bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects on the Reactivity by Changing the Electrophilic Center from CO to CS: Contrasting Reactivity of Hydroxide, p‐Chlorophenoxide, and Butan‐2,3‐dione Monoximate in DMSO/H2O Mixtures
Authors: Um Ik‐Hwan , Han Jeong‐Yoon , Buncel Erwin
Published: December 2008

Second‐order rate constants have been measured spectrophotometrically for the reactions of O‐p‐nitrophenyl thionobenzoate (1, PNPTB) with HO−, butan‐2,3‐dione monoximate (Ox−, α‐nucleophile), and p‐chlorophenoxide (p‐ClPhO−, normal nucleophile) in DMSO/H2O of varying mixtures at (25.0±0.1) °C. Reactivity of these nucleophiles significantly increases with increasing DMSO content. HO− is less reactive than p‐ClPhO− toward 1 up to 70 mol % DMSO although HO− is over six pKa units more basic in these media. Ox− is more reactive than p‐ClPhO− in all media studied, indicating that the α‐effect is in effect. The magnitude of the α‐effect (i.e., k/kp) increases with the DMSO content up to 50 mol % DMSO and decreases beyond that point. However, the dependency of the α‐effect profile on the solvent for reactions of 1 contrasts to that reported previously for the corresponding reactions of p‐nitrophenyl benzoate (2, PNPB); reactions of 1 result in much smaller α‐effects than those of 2. Breakdown of the α‐effect into ground‐state (GS) and transition‐state (TS) effects shows that the GS effect is not responsible for the α‐effect across the solvent mixtures. The role of the solvent has been discussed on the basis of the bell‐shaped α‐effect profiles found in the current study as well as in our previous studies, that is, a GS effect in the H2O‐rich region through H‐bonding interactions and a TS effect in the DMSO‐rich media through mutual polarizability interactions.
Telencephalic morphogenesis during the process of neurulation: An experimental study using quail–chick chimeras
Authors: Pombero Ana , Martinez Salvador
Published: December 2008

After gastrulation, during the process of neurulation, the anterior neural region undergoes important morphological transformations. The almost flat epithelium of the rostral neural plate becomes transformed into a spherical region, the prosencephalic vesicle, in the neural tube. Later in development, two bilateral areas (the optic and telencephalic vesicles) progressively protrude from the prosencephalon, generating the eyes and the cerebral hemispheres, respectively. Although the principal processes of neurulation have been well characterized, the growth patterns and evolution of topological relations between internal prosencephalic regions have not been experimentally analyzed. In order to better characterize morphogenetic transformations of the prosencephalon, we have realized and comparatively analyzed neuroepithelial fate maps before and after neurulation using quail/chick chimerical experiments. Since we have previously reported the fate map of the prosencephalon at the neural plate stage, in the present work we report the corresponding fate map at the neural tube stage. Comparative analysis of the two maps has allowed us to descriptively characterize the morphogenetic transformations of the alar prosencephalic regions during neurulation and to establish the topologic evolution of the principal areas of the vertebrate telencephalon. J. Comp. Neurol. 512:784–797, 2009. © 2008 Wiley‐Liss, Inc.
Gene expression regulated by pioglitazone and exenatide in normal and diabetic rat islets exposed to lipotoxicity
Authors: Ghanaat‐Pour Hamedeh , Sjöholm Åke
Published: December 2008

Background

Hyperlipidaemia has been suggested to contribute by pro‐apoptotic actions to the loss of β‐cell mass, its secretory defects, and thereby impaired β‐cell function in type 2 diabetes. Treatment of genetically diabetic rats and also type 2 diabetic patients with pioglitazone, a PPAR‐γ agonist, lowers fasting levels of plasma glucose and triglycerides, and has been suggested to protect β‐cells against diabetic lipotoxicity in vitro and in vivo. Another recently launched anti‐diabetic drug, exenatide, an incretin mimetic, has been shown to stimulate insulin secretion, growth, and proliferation of pancreatic β‐cells and to protect them against apoptosis. We aimed to investigate global alterations in β‐cell gene expression under lipotoxic conditions and the influence of in vitro treatment with pioglitazone and exenatide.

Methods

Global gene expression profiling was thus performed to characterize genes differently regulated by palmitate, pioglitazone, and exenatide in isolated islets from non‐diabetic Wistar rats and type 2 diabetic Goto‐Kakizaki (GK) rats.

Results

Gene expression profiling revealed significant changes in islet mRNAs involved in control of several aspects of β‐cell function, e.g. epigenetic regulation of gene expression, cell differentiation and morphogenesis, also metabolism, response to stimulus, transport, and signal transduction. Pioglitazone and exenatide appear to significantly impact epigenetic processes, e.g. stable alterations in gene expression potential, which arise during development and cell proliferation. Bcl2‐like 1 (Bcl2l1), an anti‐apoptotic protein, and Bcl2 modifying factor (Bmf), a pro‐apoptotic protein, were both down‐regulated by pioglitazone and exenatide in the presence of palmitate in diabetic GK islets. In contrast, Bmf was downregulated by pioglitazone in the presence of palmitate in non‐diabetic Wistar islets. Exposure of non‐diabetic Wistar islets to palmitate led to a reduction in the expression of PPAR β/δ. This suggests that palmitate may increase the accumulation of triglycerides by reducing PPAR signalling. Moreover, treatment with either pioglitazone or exenatide restored and increased the expression of PPAR β/δ in non‐diabetic Wistar islets.

