bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrepancy rates in liver biopsy reporting
Authors: Colling Richard , Verrill Clare , Fryer Eve , Wang Lai Mun , Fleming Kenneth
Published: June 2014

Medical liver biopsy reporting is challenging, and maintaining competency with small case numbers is potentially difficult. This study evaluates the discrepancies identified in cases referred to a specialist centre between the specialist reports and those of the referring general departments. Fifty consecutive recently referred cases were selected, and original and final reports were compared. Discrepancies were classified as per the Royal College of Pathologists guidelines and scored for potential clinical impact. The overall rate of discrepancy was 38% with most of these due to differences in interpretation of morphology. Seventy per cent of these discrepancies were judged to have major clinical impact (26% of all referred cases). This study highlights the need for robust systems of quality control of liver biopsies in a general setting.
Home-made explosive found inside injured Afghan
Authors: Pengelly Steven , Moore N , Burgess D , Mahlon M , Rowlands T , Cubison T
Published: June 2014

There is extensive literature on metal fragments from improvised explosive devices being embedded in patients but there are no reports describing the clinical and radiological appearances of embedded home-made explosive (HME). We present a case of partially detonated HME being found inside a patient's forearm. We discuss the medical management of the injury, the ongoing risk to the patient and surgical team associated with the explosive and the safe disposal of the substance.
Assessment of impact of a novel infectious bursal disease (IBD) vaccination programme in breeders on IBD humoral antibody levels through the laying period
Authors: Parker Daniel , de Wit Sjaak , Houghton Helen , Prandini Francesco
Published: June 2014

Objectives

The purpose of this study was to assess whether broiler breeders vaccinated in ovo with a Vaxxitek (HVT&IBD) (Merial) plus an inactivated IBD vaccine prior to the onset of lay had a significantly different humoral IBD antibody response to broiler breeders vaccinated solely with Vaxxitek (HVT&IBD) (Merial) in ovo. In addition, maternally derived antibody (MDA) passed to the progeny of these two breeders flocks was also compared at three time points during lay.

Design

The study was a case–control study where the two flocks were the same breed, reared on the same farm and transferred to the same laying farm, the only difference between the flocks being the IBD vaccination programme. The humoral IBD antibody response in the flocks and their progeny was measured using two commercial ELISA tests and a serum neutralisation (SN) test.

Results

There was no significant difference (P<0.05) in the humoral IBD antibody response in the two breeder flocks as measured by ELISA test except at a single time point at 22 weeks when measured by BioChek ELISA and at 60 weeks when measured by IDEXX ELISA. There was no significant difference (P<0.05) in the humoral IBD antibody response in the two breeder flocks as measured by SN test except at 27 and 55 weeks. There was no significant difference (P<0.05) in the levels of MDA passed to progeny of these two breeder flocks as measured by ELISA or SN test.

Conclusions

It is proposed that a single vaccination with Vaxxitek (HVT&IBD) (Merial) will provide a similar level of IBD protection to breeders and their progeny as a Vaxxitek (HVT&IBD) (Merial) plus inactivated IBD vaccine, vaccination programme. This novel IBD vaccine provides additional options for vaccination programmes for broiler breeders without impacting on the protection of the broiler progeny.
Hydrological drought and the role of refugia in an endangered riffle-dwelling fish, Nooksack dace (Rhinichthys cataractaessp.)
Authors: Avery-Gomm Stephanie , Rosenfeld Jordan S. , Richardson John S. , Pearson Michael
Published: June 2014

Understanding the impacts of hydrological drought, and the role that refugia play in mitigating these impacts, is crucial to the conservation of freshwater fishes. This is especially true for species adapted to riffles, which are typically the first habitats to dewater at low discharge. We examined the relationship among decreasing stream discharge, abundance, and habitat use for Nooksack dace (Rhinichthys cataractae ssp.), an endangered riffle-dwelling species. A complementary experimental manipulation examined the effects of flow on growth rate across a discharge gradient in riffle and pool habitats. We found that low-velocity habitats and decreased discharge in experimental channels result in reduced dace growth and that decreasing stream flow was coincident with declines in Nooksack dace abundance. This study demonstrates the sensitivity of Nooksack dace to hydrological drought, and insofar as Nooksack dace are ecologically typical of small riffle-dwelling invertivore fishes, our results suggest that use of pools does not mitigate sublethal effects of declining flows on growth, although pools may provide refuge from the most negative effects of drought (i.e., stranding of fish).
EvEel (evolutionary ecology-based model for eel): a model to explore the role of phenotypic plasticity as an adaptive response of three temperate eels to spatially structured environments
Authors: Drouineau Hilaire , Rigaud Christian , Daverat Françoise , Lambert Patrick
Published: June 2014

Anguilla anguilla, Anguilla japonica, and Anguilla rostrata are three widely distributed catadromous and semelparous species characterized by a long and passive oceanic larval drift between their marine spawning grounds and nursery areas in continental waters. Their large, spatially heterogeneous environments combined with population panmixia and long and passive larval drift impair the possibility of local adaptation and favour the development of phenotypic plasticity. In this context, we developed EvEel (evolutionary ecology-based model for eel), a model that aims to explore the role of phenotypic plasticity as an adaptive response of eels. Results suggest that the spatial patterns in terms of sex ratio, length-at-silvering, and habitat use observed at both the distribution area and river catchment scales may actually be the result of three adaptive mechanisms to maximize individual fitness in spatially structured environments. We believe that considering phenotypic plasticity as a paradigm is required to develop appropriate models for this species.
On the abundance of primordial bound states of superheavy magnetic monopoles
Authors: Gulevich Dmitry R.
Published: June 2014

