bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel nitrogen-containing compound with D-π-A structure: theoretical and experimental study
Authors: Gong Xiaoting , Zhou Ziyan , Zhang Shuguang , Zhuo Shuping , Huang Xiurong , Jiang Siquan , Su Zhongmin
Published: March 2014

2-(2-Hydroxy-styryl)-4,6-dimethyl-1,3,5-triazine (P1), a novel compound with D-π-A structure, possesses a variety of isomers. Density functional theory calculations were employed to explore the isomerization mechanisms of its various isomers at the 6-311+G** level. The calculated results show that the phenol configurations of compound P1 are more stable than the quinoid configurations, whether they exist as monomers, complexes, with methanol or dimers. The most stable structure of compound P1 was used to calculate the UV-vis and fluorescence spectra. To validate the calculated results, the title compound was synthesized and characterized by 1H NMR and 13C NMR techniques. The measured absorption and fluorescence spectra of P1 in methanol and N,N-dimethylformamide are in good agreement with the calculated ones.
Kinetics studies of rapid strain-promoted [3+2] cycloadditions of nitrones with bicyclo[6.1.0]nonyne
Authors: MacKenzie Douglas A. , Pezacki John Paul
Published: March 2014

Strain-promoted alkyne−nitrone cycloaddition (SPANC) reactions represent a bioorthogonal labeling strategy that is both very rapid and at the same time efficient and selective. Nitrones provide increased reaction rates as well as greater susceptibility toward stereoelectronic modification when compared with organic azides. We find that strain-promoted cycloadditions of cyclic nitrones with bicyclo[6.1.0]nonyne react with second-order rate constants as large as 1.49 L mol−1 s−1 at 25 °C. These reactions display rate constants that are up to 37-fold greater than those of the analogous reactions of benzyl azide with bicyclo[6.1.0]nonyne. We observed that reactions of nitrones with bicyclo[6.1.0]nonyne showed a stronger dependence on substituent effect for the reaction, as evidenced by a larger Hammett ρ value, than that for biaryl-aza-cyclooctanone. We demonstrate the ability to stereoelectronically tune the reactivity of nitrones towards different cyclooctynes in SPANC reactions. This ability to introduce selectivity into different SPANC reactions through substituent provides the opportunity to perform multiple SPANC reactions in one reaction vessel and opens up potential applications in multiplex labeling.
RECOGNITION OF BASIC HUMAN ACTIONS USING DEPTH INFORMATION
Authors: KEÇELI ALI SEYDI , CAN AHMET BURAK
Published: March 2014

Human action recognition using depth sensors is an emerging technology especially in game console industry. Depth information can provide robust features about 3D environments and increase accuracy of action recognition in short ranges. This paper presents an approach to recognize basic human actions using depth information obtained from the Kinect sensor. To recognize actions, features extracted from angle and displacement information of joints are used. Actions are classified using support vector machines and random forest (RF) algorithm. The model is tested on HUN-3D, MSRC-12, and MSR Action 3D datasets with various testing approaches and obtained promising results especially with the RF algorithm. The proposed approach produces robust results independent from the dataset with simple and computationally cheap features.
A GENERAL FRAMEWORK FOR MANIFOLD RECONSTRUCTION FROM DIMENSIONALITY REDUCTION
Authors: QIU XIAN'EN , ZHAO ZHONG , FENG GUOCAN , WANG PATRICK S. P.
Published: March 2014

Recently, many dimensionality reduction (DR) algorithms have been developed, which are successfully applied to feature extraction and representation in pattern classification. However, many applications need to re-project the features to the original space. Unfortunately, most DR algorithms cannot perform reconstruction. Based on the manifold assumption, this paper proposes a General Manifold Reconstruction Framework (GMRF) to perform the reconstruction of the original data from the low dimensional DR results. Comparing with the existing reconstruction algorithms, the framework has two significant advantages. First, the proposed framework is independent of DR algorithm. That is to say, no matter what DR algorithm is used, the framework can recover the structure of the original data from the DR results. Second, the framework is space saving, which means it does not need to store any training sample after training. The storage space GMRF needed for reconstruction is far less than that of the training samples. Experiments on different dataset demonstrate that the framework performs well in the reconstruction.
IMAGES OF WORD MAPS IN ALMOST SIMPLE GROUPS AND QUASISIMPLE GROUPS
Authors: LEVY MATTHEW
Published: March 2014

It has been shown by Lubotzky in [10] that the set of verbal images of a fixed non-abelian finite simple group G is precisely the set of automorphism invariant subsets of G. Here, we use similar methods to those of Lubotzky to determine the verbal images of certain almost simple groups and quasisimple groups.
A CACTUS THEOREM FOR END CUTS
Authors: EVANGELIDOU ANASTASIA , PAPASOGLU PANOS
Published: March 2014

Dinits–Karzanov–Lomonosov showed that it is possible to encode all minimal edge cuts of a graph by a tree-like structure called a cactus. We show here that minimal edge cuts separating ends of the graph rather than vertices can be "encoded" also by a cactus. As a corollary, we obtain a new proof of Stallings' ends theorem. We apply our methods to finite graphs as well and we show that several types of cuts can be encoded by cacti.
Locating sets and numbers of graphs associated to commutative rings
Authors: Pirzada S. , Raja Rameez , Redmond Shane
Published: March 2014

