bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Two‐Photon Excitation and d→f Energy Transfer in a Water‐Soluble IrIII/EuIII Dyad: Two Luminescence Components from One Molecule for Cellular Imaging
Authors: Baggaley Elizabeth , Cao Deng‐Ke , Sykes Daniel , Botchway Stanley W. , Weinstein Julia A. , Ward Michael D.
Published: June 2014

The first example of cell imaging using two independent emission components from a dinuclear d/f complex is reported. A water‐stable, cell‐permeable IrIII/EuIII dyad undergoes partial Ir→Eu energy transfer following two‐photon excitation of the Ir unit at 780 nm. Excitation in the near‐IR region generated simultaneously green Ir‐based emission and red Eu‐based emission from the same probe. The orders‐of‐magnitude difference in their timescales (Ir ca. μs; Eu ca. 0.5 ms) allowed them to be identified by time‐gated detection. Phosphorescence lifetime imaging microscopy (PLIM) allowed the lifetime of the Ir‐based emission to be measured in different parts of the cell. At the same time, the cells are simultaneously imaged by using the Eu‐based emission component at longer timescales. This new approach to cellular imaging by using dual d/f emitters should therefore enable autofluorescence‐free sensing of two different analytes, independently, simultaneously and in the same regions of a cell.
Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective Synthesis
Authors: Delidovich Irina V. , Simonov Alexandr N. , Taran Oxana P. , Parmon Valentin N.
Published: June 2014

The formose reaction (FR) has been long the focus of intensive investigations as a simple method for synthesis of complex biologically important monosaccharides and other sugar‐like molecules from the simplest organic substrate—formaldehyde. The fundamental importance of the FR is predominantly connected with the ascertainment of plausible scenarios of chemical evolution which could have occurred on the prebiotic Earth to produce the very first molecules of carbohydrates, amino‐ and nucleic acids, as well as other vitally important substances. The practical importance of studies on the FR is the elaboration of catalytic methods for the synthesis of rare and non‐natural monosaccharides and polyols. This Minireview considers the FR from the point of view of chemists working in the field of catalysis with emphasis on the mechanisms of numerous parallel and consequent catalytic transformations that take place during the FR. Based on its kinetics, the FR may be considered as a non‐radical chain process with degenerate branching. The Minireview also considers different approaches to the control of selectivity of carbohydrate synthesis from formaldehyde and lower monosaccharides.
Model‐based conservation planning of the genetic diversity of Phellodendron amurense Rupr due to climate change
Authors: Wan Jizhong , Wang Chunjing , Yu Jinghua , Nie Siming , Han Shijie , Zu Yuangang , Chen Changmei , Yuan Shusheng , Wang Qinggui
Published: June 2014

Climate change affects both habitat suitability and the genetic diversity of wild plants. Therefore, predicting and establishing the most effective and coherent conservation areas is essential for the conservation of genetic diversity in response to climate change. This is because genetic variance is a product not only of habitat suitability in conservation areas but also of efficient protection and management. Phellodendron amurense Rupr. is a tree species (family Rutaceae) that is endangered due to excessive and illegal harvesting for use in Chinese medicine. Here, we test a general computational method for the prediction of priority conservation areas (PCAs) by measuring the genetic diversity of P. amurense across the entirety of northeast China using a single strand repeat analysis of twenty microsatellite markers. Using computational modeling, we evaluated the geographical distribution of the species, both now and in different future climate change scenarios. Different populations were analyzed according to genetic diversity, and PCAs were identified using a spatial conservation prioritization framework. These conservation areas were optimized to account for the geographical distribution of P. amurense both now and in the future, to effectively promote gene flow, and to have a long period of validity. In situ and ex situ conservation, strategies for vulnerable populations were proposed. Three populations with low genetic diversity are predicted to be negatively affected by climate change, making conservation of genetic diversity challenging due to decreasing habitat suitability. Habitat suitability was important for the assessment of genetic variability in existing nature reserves, which were found to be much smaller than the proposed PCAs. Finally, a simple set of conservation measures was established through modeling. This combined molecular and computational ecology approach provides a framework for planning the protection of species endangered by climate change.
Vegetation effects on the water balance of mountain grasslands depend on climatic conditions
Authors: Obojes N. , Bahn M. , Tasser E. , Walde J. , Inauen N. , Hiltbrunner E. , Saccone P. , Lochet J. , Clément J. C. , Lavorel S. , Tappeiner U. , Körner Ch.
Published: June 2014

