bluuebunny/crossref_metadata_2025 huggingface dataset:
Flt3 Internal Tandem Duplication and P-Glycoprotein Functionality in 171 Patients with Acute Myeloid Leukemia
Authors: Marzac Christophe , Teyssandier I. , Calendini Ors'Anton , Perrot Jean-Yves , Faussat Anne-Marie , Tang Ruoping , Casadevall Nicole , Marie Jean-Pierre , Legrand Ollivier
Published: December 2006

Purpose: Patients with adult acute myeloid leukemia (AML) with intermediate cytogenetics remain a heterogeneous group with highly variable individual prognoses. New molecular markers could help to refine cytogenetic stratification.

Experimental Design: We assessed P-glycoprotein (Pgp) activity and Flt3 internal tandem duplication (ITD+) because of their known prognostic value and because they might lead to targeted therapy. We did a multivariate analysis on 171 patients with adult AML treated in the European Organization for Research and Treatment of Cancer protocols.

Results: ITD+ and high Pgp activity (Pgp+) were found in 26 of 171 (15%) and 55 of 171 (32%) of all patients, respectively. ITD and Pgp activities were negative in 94 of 171 (55%, Pgp−ITD− group), mutually exclusive in 73 of 171 (43%, Pgp−ITD+ and Pgp+ITD− groups), and only 4 of 171 (2%, Pgp+ITD+ group) patients were positive for both. In multivariate analyses, Pgp+ITD+ (P < 0.0001) and age (P = 0.0022) were independent prognostic factors for the achievement of complete remission (CR). Overall survival (OS), CR achievement (P < 0.0001), WHO performance status (P = 0.0007), and Pgp+ITD+ status (P = 0.0014) were also independent prognostic factors. In 95 patients with intermediate cytogenetics, the CR rates of ITD+ patients were 40% versus 62% for ITD− (P = 0.099) and 41% versus 67% (P = 0.014) for Pgp+ versus Pgp− patients. In the Pgp−ITD− group (41 of 95), CR rates were 70% versus 44% for others (P = 0.012), OS achieved 48% versus 16% (P < 0.0001) and disease-free survival was 56% versus 27% (P = 0.024), respectively. Furthermore, the OS curves of the intermediate cytogenetics-Pgp−ITD− group were not significantly different from the favorable cytogenetic group.

Conclusion: Flt3/ITD and Pgp activity are independent and additive prognostic factors which provide a powerful risk classification that can be routinely used to stratify the treatment of patients with intermediate cytogenetic AML. ITD+ and Pgp+ patients should be considered for targeted therapy.
Antitumor Activity of the Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Gefitinib (ZD1839, Iressa) in Non–Small Cell Lung Cancer Cell Lines Correlates with Gene Copy Number and EGFR Mutations but not EGFR Protein Levels
Authors: Helfrich Barbara A. , Raben David , Varella-Garcia Marileila , Gustafson Dan , Chan Daniel C. , Bemis Lynne , Coldren Chris , Barón Anna , Zeng Chan , Franklin Wilbur A. , Hirsch Fred R. , Gazdar Adi , Minna John , Bunn Paul A.
Published: December 2006

Purpose: Recognition that the epidermal growth factor receptor (EGFR) was a therapeutic target in non–small cell lung cancer (NSCLC) and other cancers led to development of the small-molecule receptor tyrosine kinase inhibitors gefitinib and erlotinib. Clinical trials established that EGFR tyrosine kinase inhibitors produced objective responses in a minority of NSCLC patients. We examined the sensitivity of 23 NSCLC lines with wild-type or mutated EGFR to gefitinib to determine genes/proteins related to sensitivity, including EGFR and HER2 cell surface expression, phosphorylated EGFR expression, EGFR gene copy number, and EGFR mutational status. Downstream cell cycle and signaling events were compared with growth-inhibitory effects.

Experimental Design: We determined gefitinib sensitivity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, EGFR expression by fluorescence-activated cell sorting and immunohistochemistry, phosphorylated EGFR by Western blotting, EGFR gene copy number by fluorescence in situ hybridization, and EGFR mutation by sequencing. The cellular effects of gefitinib on cell cycle were determined by flow cytometry and the molecular effects of gefitinib EGFR inhibition on downstream signal proteins by Western blotting. Gefitinib in vivo effects were evaluated in athymic nude mice bearing sensitive and resistant NSCLC xenografts.

