bluuebunny/crossref_metadata_2025 huggingface dataset:
The Moral Impotence of Contemporary Experts
Authors: Filion Yves R.
Published: July 2004

Technological growth in developed and developing countries in the 20th century has lent a great deal of importance to scientific reasoning in the management of human affairs. An important outgrowth has been the development of systems thinking to organize the workplace. The business reengineering process and the enterprise resource planning system are contemporary instances of the application of systems thinking that have had a serious influence on the modern work organization. This article traces the roots and evolution of systems thinking and investigates whether it is influential in shaping contemporary work organizations. The article also deals with the existential question of whether it is possible for experts to exercise morality and responsibility when they participate in complex work organizations shaped by the application of systems thinking. These concerns begin to motivate the broader question of whether it is possible for anyone to live in the age of systems.
The Effects of Social Networks on Disability in Older Australians
Authors: Giles Lynne C. , Metcalf Patricia A. , Glonek Gary F. V. , Luszcz Mary A. , Andrews Gary R.
Published: July 2004

Objective: To investigate the effects of total social networks and specific social net-works with children, relatives, friends, and confidants on disability in mobility and Nagi functional tasks. Methods: Six waves of data from the Australian Longitudinal Study of Ageing were used. Data came from 1,477 participants aged 70 years or older. The effects of total social networks and those with children, relatives, friends, and confidants on transitions in disability status were analyzed using binary and multinomial logistic regression. Results: After controlling for a range of health, environmental, and personal factors, social networks with relatives were protective against developing mobility disability (OR = 0.89; 95% CI = 0.79 to 1.00) and Nagi disability (OR = 0.85; 95% CI = 0.74 to 0.96). Other social subnetworks did not have a consistent effect on the development of disability. Discussion: The effects of social relationships extend beyond disability in activities of daily living. Networks with relatives protect against disability in mobility and Nagi tasks.
A Short-Term Intervention to Enhance Cognitive and Affective Functioning in Older Adults
Authors: Noice Helga , Noice Tony , Staines Graham
Published: July 2004

Objective: This study was designed to investigate the benefits of a short-term intervention for older adults that targeted cognitive functioning and quality of life issues important for independent living. Method: One hundred twenty-four community-dwelling participants (aged 60 to 86) took part in one of three study conditions: theater arts (primary intervention), visual arts (non-content-specific comparison group), and no-treatment controls. Results: After 4 weeks of instruction, those given theater training made significantly greater gains than did no-treatment controls on both cognitive and psychological well-being measures. A comparison of theater and visual arts training showed fewer benefits in fewer areas for visual arts. Discussion: The authors suggest reasons why various aspects of theater training appear to enhance healthy aging.
Work and Play
Authors: Klein Michael W.
Published: July 2004

This article demonstrates a link between an economic and social feature of countries, the relative labor force participation rate of women, and a high-profile characteristic, the performance of women in international sports competitions. The relative labor force participation rate of women was a significant determinant of the number and type of medals won by a country’s women in the 2000 Sydney Summer Olympics as well as the likelihood of qualifying for the 1999 Women’s Soccer World Cup and performance in that competition. Thus, societies in which women have greater economic opportunities are ones that enable athletically talented women to reach their full potential.
Paxillin selectively associates with constitutive and chemoattractant-induced high-affinity α4β1 integrins: implications for integrin signaling
Authors: Hyduk Sharon J. , Oh Jiwon , Xiao Haiyan , Chen Mian , Cybulsky Myron I.
Published: July 2004

Leukocyte α4β1 integrins regulate hematopoietic and lymphoid development, as well as the emigration of circulating cells to sites of inflammation. Because vascular cell adhesion molecule-1 (VCAM-1) binding to high-affinity α4β1 is stable, these integrins can be detected and selectively precipitated from cell lysates using VCAM-1/Fc. With this approach, high-affinity α4β1 integrin expression was demonstrated on lymphocytes in the bone marrow, thymus, spleen, and the peritoneal cavity of normal mice, but not in peripheral lymph nodes. Immature lymphocytes preferentially expressed high-affinity α4β1 in the bone marrow and thymus. Paxillin is a cytoplasmic adaptor molecule that can bind to the α4 tail and initiate signaling. Paxillin was associated selectively with high-affinity integrins that were isolated from human Jurkat T cells or from murine tissues, and blotting with a phospho-specific antibody demonstrated that Ser988 in the α4 cytoplasmic tail was dephosphorylated in high-affinity but not low-affinity integrins. A rapid and transient α4β1 affinity up-regulation in formyl peptide receptor-transfected U937 cells stimulated with N-formyl-methyonyl-leucyl-phenylalanine (fMLP) correlated temporally with induced paxillin binding to α4 integrins. These data suggest that ligand binding to high-affinity α4β1 integrins may initiate outside-in signaling cascades through paxillin that regulate leukocyte maturation and emigration. (Blood. 2004;104:2818-2824)
KCl cotransport mediates abnormal sulfhydryl-dependent volume regulation in sickle reticulocytes
Authors: Joiner Clinton H. , Rettig R. Kirk , Jiang Maorong , Franco Robert S.
Published: July 2004