For a graph G(V, E) with order n ≥ 2, the locating code of a vertex v is a finite vector representing distances of v with respect to vertices of some ordered subset W of V(G). The set W is a locating set of G(V, E) if distinct vertices have distinct codes. A locating set containing a minimum number of vertices is a minimum locating set for G(V, E). The locating number denoted by loc (G) is the number of vertices in the minimum locating set. Let R be a commutative ring with identity 1 ≠ 0, the zero-divisor graph denoted by Γ(R), is the (undirected) graph whose vertices are the nonzero zero-divisors of R with two distinct vertices joined by an edge when the product of vertices is zero. We introduce and investigate locating numbers in zero-divisor graphs of a commutative ring R. We then extend our definition to study and characterize the locating numbers of an ideal based zero-divisor graph of a commutative ring R.
Rota–Baxter operators on skew generalized power series rings
Authors: Mazurek Ryszard
Published: March 2014

Let R be a ring, S a strictly ordered monoid, and ω : S → End (R) a monoid homomorphism. The skew generalized power series ring R[[S, ω]] is a common generalization of (skew) polynomial rings, (skew) Laurent polynomial rings, (skew) power series rings, (skew) Laurent series rings, (skew) monoid rings, (skew) Mal'cev–Neumann series rings, and generalized power series rings. We characterize those subsets T of S for which the cut-off operator with respect to T is a Rota–Baxter operator on the ring R[[S, ω]]. The obtained results provide a large class of noncommutative Rota–Baxter algebras.
Leibniz central extensions of Lie superalgebras
Authors: Wang Yan , Pei Yufeng , Deng Shaoqiang
Published: March 2014

In this paper, we develop a general theory on Leibniz central extensions of Lie superalgebras and apply it to determine the second Leibniz cohomology groups for several classes of Lie superalgebras, including classical Lie superalgebras, Neveu–Schwarz superalgebras, differentiably simple Lie superalgebras, and affine (toroidal) Kac–Moody Lie superalgebras.
Algebraic functional equation for Hida family
Authors: Jha Somnath , Pal Aprameyo
Published: March 2014

We prove a functional equation for the characteristic ideal of the "big" Selmer group 𝒳(𝒯ℱ/F cyc ) associated to an ordinary Hida family of elliptic modular forms over the cyclotomic ℤp extension of a general number field F, under the assumption that there is at least one arithmetic specialization whose Selmer group is torsion over its Iwasawa algebra. For a general number field, the two-variable cyclotomic Iwasawa main conjecture for ordinary Hida family is not proved and this can be thought of as an evidence to the validity of the Iwasawa main conjecture. The central idea of the proof is to prove a variant of the result of Perrin-Riou [Groupes de Selmer et accouplements; cas particulier des courbes elliptiques, Doc. Math.2003 (2003) 725–760, Extra Volume: Kazuya Kato's fiftieth birthday] by constructing a generalized pairing on the individual Selmer groups corresponding to the arithmetic points and make use of the appropriate specialization techniques of Ochiai [Euler system for Galois deformations, Ann. Inst. Fourier (Grenoble)55(1) (2005) 113–146].
Finite element analysis of WC–Al2O3 composites
Authors: Patel Satyanarayan , Vaish Rahul
Published: March 2014

Object oriented finite element analysis (OOF2) is used to estimate the thermal and mechanical properties of WC– Al 2 O 3 composites. In the present work, five compositions of 10%, 20%, 30%, 40% and 50% Al 2 O 3 (by volume) are studied. Young's modulus, thermal conductivity and thermal expansion coefficient are estimated using OOF2 and compared with other known analytical methods. Stress and strain contours are plotted to study the thermal and mechanical behavior of composites. It is found that the stresses are largely concentrated at the interfaces of the WC– Al 2 O 3 phases.
Influence of igneous sills on Paleocene turbidite deposition in the Faroe–Shetland Basin: a case study in Flett and Muckle sub-basin and its implication for hydrocarbon exploration
Authors: Egbeni Sylvester , McClay Ken , Jian-kui Fu Jack , Bruce Duncan
Published: March 2014

A new interpretation on three-dimensional seismic data from the Flett and Muckle sub-basins of the Faroe–Shetland Basin has shown dyke and sill emplacement influencing the Paleocene turbidite deposition. Sill and dyke emplacement in the study area created significant inflation anticlines during Paleocene time and affected palaeotopography at the seafloor. The uplift of older Early Paleocene (Sullom) and Middle Paleocene (early Vaila) turbidite deposits results in their erosion and redeposition in adjacent lows or transports them further into the basin by erosive channels. By using public domain well and biostratigraphic data from wells 208/19-1, 206/2a-1 and 206/1-2, seismic data and the use of seismic sequence stratigraphy to map the onlapping seismic reflectors on the flanks of the inflated anticlines, the relative timing of sill emplacement in the study area is shown to be Early–Middle Paleocene. The ability to identify these systems and understand the interaction between palaeotopography and Paleocene turbidite deposition in the basin is key to unlocking the hydrocarbon potential in the UK flank of the Faroe–Shetland Basin.
Faroe Marine Ash Zone IV: a new MIS 3 ash zone on the Faroe Islands margin
Authors: Wastegård Stefan , Rasmussen Tine L.
Published: March 2014