Mountain regions are key for humanity's water supply, and their water yield depends on climatic, soil and vegetation effects. Here we explore the effects of vegetation composition and structure on the water balance of high elevation grasslands with different climatic conditions across the Alps. Using a total of 220 deep seepage collectors with intact soil‐vegetation monoliths in different types of mountain grasslands in the Austrian, French and Swiss Alps, we solved the water balance equation for evapotranspiration (ET) and related the results to biomass, the abundance of certain plant functional types and structural and functional vegetation properties. While daily mean ET during the growing season was similar at all sites, ET to precipitation ratios were significantly higher and ET to potential ET ratios significantly lower at the drier French sites than at the more humid Swiss and Austrian site. Large variability of ET, seepage and soil moisture within all sites pointed at a high influence of vegetation on the water balance. While ET increased significantly with biomass at all sites, the influence of other vegetation properties was site specific. At the more humid, subalpine Austrian site the effects of vegetation on ET were stronger and more diverse than at the higher elevation Swiss site and the drier French sites, where climatic drivers dominated ET. The potential to influence ET and water yield of mountain areas by manipulating the plant canopy with systematic land management is therefore higher in regions with good growing conditions than in areas with harsh climate. Copyright © 2014 John Wiley & Sons, Ltd.
Rheological, Thermal, and Physicochemical Characterization of Animal Fat Wastes for use in Biodiesel Production
Authors: Adewale Peter , Dumont Marie‐Josée , Ngadi Michael
Published: June 2014

The rheological, thermal and physicochemical properties of animal fat wastes (tallow, lard, choice white grease, and yellow grease) are important parameters for an efficient design of equipment and to optimize the processing procedures of biodiesel production. In this study, the physicochemical properties of animal fat waste samples and the correlation of these properties to their thermal and rheological behaviors were elucidated. Pure lard was equally investigated to monitor the effects of impurities on the rheological and thermal properties of the animal fat wastes. It was established that the presence of impurities had effects on the rheological and thermal properties of fats. Additionally, due to the high level of free fatty acid (FFA) present in the wastes, transesterification cannot be applied directly. It will be necessary to reduce the FFA level by using acid pretreatment or enzyme catalyzed transesterification.
Hydrogen Generation from Hydrolysis of Ball‐Milled Al/C Composite Materials: Effects of Processing Parameters
Authors: Niu Feng , Huang Xiani , Gao Tong , Wang Jingang , Qin Laishun , Huang Yuexiang
Published: June 2014

In the present work a parametric investigation on hydrogen evolution by hydrolysis of ball‐milled Al/graphite composite materials with water is reported. The results showed that the addition of NaCl produced some favorable effects on the completeness of the Al hydrolysis reaction with water, particularly at low NaCl weight percentage levels, but deteriorated the Al reactivity due to large size agglomerates formed during milling process. Using a fine aluminum powder could improve the aluminum hydrolysis reactivity and increase hydrogen generation rate. The hydrogen evolution measurements showed that Al in pellet form exhibited poor hydrolysis reactivity, and increasing the aging time significantly degraded the Al reactivity. The hydrogen evolution rate of the Al/graphite composite materials is also dependent on reaction temperature, and the maximum hydrogen generation rate of 52.4 cm3 min−1 g−1 Al was obtained if the reaction temperature was increased to 75 °C.
New evidences of hydrothermal fluids circulation at the Devonian Kess Kess mounds, Hamar Laghdad (eastern Anti‐Atlas, Morocco)
Authors: Franchi Fulvio , Cavalazzi Barbara , Pierre Catherine , Barbieri Roberto
Published: June 2014

New evidences based on a combination of field and laboratory investigations reinforce the hypotheses that the circulation of warm fluids has remarkably contributed to the origin and development of the Devonian Kess Kess mounds of the Hamar Laghdad Ridge (eastern Anti‐Atlas, Morocco). The limestones of the Hamar Laghdad Ridge were deposited above a structural high generated by calc‐alkaline volcanic activity that has probably fuelled the circulation of warm fluids throughout the overlying carbonate units. The geological and palaeontological attributes described throughout the succession of the Hamar Laghdad Ridge (from the Lochkovian to Frasnian intervals) are interpreted as the result of hydrothermal processes related to a volcanic system. In particular, these attributes seem consistent with a chemo‐physical environment fuelled by the circulation of warm and late magmatic fluids. These attributes include a very low oxygen stable isotope signature (δ18O ~ −10‰) for carbonates. Evidences for a late magmatic fluid circulation consist of volcanic glass and pyroclasts replacement with hydrothermal minerals such as quartz, anatase and clinochlore. Fluids circulating through veins and pores into sediments, and venting to the seafloor, probably induced the formation of cavities where monospecific trilobite communities were detected. The partially silicified trilobite remains are associated with traces of goethite. This iron‐bearing oxide mineral is also present in the upper part of the Hamar Laghdad Ridge. All these attributes are here interpreted as possible evidences for a low‐temperature hydrothermal venting system active during the Lochkovian–Frasnian time span. This study combines an updated revision with new petrographic, geological and geochemical results aimed at providing an overall framework on the origin and early diagenesis of the Devonian succession of Hamar Laghdad. Copyright © 2014 John Wiley & Sons, Ltd.
Wall Shape Effects on Convection Heat Transfer Over a Corrugated Channel
Authors: Jafari Mohammad , Aghajani‐Delavar Mojtaba , Farhadi Mousa , Naysari Amir
Published: June 2014