It has been suggested that superheavy charged particles might have been born in primordial bound pairs at the end of cosmic inflation. Such pairs have been proposed as a source of ultrahigh energy cosmic rays (UHECR). We show that primordial bound pairs of magnetic monopoles larger than 10-9cm quickly thermalise due to the interaction with primordial electron–positron plasma and any such initial primordial concentration is washed out. The final concentration will therefore be defined by their equilibrium abundance.
Holography as cutoff: A proposal for measure of inflationary universes
Authors: Novaes Fábio , Carneiro da Cunha Bruno
Published: June 2014

We propose the holographic principle as a dynamical cutoff for any quantum theory of gravity, incorporating ideas of effective field theory. This is done by viewing the holographic bound as a limit on the number of degrees of freedom that can be turned on before the geometrical picture of gravity loses applicability. We illustrate the proposal by revisiting the problem of defining a measure for homogeneous and isotropic space–times coupled to a scalar field and conclude by discussing the implications to the single scalar field inflationary model.
Spin and surface orientation effects of work function forCr/Ni(111),Cr/Ni(100) andCr/Ni(110) metal gates
Authors: Zhong Kehua , Xu Guigui , Cheng Yanmin , Tang Keqin , Chen Zhigao , Huang Zhigao
Published: June 2014

Work functions of Cr/Ni (111), Cr/Ni (100) and Cr/Ni (110) surfaces with different magnetic configurations for Cr atoms in the topmost Cr monolayer are investigated using first-principles methods based on density functional theory. The calculated results reveal that work functions vary with crystal orientations and magnetic configurations. The magnitude of the Cr magnetic moments for the three (111), (100) and (110) surfaces follows a change trend with MCr, Cr/Ni(111)< MCr, Cr/Ni(100)< MCr, Cr/Ni(110). Altering the magnetic configurations of the systems from an original ground state to an excited one will have the total energy and the Fermi level increase. Consequently, it will give rise to the reduction of the work function for the system. Moreover, the quite favorable variation range (4.92–4.41 eV) of the calculated work functions for Cr/Ni (100) system modulated by spin effect implies that the Cr/Ni (100) system may be a more promising candidate. Our work suggests that changing magnetic configurations can modulate the work functions of magnetic metal gates well.
Effects of different sintering temperatures on microstructural, transport, and magnetic properties of La0.93Sb0.07MnO3 compound
Authors: Wang Q. , Duan P. , Wang J. Y. , Chang L. , Deng J. X. , Yuan A. J.
Published: June 2014

Polycrystalline La 0.93 Sb 0.07 MnO 3 ceramics were synthesized using solid-state reaction method. The samples were sintered at different temperatures ranging from 1100°C to 1200°C. It is observed that microstructural, transport and magnetic properties of La 0.93 Sb 0.07 MnO 3 compounds strongly depend on sintering temperatures (TS). With TS increasing, the degree of lattice distortion has been weakened, the grain size has become larger and grain boundaries have decreased. Furthermore, the resistivity was reduced, and metal–insulator transition temperature was enhanced; the saturation magnetization per unit mass has decreased with TS increasing. These effects of different TS on physical properties can be explained by the structure distortion and grain boundary contributions for La 0.93 Sb 0.07 MnO 3 compounds.
The Impact Mechanism of Fractal Noise on PN Code Detection System
Authors: Xiong Gang , Zhang Shu-Ning , Zhao Hui-Chang
Published: June 2014

Taking the pseudo-random phase modulated CW radar for example, this paper studies the impact mechanism of a class of non-stationary fractal noise on PN code detection system, especially signal mixing and matching filter. The cross correlation function, power spectrum function and average power of pseudo-random signal and fractal noise are deduced, compared with the impact of white noise on the pseudo code detection system. We analyze the impact mechanism of three kinds of sea clutter model, namely fractal Brownian model (FBM), the multifractal (MF) model and the non-stationary random fractal model (e.g., infinitely divisible cascades, IDC), on the pseudo-random code detection system, and demonstrate the reason why the multi-scale filtering method in wavelet domain and the MF methods fail to eliminate the effect of sea clutter. Based on the natural sea clutter data, we simulate and analyze the influence of white noise and fractal noise comparatively on detection system, which indicates that the effect of fractal noise cannot be inhibited effectively by the traditional correlation detection and MF analysis, and finally we put forward possible solutions.
PARALLEL HYBRID METAHEURISTIC ON SHARED MEMORY SYSTEM FOR REAL-TIME UAV PATH PLANNING
Authors: ROBERGE VINCENT , TARBOUCHI MOHAMMED , ALLAIRE FRANÇOIS
Published: June 2014