Conclusions

Taking into account that these drugs target different components of the epigenetic machinery, our findings suggest that they might participate in restoring normal gene activity in dysfunctional islets and that additive benefits may occur. Whether such events contribute to the β‐cell sparing, proliferative, and anti‐apoptotic effects of these drugs in diabetes remains to be elucidated. Copyright © 2008 John Wiley & Sons, Ltd.
Characterization of endothelial progenitor cells in the NOD mouse as a source for cell therapies
Authors: Khoo Cheen Peen , Valorani M. G. , Brittan Mairi , Alison Malcolm R. , Warnes Gary , Johansson Ulrika , Hawa Mohammed , Pozzilli Paolo
Published: December 2008

Background

Endothelial progenitor cells (EPCs) in bone marrow (BM) and peripheral blood (PB) contribute to tissue repair in various pathological conditions via the formation of new blood vessels. Previous studies indicate that diabetic patients have reduced EPC number and deregulated EPC function, although the regenerative properties of EPCs in diabetes are unknown. We wish to characterize and compare EPCs from pre‐diabetic and diabetic non‐obese diabetic (NOD) mice, a model of type 1 diabetes (T1D), in order to delineate the role of these cells in the pathogenesis of autoimmune diabetes.

Methods

Whole BM was obtained by flushing femurs, tibias and illiac crests from pre‐diabetic and diabetic NOD mice (5–30 weeks) in which the diabetic status was confirmed by measuring blood glucose levels (≥11.5 mmol/L); PB was collected in heparin‐coated tubes and lysed after incubation with antibodies directed against EPCs.

Results

FACS analyses revealed a significant decrease in EPC number (CD31+, c‐Kit+, Sca‐1+, Lin−) in BM from diabetic compared to pre‐diabetic mice (P = 0.02). Conversely, EPC number was significantly increased in PB from diabetic compared to pre‐diabetic mice (P = 0.01).

Conclusions

These data suggest that at the onset of diabetes, BM‐derived EPCs are stimulated to enter the systemic circulation likely in response to signals from the pancreas. Further studies are required to elucidate whether EPCs home the damaged pancreas, thus representing a prospective source of autologous cells for β‐cell regeneration therapy. Copyright © 2008 John Wiley & Sons, Ltd.
Smad5 haploinsufficiency leads to hair cell and hearing loss
Authors: Yang Shi‐Ming , Guo Wei‐Wei , Hu Yin‐Yan , Sun Yan‐Xun , Hou Zhao‐Hui , Sun Jian‐He , Wang Xiang , He David Z.Z. , Zhai Suo‐Qiang , Young Wie‐Yen , Han Dong‐Yi , Yang Xiao
Published: December 2008

The Smads are a group of related intracellular proteins critical for transmitting the signals to the nucleus from the transforming growth factor‐β superfamily at the cell surface. Knockout of the Smad5 is embryonic lethal. However, the Smad5 knockout of single allele (±) could survive. We used Smad5 heterozygous knockout (±) to determine the role of Smad5 in the development of inner ear morphology and function. In situ hybridization showed that Smad5 was expressed predominantly in hair cells, spiral ganglion, and supporting cells. Measurements of hearing thresholds using auditory brainstem response showed that Smad5 defect resulted in progressive hearing loss between 4 and 24 weeks after birth. Morphological examination revealed apoptosis in the inner ear, with significant loss of outer hair cells in adult Smad5 mutant mice. Our results indicated that deficiency in the Smad5‐mediated signaling resulted in apoptosis of hair cells, suggesting Smad5 is a gene that may be related with presbycusis. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2009
Optimization of input and output filters in matrix converter drive system
Authors: Yamada Kenji , Higuchi Tsuyoshi , Hara Hidenori , Yamamoto Eiji , Kume Tsuneo , M. Swamy Mahesh
Published: December 2008

This paper presents an AC‐AC power converter integrated with techniques that provide environmental harmony. The voltage source PWM inverter has been established as the major motor drive equipment. However, it is associated with issues pertaining to PWM switching as well as issues related to the input harmonics caused by capacitor input‐type rectification. Hence, there is need for a converter that addresses these problems and provides an environmentally harmonious solution. The matrix converter has a topology that inherently exhibits sinusoidal input current waveforms and less stressful output voltage waveforms. Combining the matrix converter with certain filter topologies is shown to provide an environmentally harmonious solution. © 2008 Wiley Periodicals, Inc. Electron Comm Jpn, 91(8): 1–10, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10129
Service restoration method considering simultaneous disconnection of distributed generators by one‐bank fault of distribution system
Authors: Takano Hirotaka , Hayashi Yasuhiro , Matsuki Junya , Kobayashi Naoki
Published: December 2008

Distributed generators (DGs) such as fuel cells and solar cells are going to be installed in the demand side of distribution systems. The DGs can reduce distribution loss by appropriate allocation. However, there are several problems installing DGs such as service restoration of distribution system with DGs and so on. When one bank fault of distribution substation occurs in distribution system, since DGs are simultaneously disconnected from the system, it is not easy to restore isolated load by one bank switching in distribution substation. Therefore, a service restoration method to determine restoration configuration and restoration procedures (switching procedure from normal configuration to restoration configuration) taking into account simultaneous disconnection of DGs is needed. In this paper, the authors propose a computation method to determine the optimal restoration configuration and the restoration procedure considering simultaneous disconnection of DGs by one bank fault of distribution system. In the proposed algorithm, after all of the restoration configuration candidates are effectively enumerated under the operational constraints, the optimal configuration to restore the isolated load is selected among enumerated configuration candidates. After determining the optimal restoration configuration, the optimal restoration procedures are obtained by greedy algorithm. Numerical simulations are carried out for a real scale system model with 237 sectionalizing switches (configuration candidates are 2237) and 21 DGs (total output is 5250 kW which is 3% of total load) in order to examine the validity of the proposed algorithm. © 2008 Wiley Periodicals, Inc. Electron Comm Jpn, 91(8): 44–55, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10133
Coordinated voltage control of transformer taps with provision for hierarchical structure in power system
Authors: Nakachi Yoshiki , Kato Satoshi , Ukai Hiroyuki
Published: December 2008

