bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hebrew Bible in contemporary philosophy of religion
Authors: Gericke Jacobus W.
Published: November 2010

Some dialogue among these specialists, especially between biblical scholars and philosophers of religion, is unquestionably long overdue.(Stump 1985:1)�Over the last few decades, there has been an increased concern for the establishment of more sustained interdisciplinary dialogue between biblical scholars and philosophers of religion. In this article, aimed at biblical scholars, the author as biblical scholar offers a descriptive and historical overview of some samples of recourse to the Hebrew Bible in philosophical approaches in the study of religion. The aim is to provide a brief glimpse of how some representative philosophers from both the analytic and continental sides of the methodological divide have related to the biblical traditions in the quest for a contemporary relevant Christian philosophy of religion.
Evolution of organic aerosol mass spectra upon heating: implications for OA phase and partitioning behavior
Authors: Cappa C. D. , Wilson K. R.
Published: November 2010

Abstract. Vacuum Ultraviolet (VUV) photoionization mass spectrometry has been used to measure the evolution of chemical composition for two distinct organic aerosol types as they are passed through a thermodenuder at different temperatures. The two organic aerosol types considered are primary lubricating oil (LO) aerosol and secondary aerosol from the α-pinene + O3 reaction (αP). The evolution of the VUV mass spectra for the two aerosol types with temperature are observed to differ dramatically. For LO particles, the spectra exhibit distinct changes with temperature in which the lower m/z peaks, corresponding to compounds with higher vapor pressures, disappear more rapidly than the high m/z peaks. In contrast, the αP aerosol spectrum is essentially unchanged by temperature even though the particles experience significant mass loss due to evaporation. The variations in the LO spectra are found to be quantitatively in agreement with expectations from absorptive partitioning theory whereas the αP spectra suggest that the evaporation of αP derived aerosol appears to not be governed by partitioning theory. We postulate that this difference arises from the αP particles existing as in a glassy state instead of having the expected liquid-like behavior. To reconcile these observations with decades of aerosol growth measurements, which indicate that OA formation is described by equilibrium partitioning, we present a conceptual model wherein the secondary OA is formed and then rapidly converted from an absorbing form to a non-absorbing form. The results suggest that although OA growth may be describable by equilibrium partitioning theory, the properties of organic aerosol once formed may differ significantly from the properties determined in the equilibrium framework.
Trend analysis of wave storminess: wave direction and its impact on harbour agitation
Authors: Casas-Prat M. , Sierra J. P.
Published: November 2010

Abstract. In the context of wave climate variability, long-term alterations in the wave storminess pattern of the Catalan coast (northwestern Mediterranean Sea) are analysed in terms of wave energy content and wave direction, on the basis of wave hindcast data (from 44-year time series). In general, no significant temporal trends are found for annual mean and maximum energy. However, the same analysis carried out separately for different wave directions reveals a remarkable increase in the storm energy of events from the south, which is partly due to a rise in the annual percentage of such storms. A case study of Tarragona Port (on the southern Catalan coast) highlights the importance of including changes in wave direction in the study of potential impacts of climate change. In particular, an increase in the frequency of storms from the south leads to greater agitation inside the Port.
Analytical Methods for Risk Management: An Engineering Systems Perspective
Authors: Garvey, Paul R.
Published: November 2010

Risk is a driving consideration in decisions that determine how engineering systems are developed, produced, and sustained. Critical to these decisions is an understanding of risk and how it affects the engineering of systems. The process of identifying, measuring, and managing risk is known as risk management. Applied early, risk management can expose potentially crippling areas of risk in the engineering of systems. This provides management time to define and implement corrective strategies. Moreover, risk management can bring realism to technical and managerial decisions that define a system's overall engineering strategy. This paper presents an introduction to processes and analytical practices in the management of risk, as it arises in the engineering of systems. These practices have evolved from a variety of systems engineering projects and initiatives. Traditional engineering systems and risk analysis approaches are discussed.
Estimation of Travel Distance
Authors: Brimberg Jack , Walker John H.
Published: November 2010

In this chapter we discuss the use of empirical distance functions in business models. The traditional role of distance functions has been to estimate travel distances or times in a given transportation system. We examine the properties of distance functions that make them useful in this role, and review popular ones such as the Euclidean norm, rectangular (or Manhattan) norm, and the more general weighted ℓpnorm and block norm. Statistical methods used to estimate the parameters of an empirical distance function from actual travel distance data are presented. This includes a review of the various goodness‐of‐fit criteria appearing in the literature, and a discussion of their error term distributions. The usefulness of empirical distance functions in modeling service systems of ever‐increasing size and complexity, and their growing relevance in operational and strategic decision processes, are also investigated. Future areas of research are identified in closing.
3D Morphological Characterization of Phonic Insulation Fibrous Media
Authors: Peyrega Charles , Jeulin Dominique , Delisée Christine , Malvestio Jérôme
Published: November 2010