In this paper, we present a parallel hybrid metaheuristic that combines the strengths of the particle swarm optimization (PSO) and the genetic algorithm (GA) to produce an improved path-planner algorithm for fixed wing unmanned aerial vehicles (UAVs). The proposed solution uses a multi-objective cost function we developed and generates in real-time feasible and quasi-optimal trajectories in complex 3D environments. Our parallel hybrid algorithm simulates multiple GA populations and PSO swarms in parallel while allowing migration of solutions. This collaboration between the GA and the PSO leads to an algorithm that exhibits the strengths of both optimization methods and produces superior solutions. Moreover, by using the "single-program, multiple-data" parallel programming paradigm, we maximize the use of today's multicore CPU and significantly reduce the execution time of the parallel program compared to a sequential implementation. We observed a quasi-linear speedup of 10.7 times faster on a 12-core shared memory system resulting in an execution time of 5 s which allows in-flight planning. Finally, we show with statistical significance that our parallel hybrid algorithm produces superior trajectories to the parallel GA or the parallel PSO we previously developed.
SVM AGAINST GMM/SVM FOR DIALECT INFLUENCE ON AUTOMATIC SPEAKER RECOGNITION TASK
Authors: ZERGAT KAWTHAR YASMINE , AMROUCHE ABDERRAHMANE
Published: June 2014

A big deal for current research on automatic speaker recognition is the effectiveness of the speaker modeling techniques for the talkers, because they have their own speaking style, depending on their specific accents and dialects. This paper investigates on the influence of the dialect and the size of database on the text independent speaker verification task using the SVM and the hybrid GMM/SVM speaker modeling. The Principal Component Analysis (PCA) technique is used in the front-end part of the speaker recognition system, in order to extract the most representative features. Experimental results show that the size of database has an important impact on the SVM and GMM/SVM based speaker verification performances, while the dialect has no significant effect. Applying PCA dimensionality reduction improves the recognition accuracy for both SVM and GMM/SVM based recognition systems. However, it did not give an obvious observation about the dialect effect.
留日新华侨: 当代中国人移居日本形态及特征分析
Authors: 刘双
Published: June 2014

自上世纪70年代末以来，数以百万计的中国人来到日本。他们当中有学生、劳工、家属、定居者及许多非法居留者，如今已有几十万名中国人留在这个国家。本文介绍了这些新移民的移居形态与人员特征，特别值得一提的是他们的经济社会活动与生活设计的跨国性。2011年3月，日本发生有史以来最大的地震，本文也对这次大灾害对在日华人的影响作了分析。
Secrecy
Authors: Jones Graham M.
Published: June 2014

Although expansions of state secrecy and the countervailing leaks of classified documents imbue the anthropology of secrecy with urgent relevance, secrecy has a long-standing status as a paradigmatically anthropological topic. In the ethnographic record, initiatory secrets often stand for the quiddity of culture, and the revelation of concealed realities is an organizing trope in much ethnographic writing. While situating research on secrecy as a reflection of epistemological and ethical dimensions of cultural anthropology more broadly, this review simultaneously explores parallels between different anthropological traditions by focusing on descriptions of the media through which social relations involving secrecy are transacted. Attending to ethnographic accounts of the way secrets travel across different media and coexist simultaneously in various mediated states provides both a novel intellectual framework for surveying recent research and a basis for conceptualizing the anthropology of secrecy itself as a practice that involves intermedial and transmedial knowledge flows.
Far-Infrared Surveys of Galaxy Evolution
Authors: Lutz Dieter
Published: June 2014

Roughly half of the radiation from evolving galaxies in the early Universe reaches us in the far-infrared and submillimeter wavelength ranges. Recent major advances in observing capabilities, in particular the launch of the Herschel Space Observatory in 2009, have dramatically enhanced our ability to use this information in the context of multiwavelength studies of galaxy evolution. Near its peak, three-quarters of the cosmic infrared background is now resolved into individually detected sources. The use of far-infrared diagnostics of dust-obscured star formation and of interstellar medium conditions has expanded from extreme and rare extreme high-redshift galaxies to more typical main-sequence galaxies and hosts of active galactic nuclei out to z≳2. These studies shed light on the evolving role of steady equilibrium processes and of brief starbursts at and since the peak of cosmic star formation and black hole accretion. This review presents a selection of recent far-infrared studies of galaxy evolution with an emphasis on Herschel results.
Mass Loss: Its Effect on the Evolution and Fate of High-Mass Stars
Authors: Smith Nathan
Published: June 2014

Our understanding of massive star evolution is in flux due to recent upheavals in our view of mass loss and observations of a high binary fraction among O-type stars. Mass-loss rates for standard metallicity-dependent winds of hot stars are lower by a factor of 2–3 compared with rates adopted in modern stellar evolution codes, due to the influence of clumping on observed diagnostics. Weaker hot star winds shift the burden of H-envelope removal to the winds, pulsations, and eruptions of evolved supergiants, as well as binary mass transfer. Studies of stripped-envelope supernovae, in particular, require binary mass transfer. Dramatic examples of eruptive mass loss are seen in Type IIn supernovae, which have massive shells ejected just a few years earlier. These eruptions are a prelude to core collapse, and may signify severe instabilities in the latest nuclear burning phases. We encounter the predicament that the most important modes of mass loss are also the most uncertain, undermining the predictive power of single-star evolution models. Moreover, the influence of winds and rotation has been evaluated by testing single-star models against observed statistics that, it turns out, are heavily influenced by binary evolution. Altogether, this may alter our view about the most basic outcomes of massive-star mass loss—are Wolf-Rayet stars and Type Ibc supernovae the products of winds, or are they mostly the result of binary evolution and eruptive mass loss? This is not fully settled, but mounting evidence points toward the latter. This paradigm shift impacts other areas of astronomy, because it changes predictions for ionizing radiation and wind feedback from stellar populations, it may alter conclusions about star-formation rates and initial mass functions, it affects the origin of compact stellar remnants, and it influences how we use supernovae as probes of stellar evolution across cosmic time.
Numerical Relativity and Astrophysics
Authors: Lehner Luis , Pretorius Frans
Published: June 2014

