bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of iPLA2 in the Regulation of Src Trafficking and Microglia Chemotaxis
Authors: Lee Sang‐Hyun , Schneider Claus , Higdon Ashlee N. , Darley‐Usmar Victor M. , Chung Chang Y.
Published: March 2011

Microglia are immune effector cells in the central nervous system (CNS) and their activation, migration and proliferation play crucial roles in brain injuries and diseases. We examined the role of intracellular Ca2+‐independent phospholipase A2 (iPLA2) in the regulation of microglia chemotaxis toward ADP. Inhibition of iPLA2 by 4‐bromoenol lactone (BEL) or iPLA2 knockdown exerted a significant inhibition on phosphatidylinositol‐3‐kinase (PI3K) activation and chemotaxis. Further examination revealed that iPLA2 knockdown abrogated Src activation, which is required for PI3K activation and chemotaxis. Colocalization studies showed that cSrc‐GFP was retained in the endosomal recycling compartment (ERC) in iPLA2 knockdown cells, but the addition of arachidonic acid (AA) could restore cSrc trafficking to the plasma membrane by allowing the formation/release of recycling endosomes associated with cSrc‐GFP. Using BODIPY‐AA, we showed that AA is selectively enriched in recycling endosomes. These results suggest that AA is required for the cSrc trafficking to the plasma membrane by controlling the formation/release of recycling endosomes from the ERC.
Paediatric drug use with focus on off‐label prescriptions in Swedish outpatient care – a nationwide study
Authors: Olsson J , Kimland E , Pettersson S , Odlind V
Published: March 2011

Aim:  To determine drug prescription and proportion of off‐label dispensing in the Swedish paediatric outpatient population.

Methods:  All dispensed outpatient prescriptions to children aged 0 < 18 years as well as the proportion of off‐label drug use during 2007 were analysed using data from the Swedish Prescribed Drug Register.

Results:  In total, 2.19 million drug prescriptions of 898 different drug substances were dispensed to paediatric patients, and of those substances, 64% had been dispensed off‐label at least once. The overall off‐label rate of all prescriptions was 13.5%, among which topical drugs as well as sex hormones were the most commonly prescribed off‐label drugs. More than half of all children in Sweden had received at least one prescribed drug in 2007.

Conclusions:  There is a high prescribing of medicines to children in outpatient care in Sweden with a considerable amount of off‐label prescriptions. Topically administered drugs, sex hormones, antidepressants, hypnotics, cardiovascular drugs and nonsteroidal anti‐inflammatory drugs were commonly prescribed off‐label.
Follow‐up studies of very low birthweight children in Sweden
Authors: Gäddlin Per‐Olof
Published: March 2011

Follow‐up studies are essential to our knowledge of outcome in very low birthweight (VLBW) or extremely preterm (EPT) infants because those children have a greater risk for developing neurosensory disabilities and behavioural and educational problems and have decreased probability for an optimal transition into adulthood compared to term controls. Outcome data are of interest not only to healthcare professionals but also to parents, schoolteachers and society. The aim of this review is to describe the follow‐up studies of seven populations of VLBW or EPT infants performed in Sweden and published between 1995 and 2009.

Conclusion:  The time has come to implement evident data from these Swedish follow‐up studies into clinical practice and to perform regular and specific follow‐up examinations during childhood for all VLBW and EPT children. These assessments, specially designed for high‐risk infants, should consider the potential outcomes for neurological, visual, auditory function and cognitive function as well as behaviour and growth, from birth to school‐start.
Vulnerability for psychopathology in Klinefelter syndrome: age‐specific and cognitive‐specific risk profiles
Authors: van Rijn Sophie , Swaab Hanna
Published: March 2011

Aim:  Studying Klinefelter syndrome (KS) (47,XXY) can reveal insights into mechanisms of neurodevelopment. Our aim was to identify factors that influence risk for psychopathology in this syndrome, with a focus on age‐specific and cognitive‐specific risk profiles.

Methods:  A total of 73 subjects with KS (25 children and 48 adults) and 93 age‐matched controls (53 children and 40 adults) participated in the study. The discrepancy between verbal IQ (VIQ) and performance IQ (PIQ) was assessed using the Wechsler Intelligence Scales. IQ data were only measured in the Klinefelter group. All participants completed the Autism Questionnaire and Schizotypal Personality Questionnaire.

Results:  Increased levels of autism traits and schizotypal traits were observed in individuals with KS, with schizotypal traits increasing with age. The VIQ < PIQ group (n = 33) showed significantly increased levels of autism traits compared to the PIQ < VIQ group (n = 12) and controls. The PIQ < VIQ group showed significantly increased levels of schizotypal traits compared to the VIQ < PIQ group and controls. The VIQ–PIQ discrepancy significantly correlated with schizotypal traits and autism traits, in opposite directions.

Conclusion:  Risk for psychopathology in KS may be age specific as well as dependent on cognitive profile. Relative deficits in verbal abilities seem more strongly associated with increased autism traits, whereas relative deficits in visuospatial abilities seem more strongly associated with increased schizotypal traits.
Modelling potential distribution of the threatened tree species Juniperus oxycedrus: how to evaluate the predictions of different modelling approaches?
Authors: Rupprecht Franziska , Oldeland Jens , Finckh Manfred
Published: March 2011

Questions: How can predictions of potential species distribution derived from presence‐only data and different modelling algorithms be compared and evaluated? Where does suitable habitat for Juniperus oxycedrus exist within the study area and which bioclimatic variables prove to be most important in the prediction of J. oxycedrus potential distribution?