Participation of distributed generators (DGs), such as wind turbines, cogeneration systems, etc., is a natural trend from an ecological point of view and will continue to increase. The outputs of these DGs mainly depend on weather conditions but do not correspond to the changes of electrical load demand necessarily. On the other hand, due to deregulation of the electric power market, the power flow in a power system will uncertainly vary with several power transactions. Thus, complex power flow by DGs or transactions will cause voltage deviation. It will be difficult to sustain the voltage quality by using conventional voltage/reactive power control in the near future.

In this paper, in order to avoid such voltage deviation and to decrease the frequency of transformer tap operations, the coordinated voltage control scheme of transformer taps on account of hierarchical structure in the power system is proposed. In the proposed scheme, integral of voltage deviation at each layer bus is applied to decide the timing of each transformer tap operation. Numerical simulations confirm that the proposed scheme is able to respond to every condition on voltage deviation. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 166(4): 48–55, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20531
Application of dynamic rating to increase the available transfer capability
Authors: Miura Masaki , Satoh Takuya , Iwamoto Shinichi , Kurihara Ikuo
Published: December 2008

As the deregulated environment of power systems has spread worldwide, it is essential to operate power systems efficiently and economically. With the advance of communication technologies and sensors, so‐called dynamic rating is now to be realized. Dynamic rating is a method which determines accurate ratings by utilizing real‐time information such as conductor temperatures, ambient temperatures, and wind speeds. The dynamic rating is considered to increase the thermal capacities of overhead transmission lines and therefore take on importance in the deregulated electric power industry. The importance of the dynamic rating lies mainly in the area of Available Transfer Capability (ATC) improvement. In this paper, the validity of the proposed dynamic rating application is shown from the viewpoint of ATC, especially ATC with thermal constraints. In addition, the possibilities of ATC estimations using sensitivities are verified for the purpose of reducing calculation time, considering the importance of real‐time simulation of ATC. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 166(4): 40–47, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20537
Running stabilization control of electric vehicle based on cornering stiffness estimation
Authors: Tsumasaka Akio , Fujimoto Hiroshi , Noguchi Toshihiko
Published: December 2008

In this paper, novel direct yaw moment control (DYC) with road condition estimation and anti‐slip control is proposed for electric vehicles. An inner‐loop observer controls the vehicle traction, and an outer‐loop observer stabilizes the yawing motion of the vehicle. An immeasurable parameter known as cornering stiffness is estimated from the detected yaw‐rate, steering angle, wheel speed and yaw moment observer output in real time. Thus, the accurate control input can be generated with the estimated parameters. The proposed adaptive control is compared with a conventional robust control method under dry and snowy terrain conditions. Experimental results show that the proposed control algorithm properly attenuates the yaw‐rate error. ©2008 Wiley Periodicals, Inc. Electr Eng Jpn, 166(4): 97–104, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20569
Multi‐agent‐based autonomous power distribution network restoration using contract net protocol
Authors: Kodama Junichi , Hamagami Tomoki , Shinji Hiroshi , Tanabe Takayuki , Funabashi Toshihisa , Hirata Hironori
Published: December 2008

A novel multi‐agent‐based system based on the contract net protocol (CNP), intended to achieve a distributed approach to power distribution network restoration, is proposed. In the proposed system, agents are assigned to areas sectioned by switches and constantly exchange environmental information among themselves. The information is used to construct a CNP overlay network to guard against network accidents. The parameters of the CNP required for robustness and effectiveness are optimized by the genetic algorithm (GA) in the operation phase. When a network accident occurs, the agents restore power distribution service autonomously through the CNP overlay network constructed. Simulation experiments indicate that CNP allows an effective power distribution network restoration strategy to be created by cooperation among agents. ©2008 Wiley Periodicals, Inc. Electr Eng Jpn, 166(4): 56–63, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20661
Approaches to suppressing shaft voltage in brushless DC motor driven by PWM inverter
Authors: Iimori Kenichi , Shinohara Katsuji , Yamamoto Kichiro , Morigami Atsushi
Published: December 2008

This paper describes the approaches to suppressing the shaft voltage and bearing current by electrostatically shielding the stator end windings of the brushless DC motor driven by PWM inverter. At first, measured shaft voltage and bearing current are compared with those calculated waveforms to verify the common mode equivalent circuit of the brushless DC motor. Next, the relationship between shaft voltage and stator winding to rotor capacitance is calculated using the common mode equivalent circuit. Finally, the electrostatic shielding of the stator end windings is evaluated to reduce the shaft voltage by experiments and calculations. ©2008 Wiley Periodicals, Inc. Electr Eng Jpn, 166(4): 73–79, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20701
Perfect tracking control of servomotor based on precise model considering current loop and PWM hold
Authors: Sakata Koichi , Fujimoto Hiroshi
Published: December 2008