In the framework of the Silent Wall ANR project, the CMM and the US2B are associated in order to characterize and to model fibrous media studying 3D images acquired with an X‐Ray microtomograph used by the US2B. The device can make 3D images of maximal size 23043 voxels with resolutions in the range of 2–15 µm. Using mathematical morphology, measurements on the 3D X‐Ray CT images are performed to characterize materials. For example, measuring the covariance on these images of an acoustic insulating material made of wooden fibers highlights the transverse isotropy of the fibers orientations in the xOy planes perpendicular to the compression Oz axis. Moreover, it is possible to extract other morphological properties, such as the size distribution either of the fibers or of the pores by estimating the morphological opening granulometry of the considered medium. Finally the morphological tortuosity of the fibrous and porous networks are estimated from geodesic propagations. The tortuosity is a parameter which can help to link physical, acoustic, and morphological properties of the material. Moreover the effects of the boundary layer, where viscous and thermal damping of the sound take place, are studied from the point of view of the tortuosity.
Efficient and General Continuous‐Flow Hydroarylation and Hydroalkylation of Styrenes
Authors: Rueping Magnus , Bootwicha Teerawut , Sugiono Erli
Published: November 2010

A simple and efficient continuous‐flow hydroarylation of arenes and heteroarenes using various styrenes in conjunction with a heterogeneous catalyst has been developed. Additionally, this method has been successfully extended to the hydroalkylation of styrenes by employing 1,3‐dicarbonyl compounds as the nucleophile. Multigram quantities of diarylmethanes have been prepared using this new flow method.
Phase behavior analysis for industrial polymerization reactors
Authors: Yuan Zhihong , Chen Bingzhen , Zhao Jinsong
Published: November 2010

The production of polymer is a very important sector in the chemical processing industry as demand for polymeric materials increases, and these polymerization processes exhibit nonlinear dynamics posing difficulties on process operation and control. It is desirable to understand the relationship between open‐loop controllability and process conditions. The phase behavior that is an open‐loop indicator of the controllability for the methyl methacrylate and propylene polymerization reactor over the entire feasible operating region is determined, and the influences of design/operating parameters and model uncertainties on this inherent characteristic at the design stage are analyzed. Based on zero dynamics and singularity theory, directly in the nonlinear setting, a methodology for the preliminary analysis of the phase behavior over the whole feasible operating region is presented and applied into the above two reactors. The above research results demonstrate that to modify certain parameters in certain direction would improve the controllability and are expected to provide helpful guidelines for improving plant and control system design. This is desirable because it allows identification of the cause of the limitation to give an indication where to modify the design. © 2010 American Institute of Chemical Engineers AIChE J, 57: 2795–2807, 2011
A reinterpretation of the Odar and Hamilton data on the unsteady equation of motion of particles
Authors: Michaelides Efstathios E. , Roig Adam
Published: November 2010

The experimental data and correlations derived by Odar and Hamilton have been the basis of studies that included the history term in the expression of the unsteady drag. Recent studies have shown that the value of the added mass coefficient is constant and equal to ½ over a very large range of Reynolds numbers. Recent studies on the history term have proven that its form is not correct at high Re. However, the experimental data are accurate at low Re and, most probably, they represent the most reliable set of experimental data on the unsteady force on solid spheres. We conducted a study to re‐calculate the functional form of the history term in the unsteady equation of motion at low Re and to derive a new correlation for the so‐called “history force coefficient,” ΔH. The new correlation is expressed in terms of the Reynolds and Strouhal numbers of the particle. © 2010 American Institute of Chemical Engineers AIChE J, 2011
Molecular characterization and clinical features of a patient with an interstitial deletion of 3p25.3‐p26.1
Authors: Gunnarsson Cecilia , Foyn Bruun Cathrine
Published: November 2010

Distal chromosome 3p deletions (3p‐ syndrome) are associated with various developmental defects. The majority of cases have a terminal deletion of the short arm of chromosome 3 with loss of either the maternal or the paternal copy. A girl with an interstitial molecularly characterized 1.6 Mb deletion in cytoband 3p25.3‐26.1 of the paternal chromosome 3 is presented. To our knowledge, she possesses the smallest deletion that has ever been reported for a patient with a clinical phenotype in accordance with the 3p‐ syndrome. The boundaries of the deletion lies within nearly all previously reported terminal deletions causing this syndrome. Selected genes that are present in the hemizygous state and which might be important for the phenotype of this patient as regards the congenital heart defect, autistic behavior and mental retardation (CAV3, OXTR, and SRGAP3/MEGAP, respectively) are discussed in context of the clinical features. © 2010 Wiley‐Liss, Inc.
A review of interactions between cetaceans and fisheries in the Azores
Authors: Silva Mónica A. , Machete Miguel , Reis Dália , Santos Marco , Prieto Rui , Dâmaso Carla , Pereira João Gil , Santos Ricardo S.
Published: November 2010

Interactions between cetaceans and fishing activity in the Archipelago of the Azores were examined using information contained in grey literature and previously unpublished data collected by observer programmes and research projects from 1998 to 2006. Together with a brief description of the economics, gear, fishing effort, and past and ongoing monitoring projects, levels of cetacean bycatch and interference were reported for each major fishery.

Cetaceans were present in 7% (n = 973) and interfered in 3% (n = 452) of the fishing events monitored by observers aboard tuna‐fishing vessels. Interference resulted in a significantly higher proportion of events with zero catches but it was also associated with higher tuna catches.

There was a decreasing trend in the proportion of tuna‐fishing events with cetacean presence or interference throughout this study, as well as a reduction in the estimates of dolphins captured annually by the whole fleet.

Observers reported cetacean depredation in 16% of the sets for demersal species and in 2% of the sets for swordfish. Cetacean presence and depredation were associated with higher overall catches and higher catches per unit effort in demersal fisheries. Bottlenose dolphins (Tursiops truncatus) were responsible for most depredation events in demersal fisheries, whereas in the swordfish fishery, depredation was associated with the presence of killer whales (Orcinus orca). There were no reports of cetacean bycatch in these fisheries. There were also no reports of cetaceans interacting in the experimental deep‐sea fisheries that were examined.

