bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring serum hepatitis C virus (HCV) RNA in patients with HCV‐infected CD20‐positive B‐cell lymphoma undergoing rituximab combination chemotherapy
Authors: Ennishi Daisuke , Terui Yasuhito , Yokoyama Masahiro , Mishima Yuko , Takahashi Shunji , Takeuchi Kengo , Okamoto Hiroaki , Tanimoto Mitsune , Hatake Kiyohiko
Published: August 2007

Several studies have shown that the frequency of hepatitis C virus (HCV) infection is high in patients with B‐cell non‐Hodgkin's lymphoma (NHL). In these studies, liver dysfunction during chemotherapy has been demonstrated, but changes in HCV ribonucleic acid (RNA) levels during chemotherapy have not been well documented. In this study, we monitored serum HCV RNA levels and liver function in five HCV‐infected patients with B‐cell NHL undergoing treatment with rituximab‐combination chemotherapy. Increased HCV RNA levels during or after the chemotherapy were observed in all five patients, and a significant increase in transaminases was seen in one case. In this case, serum HCV RNA level dramatically decreased at the time of the increase of transaminases, and this suggested that the cause of liver damage was an immune reaction against hepatocytes with HCV and not any anticancer drug induced liver toxicity. Monitoring of serum HCV RNA levels and transaminases may be helpful to understand the cause of liver dysfunction in patients receiving chemotherapy. However, increases of HCV viral load were not associated with the occurrence of liver dysfunction in this study. Further studies will be necessary to investigate more fully the relationship between changes in HCV viral load and liver function during chemotherapy for HCV‐infected patients. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Comparison of gene expression profiles in erythroid‐like cells derived from mouse embryonic stem cells differentiated in simple and co‐culture systems
Authors: Boroujeni Mandana B. , Salehnia Mojdeh , Valojerdi Mojtaba R. , Mowla Seyed J. , Forouzandeh Mehdi , Hajizadeh Ebrahim
Published: August 2007

The feeder layer and the presence of specific growth factors are thought to induce the differentiation of embryonic stem cells (ESCs) in culture. The aim of this study was to evaluate the effect of erythropoietin (EPO) on the differentiation of ESCs into erythroid colonies in simple and co‐culture systems. Embryoid bodies were dissociated and replated in semisolid medium in simple culture or in a co‐culture system with bone‐marrow stromal cells (BMSCs), both in the presence or absence of EPO. Colony assays, benzidine staining, and ultrastructural studies were carried out until day 10 of culture. Expression of the ε globin, βH1 globin, runt‐related transcription factor 1 (RUNX1), βmajor globin, and erythropoietin receptor (EPOR) genes was evaluated using semi‐quantitative RT‐PCR. A comparison with the corresponding controls showed that colony size increased in both systems (P ≤≤ 0.05). The number of benzidine‐positive colonies in the co‐culture system with EPO (86.6 ± 17.86) was significantly different compared to the simple culture system with EPO (43.6 ± 4.77; P ≤≤ 0.05). The hemoglobin content of the differentiated cells was visualized in micrographs. Analysis of gene expression showed that all genes except βmajor globin were expressed in the simple culture system, whereas in the co‐culture system all genes were expressed. These results confirmed that the presence of EPO in a BMSC co‐culture system with ESCs improves the differentiation of ESCs to erythroid colonies. Moreover, evidence of primitive and definitive erythropoiesis was observed in this co‐culture system. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
A novel ϵγδβ thalassemia of 1.4 Mb deletion found in a Japanese patient
Authors: Furuya Chiemi , Yamashiro Yasuhiro , Hattori Yukio , Hino Minako , Nishioka Hiroko , Shimizu Yoshihisa , Okano Kozue , Horibe Keizou
Published: August 2007

A novel large deletion, causing ϵγδβ thalassemia (here called, ϵγδβ thalassemia Jpn‐I) was discovered in a 6‐year‐old Japanese boy. He was born uneventfully, but revealed thalassemia minor after birth. The mutation was inherited from his mother. The deletion, caused by an illegitimate recombination extended from 750 kb upstream to 660 kb downstream of e‐globin gene, and removed about 1.4 Mb of DNA, the largest in ϵγδβ thalassemias. A 19‐nucleotide orphan sequence and direct repeats were present at the junction. The deletion lost several functional genes, but no relevant symptoms manifested. The breakpoints were determined by relatively simple methods. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Cardiovascular fitness in adolescents: The influence of sexual maturation status—The AVENA and EYHS studies
Authors: Ortega Francisco B. , Ruiz Jonatan R. , Mesa Jose L. , Gutiérrez Ángel , Sjöström Michael
Published: August 2007