KCl cotransport (KCC) activation by cell swelling and pH was compared in sickle (SS) and normal (AA) red blood cells (RBCs). KCC fluxes had the same relationship to mean corpuscular hemoglobin concentration (MCHC) in SS and AA RBCs when normalized to the maximal volume-stimulated (VSmax) flux (MCHC < 270 g/L [27 g/dL]). Acid-stimulated (pH 6.9) KCC flux in SS RBCs was 60% to 70% of VSmax KCC versus 20% in AA RBCs. Density gradients were used to track changes in reticulocyte MCHC during KCC-mediated regulatory volume decrease (RVD). Swelling to MCHC of 260 g/L (26 g/dL) produced Cl-dependent RVD that resulted in higher MCHC in SS than AA reticulocytes. In acid pH, RVD was also greater in SS than AA reticulocytes. Sulfhydryl reduction by dithiothreitol (DTT) lowered VSmax KCC flux in AA and SS RBCs by one third but did not alter swelling-induced RVD. DTT lowered acid-activated KCC in SS RBCs by 50% and diminished acid-induced RVD in SS reticulocytes. Thus, swelling activation of KCC is normal in SS RBCs but KCC-mediated RVD produces higher MCHC in SS than AA reticulocytes. Acid activation of KCC is exaggerated in SS RBCs and causes dehydration in SS reticulocytes. KCC response to acid stimulation was mitigated by DTT, suggesting that it arises from sulfhydryl oxidation.
BCL2 protein expression parallels its mRNA level in normal and malignant B cells
Authors: Shen Yulei , Iqbal Javeed , Huang James Z. , Zhou Guimei , Chan Wing C.
Published: July 2004

The regulation of B-cell lymphoma 2 (BCL2) protein expression in germinal center (GC) B cells has been controversial. Previous reports have indicated posttranscriptional regulation plays a dominant role. However, a number of recent studies contradicted these reports. Using real-time polymerase chain reaction (PCR) and Standardized Reverse Transcriptase-PCR (StaRT-PCR), we measured the level of mRNA expression in GC, mantle zone (MNZ), and marginal zone (MGZ) cells from laser capture microdissection. Both quantitative RT-PCR measurements of microdissected GC cells from tonsils showed that GC cells had low expression of BCL2 transcripts commensurate with the low protein expression level. These results are in agreement with microarray studies on fluorescence-activated cell sorter (FACS)-sorted cells and microdissected GC cells. We also examined BCL2 mRNA and protein expression on a series of 30 cases of diffuse large B-cell lymphoma (DLBCL) and found, in general, a good correlation. The results suggested that BCL2 protein expression is regulated at the transcriptional level in normal B cells and in the neoplastic cells in most B-cell lymphoproliferative disorders.
NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs
Authors: Borg Christophe , Jalil Abdelali , Laderach Diego , Maruyama Kouji , Wakasugi Hiro , Charrier Sabine , Ryffel Bernhard , Cambi Alessandra , Figdor Carl , Vainchenker William , Galy Anne , Caignard Anne , Zitvogel Laurence
Published: July 2004

Mature dendritic cells (mDCs) can trigger the effector functions of natural killer (NK) cells. Knock-out, small-interfering RNA or neutralizing antibodies targeting interleukin 12 (IL-12) subunits revealed a critical role for IL-12 in NK cell interferon γ (IFN-γ) secretion promoted by mDCs. However, NK cell activation by DCs also required direct cell-to-cell contacts. DC-mediated NK cell activation involved the formation of stimulatory synapses between DCs and NK cells. The formation of DC/NK cell conjugates depended on cytoskeleton remodeling and lipid raft mobilization in DCs. Moreover, the disruption of the DC cytoskeleton using pharmacologic agents or the loss-of-function mutation of the Wiskott-Aldrich syndrome protein abolished the DC-mediated NK cell activation. Synapse formation promoted the polarized secretion of preassembled stores of IL-12 by DCs toward the NK cell. The synaptic delivery of IL-12 by DCs was required for IFN-γ secretion by NK cells, as assessed using inhibitors of cytoskeleton rearrangements and transwell experiments. Therefore, the cross-talk between DCs and NK cells is dictated by functional synapses. (Blood. 2004;104:3267-3275)
Cross-Talk between Phosphatidylinositol 3-Kinase/AKT and c-Jun NH2-Terminal Kinase Mediates Survival of Isolated Human Islets
Authors: Aikin Reid , Maysinger Dusica , Rosenberg Lawrence
Published: July 2004

Therapeutic strategies aimed at the inhibition of specific cell death mechanisms may increase islet yield and improve cell viability and function after routine isolation. The aim of the current study was to explore the possibility of AKT-JNK cross-talk in islets after isolation and the relevance of c-jun NH2-terminal kinases (JNK) suppression on islet survival. After routine isolation, increased AKT activity correlated with suppression of JNK activation, suggesting that they may be related events. Indeed, the increase in AKT activation after isolation correlated with suppression of apoptosis signal-regulating kinase 1 (ASK1), a kinase acting upstream of JNK, by phosphorylation at Ser83. We therefore examined whether modulators of phosphatidylinositol 3-kinase (PI3K)/AKT signaling affected JNK activation. PI3K inhibition led to increased JNK phosphorylation and islet cell death, which could be reversed by the specific JNK inhibitor SP600125. In addition, IGF-I suppressed cytokine-mediated JNK activation in a PI3K-dependent manner. We also demonstrate that inhibition of PI3K rendered islets more susceptible to cytokine-mediated cell death. SP600125 transiently protected islets from cytokine-mediated cell death, suggesting that JNK may not be necessary for cytokine-induced cell death. When administered immediately after isolation, SP600125 improved islet survival and function, even 48 h after removal of SP600125, suggesting that JNK inhibition by SP600125 may be a viable strategy for improving isolated islet survival. Taken together, these results demonstrate that PI3K/AKT suppresses the JNK pathway in islets, and this cross-talk represents an important antiapoptotic consequence of PI3K/AKT activation.
Role of Growth Hormone (GH) in Liver Regeneration
Authors: Pennisi Patricia A. , Kopchick John J. , Thorgeirsson Snorri , LeRoith Derek , Yakar Shoshana
Published: July 2004