This study investigates the effects of the wall waviness on forced convection and its fluid flow in a channel bound by two wavy walls. The lattice Boltzmann method based on the boundary fitting method is used to simulate flow and thermal fields in the corrugated channel. The problem is investigated for different Reynolds numbers (50 to 150), wall amplitudes (0 to 0.35), number of wall wavelength (2 to 8), and phase difference of the walls (0 to 270) when the Prandtl number is equal to 0.71 for air flow. The study represents the significant effects of wavy walls on flow and thermal fields in a two‐dimensional channel. It is found when the phase difference between the channel walls has a value equal to 90°; the best heat transfer rate can be achieved in comparison with other geometrical conditions and the flow is likely to be periodically unsteady at lower Reynolds numbers.
Refining understanding of hydrological connectivity in a boreal catchment
Authors: Spence Christopher , Phillips Ross W.
Published: June 2014

Literature has long documented how streamflow response in boreal hillslopes and catchments is influenced by storage capacities, thresholds, and landscape and runoff pathway heterogeneity. More recently, the influence these traits have on streamflow has been interpreted through the concept of hydrological connectivity. However, the nature of hydrological connectivity in boreal catchments has only begun to be described. The focus of hydrological connectivity studies at the catchment scale has been on discerning from which areas does runoff originate and when, but not necessarily discovering the source waters of this streamflow. This has been the realm of studies investigating residence time and runoff pathways. This article summarizes an investigation in a 155‐km2 catchment in Canada's Northwest Territories that applied both hydrometric and geochemical methods to measure streamflow response, storage state, connectivity and source waters. The goal of this research was to determine if a catchment scale metric of connectivity could be sensitive to changes in source waters and runoff pathways in a boreal landscape, so as to improve the predictive role of connectivity metrics. Nine runoff events from three water years were evaluated. There were distinct patterns of hydrological connectivity, which included, among others, a non‐linear relationship with the runoff ratio and hysteresis with streamflow. The results indicate that one metric of connectivity alone could not encapsulate connectivity extent and quality, identify water sources and be used successfully to predict runoff response. Multiple metrics were needed that further encapsulated the role of precipitation and hydrological processes on both structural and dynamic connectivity. © 2014 Her Majesty the Queen in Right of Canada. Hydrological Processes. © 2014 John Wiley & Sons, Ltd.
Reflux composition influences the level of NF‐κB activation and upstream kinase preference in oesophageal adenocarcinoma cells
Authors: McAdam E. , Haboubi H.N. , Griffiths A.P. , Baxter J.N. , Spencer‐Harty S. , Davies C. , Jenkins G.J.
Published: June 2014

Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease is the primary cause of OA, usually managed with acid suppression therapy. However, this often does little to control carcinogenic bile acid reflux. The transcription factor nuclear factor kappa B (NF‐κB) plays a key role in the pathogenesis of OA and its activity is associated with a poor response to chemotherapy, making it an attractive therapeutic target. We sought to decipher the role of different bile acids in NF‐κB activation in oesophageal cell lines using short, physiologically relevant exposure times. The effect of an acidic or neutral extracellular pH was investigated concurrently, to mimic in vivo conditions associated with or without acid suppression. We found that some bile acids activated NF‐κB to a greater extent when combined with acid, whereas others did so in its absence, at neutral pH. The precise composition of an individual's reflux, coupled with whether they are taking acid suppressants may therefore dictate the extent of NF‐κB activation in the oesophagus, and hence the likelihood of histological progression and chemotherapy success. Regardless of pH, the kinase inhibitor of κB kinase was pivotal in mediating reflux induced NF‐κB activation. Its importance was confirmed further as its increased activation was associated with histological progression in patient samples. We identified further kinases important in acid or bile induced NF‐κB signalling in oesophageal cells, which may provide suitable targets for therapeutic intervention.
Peripheral blood cells inform on the presence of breast cancer: A population‐based case–control study
Authors: Dumeaux Vanessa , Ursini‐Siegel Josie , Flatberg Arnar , Fjosne Hans E. , Frantzen Jan‐Ole , Holmen Marit Muri , Rodegerdts Enno , Schlichting Ellen , Lund Eiliv
Published: June 2014

Tumor–host interactions extend beyond the local microenvironment and cancer development largely depends on the ability of malignant cells to hijack and exploit the normal physiological processes of the host. Here, we established that many genes within peripheral blood cells show differential expression when an untreated breast cancer (BC) is present, and harnessed this fact to construct a 50‐gene signature that distinguish BC patients from population‐based controls. Our results were derived from a series of large datasets within our unique population‐based Norwegian Women and Cancer cohort that allowed us to investigate the influence of medications and tumor characteristics on our blood‐based test, and were further tested in two external datasets. Our 50‐gene signature contained cytostatic signals including the specific suppression of the immune response and medications influencing transcription involved in those processes were identified as confounders. Through analysis of the biological processes differentially expressed in blood, we were able to provide a rationale as to why the systemic response of the host may be a reliable marker of BC, characterized by the underexpression of both immune‐specific pathways and “universal” cell programs driven by MYC (i.e., metabolism, growth and cell cycle). In conclusion, gene expression of peripheral blood cells is markedly perturbed by the specific presence of carcinoma in the breast and these changes simultaneously engage a number of systemic cytostatic signals emerging connections with immune escape of BC.
Suitability of Ag‐agar gel for the micro‐extraction of organic dyes on different substrates: the case study of wool, silk, printed cotton and a panel painting mock‐up
Authors: Platania Elena , Lombardi John R. , Leona Marco , Shibayama Nobuko , Lofrumento Cristiana , Ricci Marilena , Becucci Maurizio , Castellucci Emilio
Published: June 2014