The purposes were: (1) to determine the influence of sexual maturation status and body composition by comparing cardiovascular fitness (CVF) level in two adolescent populations from the south and the north of Europe; (2) to describe the associations between CVF and sexual maturation status in adolescence. A total of 1,867 Spanish adolescents from the AVENA study and 472 from the Swedish part of the EYHS were selected for this report (aged 14–16 years). CVF (expressed by the maximal oxygen consumption) was estimated from 20 m shuttle run test in the AVENA study and from a maximal ergometer cycle test in the EYHS. Sexual maturation status was classified according to Tanner stages. Body fat percentage (BF%) was estimated from skinfold thicknesses. Expressing CVF in different ways (in absolute value and in relation to weight or fat free mass; FFM) resulted in two different results with regard to CVF interpretation and comparison between the study populations. A higher CVF, as expressed in relation to FFM, was observed in the Spanish when compared to Swedish adolescents (P = 0.001). However, after adjusting for both sexual maturation status and BF%, the difference disappeared in males, while it remained significant in females (P = 0.001). CVF was negatively associated with sexual maturation status in males (P = 0.001). However, after adjusting for BF%, the association disappeared in males, while it was significant in females (P = 0.05). These results suggest that for CVF comparisons and interpretation in adolescent populations, sexual maturation status and BF%, as well as the way to express the CVF, should be taken into account. Am. J. Hum. Biol., 2007. © 2007 Wiley‐Liss, Inc.
The African contribution to the present‐day population of the Azores Islands (Portugal): Analysis of the Y chromosome haplogroup E
Authors: Neto Domingos , Montiel Rafael , Bettencourt Conceição , Santos Cristina , Prata Maria J. , Lima Manuela
Published: August 2007

Among the settlers that, from 1432 onwards, arrived to the Azores Islands were individuals of North and sub‐Saharan African origin. A previous study of markers of the Y chromosome revealed that haplogroup E is the second more frequent in the Azores (13%). Since this haplogroup is heterogeneous and may contain subtypes of African or non‐African origin, we analyzed an extended sample of 319 Azoreans, originating from the three groups of islands (Eastern, Central, and Western), to evaluate the African contribution to the present‐day population of the Azores. Samples belonging to the E clade were distributed into six haplogroups, from which the most frequent was E3b1a, representing 47.2% of the E chromosomes (6.3% of the total sample). The sub‐Saharan haplogroup E3a was found in 7.1% of E chromosomes (0.9% of the total), corresponding to the highest frequency reported so far in a Portuguese population. No significant differences were detected in the haplogroup distribution among groups of islands, as well as between Azores and most of other European populations compared. The present‐day representation of sub‐Saharan lineages in Azores, although reduced, is higher than in other Portuguese populations, where the demographic representation of sub‐Saharan slaves is reported as similar. Am. J. Hum. Biol., 2007. © 2007 Wiley‐Liss, Inc.
Stature and sexual stature dimorphism in Sweden, from the 10th to the end of the 20th century
Authors: Gustafsson Anders , Werdelin Lars , Tullberg Birgitta S. , Lindenfors Patrik
Published: August 2007

Mean stature in a population has been observed to vary with living conditions. If, and how, this affects sexual dimorphism in stature is not fully understood. We analyzed stature data from Swedish populations from the 10th to the end of the 20th century to investigate if male stature is more plastic than female stature in response to environmental changes. Further, we examined if there, as a consequence of this, exists an allometric relationship between male and female stature that is not caused by genetic factors, coupling greater stature with greater dimorphism. We found no significant change in stature from the 10th century to the 17th century, but a clear increase in both male and female stature during the 20th century, most likely because of improved living conditions. Regression analyses revealed no consistent change in sexual stature dimorphism over time for any of the time periods, including the 20th century. Further, we found no significant allometric relationship between male and female stature, and could consequently not identify any significant relationship between stature and stature dimorphism. Thus, contrary to previous suggestions, the regressions did not provide support for the assertion that male stature is more sensitive to environmental changes than female stature, nor that stature dimorphism increases with increasing stature. Am. J. Hum. Biol., 2007. © 2007 Wiley‐Liss, Inc.
Zurück zur RNAi‐Welt: Gedanken zur Genexpression und Evolution (Nobel‐Vortrag)
Authors: Mello Craig C.
Published: August 2007

Es ist wunderbar, heute hier zu sein. Beginnen möchte ich mit dem wichtigsten Part, nämlich Danke zu sagen. Zu allererst danke ich Andy Fire, der mir über all die Jahre ein großartiger Kollege und Freund war. Ohne Andy stünde ich heute nicht vor Ihnen. Dank schulde ich der University of Massachusetts, nicht nur für Ausrüstung, Laborräume und Geld, sondern vor allem auch für die großartigen Kollegen, mit denen zusammen ich meinen Forschungen nachgehe. Ohne die UMass und das tolle Umfeld dort, wäre ich wahrscheinlich heute nicht hier. Und nicht zu vergessen natürlich meine Familie; ich will jetzt keine Zeit aufbringen, jedem einzelnen zu danken, aber ihr wisst, wie wichtig ihr für mich seid.
Return to the RNAi World: Rethinking Gene Expression and Evolution (Nobel Lecture)
Authors: Mello Craig C.
Published: August 2007

It's wonderful to be here today, I would like to start with the most important part, by saying thank you. First of all, I want to thank Andy Fire for being such a tremendous colleague, friend, and collaborator going back over the years. Without Andy I definitely wouldn't be here today. I need to thank the University of Massachusetts for providing for my laboratory, for believing in me, and for giving me not only a place and money, but great colleagues with whom to pursue my research. Without UMass and the great environment provided for me there, I probably would not be here today. And, of course my family; I'm not going to spend time now thanking them individually, but they know how important they are.
A preliminary study of processing seafood shells for eutrophication control
Authors: Currie J. A. , Harrison N. R. , Wang L. , Jones M. I. , Brooks M. S.
Published: August 2007