Available data suggests that levels of interaction between cetaceans and Azorean fisheries are generally low and that the economic impact of cetacean interference is probably small. However, for several traditional fisheries there are no accurate data to determine levels of cetacean interaction. We recommend that existing observer programmes be expanded to increase observer coverage of the demersal and swordfish fisheries and allow monitoring of other existing and emerging fisheries. Copyright © 2010 John Wiley & Sons, Ltd.
Serum Peptidome Profiling in Patients with Lung Cancer
Authors: Yang Juan , Yang Shuan‐Ying , Hu Xiao‐Yan , Huo Shu‐Fen , Shang Wen‐Li , Li Zong‐Fang , Ni Lei , Wang Ai‐Ying , Guo You‐Min , Song Tu‐Sheng , Chen‐Huang
Published: November 2010

Serum peptide profiling is a promising approach for classification of cancer versus noncancer samples. In this study, we aimed to search for discriminating peptide patterns in serum samples between lung cancer patients and healthy controls. The magnetic beads‐based weak cation‐exchange chromatography followed by matrix‐assisted laser desorption and ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) was used in this study to identify patients with lung cancer. In total, serum samples from 64 lung cancer patients (32 for training set and 32 for testing set), 64 healthy controls (32 for training set and 32 for testing set), and 10 COPD patients (for disease control) were analyzed in this study. The mass spectra data analyzed with ClinProTools software was used to distinguish between cancer patients and healthy individuals based on three different algorithm models (GA, SNN, and QC). In the training set, patients with lung cancer could be identified with the mean sensitivity of 98.9% and specificity of100%. Similar results could be obtained from testing set, showing 87% sensitivity and 84.8% specificity. Screening for serum peptide patterns using MALDI‐TOF MS showed high sensitivity and specificity in identifying patients with lung cancer. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Intergalactic extinction and the deceleration parameter
Authors: Meinel R.
Published: November 2010

The deceleration parameter q0 is calculated from the relation between apparent magnitudes m of the brightest galaxies in clusters and their redshifts z considering an intergalactic extinction. The calculation is valid for a Friedman universe, homogeneously filled with dust grains, assuming the extinction to be 0.5 mag at z = 1 and a λ−1‐law of extinction (according to Oleak and Schmidt 1976). Using the m,z‐values of Kristian, Sandage, and Westphal (1978) a formal value of q0 ≈︁ 2.1 is obtained instead of q0 ≈︁ 1.6 without consideration of intergalactic extinction.
Drag perturbations of artificial satellite orbits in a spherically symmetrical atmosphere
Authors: Burs L. , Minier Liceul , Pál Á.
Published: November 2010

The equations characterizing the motion of an artificial satellite in a non‐rotating spherically symmetrical atmosphere are integrated in the assumption of a linear variation of the density scale height with height, and using a new variable instead of the true anomaly. The secular perturbations in the semi‐major axis and eccentricity are deduced.
On the cause of a wobble of polar motion oscillating with a half chandler period
Authors: Jochmann H.
Published: November 2010

It is proved that a wobble of polar motion with a half Chandler period, discussed recently in several publications, may be caused by lateral heterogeneities of rheological properties of the Earth.
Parameter estimation following an adaptive treatment selection trial design
Authors: Luo Xiaolong , Wu Samuel S. , Xiong Jie
Published: November 2010

Two‐stage, drop‐the‐losers designs for adaptive treatment selection have been considered by many authors. The distributions of conditional sufficient statistics and the Rao–Blackwell technique were used to obtain an unbiased estimate and to construct an exact confidence interval for the parameter of interest. In this paper, we characterize the selection process from a binomial drop‐the‐losers design using a truncated binomial distribution. We propose a new estimator and show that it is asymptotically consistent with a large sample size in either the first stage or the second stage. Supported by simulation analyses, we recommend the new estimator over the naive estimator and the Rao–Blackwell‐type estimator based on its robustness in the finite‐sample setting. We frame the concept as a simple and easily implemented procedure for phase 2 oncology trial design that can be confirmatory in nature, and we use an example to illustrate its application.
Effect of polyethylene glycol-based preservation solutions on graft injury in experimental kidney transplantation
Authors: Thuillier R , Renard C , Rogel-Gaillard C , Demars J , Milan D , Forestier L , Ouldmoulene A , Goujon J M , Badet L , Hauet T
Published: November 2010

Background

New preservation solutions are emerging, of various ionic compositions and with hydroxyethyl starch replaced by polymers such as polyethylene glycols (PEGs), offering the potential for ‘immunocamouflage’. This experimental study investigated which of three clinically available preservation protocols offered the best graft protection, based on epithelial-to-mesenchymal transition (EMT) and fibrosis.

Methods

Kidneys were preserved for 24 h at 4 °C with University of Wisconsin solution (UW) as standard, compared with solutions containing either 1 g/l PEG 35 kDa (Institute Georges Lopez solution, IGL) or 30g/l PEG 20 kDa (solution de conservation des organes et des tissus, SCOT). Animals were followed for up to 3 months and development of EMT, tubular atrophy and fibrosis was evaluated in comparison with sham-operated animals.