Location: Central High Atlas, Morocco.

Methods: Ecological niche factor analysis (ENFA), maximum entropy approach (MAXENT) and generalized linear models (GLM) were applied to either presence‐only data of J. oxycedrus (ENFA and MAXENT) or presence–absence data (GLM), using bioclimatic variables as predictors. Model accuracy of ENFA, MAXENT and GLM was assessed using their specific evaluation measures and prediction success by means of the minimal predicted area (MPA). Finally, the three maps of potential species distribution were intersected to investigate their consistency in the geographic distribution of predicted suitable habitat.

Results: Species distribution models calculated by ENFA, MAXENT and GLM show good model quality according to their evaluation measures. However, calculation of MPA revealed considerable discrepancies in geographic distribution and spatial extent of areas predicted as suitable habitat for J. oxycedrus.

Conclusion: Suitable habitat for J. oxycedrus is predicted using all applied modelling approaches in 8% of the study area (mostly the north‐western part). MAXENT gave the best results considering model accuracy and prediction success according to the MPA scores. Predictors representing maximum temperature and potential radiation were selected in all methods to explain species occurrences. This points to a possible shift of the species' potential distribution in cases of a rise in summer temperature due to climate change.
Diagnostic value of terminal ileum biopsy in chronic diarrhea with normal endoscopic appearance
Authors: SAYILIR Abdurrahim , KURT Mevlüt , KEKILLI Murat , ONAL Ibrahim K , BEYAZIT Yavuz , TURHAN Nesrin , IBIŞ Mehmet , ARHAN Mehmet
Published: March 2011

OBJECTIVE:  To investigate the diagnostic value of a terminal ileum biopsy in chronic non‐bloody diarrhea with normal endoscopic appearance.

METHODS:  Patients who had a terminal ileum biopsy performed between January 2007 and January 2010 during a colonoscopy despite normal endoscopic appearance were reviewed. They were divided into two groups according to the indication for the colonoscopy: non‐bloody diarrhea and non‐diarrhea; and their histopathological findings were compared.

RESULTS:  By screening the colonoscopy records, 473 patients were found to have had a terminal ileum biopsy. Of these patients, 178 were excluded for various reasons. Finally, 295 patients were suitable for analysis. The non‐bloody diarrhea group consisted of 135 patients, while the remaining 160 patients constituted the non‐diarrhea group. A histopathological examination of the terminal ileum biopsy specimens in the non‐bloody diarrhea group revealed an abnormal histology in eight patients (5.9%), compared with five patients (3.1%) in the non‐diarrhea group. No statistically significant difference was found between the two groups (P = 0.26).

CONCLUSION:  Although performing a biopsy of the terminal ileum despite a macroscopically normal appearance may offer some additional benefit to the diagnosis of chronic non‐bloody diarrhea, prospective trials are needed for assessing the diagnostic value of a terminal ileum biopsy in patients with chronic diarrhea.
Prevalence of overt myeloproliferative neoplasms and JAK2 V617F mutation in Korean patients with splanchnic vein thrombosis
Authors: YOO E.‐H. , JANG J.‐H. , PARK K.‐J. , GWAK G.‐Y. , KIM H.‐J. , KIM S.‐H. , KIM D.‐K.
Published: March 2011

Introduction:  Myeloproliferative neoplasm (MPN) is known to be a major risk factor of splanchnic vein thrombosis (SVT). Recent studies revealed that a significant proportion of patients with SVT harbor a gain‐of‐function mutation in the JAK2 gene (V617F) with or without MPN. In this study, the authors investigated the prevalence of MPN and JAK2 V617F mutation in Korean patients with SVT.

Methods:  The study subjects were 26 patients diagnosed as having SVT based on Doppler ultrasound and/or computed tomography from January 2008 to January 2010 (16 men and 10 women; mean age 44 years, range 15–75 years). The clinical and laboratory data were reviewed. The JAK2 V617F mutation was detected by allele‐specific polymerase chain reaction and direct sequencing analyses using DNA from peripheral blood leukocytes.

Results:  Among 26 study patients, 12 had portal vein thrombosis, five had hepatic vein thrombosis, three had mesenteric, and two had splenic vein thrombosis. Four patients had thrombosis involving more than one splanchnic vein. Two patients (7.7%; 2/26) had overt MPN (essential thrombocythemia). JAK2 V617F was detected in three patients (11.5%) including the two patients with overt MPN. Thus, the prevalence of the JAK2 V617F mutation in patients with SVT but without overt MPN was 4.2% (1/24).

Conclusion:  The prevalence of overt MPN and that of JAK2 V617F were lower in Korean patients with SVT than in previous reports. Data from a larger number of patients with long‐term follow‐up are needed to reveal the clinical relevancy of JAK2 V617F in Korean patients with SVT.
The first use of EaeI restriction enzyme in DNA diagnosis of Hb Q‐India
Authors: KHALIL M. S. M. , HENDERSON S. , SCHUH A. , HUSSEIN M.‐R. A. , OLD J.
Published: March 2011

Introduction:  The α‐chain variant Hb Q‐India (c.193G>C) is caused by a point mutation GAC→CAC at codon 64 of the α1 globin gene and is clinically silent. Point mutations can be diagnosed easily by many simple polymerase chain reaction (PCR) techniques including PCR‐restriction digest, but for Hb Q‐India the restriction digest has never been described. In this work we aimed to develop a restriction enzyme digestion assay for DNA diagnosis of Hb Q‐India, in order to increase the panel of restriction enzymes used in DNA diagnosis of haemoglobinopathies and also as a simple cheap alternative to the ARMS‐PCR method.