Shells from the seafood processing industry in New Zealand are currently an under‐utilized waste resource. In this study we investigate the processing conditions required for the creation of calcium oxide (lime) from green‐lipped mussel (Perna canaliculus) and pacific oyster (Crassostrea gigas) shells. Lime is commonly used in wastewater treatment for the removal of phosphorous compounds from water, thus providing a means of eutrophication control. Mussel and oyster shells were processed in a horizontal tube furnace at various temperatures (650–800 °C) in both air and nitrogen environments. From X‐ray diffraction (XRD) and weight‐loss measurements, the extent of limestone calcination was found to increase with increasing furnace temperature for both shell species and furnace atmospheres. Analysis showed that the lime was present as a layer on the surface of the shell particles. From scanning electron microscope (SEM) images, significant changes in the surface morphology of the raw shells were observed as a result of heat treatment in both air and nitrogen atmospheres. Preliminary testing of shells heat‐treated in both air and nitrogen atmospheres indicated that both types of shell removed about 90% of phosphates in water within 30 min, whereas up to 40% of phosphates were removed with untreated shells. Our results for heat‐treated oyster shell differ slightly with studies in the literature, which report an absence of compositional and structural changes in an air atmosphere. Copyright © 2007 Curtin University of Technology and John Wiley & Sons, Ltd.
Computer modelling of age‐hardening for non‐isothermally aged AlMgSi alloys
Authors: Wu Linda , George Ferguson W.
Published: August 2007

A model for non‐isothermal age‐hardening for AlMgSi alloys has been developed. The model is based on the Shercliff–Ashby methodology developed for isothermal heat treatments, and is extended to non‐isothermal heat treatments by combining with the concept of internal state variable approach. During the process of non‐isothermal heat treatment, the sub‐models not only change with time but also change with temperature. However, the constants, which are calibrated by choosing suitable input data for A356, A357 and 6061 taken from open literature, will remain unchanged for any heat treatment conditions for a specific material. Then two‐step ageing is chosen as an example of non‐isothermal heat treatment. The whole ageing curves of yield strength under different two‐step ageing heat treatments are constructed. Copyright © 2007 Curtin University of Technology and John Wiley & Sons, Ltd.
Radiation‐modified copolymer for the extraction of metal ions from water
Authors: Kamal H. , Hegazy El‐Sayed A. , Mostafa Abo El‐Khair B. , Maksoud A. Abdel
Published: August 2007

The modification of heavy‐duty polyethylene films was carried out through the graft copolymerization of acrylamide and vinyl acetate mixtures of different compositions with the simultaneous radiation method. The influence of the synthesis conditions (the irradiation dose, comonomer composition, and dilution) on the degree of grafting was investigated. The grafted samples were characterized with Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The effect of the grafting degree on the thermal stability of the modified polymer was examined. The extraction of heavy and toxic metals such as cadmium, cobalt, copper, nickel, and lead by the modified heavy‐duty polyethylene was evaluated, and the metal‐ion uptake by the grafted and chemically treated samples seemed better than that of the grafted and untreated ones. Both the rate and amount of the metal‐ion uptake were affected by the temperature of the feed solution and the grafting degree. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Preparation of acacia‐stabilized silver nanoparticles: A green approach
Authors: Mohan Y. Murali , Raju K. Mohana , Sambasivudu K. , Singh Satyendra , Sreedhar B.
Published: August 2007

We report a facile approach for the spontaneous formation of silver nanoparticles in the presence of gum acacia polymer (a natural polymer) without the addition of any typical reducing agent under mild conditions. Silver nanoparticles (∼ 5 nm) have been obtained by the mixing of equal amounts of 0.5 wt % aqueous solutions of acacia and silver nitrate. The formation of silver nanoparticles has been confirmed with ultraviolet–visible, Fourier transform infrared, X‐ray diffraction, and X‐ray photoelectron spectroscopy analyses. Gum acacia polymeric chains promote the reduction process and act as good stabilizers over 5 months. To confirm the formation and stabilization of the nanoparticles, a transmission electron microscope has been employed. The advantage of this methodology is that it is possible to prepare silver nanoparticles without any organic solvents or reducing agents. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Rheology, morphology, and crystallization behavior of melt‐mixed blends of polyamide6 and acrylonitrile‐butadiene‐styrene: Influence of reactive compatibilizer premixed with multiwall carbon nanotubes
Authors: Bose Suryasarathi , Bhattacharyya Arup R. , Kodgire Pravin V. , Misra Ashok , Pötschke Petra
Published: August 2007

Blends of polyamide6 (PA6) and acrylonitrile butadiene styrene (ABS) were prepared in presence or absence of up to 5 wt % of a reactive compatibilizer [styrene maleic anhydride copolymer (SMA) modified with 5 wt % multiwall carbon nanotubes (MWNT)] by melt‐mixing using conical twin screw microcompounder where the ABS content was varied from 20 to 50 wt %. The melt viscosity of the blends was significantly enhanced in presence of SMA modified by multiwall carbon nanotubes due to the reactive compatibilization, which leads to stabilized interphase in the blends. Furthermore, the presence of MWNT in the compatibilizer phase led to additional increase in viscosity and storage modulus. Morphological studies revealed the presence of either droplet‐dispersed or cocontinuous type depending on the blend compositions. Further, reactive compatibilization led to a significant change in the morphology, namely a structure refining, which was enhanced by MWNT presence as observed from SEM micrographs. DSC crystallization studies indicated a delayed crystallization response of PA6 in presence of ABS presumably due to high melt viscosity of ABS. The crystallization temperature and the degree of crystallinity were strongly dependent on the type of morphology and content of reactive compatibilizer, whereas the presence of MWNT had an additional influence. SAXS studies revealed the formation of thinner and less perfect crystallites of PA6 phase in the blends, which showed cocontinuous morphology. A unique observation of multiple scattering maxima at higher q region has been found in the blends of cocontinuous morphology, which was observed to be successively broadened in presence of the compatibilizer. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Shear flow effect on the crystalline forms in polyamide 6/montmorillonite nanocomposites
Authors: Kelnar Ivan , Kratochvíl Jaroslav , Mikešová Jana
Published: August 2007