In motion control, position control systems for servomotors are generally designed without considering the current loop and the dynamics of a PWM inverter. In this paper, a novel precise model of a servomotor is developed, including the current loop and the PWM inverter, and a high‐speed servo system is proposed based on perfect tracking control with the precise model. Finally, simulations and experiments are performed to show the advantages of the proposed method. ©2008 Wiley Periodicals, Inc. Electr Eng Jpn, 166(4): 64–72, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20749
Differential expression of constitutive and inducible proteasome subunits in human monocyte‐derived DC differentiated in the presence of IFN‐α or IL‐4
Authors: Tosello Valeria , Zamarchi Rita , Merlo Anna , Gorza Margherita , Piovan Erich , Mandruzzato Susanna , Bronte Vincenzo , Wang Xinhui , Ferrone Soldano , Amadori Alberto , Zanovello Paola
Published: December 2008

Several studies strongly suggest that DC differentiated in vitro in the presence of type I IFN acquire more potent immune stimulatory properties, compared with DC differentiated in vitro with IL‐4. However, little is known about the molecular mechanisms underlying this phenomenon. To address this question, we compared the Ag‐processing machinery (APM) profile in human DC grown in the presence of IFN‐α (IFNDC) or IL‐4 (IL‐4DC). Using a panel of APM component‐specific mAb in Western blot experiments, we found that IFNDC preferentially express inducible proteasome subunits (LMP2, LMP7, and MECL1) both at immature and mature stages. In contrast, immature IL‐4DC co‐express both constitutive (β1, β2, and β5) and inducible subunits, as shown by Western blotting analysis. In addition, immature IFNDC express higher levels of TAP1, TAP2, calnexin, calreticulin, tapasin, and HLA class I molecules than IL‐4DC. The different proteasome profiles of IFNDC and IL‐4DC were associated with a greater ability of IFNDC to present an immunodominant epitope that requires LMP7 expression for its processing. In general, these data show the impact of cytokines on APM component expression and hence the Ag‐processing ability of DC.
CD4+ T‐cell development in a mouse expressing a transgenic TCR derived from a Treg
Authors: DiPaolo Richard J. , Shevach Ethan M.
Published: December 2008

CD4+Foxp3+ Treg maintain peripheral tolerance and influence immune responses to foreign antigens. The thymus is an important source of Treg, but controversy exists as to whether T cells are selected into the Treg lineage based on signals received through TCR specific for self‐peptides. To examine the specificity of TCR expressed by Treg and its effect on CD4+ T‐cell development, we generated Treg‐TCR transgenic mice. Deletion of >90% of CD4+ T cells in RAG‐sufficient mice, and nearly 100% deletion in RAG−/− mice expressing this TCR indicate that the TCR is specific for an unknown, naturally expressed peptide in the thymus. Deletion occurs late in development, suggesting this peptide is presented by APC in the thymic medulla. These studies are the first to describe the effects of expressing a Treg‐TCR on CD4+ T‐cell development. The implications of our data for models of Treg selection are discussed.
The Selective O‐Acylation of Hydroxyproline as a Convenient Method for the Large‐Scale Preparation of Novel Proline Polymers and Amphiphiles
Authors: Kristensen Tor E. , Hansen Finn K. , Hansen Tore
Published: December 2008

In this work we show how a direct O‐acylation of trans‐4‐hydroxy‐L‐proline with acyl chlorides in trifluoroacetic acid makes a range of novel proline derivatives readily available on large‐scale. No protecting groups or chromatographic techniques are involved in any of the procedures, and certain amphiphilic proline derivatives, which recently have received interest in synthesis, are now potentially some of the most readily accessible organocatalysts. The selective acylation was also utilized in the synthesis of a novel high‐load proline polymer, poly(O‐acryloyl‐trans‐4‐hydroxy‐L‐proline), a polymer with the highest proline loading reported and for which classical methods failed for its preparation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
An Enantioselective Synthesis of 3,4‐Benzo‐5‐oxacephams
Authors: Kozioł Anna , Frelek Jadwiga , Woźnica Magdalena , Furman Bartłomiej , Chmielewski Marek
Published: December 2008

The title compounds represent an interesting group of β‐lactam antibiotics and active inhibitors of β‐lactamase enzymes. All these compounds have one structural feature in common, an alkoxy fragment located at C4 of the azetidin‐2‐one ring. The most common strategy for the synthesis of 4‐alkoxyazetidinons involves intramolecular nucleophilic substitution at C4 that leads to ring closure. Such a displacement proceeds via the flat intermediate that suppossedly has the structure of a mezomeric acyl ammonium cation. We herein report a novel and enantioselective, chiral Lewis acid mediated cyclization that affords the corresponding 5‐oxacepham with excellent optical and chemical yields of up to 50 %. This may suggest that the high asymmetric induction is a result of a kinetic resolution of the initially formed racemic oxacepham. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Enhanced DNA Oxidative Damage by Acrylonitrile and Protecting DNA from Damage with an Outer Catalase Layer: an Electrochemical Study
Authors: Liu Yi , Hu Naifei
Published: December 2008