Methods:  A restriction enzyme digestion assay was designed for diagnosis of Hb Q‐India using the restriction enzyme EaeI enzyme as the Hb Q‐India mutation abolishes the recognition site of this enzyme. Patients were screened for an abnormal haemoglobin by high performance liquid chromatography (HPLC) and those had an abnormal peak with a retention time between 4.7 and 4.8 minutes were selected for diagnosis at the molecular level. The α1 globin gene was amplified in 12 cases with a presumed diagnosis of Hb Q‐India by HPLC and isoelectric focusing (IEF), and the amplified products were subjected to the EaeI digestion.

Results:  All the 12 cases were diagnosed positive (100%) for Hb Q‐India by the EaeI restriction enzyme digest. They were heterozygotes for the mutation.

Conclusion:  EaeI restriction enzyme digestion can be used as a simple and robust alternative method to ARMS‐PCR for DNA diagnosis of Hb Q‐India. The EaeI restriction enzyme can be added to the panel of restriction enzymes used in the DNA diagnosis of the abnormal Hb variants. Concomitant use of HPLC and IEF can be used efficiently for presumed diagnosis of this rare variant.
Shock‐metamorphic microfeatures in chert from the Jebel Waqf as Suwwan impact structure, Jordan
Authors: SCHMIEDER Martin , REIMOLD Wolf Uwe , BUCHNER Elmar , KHIRFAN Maria , SALAMEH Elias , KHOURY Hani
Published: March 2011

Abstract– The petrographic investigation of a shocked, chalcedony‐, quartzine‐, and quartz‐bearing allochthonous chert nodule (probably Upper Cretaceous) recovered from surficial wadi gravels in the inner parts of the central uplift of the approximately 6 km in diameter Jebel Waqf as Suwwan impact structure, Jordan, reveals new potential shock indicators in microfibrous–spherulitic silica, in addition to well‐established shock‐metamorphic effects in coarser crystalline quartz. The microcrystalline chert groundmass exhibits a macroscopic dendritic and suborthogonal fracture pattern commonly associated with thin “recrystallization bands” that intersect the pre‐existing diagenetic chert fabric. Fibrous aggregates of quartzine spherulites in chalcedony‐quartzine‐quartz veinlets locally have a shattered appearance and show conspicuous “curved fractures” perpendicular to the quartzine fiber direction (and parallel to [0001]) that commonly trend subparallel to planar fractures (PFs) in neighboring shocked quartz. Quartz exhibits PFs, feather features (FFs), and mainly single sets of planar deformation features (PDFs) parallel to the basal plane (0001) (Brazil twins) and, rarely, additional PDFs parallel to {101¯3}. Shock petrography indicates shock pressures of ≥10 GPa and high shock‐induced differential stresses that affected the chert nodule. The internal crosscutting relationships of primary diagenetic and impact‐related deformational features together with shockpressure estimates suggest that the curved fractures across quartzine spherulites might represent specific (low‐ to medium‐pressure) shock‐metamorphic features, possibly in structural analogy to basal plane PFs in quartz. The dendritic–suborthogonal fractures in the microcrystalline chert groundmass and recrystallization bands are likely related to impact‐induced shear deformation and recrystallization, respectively, and cannot be considered as definite shock indicators.
The influence of single elements on nested community structure
Authors: Joppa Lucas N. , Williams Rich
Published: March 2011

1. Asking whether or not an ecological community displays the structural property of nestedness is becoming increasingly common in ecological research. We note, however, a currently limited understanding of how individual matrix components (e.g. species as rows and sites as columns) and elements (e.g. a species’ occurrence at a site) contribute to overall community structure.

2. Here, we investigate the influence of single elements in a community matrix on overall community nestedness. We derive a unique extension to the popular nestedness algorithm NODF that is necessary for this analysis.

3. For 210 empirical communities, we show that elements, on average, determine a little less than 50% of a community’s nestedness value, with components determining the remainder. Looking at just matrix elements we find, on average, that 10% of elements determine 25% of a community’s nested structure. Further, we find statistical conclusions change for more than 20% of the empirical communities with the addition or removal of a single element.

4. Generally, the search for ecological pattern occurs by calculating a single metric designed to quantify the structure of an entire community. By showing the sensitivity of a metric to changes in a single element, our results cast doubt on the usefulness of this approach. That said, the extension to NODF that we present should allow researchers to better understand how individual elements in a community influence patterns of nestedness.
Transient sensitivity analysis for nonlinear population models
Authors: Tavener Simon , Mikucki Michael , Field Stuart G. , Antolin Michael F.
Published: March 2011

1. Performing sensitivity analyses for deterministic multi‐stage, multi‐parameter population models that include nonlinearity presents a significant computational challenge.

2. We implement a standard forward sensitivity analysis to evaluate partial derivatives of population state variables with respect to parameters at all times for which the solution is known. We present a hybrid Matlab Maple software package, sensai, which automates the steps required to calculate sensitivities and elasticities. We focus on sensitivities of transient states of populations. Our analysis therefore differs from the more common analysis of linear systems where sensitivities are computed for the asymptotic stable‐stage distribution assuming unbounded population growth. The method generalizes the matrix calculus methods for nonlinear, stage‐structured matrix models previously developed by Caswell (2009, Journal of Difference Equations and Applications, 15, 349–369).