The influence of shear flow on the crystallization of polyamide 6/MMT nanocomposites prepared by melt intercalation process was investigated in detail by differential scanning calorimetry. The melted nanocomposites were controlled sheared in the steady and oscillatory shear flow, using a rotational rheometer, and cooled in an inert atmosphere. The effects of shear rate or frequency, clay concentration, and crystallization conditions on PA 6 crystalline phase development were studied. As expected, an opposite impact of shearing on γ‐phase formation in the nanocomposites and neat matrix was found. Surprisingly, a critical shear frequency for the onset of γ‐form crystallinity formation in the nanocomposites, increasing with the filler content as a consequence of polymer chains confinement within oriented clay platelets was found. At higher shear frequencies, the proportion of γ‐form in the nanocomposites increased dramatically with the clay concentration and reached 30–40%. The shear flow effects were influenced by cooling conditions, and more significant effect for rapidly cooled samples was observed. The isothermal crystallization at the solidification temperature 205°C reduced the γ‐form content. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Structural Identification of DNA Adducts Derived from 3‐Nitrobenzanthrone, a Potent Carcinogen Present in the Atmosphere
Authors: Takamura‐Enya Takeji , Kawanishi Masanobu , Yagi Takashi , Hisamatsu Yoshiharu
Published: August 2007

3‐Nitrobenzanthrone is a powerful bacterial mutagen and carcinogen to mammals. To obtain precise information on DNA‐adduct formation by 3‐nitrobenzanthrone, a number of DNA adducts, including N‐(2′‐deoxyguanosin‐8‐yl)‐3‐aminobenzanthrone (13 a), 2‐(2′‐deoxyguanosin‐N2‐yl)‐3‐aminobenzanthrone (14 a), N‐(2′‐deoxyadenosin‐8‐yl)‐3‐aminobenzanthrone (15 a), 2‐(2′‐deoxyadenosin‐N6‐yl)‐3‐aminobenzanthrone (16 a), and their N‐acetylated counterparts 13 b, 14 b, 15 b, and 16 b were synthesized by palladium‐catalyzed aryl amination of the corresponding nucleoside and bromobenzanthrone derivatives. Among these DNA adducts, DNA adducts 13 a, 13 b, 14 a, 14 b, and 16 a were identified in the reaction mixture of nucleosides (2′‐deoxyguanosine, 2′‐deoxyadenosine, or DNA) with N‐acetoxy‐3‐aminobenzanthrone or N‐acetyl‐N‐acetoxy‐3‐aminobenzanthrone, both of which are recognized as activated metabolites of 3‐nitrobenzanthrone. The formation of these multiple DNA adducts may help explain the potent mutacarcinogenicity of 3‐nitrobenzanthrone.
A DFT Study on the Mechanism of Rh2II,II‐Catalyzed Intramolecular Amidation of Carbamates
Authors: Lin Xufeng , Zhao Cunyuan , Che Chi‐Ming , Ke Zhuofeng , Phillips David Lee
Published: August 2007

The potential‐energy surfaces of the reactions of dirhodium tetracarboxylate (Rh2II,II) catalyzed nitrene (NR) insertion into CH bonds were examined by a DFT computational study. A pure Becke exchange functional (B88) rather than a hybrid exchange functional (B3, BHandH) was found to be appropriate for the calculation of the energy difference between the singlet and triplet Rh2II,II–NH nitrene species. Rh2II,II–NR1 (R1=(S)‐2‐methyl‐1‐butylformyl) is thermodynamically more favorable with a free energy lower than that of Rh2II,II–N(PhI)R1. The singlet and triplet states of Rh2II,II–NR1 have similar stability. Singlet Rh2II,II–NR1 undergoes a concerted NR insertion into the CH bond with simultaneous formation of the NH and NC bonds during CH bond cleavage; triplet Rh2II,II–NR1 undergoes H atom abstraction to produce a diradical, followed by subsequent bond formation by diradical recombination. The singlet pathway is favored over the triplet in the context of the free energy of activation and leads to the retention of the chirality of the C atom in the NR insertion product. The reactivities of the CH bonds toward the nitrene‐insertion reaction follow the order tertiary>secondary>primary. Relative reaction rates were calculated for the six reaction pathways examined in this work.
On the Pharmacological Properties of Δ9‐Tetrahydrocannabinol (THC)
Authors: Costa Barbara
Published: August 2007