In the present article, an in vitro model system to mimic the transformation of acrylonitrile (ACN) from nontoxic to toxic in DNA damage and the protective function of catalase (Cat) against DNA damage in real biosystems was investigated electrochemically with (CS/DNA)3‐AQDS and (CS/DNA)3‐AQDS‐Cat multilayer films, where CS and AQDS represent chitosan and electroactive probe 9,10‐anthraquinone‐2,6‐disulfonate, respectively. The electroactive AQDS was loaded into (CS/DNA)3 layer‐by‐layer films mainly by intercalation of AQDS into the double‐helix structure of DNA and acted as the probe to detect the damage of DNA in the films. While only ACN could not induce DNA damage, the enhancement of ACN on DNA damage in the presence of Fenton reagents (Fe(II)/EDTA/H2O2) was observed. In addition, Cat in the (CS/DNA)3‐AQDS‐Cat films could protect DNA from damage to a considerable extent in both Fenton and Fenton+ACN solutions because of the high efficiency of Cat in decomposition of H2O2.
Corpus callosum damage and cognitive dysfunction in benign MS
Authors: Mesaros Sarlota , Rocca Maria A. , Riccitelli Gianna , Pagani Elisabetta , Rovaris Marco , Caputo Domenico , Ghezzi Angelo , Capra Ruggero , Bertolotto Antonio , Comi Giancarlo , Filippi Massimo
Published: December 2008

Corpus callosum (CC), the largest compact white matter fiber bundle of the human brain involved in interhemispheric transfer, is frequently damaged in the course of multiple sclerosis (MS). Cognitive impairment is one of the factors affecting quality of life of patients with benign MS (BMS). The aim of this study was to investigate the relationship between the cognitive profile of BMS patients and the extent of tissue damage in the CC. Brain conventional and DT MRI scans were acquired from 54 BMS patients and 21 healthy controls. Neuropsychological tests (NPT) exploring memory, attention, and frontal lobe cognitive domains were administered to the patients. DT tractography was used to calculate the mean diffusivity (MD) and fractional anisotropy (FA) of the CC normal appearing white matter (NAWM). An index of CC atrophy was also estimated. Nine (17%) BMS patients fulfilled criteria for cognitive impairment. Compared with controls, BMS had significantly different CC diffusivity and volumetry (P < 0.001). Compared with cognitively preserved patients, those with CI had significantly higher CC lesion volume (LV) (P = 0.02) and NAWM MD (P = 0.02). The scores obtained at PASAT were significantly correlated with CC T2 LV, and NAWM FA and MD (r values ranging from −0.31 to 0.66, P values ranging from 0.04 to <0.001). Cognitive impairment in BMS is associated with the extent of CC damage in terms of both focal lesions and diffuse fiber bundle injury. MRI assessment of topographical distribution of tissue damage may represent a rewarding strategy for understanding the subtle clinical deficits of patients with BMS. Hum Brian Mapp 2009. © 2008 Wiley‐Liss, Inc.
High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis #
Authors: Schaap Frank G. , van der Gaag Niels A. , Gouma Dirk J. , Jansen Peter L. M.
Published: December 2008

Fibroblast growth factor 19 (FGF19) is an endocrine factor produced by the small intestine in response to uptake of luminal bile salts. In the liver, FGF19 binds to FGF receptor-4, resulting in down-regulation of cytochrome P (CYP) 7A1 and reduced bile salt synthesis. Down-regulation of CYP7A1 under cholestatic conditions has been attributed to bile salt–mediated induction of the transcriptional repressor short heterodimer partner (SHP), because the interrupted enterohepatic cycle of bile salts is thought to abrogate intestinal FGF19 production and thus result in lowering of plasma FGF19 levels. Unexpectedly, we observed marked elevation of plasma FGF19 in patients with extrahepatic cholestasis caused by a pancreatic tumor (2.3 ± 2.3 in cholestatic versus 0.40 ± 0.25 ng/mL and 0.29 ± 0.12 ng/mL in postcholestatic patients who received preoperative drainage by biliary stenting, P = 0.004, and noncholestatic control patients, P = 0.04, respectively). Although FGF19 messenger RNA (mRNA) is virtually absent in normal liver, FGF19 mRNA was strongly increased (31-fold to 374-fold, P < 0.001) in the liver of cholestatic patients in comparison with drained and control patients. In the absence of changes in SHP mRNA, CYP7A1 mRNA was strongly reduced (7.2-fold to 24-fold, P < 0.005) in the liver of cholestatic patients in comparison with drained and control patients, indicating an alternative regulatory pathway. Alterations in transcripts encoding hepatobiliary transporters [adenosine triphosphate–binding cassette, subfamily C, member 3 (ABCC3)/multidrug resistance protein 3 (MRP3), organic solute transporter α/β (OSTα/β), organic anion-transporting polypeptide (OATP1B1)] further suggest that bile salts are secreted via a nonbiliary route in patients with extrahepatic cholestasis. Conclusion: The liver expresses FGF19 under conditions of extrahepatic cholestasis. This is accompanied by a number of adaptations aimed at protecting the liver against bile salt toxicity. FGF19 signaling may be involved in some of these adaptations. (Hepatology 2009.)
Hepatitis C virus drug resistance and immune-driven adaptations: Relevance to new antiviral therapy #
Authors: Gaudieri Silvana , Rauch Andri , Pfafferott Katja , Barnes Eleanor , Cheng Wendy , McCaughan Geoff , Shackel Nick , Jeffrey Gary P. , Mollison Lindsay , Baker Ross , Furrer Hansjakob , Günthard Huldrych F. , Freitas Elizabeth , Humphreys Isla , Klenerman Paul , Mallal Simon , James Ian , Roberts Stuart , Nolan David , Lucas Michaela
Published: December 2008