Liver regeneration is a fundamental mechanism by which the liver responds to injury. This process is regulated by endogenous growth factors and cytokines, and it involves proliferation of all mature cells that exist within the intact organ. To understand the role of the GH/IGF-I axis in liver regeneration, we performed partial hepatectomies in three groups of mice: GH antagonist (GHa) transgenic mice, in which the action of GH is blocked; liver IGF-I-deficient mice that lack IGF-I specifically in the liver and also lack the acid-labile subunit (ALS; LID+ALSKO mice), in which IGF-I levels are very low and GH secretion is increased; and control mice. Interestingly, the survival rate of GHa transgenic mice was dramatically reduced after partial hepatectomy (57%) compared with the survival rate of controls (100%) or LID+ALSKO mice (88%). In control mice, the liver was completely regenerated after 4 d, whereas liver regeneration required 7 d in LID+ALSKO mice. In contrast, in GHa mice, liver regeneration reached only 70% of the original liver mass after 4 d and did not improve thereafter. Strikingly, 36 and 48 h after hepatectomy, the livers of control and LID+ALSKO mice, respectively, exhibited intense 5-bromo-2′-deoxyuridine (BrdU) staining, whereas BrdU staining was dramatically decreased in the livers of GHa-treated mice. These results suggest that GH plays a critical role in liver regeneration, although whether it acts directly or indirectly remains to be determined.
Reexpression of p8 Contributes to Tumorigenic Properties of Pituitary Cells and Appears in a Subset of Prolactinomas in Transgenic Mice that Hypersecrete Luteinizing Hormone
Authors: Mohammad Helai P. , Seachrist Darcie D. , Quirk Christine C. , Nilson John H.
Published: July 2004

Targeted overexpression of LH in transgenic mice causes hyperproliferation of Pit-1-positive pituitary cells and development of functional adenomas. To characterize gene expression changes associated with pituitary tumorigenesis, we performed microarray studies using Affymetrix GeneChips comparing expression profiles from pituitary tumors in LH-overexpressing mice to wild-type control pituitaries. We identified a number of candidate genes with altered expression in pituitary tumors. One of these, p8 (candidate of metastasis-1), encodes a native high-mobility group-like transcription factor previously shown to be necessary for ras-mediated transformation of mouse embryonic fibroblasts and also implicated in breast cancer progression. Herein, we show that expression of p8, normally quiescent in adult pituitary, localizes to tumor foci containing lactotropes, suggesting a linkage with their transformation. To further establish the functional significance of p8 in pituitary tumorigenesis, we constructed several clonal cell lines with reduced expression of p8 from a parent GH3 somatolactotrope cell line. These clonal derivates, along with the parent cell line, were tested for tumorigenicity by injection into athymic mice. When compared with wild-type GH3 with higher levels of p8, GH3 cells with reduced expression of p8 displayed attenuated tumor development or failed to develop tumors at all. Similar results were obtained with gonadotrope-derived cell lines that displayed reduced expression of p8. Together, these data suggest that maintenance of the transformed phenotype of pituitary GH3 cells requires expression of p8 and that it may play a similar role when reexpressed in a subset of lactotropes that form prolactinomas in vivo.
Ab Initio Extended Density Functional Theory for Strongly Correlated Electron Systems: Fundamental Aspects of the Broken-Symmetry Approach and Possible Applications for Molecular Material Design
Authors: Yamanaka Shusuke , Yamaguchi Kizashi
Published: July 2004

We review the extended density functional theory (DFT), in which we make full use of the broken-symmetry feature of the Kohn–Sham (KS) DFT. The theory is based on the classification of broken-symmetry solutions of the Hartree–Fock theory, which has been developed by some precursors in the field “broken-symmetry quantum chemistry”. We describe the fundamental characteristics of the DFT based on generalized spin orbitals (GSOs) in relation to the extension of the constrained search region of DFT. In addition, some important applications, such as noncollinear magnetism of multicenter radicals and radical dissociation followed by spin rotations that are firstly enabled by the use of the GSO-DFT, are presented. Furthermore, future directions covering quantum fluctuations between several collective modes, ab initio molecular dynamics, and relativistic phenomena are also described from the viewpoint of search regions of the extended DFT.
Insertion of Phenylacetylene into [Pt(GeMe3)(SnMe3)(PMe2Ph)2]
Authors: Sagawa Takashi , Tanaka Rika , Ozawa Fumiyuki
Published: July 2004

The reaction of Me3GeSnMe3 with a platinum(0) complex, in situ generated from [Pt(cod)2] (cod = 1,5-cyclooctadiene) and 2 molar quantity of PMe2Ph in Et2O, formed a cis–trans mixture of [Pt(GeMe3)(SnMe3)(PMe2Ph)2] (1). Recrystallization of crude 1 from CH2Cl2–pentane gave pure cis-1, while the isolated cis isomer was again converted to an equilibrium mixture (cis:trans = 8:2) in solution. The cis–trans mixture of 1 underwent competitive insertion of phenylacetylene into Pt–Sn and Pt–Ge bonds to give cis-[Pt(GeMe3){C(Ph)=CH(SnMe3)}(PMe2Ph)2] (2a) and cis-[Pt{C(Ph)=CH(GeMe3)}(SnMe3)(PMe2Ph)2] (3a), respectively, in a ratio of 80:20, while 2a was thermodynamically less stable, and converted to 3a in solution. The insertion mechanism was examined by kinetic investigations.
Selective Detection of Human Serum Albumin Using a Fused-Silica Capillary Modified with Anti-Human Serum Albumin
Authors: Tsukagoshi Kazuhiko , Indou Hirofumi , Sawanoi Kaori , Oguni Takako , Nakajima Riichiro
Published: July 2004

A fused-silica capillary modified with anti-human serum albumin was prepared using the glutaraldehyde method after activating the inner wall with a silane coupling reagent. The antibody selectively interacted via an immune reaction with the human serum albumin, which acted as an antigen. The analytical performance of the modified capillary was examined by capillary affinity chromatography using either absorption or chemiluminescence detection. The capillary affinity chromatography required only minimal reagents and samples due to the extremely small diameter of the capillary. For chemiluminescence detection, a peroxyoxalate reagent was used and human serum albumin was labeled with fluorescamine for competitive immunoassay. After optimization of the analytical conditions, chemiluminescence detection showed a higher sensitivity than absorption detection. Furthermore, a modified capillary was also used in capillary electrophoresis with the absorption detector to allow affinity capillary electrophoresis.
The Synthesis, Crystal Structure, and Magnetic Properties of Perovskites Ba3Ln2MO9 (Ln = Lanthanides; M = Mo, W)
Authors: Oyama Shigeaki , Doi Yoshihiro , Hinatsu Yukio , Ishii Yoshinobu
Published: July 2004