A basaltic tephra layer from MIS 3 has been discovered by analysis of cores from the Faroe Islands margin. The tephra layer appears up to 20 cm thick in some records. After the first main fall-out event the tephra is believed to be mainly deposited and redistributed by bottom currents. Geochemical analyses suggest that the tephra is relatively undisturbed by allochtonous tephra grains and unmixed. The peak occurrences are in the lower part of GIS (Greenland Interstadial) 12 and we suggest naming this new tephra Faroe Marine Ash Zone IV (FMAZ IV), following the nomenclature adopted for previous ash zones found on the Faroe Islands margin. Geochemical analyses of the tephra show affinities with the Grímsvötn volcanic system in the Eastern Volcanic Zone in south Iceland. The average age of FMAZ IV from four independent age models is 46 800±1000 years BP. We suggest that the V5 ash zone, found on the Reykjanes Ridge is a correlative to the FMAZ IV.

Supplementary material:

Single-grain analyses of tephra from FMAZ IV in cores from the northern Faroe margin and the central Faroe-Shetland Channel are available at
http://www.geolsoc.org.uk/SUP18714
Temporal order judgments are disrupted more by reflexive than by voluntary saccades
Authors: Yabe Yoshiko , Goodale Melvyn A. , Shigemasu Hiroaki
Published: March 2014

We do not always perceive the sequence of events as they actually unfold. For example, when two events occur before a rapid eye movement (saccade), the interval between them is often perceived as shorter than it really is and the order of those events can be sometimes reversed (Morrone MC, Ross J, Burr DC. Nat Neurosci 8: 950–954, 2005). In the present article we show that these misperceptions of the temporal order of events critically depend on whether the saccade is reflexive or voluntary. In the first experiment, participants judged the temporal order of two visual stimuli that were presented one after the other just before a reflexive or voluntary saccadic eye movement. In the reflexive saccade condition, participants moved their eyes to a target that suddenly appeared. In the voluntary saccade condition, participants moved their eyes to a target that was present already. Similarly to the above-cited study, we found that the temporal order of events was often misjudged just before a reflexive saccade to a suddenly appearing target. However, when people made a voluntary saccade to a target that was already present, there was a significant reduction in the probability of misjudging the temporal order of the same events. In the second experiment, the reduction was seen in a memory-delay task. It is likely that the nature of the motor command and its origin determine how time is perceived during the moments preceding the motor act.
Similarities in error processing establish a link between saccade prediction at baseline and adaptation performance
Authors: Wong Aaron L. , Shelhamer Mark
Published: March 2014

Adaptive processes are crucial in maintaining the accuracy of body movements and rely on error storage and processing mechanisms. Although classically studied with adaptation paradigms, evidence of these ongoing error-correction mechanisms should also be detectable in other movements. Despite this connection, current adaptation models are challenged when forecasting adaptation ability with measures of baseline behavior. On the other hand, we have previously identified an error-correction process present in a particular form of baseline behavior, the generation of predictive saccades. This process exhibits long-term intertrial correlations that decay gradually (as a power law) and are best characterized with the tools of fractal time series analysis. Since this baseline task and adaptation both involve error storage and processing, we sought to find a link between the intertrial correlations of the error-correction process in predictive saccades and the ability of subjects to alter their saccade amplitudes during an adaptation task. Here we find just such a relationship: the stronger the intertrial correlations during prediction, the more rapid the acquisition of adaptation. This reinforces the links found previously between prediction and adaptation in motor control and suggests that current adaptation models are inadequate to capture the complete dynamics of these error-correction processes. A better understanding of the similarities in error processing between prediction and adaptation might provide the means to forecast adaptation ability with a baseline task. This would have many potential uses in physical therapy and the general design of paradigms of motor adaptation.
Expression Profiling Using a cDNA Array and Immunohistochemistry for the Extracellular Matrix Genes FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 in Colorectal Carcinoma Progression and Dissemination
Authors: Lustosa Suzana Angelica Silva , de Souza Viana Luciano , Affonso Renato José , Silva Sandra Regina Morini , Denadai Marcos Vinicius Araujo , de Toledo Silvia Regina Caminada , Oliveira Indhira Dias , Matos Delcio
Published: March 2014

Colorectal cancer dissemination depends on extracellular matrix genes related to remodeling and degradation of the matrix structure. This investigation intended to evaluate the association between FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 gene and protein expression levels in tumor tissue with clinical and histopathological neoplastic parameters of cancer dissemination. The expression associations between ECM molecules and selected epithelial markers EGFR, VEGF, Bcl2, P53, and KI-67 have also been examined in 114 patients with colorectal cancer who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry tissue microarray methods were performed in samples from the primary tumors. The gene expression results showed that the ITGA-3 and ITGB-5 genes were overexpressed in tumors with lymph node and distant metastasis (III/IV-stage tumors compared with I/II tumors). The MMP-2 gene showed significant overexpression in mucinous type tumors, and MMP-9 was overexpressed in villous adenocarcinoma histologic type tumors. The ECM genes MMP9 and ITGA-3 have shown a significant expression correlation with EGFR epithelial marker. The overexpression of the matrix extracellular genes ITGA-3 and ITGB-5 is associated with advanced stage tumors, and the genes MMP-2 and MMP-9 are overexpressed in mucinous and villous adenocarcinoma type tumors, respectively. The epithelial marker EGFR overactivity has been shown to be associated with the ECM genes MMP-9 and ITGA-3 expression.
Treatment of Anemia Progression via Magnetite and Folate NanoparticlesIn Vivo
Authors: Elsayed Hanaa Hussein , Al-Sherbini Al Sayed A. M. , Abd-Elhady Eman Elsayed , Ahmed Kawkab Abd El Aziz.
Published: March 2014