Throughout the Universe many powerful events are driven by strong gravitational effects that require general relativity to fully describe them. These include compact binary mergers, black hole accretion, and stellar collapse, where velocities can approach the speed of light and extreme gravitational fields (ΦNewt/c2≃1) mediate the interactions. Many of these processes trigger emission across a broad range of the electromagnetic spectrum. Compact binaries further source strong gravitational wave emission that could directly be detected in the near future. This feat will open up a gravitational wave window into our Universe and revolutionize our understanding of it. Describing these phenomena requires general relativity, and—where dynamical effects strongly modify gravitational fields—the full Einstein equations coupled to matter sources. Numerical relativity is a field within general relativity concerned with studying such scenarios that cannot be accurately modeled via perturbative or analytical calculations. In this review, we examine results obtained within this discipline, with a focus on its impact in astrophysics.
Hot Accretion Flows Around Black Holes
Authors: Yuan Feng , Narayan Ramesh
Published: June 2014

Black hole accretion flows can be divided into two broad classes: cold and hot. Whereas cold accretion flows consist of cool optically thick gas and are found at relatively high mass accretion rates, hot accretion flows, the topic of this review, are virially hot and optically thin, and occur at lower mass accretion rates. They are described by accretion solutions such as the advection-dominated accretion flow and luminous hot accretion flow. Because of energy advection, the radiative efficiency of these flows is in general lower than that of a standard thin accretion disk. Moreover, the efficiency decreases with decreasing mass accretion rate. Observations show that hot accretion flows are associated with jets. In addition, theoretical arguments suggest that hot flows should produce strong winds. Hot accretion flows are believed to be present in low-luminosity active galactic nuclei and in black hole X-ray binaries in the hard and quiescent states. The prototype is Sgr A*, the ultralow-luminosity supermassive black hole at our Galactic center. The jet, wind, and radiation from a supermassive black hole with a hot accretion flow can interact with the external interstellar medium and modify the evolution of the host galaxy.
Subterfuge and Sabotage: Evasion of Host Innate Defenses by Invasive Gram-Positive Bacterial Pathogens
Authors: Okumura Cheryl Y.M. , Nizet Victor
Published: June 2014

The development of a severe invasive bacterial infection in an otherwise healthy individual is one of the most striking and fascinating aspects of human medicine. A small cadre of gram-positive pathogens of the genera Streptococcus and Staphylococcus stand out for their unique invasive disease potential and sophisticated ability to counteract the multifaceted components of human innate defense. This review illustrates how these leading human disease agents evade host complement deposition and activation, impede phagocyte recruitment and activation, resist the microbicidal activities of host antimicrobial peptides and reactive oxygen species, escape neutrophil extracellular traps, and promote and accelerate phagocyte cell death through the action of pore-forming cytolysins. Understanding the molecular basis of bacterial innate immune resistance can open new avenues for therapeutic intervention geared to disabling specific virulence factors and resensitizing the pathogen to host innate immune clearance.
Bacterial Sigma Factors: A Historical, Structural, and Genomic Perspective
Authors: Feklístov Andrey , Sharon Brian D. , Darst Seth A. , Gross Carol A.
Published: June 2014

Transcription initiation is the crucial focal point of gene expression in prokaryotes. The key players in this process, sigma factors (σs), associate with the catalytic core RNA polymerase to guide it through the essential steps of initiation: promoter recognition and opening, and synthesis of the first few nucleotides of the transcript. Here we recount the key advances in σ biology, from their discovery 45 years ago to the most recent progress in understanding their structure and function at the atomic level. Recent data provide important structural insights into the mechanisms whereby σs initiate promoter opening. We discuss both the housekeeping σs, which govern transcription of the majority of cellular genes, and the alternative σs, which direct RNA polymerase to specialized operons in response to environmental and physiological cues. The review concludes with a genome-scale view of the extracytoplasmic function σs, the most abundant group of alternative σs.
Decoding Neural Representational Spaces Using Multivariate Pattern Analysis
Authors: Haxby James V. , Connolly Andrew C. , Guntupalli J. Swaroop
Published: June 2014

A major challenge for systems neuroscience is to break the neural code. Computational algorithms for encoding information into neural activity and extracting information from measured activity afford understanding of how percepts, memories, thought, and knowledge are represented in patterns of brain activity. The past decade and a half has seen significant advances in the development of methods for decoding human neural activity, such as multivariate pattern classification, representational similarity analysis, hyperalignment, and stimulus-model-based encoding and decoding. This article reviews these advances and integrates neural decoding methods into a common framework organized around the concept of high-dimensional representational spaces.
Meta-Analysis and Other Approaches for Synthesizing Structured and Unstructured Data in Plant Pathology
Authors: Scherm H. , Thomas C.S. , Garrett K.A. , Olsen J.M.
Published: June 2014

