bluuebunny/crossref_metadata_2025 huggingface dataset:
ChickPcl2regulates the left-right asymmetry by repressingShhexpression in Hensen's node
Authors: Wang Shusheng , Yu Xueyan , Zhang Tao , Zhang Xiaoyun , Zhang Zunyi , Chen YiPing
Published: August 2004

Asymmetric expression of sonic hedgehog (Shh) in the left side of Hensen's node, a crucial step for specifying the left-right (LR) axis in the chick embryo, is established by the repression of Shhexpression in the right side of the node. The transcriptional regulator that mediates this repression has not been identified. We report the isolation and characterization of a novel chick Polycomblike 2 gene, chick Pcl2, which encodes a transcription repressor and displays an asymmetric expression, downstream from Activin-βB and Bmp4, in the right side of Hensen's node in the developing embryo. In vitro mapping studies define the transcription repression activity to the PHD finger domain of the chick Pcl2 protein. Repression of chick Pcl2expression in the early embryo results in randomized heart looping direction,which is accompanied by the ectopic expression of Shh in the right side of the node and Shh downstream genes in the right lateral plate mesoderm (LPM), while overexpression of chick Pcl2 represses Shh expression in the node. The repression of Shh by chick Pcl2 was also supported by studies in which chick Pcl2 was overexpressed in the developing chick limb bud and feather bud. Similarly,transgenic overexpression of chick Pcl2 in the developing mouse limb inhibits Shh expression in the ZPA. In vitro pull-down assays demonstrated a direct interaction of the chick Pcl2 PHD finger with EZH2, a component of the ESC/E(Z) repressive complex. Taken together with the fact that chick Pcl2 was found to directly repress Shh promoter activity in vitro, our results demonstrate a crucial role for chick Pcl2 in regulating LR axis patterning in the chick by silencing Shh in the right side of the node.
Retinoic acid signalling specifies intermediate character in the developing telencephalon
Authors: Marklund Matthew , Sjödal My , Beehler Blake C. , Jessell Thomas M. , Edlund Thomas , Gunhaga Lena
Published: August 2004

The organisation of the telencephalon into its major structures depends on its early regionalisation along the dorsoventral axis. Previous studies have provided evidence that sonic hedgehog (SHH) is required for the generation of telencephalic cells of ventral character, and that sequential WNT and fibroblast growth factor (FGF) signalling specifies cells of dorsal telencephalic character. However, the signalling mechanisms that specify telencephalic cells of an intermediate character remain to be defined. We provide evidence here that retinoic acid has a crucial role in specifying telencephalic progenitor cells of intermediate character.
Development of a new automatic calibration method for control of variable valve timing
Authors: Beham M , Etzel M , Yu D L
Published: August 2004

The rising number of calibration variables and a decreasing time to market have led to the need for advanced methods of engine calibration. In this paper a new calibration method is developed for ignition timing. This calibration is based on an automated measurement and analysis method. This method enables the user to calibrate the optimal efficiency ignition angle (IA) and the torque control via the IA. The modern digital engine electronic control unit (ECU) is mainly based on look-up table methods. The combination of automatic knock detection analysis and automatic look-up table design reduces calibration time by the factor 3-4. The method was successfully applied to the low octane variation of the BMW AG 4-cylinder 2.0 l variable valve timing (VVT) spark ignition (SI) engine. The method is used in the SI combustion engine development section of the BMW AG for different types of engines. It has been shown that the application of the developed method dramatically reduces the calibration effort and time of VVT engines.
Characterization of an evaporating direct-injected gasoline spray using laser-induced exciplex fluorescence and particle image velocimetry techniques
Authors: Choi Dong-Seok , Bae Choongsik , Kim Duck-Jool
Published: August 2004

The purpose of this study is to characterize an evaporating direct-injected (DI) gasoline spray from a high-pressure swirl injector using the laser-induced exciplex fluorescence (LIEF) technique and particle image velocimetry (PIV). A fluorobenzene/diethylmethylamine (DEMA) system was used as the exciplex-forming dopants. The behaviour of the liquid and vapour phases was analysed by image processing. For the analysis of vorticity inside the spray, droplet velocity data obtained by PIV were used. The experiments were performed at two ambient temperatures (293 and 473 K) and three different ambient pressures (0.1, 0.5 and 1.0 MPa). It was found that ambient temperature had a significant effect on the axial and radial growth of the liquid phase of the evaporating spray at atmospheric pressure while it had little effect under elevated pressures. Radial growth of the vapour phase of the evaporating spray was more dominant than axial growth under high temperature and pressure conditions. As the ambient pressure was elevated, the liquid phase of the spray transformed from a hollow cone to a solid cone of bell shape, while the vapour phase varied from a widespread distribution to a compact shape with a locally richer mixture. The evaporating spray could be divided into two spray regions from the analysis of vorticity and the distributions of liquid and vapour phases. The cone region (penetrations of 0.3-0.5) was mainly liquid phase and disappeared rapidly at the end of injection. The mixing region contained the active interaction between entrained air and fuel vapour.
Modelling and analysis of an air-over-hydraulic brake system
Authors: Wang Xing-Dong , Hu Yu-Jin , Li Cheng-Gang , Wang Xue-Lin
Published: August 2004