A surface‐enhanced Raman spectroscopy (SERS) substrate made of agar gel coupled with silver nanoparticles has been applied to the micro‐extraction and the ultra‐sensitive detection of dyes on pieces of textile of different nature (silk, wool, and printed cotton) and on a mock‐up panel painting. In particular, the Ag‐agar gel substrate previously developed has been improved by the addition of the chelating agent ethylenediaminetetraacetic acid (EDTA), which has been found to play an important role as a stabilizer of the nanocomposite matrix and for the improvement of the micro‐extractive performances of the gel. The system has been confirmed to be non‐destructive and minimally invasive, showing a better capability of trapping the dye molecules inside its structure. Ag‐agar gel‐EDTA has been an invaluable and powerful tool for the characterization of the dye present in a printed cotton sample of unknown chemical composition. SERS analyses, performed on the dried cube of gel following extraction on the sample, have allowed for the identification of the dye. SERS results have been corroborated by high‐performance liquid chromatography analyses. The possibility of easily detecting compounds at very low concentration coupled with the high sensitivity of SERS makes this technique a valid and versatile method for the non‐destructive recognition of chemicals in works of art. Copyright © 2014 John Wiley & Sons, Ltd.
Destination Stakeholders' Perceptions of Volunteer Tourism: An Equity Theory Approach
Authors: Burrai Elisa , Font Xavier , Cochrane Janet
Published: June 2014

This study explores destination stakeholders' perceptions of volunteer tourism (VT) using equity theory. In this paper, 26 semi‐structured interviews were conducted to understand individuals' needs, motivations, expectations and their assessments of inputs and outcomes. Equity theory sheds light on the micro‐level of interaction between residents and volunteers and demonstrates why and how residents of Cusco (Peru) with an active role in VT develop certain perceptions in direct encounters with volunteer tourists. The data reveal how perceptions differ according to the respondents' social roles within VT. Heterogeneity, dynamism and a fluctuation between materialities and affection are discussed as important outcomes of these interactions. Copyright © 2014 John Wiley & Sons, Ltd.
Belowground Bud Bank Responses to Grazing Intensity in the Inner‐Mongolia Steppe, China
Authors: Qian Jianqiang , Wang Zhengwen , Liu Zhimin , Busso Carlos A.
Published: June 2014

Despite the predominant role of bud banks in population regeneration and community dynamics, they have received far less attention than deserved. In particular, it remains unexplored how bud bank size and composition respond to different grazing intensities in grasslands. We investigated the size and composition of bud banks under different grazing intensities and regimes on a typical steppe in Inner Mongolia, China. Our results showed that (i) the total bud density in the traditional grazing regime (grazing and haymaking within the same year in the same paddock; 2,444 ± 141 buds m−2) was 30 ± 11% higher (mean ± standard error; p < 0·05) than that in the mixed grazing regime (grazing and haymaking alternate annually in the same paddock; 1,872 ± 109 buds m−2), but they did not change with increasing grazing intensity, (ii) rhizome buds and bulb buds decreased sharply (p < 0·05) because of grazing in the mixed grazing regime, (iii) bud banks of rhizomatous grasses showed species‐specific responses to the increasing grazing intensity: decreasing in Leymus chinensis (Trin.) Tzvel., increasing in Agropyron cristatum (L.) Gaertn. and unresponsive in Carex duriuscula C. A. Mey. Data indicated that (i) the studied grazing intensities had no significant effects on the total bud bank, suggesting that belowground bud bank seems to be tolerant of grazing and (ii) the responses of bud bank to grazing differed with the bud bank type and species, indicating that bud banks could be used for explaining and predicting the dynamics of a natural grassland plant community. Copyright © 2014 John Wiley & Sons, Ltd.
Highly directional spaser array for the red wavelength region
Authors: Meng Xiangeng , Liu Jingjing , Kildishev Alexander V. , Shalaev Vladimir M.
Published: June 2014

The spaser offers an opportunity to achieve coherent optical sources at nanometer scales due to the extreme confinement of optical fields. However, achievement of spasers with directional propagation in the visible wavelength region remains a challenge thus far, owing to the unique optical feedback mechanism and large dissipative losses of the metal cavity. Here, we experimentally demonstrate for the first time a spaser showing highly directional emission in the visible by using a periodic subwavelength hole array perforated in a metal film, which function as plasmonic nanocavities, along with an organic laser dye to supply gain. The lasing occurs in the red wavelength region and shows a single mode. It is suggested that the optical feedback for spasing is provided by the SPP–Bloch wave, which is supported by the fact that no spasing was attained in aperiodic holes as well as in periodic holes that do not support the SPP–Bloch wave at the spasing wavelength.
σN‐dependent control of acid resistance and the locus of enterocyte effacement in enterohemorrhagic Escherichia coli is activated by acetyl phosphate in a manner requiring flagellar regulator FlhDC and the σS antagonist FliZ
Authors: Mitra Avishek , Fay Pamela A. , Vendura Khoury W. , Alla Zimrisha , Carroll Ronan K. , Shaw Lindsey N. , Riordan James T.
Published: June 2014