The synthesis, crystal structure, and magnetic properties of quaternary oxides Ba3Ln2MO9 (Ln = Y, Sm–Gd, Dy–Lu for M = Mo; Ln = Y, Sm–Lu for M = W) are reported. Their powder X-ray diffraction measurements and Rietveld analysis showed that they have a “disordered” perovskite structure, i.e., BaLn2/3M1/3O3 except for Ba3Tb2WO9, and that their structures are monoclinic with space group I2/c (Ln = Y, Sm–Gd, Dy–Yb for M = Mo; Ln = Y, Sm–Lu for M = W) or cubic with space group Pmm (Ln = Lu for M = Mo). Powder neutron diffraction measurements showed that Ba3Tb2WO9 has an ordered perovskite structure and is monoclinic with space group P21/n. Magnetic susceptibility measurements showed that all the Ba3Ln2MO9 compounds are paramagnetic down to 1.8 K. The Tb ions of Ba3Tb2WO9 are in the mixed valence state (+3, +4). Through 151Eu Mössbauer measurements on Ba3Eu2MoO9 and Ba3Eu2WO9, it was found that the Eu ion is in the trivalent state, and that the symmetry of the Eu site is distorted from the octahedral symmetry.
Prebiotic Inhibitory Activity of Protein-Like Molecules to the Template-Directed Formation of Oligoguanylate from Guanosine 5′-Monophosphate 2-Methylimidazolide on a Polycytidylic Acid Template
Authors: Kawamura Kunio , Kuranoue Kazuhiro , Nagahama Minoru
Published: July 2004

The influence of thermal copolymers of amino acids (TCAA) as a primitive protein enzyme model has been investigated to detect catalytic and/or inhibitory activities on the template-directed formation of oligoguanylate (oligo(G)) from guanosine 5′-monophosphate 2-methylimidazolide (2-MeImpG) on a polycytidylic acid template (poly(C)) (TD reaction). Different amino acids and compositions were used to prepare TCAAs. These TCAAs were characterized by gel filtration HPLC and the composition analysis of amino acids using phenyl isothiocyanate. It was found that TCAA including His (TCAA-His) has inhibitory activity to the TD reaction, in which TCAA-His accelerates the hydrolysis of 2-MeImpG. Other types of TCAAs, including Gly, Ala, Val, Glu, and Asp, also accelerate the formation of P1,P2-bis(5′-guanosyl) diphosphate (G5′ppG) and G5′ppG incorporated oligo(G)s during the TD reaction at high concentrations of TCAAs. These reactions are considered as primitive enzyme models for the hydrolysis of nucleotide monomer and the formation of pyrophosphate-containing oligo(G).
The Synthesis of Metal-Free Phthalocyanines from Phthalonitriles with Hexamethyldisilazane
Authors: Uchida Hitoshi , Yoshiyama Hideyuki , Reddy Paidi Yella , Nakamura Shuichi , Toru Takeshi
Published: July 2004

Metal-free phthalocyanines were prepared in good yields by heating phthalonitriles with hexamethyldisilazane, (NH4)2SO4, and DMF. Good yields of metal-free phthalocyanines involving peripherally substituted phthalocyanines were attained with a catalytic amount of hexamethyldisilazane. Naphthalocyanine was also prepared. Additional additives were examined to accelerate the formation of the phthalocyanine framework.
Unique and Convenient Use of Raney Nickel for the Reduction of Aryl Bromides, Benzyl Alcohols, Benzyl Ethers, and Benzylamines in an Acidic Medium
Authors: Okimoto Mitsuhiro , Takahashi Yukio , Nagata Yuji , Satoh Masanori , Sueda Satoru , Yamashina Tsunaki
Published: July 2004

A simple and convenient method for laboratory-scale reduction using Raney nickel is described. The reaction was achieved by the inclusion of sulfuric acid to a mixture of a substrate and Raney nickel. Using this method, several aryl bromides, benzyl alcohols, benzyl ethers, and benzylamines were cleaved at the carbon–bromine bond or at the benzylic position to afford corresponding hydrogenated products in good yields without the use of compressed hydrogen gas and without requiring any special apparatus.
Zinc-Induced Deoximation of α,α′-Dioxo-Type Oximes and Oxime Ethers Leading to α,β-Diketo Esters
Authors: Ryu Ilhyong , Kuriyama Hiroki , Miyazato Hironari , Minakata Satoshi , Komatsu Mitsuo , Yoon Joo-Yong , Kim Sunggak
Published: July 2004

The deoximation of a variety of α,α′-dioxo-type oximes and oxime ethers was achieved under mild conditions using zinc/AcOH, which gave good yields of α,β-diketo esters.
The Basicity and Catalytic Activity of Ordered Mesoporous Silicon Nitride Oxide
Authors: Wan Keshu , Liu Qian , Zhang Cunman , Wang Jiacheng
Published: July 2004

The basicity and base catalytic properties of ordered mesoporous silicon nitride oxide (MSON) were investigated in our present contribution. It was found that the basic strength of MSON was stronger and comparable to the strength of MgO. In addition, MSON had a much higher base catalytic activity than not only amorphous silicon nitride oxide but also crystallized nitrogen-containing microporous molecular sieves used in the Knoevenagel condensation reaction of benzaldehyde and malononitrile. Furthermore, the catalysts were stable both in structure and in composition below 1123 K in an inert atmosphere. These stable, solid base catalysts may find their use in some important base catalyzed reactions.
New Large Refractive-Index Change Materials: Synthesis and Photochemical Valence Isomerization of the Calixarene Derivatives Containing Norbornadiene Moieties
Authors: Kudo Hiroto , Ueda Wataru , Sejimo Kiyomitsu , Mitani Kouji , Nishikubo Tadatomi , Anada Tetsuo
Published: July 2004