This study presents the development and validation of an analytical dynamic model of an air-over-hydraulic (AOH) brake system for a commercial vehicle (CV). The brake system model includes the controller, intensifier, brake lines, wheel cylinder, and foundational drum brake, which are presented for the interaction with the application system. A generalized AOH brake system, based on systems analysis level for the components, is formulated in detail. The pipeline hysteresis and fluid fluctuation of the brake system have been investigated in detail. Many experiments were performed on a bench setup of the AOH brake system and real vehicles. The experimental data is compared with the model simulation results. Preliminary results show that the simulation matches the experimental data closely. The models, which are developed from physical laws, are intended for use in the design and analysis of vehicle control systems for CVs.
Dynamic characterization of automotive exhaust isolators
Authors: Rao M D , Wirkner K J , Gruenberg S
Published: August 2004

Different approaches to measure the dynamic stiffness and damping properties of several silicone and EPDM rubber automotive exhaust isolators were investigated in this research. Shaker excitation and electrohydraulic actuator methods were used to extract the dynamic properties, both under swept sine and random excitations. The shaker testing in the frequency domain using a frequency response function from linear theory produced good results, and the experimental set-up for this case is relatively inexpensive. The electrohydraulic excitation method, however, is more suitable for testing under low frequencies and large displacements. It is ideal to study the variations in stiffness and damping with frequency, displacement, temperature and preload. This study has confirmed that the stiffness and loss factor of the samples are highly dependent on preload and input force levels. It has also been shown that the stiffness and loss factor values are relatively insensitive to the manner in which the exhaust isolator is excited, whether it be with random, burst chirp or swept sine excitation. Of particular interest is the fact that stiffness and loss factor results are very similar between the electrohydraulic and shaker excitation, except at low frequencies.
Capillary Electrophoresis with Chemiluminescence Detector Using On-capillary Detection
Authors: Tsukagoshi Kazuhiko , Fujii Tatsuya , Nakajima Riichiro
Published: August 2004

We achieved capillary electrophoresis with chemiluminescence detector using on-capillary detection, taking advantage of the commercially available chemiluminescence reagent (LUMICA) and its oxidant. A mixture of dansyl tryptophan and dansyl glycine as a model sample migrated in two different running buffers, both containing LUMICA and the oxidant, indicating chemiluminescence was generated by the reaction of LUMICA, the oxidant, and dansyl α-amino acids. When the α-amino acids went through the detection window on the capillary, the chemiluminescence signals were observed with the chemiluminescence detector using on-capillary detection. This new concept of on-capillary chemiluminescence detection did not require any interface device between the electrophoresis capillary and the chemiluminescence detector.
Easily Oxidizable Polysulfide Anion Occluded in the Interlayer Space of Mg/Al Layered Double Hydroxide
Authors: Ogawa Makoto , Saito Fumihiro
Published: August 2004

Magnesium–aluminum layered double hydroxide containing polysulfide anions was prepared by a hydrothermal reaction from magnesium and aluminum hydroxides. Thioacetamide was used as the sulfide source. The product exhibits light green color corresponding to the S2− and S3− ions and turns to colorless when the sample was stored in air for several days or heat treated in air at 120 °C. The color change showed that the occluded polysulfide anions were oxidized to sulfate anion by atmospheric oxygen.
Efficient Electron Injection Characteristics of Triazine Derivatives for Transparent OLEDs (TOLEDs)
Authors: Oyamada Takahito , Yoshizaki Hiroki , Sasabe Hiroyuki , Adachi Chihaya
Published: August 2004

We demonstrated that triazine (TRZ) derivatives possessing metal coordination sites in their structures showed excellent electron transport and injection characteristics in transparent organic light emitting diodes (TOLEDs). High luminescence efficiency with low driving voltage was observed with a TRZ/ITO cathode configuration (ITO: indium-tin-oxide), suggesting that the TRZ layer can efficiently accept electrons from the metal-oxide cathode layer, and inject electrons into an adjacent organic layer.
Electrodeposition of Hydrophobic Nickel Composite Containing Surface-Modified SiO2 Particles under the Influence of a Surfactant with an Azobenzene Moiety
Authors: Shrestha Nabeen K , Kobayashi Genta , Saji Tetsuo
Published: August 2004

Electrodeposit of nickel with high content of the surface-modified silica particles by a silane-coupling agent was prepared from the Watts nickel bath containing the silica particles dispersed with the aid of a surfactant containing an azobenzene moiety. This composite coating plated under optimized conditions exhibited the ultra high water repellency property with the contact angle of 156°.
Mineralogical characteristics and micromorphological observations of brittle/soft Fe/Mn concretions from Okinawan soils
Authors: Vidhana Arachchi L. P. , Tokashiki Y. , Baba S.
Published: August 2004

