bluuebunny/crossref_metadata_2025 huggingface dataset:
Antisocial
luxO
Mutants Provide a Stationary-Phase Survival Advantage in Vibrio fischeri ES114
Authors: Kimbrough John H. , Stabb Eric V.
Published: December 2015

The squid light organ symbiont
Vibrio fischeri
controls bioluminescence using two acyl-homoserine lactone pheromone-signaling (PS) systems. The first of these systems to be activated during host colonization, AinS/AinR, produces and responds to
N
-octanoyl homoserine lactone (C
8
-AHL). We screened activity of a P

ainS

-
lacZ
transcriptional reporter in a transposon mutant library and found three mutants with decreased reporter activity, low C
8
-AHL output, and other traits consistent with low
ainS
expression. However, the transposon insertions were unrelated to these phenotypes, and genome resequencing revealed that each mutant had a distinct point mutation in
luxO
. In the wild type, LuxO is phosphorylated by LuxU and then activates transcription of the small RNA (sRNA) Qrr, which represses
ainS
indirectly by repressing its activator LitR. The
luxO
mutants identified here encode LuxU-independent, constitutively active LuxO* proteins. The repeated appearance of these
luxO
mutants suggested that they had some fitness advantage during construction and/or storage of the transposon mutant library, and we found that
luxO
* mutants survived better and outcompeted the wild type in prolonged stationary-phase cultures. From such cultures we isolated additional
luxO
* mutants. In all, we isolated LuxO* allelic variants with the mutations P41L, A91D, F94C, P98L, P98Q, V106A, V106G, T107R, V108G, R114P, L205F, H319R, H324R, and T335I. Based on the current model of the
V. fischeri
PS circuit,
litR
knockout mutants should resemble
luxO
* mutants; however,
luxO
* mutants outcompeted
litR
mutants in prolonged culture and had much poorer host colonization competitiveness than is reported for
litR
mutants, illustrating additional complexities in this regulatory circuit.

IMPORTANCE
Our results provide novel insight into the function of LuxO, which is a key component of pheromone signaling (PS) cascades in several members of the
Vibrionaceae
. Our results also contribute to an increasingly appreciated aspect of bacterial behavior and evolution whereby mutants that do not respond to a signal from like cells have a selective advantage. In this case, although “antisocial” mutants locked in the PS signal-off mode can outcompete parents, their survival advantage does not require wild-type cells to exploit. Finally, this work strikes a note of caution for those conducting or interpreting experiments in
V. fischeri
, as it illustrates how pleiotropic mutants could easily and inadvertently be enriched in this bacterium during prolonged culturing.
From bone to heart: a case of MRSA osteomyelitis with haematogenous spread to the pericardium
Authors: Dherange Parinita A , Patel Sarah , Enakpene Evbu , Suryanarayana Prakash
Published: December 2015

We report a case of a 55-year-old woman with a history of type 2 diabetes mellitus, Charcot arthropathy and end-stage renal disease, who presented with a syncopal episode after undergoing haemodialysis. She had a history of methicillin-resistantStaphylococcus aureus(MRSA) bacteraemia from an unknown source 3 months earlier, which was treated with an 8-week course of intravenous antibiotics. At the time of presentation to the emergency room, she was found to be in refractory shock. Bedside echocardiogram was performed, which showed moderate pericardial effusion. The effusion was later found to be due to MRSA, which was identified in blood and in pericardial fluid cultures. The patient was successfully treated with intravenous daptomycin for 6 weeks. Acute osteomyelitis of her right foot was the source of the MRSA, for which a right below-knee amputation was ultimately performed.
Intravenous leiomyomatosis with intracardiac extension: an unusual presentation of uterine leiomyoma and evaluation with 256-slice dual-source multidetector CT and cardiac MRI
Authors: Jain Neeraj , Rissam Harmeet Kaur , Mittal Umesh Kumar , Sharma Ashok
Published: December 2015

We report a case of a 40-year-old woman who presented with breathlessness, palpitations and vague pelvic pain for 6 months. The dyspnoea was non-exertional and episodic. She was a non-diabetic, non-hypertensive and had no history of prior surgeries. ECG and chest radiograph were normal. Cardiac MRI and 256-slice dual-source multidetector CT evaluation revealed the presence of a uterine and left adnexal mass with intravenous extension into the inferior vena cava via the gonadal veins, and further cephalad extension into the right atrium and ventricle. The patient was referred to the cardiothoracic surgery department and underwent two-stage surgical procedures. The first stage consisted of thoracotomy and tumour removal from the right atrium and inferior vena cava. In the second stage, hysterectomy and bilateral salpingo-oophorectomy was performed. The histological analysis of the excised specimen was consistent with an intravascular leiomyoma.
Antenatal diagnosis of aneurysmal malformation of the vein of Galen
Authors: Darji Parth J , Gandhi Viplav S , Banker Hiral , Chaudhari Hemang
Published: December 2015