Iron deficiency anemia is a major global public health problem. Food fortification with iron (Fe) can be an effective strategy to control iron deficiency. An iron oxide nanoparticle (NP) is a new physical and chemical property form. These properties (small particle size, unique physical properties) make nanoiron a great scientific interest especially in the treatment of anemia. The study aimed to reduce anemia by nanoparticles (NPs). Forty-eight adult female Sprague-Dewily rats were divided into four groups (12 rats each). Group A represented a negative control. Other groups were fed standard diet iron free and three time of require zinc to reach anemic. Group B fed standard diet with ferrous sulfate until the improvement of the situation of anemia or for 8 weeks. Groups C and D were divided into three subgroups; each subgroup was fed a dose from magnetite or folate coated magnetite NPs. Results showed that symptoms of loss of appetite and severe lethargy demonstrate that magnetite and folate-coated magnetite nanoparticles have serious toxicological effectsin vivo. Some doses from NPs improve blood picture during 2 weeks but change in histopathology examinations were occur in some groups within 2 weeks. Nanoparticles were considered the toxicological hazards especially the size of less than 54 nm.
Comparison of Metformin and Repaglinide Monotherapy in the Treatment of New Onset Type 2 Diabetes Mellitus in China
Authors: Ma J. , Liu L. Y. , Wu P. H. , Liao Y. , Tao T. , Liu W.
Published: March 2014

Objective. This study was designed to compare the effects of metformin and repaglinide on the fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in newly diagnosed type 2 diabetes in China.Methods. A total of 107 newly diagnosed type 2 diabetic patients (46 women and 61 men) participated in the study. All patients received 3-month treatment of metformin or repaglinide. Fasting blood glucose and HbA1c were determined at baseline and at the end of the 3-month of treatment.Results. FPG and HbA1c decreased in both metformin and repaglinide groups after 3 months treatment (P<0.01). The reduction of HbA1c was significantly greater in the repaglinide group(P<0.01). Metformin decreases fasting insulin concentration and HOMA-IR(P<0.01), and repaglinide improves HOMA-β  (P<0.01). Triglycerides (TG) were reduced in both groups(P<0.01in metformin group;P<0.05in repaglinide group), but total cholesterol (TC) and low-density lipoprotein (LDL) were decreased only after metformin treatment(P<0.05).Conclusions. Both repaglinide and metformin were effective in glycaemic control in new onset patients with type 2 diabetes in China. Repaglinide had no effect on insulin sensitivity, but it improvedβ-cell function.
Using Technology in Elementary Mathematics Teacher Education: A Sociocultural Perspective
Authors: Abramovich Sergei , Connell Michael L.
Published: March 2014

A central tenet of mathematics education reform is the integral role of technology at all grade levels. The current technological changes combined with the changes in the mathematics content and instructional method require elementary mathematics teachers to be able to design technology intensive lessons for exploration and discovery of these concepts through appropriate computer applications. In actual practice, however, most computer applications provided for mathematics education consist of software designed for a specific educational purpose: the solution in a can scenario. Furthermore, economic constraints often stand in the way of incorporating such special purpose software into an instructional setting. In this paper we will discuss an alternative to this traditional approach which shifts the instructional focus specific computer applications to more sophisticated uses of general purpose software. In particular educational uses of spreadsheets will be developed as an exemplar for this approach.
Effect of Fresh Orange Juice Intake on Physiological Characteristics in Healthy Volunteers
Authors: Asgary Sedigheh , Keshvari Mahtab , Afshani Mohammad Reza , Amiri Masoud , Laher Ismail , Javanmard Shaghayegh Haghjooy
Published: March 2014

Background. Impaired endothelial function is a predictor of cardiovascular events. Orange juice (OJ) is rich in dietary flavonoids and could inhibit oxidative stress and inflammatory responses. We examined the effects of commercial (COJ) and fresh orange juice (FOJ) on endothelial function and physiological characteristics in healthy humans. Materials and Methods. Twenty-two healthy volunteers years were enrolled in a single blind randomized crossover controlled trial. The two groups consumed either COJ for the first 4 weeks and then FOJ (CFOJ, 4 weeks), or FOJ for the first 4 weeks and then COJ (FCOJ, 4 weeks). We assessed endothelial function by measuring flow-mediated dilation, serum concentrations of lipids, apolipoproteins A and B (apo A-1 and apo B), and inflammatory markers such as vascular endothelial adhesion molecule 1 (VCAM-1), E-selectin, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6. Results. Consumption of both juices decreased VCAM, hs-CRP, and E-selectin but increased apo A-1. A decline in LDL occurred in the FOJ group. There were no differences between the characteristics of two groups, with the exception of apo A-1 levels that were increased with both forms of OJ. The largest variations occurred with hs-CRP, VCAM in both groups. Conclusion. Consumption of COJ and FOJ produced beneficial effects on the physiological characteristics of healthy volunteers. Although these results could encourage the consumption of OJ, intervention studies are needed to determine the long-term effects of these types of OJ on metabolic and cardiovascular endpoints.
The Many Faces of Human Leukocyte Antigen-G: Relevance to the Fate of Pregnancy
Authors: Dahl Mette , Djurisic Snezana , Hviid Thomas Vauvert F.
Published: March 2014