Manganese minerals are not common and the distinction of poorly crystalline Mn minerals from other associated minerals is important. For many years, the crystal structures of poorly crystalline Mn minerals in Fe/Mn concretions have been the subject of considerable conjecture and controversy. This study reports the micromorphological and mineralogical characteristics, and the chemical composition of Fe/Mn minerals in soft Fe/Mn concretions formed in Shimajiri Mahji soils (Typic Hapludalfs) that developed from Ryukyu limestone on Okinawa Island, Japan. The Fe/Mn minerals in brittle/soft Fe/Mn concretions were characterized using a sequential selective dissolution procedure (SSDP) by treatments with NaOH, hydroxylamine hydrochloride (HAHC) at 25°C and 60°C, and dithionite-citrate-bicarbonate (DCB) in combination with X-ray diffraction (XRD) and scanning electron microscopy (SEM). The HAHC treatment at 25°C dissolved birnessite, but not lithiophorite and goethite. A subsequent extraction with HAHC at 60°C dissolved lithiophorite but not goethite. Finally, the DCB treatment was able to dissolve goethite. The SEM images show that birnessite crystals, with a blade- or plate-like habit, form globular aggregates inside veins and cavities. Pseudo-hexagonal crystals of lithiophorite have produced thread-ball structures with crystal shape similar to birnessite and birnessite crystals are closely associated with lithiophorite. Well developed hexagonal plates of gibbsite crystals are clustered in different directions to make foliated vermiform structures. Aggregates of goethite crystals are acicular and are arranged into stars. The supplementary SSDP, in combination with XRD and SEM techniques, provides methods to distinguish and partly quantify birnessite and lithiophorite in the presence of layer silicate and Fe oxide minerals and confirm their own morphological features.
A Short and Efficient Methodology for the Synthesis of Novel 3‐Aryloxazolidin‐2‐one Derivatives
Authors: Nandakumar Mecheril V.
Published: August 2004

An efficient synthesis of novel oxazolidinone derivatives is disclosed. Novel oxazolidinone derivatives were synthesized by a copper‐catalyzed N‐arylation reaction with control of the substituents on both the sides of the phenyl ring.
Direct Sulfonation of Methane to Methanesulfonic Acid by Sulfur Trioxide Catalyzed by Cerium(IV) Sulfate in the Presence of Molecular Oxygen
Authors: Mukhopadhyay Sudip , Bell Alexis T.
Published: August 2004

Direct sulfonation of methane with SO3 to methanesulfonic acid (MSA) is accomplished in sulfuric acid with almost 100% selectivity in the presence of a catalyst, namely, Ce and Rh salts and molecular oxygen as the catalyst regenerator. In the absence of O2, the catalyst remains effective but the selectivity to MSA decreases to 53% and byproducts, principally CH3OSO3H, are formed. The effects of O2 pressure, catalyst concentration, temperature, SO3 concentration, and methane pressure have been examined on the rate of SO3 conversion to MSA. The conversion of SO3 to MSA was the same when CF3SO3H was used as the solvent instead of H2SO4.
The Art of Meeting Palladium Specifications in Active Pharmaceutical Ingredients Produced by Pd‐Catalyzed Reactions
Authors: Garrett Christine E. , Prasad Kapa
Published: August 2004

The use of palladium‐derived catalysts in the synthesis of fine chemicals, pharmaceutical intermediates and active pharmaceutical ingredients (APIs) has become quite common in the last few decades. The number of palladium‐catalyzed synthetic reactions (both achiral and chiral) available to chemists has provided access to more complex structures in fewer steps and with less waste, due to the catalytic nature of many of the methods. An unfortunate side effect of using palladium is the potential for palladium‐containing impurities to remain in the desired compound after isolation. This is an especially significant problem for the pharmaceutical industry since there is a low limit for heavy metal impurities allowed in the drug substance. Therefore, various methods of removing palladium impurities from organic compounds of pharmaceutical interest have been developed. This review will provide a survey of the published methods but is not meant to be inclusive of all published material in this area of research.
Prospective study of contrast-enhanced computed tomography, computed tomography during arterioportography, and magnetic resonance imaging for staging colorectal liver metastases for liver resection
Authors: Bhattacharjya S , Bhattacharjya T , Baber S , Tibballs J M , Watkinson A F , Davidson B R
Published: August 2004

Background

This study compared the value of contrast-enhanced helical computed tomography (CT), CT during arterioportography (CTAP), and contrast-enhanced magnetic resonance imaging (MRI) for staging patients with colorectal liver metastases.

Methods

One hundred and twenty patients with known or suspected colorectal liver metastases were evaluated prospectively. MRI and CTAP were performed within 3 weeks of CT in patients with potentially resectable tumours. Results of imaging were compared with findings at surgery, intraoperative ultrasonography and histological examination.

Results

Twenty patients were not considered for liver resection following CT. The remaining 100 patients underwent CT and CTAP, 85 of whom had CT, CTAP and MRI. The sensitivity and specificity were 73·0 and 96·5 per cent for CT, 87·1 and 89·3 per cent for CTAP, and 81·9 and 93·2 per cent for MRI. Positive predictive values were 89·7, 87·5 and 87·5 per cent respectively. Receiver–operator characteristic analysis gave an accuracy on a segment-by-segment analysis of 0·73 for CT, 0·87 for CTAP and 0·82 for MRI. Combining information from CT and CTAP, CT and MRI, or all three modalities, did not significantly increase the percentage of patients staged correctly (71, 72 and 76 per cent respectively).