Vein of Galen malformation (VGAM) results from an aneurysmal aberration with an arteriovenous shunting of blood. Vein of Galen aneurysmal malformations are the most frequent arteriovenous malformations in infants and fetuses. The congenital malformation develops during weeks 6–11 of fetal development. Infants often die from high-output congestive heart failure.
Genericity aspects of black hole formation in the collapse of spherically symmetric slightly inhomogeneous perfect fluids
Authors: Satin Seema , Malafarina Daniele , Joshi Pankaj S.
Published: December 2015

We study the complete gravitational collapse of a class of spherically symmetric inhomogeneous perfect fluid models obtained by introducing small radial perturbations in an otherwise homogeneous matter cloud. Our aim here is to study the genericity and stability of the formation of black holes and locally naked singularities in collapse. While the occurrence of naked singularities is known for many models of collapse, the key issue now in focus is genericity and stability of these outcomes. Towards this purpose, we study how the introduction of a somewhat general class of small inhomogeneities in homogeneous collapse leading to a black hole can change the final outcome to a naked singularity. The key feature that we assume for the perturbation profile is that of a mass profile that is separable in radial and temporal coordinates. The known models of dust and homogeneous perfect fluid collapse can be obtained from this choice of the mass profile as special cases. This choice is very general and physically well motivated and we show that this class of collapse models leads to the formation of a naked singularity as the final state.
A novel teleparallel dark energy model
Authors: Otalora Giovanni
Published: December 2015

Although equivalent to general relativity, teleparallel gravity (TG) is conceptually speaking a completely different theory. In this theory, the gravitational field is described by torsion, not by curvature. By working in this context, a new model is proposed in which the four-derivative of a canonical scalar field representing dark energy is nonminimally coupled to the “vector torsion”. This type of coupling is motivated by the fact that a scalar field couples to torsion through its four-derivative, which is consistent with local spacetime kinematics regulated by the de Sitter group [Formula: see text]. It is found that the current state of accelerated expansion of the universe corresponds to a late-time attractor that can be (i) a dark energy-dominated de Sitter solution ([Formula: see text]), (ii) a quintessence-type solution with [Formula: see text], or (iii) a phantom-type [Formula: see text] dark energy.
Effect of Molecular Rotation on Charge Transport Phenomena
Authors: Garg O. P. , Lamba Vijay Kr , Kaushik D. K.
Published: December 2015

The study of electron transport properties of molecular systems could be explained on the basis of the Landauer formalism. Unfortunately, due to the complexity of the experimental setup, most of these measurements have no control over the details of the electrode geometry, rotation of molecules, variation in angle of contacts, effect of fano resonances associated with side groups attached to rigid backbones, which results in a spectrum of IV-characteristics. Theoretical models can therefore help to understand and helps to develop new applications such as molecular sensors, etc. Thus we used simulation methods that generate the required structural ensemble, which is then analyzed with Green’s function methods to characterize the electronic transport properties. In present work we had discussed applications of this approach to understand the conductance in molecular system in the direction of controlling electron transport through molecules and studied the effect of rotation of sandwiched molecule.
Viral Vectors for Gene Therapy: Translational and Clinical Outlook
Authors: Kotterman Melissa A. , Chalberg Thomas W. , Schaffer David V.
Published: December 2015

In a range of human trials, viral vectors have emerged as safe and effective delivery vehicles for clinical gene therapy, particularly for monogenic recessive disorders, but there has also been early work on some idiopathic diseases. These successes have been enabled by research and development efforts focusing on vectors that combine low genotoxicity and immunogenicity with highly efficient delivery, including vehicles based on adeno-associated virus and lentivirus, which are increasingly enabling clinical success. However, numerous delivery challenges must be overcome to extend this success to many diseases; these challenges include developing techniques to evade preexisting immunity, to ensure more efficient transduction of therapeutically relevant cell types, to target delivery, and to ensure genomic maintenance. Fortunately, vector-engineering efforts are demonstrating promise in the development of next-generation gene therapy vectors that can overcome these barriers. This review highlights key historical trends in clinical gene therapy, the recent clinical successes of viral-based gene therapy, and current research that may enable future clinical application.
Behavioral Finance
Authors: Hirshleifer David
Published: December 2015

Behavioral finance studies the application of psychology to finance, with a focus on individual-level cognitive biases. I describe here the sources of judgment and decision biases, how they affect trading and market prices, the role of arbitrage and flows of wealth between more rational and less rational investors, how firms exploit inefficient prices and incite misvaluation, and the effects of managerial judgment biases. There is a need for more theory and testing of the effects of feelings on financial decisions and aggregate outcomes. Especially, the time has come to move beyond behavioral finance to social finance, which studies the structure of social interactions, how financial ideas spread and evolve, and how social processes affect financial outcomes.
Analytics of Insurance Markets
Authors: Frees Edward W.
Published: December 2015

