 6q15 did not affect NBS1 expression. High NBS1 expression was linked to biochemical recurrence in ERG‐negative and PTEN non‐deleted cancers (p < 0.0001), which was largely driven by high KPNA2 karyopherin alpha 2 expression. In conclusion, our study identifies an association of NBS1 expression with surrogates of genomic instability in prostate cancer including TMPRSS2‐ERG rearrangements and PTEN deletion. The prognostic impact of NBS1 expression in ERG‐negative, PTEN non‐deleted cancers was dependent of the expression status of its interaction partner KPNA2.
Past and Future Solid‐State NMR Spectroscopy Studies at the Convergence Point between Biology and Materials Research
Authors: Goobes Gil
Published: February 2014

Many cellular events involve attachment of proteins to the surfaces of rigid or semi‐rigid solid materials, such as the inorganic materials in the extracellular matrix of hard tissue, and the macromolecular scaffolds made of actin and tubulin filaments in the cytoskeleton. Understanding these processes on a fundamental level will have far‐reaching repercussions for the design of biomaterials, biomedical research, and biomineralization. Numerous studies have reported structural changes experienced by proteins as they adhere to surfaces, yet there are only a few examples in which detailed views of protein conformation and alignment on surfaces were measured. Modern multidimensional solid‐state NMR spectroscopy is timely situated to unveil molecular details of these processes and shed light on many fundamental questions related to recognition of surfaces by biomolecules. Targeting these questions is currently at the focal point of many research fields and can lead to insights and breakthroughs in biotechnology and in biomimetic material design.
Molecular Sensing Using Hyperpolarized Xenon NMR Spectroscopy
Authors: Palaniappan Krishnan K. , Francis Matthew B. , Pines Alexander , Wemmer David E.
Published: February 2014

Molecular imaging is the determination of the spatial location and concentration of specific molecules in a sample of interest. Sophisticated modern magnetic resonance imaging machines can collect NMR spectra from small‐volume elements within a sample, enabling local chemical analysis. However, abundant water and fat signals limit detection of metabolites to near mM concentrations. Alternatively, targeted relaxation contrast agents enhance the relaxation of the strong water signal where they bind. A comparison of images with and without a contrast agent shows the target distribution, but high µM concentrations are needed. We have developed an approach that exploits the strong signals of hyperpolarized 129Xe (an inert reporter introduced for imaging). The imaging contrast agents are composed of a biological recognition motif to localize the agent (antibodies or aptamers) and covalently tethered cryptophane cages. Xenon binds to the cryptophane and though chemical exchange saturation transfer creates contrast in a xenon image. Imaging agents can deliver many cages per target, giving detection limits in the pM concentration range. The evolution and principles of this approach are described herein.
Fish multigeneration test with preliminary short‐term reproduction assay for estrone using Japanese medaka (Oryzias latipes)
Authors: Nakamura Ataru , Tamura Ikumi , Takanobu Hitomi , Yamamuro Masumi , Iguchi Taisen , Tatarazako Norihisa
Published: February 2014

The most potent chemicals potentially causing adverse effects on fish species are estrogens in human waste. Sewage is a source of these estrogens and it is difficult to reduce. In particular, although the bioactivity of estrone is estimated to be about half of that of estradiol, multiple studies report that more than 100 ng l–1 of estrone can be detected in urban rivers, including discharges from sewage treatment works; approximately two times as high as estradiol. Few studies have been conducted to investigate the long‐term effects of estrone on wildlife; therefore, we conducted fish multigeneration test using Japanese medaka (Oryzias latipes). Medaka were exposed to estrone for 27 weeks across three generations in environmentally relevant concentrations, being 5.74, 11.4, 24.0, 47.1 and 91.4 ng l–1. No effects on reproduction were observed in the first generation; however, a decline in egg production and fertility was observed in the second generation exposed to 91.4 ng l–1 estrone, which is lower than some known environmental concentrations in urban environments. Furthermore, histopathological abnormalities were observed in the third generation exposed to both 47.1 and 91.4 ng l–1, suggesting that estrone possibly exerts severe effects on the third or later generations. However, appearances of testis–ova were observed in the second and third generation they were not consistent with actual effects on reproduction, notwithstanding the testis‐ova is regarded as the key evidence for endocrine disruption. Accordingly, we consider that qualitative measurement of abnormalities using histopathological observations is required for appropriate evaluation of endocrine disruption. Copyright © 2014 John Wiley & Sons, Ltd.
Ephrin B2/EphB4 Mediates the Actions of IGF-I Signaling in Regulating Endochondral Bone Formation
Authors: Wang Yongmei , Menendez Alicia , Fong Chak , ElAlieh Hashem Z , Chang Wenhan , Bikle Daniel D
Published: February 2014

