bluuebunny/crossref_metadata_2025 huggingface dataset:
A twin study of schizoaffective‐mania, schizoaffective‐depression, and other psychotic syndromes
Authors: Cardno Alastair G. , Rijsdijk Frühling V. , West Robert M. , Gottesman Irving I. , Craddock Nick , Murray Robin M. , McGuffin Peter
Published: December 2011

The nosological status of schizoaffective disorders remains controversial. Twin studies are potentially valuable for investigating relationships between schizoaffective‐mania, schizoaffective‐depression, and other psychotic syndromes, but no such study has yet been reported. We ascertained 224 probandwise twin pairs [106 monozygotic (MZ), 118 same‐sex dizygotic (DZ)], where probands had psychotic or manic symptoms, from the Maudsley Twin Register in London (1948–1993). We investigated Research Diagnostic Criteria schizoaffective‐mania, schizoaffective‐depression, schizophrenia, mania and depressive psychosis primarily using a non‐hierarchical classification, and additionally using hierarchical and data‐derived classifications, and a classification featuring broad schizophrenic and manic syndromes without separate schizoaffective syndromes. We investigated inter‐rater reliability and co‐occurrence of syndromes within twin probands and twin pairs. The schizoaffective syndromes showed only moderate inter‐rater reliability. There was general significant co‐occurrence between syndromes within twin probands and MZ pairs, and a trend for schizoaffective‐mania and mania to have the greatest co‐occurrence. Schizoaffective syndromes in MZ probands were associated with relatively high risk of a psychotic syndrome occurring in their co‐twins. The classification of broad schizophrenic and manic syndromes without separate schizoaffective syndromes showed improved inter‐rater reliability, but high genetic and environmental correlations between the two broad syndromes. The results are consistent with regarding schizoaffective‐mania as due to co‐occurring elevated liability to schizophrenia, mania, and depression; and schizoaffective‐depression as due to co‐occurring elevated liability to schizophrenia and depression, but with less elevation of liability to mania. If in due course schizoaffective syndromes show satisfactory inter‐rater reliability and some specific etiological factors they could alternatively be regarded as partly independent disorders. © 2011 Wiley Periodicals, Inc.
Strong nonlinear optical effects from a new polymeric silver(I)–propyl–benzotriazole complex
Authors: Xu Hong , Song Yinglin , Meng Xiangru , Hou Hongwei , Fan Yaoting
Published: December 2011

A new polymeric Ag(I) complex {[Ag2(pbbt)3](NO3)2·0.5H2O}n [where pbbt = 1,1′‐(1,3‐propylene)‐bis‐1H‐benzotriazole] was synthesized as a good optical limiter. Single‐crystal X‐ray diffraction determined that the complex assumed a rare, two‐dimensional lamellar structural motif with isolated cavities of [Ag6(pbbt)6]. The Z‐scan measurements of an 8‐ns pulsed laser at 532 nm revealed that the presented complex in dimethylformamide exhibited very strong third‐order optical nonlinear absorption. The optical‐limiting (OL) performance was investigated in the sample of the complex induced by 8‐ns and 30‐ps pulses at 532 nm. The results show that this complex exhibited large OL effects with a very low limiting threshold value of 0.16 J/cm2 under 8‐ns pulse and 0.56 J/cm2 under 30‐ps pulses, among those of the best OL materials. Density functional theory calculation results further confirmed the cooperative contributions of Ag ions and bridge ligands to the optical nonlinearities of Ag(I)‐containing metal–organic complex. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Optical properties of bi‐doped epoxy novolak resin containing Ce, Dy, and Y ions
Authors: Prajzler Václav , Lyutakov Oleksiy , Hüttel Ivan , Špirková Jarmila , Oswald Jirí , Machovic Vladimír , Jerábek Vítězslav
Published: December 2011

In this article, we report on the optical properties of Bismuth doped Epoxy Novolak Resin (ENR) co‐doped with Dysprosium, Cerium, and Yttrium ions. The polymer layers containing 1.0 to 20.0 at % of Bismuth were fabricated by spin‐coating onto silicon or quartz substrates. The properties of the material were studied using several methods with special regards to its potential utilization in photonics devices. Transmission spectra were taken in the range from 350 to 1600 nm, while photoluminescence spectra around 1300 nm were recorded by using excitation of semiconductor lasers operating at 808 nm and at 980 nm (Ex= 250 mW). Optical properties of the samples were evaluated on the bases of the concentration of the Bismuth ions as well as on the concentrations of the co‐doping ions and showed close relations between concentration of the dopants and intensity of the luminescence band at 1300 nm. Our results proved that the Bismuth doped ENR has a strong potential for application in active photonics structures, as it has excellent optical properties and very easy and not demanding fabrication procedures. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Cast polyurethane elastomers with improved dynamic fatigue resistance
Authors: Xie Rui , Lakrout Hamed , Mueller Gerhard
Published: December 2011