3. We present an example of a nonlinear, discrete‐time population model in the form of a stage‐structured Lefkovitch matrix, and another multi‐stage, continuous‐time SIR disease model in the form of a system of ordinary differential equations. In addition, we extend the framework for composite nonlinear maps of population demography to include single‐locus genetics with natural selection discriminating among genotypes.

4. SENSAI allows for the analysis of a quantity of interest (an arbitrary function of variables and parameters, e.g. the proportion of infected individuals in a disease model), and sensitivity to combinations of model parameters. For example, we can compute sensitivities with respect to parameters and initial conditions at all times during an outbreak in a disease model, before a steady state of disease prevalence is attained. Similarly, in population genetic models, we can compute sensitivity of a response to natural selection (e.g. the change in allele frequencies) in relation to fitness differences among genotypes.

5. We illustrate the capabilities of sensai through a series of canonical models with relatively few variables and parameters. However, sensai has the capability to analyse significantly more complex models.
A Computational Leakage Model for Solid Oxide Fuel Cell Compressive Seals
Authors: Green Christopher K. , Streator Jeffrey L. , Haynes Comas , Lara-Curzio Edgar
Published: March 2011

One of the key obstacles precluding the maturation and commercialization of planar solid oxide fuel cells has been the absence of a robust sealant. A computational model has been developed in conjunction with leakage experiments at Oak Ridge National Laboratory. The aforementioned model consists of three components: a macroscopic model, a microscopic model, and a mixed lubrication model. The macroscopic model is a finite element representation of a preloaded metal-metal seal interface, which is used to ascertain macroscopic stresses and deformations. The microscale contact mechanics model accounts for the role of surface roughness in determining the mean interfacial gap at the sealing interface. In particular, a new multiscale fast Fourier transform-based model is used to determine the gap. An averaged Reynolds equation derived from mixed lubrication theory is then applied to approximate the leakage flow across the rough annular interface. The composite model is applied as a predictive tool for assessing how certain physical parameters (i.e., seal material composition, compressive applied stress, surface finish, and elastic thermophysical properties) affect seal leakage rates. The leakage results predicted by the aforementioned computational leakage model are then compared with experimental results.
Quantify Resonance Inspection With Finite Element-Based Modal Analyses
Authors: Lai C. , Sun X. , Dasch C. , Harmon G. , Jones M.
Published: March 2011

Resonance inspection uses the natural acoustic resonances of a part to identify anomalous parts. Modern instrumentation can measure the many resonant frequencies rapidly and accurately. Sophisticated sorting algorithms trained on sets of good and anomalous parts can rapidly and reliably inspect and sort parts. This paper aims at using finite element-based modal analysis to put resonance inspection on a more quantitative basis. A production level automotive steering knuckle is used as the example part for our study. First, the resonance frequency spectra for the knuckle are measured with two different experimental techniques. Next, scanning laser vibrometry is used to determine the mode shape corresponding to each resonance. The material properties including anisotropy are next measured to high accuracy using resonance spectroscopy on cuboids cut from the part. Then, the finite element model of the knuckle is generated by meshing the actual part geometry obtained with computed tomography. The resonance frequencies and mode shapes are next predicted with a natural frequency extraction analysis after an extensive mesh size sensitivity study. The good comparison between the predicted and the experimentally measured resonance spectra indicates that finite element-based modal analyses have the potential to be a powerful tool in shortening the training process and improving the accuracy of the resonance inspection process for a complex production level part. The finite element-based analysis can also provide a means to computationally test the sensitivity of the frequencies to various possible defects such as porosity or oxide inclusions, especially in high stress regions that the part will experience in service.
A New Type of Muffler Based on Microperforated Tubes
Authors: Allam S. , Åbom M.
Published: March 2011

Microperforated plate (MPP) absorbers are perforated plates with holes typically in the submillimeter range and perforation ratios around 1%. The values are typical for applications in air at standard temperature and pressure (STP). The underlying acoustic principle is simple: It is to create a surface with a built in damping, which effectively absorbs sound waves. To achieve this, the specific acoustic impedance of a MPP absorber is normally tuned to be of the order of the characteristic wave impedance in the medium (∼400 Pa s/m in air at STP). The traditional application for MPP absorbers has been building acoustics often combined with a so called panel absorber to create an absorption peak at a selected frequency. However, MPP absorbers made of metal could also be used for noise control close to or at the source for noise control in ducts. In this paper, the possibility to build dissipative silencers, e.g., for use in automotive exhaust or ventilation systems, is investigated.
Analytical and Experimental Investigation of Self-Loosening of Preloaded Cap Screw Fasteners
Authors: Yang Xianjie , Nassar Sayed
Published: March 2011

In an effort to establish a theoretical outline of a criterion for preventing the vibration-induced loosening of preloaded threaded fasteners, this paper provides an experimental and analytical insight into the effect of the initial bolt preload and the excitation amplitude on the self-loosening performance of a cap screw fastener. A nonlinear model is used for predicting the clamp load loss caused by the vibration-induced loosening of cap screw fasteners under cyclic transverse loading. Experimental verification was conducted on the twisting torque variation and the effect of the preload level and transverse displacement amplitude. Comparison of the experimental and analytical results on the clamp load loss with the number of cycles verifies that the proposed model accurately predicts self-loosening performance.
A New Analytical Formulation for the Dynamics of Multipocket Thin-Walled Structures Considering the Fixture Constraints
Authors: Meshreki Mouhab , Attia Helmi , Kövecses József
Published: March 2011