Ephrin B2/EphB4 mediates interactions among osteoblasts (OBs), osteoclasts (OCLs), and chondrocytes to regulate their differentiation. We investigated the role of ephrin B2/EphB4 signaling in mediating the anabolic effects of insulin-like growth factor-I (IGF-I) and parathyroid hormone (PTH) on those cells and overall endochondral bone formation. Immunohistochemistry demonstrated that the expression of ephrin B2 in OBs, OCLs, and osteocytes, and the expression of EphB4 in OBs and osteocytes was dramatically decreased in global IGF-I knockout mice. Inactivation of EphB4 by EphB4 small, interfering RNA (siRNA) in cultured bone marrow stromal cells significantly decreased the mRNA levels of OB differentiation markers and abolished the stimulatory effects of IGF-I on these markers. Blocking the interaction of EphB4 and ephrin B2 in the OB-OCL cocultures with the EphB4 specific peptide TNYL-RAW or deletion of ephrin B2 in OCL prior to coculture led to fewer and smaller tartrate-resistant acid phosphatase (TRAP)-positive cells, decreased expression of OB differentiation markers, and blunted response to IGF-I for both OCL and OB differentiation. In the growth plate, both ephrin B2 and EphB4 are expressed in late stage proliferating and prehypertrophic chondrocytes, and their expression was decreased in mice lacking the IGF-I receptor specifically in chondrocytes. In vitro, blocking the interaction of EphB4 and ephrin B2 in chondrogenic ATDC5 cells with TNYL-RAW significantly decreased both basal and IGF1-induced expression of type II and type X collagen. In the cocultures of ATDC5 cells and spleen cells (osteoclast precursors), TNYL-RAW decreased the numbers of TRAP-positive cells and the expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and receptor activator of NF-κB (RANK), and blocked their stimulation by IGF-I. Our data indicate that IGF-I/IGF-IR signaling promotes OB, OCL, and chondrocyte differentiation via ephrin B2/EphB4 mediated cell-cell communication. © 2014 American Society for Bone and Mineral Research.
ROCK‐2 Is Associated With Focal Adhesion Maturation During Myoblast Migration
Authors: Goetsch K.P. , Snyman C. , Myburgh K.H. , Niesler C.U.
Published: February 2014

Satellite cell migration is critical for skeletal muscle growth and regeneration. Controlled cell migration is dependent on the formation of mature focal adhesions between the cell and the underlying extracellular matrix (ECM). These cell–ECM interactions trigger the activation of signalling events such as the Rho/ROCK pathway. We have previously identified a specific role for ROCK‐2 during myoblast migration. In this study we report that ROCK inhibition with Y‐27632 increases C2C12 myoblast velocity, but at the expense of directional migration. In response to Y‐27632 an increased number of smaller focal adhesions were distributed across adhesion sites that in turn were clearly larger than sites in untreated cells, suggesting a reduction in focal adhesion maturation. We also confirm ROCK‐2 localisation to the focal adhesion sites in migrating myoblasts and demonstrate a change in the distribution of these ROCK‐2 containing adhesions in response to Y‐27632. Taken together, our observations provide further proof that ROCK‐2 regulates directional myoblast migration through focal adhesion formation and maturation. J. Cell. Biochem. 115: 1299–1307, 2014. © 2014 Wiley Periodicals, Inc.
Regulatory Roles of miRNA in the Human Neural Stem Cell Transformation to Glioma Stem Cells
Authors: Liu Shuang , Yin Feng , Zhang Jianning , Wicha Max S. , Chang Alfred E. , Fan Wenhong , Chen Ling , Fan Ming , Li Qiao
Published: February 2014

To investigate the expressional alternation of microRNAs (miRNA) during the malignant transformation and development of human glioma, we measured miRNA expression profile as well as mRNA expression profile in normal human neural stem cells (hNSCs) and human glioma stem cells (hGSCs). We found 116 miRNA up‐regulated and 62 miRNA down‐regulated in GSCs. On the other hand, we identified 1,372 mRNA down‐regulated, and 1,501 mRNA up‐regulated in GSCs compared to those in NSCs. We then analyzed the pathways and the predicted target genes of the miRNAs which differ significantly in expression between GSCs and NSCs using the statistical enrichment methods. These target mRNAs are involved in many cancer‐related signaling pathways, such as cell cycle, axon guidance, glioma development, adhesion junction, MAPK and Wnt signaling. Furthermore, we obtained the differently expressed miRNA‐target relationships according to the θ value which is used to calculate the regulation extent of miRNA‐target and using the databases of miRanda, Targetscans and Pictar. Among the top 10 miRNA‐target relationships, hsa‐miR‐198 and its potential targeted gene DCX and NNAT were selected for validation, and NNAT was found to be the direct target of miR‐198. Finally, the functional roles of miR‐155–5p and miR‐124–3p whose expressions altered significantly between GSCs and NSCs were addressed. Our results provide new clues for the potential mechanisms involved in the origin and development of glioma. Clinically, the altered miRNAs may serve as potential targets and diagnostic tools for novel therapeutic strategies of glioblastoma. J. Cell. Biochem. 115: 1368–1380, 2014. © 2014 Wiley Periodicals, Inc.
Computer assisted surgery, preoperative planning and navigation for pancreatic cancer
Authors: Abe Yuta , Itano Osamu , Kitago Minoru , Shinoda Masahiro , Yagi Hiroshi , Hibi Taizo , Takano Kiminori , Chiba Naokazu , Kawachi Shigeyuki , Shimazu Motohide , Kitagawa Yuko
Published: February 2014