We have examined the synthesis of cyclic oligomers with pendant norbornadiene (NBD) moieties based on the calixarenes [p-tert-butylcalix[8]arene (BCA), p-methylcalix[6]arene (MCA), calix[4]resorcinarene (CRA), 2,8,14,20-tetradecylcalix[4]resorcinarene (CRA10), and 2,8,14,20-tetrakis(p-hydroxyphenyl)calix[4]resorcinarene (CRAph)]. The photochemical valence isomerization of the obtained calixarene derivatives containing NBD moieties proceeded very smoothly to afford the corresponding quadricyclane (QC) moieties, and it was found that the large refractive-index changes (Δn’s = 0.028–0.061) before and after photo-isomerization.
Low-Temperature Synthesis of Nanocrystalline ZrB2 via Co-reduction of ZrCl4 and BBr3
Authors: Chen Luyang , Gu Yunle , Shi Liang , Ma Jianhua , Yang Zeheng , Qian Yitai
Published: July 2004

Nanocrystalline zirconium diboride (ZrB2) has been synthesized via a sodium co-reduction of ZrCl4 and BBr3 at 400 °C. The XRD patterns can be indexed as hexagonal ZrB2 with the lattice constants a = 3.167 and c = 3.527 Å. The TEM image indicates the product has particle morphology, with size of about 20 nm.
Hydrothermal Synthesis of Layered Li[Ni0.5Mn0.5]O2 as Lithium Intercalation Material
Authors: Myung Seung-Taek , Lee Myung-Hoon , Park Sang-Ho , Sun Yang-Kook
Published: July 2004

In attempt to synthesize layered Li[Ni0.5Mn0.5]O2, a hydrothermal method has been employed. First, the spherical powder precursor, [Ni0.5Mn0.5](OH)2, was prepared via a coprecipitation. Then, the precursor was hydrothermally reacted with an excess amount of LiOH aqueous solution at 170 °C for 4 days. From X-ray diffraction investigation, it was found that the hydrothermally prepared powders showed the layered Li[Ni0.5Mn0.5]O2 having α-NaFeO2 structure (space group: ). The as-prepared powders delivered the initial discharge of about 104 mAh g−1. Further calcination of the hydrothermally prepared powders at 800 °C resulted in the well-ordered layered structure, indicating increase in the crystallinity. Subsequently, the resulting discharge capacity was also improved, 142 mAh g−1 by applying a current density of 20 mA g−1 (1/8C) and the capacity retention was relatively good during cycling.
Thermo-responsive Manipulation of a Water Plug in a Poly(N-isopropylamide)-modified Glass Capillary
Authors: Saitoh Tohru , Sekino Ayahito , Hiraide Masataka
Published: July 2004

A thermo-responsive polymer, poly(N-isopropylacrylamide), was used for the modification of the inner surface of a glass capillary. The modification was performed by the coupling Bind-SilaneTM (3-acryloxypropyltrimethoxysilane) on glass surfaces and a subsequent radical polymerization of N-isopropylacrylamide and methylenebis(acrylamide) with ammonium persulfate—N,N,N′,N′-tetramethylethylenediamine. A water plug placed in the capillary was successfully manipulated by warming the portion of the capillary. The movement was attributed to the wettability gradient of the inner surfaces of the polymer-modified capillary.
Diastereoselectivity in (2π + 2π) Photocycloaddition of Cholesteryl Cinnamate to Methyl 9-Phenanthrenecarboxylate: Control of the Stereoselectivity in Liquid Crystalline Phase
Authors: Maeda Hajime , Horiuchi Akemi , Koshio Norihiro , Mizuno Kazuhiko
Published: July 2004

Photocycloaddition of cholesteryl cinnamate with methyl 9-phenanthrenecarboxylate in benzene at ambient temperature gave a (2π + 2π) photocycloadduct in 8% diastereomeric excess (de). When the reaction was carried out in neat conditions at 150–170 °C, the major product was reversed to another diastereomer, in which de was given in 14%.
Convenient Synthesis and Photophysical Properties of Tetrabenzopentakisdehydro[12]annuleno[12]annulene
Authors: Sonoda Motohiro , Sakai Yu , Yoshimura Takashi , Tobe Yoshito , Kamada Kenji
Published: July 2004

A convenient synthesis of tetrabenzopentakisdehydro[12]annuleno[12]annulene 2c with substantial solubility was achieved by double cyclization of tetrabromotolan 3 with o-diethynylbenzene 4.
Design of FAD-binding Peptide Using a Combinatorial α-Helix Peptide Library
Authors: Sakamoto Seiji , Okano Ippei , Kudo Kazuaki
Published: July 2004

We constructed a resin-bound peptide library in which the peptide was designed to take an α-helix structure, and p-boronobenzoic acid was conjugated on the ε-amino group of the Lys side-chain placed at the middle of the helix. Screening this library allowed selection of a peptide that can bind flavin adenine dinucleotide with high affinity and selectivity.
Monolayer Formation of Cationic Polymer Particles on Hydrophobic Solid Substrates in Aqueous System
Authors: Watanabe Masaru , Kawaguchi Seigou , Nagai Katsutoshi
Published: July 2004

Monodispersed cationic polymer particles bearing quaternary ammonium groups on their surfaces were well self-organized through hydrophobic interaction on hydrophobically modified glass plates in aqueous system. We could fabricate the particle monolayer of close-packed structure with a relatively regular interval by tuning hydrophilic–hydrophobic balance of particles and temperature.
Rapid, Long-Range Molecular Haplotyping of Thiopurine S-Methyltransferase (TPMT*) *3A, *3B, and *3C
Authors: von Ahsen Nicolas , Armstrong Victor W , Oellerich Michael
Published: July 2004

Background: Haplotyping is an important technique in molecular diagnostics because haplotypes are often more predictive for individual phenotypes than are the underlying single-nucleotide polymorphisms (SNPs). Until recently, methods for haplotyping SNPs separated by kilobase distances were laborious and not applicable to high-throughput screening. In the case of thiopurine S-methyltransferase (TPMT*), differentiating among TPMT*3A, *3B, and *3C alleles is sometimes necessary for predictive genotyping.