Milling of thin-walled aerospace structures is a critical and challenging process. Available models for the prediction of the effect of the fixture on the dynamic response of flexible workpieces are computationally demanding and fail to represent practical cases for milling of thin-walled structures. Based on the analysis of typical structural components encountered in the aerospace industry, a generalized unit-element, with the shape of an asymmetric pocket, was identified to represent the dynamic response of these components. Accordingly, a computationally efficient dynamic model was developed to predict the dynamic response of typical thin-walled aerospace structures using the Rayleigh–Ritz method. In the formulation of this model, the dynamics of a 3D pocket is represented by an equivalent 2D multispan plate taking into account the effect of deformable fixture supports. The developed model was validated numerically and experimentally for different workpiece geometries and various types of loading. This model resulted in one to two orders of magnitude reduction in computation time when compared with the finite element models, with prediction errors less than 10%. The developed model meets the conflicting requirements of prediction accuracy and computational efficiency needed for interactive fixture design.
Polarized Gamma-Ray Emission from the Galactic Black Hole Cygnus X-1
Authors: Laurent P. , Rodriguez J. , Wilms J. , Cadolle Bel M. , Pottschmidt K. , Grinberg V.
Published: March 2011

This gamma-ray emission originates from a jet of relativistic particles that is formed in close proximity to the black hole.
Conserved Eukaryotic Fusogens Can Fuse Viral Envelopes to Cells
Authors: Avinoam Ori , Fridman Karen , Valansi Clari , Abutbul Inbal , Zeev-Ben-Mordehai Tzviya , Maurer Ulrike E. , Sapir Amir , Danino Dganit , Grünewald Kay , White Judith M. , Podbilewicz Benjamin
Published: March 2011

A
Caenorhabditis elegans
cell-surface fusion protein can promote viral fusion with mammalian cells.
The use of a silica-based heat sink to “uncouple” the matrix-assisted laser desorption/ionization (MALDI) mechanism
Authors: Lourantos E. , Ramirez O. M. , Giannakopulos A. E. , Beran K. A. , Derrick Peter J. , Bashir S.
Published: March 2011

The relationships between ion yield(s) as a function of desorption alone and (or) ionization was investigated using two model systems. In the first model system, a carbohydrate (2,3,6-tri-O-methyl-β-cyclodextrin, TMBCD), which could be directly laser desorbed, was analyzed with and without a silicon-based heat sink compound (HSC). The HSC allowed heat to pass through but obstructed the flow of charge. In the second model system, a peptide (substance P), which ccould not be laser desorbed, was analyzed under similar conditions. The ion yield of TMBCD under either system of heat conductivity was similar, whereas the ion yield of the peptide with the heat sink was negligible. Compounds that are predominately cationized either in the gas phase or preformed in solution give an ion yield that is not dependent upon the surface conditions, whereas compounds that are not ordinarily cationized are affected by the emission of electrons from the metal surface.
Metallacarboranes for the labelling of DNA — Synthesis of oligonucleotides bearing a 3,3′-iron-1,2,1′,2′-dicarbollide complex
Authors: Olejniczak Agnieszka B.
Published: March 2011

The present work reports the efficient synthesis of oligonucleotides bearing metallacarborane complexes containing iron (3,3′-iron-1,2,1′,2′-dicarbollide) on a solid support via the H-phosphonate method. This versatile methodology can be applied to the synthesis of DNA oligomers bearing various metallacarborane units.
One-pot domino synthesis of polyvicinalamine monomers
Authors: Kilic Cem B. , Taralp Alpay
Published: March 2011

Imidazole was generated in situ via a domino reaction between glyoxal, formaldehyde, and two units of aqueous ammonia. Aqueous bicarbonate and a carboxylic anhydride or dialkyl dicarbonate were added, yielding the corresponding N,N′-diacyl or N,N′-dicarbalkoxy-2-hydroxyimidazoline. A Bamberger ring cleavage ensued, affording cis-1,2-di(acetamido)ethene, cis-1,2-di(propylamido)ethene, cis-1,2-di(ethoxyamido)ethene, cis-1,2-di(tert-butoxyamido)ethene, or cis-1,2-di(benzamido)ethene as easily isolable solids. The convenience and generality offered by this one-pot approach implied a cost-effective route to the routine synthesis of oligo- and polyvicinalamine precursors.
Development of a solid-phase extraction – spectrofluorimetric method for trace glutathione determination
Authors: Huang Ke-Jing , Han Cong-Hui , Wu Ying-Ying , Han Chao-Qun , Niu De-Jun , Wu Zhi-Wei , Xue Ya-Ping
Published: March 2011

A simple and efficient solid-phase extraction – spectrofluorimetric method has been developed to determine glutathione (GSH). Fluorescent probe N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-yl)methyl)iodoacetamide (BODIPY Fl-C1-IA) was used as the derivatization reagent. The procedure was based on a BODIPY Fl-C1-IA selective reaction with GSH to form the highly fluorescent product BODIPY Fl-C1-IA–GSH, using a solid-phase extraction column and spectrofluorimetric determination. The variables affecting analytical performance were studied and optimized. The calibration graph using the preconcentration system for GSH was linear over the range of 1–200 nmol/L with a limit of detection of 0.05 nmol/L (signal-to-noise ratio = 3). The relative standard deviation for six replicate determinations of GSH at the 100 nmol/L concentration level was 3.9%. The method was applied to water samples and average recoveries between 87.5% and 111.5% were obtained for spiked samples.
ON A THEOREM OF BURDE AND DE RHAM
Authors: SILVER DANIEL S. , WILLIAMS SUSAN G.
Published: March 2011