Currently, the best treatment for locally advanced pancreatic cancer is considered to be safe and effective surgery, followed by appropriate additional therapies implemented as quickly as possible. The use of diagnostic imaging to assist surgery is being researched in a range of institutions. This report introduces the results of a study into the optimized contrast conditions for computed tomography (CT)‐volume rendering image generation, effective in providing image support for pancreatic surgery, and introduces actual cases in which imaging support was used in surgery. The authors demonstrated that the conventional contrast protocols used in making a diagnosis are not necessarily the optimum protocols for image creation. It is thought that the use of image‐supported surgery will improve the safety and effectiveness of pancreatic surgery.
Prevalence of HPV16 E1‐1374^63nt variants in Greek women
Authors: Tsakogiannis D. , Kyriakopoulou Z. , Darmis F. , Ruether I.G.A. , Dimitriou T.G. , Orfanoudakis G. , Panotopoulou E. , Markoulatos P.
Published: February 2014

Recent studies have focused on sequence variation of the HPV16 E1 gene. The present study investigates the prevalence of E1‐1374^63nt duplication in the Greek population, and the sequence variation at the 5′ end of the E1 and E6 genes from samples that harbored this genetic alteration. Fifty HPV16 positive cervical samples, derived from Greek patients were investigated. The 5′ end of the E1 gene was amplified through PCR and the variant amplicons were cloned, sequenced, and bioinformatically analyzed for selective pressure. The E1‐1374^63nt duplication was identified in 24% of the examined samples, with the same prevalence in both high and low‐grade cervical malignancies. The E1‐1374^63nt duplication was linked to the European variant lineage (x2 = 5.076, P < 0.024) and it was significantly associated with the nucleotide variation A1053C (x2 = 23.102, P < 0.0001). Molecular evolution analyses anticipate that the E1‐1374^63nt duplication induces functional constraints on the 5′ end of E1 gene, and it is proposed that this duplication might not affect negatively the function or structure of the E1 protein. The E1‐1374^63nt duplication is prevalent in the Greek population, whereas the A1053C variation might constitute a significant marker for the characterization of the E1‐1374^63nt variant in the Greek population, thus providing significant information about viral pathogenicity. J. Med. Virol. 86:778–784, 2014. © 2014 Wiley Periodicals, Inc.
Experimental evidence for the effects of task repetitiveness on mental strain and objective work performance
Authors: Häusser Jan Alexander , Schulz‐Hardt Stefan , Schultze Thomas , Tomaschek Anne , Mojzisch Andreas
Published: February 2014

People frequently have to work in high repetitive jobs. Previous research has focused exclusively on the effects of task repetitiveness on well‐being, while neglecting effects on work performance. In the present study, we aimed to fill this void by conducting two workplace simulations with experimental manipulations of task repetitiveness. Participants worked for about 5 hours at either a computer workstation, compiling computer hardware packages according to customer requests (Experiment 1, N = 160), or at an assembly line, piecing together equipment sets for furniture (Experiment 2, N = 213). Both experiments provide consistent evidence that high repetitiveness has a detrimental effect on well‐being, whereas work performance increases under conditions of high repetitiveness. On a practical level, our study hence shows that high task repetitiveness is a double‐edged sword for both employees and organizations. On a conceptual level, our findings emphasize the necessity to account for both mental strain and work performance when examining the effects of task repetitiveness. Copyright © 2014 John Wiley & Sons, Ltd.
Differential gene expression in Acidithiobacillus ferrooxidans LR planktonic and attached cells in the presence of chalcopyrite
Authors: Ossa Henao Diana Marcela , Vicentini Renato , Rodrigues Viviane Drumond , Bevilaqua Denise , Ottoboni Laura Maria Mariscal
Published: February 2014

Acidithiobacillus ferrooxidans is commonly used in bioleaching operations to recover copper from sulfide ores. It is commonly accepted that A. ferrooxidans attaches to mineral surfaces by means of extracellular polymeric substances (EPS), however the role of type IV pili and tight adherence genes in this process is poorly understood. Genes related to the formation of type IV pili and tight adherence were identified in the genome of the bacterium, and in this work, we show that A. ferrooxidans actively expresses these genes, as demonstrated by quantitative real‐time PCR analysis using cells incubated with chalcopyrite for 2 h. Significant differences in gene expression were observed between planktonic and adhered cells, with the level of expression being much greater in planktonic cells. These results might indicate that planktonic cells can actively adhere to the substrate. A bioinformatics analysis of interaction networks of the tight adherence and type IV pilus assembly genes revealed a strong relationship between conjugation systems (tra operon) and regulatory systems (PilR, PilS).
Southern Hemisphere winter cyclone activity under recent and future climate conditions in multi‐model AOGCM simulations
Authors: Grieger J. , Leckebusch G.C. , Donat M.G. , Schuster M. , Ulbrich U.
Published: February 2014