Methods: The genomic region including the two SNPs that define TPMT*3A, *3B, and *3C alleles was amplified by long-range PCR. The resulting PCR product was circularized by ligation and haplotyped by allele-specific amplification PCR followed by product identification with hybridization probes.

Results: Critical points were the long-range PCR conditions, including choice of buffer and primers, optimization of the ligation reaction, and selection of primers that allowed for strict allele-specific amplification in the second-round PCR. Different underlying TPMT haplotypes could then be differentiated. Results from the haplotyping method were in full agreement with those from our standard real-time PCR method: TPMT*1/*3A (n = 20); TPMT*1/*3C (n = 4); TPMT*1/*1 (n = 6); and TPMT*3A/*3A (n = 6). One TPMT*1/*3A sample failed to amplify, and no whole blood was available for repeat DNA isolation.

Conclusions: This method for rapid-cycle real-time, allele-specific amplification PCR-assisted long-range haplotyping has general application for the haplotyping of distant SNPs. The procedure is simpler and more rapid than previous methods. With respect to TPMT, haplotyping has the potential to discriminate the genotypes TPMT*1/*3A (intermediate metabolizer) and TPMT*3B/*3C (poor metabolizer).
Issues and challenges arising from the application of innovation strategies based on the triple helix culture
Authors: Saad Mohammed
Published: July 2004

The incubation system is discussed in this paper as an aspect of the ‘triple helix’ model of innovation in which universities feature as organizational actors interfacing the public-private/voluntary sector nexus in the process of economic growth and development. Questions arise, however, as to how effectively the incubation, and indeed the triple helix, system can be implemented in developing countries as a strategy of innovation. The introduction of the incubation system in Algeria shows the difficulties involved in implementing innovation strategies based on the ‘triple helix’ model in developing countries in general. It also shows the vulnerability of the triple helix model itself when one of the key actors does not possess the capability and power to play its role effectively. The paper explores the main issues and challenges to be envisaged in the course of implementation of innovation strategies based on the ‘triple helix’ culture. It argues that policy in developing countries like Algeria should seek to promote learning and innovation through an effective system of interactions between and within the main components of the triple helix model, namely government, university and industry.
A no-carrier-added 72Se/72As radionuclide generator based on distillation
Authors: Jennewein M. , Schmidt A. , Novgorodov A. F. , Qaim Syed M. , Rösch Frank
Published: July 2004

Arsenic-72 is a positron emitting isotope with promising properties for syntheses of 72As-labelled radiopharmaceuticals for future application in positron emission tomography. This work describes the radiochemical separation of no-carrier-added 72Se from cyclotron irradiated germanium targets and the development of a 72Se/72As radionuclide generator, avoiding the addition of any selenium carrier. Using a vertical quartz tube device, no-carrier-added 72As is nearly quantitatively released from various chloride salt solutions containing 72Se within 10 min at a temperature of 100 °C in an HCl gas flow. The kinetics of the 72Se/72As isotope generator has been studied in relation to temperature, salt charge, and redox-stability. Under optimised conditions, 72Se remains almost quantitatively (>99.7%) in solution.
Structure of [N,N´-bis(3,5-di-t-butyl-salicylidene)-2-benzyl-1,3-propanediaminato]nitridotechnetium(V) complex, TcN(bzdbsalpn), and nitrido-bridged linear polymeric chains in crystalline syn-isomer
Authors: Takayama Tsutomu , Abe Yuko , Sekine Tsutomu , Kudo Hiroshi
Published: July 2004

A novel nitridotechnetium(V) complex with a tetradentate Schiff base ligand, TcN(bzdbsalpn), was synthesized by the reaction of TcNCl2(PPh3)2 and N , N´-bis(3,5-di- t-butyl-salicylidene)-2-benzyl-1,3-propanediamine (H2bzdbsalpn). Both the syn- and anti-isomers of TcN(bzdbsalpn) were formed in the solution, but recrystallization of a mixture of syn- and anti-TcN(bzdbsalpn) gave a single crystal only for the syn-isomer. X-ray crystallography showed that the syn-TcN(bzdbsalpn) was in a distorted octahedral structure. The planar tetradentate bzdbsalpn ligand coordinates to the technetium atom in an O-N-N-O equatorial plane and the six-membered Nimine-Nimine chelate ring that includes the propylene group adopts a chair conformation. The nitrido ligand (Tc≡N) is at an apical position and the Tc≡N triple bond length is 1.6 Å. Interestingly, the crystal of syn-TcN(bzdbsalpn) has a nitrido-bridged linear polymeric structure (···Tc≡N···Tc≡N···) running along the 21 screw axes parallel to the b axis. The intermolecular N···Tc distance in the syn-TcN(bzdbsalpn) crystal (∼2.8 Å) is fairly long compared with that reported for Cr(V) and Mn(V) nitrido complexes with analogous Schiff base ligands (∼2.5 Å).
[123/131I]Iodometomidate as a radioligand for functional diagnosis of adrenal disease: synthesis, structural requirements and biodistribution
Authors: Schirbel A. , Zolle I. , Hammerschmidt F. , Berger M. L. , Schiller D. , Kvaternik H. , Reiners Chr.
Published: July 2004