Pregnancy is an immunological paradox, where fetal antigens encoded by polymorphic genes inherited from the father do not provoke a maternal immune response. The fetus is not rejected as it would be theorized according to principles of tissue transplantation. A major contribution to fetal tolerance is the human leukocyte antigen (HLA)-G, a nonclassical HLA protein displaying limited polymorphism, restricted tissue distribution, and a unique alternative splice pattern. HLA-G is primarily expressed in placenta and plays multifaceted roles during pregnancy, both as a soluble and a membrane-bound molecule. Its immunomodulatory functions involve interactions with different immune cells and possibly regulation of cell migration during placental development. Recent findings include HLA-G contributions from the father and the fetus itself. Much effort has been put into clarifying the role of HLA-G during pregnancy and pregnancy complications, such as preeclampsia, recurrent spontaneous abortions, and subfertility or infertility. This review aims to clarify the multifunctional role of HLA-G in pregnancy-related disorders by focusing on genetic variation, differences in mRNA stability betweenHLA-Galleles, differences in HLA-G isoform expression, and possible differences in functional activity. Furthermore, we highlight important observations regardingHLA-Ggenetics and expression in preeclampsia that future research should address.
On Formal and Automatic Security Verification of WSN Transport Protocols
Authors: Ta Vinh Thong , Buttyán Levente , Dvir Amit
Published: March 2014

We address the problem of formal and automated security verification of transport protocols for wireless sensor networks (WSN) that may perform cryptographic operations. The verification of this class of protocols is difficult because they typically consist of complex behavioral characteristics, such as real-time, probabilistic, and cryptographic operations. To solve this problem, we propose a probabilistic timed calculus for cryptographic protocols and demonstrate how to use this formal language for proving security or vulnerability of protocols. The main advantage of the proposed language is that it supports an expressive syntax and semantics, allowing for studying real-time, probabilistic, and cryptographic issues at the same time. Hence, it can be used to verify systems that involve these three properties in a convenient way. In addition, we propose an automatic verification method, based on the well-known PAT process analysis toolkit, for this class of protocols. For demonstration purposes, we apply the proposed manual and automatic proof methods for verifying the security of DTSN and SDTP, which are two of the recently proposed WSN transport protocols.
Auditory Steady-State Response in the First Six Months of Life
Authors: Oliveira Luciana Cristina , Alvarenga Kátia de Freitas , Araújo Eliene Silva , Salgado Manoel Henrique , Costa Filho Orozimbo Alves
Published: March 2014

Objective: To characterize the thresholds of the auditory steady-state response that relates to term newborns and infants. Design: The study was cross-sectional using auditory steady-state response assessment, and the real-ear-to-dial difference was measured in the external auditory canal. Study Sample: The study group included 60 newborns and infants between the age of 0 and 6 months. Results: A statistically significant difference was found in the carrier frequency variable for auditory steady-state response thresholds but not in comparison to ages. Furthermore, there is an association between auditory steady-state response thresholds and the real-ear-to-dial difference. Conclusion: The same threshold can be used as a normality reference for this age range, with distinct values for the different carrier frequencies. The influence of external auditory canal amplification should be taken into account.
Decreased Level of sRAGE in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset
Authors: Glasnović Anton , Cvija Hrvoje , Stojić Maristela , Tudorić-Đeno Ivana , Ivčević Sanja , Romić Dominik , Tičinović Nino , Vuletić Vladimira , Lazibat Ines , Grčević Danka
Published: March 2014

Objectives: Receptor for advanced glycation end products (RAGE) ligands/RAGE interactions have been proposed to have a pathogenic role in neuroinflammatory disorders. Our study aimed to assess changes in high-mobility group box (HMGB)1 and its receptor RAGE in peripheral blood (PBL) and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) at the disease onset compared with control subjects. Methods: PBL and CSF were collected from control subjects (n = 30) and MS patients (n = 27) at clinical onset. Soluble RAGE (sRAGE), HMGB1, S100 calcium-binding protein A12 (S100A12), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured in the CSF and plasma by enzyme-linked immunosorbent assay. Gene expression in PBL mononuclear cells (PBMCs) was detected by quantitative PCR for RAGE, HMGB1, S100A12 and several proinflammatory/immunoregulatory cytokines. Results: We found a significantly lower expression of IL-10 (p = 0.031) in the PBMCs of MS patients. The level of sRAGE in the CSF of MS patients was lower (p = 0.021), with the ability to discriminate between MS patients and control subjects. Moreover, PBMC gene expression for HMGB1 and S100A12 positively correlated with IL-6. Conclusions: Our study confirmed that the cytokine network is disturbed in PBL and CSF at MS clinical onset. The deregulated HMGB1/RAGE axis found in our study may present an early pathogenic event in MS, proposing sRAGE as a possible novel therapeutic strategy for MS treatment.
Epidemiology of Eosinophilic Esophagitis
Authors: Hruz Petr
Published: March 2014