We generalize a theorem of Burde and de Rham characterizing the zeros of the Alexander polynomial. Given a representation of a knot group π, we define an extension [Formula: see text] of π, the Crowell group. For any GL Nℂ representation of π, the zeros of the associated twisted Alexander polynomial correspond to representations of [Formula: see text] into the group of dilations of ℂN.
FIRST NON-VANISHING SELF-LINKING OF KNOT (III) MASSEY–MILNOR THEORY
Authors: HSIEH CHUN-CHUNG
Published: March 2011

In this paper, following the scheme of [11–13, 16, 17], we study the first non-vanishing self-linkings of knots in both combinatoric and diagrammatic aspects. The method of attack comes from Massey–Milnor linking theory.
PLANAR AND SPHERICAL STICK INDICES OF KNOTS
Authors: ADAMS COLIN , COLLINS DAN , HAWKINS KATHERINE , SIA CHARMAINE , SILVERSMITH ROB , TSHISHIKU BENA
Published: March 2011

The stick index of a knot is the least number of line segments required to build the knot in space. We define two analogous 2-dimensional invariants, the planar stick index, which is the least number of line segments in the plane to build a projection, and the spherical stick index, which is the least number of great circle arcs to build a projection on the sphere. We find bounds on these quantities in terms of other knot invariants, and give planar stick and spherical stick constructions for torus knots and for compositions of trefoils. In particular, unlike most knot invariants, we show that the spherical stick index distinguishes between the granny and square knots, and that composing a nontrivial knot with a second nontrivial knot need not increase its spherical stick index.
2-KNOTS WITH SOLVABLE GROUPS
Authors: HILLMAN JONATHAN A.
Published: March 2011

We show that fibered 2-knots with closed fiber the Hantzsche–Wendt flat 3-manifold are not reflexive, while every fibered 2-knot with closed fiber a Nil-manifold with base orbifold S(3, 3, 3) is reflexive. We also determine when the knots are amphicheiral or invertible, and give explicit representatives for the possible meridians (up to automorphisms of the knot group which induce the identity on abelianization) for the groups of all knots in either class. This completes the TOP classification of 2-knots with torsion-free, elementary amenable knot group. In the final section, we show that the only non-trivial doubly null-concordant knots with such groups are those with the group of the 2-twist spin of the knot 946.
A GEOMETRIC CHARACTERIZATION OF THE UPPER BOUND FOR THE SPAN OF THE JONES POLYNOMIAL
Authors: GONZÁLEZ-MENESES JUAN , MANCHÓN PEDRO M. G.
Published: March 2011

Let D be a link diagram with n crossings, sA and sB be its extreme states and |sAD| (respectively, |sBD|) be the number of simple closed curves that appear when smoothing D according to sA (respectively, sB). We give a general formula for the sum |sAD| + |sBD| for a k-almost alternating diagram D, for any k, characterizing this sum as the number of faces in an appropriate triangulation of an appropriate surface with boundary. When D is dealternator connected, the triangulation is especially simple, yielding |sAD| + |sBD| = n + 2 - 2k. This gives a simple geometric proof of the upper bound of the span of the Jones polynomial for dealternator connected diagrams, a result first obtained by Zhu [On Kauffman brackets, J. Knot Theory Ramifications6(1) (1997) 125–148.]. Another upper bound of the span of the Jones polynomial for dealternator connected and dealternator reduced diagrams, discovered historically first by Adams et al. [Almost alternating links, Topology Appl.46(2) (1992) 151–165.], is obtained as a corollary. As a new application, we prove that the Turaev genus is equal to the number k of dealternator crossings for any dealternator connected diagram.
A BRACKET POLYNOMIAL FOR GRAPHS, IV: UNDIRECTED EULER CIRCUITS, GRAPH-LINKS AND MULTIPLY MARKED GRAPHS
Authors: TRALDI LORENZO
Published: March 2011

In earlier work we introduced the graph bracket polynomial of graphs with marked vertices, motivated by the fact that the Kauffman bracket of a link diagram D is determined by a looped, marked version of the interlacement graph associated to a directed Euler system of the universe graph of D. Here we extend the graph bracket to graphs whose vertices may carry different kinds of marks, and we show how multiply marked graphs encode interlacement with respect to arbitrary (undirected) Euler systems. The extended machinery brings together the earlier version and the graph-links of Ilyutko and Manturov [J. Knot Theory Ramifications18 (2009) 791–823]. The greater flexibility of the extended bracket also allows for a recursive description much simpler than that of the earlier version.
BRAID ORDERING AND KNOT GENUS
Authors: ITO TETSUYA
Published: March 2011

The genus of knots is one of the fundamental invariants and can be seen as a complexity of knots. In this paper, we give a lower bound of the knot genus using the Dehornoy floor, which is a measure of complexity of braids in terms of the Dehornoy ordering.
GENERALIZED ATMOSPHERIC SAMPLING OF KNOTTED POLYGONS
Authors: JANSE VAN RENSBURG E. J. , RECHNITZER A.
Published: March 2011