Cannabis is one of the first plants used as medicine, and the notion that it has potentially valuable therapeutic properties is a matter of current debate. The isolation of its main constituent, Δ9‐tetrahydrocannabinol (THC), and the discovery of the endocannabinoid system (cannabinoid receptors CB1and CB2and their endogenous ligands) made possible studies concerning the pharmacological activity of cannabinoids. This paper reviews some of the most‐important findings in the field of THC pharmacology. Clinical trials, anecdotal reports, and experiments employing animal models strongly support the idea that THC and its derivatives exhibit a wide variety of therapeutic applications. However, the psychotropic effects observed in laboratory animals and the adverse reactions reported during human trials, as well as the risk of tolerance development and potential dependence, limit the application of THC in therapy. Nowadays, researchers focus on other therapeutic strategies by which the endocannabinoid system might be modulated to clinical advantage (inhibitor or activator of endocannabinoid biosynthesis, cellular uptake, or metabolism). However, emerging evidence highlights the beneficial effects of the whole cannabis extract over those observed with single components, indicating cannabis‐based medicines as new perspective to revisit the pharmacology of this plant.
Medicinal Chemistry Endeavors around the Phytocannabinoids
Authors: Stern Eric , Lambert Didier M.
Published: August 2007

Over the past 50 years, a considerable research in medicinal chemistry has been carried out around the natural constituents ofCannabis sativaL. Following the identification of Δ9‐tetrahydrocannabinol (Δ9‐THC) in 1964, critical chemical modifications,e.g., variation of the side chain at C(3) and the opening of the tricyclic scaffold, have led to the characterization of potent and cannabinoid receptor subtype‐selective ligands. Those ligands that demonstrate high affinity for the cannabinoid receptors and good biological efficacy are still used as powerful pharmacological tools. This review summarizes past as well as recent developments in the structure–activity relationships of phytocannabinoids.
The Toxicology of Cannabis and Cannabis Prohibition
Authors: Grotenhermen Franjo
Published: August 2007

The acute side effects caused by cannabis use are mainly related to psyche and cognition, and to circulation. Euphoria, anxiety, changes in sensory perception, impairment of memory and psychomotor performance are common effects after a dose is taken that exceeds an individually variable threshold. Cannabis consumption may increase heart rate and change blood pressure, which may have serious consequences in people with heart disease. Effects of chronic use may be induction of psychosis and development of dependency to the drug. Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users. Cannabis exposure in utero may have negative consequences on brain development with subtle impairment of cognitive abilities in later life. Consequences of cannabis smoking may be similar to those of tobacco smoking and should be avoided. Use by young people has more detrimental effects than use by adults. There appear to be promising therapeutic uses of cannabis for a range of indications. Use of moderate doses in a therapeutic context is usually not associated with severe side effects. Current prohibition on cannabis use may also have harmful side effects for the individual and the society, while having little influence on prevalence of use. Harm is greatest for seriously ill people who may benefit from a treatment with cannabis. This makes it difficult to justify criminal penalties against patients.
Blocking the Cannabinoid Receptors: Drug Candidates and Therapeutic Promises
Authors: Muccioli Giulio G.
Published: August 2007

The CB1and CB2cannabinoid receptors have been described as two prime sites of action for endocannabinoids. Both the localization and pharmacology of these two G‐protein‐coupled receptors are well‐described, and numerous selective ligands have been characterized. The physiological effects ofCannabis sativa(cannabis) and a throughout study of the endocannabinoid system allowed for the identification of several pathophysiological conditions – including obesity, dyslipidemia, addictions, inflammation, and allergies – in which blocking the cannabinoid receptors might be beneficial. Many CB1receptor antagonists are now in clinical trials, and the results of several studies involving the CB1antagonist lead compound rimonabant (SR141716A) are now available. This review describes the pharmacological tools that are currently available and the animal studies supporting the therapeutic use of cannabinoid receptor antagonists and inverse agonists. The data available from the clinical trials are also discussed.
Biosynthetic Pathways of the Endocannabinoid Anandamide
Authors: Okamoto Yasuo , Wang Jun , Morishita Jun , Ueda Natsuo
Published: August 2007

Anandamide (=N‐arachidonoylethanolamine) is the first discovered endocannabinoid, and belongs to the class of bioactive, long‐chainN‐acylethanolamines (NAEs). In animal tissues, anandamide is principally formed together with other NAEs from glycerophospholipid by two successive enzymatic reactions:1)N‐acylation of phosphatidylethanolamine to generateN‐acylphosphatidylethanolamine (NAPE) by Ca2+‐dependentN‐acyltransferase;2) release of NAE from NAPE by a phosphodiesterase of the phospholipase D type (NAPE‐PLD). Although these anandamide‐synthesizing enzymes were poorly understood until recently, our cDNA cloning of NAPE‐PLD in 2004 enabled molecular‐biological approaches to the enzymes. NAPE‐PLD is a member of the metallo‐β‐lactamase family, which specifically hydrolyzes NAPE among glycerophospholipids, and appears to be constitutively active. Mutagenesis studies suggested that the enzyme functions through a mechanism similar to those of other members of the family. NAPE‐PLD is widely expressed in animal tissues, including various regions in rat brain. Its expression level in the brain is very low at birth, and remarkably increases with development. Analysis of NAPE‐PLD‐deficient mice and other recent studies revealed the presence of NAPE‐PLD‐independent pathways for the anandamide formation. Furthermore, calcium‐independentN‐acyltransferase was discovered and characterized. In this article, we will review recent progress in the studies on these enzymes responsible for the biosynthesis of anandamide and other NAEs.
Fatty Acid Amide Hydrolase: From Characterization to Therapeutics
Authors: Labar Geoffray , Michaux Catherine
Published: August 2007