Eosinophilic esophagitis (EoE) is an allergy-associated disease defined clinically by esophagus-related symptoms in combination with a dense esophageal eosinophilia, both of which are unresponsive to prolonged acid suppression with proton pump inhibitors. Over the last two decades EoE has increasingly been recognized in various geographical areas (mostly industrialized countries) with high socioeconomic development. The prevalence rate is increasing and reaches up to 50 patients per 100,000 inhabitants in some indicator regions. Whether this increased prevalence is due to a real increase in incidence, a result of increased awareness by health care providers or because of the nonfatal nature of EoE adding more and more cases to the patient pool is still a matter of controversy. Several studies have consistently demonstrated a male predominance in EoE, with a male-to-female risk ratio of 3:1. The average age at diagnosis ranges between 30 and 50 years and suggests that EoE is a disease of the middle-aged man. It can affect patients of every race, but the disease is more common among Caucasians. In both children and adults, EoE has been clearly associated with allergies to food and aeroallergens, and most EoE patients present with a personal allergic background (e.g. asthma, rhinoconjunctivitis or oral allergy syndrome). In conclusion, knowledge of epidemiologic parameters of EoE is crucial for identifying risk factors as well as pathogenic mechanisms, planning preventive measures and determining optimal treatment strategies.
Diagnostics of Eosinophilic Esophagitis: Clinical, Endoscopic, and Histologic Pitfalls
Authors: Dellon Evan S.
Published: March 2014

Eosinophilic esophagitis (EoE) is currently defined as an immune-mediated chronic esophageal disorder that is diagnosed using both clinical and pathologic information. A series of consensus diagnostic guidelines for EoE have brought a measure of consistency to the field, but in practice the diagnosis of EoE can be challenging. Typical clinical symptoms of EoE, including dysphagia, heartburn, and chest pain, can overlap with gastroesophageal reflux disease, which itself is a common indication for performing endoscopic evaluation. The endoscopic findings of EoE, such as esophageal rings, strictures, linear furrows, and white exudates, are not specific. Esophageal eosinophilia, the histologic hallmark of EoE, is also not pathognomonic and can be seen in a range of conditions. Further complicating the diagnosis of EoE is the newly recognized entity of proton pump inhibitor-responsive esophageal eosinophilia, a condition that must be excluded prior to confirming a diagnosis of EoE. This paper will review the current diagnostic criteria for EoE and discuss multiple clinical, endoscopic, and histologic pitfalls in making the diagnosis of EoE.
Eosinophilic Esophagitis: Asthma of the Esophagus?
Authors: Virchow J. Christian
Published: March 2014

The question whether eosinophilic esophagitis (EoE) might be an ‘asthma of the esophagus' is reasonable. There are a number of similarities between the two diseases: EoE and asthma, as well as other atopic diseases, are frequently associated and have a number of similarities in their pathogenesis. Thus, investigating differences and similarities between the diseases might be a worthwhile endeavor. Both EoE and asthma are chronic immune-mediated conditions characterized by inflammatory changes in the mucosa and submucosa with a characteristic and diagnostic infiltration of eosinophils. They result in organ dysfunction with considerable morbidity and (in the case of asthma) even mortality. Asthma and EoE affect all ages, but frequently start in childhood or adolescence. While asthma has seen a large increase in its prevalence in the past 50 years, EoE was first described in the 1970s. Since then the frequency of the diagnosis of EoE has increased significantly. The prevalence for both diseases seems to be highest in the Western world. In contrast to asthma, where females are more often affected, EoE is more frequent in males. Asthma in children, however, is also more common in boys, but this changes after puberty. EoE is frequently associated with asthma, and up to 80% of patients with EoE are atopic, similar to childhood asthma. Adult-onset asthma is not necessarily associated with atopy (termed intrinsic asthma) and similar observations have been made for EoE. Endoscopically, asthmatic airway mucosa as well as esophageal mucosa in EoE can appear normal, and biopsies are required for diagnosis. Long-standing disease in asthma has been associated with ‘remodeling' compared to predominantly reversible inflammatory changes early in the course of the disease. Similar observations have been made in EoE. Toxic proteins derived from eosinophils such as major basic protein, eosinophil-derived neurotoxin and eosinophil cationic protein can be found in the mucosa of both diseases, which are also characterized by a thickening of the lamina propria or basement membrane, respectively. Despite these histologic and immunochemistry findings, asthma as well as EoE remain clinical diagnoses, and diagnosing either condition can be challenging. Therapeutically, both diseases respond well to corticosteroids. Ironically, corticosteroids for inhalation are deliberately swallowed in EoE to reach the esophageal mucosa. Allergen/food avoidance can improve symptoms in asthma and EoE. Taken together, allergic asthma and EoE have a number of common features which make a common pathogenesis manifested in different organs for reasons not yet fully understood likely. Combining allergological research with gastroenterologic and pneumologic expertise with a focus on similarities between these diseases might be a way forward.
Clinical Features of Eosinophilic Esophagitis
Authors: Miehlke Stephan
Published: March 2014