The term data deluge is used widely to describe the rapidly accelerating growth of information in the technical literature, in scientific databases, and in informal sources such as the Internet and social media. The massive volume and increased complexity of information challenge traditional methods of data analysis but at the same time provide unprecedented opportunities to test hypotheses or uncover new relationships via mining of existing databases and literature. In this review, we discuss analytical approaches that are beginning to be applied to help synthesize the vast amount of information generated by the data deluge and thus accelerate the pace of discovery in plant pathology. We begin with a review of meta-analysis as an established approach for summarizing standardized (structured) data across the literature. We then turn to examples of synthesizing more complex, unstructured data sets through a range of data-mining approaches, including the incorporation of 'omics data in epidemiological analyses. We conclude with a discussion of methodologies for leveraging information contained in novel, open-source data sets through web crawling, text mining, and social media analytics, primarily in the context of digital disease surveillance. Rapidly evolving computational resources provide platforms for integrating large and complex data sets, motivating research that will draw on new types and scales of information to address big questions.
The four phases of esophageal bolus transit defined by high-resolution impedance manometry and fluoroscopy
Authors: Lin Zhiyue , Yim Brandon , Gawron Andrew , Imam Hala , Kahrilas Peter J. , Pandolfino John E.
Published: June 2014

We aimed to model esophageal bolus transit based on esophageal pressure topography (EPT) landmarks, concurrent intrabolus pressure (IBP), and esophageal diameter as defined with fluoroscopy. Ten healthy subjects were studied with high-resolution impedance manometry and videofluoroscopy. Data from four 5-ml barium swallows (2 upright, 2 supine) in each subject were analyzed. EPT landmarks were utilized to divide bolus transit into four phases: phase I, upper esophageal sphincter (UES) opening; phase II, UES closure to the transition zone (TZ); phase III, TZ to contractile deceleration point (CDP); and phase IV, CDP to completion of bolus emptying. IBP and esophageal diameter were analyzed to define functional differences among phases. IBP exhibited distinct changes during the four phases of bolus transit. Phase I was associated with filling via passive dilatation of the esophagus and IBP reflective of intrathoracic pressure. Phase II was associated with auxotonic relaxation and compartmentalization of the bolus distal to the TZ. During phase III, IBP exhibited a slow increase with loss of volume related to peristalsis (auxotonic contraction) and passive dilatation in the distal esophagus. Phase IV was associated with the highest IBP and exhibited isometric contraction during periods of nonemptying and auxotonic contraction during emptying. IBP may be used as a marker of esophageal wall state during the four phases of esophageal bolus transit. Thus abnormalities in IBP may identify subtypes of esophageal disease attributable to abnormal distensibility or neuromuscular dysfunction.
Stimulation of intestinal growth and function with DPP4 inhibition in a mouse short bowel syndrome model
Authors: Sueyoshi Ryo , Woods Ignatoski Kathleen M. , Okawada Manabu , Hartmann Bolette , Holst Jens , Teitelbaum Daniel H.
Published: June 2014

Glucagon-like peptide-2 (GLP-2) has been shown to be effective in patients with short bowel syndrome (SBS), but it is rapidly inactivated by dipeptidyl peptidase IV (DPP4). We used an orally active DPP4 inhibitor (DPP4-I), MK-0626, to determine the efficacy of this approach to promote adaptation after SBS, determined optimal dosing, and identified further functional actions in a mouse model of SBS. Ten-week-old mice underwent a 50% proximal small bowel resection. Dose optimization was determined over a 3-day post-small bowel resection period. The established optimal dose was given for 7, 30, and 90 days and for 7 days followed by a 23-day washout period. Adaptive response was assessed by morphology, intestinal epithelial cell (IEC) proliferation (proliferating cell nuclear antigen), epithelial barrier function (transepithelial resistance), RT-PCR for intestinal transport proteins and GLP-2 receptor, IGF type 1 receptor, and GLP-2 plasma levels. Glucose-stimulated sodium transport was assessed for intestinal absorptive function. Seven days of DPP4-I treatment facilitated an increase in GLP-2 receptor levels, intestinal growth, and IEC proliferation. Treatment led to differential effects over time, with greater absorptive function at early time points and enhanced proliferation at later time points. Interestingly, adaptation continued in the group treated for 7 days followed by a 23-day washout. DPP4-I enhanced IEC proliferative action up to 90 days postresection, but this action seemed to peak by 30 days, as did GLP-2 plasma levels. Thus DPP4-I treatment may prove to be a viable option for accelerating intestinal adaptation with SBS.
AR-Regulated TWEAK-FN14 Pathway Promotes Prostate Cancer Bone Metastasis
Authors: Yin JuanJuan , Liu Yen-Nien , Tillman Heather , Barrett Ben , Hewitt Stephen , Ylaya Kris , Fang Lei , Lake Ross , Corey Eva , Morrissey Colm , Vessella Robert , Kelly Kathleen
Published: June 2014