Cast polyurethane (PU) elastomers have been widely used in dynamic applications, such as rollers and wheels, where a low heat buildup, high‐loading resistance, and good cut‐growth resistance are desired. Because of their different molecular structure, cast PU elastomers do not perform in the same way in highly demanding dynamic applications. Small variations in the viscoelastic properties can result in significant differences in the longevity of the wheels and rollers that are subjected to a large number of cyclic compressive deformations. Therefore, it is of great interest to understand dynamic performance of urethane elastomers based on various backbones. Dynamic mechanical analysis (DMA) is commonly used to differentiate the dynamic performance of elastomers, but it only provides characterization of the dynamic behavior of a given elastomer at small deformation in the linear viscoelastic regime, where information such as the heat buildup and load‐bearing capability of elastomers cannot be obtained. As such, we developed a stress‐controlled flexometer on the basis of the ISO4666/4 method that enabled measurement of the heat buildup and load‐bearing capabilities of urethane elastomers in a large dynamic deformation environment. Moreover, a dynamometer was constructed to evaluate wheels based on different urethane elastomers under load at various speeds; this allowed close simulation of the urethane elastomers in a real application environment. In this article, the viscoelastic properties of cast urethane elastomers based on different backbones were studied by DMA. The heat buildup and load‐bearing capabilities of the elastomers were investigated via the stress‐controlled flexometer, and the performance of the wheels based on various prepolymer systems were evaluated with the dynamometer. Correlations between the material viscoelastic behavior and the heat buildup were established. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Effect of glycidyl methacrylate‐grafted natural rubber on physical properties of polylactic acid and natural rubber blends
Authors: Juntuek Punmanee , Ruksakulpiwat Chaiwat , Chumsamrong Pranee , Ruksakulpiwat Yupaporn
Published: December 2011

Natural rubber (NR) was melt blended with polylactic acid (PLA) at various ratios using an internal mixer. The impact strength and elongation at break of PLA/NR blend dramatically increased with increasing NR content up to 10% (w/w). Glycidyl methacrylate‐grafted natural rubber (NR‐g‐GMA) was used as a compatibilizer for PLA/NR blend. The effects of content and %grafting of NR‐g‐GMA on mechanical properties of PLA/NR blend were studied. The experimental result showed that the addition of NR‐g‐GMA in PLA/NR blend significantly improved impact strength and elongation at break of PLA/NR blend when compared with that of neat PLA and PLA/NR blend without NR‐g‐GMA. The impact strength and elongation at break of PLA/NR blend increased with increasing NR‐g‐GMA content up to 1% (w/w). Moreover, with increasing % grafting of NR‐g‐GMA in PLA/NR blend up to 4.35, the impact strength and elongation at break of the blend increased. Morphological and thermal property of PLA, PLA/NR, and PLA/NR/NR‐g‐GMA were elucidated as well. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Dry‐jet wet‐spun PAN/MWCNT composite fibers with homogeneous structure and circular cross‐section
Authors: Zhang Jian , Zhang Youwei , Zhang Degang , Zhao Jiongxin
Published: December 2011

To produce polyacrylonirtile (PAN) fiber precursor with desired cross‐section shape, microstructure and mechanical properties, several measurements including adopting DMSO/water (95/5, v/v) mixture as the solvent of the spinning dope, ethanol/DMSO (60/40, v/v) mixture at 10°C as the coagulation medium, and modified multi‐walled carbon nanotube (MWCNT) as the reinforcing nanofiller, as well as extra‐drawing the as‐spun fiber in air, were taken in the preparation of PAN fibers via dry‐jet wet spinning. The morphology, structure, and properties, thermal behavior of the resultant fibers were studied. The results show that gel fibers with homogeneous dense structure and circular cross‐section were obtained. High orientation of PAN molecules in fiber was achieved by additional drawing the as‐spun fiber in air. After the introduction of a very small amount of modified MWCNT, the tensile strength and modulus of the fiber enhance substantially: there is a 19% increase in strength and a 62% increase in modulus at a MWCNT content of 1.0 wt %. Also, the heat release rate decreases during the oxidative stabilization. The uniform microstructure, circular cross‐section, high orientation of PAN molecules, high tensile strength and modulus, as well as the gentle oxidative cyclization behavior, make the PAN/MWCNT composite fiber an attractive precursor candidate for carbon fiber. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Morphology of the Eye of the Southern Right Whales (Eubalaena australis)
Authors: Buono Mónica R. , Fernández Marta S. , Herrera Yanina
Published: December 2011

Recently, there has been a growing interest in the anatomy and optics of the visual system of cetaceans. However, much of the new information has been focused on odontocetes, and relatively little is known about the visual anatomy of baleen whales. The aim of this study was describe the eye anatomy of the southern right whale (Eubalaena australis). Eye samples were collected from 26 calves, four adults with known body length, as well as two specimens of unknown body length that had stranded near their nursery ground at Península Valdés, Argentina, over 6 years. We provide anatomical descriptions of the eyeball and extraocular structures, as well as quantitative data in the form of eyeball, corneal, scleral, and lens measurements. To explore the sensitivity of the eye to light, the f‐number was estimated in one specimen. We found that the eyes of the calves differed from those of the adults in having less periorbital fat surrounding the eyeball. We also observed variations in the abundance of periorbital fat among the adult specimens. The regression analysis revealed a correlation between body length and eyeball size. By contrast, the dimensions of the cornea were only weakly correlated with body length. The estimated f‐number suggests that the optical sensitivity of the Eubalaena australis eye is relatively low. However, caution had to be taken in interpreting f‐number as a proxy of eye sensitivity because it depends on the lens size, which can be affected by the fixation methods used. Anat Rec, 2012. © 2011 Wiley Periodicals, Inc.
Spinal cathepsin S and fractalkine contribute to chronic pain in the collagen‐induced arthritis model
Authors: Clark Anna K. , Grist John , Al‐Kashi Adam , Perretti Mauro , Malcangio Marzia
Published: December 2011

Objective

The induction of rheumatoid arthritis (RA) by active and passive immunization of mice results in the development of pain at the same time as the swelling and inflammation, with both peripheral and central sensitization contributing to joint pain. The purpose of this study was to examine the development of pain in the rat model of collagen‐induced arthritis (CIA) and to evaluate the contribution of neuroimmune interactions to established arthritis pain.