Results: There was a significant correlation between EGFR gene copy number, EGFR gene mutations, and gefitinib sensitivity. EGFR protein was necessary but not sufficient for predicting sensitivity. Gefitinib-sensitive lines showed a G1 cell cycle arrest and inactivation of downstream signaling proteins; resistant cell lines had no changes. The in vivo effects mirrored the in vitro effects.

Conclusions: This panel of NSCLC lines characterized for gefitinib response was used to identify predictive molecular markers of response to gefitinib. Several of these have subsequently been shown to identify NSCLC patients likely to benefit from gefitinib therapy.
Synergistic Antitumor Activity of ZD6474, An Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor Signaling, with Gemcitabine and Ionizing Radiation against Pancreatic Cancer
Authors: Bianco Cataldo , Giovannetti Elisa , Ciardiello Fortunato , Mey Valentina , Nannizzi Sara , Tortora Giampaolo , Troiani Teresa , Pasqualetti Francesco , Eckhardt Gail , de Liguoro Mario , Ricciardi Simona , Del Tacca Mario , Raben David , Cionini Luca , Danesi Romano
Published: December 2006

Purpose: Standard treatments have modest effect against pancreatic cancer, and current research focuses on agents targeting molecular pathways involved in tumor growth and angiogenesis. This study investigated the interactions between ZD6474, an inhibitor of tyrosine kinase activities of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor (EGFR), gemcitabine, and ionizing radiation in human pancreatic cancer cells and analyzed the molecular mechanisms underlying this combination.

Experimental Design: ZD6474, ionizing radiation, and gemcitabine, alone or in combination, were given in vitro to MIA PaCa-2, PANC-1, and Capan-1 cells and in vivo to MIA PaCa-2 tumor xenografts. The effects of treatments were studied by the evaluation of cytotoxicity, apoptosis, cell cycle, EGFR and Akt phosphorylation, modulation of gene expression of enzymes related to gemcitabine activity (deoxycytidine kinase and ribonucleotide reductase), as well as vascular endothelial growth factor immunohistochemistry and microvessel count.

Results: In vitro, ZD6474 dose dependently inhibited cell growth, induced apoptosis, and synergistically enhanced the cytotoxic activity of gemcitabine and ionizing radiation. Moreover, ZD6474 inhibited phosphorylation of EGFR and Akt and triggered cell apoptosis. PCR analysis showed that ZD6474 increased the ratio between gene expression of deoxycytidine kinase and ribonucleotide reductase. In vivo, ZD6474 showed significant antitumor activity alone and in combination with radiotherapy and gemcitabine, and the combination of all three modalities enhanced MIA PaCA-2 tumor growth inhibition compared with gemcitabine alone.

Conclusions: ZD6474 decreases EGFR and Akt phosphorylation, enhances apoptosis, favorably modulates gene expression in cancer cells, and acts synergistically with gemcitabine and radiotherapy to inhibit tumor growth. These findings support the investigation of this combination in the clinical setting.
Increased Frequency of CD4+ Cells Expressing CD161 in Cancer Patients
Authors: Iliopoulou Eleni G. , Karamouzis Michalis V. , Missitzis Ioannis , Ardavanis Alexandros , Sotiriadou Nectaria N. , Baxevanis Constantin N. , Rigatos Gerasimos , Papamichail Michael , Perez Sonia A.
Published: December 2006

Purpose: Although the function of natural killer receptors on T cells infiltrating tumors and their potential effect on antitumor immunity has been investigated, little is known about T cells expressing NKR-P1A (CD161) in cancer patients. In the present study, we examined T cells expressing CD161 in the peripheral blood, the tumor tissue and in malignant effusions of patients with several types of malignancies.

Experimental Design: Expression of CD161 in CD4+ or CD8+ (lacking CD56) T cells isolated from peripheral blood (n = 61), tumor specimens (n = 8), and malignant effusions (n = 37) of cancer patients was examined using four-color flow cytometry. Proliferative capacity and cytokine production of purified CD4+CD161+CD56− cells were studied after weak or strong stimulation, with or without costimulation, in the presence or absence of interleukin 2. The possible regulatory function of activated CD4+CD161+CD56− cells on T-cell alloresponses was also investigated.