This article investigates extratropical winter cyclone activity in the Southern Hemisphere (SH) in a multi‐model ensemble (MME) of coupled atmosphere–ocean general circulation model (AOGCM) simulations of recent and potential future climate conditions. Most individual models and also the ensemble mean yield good reproductions of the typical cyclone characteristics found in reanalysis data, although some individual models show peculiarities, and a large inter‐model spread in terms of quantity of identified cyclone tracks is found. We use a scaling approach to combine the cyclone statistics from different models into a MME. In the future climate simulations, the total number of SH cyclones is reduced, whereas an increased number of strong cyclones is found in most models and in the ensemble mean. The long term trend with respect to all cyclones is a robust feature throughout the simulations. It is associated with a general poleward shift, shown to be related to both tropical upper tropospheric warming and shifting meridional sea surface temperature gradients in the Southern Ocean. The magnitude of increased strong cyclone activity has a focus on the Eastern Hemisphere. It is clearly influenced by natural variability and thus depends on specific time periods considered.
Utilization of climate information and soil moisture estimates to provide monthly and sub‐monthly streamflow forecasts
Authors: Wang Hui , Fu Xiang
Published: February 2014

Streamflow forecasts at monthly and sub‐monthly time scales, e.g. 10‐day period, are critical for making decisions to allocate water for different users and mitigate possible flooding. Adaptive forecasting of 10‐day streamflow is still challenging, although persistence prediction models sometimes have good performance when streamflow has strong lag‐correlation. This study proposes a scheme of proving monthly and sub‐monthly flow forecasts at the beginning of the month and updating sub‐monthly forecasts subsequently. It examines a principal component regression method to provide monthly average streamflow and sub‐monthly, e.g. 10‐day, average streamflow forecasts, utilizing gridded precipitation forecasts from climate models and soil moisture estimates from hydrological models. Monthly streamflow forecasts are first obtained. It is then disaggregated to 10‐day streamflow based on historical observations using a nonparametric approach. The disaggregated 10‐day streamflow forecasts are further improved by incorporating streamflow and soil moisture estimates in the previous 10 days. Hence, sub‐monthly flow can be improved adaptively. The proposed approach is demonstrated for monthly and sub‐monthly streamflow forecasts in July at the Yangtze River, the largest river in China. The correlation between monthly streamflow forecasts and observation is 0.46 in leave‐one‐out cross‐validation mode. Updated sub‐monthly streamflow shows better skill than disaggregated sub‐monthly forecasts. To examine the impact of the accuracy of monthly streamflow forecasts on disaggregated 10‐day streamflow, synthetic streamflow time series of different level of forecasting skills were examined. Results show that the higher skill of synthetic monthly streamflow forecasts, the lower forecasts error. The value of soil moisture estimates in proving streamflow forecasts is also examined.
Regional changes of climate extremes over Australia – a comparison of regional dynamical downscaling and global climate model simulations
Authors: Perkins Sarah E. , Moise Aurel , Whetton Penny , Katzfey Jack
Published: February 2014

Dynamically downscaled simulations are an attractive source of information for those requiring greater regional detail than what Global Climate Models (GCMs) can provide. However, an important question is whether the information derived from downscaled simulations is plausible. Some recent studies have attempted to answer this question using an ‘added value’ framework. This study takes an alternate approach by comparing projectedchangesof climate extremes from Regionally Dynamically Downscaled Model (RDM) ensembles to the hostGCMensemble over the Australian continent. Bias‐corrected sea‐surface temperatures (SSTs) from five Coupled Model Inter‐comparison Program Phase 3 (CMIP3)GCMsare used to force two different configurations of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) Conformal Cubic Atmosphere Model (CCAM), run at 60 km. For each member of the twoCCAMensembles and eachGCMensemble member, a selection of extreme events and their changes were calculated for minimum temperature, maximum temperature and precipitation for the climate of the 20th century (20c3m; 1980–1999) andA2(2081–2100) simulations. We find thatCCAMshows finer spatial detail in the current distribution of extremes and also the projected climate change signal thanGCMs. While the projected change in extreme temperatures has a similar pattern inCCAMcompared to the hostGCMs, the projected changes in rainfall are not only more spatially detailed but also different at the large scale. This, however, does not infer that climate change signal inCCAMis necessarily more or less physically plausible than theGCMs. In order to ascertain the plausibility and usefulness ofRDMsimulations, we strongly encourage a critical assessment of the required simulations before their use in adaptation and impacts planning, which includes a comparison to similar simulations from the hostGCM(s).
Hydrological links in Southeastern South America: soil moisture memory and coupling within a hot spot
Authors: Ruscica R. C. , Sörensson A. A. , Menéndez C. G.
Published: February 2014

Southeastern South America has been identified as a hot spot of soil moisture and evapotranspiration coupling efficiency during austral summer in a previous study. Here, hydrological processes such as coupling and memory of soil moisture, evapotranspiration and precipitation and the links between these variables are discussed on the daily time scale over this region. The correlations between surface variables, rainfall persistence and soil moisture memory are discussed over three subregions selected on basis of their coupling efficiency and mean daily intensity of precipitation. The relationship between surface climate and land cover is qualitatively assessed. The memory, or statistical persistence, is longer and has a more robust spatial pattern for the root zone than for the top soil moisture. Where the coupling efficiency between soil moisture and evapotranspiration is high, the evapotranspiration is regulated by soil moisture conditions independently on the intensity of precipitation, whereas in a region with low coupling efficiency and high intensity, the evapotranspiration is regulated by the atmosphere. The coupling efficiency is in general related to the memory of the root‐zone layer, since the soil state is modified when the soil moisture and the atmosphere interact, resulting in an anticorrelation between these metrics. The persistence of rainfall is another factor that modulates the memory. Nevertheless, there are some areas around the La Plata River where both the coupling efficiency and the memory are relatively high, such as Uruguay and the northeast of Argentina, where an improvement of soil moisture initial conditions could improve predictability of surface variables on a monthly timescale.
Isolated limb infusion with melphalan and actinomycin D for melanoma: A systematic review
Authors: Kroon Hidde M. , Huismans Anna M. , Kam Peter C.A. , Thompson John F.
Published: February 2014