This article describes contributions of analytics and statistical methods to our understanding of insurance operations and markets. Specifically, it introduces insurance analytics, the foundations of the discipline, and the supporting literature. It also describes current trends in analytics. Insurance as a discipline has long embraced analytics, and market trends signal an even stronger relationship going forward.
Contributions to Defined Contribution Pension Plans
Authors: Choi James J.
Published: December 2015

Defined contribution (DC) pension plans are an increasingly important means of financing retirement consumption. Because individuals often have substantial discretion over how much is contributed to their DC pension plan, studying DC contribution choices provides general insights into the determinants of individual economic decision making. The literature has found strong deviations from many predictions of classical frictionless optimizing models. I provide an overview of the US DC pension system and review the literature on the effect of matching contributions, automatic enrollment, active choice deadlines, choice overload, financial literacy, peer effects, mental accounting, and personal experience on individuals' DC contributions.
Private Equity Performance: A Survey
Authors: Kaplan Steven N. , Sensoy Berk A.
Published: December 2015

We survey the literature on private equity performance, focusing on venture capital and buyout funds rather than on portfolio companies. We describe recent findings on performance measures, average fund returns, risk adjustments, cyclicality and liquidity, persistence, interim returns and self-reported net asset values, the performance of different types of investors in funds, and the links between management contracts and fund returns. Buyout funds have outperformed the S&P 500 net of fees on average by approximately 20% over the life of the fund. Venture capital funds raised in the 1990s outperformed the S&P 500, whereas those raised in the 2000s underperformed. The results are consistent across a number of data sets and papers. Before the 2000s, buyout and venture capital fund performance showed strong evidence of persistence. Since 2000, buyout fund persistence has declined, whereas venture capital fund persistence has remained equally strong.
Finance, Theoretical and Applied
Authors: Myers Stewart C.
Published: December 2015

Like Caesar's Gaul, corporate finance is divided into three parts: theoretical, empirical, and normative. Important advances in any one of these three typically generate good ideas for the other two. I have been fortunate not to specialize in one part only. This review covers the history of capital structure theories, including the trade-off and pecking-order theories, and takes a skeptical view of how those theories have been tested so far. I give roughly equal space to normative, practical applications, including adjusted present value (APV), the valuation of real options, and the application of modern finance to regulation, insurance, the valuation of R&D, and the role of risk capital in financial institutions. Looking back, I realize that the supply of intriguing financial questions is inexhaustible.
A New Approach to Improve Accuracy of Grey Model GMC(1,n)in Time Series Prediction
Authors: Moonchai Sompop , Rakpuang Wanwisa
Published: December 2015

This paper presents a modified grey model GMC(1,n)for use in systems that involve one dependent system behavior andn-1relative factors. The proposed model was developed from the conventional GMC(1,n)model in order to improve its prediction accuracy by modifying the formula for calculating the background value, the system of parameter estimation, and the model prediction equation. The modified GMC(1,n)model was verified by two cases: the study of forecasting CO2emission in Thailand and forecasting electricity consumption in Thailand. The results demonstrated that the modified GMC(1,n)model was able to achieve higher fitting and prediction accuracy compared with the conventional GMC(1,n)and D-GMC(1,n)models.
Ballistic Reconstruction of a Migrating Bullet in the Parapharyngeal Space
Authors: Bächinger David , Bolliger Stephan , Huber Gerhard F. , Laske Roman D.
Published: December 2015

A 21-year-old male suffering from severe throat pain after being hit by a bullet in Syria claimed that he was shot through his eye and that the bullet subsequently descended behind his throat. Even though the first medical report stated that this course is implausible, meticulous workup provided evidence that the bullet might have entered the parapharyngeal space in a more cranial position than the one it was found eight months later. Our case highlights that bullets are able to move within the body, rendering ballistic reconstruction difficult. However, after removal of the bullet the patient’s symptoms completely resolved.
Perspectives for Sustainable Aviation Biofuels in Brazil
Authors: Cortez Luís A. B. , Nigro Francisco E. B. , Nogueira Luiz A. H. , Nassar André M. , Cantarella Heitor , Moraes Márcia A. F. D. , Leal Rodrigo L. V. , Franco Telma T. , Schuchardt Ulf F. , Baldassin Junior Ricardo
Published: December 2015

The aviation industry has set ambitious goals to reduce carbon emissions in coming decades. The strategy involves the use of sustainable biofuels, aiming to achieve benefits from environmental, social, and economic perspectives. In this context, Brazilian conditions are favorable, with a mature agroindustry that regularly produces automotive biofuel largely adopted by Brazilian road vehicles, while air transportation has been growing at an accelerating pace and a modern aircraft industry is in place. This paper presents the main conclusions and recommendations from a broad assessment of the technological, economic, and sustainability challenges and opportunities associated with the development of drop-in aviation biofuels in Brazil. It was written by a research team that prepared the initial reports and conducted eight workshops with the active participation of more than 30 stakeholders encompassing the private sector, government institutions, NGOs, and academia. The main outcome was a set of guidelines for establishing a new biofuels industry, including recommendations for (a) filling the identified research and development knowledge gaps in the production of sustainable feedstock; (b) overcoming the barriers in conversion technology, including scaling-up issues; (c) promoting greater involvement and interaction between private and government stakeholders; and (d) creating a national strategy to promote the development of aviation biofuels.
Design of Solar Optical Fiber Lighting System for Enhanced Lighting in Highway Tunnel Threshold Zone: A Case Study of Huashuyan Tunnel in China
Authors: Qin Xiaochun , Zhang Xuefeng , Qi Shuai , Han Hao
Published: December 2015