Methods

Mechanical hypersensitivity was assessed in female Lewis rats before and up to 18 days after induction of CIA by immunization with type II collagen. The effect of selective inhibitors of microglia were then evaluated by prolonged intrathecal delivery of a cathepsin S (CatS) inhibitor and a fractalkine (FKN) neutralizing antibody, from day 11 to day 18 following immunization.

Results

Rats with CIA developed significant mechanical hypersensitivity, which started on day 9, before the onset of clinical signs of arthritis. Mechanical hypersensitivity peaked with the severity of the disease, when significant microglial and astrocytic responses, alongside T cell infiltration, were observed in the spinal cord. Intrathecal delivery of microglial inhibitors, a CatS inhibitor, or an FKN neutralizing antibody attenuated mechanical hypersensitivity and spinal microglial response in rats with CIA.

Conclusion

The inhibition of microglial targets by centrally penetrant CatS inhibitors and CX3CR1 receptor antagonists represents a potential therapeutic avenue for the treatment of pain in RA.
T cell lessons from the rheumatoid arthritis synovium SCID mouse model: CD3‐rich synovium lacks response to CTLA‐4ig but is successfully treated by interleukin‐17 neutralization
Authors: Koenders Marije I. , Marijnissen Renoud J. , Joosten Leo A. B. , Abdollahi‐Roodsaz Shahla , Di Padova Franco E. , van de Loo Fons A. , Dulos John , van den Berg Wim B. , Boots Annemieke M. H.
Published: December 2011

Objective

To provide an intermediate step between classic arthritis models and clinical trials, the rheumatoid arthritis (RA) synovium SCID mouse model is a valuable tool for use during preclinical research. We undertook this study to investigate the validity of this humanized mouse model using anti–tumor necrosis factor (anti‐TNF) and anti–interleukin‐1 (anti–IL‐1) treatment and to investigate the direct effect of T cells– and B cell–related therapies on the transplanted RA synovial tissue.

Methods

CB17/SCID mice were engrafted with human RA synovial tissue and systemically treated with anti‐TNF, anti–IL‐1, anti–IL‐17, CTLA‐4Ig, anti‐CD20, or isotype control antibodies.

Results

Validation of the model with anti‐TNF treatment significantly reduced serum cytokine levels and decreased histologic inflammation, whereas anti–IL‐1 therapy did not show any effect on the RA synovial grafts. In mice engrafted with B cell–rich synovial tissue, anti‐CD20 treatment showed clear therapeutic effects. Surprisingly, CTLA‐4Ig treatment did not show any effects in this transplantation model, despite prescreening of the synovial tissue for the presence of CD3+ T cells and the costimulatory molecules CD80 and CD86. In contrast, great therapeutic potential was observed for anti–IL‐17 treatment, but only when CD3+ T cells were abundantly present in the RA synovial tissue.

Conclusion

This human RA synovium SCID mouse model enabled us to show that CTLA‐4Ig lacks direct effects on T cell activation processes in the synovial tissue. Further evidence was obtained that IL‐17 might indeed be an interesting therapeutic target in RA patients with CD3‐rich synovial tissue. Further characterization of the RA patients' individual synovial profiles is of great importance for achieving tailored therapy.
Enhancement of Photoresponse Properties of Conjugated Polymers/Inorganic Semiconductor Nanocomposites by Internal Micro‐Magnetic Field
Authors: Hu Chenglong , Chen Yujie , Chen Xudong , Zhang Bin , Yang Jin , Zhou Juying , Zhang Ming Qiu
Published: December 2011

In this paper, the effect of the internal micro‐magnetic field (IMMF) on the photocurrent property of conjugated polymer/inorganic semiconductor nanocomposites is reported and analyzed. By using the redox reaction, magnetic Fe3O4 nanoparticles were coated on the surface of highly active nanorods of conjugated polyaniline (PANI), forming an internal micro‐magnetic electron donor (i.e., Fe3O4@PANI). After subsequent incorporation of CdS nanoparticles (serving as electron acceptors), the power conversion efficiency (PCE) of the system (Fe3O4@PANI‐CdS) was found to be as high as 3.563 %, contrasting sharply with the value (1.135 %) of the hybrid without Fe3O4 (PANI‐CdS). This obvious enhancement originated from the fact that the IMMF increased the number of singlet polaron pairs through field‐dependent intersystem crossing (ISC), giving a positive contribution to the photocurrent generation. Additionally, the dependence of the photocurrent on the remnant magnetization of the Fe3O4@PANI‐CdS nanocomposites was investigated. A percolation behavior was observed, which was due to the appearance of interpenetrating networks consisting of donor and acceptor phases, leading to the recombination of charge carriers through trapping. The outcomes of the present work might help to produce a new family of conjugated organic/inorganic semiconductor nanocomposites with designed optoelectronic performances.
N‐Bound Primary Nitramines Based on 1,5‐Diaminotetrazole
Authors: Klapötke Thomas M. , Martin Franz A. , Stierstorfer Jörg
Published: December 2011