The efficacy of specifically targeted anti-viral therapy for hepatitis C virus (HCV) (STAT-C), including HCV protease and polymerase inhibitors, is limited by the presence of drug-specific viral resistance mutations within the targeted proteins. Genetic diversity within these viral proteins also evolves under selective pressures provided by host human leukocyte antigen (HLA)-restricted immune responses, which may therefore influence STAT-C treatment response. Here, the prevalence of drug resistance mutations relevant to 27 developmental STAT-C drugs, and the potential for drug and immune selective pressures to intersect at sites along the HCV genome, is explored. HCV nonstructural (NS) 3 protease or NS5B polymerase sequences and HLA assignment were obtained from study populations from Australia, Switzerland, and the United Kingdom. Four hundred five treatment-naïve individuals with chronic HCV infection were considered (259 genotype 1, 146 genotype 3), of which 38.5% were coinfected with human immunodeficiency virus (HIV). We identified preexisting STAT-C drug resistance mutations in sequences from this large cohort. The frequency of the variations varied according to individual STAT-C drug and HCV genotype/subtype. Of individuals infected with subtype 1a, 21.5% exhibited genetic variation at a known drug resistance site. Furthermore, we identified areas in HCV protease and polymerase that are under both potential HLA-driven pressure and therapy selection and identified six HLA-associated polymorphisms (P ≤ 0.05) at known drug resistance sites. Conclusion: Drug and host immune responses are likely to provide powerful selection forces that shape HCV genetic diversity and replication dynamics. Consideration of HCV viral adaptation in terms of drug resistance as well as host “immune resistance” in the STAT-C treatment era could provide important information toward an optimized and individualized therapy for chronic hepatitis C. (Hepatology 2009.)
Forced Detection Monte Carlo Algorithms for Accelerated Blood Vessel Image Simulations
Authors: Fredriksson Ingemar , Larsson Marcus , Strömberg Tomas
Published: December 2008

Two forced detection (FD) variance reduction Monte Carlo algorithms for image simulations of tissue‐embedded objects with matched refractive index are presented. The principle of the algorithms is to force a fraction of the photon weight to the detector at each and every scattering event. The fractional weight is given by the probability for the photon to reach the detector without further interactions. Two imaging setups are applied to a tissue model including blood vessels, where the FD algorithms produce identical results as traditional brute force simulations, while being accelerated with two orders of magnitude. Extending the methods to include refraction mismatches is discussed. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Characterization and osteogenic effects of mesenchymal stem cells on microbeads composed of hydroxyapatite nanoparticles/reconstituted collagen
Authors: Jeng Long‐Bin , Chung Hui‐Ying , Lin Tsung‐Min , Chen Jyh‐Ping , Chen Yi‐Ling , Lu Yi‐Lung , Wang Yng‐Jiin , Chang Sophia Chia‐Ning
Published: December 2008

Natural bone is comprised of nanosized blade‐like crystals of hydroxyapatite grown in close contact with collagen (Col) fibers. Characteristics of artificial bone tissue differ considerably with those of natural ones, mainly from the unusual self‐organizing interaction between the apatite crystals and the proteic components. Nanoparticle spheres of hydroxyapatite (n‐HA), dispersed in reconstituted fibrous Col, were prepared in three weight ratios of 75:25, 65:35, and 50:50 (n‐HA:Col). Bone marrow mesenchymal stem cells (MSCs) from rabbits were seeded and cultured on the n‐HA/Col microbeads and characterized. n‐HA were evenly distributed throughout the Col matrix and aggregated to microbeads as determined by scanning electron microscopy. Electron and confocal microscopy showed that the MSCs spread and attached to microbeads via focal adhesions, while staining for F‐actin and DNA revealed the presence of stress fibers. The phenotype of the MSCs in the flow cytometry was identified as CD11a−, CD44+, and CD90.1+. The optimal weight ratio is 65:35 for the normalized alkaline phosphatase activities. The transduced MSCs, engineered by replication‐defective adenovirus to express the BMP‐2 gene, demonstrated synergic osteogenic effects in the microbeads. MSCs are capable of proliferating and differentiating in appropriate combinations of n‐HA/Col. Thus it is a promising composite for future clinical applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
The beneficial role of intermediate clarification in a novel MBR based process for biological nitrogen and phosphorus removal
Authors: Kim MinGu , Nakhla George
Published: December 2008

BACKGROUND: A novel membrane bioreactor (MBR) is described, employing an intermediate clarifier. Unlike the established function of a final clarifier in a conventional biological nutrient removal system, the role of an intermediate clarifier has rarely been studied. Thus, this work focused on explaining the fate of nutrients in the intermediate clarifier, as influenced by the hydraulic retention time (HRT) of the preceding anaerobic bioreactor.

RESULTS: The system was tested with two different anaerobic/anoxic/aerobic biomass fractions of 0.25/0.25/0.5 (run 1) and 0.15/0.35/0.45 (run 2) using synthetic wastewater. The major findings of the study were that phosphorus (P) removal was affected by the role of the intermediate clarifier. In run 1, P was removed at a rate 0.16 g d−1 in the intermediate clarifier while in run 2, additional P was released at 0.49 g d−1. The nitrogen (N) removal efficiencies were 74 and 75% for runs 1 and 2 respectively, while P removal was 91 and 96%. P uptake by denitrifying phosphate accumulating organisms (DPAOs) accounted for 41–52% of the total uptake in the MBR.