In this paper, the principle, structural composition, materials, and characteristics of solar optical fiber lighting system were discussed. The different luminance requirements of different zones of highway tunnel were identified on the basis of the analysis of tunnel lighting considering drivers’ visually self-accommodating physiological function for luminance change. Taken Huashuyan Tunnel of G109 Highway located in Hohhot of Inner Mongolia in China as the case study, the system design of solar optical fiber lighting for enhanced lighting in threshold zone of highway tunnel was made. It was indicated through calculation that the design length of solar optical fiber enhanced lighting was related to the design speed, longitudinal slope, and overhead clearance of the tunnel, and the design luminance of solar optical fiber enhanced lighting was related to the luminance outside the tunnel, the design speed, and the design traffic flow of the tunnel. Luminance analysis of the solar optical fiber lighting system of Huashuyan Tunnel was made based on the on-site experiment. Also, the 3D illuminance simulation results by DIALux software were made to indicate that the solar optical fiber lighting system in Huashuyan Tunnel still well met the enhanced lighting demand even not considering the contribution of LED lighting.
Advances in T Helper 17 Cell Biology: Pathogenic Role and Potential Therapy in Multiple Sclerosis
Authors: Volpe Elisabetta , Battistini Luca , Borsellino Giovanna
Published: December 2015

The discovery of the T helper (Th) 17 lineage, involved in the protection against fungal and extracellular bacterial infections, has profoundly revolutionized our current understanding of T cell‐mediated responses in autoimmune diseases, including multiple sclerosis (MS). Indeed, recent data demonstrate the pathogenic role of Th17 cells in autoimmune disorders. In particular, studies in MS and in its animal model (EAE, experimental autoimmune encephalomyelitis) have revealed a crucial role of Th17 cells in the pathogenesis of autoimmune demyelinating diseases in both mice and humans. Over the past years, several important aspects concerning Th17 cells have been elucidated, such as the factors which promote or inhibit their differentiation and the effector cytokines which mediate their responses. The identification of the features endowing Th17 cells with high pathogenicity in MS is of particular interest, and discoveries in Th17 cell biology and function could lead to the design of new strategies aimed at modulating the immune response in MS. Here, we will discuss recent advances in this field, with particular focus on the mechanisms conferring pathogenicity in MS and their potential modulation.
Metastatic Colorectal Cancer Resembling Severe Preeclampsia in Pregnancy
Authors: Khangura Raminder Kaur , Khangura Charanpreet Kaur , Desai Anagha , Goyert Gregory , Sangha Roopina
Published: December 2015

Although colorectal cancer (CRC) is the third most common cancer in women, it is a rare malignancy in pregnancy. Symptoms of CRC such as fatigue, malaise, nausea, vomiting, rectal bleeding, anemia, altered bowel habits, and abdominal mass are often considered typical symptoms of pregnancy. Many cases of CRC are diagnosed in advanced stages due to missed warning signs of CRC, which may be misinterpreted as normal symptoms related to pregnancy. This report reviews 2 cases of CRC diagnosed within a 4-month interval at our institution. Both cases were initially thought to be atypical presentations of preeclampsia. Prenatal history, hospital course, and postpartum course were reviewed for both patients. CRC is often diagnosed at advanced stages in pregnancy. Common physiological symptoms of pregnancy should be scrutinized carefully and worked up appropriately, especially if symptoms remain persistent or increase in intensity or severity.
Relevance Feedback Based Query Expansion Model Using Borda Count and Semantic Similarity Approach
Authors: Singh Jagendra , Sharan Aditi
Published: December 2015

Pseudo-Relevance Feedback (PRF) is a well-known method of query expansion for improving the performance of information retrieval systems. All the terms of PRF documents are not important for expanding the user query. Therefore selection of proper expansion term is very important for improving system performance. Individual query expansion terms selection methods have been widely investigated for improving its performance. Every individual expansion term selection method has its own weaknesses and strengths. To overcome the weaknesses and to utilize the strengths of the individual method, we used multiple terms selection methods together. In this paper, first the possibility of improving the overall performance using individual query expansion terms selection methods has been explored. Second, Borda count rank aggregation approach is used for combining multiple query expansion terms selection methods. Third, the semantic similarity approach is used to select semantically similar terms with the query after applying Borda count ranks combining approach. Our experimental results demonstrated that our proposed approaches achieved a significant improvement over individual terms selection method and related state-of-the-art methods.
Passivation and Stabilization of Aluminum Nanoparticles for Energetic Materials
Authors: Flannery Matthew , Desai Tapan G. , Matsoukas Themis , Lotfizadeh Saba , Oehlschlaeger Matthew A.
Published: December 2015