Conclusion

The diagnostic accuracy of spiral CT, MRI and CTAP was similar. Combining modalities did not improve accuracy.
The Calculation of Indirect Nuclear Spin–Spin Coupling Constants in Large Molecules
Authors: Watson Mark A. , Sałek Paweł , Macak Peter , Jaszuński Michał , Helgaker Trygve
Published: August 2004

We present calculations of indirect nuclear spin–spin coupling constants in large molecular systems, performed using density functional theory. Such calculations, which have become possible because of the use of linear‐scaling techniques in the evaluation of the Coulomb and exchange‐correlation contributions to the electronic energy, allow us to study indirect spin–spin couplings in molecules of biological interest, without having to construct artificial model systems. In addition to presenting a statistical analysis of the large number of short‐range coupling constants in large molecular systems, we analyse the asymptotic dependence of the indirect nuclear spin–spin coupling constants on the internuclear separation. In particular, we demonstrate that, in a sufficiently large one‐electron basis set, the indirect spin–spin coupling constants become proportional to the inverse cube of the internuclear separation, even though the diamagnetic and paramagnetic spin‐orbit contributions to the spin–spin coupling constants separately decay as the inverse square of this separation. By contrast, the triplet Fermi contact and spin‐dipole contributions to the indirect spin–spin coupling constants decay exponentially and as the inverse cube of the internuclear separation, respectively. Thus, whereas short‐range indirect spin–spin coupling constants are usually dominated by the Fermi contact contribution, long‐range coupling constants are always dominated by the negative diamagnetic spin‐orbit contribution and by the positive paramagnetic spin‐orbit contribution, with small spin‐dipole and negligible Fermi contact contributions.
The Induced Magnetic Field in Cyclic Molecules
Authors: Merino Gabriel , Heine Thomas , Seifert Gotthard
Published: August 2004

The response of a molecule to an applied external magnetic field can be evaluated by a graphical representation of the induced magnetic field. We have applied this technique to four representative, cyclic organic molecules, that is, to aromatic (C6H6, D6h), anti‐aromatic (C4H4, D2h) and non‐aromatic (C4H8, D4h, and C6H12, D3d) molecules. The results show that molecules that contain a π system possess a long‐range magnetic response, while the induced magnetic field is short‐range for molecules without π systems. The induced magnetic field of aromatic molecules shields the external field. In contrast, the anti‐aromatic molecules increase the applied field inside the ring. Aromatic, anti‐aromatic, and non‐aromatic molecules can be characterized by the appearance of the magnetic response. We also show that the magnetic response is directly connected to nucleus‐independent chemical shifts (NICS).
Quantitative, not qualitative, differences in CD8+ T cell responses to Theiler's murine encephalomyelitis virus between resistant C57BL/6 and susceptible SJL/J mice
Authors: Lyman Michael A. , Myoung Jinjong , Mohindru Mani , Kim Byung S.
Published: August 2004

Theiler's murine encephalomyelitis virus (TMEV) infection of the CNS induces an immune‐mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis. However, it is not yet clear what immunological parameters determine the susceptibility of SJL/J mice compared to resistant mice. We have here compared the TMEV‐specific CD8+ T cell responses in highly susceptible SJL/J mice with those of highly resistant C57BL/6 mice. Our results clearly indicate that the levels of initial responses of infiltrating CD8+ T cells to viral capsid proteins are higher in resistant C57BL/6 mice compared to susceptible SJL/J mice. However, the level of virus‐specific CD8+ T cells was much more rapidly reduced in resistant C57BL/6, resulting in a higher CD8+ T cell level in SJL/J mice later in viral infection. The activation states, cytokine production, as well as the cytolytic function of the CD8+ T cells were similar to each other in these mice. These results suggest that an initial induction of a vigorous CD8+ T cell response to TMEV is critically important for the resistance to virally induced demyelinating disease.
BAFF binding to T cell‐expressed BAFF‐R costimulates T cell proliferation and alloresponses
Authors: Ye Qunrui , Wang Liqing , Wells Andrew D. , Tao Ran , Han Rongxiang , Davidson Anne , Scott Martin L. , Hancock Wayne W.
Published: August 2004

Binding of the TNF family member, B cell activating factor (BAFF), to its receptor (BAFF‐R, TNFRSF13C) is required for generation and maintenance of mature B cells, but there are no data as to any role for the BAFF/BAFF‐R pathway in T cell functions. We report that the binding of BAFF to BAFF‐R expressed by a subset of primarily CD4+ T cells costimulates T cell activation and allo‐proliferation in vitro and in vivo, and that mice with a mutation in the BAFF‐R, or with a targeted deletion of BAFF, show prolonged cardiac allograft survival as compared to wild‐type or transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)–/– controls. Taken together, these data indicate the BAFF/BAFF‐R pathway contributes to both T and B cell responses and may be an attractive target for control of acute and chronic allograft rejection.
Dissecting cytotoxic T cell responses towards the NY‐ESO‐1 protein by peptide/MHC‐specific antibody fragments
Authors: Held Gerhard , Matsuo Mitsutoshi , Epel Malka , Gnjatic Sacha , Ritter Gerd , Lee Sang Yull , Tai Tsin Yee , Cohen Cyril J. , Old Lloyd J. , Pfreundschuh Michael , Reiter Yoram , Hoogenboom Hennie R. , Renner Christoph
Published: August 2004