In enterohemorrhagic Escherichia coli (EHEC), sigma factor N (σN) regulates glutamate‐dependent acid resistance (GDAR) and the locus of enterocyte effacement (LEE); discrete genetic systems that are required for transmission and virulence of this intestinal pathogen. Regulation of these systems requires nitrogen regulatory protein C, NtrC, and is a consequence of NtrC‐σN‐dependent reduction in the activity of sigma factor S (σS). This study elucidates pathway components and stimuli for σN‐directed regulation of GDAR and the LEE in EHEC. Deletion of fliZ, the product of which reduces σS activity, phenocopied rpoN (σN) and ntrC null strains for GDAR and LEE control, acid resistance, and adherence. Upregulation of fliZ by NtrC‐σN was shown to be indirect and required an intact flagellar regulator flhDC. Activation of flhDC by NtrC‐σN and FlhDC‐dependent regulation of GDAR and the LEE was dependent on σN‐promoter flhDP2, and a newly described NtrC upstream activator sequence. Addition of ammonium chloride significantly altered expression of GDAR and LEE, acid resistance, and adherence, independently of rpoN, ntrC, and the NtrC sensor kinase, ntrB. Altering the availability of NtrC phosphodonor acetyl phosphate by growth without glucose, with acetate addition, or by deletion of acetate kinase ackA, abrogated NtrC‐σN‐dependent control of flhDC, fliZ, GDAR, and the LEE.
The burglar problem with multiple options
Authors: Chen Kai , Ross Sheldon M.
Published: June 2014

We consider the burglar problem in which a burglar can either retire or choose among different types of burglaries, with each type having its own success probability and reward distribution. Some general structural results are established and, in the case of exponentially distributed reward distributions, a solution technique is presented. The burglar problem's relationship to a stochastic knapsack problem with a random exponentially distributed knapsack capacity is shown. © 2014 Wiley Periodicals, Inc. Naval Research Logistics 61: 359–364, 2014
New Equations for the Size Reconstruction of Sturgeon from Isolated Cranial and Pectoral Girdle Bones
Authors: Thieren E. , Van Neer W.
Published: June 2014

Measurements on cranial and pectoral girdle bones of 56 museum specimens of modern sturgeon (Acipenser sturio and A. oxyrinchus) were used for the establishment of regression equations allowing back‐calculation of size from isolated sturgeon remains. Different curve fittings (power, linear, logarithmic and exponential fit) were modeled to retain the most accurate regression. These were then applied to archaeological sturgeon remains (A. sturio/A. oxyrinchus) from Vlaardingen, a Dutch late Neolithic settlement. The back‐calculated lengths obtained on the archaeological remains all stayed within the known size ranges of the two species and allowed making inferences on the possible place of capture of the fish. Copyright © 2014 John Wiley & Sons, Ltd.
KPNA2 is overexpressed in human and mouse endometrial cancers and promotes cellular proliferation
Authors: Ikenberg Kristian , Valtcheva Nadejda , Brandt Simone , Zhong Qing , Wong Christine E , Noske Aurelia , Rechsteiner Markus , Rueschoff Jan H , Caduff Rosmarie , Dellas Athanassios , Obermann Ellen , Fink Daniel , Fuchs Thomas , Krek Wilhelm , Moch Holger , Frew Ian J , Wild Peter J
Published: June 2014

Endometrial cancer is the most frequently occurring malignancy of the female genital tract in Western countries. Although in many cases surgically curable, about 30% of the tumours represent an aggressive and untreatable disease. In an attempt to establish a reliable prognostic marker for endometrial carcinomas disregarding their histological diversity, we investigated the expression of KPNA2, a mediator of nucleocytoplasmic transport, and other cell proliferation‐associated proteins and their correlation with cancer progression. We analysed patient tissue microarrays (TMAs) assembled from 527 endometrial cancer tissue specimens and uterus samples from a Trp53 knockout mouse model of endometrial cancer. Our data show that KPNA2 expression was significantly up‐regulated in human endometrial carcinomas and associated with higher tumour grade (p = 0.026), higher FIGO stage (p = 0.027), p53 overexpression (p < 0.001), activation of the PI3K/AKT pathway, and epithelial–mesenchymal transition. Increased nuclear KPNA2 immunoreactivity was identified as a novel predictor of overall survival, independent of well‐established prognostic factors in Cox regression analyses (hazard ratio 1.7, 95% CI 1.13–2.56, p = 0.01). No significant association between KPNA2 expression and endometrial cancer subtype was detected. In the mouse model, KPNA2 showed increased expression levels from precancerous (EmgD, EIC) to far‐advanced invasive lesions. We further investigated the cell proliferation capacity after siRNA‐mediated KPNA2 knockdown in the human endometrial cancer cell line MFE‐296. KPNA2 silencing led to decreased proliferation of the cancer cells, suggesting interplay of the protein with the cell cycle. Taken together, increased expression of KPNA2 is an independent prognostic marker for poor survival. The mechanism of enhanced nucleocytoplasmic transport by KPNA2 overexpression seems a common event in aggressive cancers since we have shown a significant correlation of KPNA2 expression and tumour aggressiveness in a large variety of other solid tumour entities. Introducing KPNA2 immunohistochemistry in routine diagnostics may allow for the identification of patients who need more aggressive treatment regimens. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Parental acceptance of minimally invasive fetal and neonatal autopsy compared with conventional autopsy
Authors: Kang Xin , Cos Teresa , Guizani Meriem , Cannie Mieke M. , Segers Valérie , Jani Jacques C.
Published: June 2014