CONCLUSIONS: This study found that the intermediate clarifier assisted chemical oxygen demand (COD), N, and P removal. With respect to the fate of P, the intermediate clarifier functioned as an extended anaerobic zone when the HRT of the preceding anaerobic zone was insufficient for P release, and as a pre‐anoxic zone when the anaerobic HRT was adequate for P release. Copyright © 2008 Society of Chemical Industry
Applying alpha‐phenacyl chloride to the enantioselective reduction of ethyl 2‐oxo‐4‐phenylbutyrate with baker's yeast
Authors: Shi Yu‐gang , Fang Yun , Ren Yue‐ping , Guan Hui‐lei , Zhang Jing‐Yang
Published: December 2008

BACKGROUND: The enantioselectivity of reduction of ethyl 2‐oxo‐4‐phenylbutyrate (EOPB) to synthesize ethyl (R)‐2‐hydroxy‐4‐phenylbutyrate ((R)‐EHPB) catalyzed with baker's yeast in diethyl ether can be improved by the introduction of alpha‐phenacyl chloride (PC). However, the toxicity of PC to the yeast results in a decrease in the catalytic activity of yeast. In order to overcome this limitation, four strategies for PC addition were designed. The effect of PC on the catalytic behavior of baker's yeast was studied using spectrum analysis of alcohol dehydrogenase from yeast (YADH).

RESULTS: After being pretreated with PC according to Strategy 4, the pretreated baker's yeast possessed good catalytic activity and enantioselectivity for the reduction of EOPB to produce (R)‐EHPB. Under the optimum pretreatment conditions, the conversion of EOPB, the yield of EHPB and the enantiomeric excess of (R)‐EHPB reached 96%, 90% and 92%, respectively. Significant changes were observed in the UV absorption and fluorescence spectra of the YADH from the yeast pretreated by PC.

CONCLUSION: The change of catalytic behavior of yeast after the pretreatment was probably caused by an interaction between yeast and PC. The reactive halomethyl group in PC molecule plays a key role for the interaction. Copyright © 2008 Society of Chemical Industry
The sandwich sign of nonlymphomatous origin
Authors: Lien Wan‐Ching , Huang Shih‐Pei , Liu Kao‐Lang , Chang Jia‐How , Lai Ting‐I , Liu Yueh‐Ping , Wang Hsiu‐Po
Published: December 2008

Purpose.

To investigate the etiologies of the sandwich sign other than lymphoma.

Method.

The images of 34 patients with sonographic sandwich sign over a 5‐year period were retrospectively reviewed. The etiology was based on the pathologic report of mesenteric lymph nodes, or the presence of extensive metastatic disease in case of known advanced primary cancer or disappearance of the sign after specific treatments.

Results.

Malignancy accounted for the majority of cases (91%), and was divided into nonHodgkin's lymphoma (50%) and metastatic carcinomas (41%). Mycobacterium tuberculosis infection was diagnosed in a previously healthy patient, and 2 patients with acquired immunodeficiency syndrome had Mycobacterium avium‐complex infection. The sandwich sign was 1 of the initial presentations in 11 cases with newly diagnosed malignancies, including 6 cases of nonHodgkin's lymphoma and 5 cases of metastatic carcinomas.

Conclusion.

Metastatic carcinomas, M. avium‐complex, and M. tuberculosis infection may produce the sandwich sign. Searching for etiologies other than lymphoma is important in patients presenting with the sandwich sign. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
Human dental pulp stem cells: from biology to clinical applications
Authors: d'Aquino Riccardo , De Rosa Alfredo , Laino Gregorio , Caruso Filippo , Guida Luigi , Rullo Rosario , Checchi Vittorio , Laino Luigi , Tirino Virginia , Papaccio Gianpaolo
Published: December 2008

Dental pulp stem cells (DPSCs) can be found within the “cell rich zone” of dental pulp. Their embryonic origin, from neural crests, explains their multipotency. Up to now, two groups have studied these cells extensively, albeit with different results. One group claims that these cells produce a “dentin‐like tissue”, whereas the other research group has demonstrated that these cells are capable of producing bone, both in vitro and in vivo. In addition, it has been reported that these cells can be easily cryopreserved and stored for long periods of time and still retain their multipotency and bone‐producing capacity. Moreover, recent attention has been focused on tissue engineering and on the properties of these cells: several scaffolds have been used to promote 3‐D tissue formation and studies have demonstrated that DPSCs show good adherence and bone tissue formation on microconcavity surface textures. In addition, adult bone tissue with good vascularization has been obtained in grafts. These results enforce the notion that DPSCs can be used successfully for tissue engineering. J. Exp. Zool. (Mol. Dev. Evol.) 312B:408–415, 2009. © 2008 Wiley‐Liss, Inc.
The school shooting/violent video game link: causal relationship or moral panic?
Authors: Ferguson Christopher J.
Published: December 2008

In the last 10 years, following the incidence of serious acts of school violence—particularly multiple homicides on school campuses—much attention has focused on the potential causal role of violent video game exposure. Some scholars have attempted to draw links between laboratory and correlational research on video game playing and school shooting incidents. This paper argues that such claims are faulty and fail to acknowledge the significant methodological and constructional divides between existing video game research and acts of serious aggression and violence. It is concluded that no significant relationship between violent video game exposure and school shooting incidents has been demonstrated in the existing scientific literature, and that data from real world violence call such a link into question. Copyright © 2008 John Wiley & Sons, Ltd.
Preferential extractability of γ‐oryzanol from dried soapstock using different solvents
Authors: Kumar Raj R , Tiku Purnima Kaul , Prakash Vishveshwaraiah
Published: December 2008

BACKGROUND: γ‐Oryzanol from rice bran has lately gained potential importance because of its proven health benefits. Thus the extractability of γ‐oryzanol from the soapstock of crude rice bran oil is important from the perspective of future large‐scale production, which would give value addition to this by‐product obtained from the rice bran oil industry. The aim of the present study was to investigate the extraction of γ‐oryzanol from the drum‐dried soapstock of rice bran oil using various solvents.