In aircraft applications, fuel is used not only as a propellant but also as a coolant and improving both the thermal conductivity and combustion enthalpy of the fuel is beneficial in these applications. These properties can be enhanced by dispersing aluminum nanoparticles into the fuel; however, the nanoparticles require stabilization from agglomeration and passivation from oxidation in order for these benefits to be realized in aircraft applications. To provide this passivation and stabilization, aluminum nanoparticles were encapsulated with a coating by the plasma enhanced chemical vapor deposition (PE‐CVD) method from toluene precursors. The thermal conductivity, combustion and ignition properties, and stability of the nanoparticles dispersed in RP‐2 fuel were subsequently evaluated. In addition, the effect of dispersing aluminum nanoparticles in RP‐2 fuel on the erosion rate of fuel nozzles was evaluated. The dispersion of PE‐CVD coated aluminum nanoparticles at a concentration of 3.0% by volume exhibited a 17.7% and 0.9% increase in thermal conductivity and volumetric enthalpy of combustion, respectively, compared to the baseline RP‐2 fuel. Additionally, particle size analysis (PSA) of the PE‐CVD coated aluminum nanofuel exhibited retention of particle size over a five‐month storage period and erosion testing of a 1 mm stainless steel nozzle exhibited a negligible 1% change in discharge coefficient after 100 hours of testing.
Settlement Behaviors of Metro Tunnels during the Metro Operation
Authors: Shi Wenbo , Miao Linchang , Wang Zhengxing , Luo Junhui
Published: December 2015

This paper investigates the settlement behaviors of a metro tunnel during metro operation. A nonlinear vibration model of vehicle-track is established, and a series of vibration loadings for the frequency domain acting on segments are obtained based on a modal analysis method and applying the Fourier transformation algorithm. The displacements at any position in the soil are derived from the segment-soil interaction coupled model with the elastic continuum theory, and its accuracy is verified by comparing with the calculation result obtained by elastic-plastic finite element model.
SO2Gas Physicochemical Removal through Pulse Streamer Discharge Technique Assisted by Vapor Additive
Authors: Wang Xiaojun , Zhang Lianshui
Published: December 2015

SO2removal has drawn extensive attentions for air pollution treatment. In this paper, the pulse streamer discharge technique is investigated. Emission spectra diagnosis experimentally indicates that the SO2molecule has been physically dissociated into SO and O radicals by electron collision and can be remediated through further chemical reactions during and after discharge. In order to quantitatively analyze the removal physical chemistry kinetics, a zero-dimensional physicochemical reaction model is established. Without H2O vapor additive, the SO2removal efficiency is leanly low and only 0.296% has been achieved under pulse discharge duration of 0.5 μs. Through increasing the electrical concentration six times, the removal efficiency has been slightly heightened to 1.796% at pulse duration of 3 μs. Contrarily, vapor additive can effectively improve the removal kinetics, and removal efficiency has been remarkably heightened to 13.0195% at pulse duration of 0.5 μs with H2O/SO2initial concentration ratio of 0.1 : 1. OH radicals decomposed from H2O through electron collision are the essential factor to achieve such improvement, which have effectively adjusted the chemical removal process to the favorite directions. The major productions have been transformed from HSO3and HOSO2to H2SO4when vapor ratio increased above 1.27 : 1.
Comparison of the Effects of Different Cryoprotectants on Stem Cells from Umbilical Cord Blood
Authors: Chen Gecai , Yue Aihuan , Ruan Zhongbao , Yin Yigang , Wang Ruzhu , Ren Yin , Zhu Li
Published: December 2015

Purpose. Cryoprotectants (CPA) for stem cells from umbilical cord blood (UCB) have been widely developed based on empirical evidence, but there is no consensus on a standard protocol of preservation of the UCB cells. Methods. In this study, UCB from 115 donors was collected. Each unit of UCB was divided into four equal parts and frozen in different kinds of cryoprotectant as follows: group A, 10% ethylene glycol and 2.0% dimethyl sulfoxide (DMSO) (v/v); group B, 10% DMSO and 2.0% dextran‐40; group C, 2.5% DMSO (v/v) + 30 mmol/L trehalose; and group D, without CPA. Results. CD34+, cell viability, colony forming units (CFUs), and cell apoptosis of pre‐ and postcryopreservation using three cryoprotectants were analyzed. After thawing, significant differences in CD34+ count, CFUs, cell apoptosis, and cell viability were observed among the four groups (P < 0.05).  Conclusion. The low concentration of DMSO with the addition of trehalose might improve the cryopreservation outcome.
Bioluminescence-Sensing Assay for Microbial Growth Recognition
Authors: Eed Heba Ramadan , Abdel-Kader Nora S. , El Tahan Mahmoud Helmy , Dai Tianhong , Amin Rehab
Published: December 2015