Results

Functional recovery was better in the SCOT group compared with the other groups. Chronic fibrosis, EMT and inflammation were observed in the UW and IGL groups, but limited in the SCOT group. Levels of profibrosis markers such as transforming growth factor β1, plasminogen activator inhibitor 1 and connective tissue growth factor were increased in IGL and UW groups compared with the SCOT group. Hypoxia-inducible factor (HIF) 1α and 2α expression was increased at 3 months in grafts preserved in UW and IGL, but detected transiently on day 14 when SCOT was used. Expression of HIF-regulated genes vascular endothelial growth factor and erythropoietin was increased in UW and IGL groups.

Conclusion

The choice of colloid and ionic content is paramount in providing long-term protection against chronic graft injury after renal transplantation. Preservation solutions based on PEGs may optimize graft quality.
Halide‐Guided Oligo(aryl‐triazole‐amide)s Foldamers: Receptors for Multiple Halide Ions
Authors: Wang Ying , Xiang Junfeng , Jiang Hua
Published: November 2010

We synthesized and characterized a series of oligo(phenyl‐amide‐triazole)s that can fold into a helical conformation guided by halide ions. Their binding models and affinities are highly dependent on the length of the foldamer, media and the inducing capability of halide ions. The short foldamer with one helical turn shows a 1:1 binding stoichiometry to all halides, while the longer foldamer with two or three helical turns in principle can form 1:2 complexes with chloride anions even bromide anions with an enhancement on binding affinities. A result of quantitative NOE calculations imply that the longer foldamer should increase its helical pitch so as to release the electrostatic repulsion between halide ions.
A Flexible Asymmetric Approach to Methyl 5‐Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A
Authors: Lan Hong‐Qiao , Ye Jian‐Liang , Wang Ai‐E , Ruan Yuan‐Ping , Huang Pei‐Qiang
Published: November 2010

By using a methyl tetramate derivative (R)‐ or (S)‐9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)‐ or (S)‐5‐alkyltetramates (2) is disclosed. Among the synthesized methyl 5‐alkyltetramates 2, methyl 5‐methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5‐benzyltetramate (2 g) is a substructure in the potent antineoplastic dolastatin 15 (3). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A (7) has been achieved in seven steps from (S)‐9, with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)‐belamide A (7) been confirmed, but also the solvent used for recording the 13C NMR spectrum, the 13C NMR spectrum data correlation, and optical rotation data of natural belamide A (7) have been revised.
Domino Pd‐Catalyzed Heck Cyclization and Bismuth‐Catalyzed Hydroamination: Formal Synthesis of Elacomine and Isoelacomine
Authors: Kamisaki Haruhi , Nanjo Takeshi , Tsukano Chihiro , Takemoto Yoshiji
Published: November 2010

The formal synthesis of hemiterpene spirooxindole alkaloids elacomine (1) and isoelacomine (2) is described. Heck reaction of protected iodoanilines with 5,6‐dihydro‐2H‐pyran‐2‐one or six‐membered unsaturated lactams was investigated. The coupling product was readily converted to a carbamoyl chloride with an incorporated diene unit. The spiro(pyrrolidine‐3,3′‐oxindole) skeleton, which corresponds to the carbon skeleton of1and2, was efficiently constructed from this intermediate by using a domino palladium‐catalyzed Heck reaction and bismuth‐catalyzed hydroamination. An isolated byproduct of the reaction could also be converted to the spirooxindole skeleton.
Design of Polymeric Porous Adsorbent Media and the Dynamic Behavior of Transport and Adsorption of Bioactive Molecules in Such Media
Authors: Liapis Athanasios I. , Wang Jee‐Ching
Published: November 2010

A systematic methodology based on molecular dynamics (MD) modeling and simulation was developed to study ion exchange chromatography (IEC) that utilizes polymeric porous adsorbent media in which charged affinity ligands are linked to the base matrix of the porous media via a grafted polysaccharide extender. During its transport in a porous polymeric medium, a charged adsorbate biomolecule is found to exhibit decreased mass transport coefficients, changes in shape, orientation and lateral position, and to displace the counterions in the proximity of the adsorption site in order to become adsorbed. The ligand density distributions from the MD studies as well as other ligand density distributions of interest are considered in macroscopic continuum models and this leads to a multiscale modeling study of adsorption systems.
New cis‐Configured Aziridine‐2‐carboxylates as Aspartic Acid Protease Inhibitors
Authors: Büchold Christian , Hemberger Yasmin , Heindl Cornelia , Welker Armin , Degel Björn , Pfeuffer Thomas , Staib Peter , Schneider Sabrina , Rosenthal Philip J. , Gut Jiri , Morschhäuser Joachim , Bringmann Gerhard , Schirmeister Tanja
Published: November 2010