Fatty acid amide hydrolase (FAAH) is an integral membrane enzyme within the amidase‐signature family that terminates the action of several endogenous lipid messengers, including oleamide and the endocannabinoid anandamide. The hydrolysis of such messengers leads to molecules devoid of biological activity, and, therefore, modulates a number of neurobehavioral processes in mammals, including pain, sleep, feeding, and locomotor activity. Investigations into the structure and function of FAAH, its biological and therapeutic implications, as well as a description of different families of FAAH inhibitors are the topic of this review.
The N‐Acylethanolamine‐Hydrolyzing Acid Amidase (NAAA)
Authors: Tsuboi Kazuhito , Takezaki Naoko , Ueda Natsuo
Published: August 2007

Bioactive N‐acylethanolamines, including the endocannabinoid anandamide and anti‐inflammatory N‐palmitoylethanolamine, are hydrolyzed to fatty acids and ethanolamine in animal tissues by the catalysis of fatty acid amide hydrolase (FAAH). We recently cloned cDNA of N‐acylethanolamine‐hydrolyzing acid amidase (NAAA), another enzyme catalyzing the same reaction, from human, rat, and mouse. NAAA reveals no sequence homology with FAAH and belongs to the choloylglycine hydrolase family. The most striking catalytic property of NAAA is pH optimum at 4.5–5, which is consistent with its immunocytochemical localization in lysosomes. In rat, NAAA is highly expressed in lung, spleen, thymus, and intestine. Notably, the expression level of NAAA is exceptionally high in rat alveolar macrophages. The primary structure of NAAA exhibits 33–35% amino acid identity to that of acid ceramidase, a lysosomal enzyme hydrolyzing ceramide to fatty acid and sphingosine. NAAA actually showed a low, but detectable ceramide‐hydrolyzing activity, while acid ceramidase hydrolyzed N‐lauroylethanolamine. Thus, NAAA is a novel lysosomal hydrolase, which is structurally and functionally similar to acid ceramidase. These results suggest a unique role of NAAA in the degradation of N‐acylethanolamines.
Genetic Polymorphisms of the Endocannabinoid System
Authors: Norrod Allison G. , Puffenbarger Robyn A.
Published: August 2007

Disturbances in the endocannabinoid system has been linked to diseases and conditions such as Parkinson's, schizophrenia, pain, energy metabolism, immune modulation, and bone density. Since the early 1990s, a number of genetic polymorphisms in the genes and proteins of the endocannabinoid system have been characterized. Currently identified genetic polymorphisms of the endocannabinoid system are reviewed here with particular consideration given to polymorphisms linked to drug and alcohol abuse, schizophrenia, other mental disorders, and energy metabolism.
The N‐Acylethanolamine‐Mediated Regulatory Pathway in Plants
Authors: Kilaru Aruna , Blancaflor Elison B. , Venables Barney J. , Tripathy Swati , Mysore Kirankumar S. , Chapman Kent D.
Published: August 2007

While cannabinoids are secondary metabolites synthesized by just a few plant species, N‐acylethanolamines (NAEs) are distributed widely in the plant kingdom, and are recovered in measurable, bioactive quantities in many plant‐derived products. NAEs in higher plants are ethanolamides of fatty acids with acyl‐chain lenghts of C12C18 and zero to three CC bonds. Generally, the most‐abundant NAEs found in plants and vertebrates are similar, including NAE 16 : 0, 18 : 1, 18 : 2, and 18 : 3. Like in animal systems, NAEs are formed in plants from N‐acylphosphatidylethanolamines (NAPEs), and they are hydrolyzed by an amidase to yield ethanolamine and free fatty acids (FFA). Recently, a homologue of the mammalian fatty acid amide hydrolase (FAAH‐1) was identified in Arabidopsis thaliana and several other plant species. Overexpression of Arabidopsis FAAH (AtFAAH) resulted in plants that grew faster, but were more sensitive to biotic and abiotic insults, suggesting that the metabolism of NAEs in plants resides at the balance between growth and responses to environmental stresses. Similar to animal systems, exogenously applied NAEs have potent and varied effects on plant cells. Recent pharmacological approaches combined with molecular‐genetic experiments revealed that NAEs may act in certain plant tissues via specific membrane‐associated proteins or by interacting with phospholipase D‐α, although other, direct targets for NAE action in plants are likely to be discovered. Polyunsaturated NAEs can be oxidized via the lipoxygenase pathway in plants, producing an array of oxylipin products that have received little attention so far. Overall, the conservation of NAE occurrence and metabolic machinery in plants, coupled with the profound physiological effects of elevating NAE content or perturbing endogenous NAE metabolism, suggest that an NAE‐mediated regulatory pathway, sharing similarities with the mammalian endocannabinoid pathway, indeed exists.
Evidence that PAR2‐triggered prostaglandin E2 (PGE2) formation involves the ERK‐cytosolic phospholipase A2‐COX‐1‐microsomal PGE synthase‐1 cascade in human lung epithelial cells
Authors: Nagataki Mami , Moriyuki Kazumi , Sekiguchi Fumiko , Kawabata Atsufumi
Published: August 2007