Results: CD4+ cells expressing CD161 were increased in cancer patients, compared with healthy individuals. This increase in the peripheral blood of cancer patients positively correlated with disease stage and was augmented at the tumor site. Phenotypic analysis revealed that CD4+CD161+ cells are memory T cells, with low expression of activation markers. CD4+CD161+ cells play an immunoregulatory role through cytokine production, because upon receiving costimulatory signals via CD28, they exert suppressive activity on autologous peripheral blood mononuclear cell alloresponses.

Conclusions: CD4+CD161+CD56− cells represent a distinct memory T-cell population significantly increased in cancer patients. Depending on the type of signals provided by the tumor microenvironment, CD4+CD161+ cells may regulate the immune response.
Chelators at the Cancer Coalface: Desferrioxamine to Triapine and Beyond
Authors: Yu Yu , Wong Jacky , Lovejoy David B. , Kalinowski Danuta S. , Richardson Des R.
Published: December 2006

The importance of iron and copper in cancer biology has been well established. Iron plays a fundamental role in cellular proliferation and copper has been shown to be a significant cofactor for angiogenesis. Early observations with the chelator used for the treatment of iron overload, desferrioxamine, showed that it had promise as an anticancer agent. These results sparked great interest in the possibility of developing more effective iron chelators for cancer therapy. The recent entry into clinical trials of the iron-binding drug, Triapine, provides evidence of the potential of this antitumor strategy. Likewise, chelators originally designed to treat disorders of copper overload, such as penicillamine, trientine, and tetrathiomolybdate, have also emerged as potential anticancer drugs, as they are able to target the key angiogenic cofactor, copper. In this review, we will discuss the development of these and other chelators that show potential as anticancer agents.
Role of Endothelium Sensitivity to Shear Stress in Noradrenaline-Induced Constriction of Feline Femoral Arterial Bed under Constant Flow and Constant Pressure Perfusions
Authors: Kartamyshev Sergey P. , Balashov Sergey A. , Melkumyants Arthur M.
Published: December 2006

The effect of shear stress at the endothelium in the attenuation of the noradrenaline-induced constriction of the femoral vascular bed perfused at a constant blood flow was investigated in 16 anesthetized cats. It is known that the adrenergic vasoconstriction of the femoral vascular bed is considerably greater at a constant pressure perfusion than at a constant blood flow. This difference may depend on the ability of the endothelium to relax smooth muscle in response to an increase in wall shear stress. Since the shear stress is directly related to the blood flow and inversely related to the third power of vessel diameter, vasoconstriction at a constant blood flow increases the wall shear stress that is the stimulus for smooth muscle relaxation opposing constriction. On the other hand, at a constant perfusion pressure, vasoconstriction is accompanied by a decrease in flow rate, which prevents a wall shear stress increase. To reveal the effect of endothelial sensitivity to shear stress, we compared noradrenaline-induced changes in total and proximal arterial resistances during perfusion of the hind limb at a constant blood flow and at a constant pressure in vessels with intact and injured endothelium. We found that in the endothelium-intact bed the same concentration of noradrenaline at a constant flow caused an increase in overall vascular peripheral resistance that was half as large as at a constant perfusion pressure. This difference is mainly confined to the proximal arterial vessels (arteries and large arterioles) whose resistance at a constant flow increased only 0.19 ± 0.03 times compared to that at a constant pressure. The removal of the endothelium only slightly increased constrictor responses at the perfusion under a constant pressure (noradrenaline-induced increases of both overall and proximal arterial resistance augmented by 12%), while the responses of the proximal vessels at a constant flow became 4.7 ± 0.4 times greater than in the endothelium-intact bed. A selective blockage of endothelium sensitivity to shear stress using a glutaraldehyde dimer augmented the constrictor responses of the proximal vessels at a constant flow 4.6-fold (±0.3), but had no significant effect on the responses at a constant pressure. These results are consistent with the conclusion that the difference in constrictor responses at constant flow and pressure perfusions depends mainly on the smooth muscle relaxation caused by increased wall shear stress.
A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease
Authors: Herrmann Nathan , Lanctôt Krista L. , Rothenburg Lana S. , Eryavec Goran
Published: December 2006