A series of 52 cis‐configured 1‐alkyl‐3‐phenylaziridine‐2‐carboxylates were synthesized as new pseudo‐irreversible inhibitors of Candida albicans secreted aspartic acid protease 1 (SAP1), SAP2, SAP3, and SAP8. Some of the compounds, which were obtained as diastereomers with S,S‐ and R,R‐configured aziridine rings by Cromwell synthesis of racemic (2R,3S+2S,3R)‐dibromophenylpropionic acid ester with amines, followed by ester hydrolysis and coupling to hydrophobic amino acid esters, were separated by preparative HPLC. The absolute configuration of the aziridine ring was assigned by a combination of experimental circular dichroism (CD) investigations and quantum chemical CD calculations. In agreement with previous docking studies, the diastereomers all exhibit similar activity. The compounds were found to be more active against the related mammalian enzyme cathepsin D, presumably due to productive interactions of the N‐alkyl substituent with the highly lipophilic S2 pocket. The most active inhibitors (5, 9, 10, 21, and 28), characterized by benzyl, cyclohexylmethyl, tert‐butyl, or 1,4‐dimethylpentyl moieties at the aziridine nitrogen atom, exhibit k2nd values between 500 and 900×103 M−1 min−1 and Ki values near or below 1 μM for cathepsin D.
Galectin‐9 ameliorates acute GVH disease through the induction of T‐cell apoptosis
Authors: Sakai Kazuki , Kawata Eri , Ashihara Eishi , Nakagawa Yoko , Yamauchi Akira , Yao Hisayuki , Nagao Rina , Tanaka Ruriko , Yokota Asumi , Takeuchi Miki , Hirai Hideyo , Kimura Shinya , Hirashima Mitsuomi , Yoshimura Norio , Maekawa Taira
Published: November 2010

Galectins comprise a family of animal lectins that differ in their affinity for β‐galactosides. Galectin‐9 (Gal‐9) is a tandem‐repeat‐type galectin that was recently shown to function as a ligand for T‐cell immunoglobin domain and mucin domain‐3 (Tim‐3) expressed on terminally differentiated CD4+ Th1 cells. Gal‐9 modulates immune reactions, including the induction of apoptosis in Th1 cells. In this study, we investigated the effects of Gal‐9 in murine models of acute GVH disease (aGVHD). First, we demonstrated that recombinant human Gal‐9 inhibit MLR in a dose‐dependent manner, involving both Ca2+ influx and apoptosis in T cells. Next, we revealed that recombinant human Gal‐9 significantly inhibit the progression of aGVHD in murine BM transplantation models. In conclusion, Gal‐9 ameliorates aGVHD, possibly by inducing T‐cell apoptosis, suggesting that gal‐9 may be an attractive candidate for the treatment of aGVHD.
Negative regulation of Toll‐like receptor signaling plays an essential role in homeostasis of the intestine
Authors: Biswas Amlan , Wilmanski Jeanette , Forsman Huamei , Hrncir Tomas , Hao Liming , Tlaskalova‐Hogenova Helena , Kobayashi Koichi S.
Published: November 2010

A healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases. However, it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, commensal bacteria‐dependent colitis model in IL‐10‐deficient mice, we investigated the role of TLR and their negative regulation in intestinal homeostasis. In addition to IL‐10−/−MyD88−/− mice, IL‐10−/−TLR4−/− mice exhibited reduced colitis compared to IL‐10−/− mice, indicating that TLR4 signaling plays an important role in inducing colitis. Interestingly, the expression of IRAK‐M, a negative regulator of TLR signaling, is dependent on intestinal commensal flora, as IRAK‐M expression was reduced in mice re‐derived into a germ‐free environment, and introduction of commensal bacteria into germ‐free mice induced IRAK‐M expression. IL‐10−/−IRAK‐M−/− mice exhibited exacerbated colitis with increased inflammatory cytokine gene expression. Therefore, this study indicates that intestinal microflora stimulate the colitogenic immune system through TLR and negative regulation of TLR signaling is essential in maintaining intestinal homeostasis.
CD68‐expressing cells can prime T cells and initiate autoimmune arthritis in the absence of reactive oxygen species
Authors: Pizzolla Angela , Gelderman Kyra A. , Hultqvist Malin , Vestberg Mikael , Gustafsson Kenth , Mattsson Ragnar , Holmdahl Rikard
Published: November 2010

It is widely believed that DC, but not macrophages, prime naïve T cells in vivo. Here, we investigated the ability of CD68‐expressing cells (commonly defined as macrophages) in priming autoreactive T cells and initiating collagen‐induced arthritis (CIA) in the mouse. For this purpose, a transgenic mouse was developed (MBQ mouse) where macrophages exclusively expressed the MHC class II H2‐Aq (Aq) on an H2‐Ap (Ap) background. Aq, but not Ap expression mediates susceptibility to CIA through presentation of type II collagen (CII) to T cells. CIA severity is enhanced by a mutation in the Ncf1 gene, impairing reactive oxygen species (ROS) production by the phagocyte NADPH oxidase (NOX2) complex. Expression of functional Ncf1 on macrophages was previously shown to protect from severe CIA. To study the effect of ROS on macrophage‐mediated priming of T cells, the Ncf1 mutation was introduced in the MBQ mouse. Upon CII immunization, Ncf1‐mutated MBQ mice, but not Ncf1 wild‐type MBQ mice nor Ncf1‐mutated Ap mice, activated autoreactive T cells and developed CIA. These findings demonstrate for the first time that macrophages can initiate arthritis and that the process is negatively regulated by ROS produced via the NOX2 complex.
Overexpression of phospholipase Cε in keratinocytes upregulates cytokine expression and causes dermatitis with acanthosis and T‐cell infiltration
Authors: Takenaka Nobuyuki , Edamatsu Hironori , Suzuki Noboru , Saito Hiromitsu , Inoue Yukiko , Oka Masahiro , Hu Lizhi , Kataoka Tohru
Published: November 2010