The recurrence of prostate cancer metastases to bone after androgen deprivation therapy is a major clinical challenge. We identified FN14 (TNFRSF12A), a TNF receptor family member, as a factor that promotes prostate cancer bone metastasis. In experimental models, depletion of FN14 inhibited bone metastasis, and FN14 could be functionally reconstituted with IKKβ-dependent, NFκB signaling activation. In human prostate cancer, upregulated FN14 expression was observed in more than half of metastatic samples. In addition, FN14 expression was correlated inversely with androgen receptor (AR) signaling output in clinical samples. Consistent with this, AR binding to the FN14 enhancer decreased expression. We show here that FN14 may be a survival factor in low AR output prostate cancer cells. Our results define one upstream mechanism, via FN14 signaling, through which the NFκB pathway contributes to prostate cancer metastasis and suggest FN14 as a candidate therapeutic and imaging target for castrate-resistant prostate cancers. Cancer Res; 74(16); 4306–17. ©2014 AACR.
High-Throughput Time-Resolved FRET Reveals Akt/PKB Activation as a Poor Prognostic Marker in Breast Cancer
Authors: Veeriah Selvaraju , Leboucher Pierre , de Naurois Julien , Jethwa Nirmal , Nye Emma , Bunting Tamara , Stone Richard , Stamp Gordon , Calleja Véronique , Jeffrey Stefanie S. , Parker Peter J. , Larijani Banafshé
Published: June 2014

Dysregulation of the Akt/PKB pathway has been associated with poor prognosis in several human carcinomas. Current approaches to assess Akt activation rely on intensity-based methods, which are limited by the subjectivity of manual scoring and poor specificity. Here, we report the development of a novel assay using amplified, time-resolved Förster resonance energy transfer (FRET), which is highly specific and sensitive and can be adapted to any protein. Using this approach to analyze primary breast tissue microarrays, we quantified levels of activated pAkt at a spatial resolution that revealed molecular heterogeneity within tumors. High pAkt status assessed by amplified FRET correlated with worse disease-free survival. Our findings support the use of amplified FRET to determine pAkt status in cancer tissues as candidate biomarker for the identification of high-risk patients. Cancer Res; 74(18); 4983–95. ©2014 AACR.
Skin Wound Healing and Phytomedicine: A Review
Authors: Pazyar Nader , Yaghoobi Reza , Rafiee Esmail , Mehrabian Abolfath , Feily Amir
Published: June 2014

Skin integrity is restored by a physiological process aimed at repairing the damaged tissues. The healing process proceeds in four phases: hemostasis, inflammation, proliferation and remodeling. Phytomedicine presents remedies, which possess significant pharmacological effects. It is popular amongst the general population in regions all over the world. Phytotherapeutic agents have been largely used for cutaneous wound healing. These include Aloe vera, mimosa, grape vine, Echinacea, chamomile, ginseng, green tea, jojoba, tea tree oil, rosemary, lemon, soybean, comfrey, papaya, oat, garlic, ginkgo, olive oil and ocimum. Phytotherapy may open new avenues for therapeutic intervention on cutaneous wounds. This article provides a review of the common beneficial medicinal plants in the management of skin wounds with an attempt to explain their mechanisms.
Investigations into the Role of 26S Proteasome Non-ATPase Regulatory Subunit 13 in Neuroinflammation
Authors: Bi Wei , Zhu Lihong , Zeng Zhifen , Jing Xiuna , Liang Yanran , Guo Li , Shi Qiaoyun , Xu Anding , Tao Enxiang
Published: June 2014

Objective: To investigate 26S proteasome non-ATPase regulatory subunit 13 (PSMD13) gene silencing as a potential treatment for neuroinflammatory disorders via regulation of microglial activation and production of inflammatory mediators. Methods: RNA interference was used to knockdown PSMD13 gene expression, followed by inhibitors of κB (IκBa) protein degradation and nuclear factor κB (NF-κB) activity measurement in lipopolysaccharide (LPS)-stimulated BV2 microglia. Nitrite (Griess) assay, reporter gene assay, enzyme-linked immunosorbent assay and Western blot were used to investigate the role of PSMD13 in microglial activation and inflammation. Results: PSMD13 gene knockdown significantly reduced IκBa degradation and NF-κB activation in LPS-stimulated murine BV2 microglia. It also decreased the production of LPS-induced proinflammatory mediators, such as inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and prostaglandin E2. Conclusions: PSMD13 gene silencing suppressed the production of proinflammatory mediators by modulating ubiquitin-proteasome system-mediated neuroinflammation via the downregulation of IκBa degradation and NF-κB activation in LPS-stimulated BV2 microglia. PSMD13 gene knockdown may have therapeutic implications for the treatment of neuroinflammatory disorders.
Determination of Toll-Like Receptor-Induced Cytokine Profiles in the Blood and Cerebrospinal Fluid of Chikungunya Patients
Authors: Kashyap Rajpal Singh , Morey Shweta , Bhullar Shradha , Baheti Neeraj , Chandak Nitin , Purohit Hemant , Taori Girdhar , Daginawala Hatim
Published: June 2014