Objective

To determine parental acceptance of minimally invasive autopsy (MIA) involving postmortem imaging and organ tissue sampling compared with conventional autopsy and to compare the acceptability of percutaneous versus laparoscopic‐guided biopsy.

Methods

Following termination of pregnancy parents were offered the option of traditional autopsy and subsequently interviewed about their acceptance of MIA. The McNemar test for paired samples was used to assess the difference in acceptance of MIA and conventional autopsy. The Wilcoxon signed‐rank test for paired samples was used to compare the acceptance score for percutaneous versus laparoscopic‐guided biopsy. Logistic regression was selected to study the association of parental acceptance of conventional autopsy and MIA with different variables.

Results

Conventional autopsy was accepted by 42 (60.0%) of the 70 parents. Regression analysis showed that non‐Muslim faith was the only factor significantly associated with acceptance of conventional autopsy (p = 0.030). Of 28 parents who initially refused conventional autopsy, 13(46.4%) subsequently accepted MIA, increasing acceptance to 78.6% (p < 0.001). Regression analysis showed that none of the factors significantly affected MIA acceptance. Parents expressed no preference between postmortem percutaneous versus laparoscopic‐guided biopsy (p = 0.061).

Conclusion

Post‐mortem imaging combined with systematic organ biopsies is highly acceptable among all parents independent of their religion and the method used for organ biopsy. © 2014 John Wiley & Sons, Ltd.
Conserved evolutionary units in the heme‐copper oxidase superfamily revealed by novel homologous protein families
Authors: Pei Jimin , Li Wenlin , Kinch Lisa N. , Grishin Nick V.
Published: June 2014

The heme‐copper oxidase (HCO) superfamily includes HCOs in aerobic respiratory chains and nitric oxide reductases (NORs) in the denitrification pathway. The HCO/NOR catalytic subunit has a core structure consisting of 12 transmembrane helices (TMHs) arranged in three‐fold rotational pseudosymmetry, with six conserved histidines for heme and metal binding. Using sensitive sequence similarity searches, we detected a number of novel HCO/NOR homologs and named them HCO Homology (HCOH) proteins. Several HCOH families possess only four TMHs that exhibit the most pronounced similarity to the last four TMHs (TMHs 9–12) of HCOs/NORs. Encoded by independent genes, four‐TMH HCOH proteins represent a single evolutionary unit (EU) that relates to each of the three homologous EUs of HCOs/NORs comprising TMHs 1–4, TMHs 5–8, and TMHs 9–12. Single‐EU HCOH proteins could form homotrimers or heterotrimers to maintain the general structure and ligand‐binding sites defined by the HCO/NOR catalytic subunit fold. The remaining HCOH families, including NnrS, have 12‐TMHs and three EUs. Most three‐EU HCOH proteins possess two conserved histidines and could bind a single heme. Limited experimental studies and genomic context analysis suggest that many HCOH proteins could function in the denitrification pathway and in detoxification of reactive molecules such as nitric oxide. HCO/NOR catalytic subunits exhibit remarkable structural similarity to the homotrimers of MAPEG (membrane‐associated proteins in eicosanoid and glutathione metabolism) proteins. Gene duplication, fusion, and fission likely play important roles in the evolution of HCOs/NORs and HCOH proteins.
Missing data sensitivity analysis for recurrent event data using controlled imputation
Authors: Keene Oliver N. , Roger James H. , Hartley Benjamin F. , Kenward Michael G.
Published: June 2014

Statistical analyses of recurrent event data have typically been based on the missing at random assumption. One implication of this is that, if data are collected only when patients are on their randomized treatment, the resulting de jure estimator of treatment effect corresponds to the situation in which the patients adhere to this regime throughout the study. For confirmatory analysis of clinical trials, sensitivity analyses are required to investigate alternative de facto estimands that depart from this assumption. Recent publications have described the use of multiple imputation methods based on pattern mixture models for continuous outcomes, where imputation for the missing data for one treatment arm (e.g. the active arm) is based on the statistical behaviour of outcomes in another arm (e.g. the placebo arm). This has been referred to as controlled imputation or reference‐based imputation. In this paper, we use the negative multinomial distribution to apply this approach to analyses of recurrent events and other similar outcomes. The methods are illustrated by a trial in severe asthma where the primary endpoint was rate of exacerbations and the primary analysis was based on the negative binomial model. Copyright © 2014 John Wiley & Sons, Ltd.
Subgroup analyses in cost‐effectiveness analyses to support health technology assessments
Authors: Fletcher Christine , Chuang‐Stein Christy , Paget Marie‐Ange , Reid Carol , Hawkins Neil
Published: June 2014