Phospholipase Cε (PLCε) is an effector of Ras and Rap small GTPases. We showed previously using PLCε‐deficient mice that PLCε plays a critical role in activation of cytokine production in non‐immune skin cells in a variety of inflammatory reactions. For further investigation of its role in inflammation, we created transgenic mice overexpressing PLCε in epidermal keratinocytes. The resulting transgenic mice spontaneously developed skin inflammation as characterized by formation of adherent silvery scales, excessive growth of keratinocytes, and aberrant infiltration of immune cells such as T cells and DC. Development of the skin symptoms correlated well with increased expression of factors implicated in human inflammatory skin diseases, such as IL‐23, in keratinocytes, and with the accumulation of CD4+ T cells producing IL‐22, a potent inducer of keratinocyte proliferation. Intradermal injection of a blocking antibody against IL‐23 as well as treatment with the immunosuppressant FK506 reversed these skin phenotypes, which was accompanied by suppression of the IL‐22‐producing T‐cell infiltration. These results reveal a crucial role of PLCε in the development of skin inflammation and suggest a mechanism in which PLCε induces the production of cytokines including IL‐23 from keratinocytes, leading to the activation of IL‐22‐producing T cells.
Generation of human Th1‐like regulatory CD4+ T cells by an intrinsic IFN‐γ‐ and T‐bet‐dependent pathway
Authors: Zheng Jian , Liu Yinping , Qin Gang , Lam Kwok‐Tai , Guan Jing , Xiang Zheng , Lewis David B. , Lau Yu‐Lung , Tu Wenwei
Published: November 2010

Murine Foxp3+ Treg have recently been shown to express T‐bet, a transcription factor characteristic of Th1 effector cells. A human Treg phenotype equivalent has not been reported. Here, we show that naïve human CD4+ T cells incubated with low numbers of CD40‐activated allogeneic B cells preferentially differentiate into alloantigen‐specific CD4hiCD25hi Treg. These differentiated cells potently suppress effector T‐cell responses and express T‐bet, IFN‐γ, and CXCR3, the features of Th1 effector cells. In contrast, co‐culture of naïve CD4+ T cells with high numbers of allogeneic B cells results in CD4+CD25+ T cells that promote, rather than inhibit, effector T‐cell responses, demonstrating the plasticity of CD4+ T‐cell differentiation in response to alloantigen‐presenting B cells. The optimal accumulation of CD4hiCD25hi Treg induced using higher T cell:B cell co‐culture ratios was dependent on the expression of T‐bet and endogenously produced IFN‐γ. Induction of Treg‐mediated suppression function in the Treg population was not. As CXCR3 confers the preferential trafficking of T cells to tissue sites of IFN‐γ, these human Th1‐like Treg might be useful for modulating pathological Th1 effector responses, such as that occurring during graft‐versus‐host disease or graft rejection.
CD4+T‐cell immunity to theBurkholderia pseudomalleiABC transporter LolC in melioidosis
Authors: Chu Karen K. , Tippayawat Patcharaporn , Walker Nicola J. , Harding Sarah V. , Atkins Helen S. , Maillere Bernard , Bancroft Gregory J. , Lertmemongkolchai Ganjana , Altmann Daniel M.
Published: November 2010

Burkholderia pseudomalleicauses melioidosis, a disease with a wide range of possible outcomes, from seroconversion and dormancy to sepsis and death. This spectrum of host–pathogen interactions poses challenging questions about the heterogeneity in immunity toB. pseudomallei. Models show protection to be dependent on CD4+cells and IFN‐γ, but little is known about specific target antigens. Having previously implicated the ABC transporter, LolC, in protective immunity, we here use epitope prediction, HLA‐binding studies, HLA‐transgenic models and studies of T cells from seropositive individuals to characterize HLA‐restricted LolC responses. Immunized mice showed long‐lasting memory to the protein, whereas predictive algorithms identified epitopes within LolC that subsequently demonstrated strong HLA class II binding. Immunization of HLA‐DR transgenics with LolC stimulated T‐cell responses to four of these epitopes. Furthermore, the responsiveness of HLA transgenics to LolC revealed a hierarchy supportive of HLA polymorphism‐determined differential susceptibility. Seropositive human donors of diverse HLA class II types showed T‐cell responses to LolC epitopes, which are conserved amongBurkholderiaspecies includingBurkholderia cenocepacia, associated with life‐threateningcepaciacomplex in cystic fibrosis patients andBurkholderia mallei, which causes glanders. These findings suggest a role for LolC epitopes in multiepitope vaccine design for melioidosis and related diseases.
Space–time regression modeling of tree growth using the skew‐t distribution
Authors: Nathoo F. S.
Published: November 2010

In this paper, we present new statistical methodology for the analysis of repeated measures of spatially correlated growth data. Our motivating application, a 10 year study of height growth in a plantation of even‐aged white spruce, presents several challenges for statistical analysis. Here, the growth measurements arise from an asymmetric distribution, with heavy tails, and thus standard longitudinal regression models based on a Gaussian error structure are not appropriate. We seek more flexibility for modeling both skewness and fat tails, and achieve this within the class of skew‐elliptical distributions. Within this framework, robust space–time regression models are formulated using random effect growth curves, with coefficients arising from an underlying multivariate spatial process. Computational difficulties arise when data are collected at a large number of locations, and we consider two approaches for spatial modeling in the large data context. Both approaches are compared within the context of our application, and inference is conducted in a Bayesian framework, with implementation based on hybrid Monte Carlo. Copyright © 2010 John Wiley & Sons, Ltd.
Impact of gavage dosing procedure and gastric content on adverse respiratory effects and mortality in rat toxicity studies
Authors: Eichenbaum G. , Damsch S. , Looszova A. , Vandenberghe J. , Van den Bulck K. , Roels K. , Megens A. , Knight E. , Hillsamer V. , Feyen B. , Kelley M. F. , Tonelli A. , Lammens L.
Published: November 2010