Eosinophilic esophagitis (EoE) may affect individuals at any age with a predominance for Caucasian males. The clinical manifestation of EoE is strongly age dependent. While dysphagia and food impaction are typical lead symptoms in adults and adolescents, infants often present with unspecific symptoms such as feeding problems, abdominal pain and vomiting. Some EoE patients may also experience heartburn. Therefore, EoE should always be considered in cases of heartburn refractory to antireflux therapy. Concomitant allergic diseases such as asthma, rhinitis and eczema are prevalent. Peripheral eosinophilia and elevated total serum IgE values are found in up to 50 and 70% of cases, respectively. Endoscopic features of EoE are variable and none of them is pathognomonic. Frequent findings are mucosal edema, furrows, exudates and corrugated rings. These endoscopic abnormalities have high specificities (90-95%), but low sensitivities (15-48%). A novel grading and classification system for the endoscopic assessment of EoE has been proposed which includes fixed rings, exudates, furrows and edema as major features. This classification system demonstrated good interobserver agreement among pediatric and adult gastroenterologists, and presents a useful tool to standardize endoscopic assessments and to further investigate the relation between endoscopic manifestation, clinical activity and response to treatment in EoE. Long-term follow-up studies have shown that EoE is a chronic disease causing recurrent dysphagia in the majority of cases. The prevalence of strictures significantly increases with the duration of disease, which stresses the importance of early diagnosis and consequent treatment of EoE.
Histopathology of Eosinophilic Esophagitis
Authors: Collins Margaret H.
Published: March 2014

Eosinophilic esophagitis (EoE), a chronic relapsing antigen-driven disease, is associated with characteristic esophageal histopathology, including ≥15 intraepithelial eosinophils in at least one high-power field (HPF), and alterations in the epithelium and subepithelial connective tissue. Currently, the pathologic changes in EoE are characteristic but not pathognomonic: the differential diagnosis includes gastroesophageal reflux disease, proton pump inhibitor-responsive esophageal eosinophilia, EoE with significant eosinophilic inflammation in other parts of the gastrointestinal tract (eosinophilic gastrointestinal disorder), etc. EoE biopsy pathology does not vary according to age, sex, or familial predisposition. Genetic analyses of EoE esophageal biopsies have identified a characteristic transcriptome that includes upregulation of several genes that relate to histopathology, such as periostin, thymic stromal lymphopoietin, and desmoglein. Diagnostic pitfalls include the patchy distribution of the characteristic EoE pathology; examining multiple biopsies increases the disease detection rate. The method used to quantitate eosinophils, including the size of the HPF, influences the diagnostic yield, but excellent interobserver variability is achieved among pathologists who agree to a uniform methodology. Therapy for EoE includes diet-based approaches to eliminate offending antigens, topical steroid therapy, and novel biologic agents including monoclonal antibodies. Following appropriate therapy, biopsies may revert to normal histology, but signs and symptoms of esophageal dysfunction may persist. A potential explanation is that endoscopic biopsies obtain very small superficial fragments of tissue from an organ that has complex underlying neuromuscular components; unseen pathology in those loci may influence the clinical state of patients with normal epithelial biopsies.
Requirements of the Pathologist to the Endoscopist (Biopsy Sampling)
Authors: Bussmann Christian
Published: March 2014

The diagnosis of eosinophilic esophagitis is based upon corresponding histological and clinical findings. To obtain a reliable diagnosis, the clinician should ideally submit four biopsies each of the proximal and distal esophagus, respectively. The biopsies should not only encompass the full thickness of the epithelium, but parts of the lamina propria as well.
Reduced Serum Adiponectin Levels in Alexithymia
Authors: Honkalampi Kirsi , Viinamäki Heimo , Niskanen Leo , Koivumaa-Honkanen Heli , Valkonen-Korhonen Minna , Elomaa Antti-Pekka , Harvima Ilkka , Herzig Karl-Heinz , Lehto Soili M.
Published: March 2014

Objectives: Clinical studies have demonstrated that circulating cytokine profiles may differ between alexithymic and non-alexithymic subjects. We examined whether the levels of adiponectin (μg/ml) and resistin (ng/ml) are independently related to alexithymic features in a population-based sample. Methods: In 2005, clinical data including laboratory assessments were obtained from a sub-sample (n = 308) of the Kuopio Depression Study general population study including subjects aged 25-64 years. Based on the Toronto Alexithymia Scale score in 1998, 1999, 2001 and 2005, a group of subjects with high alexithymic features (n = 85) was formed and compared with non-alexithymic controls (n = 206). Results: Serum adiponectin levels were significantly lower in subjects with alexithymic features than in non-alexithymic control subjects. No difference was found in resistin levels. Similarly, in a logistic regression model adjusted for age, gender and body mass index (BMI), lowered levels of adiponectin, but not resistin, were associated with an increased likelihood of belonging to the group with alexithymic features. Further adjustments for cardiovascular risk factors (i.e. smoking, BMI, metabolic syndrome, alcohol use, and coronary heart disease), depressive symptoms (Hamilton Depression Rating Scale with 17 items) and the use of antidepressants in addition to age and gender did not change these patterns. Conclusions: Our findings suggest that a disturbed anti-inflammatory balance may characterize alexithymia. In addition, our results widen the concept of alexithymia and highlight the role of immune system alterations and stress in alexithymic individuals.
Unmet Diagnostic Needs in Eosinophilic Esophagitis
Authors: Katzka David A.
Published: March 2014