1,5‐Diaminotetrazole can be nitrated under very mild conditions by using nitronium tetrafluoroborate to result in 5‐amino‐1‐nitriminotetrazole (1) in good yields. The same reaction can be performed with 1‐amino‐5‐amino‐4‐methyltetrazole to yield 5‐amino‐4‐methyl‐1‐nitriminotetrazole (2). Both compounds have been isolated and completely characterized by using vibrational spectroscopy, mass spectrometry, and differential scanning calorimetry. Additionally, X‐ray diffraction measurements of the neutral compounds could be obtained; they indicated the structure of both compounds to be zwitterionic. Compounds 1 and 2 exhibit extremely high sensitivities to impact and friction and high positive heats of formation of 496 (1) and 453 kJ mol−1 (2), respectively. Additionally, high‐nitrogen‐containing salts of 1 have been synthesized by metathesis reactions of silver 5‐amino‐1‐nitriminotetrazolate with the corresponding halides so as to investigate the changes in sensitivity and thermal stability. All ionic compounds have been synthesized in good yields and characterized by means of vibrational and multinuclear NMR spectroscopy as well as X‐ray diffraction measurements. Thermal stabilities have been evaluated by differential scanning calorimetry, whereas sensitivity measurements have been performed according to standardized Bundesanstalt für Materialforschung und ‐prüfung (BAM) tests. Theoretical calculations have been performed to investigate the heats of formation as well as the performance characteristics of the compounds.
Morphology‐Controlled Synthesis of Poly(oxyethylene)silicone or Alkylsilicone Surfactants with Explicit, Atomically Defined, Branched, Hydrophobic Tails
Authors: Gonzaga Ferdinand , Grande John B. , Brook Michael A.
Published: December 2011

Silicone surfactants are widely used in commerce because of the unusual surface activity when compared with fluorocarbon or hydrocarbon surfactants. However, most silicone surfactants are comprised of ill‐defined mixtures, which preclude the development of an understanding of structure–surface activity relationships. Herein, we report a synthetic strategy that permits exquisite control over silicone structure by using the B(C6F5)3‐catalyzed condensation of hydro‐ and alkoxysilanes. Six different, precise hydrophobes were then mated to hydrophilic poly(oxyethylene)s of three different molecular weights by a metal‐free click cyclization to generate a library of explicit silicone surfactants. These compounds were calculated to have a relatively linear value range of the hydrophilic–lipophilic balance, ranging from about 8 to about 15. The solubility of some of the compounds was too low to measure a critical micelle concentration (CMC). The others exhibited a broad range of surface tension values at the CMC that depend both on the length of the hydrophilic tail and, more importantly, the nature of the hydrophobic head group. Subtle distinctions in surfactant‐related properties, which can be attributed to the three‐dimensional structures, can be seen for compounds with comparable numbers of hydrocarbons and silicon groups.
Synthesis of hierarchical structured porous MoS2/SiO2 microspheres by ultrasonic spray pyrolysis
Authors: Yao Songdong , Song Chaojie , Nan Feihong , Botton Gianluigi A. , Chen Jinwen , Fairbridge Craig , Hui Rob , Zhang Jiujun
Published: December 2011

Hierarchical structure porous MoS2/SiO2 microspheres were prepared by ultrasonic pyrolysis technique. The nanostructured MoS2/SiO2 materials were characterised by scanning electron micrograph (SEM), energy dispersive X‐ray spectroscopy (EDX), X‐ray diffraction (XRD), high‐resolution transmission electron microscope (HRTEM), as well as nitrogen isotherm. The MoS2/SiO2 microspheres, synthesised using polystyrene latex spheres as a template, showed two pore sizes: 5.8 and 68 nm. The micro‐, meso‐ and macropore volume was also calculated. Effect of PSL:SiO2 ratio on the hierarchical structure was also investigated. © 2011 Canadian Society for Chemical Engineering
Effect of impeller type on continuous‐flow mixing of non‐Newtonian fluids in stirred vessels through dynamic tests
Authors: Patel Dineshkumar , Ein‐Mozaffari Farhad , Mehrvar Mehrab
Published: December 2011

Mixing of non‐Newtonian fluids with axial and radial flow impellers is prone to a significant extent of nonideal flows (e.g., dead zones and channelling) within the stirred reactors. To enhance the performance of the continuous‐flow mixing of pseudoplastic fluids with yield stress, close‐clearance impellers were utilised in this study. We explored the effects of various parameters such as the type of close‐clearance impeller (i.e., the double helical ribbon (DHR) and anchor impellers), impeller speed (25–500 rpm), impeller pumping direction, fluid rheology (0.5–1.5% xanthan gum solution), fluid flow rate (3.20–14.17 L min−1) and the locations of outlet (configurations: top inlet–top outlet, top inlet–bottom outlet) on the dynamic performance of the mixing vessel. The performance of the DHR impeller was then compared to the performance of various types of impellers such as axial‐flow (Lightnin A320) and radial‐flow (Scaba 6SRGT) impellers. The dynamic tests showed that the DHR impeller was the most efficient impeller for reducing the extent of nonideal flows in the continuous‐flow mixer among the impellers employed in this study. In addition, the mixing quality was further improved by optimising the power input, increasing the mean residence time, decreasing the fluid yield stress, using the up‐pumping impeller mode and using the top inlet–bottom outlet configuration. © 2011 Canadian Society for Chemical Engineering
Meso‐scale simulations of solid–liquid flow and strategies for meso–macro coupling
Authors: Derksen J. J.
Published: December 2011