The conventional methods for microbial viability quantification require cultivation and are laborious. There is consequently a widespread need for cultivation-free methods. The adenosine triphosphate (ATP) bioluminescence-sensing assay is considered an extremely effective biosensor; hence ATP is the energy currency of all living microbes and can be used as a rapid indicator of microbial viability. We developed an ATP bioluminescence-sensing assay to detect microbial viability. A bioluminescent recombinantE. colistrain was used with luciferase extracted from transformed bacteria. Results showed that there is a direct correlation between the bioluminescence intensity of the ATP bioluminescence-sensing assay and the microbial viability. Bacterial counts from food samples were detected using the developed sensing assay and validated by the traditional plate-counting method. Compared with the plate-counting method, ATP bioluminescence-sensing assay is a more rapid and efficient approach for detecting microbial viability.
Antioxidant, Anti‐inflammatory, and Antiulcer Potential of Manuka Honey against Gastric Ulcer in Rats
Authors: Almasaudi Saad B. , El-Shitany Nagla A. , Abbas Aymn T. , Abdel-dayem Umama A. , Ali Soad S. , Al Jaouni Soad K. , Harakeh Steve
Published: December 2015

Gastric ulcers are among the most common diseases affecting humans. This study aimed at investigating the gastroprotective effects of manuka honey against ethanol‐induced gastric ulcers in rats. The mechanism by which honey exerts its antiulcer potential was elucidated. Four groups of rats were used: control, ethanol (ulcer), omeprazole, and manuka honey. Stomachs were examined macroscopically for hemorrhagic lesions in the glandular mucosa, histopathological changes, and glycoprotein detection. The effects of oxidative stress were investigated using the following indicators: gastric mucosal nitric oxide (NO), reduced glutathione (GSH), lipid peroxide (MDA, measured as malondialdehyde) glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Plasma tumour necrosis factor‐α, interleukin‐1β, and IL‐6 were also measured. Manuka honey significantly decreased the ulcer index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. It significantly increased gastric mucosal levels of NO, GSH, GPx, and SOD. Manuka honey also decreased gastric mucosal MDA and plasma TNF‐α, IL‐1β, and IL‐6 concentrations. In conclusion, manuka honey likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF‐α, IL‐1β, and IL‐6) in a reduced form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels.
Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease
Authors: Oliveira Claudia P. , de Lima Sanches Priscila , de Abreu-Silva Erlon Oliveira , Marcadenti Aline
Published: December 2015

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM), but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD.
A Game Theory Based Congestion Control Protocol for Wireless Personal Area Networks
Authors: Ma Chuang , Sheu Jang-Ping , Hsu Chao-Xiang
Published: December 2015

In wireless sensor networks (WSNs), the presence of congestion increases the ratio of packet loss and energy consumption and reduces the network throughput. Particularly, this situation will be more complex in Internet of Things (IoT) environment, which is composed of thousands of heterogeneous nodes. RPL is an IPv6 routing protocol in low power and lossy networks standardized by IETF. However, the RPL can induce problems under network congestion, such as frequently parent changing and throughput degradation. In this paper, we address the congestion problem between parent nodes and child nodes in RPL-enabled networks, which typically consist of low power and resource constraint devices. To mitigate the effect of network congestion, we design a parent-change procedure by game theory strategy, by which the child nodes can change next hop neighbors toward the sink. Comparing to the ContikiRPL implementation, the simulation results show that our protocol can achieve more than two times improvement in throughput and reduce packet loss rate with less increasing of average hop count.
BMP6‐Engineered MSCs Induce Vertebral Bone Repair in a Pig Model: A Pilot Study
Authors: Pelled Gadi , Sheyn Dmitriy , Tawackoli Wafa , Jun Deuk Soo , Koh Youngdo , Su Susan , Cohn Yakubovich Doron , Kallai Ilan , Antebi Ben , Da Xiaoyu , Gazit Zulma , Bae Hyun , Gazit Dan
Published: December 2015

Osteoporotic patients, incapacitated due to vertebral compression fractures (VCF), suffer grave financial and clinical burden. Current clinical treatments focus on symptoms’ management but do not combat the issue at the source. In this pilot study, allogeneic, porcine mesenchymal stem cells, overexpressing the BMP6 gene (MSC‐BMP6), were suspended in fibrin gel and implanted into a vertebral defect to investigate their effect on bone regeneration in a clinically relevant, large animal pig model. To check the effect of the BMP6‐modified cells on bone regeneration, a fibrin gel only construct was used for comparison. Bone healing was evaluated in vivo at 6 and 12 weeks and ex vivo at 6 months. In vivo CT showed bone regeneration within 6 weeks of implantation in the MSC‐BMP6 group while only minor bone formation was seen in the defect site of the control group. After 6 months, ex vivo analysis demonstrated enhanced bone regeneration in the BMP6‐MSC group, as compared to control. This preclinical study presents an innovative, potentially minimally invasive, technique that can be used to induce bone regeneration using allogeneic gene modified MSCs and therefore revolutionize current treatment of challenging conditions, such as osteoporosis‐related VCFs.
Worldwide Incidence of Autoimmune Liver Disease
Authors: Jepsen Peter , Grønbæk Lisbet , Vilstrup Hendrik
Published: December 2015