We investigated possible involvement of three isozymes of prostaglandin E synthase (PGES), microsomal PGES‐1 (mPGES‐1), mPGES‐2 and cytosolic PGES (cPGES) in COX‐2‐dependent prostaglandin E2 (PGE2) formation following proteinase‐activated receptor‐2 (PAR2) stimulation in human lung epithelial cells. PAR2 stimulation up‐regulated mPGES‐1 as well as COX‐2, but not mPGES‐2 or cPGES, leading to PGE2 formation. The PAR2‐triggered up‐regulation of mPGES‐1 was suppressed by inhibitors of COX‐1, cytosolic phospholipase A2 (cPLA2) and MEK, but not COX‐2. Finally, a selective inhibitor of mPGES‐1 strongly suppressed the PAR2‐evoked PGE2 formation. PAR2 thus appears to trigger specific up‐regulation of mPGES‐1 that is dependent on prostanoids formed via the MEK/ERK/cPLA2/COX‐1 pathway, being critical for PGE2 formation. Copyright © 2007 John Wiley & Sons, Ltd.
Gluconeogenesis and ketogenesis in perfused liver of rats submitted to short‐term insulin‐induced hypoglycaemia
Authors: Albuquerque G. G. , Gazola V. A. F. G. , Garcia R. F. , Souza K. L. A. , Barrena H. C. , Curi R. , Bazotte R. B.
Published: August 2007

Gluconeogenesis and ketogenesis of in situ rat perfused liver submitted to short‐term insulin‐induced hypoglycaemia (IIH) were investigated. For this purpose, 24‐h fasted rats that received intraperitoneal (ip) regular insulin (1.0 U kg−1) or saline were compared. The studies were performed 30 min after insulin (IIH group) or saline (COG group) injection. For gluconeogenesis studies, livers from the IIH and COG groups were perfused with increasing concentrations (from basal blood concentrations until saturating concentration) of glycerol, L‐lactate (Lac) or pyruvate (Pyr). Livers of the IIH group showed maintained efficiency to produce glucose from glycerol and higher efficiency to produce glucose from Lac and Pyr. In agreement with these results the oral administration of glycerol (100 mg kg−1), Lac (100 mg kg−1), Pyr (100 mg kg−1) or glycerol (100 mg kg−1) + Lac (100 mg kg−1) + Pyr (100 mg kg−1) promoted glycaemia recovery. It can be inferred that the increased portal availability of Lac, Pyr and glycerol could help glycaemia recovery by a mechanism mediated, partly at least, by a maintained (glycerol) or increased (Lac and Pyr) hepatic efficiency to produce glucose. Moreover, in spite of the fact that insulin inhibits ketogenesis, the capacity of the liver to produce ketone bodies from octanoate during IIH was maintained. Copyright © 2007 John Wiley & Sons, Ltd.
Tuning the Stacking Properties of C3‐Symmetrical Molecules by Modifying a Dipeptide Motif
Authors: van den Hout Kelly P. , Martín‐Rapún Rafael , Vekemans Jef A. J. M. , Meijer E. W.
Published: August 2007

C3‐symmetrical molecules are described which consists of a 1,3,5‐benzenetricarboxamide core extended with dipeptide fragments bearing peripheral mesogenic groups. Small structural modifications in the dipeptide fragment have been performed to demonstrate their influence on the stability of the stacks and on the order within the self‐assemblies formed. Seven C3‐symmetrical discs have been investigated, all with different combinations of glycine, L‐ and/or D‐phenylalanine in the dipeptide fragments. Characterization of these discotics in the neat state using differential scanning calorimetry (DSC), X‐ray diffraction (XRD) and polarized optical microscopy (POM) and in solution with circular dichroism (CD), UV‐visible spectroscopy, low‐concentration proton nuclear magnetic resonance and IR spectroscopy reveals that there is a clear trend in the stack stability, going from the glycine–phenylalanine motifs to the phenylalanine–phenylalanine ones. The combination of a larger hydrophobic core, more confinement of space and the possibility of additional π–π interactions leads to more stable stacks. Surprisingly, the weakest stacks consist of discotics of which the center is extended with L‐phenylalanyl–glycines and not of discotics of which the center is extended with the glycyl–L‐phenylalanine sequences. Furthermore, the XRD investigations show that it is difficult to form well‐ordered self‐assemblies in the neat state. And, CD measurements point out that some of the discs have a very complex energy landscape in solution. These observations suggest that small differences in the balance between the secondary interactions originating from the benzenetricarboxamide core and the dipeptide fragments, have a strong influence on the order within the stack. From these results it can be concluded that subtle modifications in the peptide fragments of the discs cause significant changes in the stacking properties, stressing the importance of understanding the self‐assembly mechanism of each discotic in order to clarify its self‐assembly behavior.
Carbohydrates as Synthetic Tools in Organic Chemistry
Authors: Boysen Mike M. K.
Published: August 2007

While amino acids, terpenes and alkaloids have found broad application as tools in stereoselective organic synthesis, carbohydrates have only lately been recognised as versatile starting materials for chiral auxiliaries, reagents, ligands and organocatalysts. The structural diversity of carbohydrates and the high density of functional groups offer a wide variety of opportunities for derivatization and tailoring of synthetic tools to a specific problem.
Flow cytometric method for determining folate receptor expression on ovarian carcinoma cells
Authors: Forster Martin D. , Ormerod Michael G. , Agarwal Roshan , Kaye Stanley B. , Jackman Ann L.
Published: August 2007