Unscheduled mortality preceded by adverse respiratory clinical signs in rats dosed by oral gavage may not only be caused by technical gavage error or systemic toxicity but may also be caused by gastro‐esophageal reflux and subsequent aspiration of high concentrations of drug formulation. In a 3 week oral gavage rat toxicity study for an early drug development compound, preterminal deaths (approximately 20% of animals) at high doses (≥1000 mg kg−1) and concentrations (≥60 mg ml−1) were preceded by recurrent dyspnea, rales or excessive salivation, without evidence of accidental intrapulmonary gavage error. Histological evaluation revealed extensive necrosis and inflammatory changes in the upper respiratory tract, especially in the nasal turbinates and/or nasopharynx. The presence of food particles in inflammatory exudates suggested a retrograde aspiration of stomach content with test formulation via the nasopharyngeal duct into the posterior region of the nose. In contrast, no mortality or adverse respiratory effects were observed in rats following 2 week intravenous administration at comparable exposures or oral gavage administration at lower concentrations (≤20 mg ml−1). In a pharmacology study, the compound caused a dose‐dependent increase in gastric content (partly due to inhibition of gastric emptying), providing a pharmacological basis for the suspected gavage‐mediated gastroesophageal reflux. Reducing the dose volume and dosing fasted animals substantially reduced or eliminated the respiratory effects and mortality at the high test article concentrations, demonstrating that the adverse effects are related to the gavage method. Copyright © 2010 John Wiley & Sons, Ltd.
Different reaction patterns of dopamine content to prenatal exposure to chlorpyrifos in different periods
Authors: Chen Xiao‐Ping , Wang Xiang , Dong Jing‐Yin
Published: November 2010

Developmental exposure to chlorpyrifos (CPF) induces abnormalities in neurotransmission. In the present study, we evaluated the dopamine reaction patterns in brain regions after CPF exposure during different prenatal periods. Animals were exposed on gestational days (GD) 7.5–11.5 or 13–17 and assessed at GD17, and at postnatal days (PN) 14 and 60. CPF exposure during GD7.5–11.5 elicited a decrease in dopamine content at each measurement stages, with more changes in the hippocampus than in the cerebral cortex. In contrast, CPF exposure in GD13–17 elicited a decrease in dopamine content at PN14 and PN60, with more changes in the cerebral cortex than in the hippocampus. These results suggest that the two key brain regions involved in learning and memory, the cerebral cortex and hippocampus, react differently to CPF exposure in different prenatal periods. The abnormalities did not recover long after cessation of CPF exposure and deficiencies persisted into pre‐puberty and adulthood. Copyright © 2010 John Wiley & Sons, Ltd.
Application of dosimetry systems and cytogenetic status of the child population exposed to diagnostic X‐rays by use of the cytokinesis‐block micronucleus cytome assay
Authors: Gajski Goran , Milković Đurđica , Ranogajec‐Komor Mária , Miljanić Saveta , Garaj‐Vrhovac Vera
Published: November 2010

Low‐dose ionizing radiation used for medical purposes is one of the definite risk factors for cancer development, and children exposed to ionizing radiation are at a relatively greater cancer risk as they have more rapidly dividing cells than adults and have longer life expectancy. Since cytokinesis‐block micronucleus cytome (CBMN Cyt) assay has become one of the standard endpoints for radiation biological dosimetry, we used that assay in the present work for the assessment of different types of chromosomal damage in children exposed to diagnostic X‐ray procedures. Twenty children all with pulmonary diseases between the ages of 4 and 14 years (11.30 ± 2.74) were evaluated. Absorbed dose measurements were conducted for posterior–anterior projection on the forehead, thyroid gland, gonads, chest and back. Doses were measured using thermoluminescence and radiophotoluminescent dosimetry systems. It was shown that, after diagnostic X‐rays, the mean total number of CBMN Cyt assay parameters (micronucleus, nucleoplasmic bridges and nuclear buds) was significantly higher than prior to diagnostic procedure and that interindividual differences existed for each monitored child. For the nuclear division index counted prior and after examination, no significant differences were noted among mean group values. These data suggest that even low‐dose diagnostic X‐ray exposure may induce damaging effect in the somatic DNA of exposed children, indicating that immense care should be given in both minimizing and optimizing radiation exposure to diminish the radiation burden, especially in the youngest population. Copyright © 2010 John Wiley & Sons, Ltd.
THE GENDERED BURDEN OF LIBERALISATION: THE IMPACT OF INDIA'S ECONOMIC REFORMS ON ITS FEMALE AGRICULTURAL LABOUR
Authors: Garikipati Supriya , Pfaffenzeller Stephan
Published: November 2010