Background: The variation that occurs in the incidence patterns of autoimmune liver diseases may provide insight into the risk factors causing the diseases. We systematically reviewed studies on the incidence of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and immunoglobulin G4-associated cholangitis (IAC) in general populations. Key Messages: We found relevant studies through Medline and Scopus, and we examined whether they were population-based; the way they found cases for inclusion and which diagnostic criteria they used; and whether they used standardization to facilitate comparison with other studies. The 55 identified studies varied greatly in their case-finding methods, and only 14 (25%) of them used a standard population. Reported incidence rates of AIH were around 1 per 100,000 population per year, possibly higher in Scandinavia than in other countries, and a Danish study of the 1994-2012 period found an increasing incidence. A majority of PBC studies found incidence rates of 1-2 per 100,000 population per year and an increasing time trend, but incidence was lower in the Netherlands and New Zealand and higher in North East England. Most studies of PSC found incidence rates around 1 per 100,000 population per year, but there were no incident cases among 100,000 Alaska natives during the period 1984-2000. The incidence of IAC remains unknown. Conclusions: The incidence of the autoimmune liver diseases is around 1-2 per 100,000 population per year for each disease. The variation in incidence over time and place suggests that there are differences in the prevalence of risk factors for the diseases, but the studies used different methods and so it is difficult to draw firm conclusions. We recommend that groups of investigators conduct multisite studies with identical case-finding methods, and that they use a standard population to account for differences in demographics.
Association of Extrahepatic Manifestations with Autoimmune Hepatitis
Authors: Wong Guan Wee , Heneghan Michael A.
Published: December 2015

For many patients with autoimmune hepatitis (AIH), the presence of extrahepatic features is well recognised both at the time of presentation and during long-term follow-up. Concomitant ‘autoimmune disorders' have been described in 20-50% of patients with AIH, both in adults and children. Indeed, the presence of these associated phenomena has been incorporated into both the original and revised International AIH group scoring systems as an aid to codifying the diagnosis. In acute index presentations, non-specific joint pains sometimes flitting in nature have been reported in 10-60% of patients, and while joint swelling is uncommon, rheumatoid arthritis and mixed connective tissue disease have been reported in 2-4% of patients with AIH. For a majority of patients, these joint symptoms resolve within days of the introduction of immunosuppressive therapy. Rarer features at index presentation include a maculopapular skin rash and unexplained fever, which are features that tend to resolve quickly with treatment. Interestingly, joint pain and stiffness are also well recognised in the context of steroid withdrawal and cessation in AIH. The occasional co-presentation of AIH with coeliac disease is clinically important (1-6%), since for some patients, there is a risk of immunosuppression malabsorption, thus delaying effective treatment. Similarly, the co-existence of selective IgA deficiency (IgAD) can occur in patients with coeliac disease or in isolation. Selective IgAD as a co-existing extraheaptic feature seems to be more common in paediatric patients with AIH. For these patients, they are at an increased risk of respiratory and sinus infections. Although, typically associated with primary sclerosing cholangitis, the presence of inflammatory bowel disease (IBD; both Crohn's disease and ulcerative colitis) has been described in 2-8% of patients with AIH. Interestingly, for patients with autoimmune sclerosing cholangitis, a distinct pattern of IBD has been recently described. Other conditions have been reported at a lower frequency, including Sjogren's syndrome 1-7%, systemic lupus erythematosus 1-3% and glomerulonephritis 1%. Rarer still and at a frequency of <1% include fibrosing alveolitis, haemolytic anaemia, uveitis, mononeuritis multiplex, polymyositis and multiple sclerosis. In contrast, the reported associations between AIH and thyroiditis 8-23%, diabetes 1-10% and psoriasis 3% are commonly seen and notable in clinical practice.
Paediatric Autoimmune Liver Disease
Authors: Liberal Rodrigo , Vergani Diego , Mieli-Vergani Giorgina
Published: December 2015