Self-avoiding polygons in the cubic lattice are models of ring polymers in dilute solution. The conformational entropy of a ring polymer is a dominant factor in its physical and chemical properties, and this is modeled by the large number of conformations of lattice polygons. Cubic lattice polygons are embeddings of the circle in three space and may be used as a model of knotting in ring polymers. In this paper we study the effects of knotting on the conformational entropy of lattice polygons and so determine the relative fraction of polygons of different knot types at large lengths. More precisely, we consider the number of cubic lattice polygons of n edges with knot type K, pn(K). Numerical evidence strongly suggests that [Formula: see text] as n → ∞, where μ0 is the growth constant of unknotted lattice polygons, α is the entropic exponent of lattice polygons, and NK is the number of prime knot components in the knot type K (see the paper [Asymptotics of knotted lattice polygons, J. Phys. A: Math. Gen.31 (1998) 5953–5967]). Determining the exact value of pn(K) is far beyond current techniques for all but very small values of n. Instead we use the GAS algorithm (see the paper [Generalised atmospheric sampling of self-avoiding walks, J. Phys. A: Math. Theor.42 (2009) 335001–335030]) to enumerate pn (K) approximately. We then extrapolate ratios [pn(K)/pn(L)] to larger values of n for a number of given knot types. We give evidence that for the unknot 01 and the trefoil knot 31, there exists a number M01, 31 ≈170000 such that pn (01) > pn (31) if n < M01, 31 and pn (01) ≤pn (31) if n ≥M01, 31. In addition, the asymptotic relative frequencies for a variety of knot types are determined. For example, we find that [pn(31)/pn(41)] → 27.0 ± 2.2, implying that there are approximately 27 polygons of the trefoil knot type for every polygon of knot of type 41 (the figure eight knot), in the asymptotic limit. Finally, we examine the dominant knot types at moderate values of n and conjecture that the most frequent knot types in polygons of any given length n are of the form [Formula: see text] (or its chiral partner), where [Formula: see text] are right- and left-handed trefoils, and N increases with n.
THE JONES POLYNOMIAL AND BOUNDARY SLOPES OF ALTERNATING KNOTS
Authors: CURTIS CYNTHIA L. , TAYLOR SAMUEL J.
Published: March 2011

We show for an alternating knot the minimal boundary slope of an essential spanning surface is given by the signature plus twice the minimum degree of the Jones polynomial and the maximal boundary slope of an essential spanning surface is given by the signature plus twice the maximum degree of the Jones polynomial. For alternating Montesinos knots, these are the minimal and maximal boundary slopes.
LINK INVARIANTS FROM FINITE COXETER RACKS
Authors: NELSON SAM , WIEGHARD RYAN
Published: March 2011

We study Coxeter racks over ℤn and the knot and link invariants they define. We exploit the module structure of these racks to enhance the rack counting invariants and give examples showing that these enhanced invariants are stronger than the unenhanced rack counting invariants.
AN ESTIMATION OF HEMPEL DISTANCE BY USING REEB GRAPH
Authors: IDO AYAKO
Published: March 2011

Let P, Q be Heegaard surfaces of a closed orientable 3-manifold. In this paper, we introduce a method for giving an upper bound of (Hempel) distance of P by using the Reeb graph derived from a certain horizontal arc in the ambient space [0, 1] × [0, 1] of the Rubinstein–Scharlemann graphic derived from P and Q. This is a refinement of a part of Johnson's arguments used for determining stable genera required for flipping high distance Heegaard splittings.
A DETERMINISTIC METHODOLOGY FOR ESTIMATION OF PARAMETERS IN DYNAMIC MARKOV CHAIN MODELS
Authors: ORTIZ A. R. , BANKS H. T. , CASTILLO-CHAVEZ C. , CHOWELL G. , WANG X.
Published: March 2011

A method for estimating parameters in dynamic stochastic (Markov Chain) models based on Kurtz's limit theory coupled with inverse problem methods developed for deterministic dynamical systems is proposed and illustrated in the context of disease dynamics. This methodology relies on finding an approximate large-population behavior of an appropriate scaled stochastic system. The approach leads to a deterministic approximation obtained as solutions of rate equations (ordinary differential equations) in terms of the large sample size average over sample paths or trajectories (limits of pure jump Markov processes). Using the resulting deterministic model, we select parameter subset combinations that can be estimated using an ordinary-least-squares (OLS) or generalized-least-squares (GLS) inverse problem formulation with a given data set. The selection is based on two criteria of the sensitivity matrix: the degree of sensitivity measured in the form of its condition number and the degree of uncertainty measured in the form of its parameter selection score. We illustrate the ideas with a stochastic model for the transmission of vancomycin-resistant enterococcus (VRE) in hospitals and VRE surveillance data from an oncology unit.
Fluoxetine inhibits NF-κB signaling in intestinal epithelial cells and ameliorates experimental colitis and colitis-associated colon cancer in mice
Authors: Koh Seong-Joon , Kim Jung Mogg , Kim In-Kyoung , Kim Nayoung , Jung Hyun Chae , Song In Sung , Kim Joo Sung
Published: March 2011

Although fluoxetine, a selective serotonin reuptake inhibitor, is known to demonstrate anti-inflammatory activity, little information is available on the effect of fluoxetine regarding intestinal inflammation. This study investigates the role of fluoxetine in the attenuation of acute murine colitis by suppression of the NF-κB pathway in intestinal epithelial cells (IEC). Fluoxetine significantly inhibited activated NF-κB signals and the upregulated expression of interleukin-8 (IL-8) in COLO 205 colon epithelial cells stimulated with tumor necrosis factor-α (TNF-α). Pretreatment with fluoxetine attenuated the increased IκB kinase (IKK) and IκBα phosphorylation induced by TNF-α. In a murine model, administration of fluoxetine significantly reduced the severity of dextran sulfate sodium (DSS)-induced colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phospho-IKK activation, myeloperoxidase activity, a parameter of neutrophil accumulation, and the secretion of macrophage-inflammatory protein-2, a mouse homolog of IL-8, were significantly decreased in fluoxetine-pretreated mice. Moreover, fluoxetine significantly attenuated the development of colon cancer in mice inoculated with azoxymethane and DSS. These results indicate that fluoxetine inhibits NF-κB activation in IEC and that it ameliorates DSS-induced acute murine colitis and colitis-associated tumorigenesis, suggesting that fluoxetine is a potential therapeutic agent for the treatment of inflammatory bowel disease.
Serine proteases mediate inflammatory pain in acute pancreatitis
Authors: Ceppa Eugene P. , Lyo Victoria , Grady Eileen F. , Knecht Wolfgang , Grahn Sarah , Peterson Anders , Bunnett Nigel W. , Kirkwood Kimberly S. , Cattaruzza Fiore
Published: March 2011