Metomidate [(R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid methyl ester] (MTO, 1, Fig. 1) is a potent and selective inhibitor of the cytochrome P-450 enzyme system in the adrenal cortex. Labelled in the 4-position with radioiodine, (R)-4-[131I]iodometomidate, 2, [131I]IMTO has been evaluated by in-vitro studies and also ex-vivo in rats. [131I]IMTO was synthesized by oxidative radioiododestannylation using a suitable precursor which was prepared by a new stereoselective synthesis. Optimization of the labelling reaction was performed by systematic variation of the most important reaction parameters. Under optimum reaction conditions, a labelling yield of 95% was obtained. In-vitro-stability of the tracer was studied over 8 days, indicating slow deiodination (0.27%/h). Displacement studies using [131I]IMTO and rat adrenal membranes revealed the structural requirements for high affinity binding, namely an intact ester group and (R)-configuration of the radioligand. Pharmacokinetic studies in rats showed fast accumulation of [131I]IMTO in the adrenals (approx. 10% ID/g tissue) with an activity plateau for 2 hours. Metabolic degradation was indicated by a steady increase of renal activity up to 4 hours post injection. Based on target to non-target ratios the highest contrast for imaging of the adrenals was observed between 30 and 60 min post injection of [131I]IMTO. We conclude that SPECT using [123I]IMTO will be a promising method for the characterization of adrenal incidentalomas.
Chemoselective pre-conjugate radiohalogenation of unprotected mono- and multimeric peptides via oxime formation
Authors: Poethko Thorsten , Schottelius Margret , Thumshirn Georgette , Herz Michael , Haubner Roland , Henriksen Gjermund , Kessler Horst , Schwaiger Markus , Wester Hans-Jürgen
Published: July 2004

As part of our ongoing efforts in the development of new 18F-labeled peptides for clinical PET imaging, a new two-step 18F-labeling methodology based on the chemoselective oxime formation between an unprotected aminooxy-functionalized peptide and a 18F-labeled aldehyde was investigated and optimized.

4-[18F]Fluorobenzaldehyde ([18F]FB-CHO) was prepared by direct n.c.a. fluorination of 4-formyl-N,N,N-trimethylanilinium triflate and purified by radio-HPLC or a strong-cation-exchange/reverse phase cartridge system. The aminooxyacetic acid (Aoa) modified model peptide LEF-NH2 (Leu-Glu-Phe-NH2) and monomeric, dimeric and tetrameric RGD-containing cyclopeptides were synthesized by solid phase peptide synthesis. Radiochemical yields of N-(4-[18F]fluorobenzylidene)-oxime-formation ([18F]FBOA) with the Aoa-modified unprotected peptides were investigated. Optimized reaction conditions (60 °C, 0.5 mM peptide, 15 min, aqueous solution, pH 2.5) resulted in 70%-90% conjugation yields for all unprotected peptides studied. Chemoselectivity was demonstrated in competition experiments with amino acid mixtures. Biodistribution in M21 melanoma bearing mice showed improved tumor uptake and excretion behaviour in the series c(RGDfE)HEG-Dpr-[18F]FBOA < (c(RGDfE)HEG)2K-Dpr-[18F]FBOA < ((c(RGDfE)HEG)2K)2K-Dpr-[18F]FBOA. Two hours p.i. the fraction of intact c(RGDfE)HEG-K-Dpr-[18F]FBOA in blood, liver, kidney and tumor was >90%, indicating high in vivo stability of the oxime linkage. Initial PET studies with ((c(RGDfE)HEG)2-K)2-K-Dpr-[18F]FBOA showed excellent imaging of M21-melanomas in mice.

In conclusion, the new two-step chemoselective 18F-labeling fulfills all requirements for large scale syntheses of peptides in clinical routine. This methodology is also adaptable to other radioisotopes (e.g. radiohalogenation in general) and will thus offer a broad field of application.
A rapid, almost quantitative conversion of [11C]carbon dioxide into [11C]carbon monoxide via [11C]formate and [11C]formyl chloride
Authors: Roeda Dirk , Crouzel Christian , Dollé Frédéric
Published: July 2004

[11C]Formic acid can be produced from no-carrier-added [11C]carbon dioxide reliably and instantaneously in almost quantitative radiochemical yield using lithium triethylborohydride in THF. It can react, either on a solid support or as its non-hydrolysed LiEt3B-adduct, with a complex formed from hexachloroacetone and triphenylphosphine in THF at room temperature to give, again almost quantitatively, [11C]formyl chloride. The latter decomposes instantaneously to give [11C]carbon monoxide, providing an interesting alternative for current methods of [11C]carbon monoxide production in radiopharmaceutical chemistry. [11C]Formyl chloride has also potential in low-temperature N-formylation.
Determination of reaction parameters for the synthesis of the serotonin transporter ligand [11C]DASB: Application to a remotely controlled high yield synthesis
Authors: Solbach C. , Reischl G. , Machulla H.-J.
Published: July 2004

The synthesis of [11C]DASB is known to be performed by reacting the demethyl-DASB precursor with [11C]methyl iodide but the necessary reaction parameters had hitherto not been determined. In this work the dependence of the labelling yield on reaction temperature, reaction time, precursor concentration and type of solvent was investigated. Best results were found when methylation was carried out at 100 °C within 2 min using 4 mg/ml demethyl precursor in DMSO. With respect to [11C]methyl iodide a radiochemical yield of 74%±3% [11C]DASB was achieved. In addition, the synthesis was transferred to a remotely controlled module. A carbon-11 production for 1 h at 50 μA resulted in 3800-4300 MBq [11C]DASB with a specific activity of 152-211 GBq/μmol (4.1-5.7 Ci/μmol) (EOS) and a radiochemical purity of >95% in a sterile solution ready for injection. The total synthesis time was 45 min after EOB.
Synthesis of 4-([18F]fluoromethyl)-2-chlorophenylisothiocyanate: A novel bifunctional 18F-labelling agent
Authors: Wüst F. , Müller M. , Bergmann R.
Published: July 2004