Isolated limb infusion (ILI) was developed as a simplified and minimally invasive alternative to isolated limb perfusion (ILP) to treat unresectable limb melanoma. A number of centers around the world have reported their results using this procedure. In this study a systematic review of reported ILI experiences was undertaken. A literature search was conducted according to the guidelines for systematic reviews in order to select eligible papers reporting limb toxicity and response rates following ILI using melphalan and actinomycin D to treat limb melanoma. A total of 576 patients from seven publications were included. Regional toxicity following ILI was low: no visible effect of the treatment or slight erythema or edema was observed in 79% of the patients, while considerable erythema and/or edema with blistering was experienced by 19%. In 2% there was a threatened or actual compartment syndrome. No procedure‐related amputation was reported. Complete response occurred in 33% of the patients and partial response in 40%, an overall response rate of 73%. Stable disease and progressive disease were achieved in 14% and 13% of the patients, respectively. This first systematic review of ILI procedures using melphalan and actinomycin D indicates that regional toxicity was generally low, with satisfactory response rates. When comparing ILI and ILP, it must be borne in mind that ILI is often performed in significantly older patients and in patients with higher stages of disease, which decreases the likelihood of a favorable response. J. Surg. Oncol. 2014 109:348–351. © 2014 Wiley Periodicals, Inc.
Swallowing function after laryngeal cleft repair: More than just fixing the cleft
Authors: Osborn Alexander J. , de Alarcon Alessandro , Tabangin Meredith E. , Miller Claire K. , Cotton Robin T. , Rutter Michael J.
Published: February 2014

Objectives/Hypothesis

To evaluate and describe the swallowing function in children after laryngeal cleft repair.

Study Design

Ten‐year (2002–2012) retrospective chart review. Setting: Academic tertiary care pediatric otolaryngology practice.

Methods

Records of 60 children who had surgical repair of laryngeal cleft (ages 2 weeks–14 years) and postoperative functional endoscopic evaluation of swallowing or videofluoroscopic swallow studies were examined retrospectively.

Results

Twenty‐nine children had one postoperative swallow evaluation, 19 children had two, 4 children had three, 5 children had four, and 3 children had five. Median time to the first evaluation was 10.8 weeks (interquartile range [IQR]: 36.5, 231). On the final swallow evaluation, 34 (57%) children demonstrated normal swallowing parameters, 12 (20%) children showed penetration, and 14 (23%) children showed aspiration. Forty‐three (72%) children were able to take everything by mouth normally or with minor behavioral modifications, 11 (18%) children required thickened fluids, and six (10%) children were kept nil per os (NPO). Mean improvement on the penetration‐aspiration (pen‐asp) scale was 2.13. On multivariable analysis, neurodevelopmental issues and gastronomy tube use were associated with the need for NPO status.

Conclusion

Despite a high rate of surgical success, a substantial minority of children have persistent swallowing dysfunction after laryngeal cleft repair. Swallowing dysfunction after repair is multifactorial and arises from concomitant neurologic, anatomic, or other comorbidities that contribute to oropharyngeal and pharyngeal dysphagia. Based on our results, we recommend a testing schedule for postoperative swallowing evaluations after cleft repair.

Level of Evidence

4. Laryngoscope, 124:1965–1969, 2014
Terrestrial Arthropods in the Initial Restoration Stages of Anthracite Coal Mine Spoil Heaps in Northwestern Spain: Potential Usefulness of Higher Taxa as Restoration Indicators
Authors: Tizado Emilio Jorge , Núñez‐Pérez Etelvina
Published: February 2014

An “edaphic‐landscape” restoration was performed in two anthracite coal mine spoil heaps located in NW Spain as a demonstration and pilot program for the restoration of coal mine spoils. Terrestrial arthropods were used to monitor the process as an alternative to the use of secondary succession of plants or physico‐chemical indicators of soils. This study analyzes the usefulness of the terrestrial arthropods at different taxonomic levels (orders of Arthropoda, families of Coleoptera, and species of Carabidae) as restoration indicators in the initial restoration stages. The terrestrial arthropods respond rapidly to restoration, and the results may be explained by short‐term increase in abiotic factors resulting from the applied techniques, mainly the animal origin of the organic matter added and the biodegradable coconut geotextile. Carabidae is of relatively low value as a short‐term restoration indicator at a specific level. Coleoptera provided the best information for interpreting the ecological results over the short term and had the best relationship with the cost of identification. Likewise, the results showed that the edaphic‐landscape restoration leads to an abnormal arthropod assemblage in the short term because of an excessive abundance of isopods and polydesmids. No clear convergence appeared toward any of the terrestrial arthropod communities present in the grassland, scrubland, or woodland semi‐natural areas, which were used as reference end point. The restoration indicator value produced by the higher taxonomic levels of the studied terrestrial arthropods may be useful and cost‐effective for assessing short‐term changes caused by environmental restorations performed to recover ecosystems affected by mining activities. Copyright © 2014 John Wiley & Sons, Ltd.
On ultra‐high temperature oxidation of Cr–Cr3Si alloys: Effect of germanium
Authors: Soleimani‐Dorcheh A. , Donner W. , Galetz M. C.
Published: February 2014