NY‐ESO‐1 is a germ cell antigen aberrantly expressed by different tumor types that elicits strong humoral and cellular immune responses, representing one of the most promising candidates for vaccination of cancer patients. A detailed analysis of CD8+ T cells generated in vaccine trials using NY‐ESO‐1‐derived peptides (157–165 and 157–167) revealed that the dominant immune response was directed against a cryptic epitope (159–167) diverting the immune response from tumor recognition. Only CTL reactivity to the NY‐ESO‐1157–165 peptide appeared to be capable of lysing NY‐ESO‐1/HLA‐A0201‐expressing tumor cells. To study the process of NY‐ESO‐1 peptide presentation by tumor cells in more detail we generated a high‐affinity (KD=60 nM) antibody fragment that specifically recognizes the NY‐ESO‐1157–165 peptide/HLA‐A0201 complex. Peptide variants such as the NY‐ESO‐1157–167 peptide or the cryptic NY‐ESO‐1159–167 peptide were not recognized. The antibody fragment blocked in a dose‐dependent fashion the recognition of NY‐ESO‐1/HLA‐A2‐positive tumor cells by NY‐ESO‐1157–165 peptide‐specific CD8+ T cells. This antibody fragment is a novel reagent that binds with TCR‐like specificity to the NY‐ESO‐1157–165/HLA‐A2 complex thus distinguishing between CTL responses against immunological meaningful or cryptic NY‐ESO‐1‐derived peptides. It may therefore become a useful monitoring tool for the development of NY‐ESO‐1‐based cancer vaccines.
Arginine and glutamine availability and macrophage functions in the obese insulin‐resistant Zucker Rat
Authors: Blanc Marie‐Céline , Moinard Christophe , Béziel Aurélie , Darquy Sylviane , Cynober Luc , De Bandt Jean‐Pascal
Published: August 2004

Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin‐resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 μg/ml), productions of tumour necrosis factor α (TNFα) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 ± 1,174 vs. 2 mM: 198 ± 31 μM/mg protein/24 h; P < 0.05), but not in those from obese rats, when glutamine was added. TNFα production, lower in macrophages from obese rats, was inversely correlated with glutamine concentration. In the presence of arginine, NO production was constantly higher in macrophages from obese rats. It peaked at 0.5 mM arginine and decreased thereafter in both groups. TNFα production in macrophages from lean rats was unaffected by arginine, but decreased in macrophages from obese rats (0 mM: 1920 ± 450 vs. 2 mM: 810 ± 90 μM/mg protein/3 h; P < 0.05). These results suggest that abnormalities in cell signalling or in arginine and glutamine metabolism in macrophages of obese rats, resulting in decreased TNFα production and increased NO release, may contribute to increased susceptibility to infection in insulin‐resistant states. © 2005 Wiley‐Liss, Inc.
Involvement of p42/p44 MAPK, JNK, and NF‐κB in IL‐1β‐induced ICAM‐1 expression in human pulmonary epithelial cells
Authors: Lin Feng‐Shu , Lin Chih‐Chung , Chien Chin‐Sung , Luo Shu‐Feng , Yang Chuen‐Mao
Published: August 2004

Interleukin‐1β (IL‐1β) has been shown to induce the expression of intercellular adhesion molecule‐1 (ICAM‐1) on airway epithelial cells and contributes to inflammatory responses. However, the mechanisms regulating ICAM‐1 expression by IL‐1β in human A549 cells was not completely understood. Here, the roles of mitogen‐activated protein kinases (MAPKs) and NF‐κB pathways for IL‐1β‐induced ICAM‐1 expression were investigated in A549 cells. IL‐1β induced expression of ICAM‐1 protein and mRNA in a time‐ and concentration‐dependent manner. The IL‐1β induction of ICAM‐1 mRNA and protein were partially inhibited by U0126 and PD98059 (specific inhibitors of MEK1/2) and SP600125 [a specific inhibitor of c‐Jun‐N‐terminal kinase (JNK)]. U0126 was more potent than other inhibitors to attenuate IL‐1β‐induced ICAM‐1 expression. Consistently, IL‐1β stimulated phosphorylation of p42/p44 MAPK and JNK which was attenuated by pretreatment with U0126 or SP600125, respectively. Moreover, transfection with dominant negative mutants of MEK1/2 (MEK K97R) or ERK2 (ERK2 K52R) also attenuated IL‐1β‐induced ICAM‐1 expression. The combination of PD98059 and SP600125 displayed an additive effect on IL‐1β‐induced ICAM‐1 gene expression. IL‐1β‐induced ICAM‐1 expression was almost completely blocked by a specific NF‐κB inhibitor helenalin. Consistently, IL‐1β stimulated translocation of NF‐κB into the nucleus and degradation of IκB‐α which was blocked by helenalin, U0126, or SP600125. Taken together, these results suggest that activation of p42/p44 MAPK and JNK cascades, at least in part, mediated through NF‐κB pathway is essential for IL‐1β‐induced ICAM‐1 gene expression in A549 cells. These results provide new insight into the mechanisms of IL‐1β action that cytokines may promote inflammatory responses in the airway disease. © 2004 Wiley‐Liss, Inc.
Preferential production of latent transforming growth factor β‐2 by primary prostatic epithelial cells and its activation by prostate‐specific antigen
Authors: Dallas S.L. , Zhao S. , Cramer S.D. , Chen Z. , Peehl D.M. , Bonewald L.F.
Published: August 2004