‘Success’ in drug development is bringing to patients a new medicine that has an acceptable benefit–risk profile and that is also cost‐effective. Cost‐effectiveness means that the incremental clinical benefit is deemed worth paying for by a healthcare system, and it has an important role in enabling manufacturers to obtain new medicines to patients as soon as possible following regulatory approval. Subgroup analyses are increasingly being utilised by decision‐makers in the determination of the cost‐effectiveness of new medicines when making recommendations. This paper highlights the statistical considerations when using subgroup analyses to support cost‐effectiveness for a health technology assessment. The key principles recommended for subgroup analyses supporting clinical effectiveness published by Pagetet al. are evaluated with respect to subgroup analyses supporting cost‐effectiveness. A health technology assessment case study is included to highlight the importance of subgroup analyses when incorporated into cost‐effectiveness analyses. In summary, we recommend planning subgroup analyses for cost‐effectiveness analyses early in the drug development process and adhering to good statistical principles when using subgroup analyses in this context. In particular, we consider it important to provide transparency in how subgroups are defined, be able to demonstrate the robustness of the subgroup results and be able to quantify the uncertainty in the subgroup analyses of cost‐effectiveness. Copyright © 2014 John Wiley & Sons, Ltd.
Reversible data embedding for vector quantization compressed images using search‐order coding and index parity matching
Authors: Qin Chuan , Chang Chin‐Chen , Horng Gwoboa , Huang Ying‐Hsuan , Chen Yen‐Chang
Published: June 2014

Embedding secret data in vector quantization (VQ) compressed images with reversibility has been studied extensively in recent years. However, to date, the reported methods have not achieved satisfactory performances of hiding capacity and image compression ratio simultaneously. In this paper, we propose a reversible embedding method based on search‐order coding (SOC) and index parity matching that can hide secret data into the compressed VQ index, that is, SOC index. If the parity of the candidate SOC index matches the current embedding bit and the error caused by SOC encoding is smaller than a pre‐determined threshold, the length of the stego SOC index after embedding is significantly shorter than the original VQ index. On the receiver side, the embedded secret bits can be easily extracted by checking the parity of stego SOC indices, and all original VQ indices can be recovered correctly. Experimental results demonstrate that our method can achieve greater hiding capacity than the recently reported methods for the same image decompression quality. Copyright © 2014 John Wiley & Sons, Ltd.
Elliptic‐curve scalar multiplication algorithm using ZOT structure
Authors: Almimi Hani , Samsudin Azman , Jahani Shahram
Published: June 2014

The computation of kP over elliptic curves is the dominant operation. It depends on the representation of the scalar k. The binary method is the standard unsigned method that is used to compute the elliptic‐curve (EC) point Q = kP. Researchers found that it is not the most efficient way for implementing EC computations. Other recoding methods such as complementary recoding (CR), nonadjacent form (NAF), and mutual opposite form (MOF) were presented in order to enhance the efficiency of EC computations. Our ZOTEC method that is based on ZOT recoding method was proposed to accelerate the EC computations. ZOTEC can be computed right‐to‐left or left‐to‐right. The recoding process is also faster than NAF and as fast as CR and MOF if the binary conversion is included or excluded. ZOTEC method is more efficient than BIN, CR, MOF, and NAF methods in terms of field complexity and time complexity whenever a field inversion is more expensive than six multiplications for BIN, CR, and MOF, and 8.3 for NAF. Copyright © 2014 John Wiley & Sons, Ltd.
Data privacy breach prevention framework for the cloud service
Authors: Dhasarathan Chandramohan , Thirumal Vengattaraman , Ponnurangam Dhavachelvan
Published: June 2014

This paper examines the privacy awareness and importance of user's secrecy preserving in current ubiquitous cloud computing world. Data stored in the cloud have highly sensitive information. Once the private information gets misused, the probability of privacy breaching increases, which thereby reduces user's trust on cloud providers. In the emerging cloud service‐based internet world, user's information management is a most decisive task. Information stored in the cloud by the finance, healthcare and government sectors makes it all the more challenging because such tasks are to be handled globally. The present scenario therefore demands a new Petri net privacy preserving framework for safeguarding user's privacy and providing consistent and breachless services from the cloud. This is carried out by designing Petri net privacy preserving framework and mitigating privacy using proposed synchronization, sequential, concurrency and conflicts technique. Synchronization, sequential, concurrency and conflicts technique adopts the Petri net model in which employs multi‐agent‐based privacy preserving cohesion technique for handling multiple tasks to prevent the user private information. The proposed technique conveys and collaborates with leading cloud providers to develop, validate, promote, adapt and also increase the need for privacy, flexibility and availability without affecting the performance of cloud service providers and consumers. It acts as an information preserving guard for high secrecy data storage areas. This paper summarizes with few directives towards future research. Copyright © 2014 John Wiley & Sons, Ltd.
Using an instrumental variable to test for unmeasured confounding
Authors: Guo Zijian , Cheng Jing , Lorch Scott A. , Small Dylan S.
Published: June 2014