The oxidation behavior of Cr–Cr3(Si1−XGeX) alloys with the composition range Cr85GeXSi1−X (0 < X < 15) was studied at 1350 °C. Thermogravimetric measurements showed improved oxidation kinetics by alloying up to 2 at% of Ge, but a significant weight loss was observed when higher Ge was added. Phase analysis and composition of the spalled oxide scales and subscale alloy substrates revealed that eskolaite (Cr2O3) forms the protective scale, while SiO2 (cristobalite) is locally formed below the chromia scale. Addition of up to 2 at% altered the morphology of locally formed silica and subsequently affected the spallation of chromia scale. The morphological observations of the different chromia scales are discussed for all alloys oxidized at 1350 °C.
PEG‐Based Microgels Formed by Visible‐Light‐Mediated Thiol‐Ene Photo‐Click Reactions
Authors: Fraser Andrew K. , Ki Chang Seok , Lin Chien‐Chi
Published: February 2014

Step‐growth PEG‐based microgels are produced via three liquid–liquid two‐phase suspension polymerization systems: i) hexane with surfactants Span80/Tween80; ii) mineral oil with surfactant Pluronic F‐68; and iii) surfactant‐free dextran‐rich aqueous solution. Following short vortexing to create monomer droplets, microgels are polymerized by a visible‐light‐initiated thiol‐ene photo‐click reaction using eosin‐Y as the only photoinitiator. The use of hexane as the organic phase and Span‐80/Tween‐80 as the surfactants leads to PEG microgels with entrapped solvent droplets that dissolve rapidly with time. Microgels polymerized in mineral oil with surfactant Pluronic F‐68 contain no entrapped droplets and are more uniform with smaller sizes. Visible‐light‐cured step‐growth thiol‐ene microgels can also be photo­polymerized in a surfactant‐free aqueous two‐phase system. The sizes of the microgels formed in aqueous phase are one order of magnitude smaller than those formed in organic solvent. Dual‐layer microgels are also prepared using two‐step thiol‐ene reactions.

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Bilinear decompositions for the product space
Authors: Ky Luong Dang
Published: February 2014

In this paper, we improve a recent result by Li and Peng on products of functions in and , where is a Schrödinger operator with V satisfying an appropriate reverse Hölder inequality. More precisely, we prove that such products may be written as the sum of two continuous bilinear operators, one from into , the other one from into , where the space is the set of distributions f whose grand maximal function satisfies

urn:x-wiley:dummy:mana201200101:equation:mana201200101-math-0012
Fourier transform ion cyclotron resonance (FT ICR) mass spectrometry: Theory and simulations
Authors: Nikolaev Eugene N. , Kostyukevich Yury I. , Vladimirov Gleb N.
Published: February 2014

Fourier transform ion cyclotron resonance (FT ICR) mass spectrometer offers highest resolving power and mass accuracy among all types of mass spectrometers. Its unique analytical characteristics made FT ICR important tool for proteomics, metabolomics, petroleomics, and investigation of complex mixtures. Signal acquisition in FT ICR MS takes long time (up to minutes). During this time ion–ion interaction considerably affects ion motion and result in decreasing of the resolving power. Understanding of those effects required complicated theory and supercomputer simulations but culminated in the invention of the ion trap with dynamic harmonization which demonstrated the highest resolving power ever achieved. In this review we summarize latest achievements in theory and simulation of FT ICR mass spectrometers. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:219–258, 2016.
Experimental Method to Discriminate RAFT Models between Intermediate Termination and Slow Fragmentation via Comparison of Rates of Miniemulsion and Bulk Polymerization
Authors: Suzuki Kiyoshi , Kanematsu Yuta , Miura Takashi , Minami Masayuki , Satoh Shuzaemon , Tobita Hidetaka
Published: February 2014

A simple model discrimination method for RAFT polymerization mechanism, proposed on a theoretical basis, is applied to the polystyryl dithiobenzoate‐mediated styrene polymerization. It is confirmed that the intermediate termination (IT) is the major reason for the rate retardation. The method utilizes the theoretical finding that the IT model shows a significantly larger polymerization rate in miniemulsion compared with the corresponding bulk polymerization, while the slow fragmentation model does not change the polymerization rate. The miniemulsion polymerization rate increases as the droplet size is made smaller, which agrees reasonably well with the theoretical prediction. The present model discrimination method is easy to apply, and would provide great insight into both basic and applied research in RAFT polymerization.
A practical approach to remote longitudinal follow‐up of Parkinson's disease: The FOUND study
Authors: Tanner Caroline M. , Meng Cheryl C. , Ravina Bernard , Lang Anthony , Kurlan Roger , Marek Kenneth , Oakes David , Seibyl John , Flagg Emily , Gauger Lisa , Guest Dolores D. , Goetz Christopher G. , Kieburtz Karl , DiEuliis Diane , Fahn Stanley , Elliott Robin A. , Shoulson Ira
Published: February 2014