Solid–liquid flows span a large parameter space, with dimensionless coordinates such as Stokes numbers, the solids volume fraction, the density ratio between the phases, and Reynolds numbers (e.g., associated with the continuous phase flow). We are interested in systems with appreciable inertia effects—that is, nonzero Stokes and Reynolds numbers—having density ratios of the order of one and solids volume fractions of order 0.1. In such flows, direct numerical simulations are desired to reveal the relevant interactions. The resolution required for DNS limits the size of the systems that we are able to simulate to the meso‐scale. In this article, examples of direct simulations based on the lattice‐Boltzmann method of dense solid–liquid flows are presented, along with suggestions as to how to use their results at the macro‐scale. © 2011 Canadian Society for Chemical Engineering
Retracted: Correlation of the performance of a PEM fuel cell at different channel geometries
Authors: Khazaee I. , Ghazikhani M.
Published: December 2011

The following article from The Canadian Journal of Chemical Engineering, “Correlation of the Performance of a PEM Fuel Cell at Different Channel Geometries” by I. Khazaee and M. Ghazikhani, published online on December 27, 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor‐in‐Chief, João B. P. Soares, and Wiley Periodicals, Inc. The retraction has been agreed upon due to dual submission to another publication.
The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma
Authors: Chen Miao‐Fen , Lu Ming‐Shian , Lin Paul‐Yang , Chen Ping‐Tsung , Chen Wen‐Cheng , Lee Kuan‐Der
Published: December 2011

BACKGROUND:

The identification of potential tumor markers can improve therapeutic planning and patient management. The objective of this study was to highlight the role of DNA methyltransferase 3b (DNMT3b) in esophageal squamous cell carcinoma (SCC).

METHODS:

One hundred seventy‐three esophageal SCC samples were analyzed using immunohistochemical staining to correlate the expression of DNMT3b with clinical outcome. Furthermore, a human esophageal SCC cell line, CE81T, was selected for cellular and animal experiments to investigate changes in tumor behavior and treatment response after the manipulation of DNMT3b expression.

RESULTS:

The incidence of nuclear DNMT3b immunoreactivity in esophageal cancer specimens was significantly higher than in nonmalignant epithelium, and this incidence was linked positively to developing distant metastasis (56% in localized disease vs 80% in distant metastasis; P = .002). Furthermore, increased expression of DNMT3b was linked significantly to lower treatment response rates (P = .002) and reduced survival rates (P = .000). Inhibition of DNMT3b expression resulted in slower cellular proliferation, increased cell death, a less invasive capacity, and less epithelial‐mesenchymal‐transition changes. Moreover, DNMT3b silencing vectors sensitized esophageal cancer cells to irradiation and cisplatin treatment. The current results also indicated that constitutional activation of signal transducer and activator of transcription 3 (STAT3) signaling associated with inhibited expression of suppressor of cytokine signaling 3 (SOCS3) may be the mechanism underlying more aggressive tumor growth in DNMT3b‐positive esophageal cancer.

CONCLUSIONS:

DNMT3b was linked significantly to a poor prognosis for patients with esophageal cancer. Moreover, the current results indicated that targeting this enzyme may be a promising strategy for treating esophageal cancer, as evidenced by inhibited aggressive tumor behavior and treatment resistance. Cancer 2012. © 2012 American Cancer Society.
Prognostic impact of extranodal involvement in diffuse large B‐cell lymphoma in the rituximab era
Authors: Takahashi Hiroyuki , Tomita Naoto , Yokoyama Masahiro , Tsunoda Saburo , Yano Takahiro , Murayama Kayoko , Hashimoto Chizuko , Tamura Kazuo , Sato Kazuya , Ishigatsubo Yoshiaki
Published: December 2011

BACKGROUND:

Extranodal involvement is considered a poor prognostic factor for patients with diffuse large B‐cell lymphoma (DLBCL); however, the prognostic impact of specific sites of involvement has not been fully elucidated.

METHODS:

The authors retrospectively analyzed 1221 patients treated uniformly with standard R‐CHOP therapy between 2003 and 2006. Patients with distinct forms of DLBCL such as intravascular lymphoma, primary effusion lymphoma, pyothorax‐associated lymphoma, primary central nervous system lymphoma, and intraocular lymphoma were also excluded. The authors evaluated 26 extranodal sites of involvement with respect to prognostic impact. The median age was 64 years (range, 15‐91 years).

RESULTS:

Univariate analysis revealed that patients with involvement of specific extranodal sites had significantly worse overall survival (OS) than did patients without such involvement; these sites included nasal cavity, paranasal sinus, lung, pleura, small intestine, peritoneum, liver, pancreas, stomach, spleen, adrenal gland, testis, bone, bone marrow, peripheral blood, skin, and subcutaneous tissue. Patients with Waldeyer ring involvement had significantly better OS. Multivariate analysis revealed that patients with the involvement of the pleura (P < .001), small intestine (P = .015), peritoneum (P = .002), adrenal gland (P < .001), testis (P = .005), bone marrow (P < .001), and peripheral blood (P = .002) had significantly worse OS, whereas those with Waldeyer ring involvement had significantly better OS (P = .038). Subgroup analysis with the nodal and/or Waldeyer patient group also showed prognostic impact of Waldeyer ring by multivariate analysis (relative risk, 0.3; P = .04).