In paediatrics, there are 2 liver disorders in which liver damage most likely stems from an autoimmune attack: ‘classical' autoimmune hepatitis (AIH) and the AIH/sclerosing cholangitis overlap syndrome (also known as autoimmune sclerosing cholangitis, ASC). The presentation of childhood autoimmune liver disease (AILD) is non-specific and can mimic most other liver disorders. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival. Difficult-to-treat or non-responsive patients should be treated with mycophenolate mofetil; if this fails then calcineurin inhibitors can be tried. Persistent failure to respond or lack of adherence to treatment result in end-stage liver disease. These patients, and those with fulminant liver failure at diagnosis, will require liver transplantation. ASC responds to the same immunosuppressive treatment used for AIH when treatment is initiated early. Abnormal liver function tests often resolve within a few months of treatment, although medium- to long-term prognosis is worse than that of AIH because bile duct disease continues to progress despite treatment in approximately 50% of patients. Ursodeoxycholic acid is usually added to conventional treatment regimen in ASC, but whether this actually helps arrest the progression of bile duct disease remains to be established. The pathogenesis of paediatric-onset AILD is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4pos T-cells. While Th1 effector cells are associated with hepatocyte damage in both AIH and ASC, Th17 immune responses predominate in the latter where they correlate with biochemical indices of cholestasis, indicating that IL-17 is involved in the bile duct damage characteristic of this condition. Since a substantial difference between these 2 pathologies is the frequent association of ASC with inflammatory bowel disease, it can be speculated that lymphocytes of intestinal origin are present in patients with a diagnosis of ASC rather than in those with AIH. Animal models faithfully representing the human conditions are needed to unravel the contribution of innate and adaptive, effector and regulatory immune responses. A deeper understanding of the pathogenesis of AILD is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigen-specific regulatory T-cells, which ultimately aim at restoring tolerance to liver-derived antigens.
Regulatory T Cells in Hepatic Immune Tolerance and Autoimmune Liver Diseases
Authors: Herkel Johannes
Published: December 2015

Regulatory T cells (Tregs) have a profound ability to control immune responses. A majority of Tregs are derived from the thymus; yet a substantial Treg fraction is derived from the periphery. The liver seems to be an important source of peripherally derived Tregs. Indeed, the liver's well-known ability to induce immune tolerance is at least partly based on hepatic Treg generation. With recently developed tools to deliver antigens to tolerance-inducing liver cells, it is now possible to harness liver-derived Tregs for specific control of unwanted immune responses. Indeed, the selective delivery of autoantigens to liver sinusoidal endothelial cells could induce autoantigen-specific Tregs in vivo, providing effective treatment of autoimmune disease. Owing to the fundamental role Tregs play in controlling immune responses, an impairment of Tregs seems to be a plausible explanation for the development of autoimmune diseases, for example, in the liver. However, the actual role of Treg impairment in autoimmune liver diseases, such as autoimmune hepatitis (AIH), remains controversial. Major obstacles for clarifying the role of Tregs in autoimmune liver diseases are related to the difficulty to identify human Tregs unambiguously and to the difficulty to identify those Tregs and effector T cells that specifically recognize disease-driving autoantigens. However, even if AIH turned out to be a disease that is not driven by Treg impairment, Treg-based therapies for autoimmune liver diseases might still be effective, provided the Tregs for therapeutic use recognize the relevant antigens.
Standard Treatment in Adults: Which Steroid? Or without Steroids?
Authors: Gleeson Dermot
Published: December 2015

Key Messages: (1) Standard treatment of autoimmune hepatitis in adults should be steroid based. In early trials, prednisolone +/- azathioprine was superior to the azathioprine mono-therapy (which was not significantly better than placebo). Prednisolone plus azathioprine has similar efficacy to, but is better tolerated than a higher-dose of prednisolone alone and therefore has become standard therapy. (2) In most treated patients, serum transaminases and globulin/IgG fall, but percentage attaining normal values within 6 months varies between 10 and 90%. Patients failing to do so have a worse longer-term outcome. (3) A higher initial prednisolone dose (1 mg/kg/day) plus azathioprine achieved 76% serum transaminase normalisation after 6 months but needs longer-term evaluation. (4) Histological remission (minimal hepatitis on re-biopsy) lags behind transaminase normalisation by 6-12 months and is achieved in 55-70% of patients after 24-36 months prednisolone. This lag and the inefficacy of azathioprine mono-therapy justifies continuing prednisolone (5-10 mg/day), even after transaminase normalisation, for a total of >2 years. (5) Repeat biopsy should be considered because 40-60% of patients still have (usually mild) persisting inflammation, despite normal serum transaminases and IgG. In such patients, fibrosis is less likely to regress and long-term mortality is higher. (6) In a large trial, non-cirrhotic treatment-naïve patients given budesonide (9 mg/day) plus azathioprine were more likely to achieve normal serum ALT after 6 months than those receiving prednisolone plus azathioprine and had less side effects. This trial was short term in nature and lacked follow-up histology. Budesonide is recommended in non-cirrhotic patients who develop prednisolone-related side effects. In an open study of mycophenolate plus prednisolone, 88% of treatment-naïve patients achieved normal serum transaminases. However, half relapsed during or after steroid withdrawal and only one of eight re-biopsied patients achieved histological remission. Mycophenolate is teratogenic, limiting its use in younger women. Conclusion: Despite its limitations, no regime has yet been shown clearly to be better than prednisolone and azathioprine-based therapy.