RESULTS: It was found that γ‐oryzanol could be extracted most effectively using ethyl acetate, followed by dichloromethane and ethyl methyl ketone. All components of γ‐oryzanol have an alcohol group in the ferulate portion giving rise to relatively high polarity, thereby increasing the extraction in more polar solvents efficiently. Ethyl acetate showed maximum extractability of γ‐oryzanol by the Soxhlet method. To quantify γ‐oryzanol, reverse phase high‐performance liquid chromatography (RP‐HPLC) was used for fingerprinting the γ‐oryzanol analogues with respect to standard γ‐oryzanol.

CONCLUSION: A new RP‐HPLC method for determining the individual components of γ‐oryzanol has been reported that can be used for performing an online characterisation of γ‐oryzanol analogues by liquid chromatography/mass spectrometry. Copyright © 2008 Society of Chemical Industry
Lymph node assessment in melanoma
Authors: Easson Alexandra M. , Rotstein Lorne E. , McCready David R.
Published: December 2008

The surgical management of lymph nodes continues to be important in melanoma since effective systemic therapies are not available. Controversy exists around the significance of the early detection and management of microscopically positive lymph nodes detected by sentinel lymph node biopsy and this is the subject of current surgical clinical trials. Complete lymphadenectomy is recommended for lymph node metastases. The importance of proper surgical technique is discussed. J. Surg. Oncol. 2009;99:176–185. © 2008 Wiley‐Liss, Inc.
Laparoscopic enucleation of liver tumors. Corkscrew technique revisited
Authors: Makdissi Fabio F. , Surjan Rodrigo C. T. , Machado Marcel Autran C.
Published: December 2008

Background

Enucleation of small lesions located near the hepatic surface can be achieved with low morbidity and mortality. This article describes a simple laparoscopic technique for enucleation of liver tumors.

Methods

After inspection and intraoperative ultrasonography, Glisson's capsule is marked with eletrocautery 2 cm away from the tumor margin. Ultrasonography is used to ascertain surgical margin right before liver transection. Hemihepatic ischemia is applied and marked area is anchored by stitches. The suture is held together by metallic clips and upward traction is performed, facilitating the transection of the parenchyma and correct identification of vascular and biliary structures.

Results

This technique has been successfully employed in six consecutive patients. There were four men and two women, mean age 50.3 years. Four patients underwent liver resection for malignant disease and two for benign liver neoplasm. Pathologic surgical margins were free in all cases and mean hospital stay was 2 days. No postoperative mortality was observed.

Conclusion

This technique may facilitate laparoscopic nonanatomical liver resection and reduce risk of positive surgical margins. It is also useful in combination with anatomical laparoscopic liver resections such as right or left hemihepatectomies in patients with bilateral liver tumors as occurred in one of our patients. J. Surg. Oncol. 2009;99: 166–168. © 2008 Wiley‐Liss, Inc.
Health or self‐indulgence? The motivations and characteristics of spa‐goers
Authors: Mak Athena H. N. , Wong Kevin K. F. , Chang Richard C. Y.
Published: December 2008

This study examines the underlying factors that motivate travellers to search for spa experiences while travelling. It also attempts to explore the different perceptions of the spa experience and identify the relevant socio‐demographic characteristics of spa‐goers. Based on the findings from a focus group interview and a review of literature, an instrument consisting of 21 motivating items was developed and used in a survey of Hong Kong spa‐goers. Factor analysis revealed that ‘relaxation and relief’, ‘escape’, ‘self‐reward and indulgence’, and ‘health and beauty’ are important factors that motivate travellers to visit spas. The findings of this study will provide researchers and practitioners in the spa industry with useful insights into understanding the present nature of the demand of spa in the Asian market. Copyright © 2008 John Wiley & Sons, Ltd.
Histological changes occurring after endoluminal ablation with two diode lasers (940 and 1319 nm) from acute changes to 4 months
Authors: Bush Ronald G. , Shamma H. Nicholas , Hammond Karin
Published: December 2008

Background

Endovenous laser ablation of the saphenous vein was studied from a histologic analysis to establish changes that occur from time of injury to 4 months when the vein is difficult to visualize by ultrasound.

Methods

Twenty‐four patients were examined after treatment with either a 1319 nm diode laser (Sciton, Palo Alto, CA) or a 940 nm diode (Dornier, Kennasaw, GA) 12 patients were randomly assigned to the 940 nm group and 12 patients to the 1319 nm group. Histologic evaluations were only done once per patient. All patients had symptomatic saphenous insufficiency with varicosities. All were in CEAP class 3 or 4. Sections of treated veins were submitted for evaluation after staining with hematoxylin–eosin. The evaluations were done acutely, at 1 and 4 months. Ultrasound findings were also evaluated and compared at the same intervals.

Results

Acutely, all examined veins revealed loss of intima. In the 1319 nm group numerous vacuoles were present in the subintimal layer. On gross exam at 1 month, both groups showed vein wall thickening, intraluminal thrombus and inflammatory changes. Histologic evaluation showed thrombus was present with many fibroblasts and inflammatory cells. At 4 months, collagen was the predominant histologic finding. However, the changes were less in regards to the injury response with the 1,319 nm group as manifested by less collagen deposition at 4 months.

Conclusion

This study demonstrates the cellular sequence that occurs after endovenous ablation. Fibroblast infiltration is a result of the injury response which leads to negative modeling of the thrombus and eventual collagen deposition. Replacement of the thrombus with collagen is necessary for eventual long‐term success. Lasers Surg. Med. 40:676–679, 2008. © 2008 Wiley‐Liss, Inc.