Background: Chikungunya infection caused by Chikungunya virus (CHIKV) is an inflammatory disease affecting the joints and may also lead to neurological complications. We investigated a panel of human Toll-like receptor (TLR)-induced cytokines in Chikungunya patients with and without neurological complications. Methods: In a case-control study, a panel of 12 cytokines and chemokines, TNF-α, IFN-α, IL-1β, IL-6, IL-12, IL-17A, IL-8, monocyte chemotactic protein (MCP)-1, RANTES, interferon (IFN)-γ-induced protein (IP)-10, monokine induced by IFN-γ (MIG) and thymus and activation-regulated chemokine (TARC), was analysed using a conventional ELISA protocol in the serum samples of Chikungunya patients without neurological complications and in the cerebrospinal fluid (CSF) and paired serum samples of Chikungunya patients with neurological complications. Results: The levels of 3 cytokines, IL-1β, IL-17A and IL-8, and 4 chemokines, MCP-1, RANTES, IP-10 and TARC, were raised in serum samples of Chikungunya patients without neurological complications, whereas, 4 cytokines, TNF-α, IFN-α, IL-6 and IL-8, and 4 chemokines, MCP-1, RANTES, MIG and TARC, were elevated in CSF samples of Chikungunya patients with neurological complications. Moreover, the levels of IL-6 and IL-8 cytokines were significantly elevated in the CSF compared to paired serum samples in Chikungunya patients with neurological complications. Conclusions: In CHIKV infection, multiple cytokines are elevated in serum and CSF. The elevation in IL-6 and IL-8 cytokines in CSF correlates with neurological involvement.
Gestational Age-Specific Reference Ranges of Hepcidin in Cord Blood
Authors: Lorenz Laila , Herbst Johanna , Engel Corinna , Peter Andreas , Abele Harald , Poets Christian F. , Westerman Mark , Franz Axel R.
Published: June 2014

Background: Iron deficiency (ID) contributes to anaemia of prematurity, and hence the reliable assessment of iron nutrition status appears to be mandatory. Objective: To establish gestational age (GA)-specific reference ranges for hepcidin concentrations in cord blood [Hep(CB)] of preterm and term infants and to identify pre- and perinatal confounding factors. Methods: This is a prospective observational study including 221 infants (GA at birth: 24-42 weeks). Hep(CB) along with complete blood counts, ferritin and parameters of inflammation and clinical data were recorded. Data are presented as medians (IQR). Results: The Hep(CB) of very preterm infants (GA <30 weeks, n = 40) was 26.9 ng/ml (13.5-63.1), for moderately preterm infants (GA 30-36 weeks, n = 81) it was 45.9 ng/ml (24.7-74.5) and for term infants (GA ≥37 weeks, n = 100) it was 103.9 ng/ml (61.4-149.2). The Hep(CB) of infants with ID was lower [36.9 ng/ml (18.0-58.3)] than that of iron-replete infants [86.6 ng/ml (51.9-143.8)]. The Hep(CB) of infants delivered by elective caesarean section was lower [38.3 ng/ml (15.5-73.7)] than that of infants after spontaneous vaginal delivery or secondary caesarean section [80.3 ng/ml (48.5-137.6)]. Infants with a standard deviation score for birth weight (SDSBW) <-2 had a lower Hep(CB) [23.1 ng/ml (11.7-61.5)] compared to infants with SDSBW ≥-2 [71.1 ng/ml (34.0-121.7)]. The highest Hep(CB) (437.6 ng/ml) was recorded in an infant with Enterococcus faecalis sepsis. Multiple logistic regression analysis confirmed ferritin, GA and mode of delivery as important factors associated with Hep(CB). Conclusion: This is the first report on GA-specific reference ranges for Hep(CB) in preterm infants. Whereas iron stores, GA and mode of delivery were associated with Hep(CB), the association with inflammation and intra-uterine growth retardation was less clear.
Protecting Personal Data in Epidemiological Research: DataSHIELD and UK Law
Authors: Wallace Susan E. , Gaye Amadou , Shoush Osama , Burton Paul R.
Published: June 2014

Background: Data from individual collections, such as biobanks and cohort studies, are now being shared in order to create combined datasets which can be queried to ask complex scientific questions. But this sharing must be done with due regard for data protection principles. DataSHIELD is a new technology that queries nonaggregated, individual-level data in situ but returns query data in an anonymous format. This raises questions of the ability of DataSHIELD to adequately protect participant confidentiality. Methods: An ethico-legal analysis was conducted that examined each step of the DataSHIELD process from the perspective of UK case law, regulations, and guidance. Results: DataSHIELD reaches agreed UK standards of protection for the sharing of biomedical data. All direct processing of personal data is conducted within the protected environment of the contributing study; participating studies have scientific, ethics, and data access approvals in place prior to the analysis; studies are clear that their consents conform with this use of data, and participants are informed that anonymisation for further disclosure will take place. Conclusion: DataSHIELD can provide a flexible means of interrogating data while protecting the participants' confidentiality in accordance with applicable legislation and guidance.
Geographic Atrophy Progression in Eyes with Age-Related Macular Degeneration: Role of Fundus Autofluorescence Patterns, Fellow Eye and Baseline Atrophy Area
Authors: Batıoğlu Figen , Gedik Oğuz Yeşim , Demirel Sibel , Özmert Emin
Published: June 2014

Background/Objective: To evaluate if fundus autofluorescence (FAF) patterns around geographic atrophy (GA) and the status of the fellow eye have an impact on GA progression. Methods: We included 54 eyes of 35 patients with GA. Areas of GA were quantified by RegionFinder software. Results: GA progression rates in eyes with a diffuse trickling pattern (median 1.42 mm2/year) were significantly higher than in normal eyes (median 0.22 mm2/year) and eyes with other diffuse FAF patterns (median 0.46 mm2/year). Eyes with a banded pattern had a significantly higher progression rate (median 0.81 mm2/year) than those without any FAF abnormalities (p = 0.038). The group with baseline total atrophy of the eyes <1 disk area (DA; median 0.42 mm2) had an inverse relation with GA progression compared to the groups with baseline atrophy >1 DA (p < 0.05). Conclusion: Diffuse trickling and banded patterns may have an impact on GA progression and may serve as prognostic factors.
Hypoxia-Induced Tau Phosphorylation and Memory Deficit in Rats
Authors: Zhang Chang-E. , Yang Xifei , Li Lingyun , Sui Xiaojing , Tian Qing , Wei Wei , Wang Jianzhi , Liu Gongping
Published: June 2014