CONCLUSIONS:

Extranodal involvement affects the prognosis of patients undergoing R‐CHOP therapy for DLBCL. Cancer 2012. © 2011 American Cancer Society.
The citation networks model with random aging
Authors: Geng Xianmin , Wang Ying
Published: December 2011

In citation networks, the age of the articles published plays an important role in deciding the preferential attachment probability of the publishing article. In this article, we consider the aging to be cited of the article decays as (t−ti) −η, where t − ti denotes the time when node i exists in the networks, η is a random variable and denotes the aging decay exponent of the article published. We deduce that the degree distribution of a citation network also shows power‐law dependence P(k) ∼ k −γ with exponent γ ≈ 3. At the same time, we study the clustering property of this networks, calculate the clustering coefficient of node i in citation network. We find that the clustering coefficient of node i is larger if its neighbors add into the net earlier. © 2011 Wiley Periodicals, Inc. Complexity, 2012.
Human mate choice is a complex system
Authors: Smaldino Paul E. , Schank Jeffrey C.
Published: December 2011

From a psychological perspective, human mate choice has been viewed as a problem of identifying the individual cognitive preferences and decisions that explain empirical results such as similarity in attractiveness between mates and the right‐skewed unimodal marriage hazard curves for marriage rates. Agent‐based models provide a powerful theoretical tool for investigating this relationship, but until now have not considered the effects of local neighborhoods or mobility on emergent population dynamics. In failing to do so, they have effectively ruled out the population‐level complexity inherent in human mate choice. Real people live in physical space, and their interactions are constrained by their location in and mobility among physical neighborhoods and social networks. We developed a general model of human mate choice in which agents are localized in space, interact with close neighbors, and tend to range either near or far. At the individual level, our model uses two oft‐used but incompletely understood decision rules: one based on preferences for similar partners, the other for maximally attractive partners. We show that space and mobility can interact nonlinearly with these individual decision rules and nonspatial aspects of the population structure. In particular, local interactions and limited mobility decrease interpair matching and increase mate search time. We also show that it is too easy to fit various model configurations to the scant available data. More data and more specific predictions are required. Human mate choice is a complex system with properties that emerge from space, mobility, and other factors that structure social dynamics. © 2011 Wiley Periodicals, Inc. Complexity, 2011.
Redox Reactions of a [RuIII(hedtra)(pz)] Complex with Biochemically Important Reductants: Kinetic, Mechanistic and Antimicrobial Studies
Authors: Chatterjee Debabrata , Ghosh Sarita , Pal Ujjwal , Mukhopadhyay Sudit
Published: December 2011

The kinetics of the reduction of [RuIII(hedtra)(pz)] (hedtra3– = N‐hydroxyethylethylenediaminetriacetate; pz = pyrazine) by biologically important reducing agents, Red (Red = L‐ascorbic acid, catechol and cysteine), resulting in the formation of the corresponding red‐coloured ruthenium(II) complex has been studied spectrophotometrically using both conventional mixing and stopped‐flow techniques. The time course of the reaction was followed as a function of [Red], pH and temperature. Alkali metal ions were found to have an insignificant effect on the reaction rate. Kinetic data and activation parameters are interpreted in terms of an outer‐sphere electron‐transfer mechanism, and discussed with reference to the data reported for the corresponding RuIII–edta (edta4– = ethylenediamineteraacetate) complex. The antibacterial activity of the [RuIII(hedtra)(pz)] complex in inhibiting the growth has been explored. Results of the biological studies have been discussed in terms of the cleavage of chromosomal DNA of the bacteria by the [RuIII(hedtra)(pz)] complex in the presence of cysteine under aerobic conditions.
Towards the Total Synthesis of Mycaperoxide B: Probing Biosynthetic Rationale
Authors: Silva Eduarda M. P. , Pye Richard J. , Brown Geoffrey D. , Harwood Laurence M.
Published: December 2011

Studies towards the biomimetic synthesis of mycaperoxide B (1) are described. We have established the synthesis of four diastereoisomers of mycaperoxide B methyl ester (1a) by employing a Michael addition across an α,β‐unsaturated ester precursor 2 as the key step. This result strongly suggestsstereocontrol in the addition of the hydroperoxide functionality to the E double bond and discloses the importance of choosing the correct geometry of the α,β‐unsaturated double bond when attempting to synthesise mycaperoxide B. Four diastereoisomeric tetrahydrofurans derived from an intramolecular rearrangement of the 1,2‐dioxolane enolate 12 were also isolated and characterised.
Galectin-3 deficiency prevents concanavalin A–induced hepatitis in mice
Authors: Volarevic Vladislav , Milovanovic Marija , Ljujic Biljana , Pejnovic Nada , Arsenijevic Nebojsa , Nilsson Ulf , Leffler Hakon , Lukic Miodrag L.
Published: December 2011

We used concanavalin A (Con A)-induced liver injury to study the role of galectin-3 (Gal-3) in the induction of inflammatory pathology and hepatocellular damage. We tested susceptibility to Con A–induced hepatitis in galectin-3-deficient (Gal-3−/−) mice and analyzed the effects of pretreatment with a selective inhibitor of Gal-3 (TD139) in wild-type (WT) C57BL/6 mice, as evaluated by a liver enzyme test, quantitative histology, mononuclear cell (MNC) infiltration, cytokine production, intracellular staining of immune cells, and percentage of apoptotic MNCs in the liver. Gal-3−/− mice were less sensitive to Con A–induced hepatitis and had a significantly lower number of activated lymphoid and dendritic cells (DCs) in the liver. The level of tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin (IL)-17 and -4 in the sera and the number of TNFα-, IFNγ-, and IL-17- and -4-producing cluster of differentiation (CD)4+ cells as well as IL-12-producing CD11c+ DCs were lower, whereas the number of IL-10-producing CD4+ T cells and F4/80+ macrophages were significantly higher in livers of Gal-3−/− mice. Significantly higher percentages of late apoptotic Annexin V+ propidium-idodide+ liver-infiltrating MNCs and splenocytes were observed in Gal-3−/− mice, compared to WT mice. Pretreatment of WT C57BL/6 mice with TD139 led to the attenuation of liver injury and milder infiltration of IFNγ- and IL-17- and -4-producing CD4+ T cells, as well as an increase in the total number of IL-10-producing CD4+ T cells and F4/80+ CD206+ alternatively activated macrophages and prevented the apoptosis of liver-infiltrating MNCs.