Three mammalian isoforms of transforming growth factor‐β (TGFβ) are known, TGFβ1, 2, and 3, that have non‐overlapping functions during development. However, their specific roles in cancers such as prostate cancer are less clear. Here we show that primary cultures of prostatic epithelial cells preferentially produce and activate the latent TGFβ2 isoform. Paired cultures of normal and malignant prostate cells from prostate cancer patients produced predominantly the TGFβ2 isoform, with 30‐ to 70‐fold less TGFβ1. By mono‐Q ion exchange chromatography, three major peaks of latent TGFβ2 activity were observed corresponding to the known small latent TGFβ2 complex, the known large latent TGFβ2 complex and a novel eluting peak of latent TGFβ2. Although prostate cells are known to activate latent TGFβ, the mechanism for activation is currently unclear. We investigated whether prostate specific antigen (PSA), a serine protease used as a clinical marker for prostate cancer, could play a role in the activation of latent TGFβ. Unlike plasmin, a known activator of both latent TGFβ1 and 2, PSA specifically activated the recombinant small latent form of TGFβ2, but not TGFβ1. Prostate epithelial cells, therefore, preferentially produce the TGFβ2 isoform and PSA, a protease produced by the prostate, specifically targets the activation of this TGFβ isoform. PSA‐mediated activation of latent TGFβ2 may be an important mechanism for autocrine TGFβ regulation in the prostate and may potentially contribute to the formation of osteoblastic lesions in bone metastatic prostate cancer. © 2004 Wiley‐Liss, Inc.
Effects of thermal food processing on the chemical structure and toxicity of fumonisin mycotoxins
Authors: Humpf Hans‐Ulrich , Voss Kenneth A.
Published: August 2004

Fumonisins are Fusarium mycotoxins that occur in corn and corn‐based foods. They are toxic to animals and at least one analogue, fumonisin B1, is carcinogenic to rodents. Their effect on human health is unclear, however, fumonisins are considered to be risk factors for cancer and possibly neural tube defects in some heavily exposed populations. It is therefore important to minimize exposures in these populations. Cleaning corn to remove damaged or moldy kernels reduces fumonisins in foods while milling increases their concentration in some and reduces their concentration in other products. Fumonisins are water‐soluble and nixtamalization (cooking in alkaline water) lowers the fumonisin content of food products if the cooking liquid is discarded. Baking, frying, and extrusion cooking of corn at high temperatures (⪈ 190°C) also reduces fumonisin concentrations in foods, with the amount of reduction achieved depending on cooking time, temperature, recipe, and other factors. However, the chemical fate of fumonisins in baked, fried, and extruded foods is not well understood and it is not known if the reduced concentrations result from thermal decomposition of fumonisins or from their binding to proteins, sugars or other compounds in food matrices. These possibilities might or might not be beneficial depending upon the bioavailability and inherent toxicity of decomposition products or the degree to which bound fumonisins are released in the gastrointestinal tract. In this review the affects of cooking and processing on the concentration and chemical structure of fumonisins as well as the toxicological consequences of known and likely fumonisin reaction products are discussed.
Self‐assembly structure of the levulinic acid–melamine lattice
Authors: Venkatraman Ramaiyer , Ray Paresh Chandra , Choi Chan Soo
Published: August 2004

Equimolar amounts of levulinic acid and melamine formed a self‐assembled unit through a hydrogen‐bonding network. Room‐temperature single‐crystal diffraction studies and FTIR spectroscopy of the system indicated adduct formation between melamine and levulinic acid. Ab initio Hartree–Fock (HF) and density functional theory (DFT) calculations, using the 6‐31G(d,p) basis set, have been performed to investigate the gas‐phase structure and IR frequencies. The theoretical parameters (geometry and vibrational frequencies) predicted by HF and DFT methods for the adduct are in good agreement with the experimental data. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Is the isotopic composition of nitrous oxide an indicator for its origin from nitrification or denitrification? A theoretical approach from referred data and microbiological and enzyme kinetic aspects
Authors: Schmidt Hanns‐Ludwig , Werner Roland A. , Yoshida Naohiro , Well Reinhard
Published: August 2004

Literature data on the isotopic composition of nitrous oxide indicate a general predominance of the α‐15N‐isotopomer and a parallel 18O‐enrichment in N2O from nitrification and denitrification, respectively. As the kinetic isotope effects on any individual reactions of the two processes lead to depletions of the heavy isotopes of nitrogen and oxygen in the products, the observed enrichments could mainly be caused by enzymatic reduction of NO, provided it occurs via a symmetric intermediate like hyponitrite; infrared data are in favour of large differences between the binding constants of the isotopomers and isotopologues of this compound. As a matter of fact one of the mechanisms discussed for the nitric oxide reductase from certain microorganisms implies the parallel binding of two NO molecules and the formation of a symmetrical intermediate, while that of the enzyme from other microorganisms reduces NO in a sequential mechanism. In addition, isotope effects on the reduction of N2O to N2 must contribute to the observed isotope characteristics of N2O, especially in context with denitrification. Therefore, the known enzymatic reaction pathways suggest that the α‐15N‐isotopomer preference and the 18O‐signature of the produced N2O is not essentially characteristic for its origin from nitrification or denitrification, respectively, but rather from the involved population of microorganisms and the type of their nitric oxide reductases. This has to be confirmed experimentally. Copyright © 2004 John Wiley & Sons, Ltd.
Performance of the combining received differential encoding transmit diversity with imperfect carrier recovery over correlated Nakagami fading channels
Authors: Fan Guoping , Fan Pingyi , Cao Zhigang
Published: August 2004