Hypoxia was shown to be associated with an increased risk of Alzheimer's disease (AD). The effects of hypoxia on the development of AD pathology and spatial memory ability and the possible molecular mechanisms remain poorly understood. In this study, we demonstrate that rats exposed to a hypoxic condition (10% oxygen concentration) for 1, 2, 4 and 8 weeks (6 h each day) displayed spatial memory impairment and increased tau phosphorylation at Ser198/199/202, Thr205, Ser262, Ser396 and Ser404 in the hippocampus. Concomitantly, the levels of Tyr216-phosphorylated glycogen synthase kinase (GSK)-3β (activated form of GSK-3β) and Tyr307-phosphorylated protein phosphatase 2A (inactivated form of PP2A) were significantly increased in the hippocampus of the rats with 1, 2, 4 and 8 weeks of hypoxia exposure, while the levels of methylated PP2A (activated form of PP2A) were significantly decreased in the hippocampus of the rats with 4 and 8 weeks of hypoxia exposure. In addition, the content of malondialdehyde, an indicator of oxidative stress, was elevated, whereas the activity of superoxide dismutase was not significantly changed in the hippocampus of the rats exposed to hypoxia. Taken together, these data demonstrated that hypoxia induced tau hyperphosphorylation and memory impairment in rats, and that the increased tau phosphorylation could be attributed to activation of GSK-3β and inactivation of PP2A. These data suggest that interventions to improve hypoxia may be helpful to prevent the development of AD pathology and cognitive impairment.
Impact of Early Synchronous Lip and Palatal Repair on Speech
Authors: Luyten Anke , Bettens Kim , D'haeseleer Evelien , De Ley Sophia , Hodges Andrew , Galiwango George , Vermeersch Hubert , Van Lierde Kristiane
Published: June 2014

Aims: The purpose of this study was to describe articulation and resonance characteristics of Ugandan English-speaking children with cleft lip and palate (CLP) after synchronous lip and palatal closure (Sommerlad technique) prior to the age of 6 months in comparison with an age- and gender-matched control group. Methods: Eleven Ugandan patients with CLP (mean age 4;9 years), repaired during a synchronous lip and (soft and hard) palatal closure at a mean age of 3.4 months, were included as well as a control group (n = 22) consisting of 2 Ugandan age- and gender-matched noncleft children for each patient (mean age 4;10 years). Objective and perceptual speech assessment techniques were applied. Results: Consonant inventories were significantly smaller in the CLP group. Moreover, phonetic disorders and phonological processes occurred in 91 and 100% of the CLP group, respectively. Perceptual consensus evaluation revealed absence of hyponasality and cul-de-sac resonance in all patients. Hypernasality and nasal emission/turbulence occurred in 18 and 27% of the patients, respectively. No significant group differences were observed regarding the mean nasalance values of oral speech samples. Conclusion: Various deviations from normal speech development seem to occur in patients with CLP following synchronous lip and palatal closure before 6 months of age.
Expression of Porcine Respiratory and Reproductive Syndrome Virus Membrane-Associated Proteins in Listeria ivanovii via a Genome Site-Specific Integration and Expression System
Authors: Wang Chuan , Zhang Fuqin , Yang Jianglong , Khanniche Asma , Shen Hao
Published: June 2014

Listeria ivanovii (LI) possesses a facultative intracellular life cycle in macrophages and non-professional phagocytes thus making it a potential novel vaccine vector. We have developed a genome site-specific integration system as a universal tool for constructing the live LI-based vaccines. Using this system, the porcine reproductive and respiratory syndrome virus (PRRSV) orf5 and orf6 genes, coding for PRRSV membrane-associated protein GP5 and M, respectively, were integrated into the LI genome. Genome PCR and sequencing results showed that the orf5 or orf6 gene had been integrated into the LI genome downstream of orfXYZ or mpl gene. Western blot analysis of the non-secreted and secreted bacterial protein samples showed the expression and secretion of GP5 or M protein from the recombinant LI strains. The secretion of the heterologous proteins is a key step for bacterial vaccine vectors to deliver the antigens to the immune system to stimulate antigen-specific immune responses. Therefore, this integration system may be a potential tool for constructing novel vaccines using live LI as vector.
Successful Treatment of Eccrine Porocarcinoma Metastasized to a Cervical Lymph Node with CyberKnife Radiosurgery
Authors: Fujimura Taku , Hashimoto Akira , Furudate Sadanori , Kambayashi Yumi , Haga Takahiro , Aiba Setsuya
Published: June 2014

Eccrine porocarcinoma is a rare type of skin cancer that originates from eccrine sweat glands or acrosyringium and mainly occurs in the elderly. In this report, we describe an 85-year-old Japanese woman with eccrine porocarcinoma that metastasized to a cervical lymph node who was cured with CyberKnife radiosurgery. Because our patient had a high risk of perioperative complication, standard surgical therapy with a wide margin was impractical. Our present study suggests the novel possibility of using CyberKnife for the treatment of inoperable metastatic porocarcinoma.