Conclusions:

Gal-3 plays an important proinflammatory role in Con A–induced hepatitis by promoting the activation of T lymphocytes and natural killer T cells, maturation of DCs, secretion of proinflammatory cytokines, down-regulation of M2 macrophage polarization, and apoptosis of MNCs in the liver.
Argininosuccinate synthase conditions the response to acute and chronic ethanol-induced liver injury in mice
Authors: Leung Tung Ming , Lu Yongke , Yan Wei , Morón-Concepción José A. , Ward Stephen C. , Ge Xiaodong , de la Rosa Laura Conde , Nieto Natalia
Published: December 2011

Argininosuccinate synthase (ASS) is the rate-limiting enzyme in both the urea and the l-citrulline/nitric oxide (NO·) cycles regulating protein catabolism, ammonia levels, and NO· generation. Because a proteomics analysis identified ASS and nitric oxide synthase-2 (NOS2) as coinduced in rat hepatocytes by chronic ethanol consumption, which also occurred in alcoholic liver disease (ALD) and in cirrhosis patients, we hypothesized that ASS could play a role in ethanol binge and chronic ethanol-induced liver damage. To investigate the contribution of ASS to the pathophysiology of ALD, wildtype (WT) and

Ass

+/− mice (

Ass

−/− are lethal due to hyperammonemia) were exposed to an ethanol binge or to chronic ethanol drinking. Compared with WT,

Ass

+/− mice given an ethanol binge exhibited decreased steatosis, lower NOS2 induction, and less 3-nitrotyrosine (3-NT) protein residues, indicating that reducing nitrosative stress by way of the l-citrulline/NO· pathway plays a significant role in preventing liver damage. However, chronic ethanol-treated

Ass

+/− mice displayed enhanced liver injury compared with WT mice. This was due to hyperammonemia, lower phosphorylated AMP-activated protein kinase alpha (pAMPKα) to total AMPKα ratio, decreased sirtuin-1 (

Sirt-1

) and peroxisomal proliferator-activated receptor coactivator-1α (

Pgc1

α) messenger RNAs (mRNAs), lower fatty acid β-oxidation due to down-regulation of carnitine palmitoyl transferase-II (CPT-II), decreased antioxidant defense, and elevated lipid peroxidation end-products in spite of comparable nitrosative stress but likely reduced NOS3.

Conclusion:

Partial

Ass

ablation protects only in acute ethanol-induced liver injury by decreasing nitrosative stress but not in a more chronic scenario where oxidative stress and impaired fatty acid β-oxidation are key events. (Hepatology 2012)
Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis: Exploratory analysis from the UNOS database
Authors: Singal Ashwani K. , Bashar Hmoud , Anand Bhupinderjit S. , Jampana Sarat C. , Singal Vineet , Kuo Yong-Fang
Published: December 2011

Data on liver transplantation for patients with alcoholic hepatitis are limited. Using the United Network for Organ Sharing database (2004-2010), adults undergoing liver transplantation for a listing diagnosis of alcoholic hepatitis were matched for age, gender, ethnicity, and model for endstage disease (MELD) score, donor risk index, and year of transplantation with three patients transplanted for a listing diagnosis of alcoholic cirrhosis. Study outcomes of graft and patient survival on follow-up were also analyzed for cohorts based on the diagnosis of the explant (46 alcoholic hepatitis and 138 alcoholic cirrhosis) and diagnosis at both listing as well as of the explant (11 alcoholic hepatitis and 33 alcoholic cirrhosis). Five-year graft and patient survival of alcoholic hepatitis and alcoholic cirrhosis patients were 75% and 73% (

P

= 0.97) and 80% and 78% (

P

= 0.90), respectively. Five-year graft and patient survival rates were also similar for cohorts based on diagnosis of the explant and diagnosis at listing as well as explant. Cox proportional regression analysis adjusting for other variables showed no impact of the etiology of liver disease (alcoholic hepatitis versus alcoholic cirrhosis) on the graft and patient survival. The causes of graft loss and patient mortality were similar in the two groups, and were not alcohol-related in any patient.