An important concern in an observational study is whether or not there is unmeasured confounding, that is, unmeasured ways in which the treatment and control groups differ before treatment, which affect the outcome. We develop a test of whether there is unmeasured confounding when an instrumental variable (IV) is available. An IV is a variable that is independent of the unmeasured confounding and encourages a subject to take one treatment level versus another, while having no effect on the outcome beyond its encouragement of a certain treatment level. We show what types of unmeasured confounding can be tested for with an IV and develop a test for this type of unmeasured confounding that has correct type I error rate. We show that the widely used Durbin–Wu–Hausman test can have inflated type I error rates when there is treatment effect heterogeneity. Additionally, we show that our test provides more insight into the nature of the unmeasured confounding than the Durbin–Wu–Hausman test. We apply our test to an observational study of the effect of a premature infant being delivered in a high‐level neonatal intensive care unit (one with mechanical assisted ventilation and high volume) versus a lower level unit, using the excess travel time a mother lives from the nearest high‐level unit to the nearest lower‐level unit as an IV. Copyright © 2014 John Wiley & Sons, Ltd.
Weighted hurdle regression method for joint modeling of cardiovascular events likelihood and rate in the US dialysis population
Authors: Şentürk Damla , Dalrymple Lorien S. , Mu Yi , Nguyen Danh V.
Published: June 2014

We propose a new weighted hurdle regression method for modeling count data, with particular interest in modeling cardiovascular events in patients on dialysis. Cardiovascular disease remains one of the leading causes of hospitalization and death in this population. Our aim is to jointly model the relationship/association between covariates and (i) the probability of cardiovascular events, a binary process, and (ii) the rate of events once the realization is positive—when the ‘hurdle’ is crossed—using a zero‐truncated Poisson distribution. When the observation period or follow‐up time, from the start of dialysis, varies among individuals, the estimated probability of positive cardiovascular events during the study period will be biased. Furthermore, when the model contains covariates, then the estimated relationship between the covariates and the probability of cardiovascular events will also be biased. These challenges are addressed with the proposed weighted hurdle regression method. Estimation for the weighted hurdle regression model is a weighted likelihood approach, where standard maximum likelihood estimation can be utilized. The method is illustrated with data from the United States Renal Data System. Simulation studies show the ability of proposed method to successfully adjust for differential follow‐up times and incorporate the effects of covariates in the weighting. Copyright © 2014 John Wiley & Sons, Ltd.
Interdisciplinary assessment of complex regional water systems and their future evolution: how socioeconomic drivers can matter more than climate
Authors: Reynard Emmanuel , Bonriposi Mariano , Graefe Olivier , Homewood Christine , Huss Matthias , Kauzlaric Martina , Liniger Hanspeter , Rey Emmanuel , Rist Stephan , Schädler Bruno , Schneider Flurina , Weingartner Rolf
Published: June 2014

Modeling of future water systems at the regional scale is a difficult task due to the complexity of current structures (multiple competing water uses, multiple actors, formal and informal rules) both temporally and spatially. Representing this complexity in the modeling process is a challenge that can be addressed by an interdisciplinary and holistic approach. The assessment of the water system of the Crans‐Montana‐Sierre area (Switzerland) and its evolution until 2050 were tackled by combining glaciological, hydrogeological, and hydrological measurements and modeling with the evaluation of water use through documentary, statistical and interview‐based analyses. Four visions of future regional development were co‐produced with a group of stakeholders and were then used as a basis for estimating future water demand. The comparison of the available water resource and the water demand at monthly time scale allowed us to conclude that for the four scenarios socioeconomic factors will impact on the future water systems more than climatic factors. An analysis of the sustainability of the current and future water systems based on four visions of regional development allowed us to identify those scenarios that will be more sustainable and that should be adopted by the decision‐makers. The results were then presented to the stakeholders through five key messages. The challenges of communicating the results in such a way with stakeholders are discussed at the end of the article. WIREs Water 2014, 1:413–426. doi: 10.1002/wat2.1032

This article is categorized under:

Science of Water > Hydrological Processes

Science of Water > Water and Environmental Change

Human Water > Water Governance
The intriguing complexities of mammalian gene regulation: How to link enhancers to regulated genes. Are we there yet?
Authors: Daniel Bence , Nagy Gergely , Nagy Laszlo
Published: June 2014

The information encoded in genomes supports the differentiation and function of the more than 200 unique cell types, which exist in various mammalian species. The major mechanism driving cellular differentiation and specification is differential gene expression regulation. Cis‐acting enhancers and silencers appear to have key roles in regulating the expression of mammalian genes. However, these cis‐acting elements are often located very far away from the regulated gene. Therefore, it is hard to find all of them and link them to the regulated gene. An intriguing and unresolved issue of the field is to identify all of the enhancers of a particular gene and link these short regulatory sequences to the genes they regulate and thus, reliably identify gene regulatory enhancer networks. Recent advances in molecular biological methods coupled with Next‐Generation Sequencing (NGS) technologies have opened up new possibilities in this area of genomics. In this review we summarize the technological advances, bioinformatics challenges and the potential molecular mechanisms allowing the construction of enhancer networks operating in specific cell types and/or activated by various signals.