Acute pancreatitis is a life-threatening inflammatory disease characterized by abdominal pain of unknown etiology. Trypsin, a key mediator of pancreatitis, causes inflammation and pain by activating protease-activated receptor 2 (PAR2), but the isoforms of trypsin that cause pancreatitis and pancreatic pain are unknown. We hypothesized that human trypsin IV and rat P23, which activate PAR2and are resistant to pancreatic trypsin inhibitors, contribute to pancreatic inflammation and pain. Injections of a subinflammatory dose of exogenous trypsin increased c-Fos immunoreactivity, indicative of spinal nociceptive activation, but did not cause inflammation, as assessed by measuring serum amylase and myeloperoxidase activity and by histology. The same dose of trypsin IV and P23 increased some inflammatory end points and caused a more robust effect on nociception, which was blocked by melagatran, a trypsin inhibitor that also inhibits polypeptide-resistant trypsin isoforms. To determine the contribution of endogenous activation of trypsin and its minor isoforms, recombinant enterokinase (ENK), which activates trypsins in the duodenum, was administered into the pancreas. Intraductal ENK caused nociception and inflammation that were diminished by polypeptide inhibitors, including soybean trypsin inhibitor and a specific trypsin inhibitor (type I-P), and by melagatran. Finally, the secretagogue cerulein induced pancreatic nociceptive activation and nocifensive behavior that were reversed by melagatran. Thus trypsin and its minor isoforms mediate pancreatic pain and inflammation. In particular, the inhibitor-resistant isoforms trypsin IV and P23 may be important in mediating prolonged pancreatic inflammatory pain in pancreatitis. Our results suggest that inhibitors of these isoforms could be novel therapies for pancreatitis pain.
Hypoxia-inducible factor-2α and iron absorptive gene expression in Belgrade rat intestine
Authors: Yeh Kwo-yih , Yeh Mary , Polk Paula , Glass Jonathan
Published: March 2011

The divalent metal transporter (DMT1, Slc11a2) is an important molecule for intestinal iron absorption. In the Belgrade (b/b) rat, the DMT1 G185R mutation markedly decreases intestinal iron absorption. We used b/b rats as a model to examine the genes that could be compensatory for decreased iron absorption. When tissue hypoxia was assayed by detecting pimonidazole HCl adducts, the b/b liver and intestine exhibited more adducts than the +/+ rats, suggesting that hypoxia might signal altered gene expression. Total RNA in the crypt-villus bottom (C-pole) and villus top (V-pole) of +/+, b/b, and iron-fed b/b rats was isolated for gene array analyses. In addition, hepatic hepcidin and intestinal hypoxia-inducible factor-α (Hifα) expression were examined. The results showed that expression of hepatic hepcidin was significantly decreased and intestinal Hif2α was significantly increased in b/b and iron-fed b/b than +/+ rats. In b/b rats, the expression of Tfrc mRNA in the C-pole and of DMT1, Dcytb, FPN1, Heph, Hmox1, and ZIP14 mRNAs in the V-pole were markedly enhanced with increases occurring even in the C-pole. After iron feeding, the increased expression found in b/b rats persisted, except for Heph and ZIP14, which returned to normal levels. Thus in b/b rats depressed liver hepcidin production and activated intestinal Hif2α starting at the C-pole resulted in increasing expression of iron transport genes, including DMT1 G185R, in an attempt to compensate for the anemia in Belgrade rats.
Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression
Authors: Favre Julie , Gao Ji , Zhang An Di , Remy-Jouet Isabelle , Ouvrard-Pascaud Antoine , Dautreaux Brigitte , Escoubet Brigitte , Thuillez Christian , Jaisser Frédéric , Richard Vincent
Published: March 2011

The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between mineralocorticoid receptor (MR)-mediated effects on the cardiomyocyte and the coronary arteries is unknown. Thus we used a mouse model with conditional, cardiomyocyte-specific overexpression of human MR (hMR) and observed the effects on endothelial function in isolated coronary segments. hMR overexpression decreased the nitric oxide (NO)-mediated relaxing responses to acetylcholine in coronary arteries (but not in peripheral arteries), and this was prevented by a 1-mo treatment either with an MR antagonist, vitamin E/vitamin C, or a NADPH oxidase inhibitor. hMR overexpression did not affect coronary endothelial NO synthase content nor its level of phosphorylation on serine 1177, but increased cardiac levels of reactive oxygen species, cardiac NADPH oxidase (NOX) activity, and expression of the NOX subunit gp91phox, which was limited to endothelial cells. Thus an increase in hMR activation, restricted to cardiomyocytes, is sufficient to induce a severe coronary endothelial dysfunction. We suggest a new paracrine mechanism by which cardiomyocytes trigger a NOX-dependent, reactive oxygen species-mediated coronary endothelial dysfunction.