Conclusion:

Compared with alcoholic cirrhosis, patients with alcoholic hepatitis have similar posttransplantation graft and patient survival. Based on these preliminary findings, liver transplantation may be considered in a select group of patients with alcoholic hepatitis who fail to improve with medical therapy. Prospective studies are needed to assess the long-term outcome after liver transplantation in patients with alcoholic hepatitis. (Hepatology 2012)
Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease
Authors: Sullivan Shelby , Kirk Erik P. , Mittendorfer Bettina , Patterson Bruce W. , Klein Samuel
Published: December 2011

Nonalcoholic fatty liver disease (NAFLD) and alterations in hepatic lipoprotein kinetics are common metabolic complications associated with obesity. Lifestyle modification involving diet-induced weight loss and regular exercise decreases intrahepatic triglyceride (IHTG) content and very low density lipoprotein (VLDL) triglyceride (TG) secretion rate. The aim of this study was to evaluate the weight loss-independent effect of following the physical activity guidelines recommended by the Department of Health and Human Services on IHTG content and VLDL kinetics in obese persons with NAFLD. Eighteen obese people (body mass index [BMI]: 38.1 ± 4.6 kg/m2) with NAFLD were randomized to 16 weeks of exercise training (45%-55% VO2peak, 30–60 minutes × 5 days/week; n = 12) or observation (control; n = 6). Magnetic resonance spectroscopy and stable isotope tracer infusions in conjunction with compartmental modeling were used to evaluate IHTG content and hepatic VLDL-TG and apolipoprotein B-100 (apoB-100) secretion rates. Exercise training resulted in a 10.3% ± 4.6% decrease in IHTG content (
P

< 0.05), but did not change total body weight (103.1 ± 4.2 kg before and 102.9 ± 4.2 kg after training) or percent body fat (38.9% ± 2.1% before and 39.2% ± 2.1% after training). Exercise training did not change the hepatic VLDL-TG secretion rate (17.7 ± 3.9 μmol/min before and 16.8 ± 5.4 μmol/min after training) or VLDL-apoB-100 secretion rate (1.5 ± 0.5 nmol/min before and 1.6 ± 0.6 nmol/min after training).

Conclusion:

Following the Department of Health and Human Services recommended physical activity guidelines has small but beneficial effects on IHTG content, but does not improve hepatic lipoprotein kinetics in obese persons with NAFLD.
Amplified in breast cancer 1 enhances human cholangiocarcinoma growth and chemoresistance by simultaneous activation of Akt and Nrf2 pathways
Authors: Chen Qiang , Li Wenjiao , Wan Yunyan , Xia Xiaochun , Wu Qiao , Chen Yanling , Lai Zhide , Yu Chundong , Li Wengang
Published: December 2011

Transcriptional coactivator amplified in breast cancer 1 (AIB1) plays important roles in the progression of several cancers such as prostate cancer, breast cancer, and hepatocellular carcinoma. However, its role in cholangiocarcinoma (CCA), a chemoresistant bile duct carcinoma with a poor prognosis, remains unclear. In this study we found that AIB1 protein was frequently overexpressed in human CCA specimens and CCA cell lines. Down-regulation of AIB1 induced the G2/M arrest and decreased the expression of mitosis-promoting factors including Cyclin A, Cyclin B, and Cdk1 through suppressing the Akt pathway, which resulted in inhibiting CCA cell proliferation. In addition, AIB1 enhanced the chemoresistance of CCA cells at least in part through up-regulating the expression of antiapoptotic protein Bcl-2. AIB1 regulated the expression of Bcl-2 in CCA cells through activating the Akt pathway as well as suppressing intracellular reactive oxygen species (ROS). AIB1 suppressed ROS by up-regulating antioxidants such as glutathione synthetase and glutathione peroxidase, which are targets of the NF-E2-related factor 2 (Nrf2), a critical transcription factor that regulates antioxidants, detoxification enzymes, and drug efflux proteins. AIB1 also increased the expression of another two Nrf2 targets, ABCC2 and ABCG2, to enhance drug efflux. AIB1 served as an essential coactivator for Nrf2 activation by physically interacting with Nrf2 to enhance its transcriptional activity.

Conclusion:

AIB1 plays an important role in proliferation and chemoresistance of CCA through simultaneous activation of Akt and Nrf2 pathways, suggesting that AIB1 is a potential molecular target for CCA treatment.
Hedgehog pathway activation parallels histologic severity of injury and fibrosis in human nonalcoholic fatty liver disease
Authors: Guy Cynthia D. , Suzuki Ayako , Zdanowicz Marzena , Abdelmalek Manal F. , Burchette James , Unalp Aynur , Diehl Anna Mae
Published: December 2011

The Hedgehog (HH)-signaling pathway mediates several processes that are deregulated in patients with metabolic syndrome (e.g., fat mass regulation, vascular/endothelial remodeling, liver injury and repair, and carcinogenesis). The severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome generally correlate. Therefore, we hypothesized that the level of HH-pathway activation would increase in parallel with the severity of liver damage in NAFLD. To assess potential correlations between known histologic and clinical predictors of advanced liver disease and HH-pathway activation, immunohistochemistry was performed on liver biopsies from a large, well-characterized cohort of NAFLD patients (n = 90) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Database 1 study. Increased HH activity (evidenced by accumulation of HH-ligand–producing cells and HH-responsive target cells) strongly correlated with portal inflammation, ballooning, and fibrosis stage (each

P

< 0.0001), supporting a relationship between HH-pathway activation and liver damage. Pathway activity also correlated significantly with markers of liver repair, including numbers of hepatic progenitors and myofibroblastic cells (both

P

< 0.03). In addition, various clinical parameters that have been linked to histologically advanced NAFLD, including increased patient age (
P

< 0.005), body mass index (
P

< 0.002), waist circumference (
P

< 0.0007), homeostatic model assessment of insulin resistance (
P

< 0.0001), and hypertension (
P

< 0.02), correlated with hepatic HH activity.

Conclusion:

In NAFLD patients, the level of hepatic HH-pathway activity is highly correlated with the severity of liver damage and with metabolic syndrome parameters that are known to be predictive of advanced liver disease. Hence, deregulation of the HH-signaling network may contribute to the pathogenesis and sequelae of liver damage that develops with metabolic syndrome.