The one-step radiosynthesis of 4-([18F]fluoromethyl)-2-chlorophenylisothiocyanate 18F-7 as a novel bifunctional 18F-labelling agent is described. Optimised reaction conditions in a remotely controlled synthesis module gave isothiocyanate 18F-7 in radiochemical yields of 45% (decay-corrected) within 40 min and high radiochemical purity of >95% after solid-phase-extraction. Coupling of compound 18F-7 with the primary amine benzylamine as a model reaction afforded the corresponding ((4-[18F]fluoromethyl)-2-chloro-phenyl)-benzyl thiourea 18F-8 in a high radiochemical yield of >90%. Stability studies of thiourea 18F-8 in terms of radiodefluorination showed appreciable buffer stability at pH 7.4, whereas significant radiodefluorination was observed when 18F-8 was incubated in buffers at pH 3.6 and pH 9.4. Preliminary dynamic PET studies with thiourea 18F-8 in male Wistar rats showed high bone accumulation, indicative of high in vivo radiodefluorination.
A new technique for radiolabelling of humic substances
Authors: Franke K. , Patt J. T. , Patt M. , Kupsch H. , Steinbach J.
Published: July 2004

A new method of radiolabelling of humic substances (HS) in the aqueous phase has been developed. Radiolabelling with the short-lived positron-emitter18F was carried outviadiazonium coupling to electron-rich aromatic residues of the humic substances. Labelling yields of up to 75% were obtained after optimization of the synthetic procedure. Introductory experimental steps were performed for testing the labelling stability of the humic substances with ultrafiltration, electrophoretic and chromatographic methods.
Clinical presentation of 13 patients with subtelomeric rearrangements and a review of the literature
Authors: Roberts Amy E. , Cox Gerald F. , Kimonis Virginia , Lamb Allen , Irons Mira
Published: July 2004

To re‐examine the potential clinical indications for subtelomeric FISH testing and to provide additional cases to the growing literature on subtelomeric abnormalities and their genotype‐phenotype correlations, we present a single center case series of 13 patients with chromosomal abnormalities detected by subtelomeric FISH testing over a 21 month period. The most common abnormality involved chromosome 1p (23%). Partial monosomy was present in 69% of the patients, complex rearrangements in 23%, and partial trisomy in 8%. The mean time from first normal karyotype to positive subtelomeric FISH result was 3.8 years (n = 11, median 3.5 years, range: 6 months–10 years). One patient had an abnormal high resolution karyotype recognized retrospectively, and two other patients had abnormal karyotypes that were fully deciphered only after subtelomeric FISH analysis. Eighty five percent of cases occurred de novo. The subtelomeric FISH results were useful for adjusting the recurrence risks and helping to focus medical screening and monitoring. The results impacted family planning and satisfied families in search of a diagnosis. Our findings support the use of subtelomeric FISH analysis as a second tier test in patients suspected of having a chromosomal abnormality with a normal karyotype. Potential benefits of subtelomeric FISH testing include faster time to diagnosis, better informed patient prognosis, and more accurate genetic counseling. © 2004 Wiley‐Liss, Inc.
Genome‐wide linkage survey for genetic loci that affect the risk of suicide attempts in families with recurrent, early‐onset, major depression
Authors: Zubenko George S. , Maher Brion S. , Hughes Hugh B. , Zubenko Wendy N. , Scott Stiffler J. , Marazita Mary L.
Published: July 2004

We previously described the results of a genome‐wide linkage survey for genetic loci that influenced the development of unipolar mood disorders in 81 families identified by individuals with Recurrent, Early‐Onset, Major Depressive Disorder (RE‐MDD) [Zubenko et al. 2003b; Am J Med Genet (Neuropsychiatr Genet) 123B:1–18]. In the current study, we extended this linkage analysis by including the history of a suicide attempt as a covariate to identify chromosomal regions that harbor genes that influence the risk of this behavior in the context of mood disorders. This approach identified six linkage peaks with maximum multipoint ΔLOD scores that reached genome‐wide adjusted levels of significance (2p, 5q, 6q, 8p, 11q, and Xq). Four of these (2p, 6q, 8p, and Xq) exceeded the criterion for “highly‐significant linkage” (genome‐wide adjusted P < 0.001) recommended by Lander and Kruglyak [1995; Nat Genet 11:241–246]. The strongest evidence for linkage was observed in analyses employing affected relative pairs (ARPs) with the most severe and disabling Mood Disorders: Depression Spectrum Disorder and RE‐MDD. The highest ΔLOD score that emerged from this linkage analysis, 5.08, occurred for ARPs with Depression Spectrum Disorder at D8S1145 (37.0 cM, 18.2 Mbps, P < 0.0001) at cytogenetic location 8p22‐p21. Significant linkage results on Xq arose from analyses of ARPs with RE‐MDD at DXS1047 (143 cM, 127.8 Mbps, ΔLOD = 3.87, P < 0.0001), a finding that may contribute to the higher rate of suicide attempts among women than men. These findings provide evidence for suicide risk loci that are independent of susceptibility loci for Mood Disorders, and suggest that the capacity for suicide risk loci to affect the development of suicidal behavior depends on the psychiatric disorder or subtype with which they interact. © 2004 Wiley‐Liss, Inc.
Genetic conditions associated with intestinal juvenile polyps
Authors: Merg Anders , Howe James R.
Published: July 2004

Juvenile polyps are hamartomatous polyps found primarily in infants and children, and in association with juvenile polyposis (JP; OMIM# 174900), Cowden syndrome (CS; OMIM# 158350), and Bannayan‐Riley‐Ruvalcaba syndrome (BRRS; OMIM# 153480). Although solitary juvenile polyps are benign lesions, when present in JP patients they may lead to gastrointestinal cancers. Germline mutations in MADH4 and BMPR1A predispose to JP, and both genes are involved in TGF‐β superfamily signaling pathways. In CS and BRRS, juvenile polyps are a less consistent feature, and CS patients are at risk for breast and thyroid cancers. Mutations of the tumor suppressor gene PTEN have been found in the germline of both CS and BRRS patients. Despite different underlying genetic mechanisms, these and other syndromes share the same phenotypic feature of juvenile polyps. © 2004 Wiley‐Liss, Inc.