The α‐folate receptor (α‐FR) is a folate transporter with restricted expression levels in normal tissues. It is over‐expressed in several cancers, particularly epithelial carcinomas, including nonmucinous ovarian carcinoma. It offers a novel therapeutic target for selective imaging and cytotoxic agents. Measurement of the receptor could be a valuable tool in selecting patients more likely to respond to new drugs that target the α‐FR, and monitoring them while on treatment. While tumor samples are often unavailable, a number of patients who relapse develop ascites, which are often rich in tumor cells. We have therefore developed a triple antibody flow cytometric method to assess α‐FR expression on tumor cells from ascites. An antibody to BerEP4, an epithelial cell marker expressed on >90% ovarian cancers, labeled with fluorescein, and an α‐FR antibody labeled with antimouse‐phycoerythrin have been used to label tumor cells, with a CD45‐phycoerythrin‐cyanine5 antibody used to exclude white blood cells from the analysis. The method was optimized using human carcinoma cell lines (JEG‐3, IGROV‐1, and KB cells). Calibrated beads were used to quantify the number of antibodies bound per cell. The triple antibody protocol successfully measured α‐FR expression levels in cell lines spiked with blood. Tumor cells were obtained from ascites in 25 patients with relapsed ovarian cancer. In each case sufficient cells were harvested to identify an epithelial cell population to estimate the number of binding sites/cell. All the samples contained a single population of BerEP4, α‐FR positive cells between 5 × 103 and 5 × 105 antibody binding sites/cell. The method can be used to determine the number of anti‐α‐FR antibodies bound per epithelial cell in ascites from patients with ovarian carcinoma. The results obtained were reproducible and the method could be applied to specimens that had been stored at −80°C. © 2007 International Society for Analytical Cytology.
A feasibility study for reducing common‐mode current on the wire harness connected to electronic control units
Authors: Mabuchi Yuichi , Nakamura Atsushi , Hayashi Tohru , Ichikawa Koji , Uno Takanori , Mizuno Hiroshi
Published: August 2007

With the recent progress in high‐speed and high‐density implementation, EMI (electromagnetic interference) by the electronic equipment in operation with other equipment by electromagnetic wave emission is a problem. In vehicular electronic equipment, the radio frequency (∼100 MHz) is a particular problem, and the common‐mode current flowing in the wire harness connected to the electronic control unit is considered to be a major factor in radiating interference electromagnetic waves. This study investigates the common‐mode current of electronic control units as a major source of EMI. A double‐layer printed board, which forms the mainstream of vehicular electronic control units, is assumed, and the mechanism of the problem and effective means of combating it are investigated. It is found that, for the odd harmonic frequencies of microcontroller operation, the common‐mode current due to voltage fluctuation is the dominant factor, and for the even harmonic frequencies, the common‐mode current due to current fluctuation is the dominant factor. In particular, for the common‐mode current produced by current fluctuation, analysis shows that the generation of the common‐mode current can be reduced by adequately balancing the parasitic inductances and capacitances of the wiring patterns on the printed circuit board. The results of analysis are verified by measurements using an evaluation board. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(9): 19–31, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20337
Dimensionality reduction by simultaneous low‐rank approximation of matrix data
Authors: Inoue Kohei , Urahama Kiichi
Published: August 2007

The authors propose a method of obtaining a direct solution of a simultaneous low‐rank approximation of multiple matrices by using a tensor–matrix product relation to derive a method of obtaining an approximate solution of an optimization problem for performing a simultaneous low‐rank approximation of multiple matrices from a higher‐order singular value decomposition of a tensor. Since the proposed method is a direct solution method, it is faster than a generalized low‐rank approximation algorithm, which is an iterative solution method. They apply the proposed method to face image recognition to show experimentally that its recognition rate is higher and its processing is faster than the eigenface method. They also applied it to an image similarity search to show experimentally that its precision is higher than a dimensionality reduction method for simply reducing the image size. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(9): 42–49, 2007; Published online in Wiley InterScience (www.interscience.wiley. com). DOI 10.1002/ecjb.20379
Estimating the pitch of polyphonic vocal music using comb filters connected in parallel and singular value decomposition
Authors: Yamaguchi Michiru , Miwa Taeko , Tadokoro Yoshiaki
Published: August 2007

Pitch estimation processing is an essential process in the automatic scoring of music. In this paper we propose a method for estimating the pitch of polyphonic vocal lines, an area that has received almost no research. The proposed method estimates pitch by using 12 comb filters connected together in parallel (corresponding to the 12 notes of an octave) together with singular value decomposition (SVD). The approach is based on the fact that a comb filter (H(z)=1−z−N) is able to eliminate all the harmonic components of the note to which it corresponds and also that the SVD of the matrix of signal samples enables us to distinguish the number of harmonic components in the signal from the number of singular values obtained. In other words, together with the above‐mentioned structure we are able to use the SVD to detect outputs in which the number of harmonic components has been reduced and thereby estimate the pitch of a note. We confirm the effectiveness of the proposed method by presenting the results of estimating pitch using the proposed method on polyphonic vocal music with both two and three voices singing at the same time. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(9): 62–74, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20381
Authentication mechanisms in LIN6 and HLIN6
Authors: Tanaka Yasuyuki , Kunishi Mitsunobu , Ishiyama Masahiro , Teraoka Fumio
Published: August 2007

In this paper, the authors propose a mobile node authentication mechanism in LIN6 and HLIN6, which are protocols that guarantee mobility transparency. The proposed method enables authentication that does not depend on IPsec to be performed between a mobile node and an unspecified node such as a communication node or an intermediate router. The proposed method, which is resistant to interception by an attacker, has sufficient strength for practical use. Also, its authentication between a communication node and mobile node is stronger than Return Routability, which is utilized by Mobile IPv6. The authors implemented the proposed method on NetBSD 1.6.1‐RELEASE and compared the processing time with that of the conventional LIN6 or HLIN6. The results indicated that introducing the proposed method had little effect on communication and that the proposed method was effective. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(9): 50– 61, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20382