The description of eosinophilic esophagitis (EoE) from a clinical, endoscopic, histologic and mechanistic perspective has emerged at a rapid pace. Nevertheless, there are many key areas of diagnosis which remain problematic. The first area is trying to identify a gold standard for EoE, particularly in its differentiation from gastroesophageal reflux disease. As a result, many of the consensus guidelines advise expensive and cumbersome steps with endoscopy and empiric courses of medication that would not be needed should a completely accurate method for identifying EoE be developed. We also grapple with the lack of an accurate test short of endoscopy and biopsy to diagnose and monitor treatment response in EoE. This is particularly problematic in food elimination diets where patients may require up to ten endoscopies to determine precise food avoidance. Finally, it is imperative that we diagnose factors that predict severity and phenotype of the disease. This will yield far clearer guidance concerning the level and duration of therapy needed on EoE patients.
Choroidal Thickness in Idiopathic Subfoveal Choroidal Neovascularization
Authors: Cao Xu-Sheng , Peng Xiao-Yan , You Qi-Sheng , Zhang Yong-Peng , Jonas Jost B.
Published: March 2014

Purpose: To evaluate choroidal thickness in patients with idiopathic choroidal neovascularization. Methods: The observational case series study included patients who were consecutively diagnosed with idiopathic unilateral choroidal neovascularization as demonstrated by ophthalmoscopy, fluorescein angiography and enhanced depth imaging optical coherence tomography (EDI-OCT). Using EDI-OCT, choroidal thickness was measured at the fovea and at locations in a distance of 500, 1,000 and 1,500 μm temporal and nasal to the fovea. Results: Mean subfoveal choroidal thickness was significantly (p = 0.002) thicker in the study group than in the control group (357 ± 99 vs. 316 ± 83 μm). In a parallel manner, the differences between the study group and the control group in choroidal thickness were significant for all other measurement points, except for the examination at 1,500 μm nasal to the fovea (p = 0.09). The results remained unchanged after adjusting for axial length and age. Conclusions: Idiopathic unilateral choroidal neovascularization is associated with a thickening of the choroid.
Management of Gastroesophageal Reflux Disease: Lifestyle Modification and Alternative Approaches
Authors: Eherer Andreas
Published: March 2014

The first step in the management of gastroesophageal reflux disease (GERD) is lifestyle modification, with dietary recommendations such as increasing fiber intake and lowering dietary fat. While there is some physiological evidence that various foods as well as alcohol and tobacco affect the pressure of the lower esophageal sphincter (LES), targeted interventions have not shown any benefit in clinical trials. The general recommendation is for the patient to avoid foods and beverages that in his or her experience trigger GERD symptoms. The only measures that have been shown with some degree of scientific evidence to be beneficial are weight loss on the part of obese patients and elevation of the head of the bed. We, in contrast, developed a training program that induces a change from thoracic to abdominal breathing. We hypothesized that this change in breathing actively trains the diaphragm, and so potentially strengthens the LES. In a randomized trial using breathing exercises as the intervention, we found an improvement in gastroesophageal reflux symptoms, assessed by quality of life, pH-metry and proton pump inhibitor use. Most patients would prefer to take proton pump inhibitors than to do exercises, but at least for a subgroup of highly motivated patients who would prefer an alternative to medication, structured physical exercises could offer new help with their GERD.
Management of Refractory Eosinophilic Esophagitis
Authors: Mukkada Vincent A. , Furuta Glenn T.
Published: March 2014

Background/Aims: Whereas most children and adults respond to traditional eosinophilic esophagitis (EoE) treatments, such as exclusion of dietary allergens or the use of topical steroids, a small fraction may not. Methods: Based on clinical experience and a review of the literature, the aim of this work is to provide practical advice for caring for ‘refractory' patients with EoE. Results: The approach to this type of patient continues to evolve and decision-making should consider a number of issues including the patient's age, lack of a complete understanding of the natural history of this disease, risks of monitoring, and side effects of treatments. Next, one needs to define the term ‘refractory' in that this can refer either to persistent symptoms or to continued inflammation in the face of presumably effective drug or diet therapy. Before considering alternative treatments, it is important to rule out any other cause of persistent symptoms. For instance, could they be related to an occult esophageal narrowing not identified at the time of endoscopy? Esophagrams may be necessary to identify localized or longitudinal narrowing that could be amenable to dilation. If symptoms and inflammation persist and no narrowing is appreciated, an elemental diet can be considered; however, the long-term use of this in older children and adults may be difficult. Prednisone or systemic steroids may be indicated to induce remission, but side effects and complications associated with chronic use are limiting. Finally, the use of immunosuppression or biological agents has been reported in case reports and studies; use of these may be limited by side effects or the need to utilize compassionate use protocols. Conclusions: As the scope of esophageal eosinophilia continues to evolve, the clinical and molecular characterization of new clinical phenotypes will be important so that new therapeutic targets can be identified.
Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α
Authors: Mehta Shraddha , Mukherjee Sandeepan , Balasubramanian Deepa , Chowdhary Abhay
Published: March 2014

Objective: Recombinant human interferon (rhIFN)-α is a potent immunoregulator having a wide range of therapeutic applications. In the present study, rhIFN-α was evaluated for its neuroimmunomodulatory activity. Method: Dose-dependent gene expression of cytokines and chemokines in the brain of rhIFN-administered mice was studied using real-time SYBR green PCR. Results: Statistically significant increase in expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IFN-γ were observed. Conclusion: The findings indicate that rhIFN-α may be used at an optimized dose to cause appropriate neuromodulation of cytokine/chemokine secretion that can aid in the development of therapeutic approaches for many infectious diseases of the central nervous system for which therapies are lacking.