The objective of this study was to examine a remote method for maintaining long‐term contact with Parkinson's disease (PD) patients participating in clinical studies. Long‐term follow‐up of PD patients is needed to fill critical information gaps on progression, biomarkers, and treatment. Prospective in‐person assessment can be costly and may be impossible for some patients. Remote assessment using mail and telephone contact may be a practical follow‐up method. Patients enrolled in the multi‐center Longitudinal and Biomarker Study in Parkinson's Disease (LABS‐PD) in‐person follow‐up study in 2006 were invited to enroll in Follow‐up of Persons With Neurologic Diseases (FOUND), which is overseen by a single center under a separate, central institutional review board protocol. FOUND uses mailed questionnaires and telephone interviews to assess PD status. FOUND follow‐up continued when LABS‐PD in‐person visits ended in 2011. Retention and agreement between remote and in‐person assessments were determined. In total, 422 of 499 (84.5%) of eligible patients volunteered, AND 96% of participants were retained. Of 60 patients who withdrew consent from LABS‐PD, 51 were retained in FOUND. Of 341 patients who were active in LABS‐PD, 340 were retained in FOUND (99.7%) when the in‐person visits ceased. Exact agreement between remote and in‐person assessments was ≥ 80% for diagnosis, disease features (eg, dyskinesias), and PD medication. Correlation between expert‐rated and self‐reported Unified Parkinson's Disease Rating Scale and Movement Disorder Society Unified Parkinson's Disease Rating Scale, which were examined at times separated by several months, was moderate or substantial for most items. Retention was excellent using remote follow‐up of research participants with PD, providing a safety net when combined with in‐person visits, and also is effective as a stand‐alone assessment method, providing a useful alternative when in‐person evaluation is not feasible. © 2014 International Parkinson and Movement Disorder Society
Mood‐stabilizers differentially affect housekeeping gene expression in human cells
Authors: Powell Timothy R. , Powell‐Smith Georgia , Haddley Kate , Mcguffin Peter , Quinn John , Schalkwyk Leonard C. , Farmer Anne E. , D'Souza Ursula M.
Published: February 2014

Recent studies have revealed that antidepressants affect the expression of constitutively expressed “housekeeping genes” commonly used as normalizing reference genes in quantitative polymerase chain reaction (qPCR) experiments. There has yet to be an investigation however on the effects of mood‐stabilizers on housekeeping gene stability. The current study utilized lymphoblastoid cell lines (LCLs) derived from patients with mood disorders to investigate the effects of a range of doses of lithium (0, 1, 2 and 5 mM) and sodium valproate (0, 0.06, 0.03 and 0.6 mM) on the stability of 12 housekeeping genes. RNA was extracted from LCLs and qPCR was used to generate cycle threshold (Ct) values which were input into RefFinder analyses. The study revealed drug‐specific effects on housekeeping gene stability. The most stable housekeeping genes in LCLs treated: acutely with sodium valproate wereACTBandRPL13A;acutely with lithium wereGAPDHandATP5B; chronically with lithium wereATP5BandCYC1. The stability ofGAPDHandB2Mwere particularly affected by duration of lithium treatment. The study adds to a growing literature that the selection of appropriate housekeeping genes is important for the accurate normalization of target gene expression in experiments investigating the molecular effects of mood disorder pharmacotherapies.Copyright © 2014 John Wiley & Sons, Ltd.
MRI contrasts in high rank rotating frames
Authors: Liimatainen Timo , Hakkarainen Hanne , Mangia Silvia , Huttunen Janne M.J. , Storino Christine , Idiyatullin Djaudat , Sorce Dennis , Garwood Michael , Michaeli Shalom
Published: February 2014

Purpose

MRI relaxation measurements are performed in the presence of a fictitious magnetic field in the recently described technique known as RAFF (Relaxation Along a Fictitious Field). This method operates in the 2nd rotating frame (rank n = 2) by using a nonadiabatic sweep of the radiofrequency effective field to generate the fictitious magnetic field. In the present study, the RAFF method is extended for generating MRI contrasts in rotating frames of ranks 1 ≤ n ≤ 5. The developed method is entitled RAFF in rotating frame of rank n (RAFFn).

Theory and Methods

RAFFn pulses were designed to generate fictitious fields that allow locking of magnetization in rotating frames of rank n. Contrast generated with RAFFn was studied using Bloch‐McConnell formalism together with experiments on human and rat brains.

Results

Tolerance to B0 and B1 inhomogeneities and reduced specific absorption rate with increasing n in RAFFn were demonstrated. Simulations of exchange‐induced relaxations revealed enhanced sensitivity of RAFFn to slow exchange. Consistent with such feature, an increased grey / white matter contrast was observed in human and rat brain as n increased.