A differential detection scheme for transmit diversity was proposed by Tarokh, which can achieve full diversity order without the requirement to estimate the channel state at the receiver. This paper investigates the potential of using multiple receive antennas for differential space time coded MPSK signals over correlated Nakagami fading channels. We also investigate the effect of the carrier frequency offset (CFO) and channel correlation on its performance and present some results on its maximal tolerable frequency offsets for different MPSK signals. The results have shown that the differential encoding transmit diversity is very robust to the CFO and channel correlation. Copyright © 2004 John Wiley & Sons, Ltd.
Circular shifted transmit diversity
Authors: Wu Gang , Cheng Shixin
Published: August 2004

Three design requirements of space‐time block code, full diversity order, full data rate and orthogonality, cannot be achieved simultaneously when the number of transmit antenna is more than two. In this paper, we propose a transmit diversity scheme—circular shifted transmit diversity (CSTD). CSTD can always achieve the full data rate and has very low decoding complexity. Through the performance analysis and simulation comparison in the case of same spectrum efficiency between CSTD and other well‐known proposed schemes, it can be proved that CSTD always significantly outperforms the other transmit diversity schemes with full data rate. Additionally, compared with the transmit diversity schemes with full diversity order, CSTD has lower complexity and approximately the same performance when channel coding is concatenated. Copyright © 2004 John Wiley & Sons, Ltd.
Nuclear export of RNA
Authors: Rodriguez Manuel S. , Dargemont Catherine , Stutz Françoise
Published: August 2004

Abstract A defining feature of eukaryotic cells is the presence of a nuclear envelope separating transcription and DNA replication in the nucleus from the site of protein synthesis in the cytoplasm. The regulation of gene expression relies in part on the controlled exchange of molecules between these two compartments. Factors implicated in transcription regulation and DNA replication have to be imported into the nucleus, whereas RNAs produced in the nucleus have to be exported, either to fulfill their function in protein synthesis or to mature into functional particles. This review summarizes studies performed over the last 15 years that led to the identification of cellular factors mediating nuclear export of the different classes of RNAs, including tRNAs, UsnRNAs, micro‐RNAs, ribosomal RNAs and mRNAs. We also discuss recent evidence indicating that the nuclear transport step is intimately linked to RNA synthesis, processing and mRNP assembly, thus ensuring that only properly matured ribonucleoprotein (RNP) complexes reach the cytoplasm.
Altered hetero‐ and homeometric autoregulation in the terminally failing human heart
Authors: Brixius Klara , Reuter Hannes , Bloch Wilhelm , Schwinger Robert H.G.
Published: August 2004

Objective and methods:

To further investigate length‐dependent force generation in human heart, nonfailing (donor hearts, NF) and terminally failing (heart transplants, dilated cardiomyopathy, DCM) left ventricular myocardium was studied under various preload (4–40 mN/mm2) or length conditions. In addition, morphological studies (van Giesson Trichrome staining, electron microscopy) were performed.

Results:

In NF, a biphasic increase in force of contraction (FOC) was observed after elevating the preload (4–40 mN/mm2): there was an immediate fast increase (FOCf,), followed by a slow increase over several minutes (FOCs), which was paralleled by an increase in the systolic fura‐2 transient. In DCM, FOCf, FOCs and the systolic fura‐2 transient were blunted and diastolic tension was increased at increasing muscle length. Only in NF, a stretched induced increase in diastolic fura‐2 ratio was observed. In DCM, no obvious interstitial fibrosis and no difference in basement membrane structure and attachment were observed.

Conclusions:

Since FOCf has been attributed to the Frank‐Starling mechanism, whereas FOCs represents a length‐dependent increase in the intracellular Ca2+‐transient, the impaired length‐dependent force generation in failing myocardium results from a dysregulation of both myofibrillar Ca2+‐sensitivity as well as the intracellular Ca2+‐homeostasis. Interstitial fibrosis may have only minor impact on force generation in human end‐stage heart failure.
Book reviews
Authors: Cleland John , Ford S.
Published: August 2004

Case Studies in Interventional Cardiology Ed Martin Rothman Published Martin Dunitz (London 2004)

Caring for the Heart Patient‐A textbook for the Health Care Professional Edited by: Simon Stewart, Debra K. Moser, David R. Thompson (2004) London, Martin Dunitz ISBN: 1‐4184‐041‐6
Breakthrough pain in malignant and non‐malignant diseases: a review of prevalence, characteristics and mechanisms
Authors: Svendsen Kristina B. , Andersen Steen , Arnason Sigurdur , Arnér Staffan , Breivik Harald , Heiskanen Tarja , Kalso Eija , Kongsgaard Ulf E. , Sjogren Per , Strang Peter , Bach Flemming W. , Jensen Troels S.
Published: August 2004

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non‐malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non‐malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP. Mechanical stimuli (e.g. micro‐fractures) changes in chemical environments and release of tumour growth factors may initiate sensitization both peripherally and centrally. It is suggested that sensitization could be the common denominator of BTP in malignant and non‐malignant pain.
Comorbid psychiatric diagnoses in kleptomania and pathological gambling: a preliminary comparison study
Authors: Dannon Pinhas N. , Lowengrub Katherine , Sasson Marina , Shalgi Bosmat , Tuson Lali , Saphir Yafa , Kotler Moshe
Published: August 2004