India has experienced unprecedented growth in the last two decades—a development largely attributed to economic reforms initiated in the early 1990s. India's approach to liberalisation has been commended for its gradual implementation and its sympathy for poor rural workers. Studies examining the relevance of this claim generally use national survey data, which are seriously limited. So far little effort has been focussed on understanding what reforms actually mean for the rural poor using primary data. In this paper, we use data from a household survey carried out in the villages of Andhra Pradesh. We ask what impact India's reforms have had on its female agricultural labour—who are arguably among its poorest. Specifically, we investigate the impact of three developments considered fundamental to India's economic transformation: a sectoral shift in favour of industry, credit market reforms and poverty alleviation strategies. We argue that despite having a beneficial impact overall, economic reforms have resulted in further marginalising rural women into badly paid and socially debasing waged work. Copyright © 2010 John Wiley & Sons, Ltd.
Surgical preparation of bone–scaffold interface is critical for bone regeneration inside tissue engineering scaffold
Authors: Roshan‐Ghias Alireza , Pioletti Dominique P.
Published: November 2010

The goal of this study was to investigate if the preparation of implantation site affects bone formation inside tissue engineering scaffolds. For this purpose, two different drilling techniques were used to create a hole in distal femurs of rats before the insertion of a bone scaffold: a manually driven wood drill bit and an electrically driven metal drill bit. The size and the position of the hole were identical for the two cases. The bone volume, bone mineral density, and callus formation were assessed noninvasively using micro‐CT tomography at several time points after implantation. The formation of bone and soft tissue inside scaffold were evaluated by histology. The bone structure around the holes made by the two techniques was compared ex vivo. The long‐term study of bone formation showed that when a wood drill bit was used, the bone formation is accelerated by 3 weeks compared to when a metal drill bit was used. The ex vivo studies suggest that this result is due to the drilling methods differentially affecting the structure of the bone surrounding the generated defects. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:767–772, 2011
Raising the rate of venture capital: A foreword note
Authors: Kianfar Michael , Milana Carlo , Smith Helen Lawton
Published: November 2010

The contributions in this issue show that the role played by venture capital can be active and positive in determining and sustaining a high growth profile of the backed firms provided that agency problems are minimized and appropriate financial instruments are devised to contain the increase in the risk premium of the operations.
Sensitivity enhancement of CE and CE‐MS for the analysis of peptides by a dynamic pH junction
Authors: Hasan Md. Nabiul , Park Soo Hyun , Oh Eulsik , Song Eun Joo , Ban Eunmi , Yoo Young Sook
Published: November 2010

An analytical method of CE‐MS and CE with an online preconcentration technique induced by a dynamic pH junction, addition of organic solvent and large volume injection was developed for sensitive determination of peptides in biological samples. Leucine enkephalin, methionine enkephalin, dynorphin A, β‐endorphin and angiotensin II were used as model peptides. The optimal online preconcentration conditions were obtained at a sample matrix consisting of 100 mM borate buffer (pH 10.0) with 50% v/v acetonitrile and a BGE containing 1 M formic acid at pH 2.0, along with a 25‐cm injection length. Under the optimized conditions, a 4.0×103–1.1×104‐fold increase in peak intensity was achieved without degrading the peak shape. This online preconcentration method was applied to analyze the intracellular angiotensin II within the peptides extracted from HL1 cells and approximately increase of 1×104‐fold sensitivity was achieved compared to normal condition. Thus, the developed method could be applied to the analysis of various peptides for peptidomics study in biological samples.
Development and optimization of an LC‐MS/MS‐based method for simultaneous quantification of vitamin D2, vitamin D3, 25‐hydroxyvitamin D2 and 25‐hydroxyvitamin D3
Authors: Adamec Jiri , Jannasch Amber , Huang Jianjie , Hohman Emily , Fleet James C. , Peacock Munro , Ferruzzi Mario G. , Martin Berdine , Weaver Connie M.
Published: November 2010

Simultaneous and accurate measurement of vitamin D and 25‐hydroxyvitamin D in biological samples is a barrier limiting our ability to define “optimal” vitamin D status. Thus, our goal was to optimize conditions and evaluate an LC‐MS method for simultaneous detection and quantification of vitamin D2, vitamin D3, 25‐hydroxyvitamin D2 and 25‐hydroxyvitamin D3 in serum. Extraction and separation of vitamin D forms were achieved using acetone liquid–liquid extraction and by a reversed phase C8 column, respectively. Detection was performed on a triple quadrupole tandem mass spectrometer (QQQ‐MS/MS) equipped with atmospheric pressure photo ionization source. The LOQs for all analytes tested were 1 ng/mL for hydroxylated molecules and 2 ng/mL for the parent vitamin Ds. RSD at lower LOQ (2 ng/mL) and in medium (80 ng/mL) and high (200 ng/mL) quality control samples did not exceed 20 and 15% CV, respectively. Accuracy of the method for determination of hydroxylated molecules was also validated using National Institutes of Standards and Technology standard samples and found to be in the range of 90.9–111.2%. In summary, a sensitive and reproducible method is reported for simultaneous quantification of vitamin D2, vitamin D3, 25‐hydroxyvitamin D2 and 25‐hydroxyvitamin D3 molecules in biological samples.
Connectivity in Lattice‐Ordered Spaces
Authors: Erné M. , Vainio R.
Published: November 2010

The classical order‐theoretical characterizations of compact and connected chains, respectively, are extended to wider classes of lattices, using the fact that compactness and (path‐) connectedness of maximal chains are closely related to the corresponding properties of the whole lattice (as was already pointed out in an earlier paper due to the second author). Here we replace maximal chains by “links” and study several new types of connectedness in ordered convergence spaces, such as path‐connectedness, link‐connectedness and 1‐connectedness. As a useful framework for these studies, we introduce the concept of “connectivity systems”.