Conclusion

RAFFn is a robust and safe rotating frame relaxation method to access slow molecular motions in vivo. Magn Reson Med 73:254–262, 2015. © 2014 Wiley Periodicals, Inc.
Prediction of cartilage compressive modulus using multiexponential analysis of T2 relaxation data and support vector regression
Authors: Irrechukwu Onyi N. , Thaer Sarah Von , Frank Eliot H. , Lin Ping‐Chang , Reiter David A. , Grodzinsky Alan J. , Spencer Richard G.
Published: February 2014

Evaluation of mechanical characteristics of cartilage by magnetic resonance imaging would provide a noninvasive measure of tissue quality both for tissue engineering and when monitoring clinical response to therapeutic interventions for cartilage degradation. We use results from multiexponential transverse relaxation analysis to predict equilibrium and dynamic stiffness of control and degraded bovine nasal cartilage, a biochemical model for articular cartilage. Sulfated glycosaminoglycan concentration/wet weight (ww) and equilibrium and dynamic stiffness decreased with degradation from 103.6 ± 37.0 µg/mg ww, 1.71 ± 1.10 MPa and 15.3 ± 6.7 MPa in controls to 8.25 ± 2.4 µg/mg ww, 0.015 ± 0.006 MPa and 0.89 ± 0.25MPa, respectively, in severely degraded explants. Magnetic resonance measurements were performed on cartilage explants at 4 °C in a 9.4 T wide‐bore NMR spectrometer using a Carr–Purcell–Meiboom–Gill sequence. Multiexponential T2 analysis revealed four water compartments with T2 values of approximately 0.14, 3, 40 and 150 ms, with corresponding weight fractions of approximately 3, 2, 4 and 91%. Correlations between weight fractions and stiffness based on conventional univariate and multiple linear regressions exhibited a maximum r2 of 0.65, while those based on support vector regression (SVR) had a maximum r2 value of 0.90. These results indicate that (i) compartment weight fractions derived from multiexponential analysis reflect cartilage stiffness and (ii) SVR‐based multivariate regression exhibits greatly improved accuracy in predicting mechanical properties as compared with conventional regression. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
A hybrid geometric + algebraic multigrid method with semi‐iterative smoothers
Authors: Lu Cao , Jiao Xiangmin , Missirlis Nikolaos
Published: February 2014

We propose a multigrid method for solving large‐scale sparse linear systems arising from discretizations of partial differential equations, such as those from finite element and generalized finite difference methods. Our proposed method has the following two characteristics. First, we introduce a hybrid geometric+algebraic multigrid method, or HyGA, to leverage the rigor, accuracy, and efficiency of geometric multigrid (GMG) for hierarchical unstructured meshes, with the flexibility of algebraic multigrid (AMG). Second, we introduce efficient smoothers based on the Chebyshev–Jacobi method for both symmetric and asymmetric matrices. We also introduce a unified derivation of restriction and prolongation operators for weighted‐residual formulations over unstructured hierarchical meshes and apply it to both finite element and generalized finite difference methods. We present numerical results of our method for Poisson equations in both 2‐D and 3‐D and compare our method against the classical GMG and AMG as well as Krylov subspace methods. Copyright © 2014 John Wiley & Sons, Ltd.
Fibroblast growth factor receptor 3 activation plays a causative role in urothelial cancer pathogenesis in cooperation with Pten loss in mice
Authors: Foth Mona , Ahmad Imran , van Rhijn Bas WG , van der Kwast Theodorus , Bergman Andre M , King Louise , Ridgway Rachel , Leung Hing Y , Fraser Sioban , Sansom Owen J , Iwata Tomoko
Published: February 2014

Although somatic mutations and overexpression of the tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) are strongly associated with bladder cancer, evidence for their functional involvement in the pathogenesis remains elusive. Previously we showed that activation of Fgfr3 alone is not sufficient to initiate urothelial tumourigenesis in mice. Here we hypothesize that cooperating mutations are required for Fgfr3‐dependent tumourigenesis in the urothelium and analyse a mouse model in which an inhibitor of Pi3k–Akt signalling, Pten, is deleted in concert with Fgfr3 activation (UroIICreFgfr3+/K644EPtenflox/flox). Two main phenotypical characteristics were observed in the urothelium: increased urothelial thickness and abnormal cellular histopathology, including vacuolization, condensed cellular appearance, enlargement of cells and nuclei, and loss of polarity. These changes were not observed when either mutation was present individually. Expression patterns of known urothelial proteins indicated the abnormal cellular differentiation. Furthermore, quantitative analysis showed that Fgfr3 and Pten mutations cooperatively caused cellular enlargement, while Pten contributed to increased cell proliferation. Finally, FGFR3 overexpression was analysed along the level of phosphorylated mTOR in 66 T1 urothelial tumours in tissue microarray, which supported the occurrence of functional association of these two signalling pathways in urothelial pathogenesis. Taken together, this study provides evidence supporting a functional role of FGFR3 in the process of pathogenesis in urothelial neoplasms. Given the wide availability of inhibitors specific to FGF signalling pathways, our model may open the avenue for FGFR3‐targeted translation in urothelial disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.