Kleptomania and pathological gambling (PG) are currently classified in the DSM IV as impulse control disorders. Impulse control disorders are characterized by an overwhelming temptation to perform an act that is harmful to the person or others. The patient usually feels a sense of tension before committing the act and then experiences pleasure or relief while in the process of performing the act. Kleptomania and PG are often associated with other comorbid psychiatric diagnoses. Forty-four pathological gamblers and 19 kleptomanics were included in this study. All enrolled patients underwent a complete diagnostic psychiatric evaluation and were examined for symptoms of depression and anxiety using the Hamilton depression rating scale and the Hamilton anxiety rating scale, respectively. In addition, the patients completed self-report questionnaires about their demographic status and addictive behavior. The comorbid lifetime diagnoses found at a high prevalence among our kleptomanic patients included 47% with affective disorders (9/19) and 37% with anxiety disorders (7/19). The comorbid lifetime diagnoses found at a high prevalence in our sample of pathological gamblers included 27% with affective disorders (12/44), 21% with alcohol abuse (9/44), and 7% with a history of substance abuse (3/44). A larger study is needed to confirm these preliminary results.
Obsessive–compulsive disorder and body dysmorphic disorder: a comparison of clinical features
Authors: Frare Franco , Perugi Giulio , Ruffolo Giuseppe , Toni Cristina
Published: August 2004

Body dysmorphic disorder (BDD) is currently classified as a somatoform disorder in DSM-IV, but has been long noted to have some important similarities with obsessive—compulsive disorder (OCD). In addition, BDD and OCD have been often reported to be comorbid with each other. In the present study, we compared demographic characteristics, clinical features and psychiatric comorbidity in patients with OCD, BDD or comorbid BDD—OCD (34 subjects with BDD, 79 with OCD and 24 with BDD—OCD). We also compared the pattern of body dysmorphic concerns and associated behaviors in BDD patients with or without OCD comorbidity. In our sample, BDD and OCD groups showed similar sex ratio. Both groups with BDD and BDD—OCD were significantly younger, and experienced the onset of their disorder at a significantly younger age than subjects with OCD. The two BDD groups were also less likely to be married, and more likely to be unemployed and to have achieved lower level degree, than OCD subjects even when controlling for age. The three groups were significantly different in the presence of comorbid bulimia, alcohol-related and substance-use disorders, BDD—OCD patients showing the highest rate and OCD the lowest. BDD—OCD reported more comorbid bipolar II disorder and social phobia than in the other two groups, while generalized anxiety disorder was observed more frequently in OCD patients. Patients with BDD and BDD—OCD were similar as regards the presence of repetitive BDD-related behaviors, such as mirror-checking or camouflaging. Both groups also did show a similar pattern of distribution as regards the localization of the supposed physical defects in specific areas of the body. The only significant difference concerned the localization in the face, that was more frequent in the BDD group. Our results do not contradict the proposed possible conceptualization of BDD as an OCD spectrum disorder. However, BDD does not appear to be a simple clinical variant of OCD and it seems to be also related to social phobia, mood, eating and impulse control disorders. The co-presence of BDD and OCD features appears to possibly individuate a particularly severe form of the syndrome, with a greater load of psychopathology and functional impairment and a more frequent occurrence of other comorbid mental disorders.
Dimensions of mania: differences between mixed and pure episodes
Authors: González-Pinto Ana , Aldama Ana , González Pinto Asunción , Mosquera Fernando , de Heredia José Luis Pérez , Ballesteros Javier , Gutiérrez Miguel
Published: August 2004

Objective

The presence of at least five dimensions in mania has recently been established. This study extends previous findings by comparing the dimensions of pure vs. mixed mania.

Materials and method

One hundred and three inpatients with bipolar I disorder, manic or mixed (DSM IV), were assessed with SCID-I, YMRS and HDRS-21. The five-factor solution found after applying factorial analysis with Varimax rotation was compared between manic and mixed patients.

Results

There were differences between pure mania and mixed states on factor 1 (depression) and factor 3 (hedonism). There was a tendency to present higher values on factor 5 (activation) in the pure manic group. No differences were found in factor 2 (dysphoria) and factor 4 (psychosis).

Discussion

Hedonism and activation dimensions are present to a lesser degree in mixed states. Although the principal difference between mixed and pure bipolar disorder is the existence of depressive symptoms, the depressive dimension is strongly present in patients with pure mania.

Conclusions

There is need to search for core depressive symptoms in all patients suffering from mania and to evaluate their outcome in clinical trials.
Attention deficit hyperactivity disorder (ADHD) in a 19th century children’s book
Authors: Thome Johannes , Jacobs Kerrin A.
Published: August 2004

Attention deficit hyperactivity disorder (ADHD) is a major mental disorder in children. Presently, its pathogenesis and treatment as well as its role in adult psychiatry are subjects of heated debate. As early as 1846, the typical symptoms of ADHD were described by Heinrich Hoffmann, a physician who later founded the first mental hospital in Frankfurt. Interestingly, his description was published in a children's book entitled “Struwwelpeter” which he had designed for his 3-year-old son Carl Philipp. The symptomatology is impressively depicted in the colourfully illustrated story of “Zappel-Philipp” (“Fidgety Philip”), probably the first written mention of ADHD by a medical professional. This clearly shows that the diagnosis of ADHD is not an “invention” of modern times.