Background/Aims: To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer’s disease (AD). Methods: This was a randomized, double-blind, placebo-controlled crossover trial of valproate in institutionalized AD patients. Patients were assessed with the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory at baseline and after 6 weeks of treatment with valproate and placebo, with 2 weeks between phases to allow for placebo washout and tapering. Results: Fourteen patients (8 male/6 female) aged 85.6 ± 4.5 years with baseline Mini Mental State Examination scores of 4.5 ± 4.6 and NPI agitation/aggression scores of 6.4 ± 3.5 were randomized to treatment. NPI agitation/aggression treatment change scores significantly worsened during valproate treatment compared with placebo (Z = –2.03, p = 0.04). Tolerability of valproate was also poor, with patients experiencing a significantly greater mean number of adverse events during valproate therapy compared to placebo (Z = –2.82, p = 0.005). Conclusion: Valproate is not effective for the management of agitation in moderate-to-severe AD, and may be poorly tolerated in this population.
What Difference Does Ius Inter Gentes Make? Changing Diplomatic Rights and Duties and the Modern European States-System
Authors: Lechner Silviya
Published: December 2006

The legal status of diplomats underwent a dramatic change between the sixteenth and eighteenth centuries as a consequence of a transformed European states-system. Its transformation is linked to ius inter gentes, a 'law between nations' whose emergence not only created a Europe of sovereign states but simultaneously affected the scope, definition and justification of rights and duties held by diplomatic representatives. It is generally acknowledged that diplomacy as an institution exists by virtue of rules that are embodied in the modern system of states and defined as 'international society' or the 'society of states'. What needs to be better understood is that diplomatic rights and duties are made possible by this framework of an international society, which has discernible historical and analytical boundaries, and that the relationship between such a framework and its diplomatic institutions is not contingent but logical.
A Case Study in Summitry: The Experience of Britain's Edward Heath, 1970-74
Authors: Young John
Published: December 2006

While summits are well served in the literature on diplomacy, the focus tends to be on specific, high-profile occasions such as Munich and Yalta or on the broad experience of multilateral conferences. Such approaches may obscure the full range of summits that were taking place by the later twentieth century. By focusing on a four-year period in the experience of a particular leader, this article provides a case study of summitry, which might serve as the basis for comparisons with other countries and time periods. It draws out the frequency, type and geographical range of summits experienced by Edward Heath as British premier and, in doing so, also raises issues about how types of summits are defined, the relationship between bilateral and multilateral meetings and the way that summitry has evolved as a diplomatic practice. In particular it emerges that summits were frequent and ofen perfunctory affairs, sometimes held as a simple courtesy to leaders who were passing through London. In this sense the British experience may have been unusual, but it is also evident from the number of Heath's interlocutors and the multilateral conferences that he attended that summits had become an integral part of political life for world leaders in the jet age.
The Outsourcing of Public Library Management
Authors: Ward Robert C.
Published: December 2006

Advocates of new public management (NPM) claim that private service delivery promotes efficiency, effectiveness, and cost savings in government. Critics of NPM cite numerous examples of failed attempts to apply NPM. This article examines multiple case studies to determine the strengths and weaknesses of NPM when applied to the outsourcing of public library management. Particular attention focuses on several predicted NPM outcomes including accountability, cost savings, and citizen use/satisfaction. The findings from the cases show that NPM claims related to returning government to its proper principal-agent focus, and thus achieving gains in efficiency and citizen use/satisfaction, are questionable.
The Next Generation of Prisoners
Authors: Blackburn Ashley G. , Mullings Janet L. , Marquart James W. , Trulson Chad R.
Published: December 2006

Violent behavior by juveniles, along with the juvenile incarceration rate, has been on the decline in the past several years. Despite these declines, institutionalized juveniles, particularly violent offenders, constitute the population most at risk of becoming the next generation of adult prisoners. Using a sample of youth incarcerated in the Texas Youth Commission (TYC), this article first examines gender differences among numerous self-report measures including but not limited to violence, maltreatment, life stress, and depression. Next, multivariate analysis revealed that age, minority status, substance dependency, life stress, and gang membership were significantly related to violent offending. Analyses also revealed that numerous variables were related to depression among incarcerated male and female delinquents. This article ends with a discussion of policy implications for incarcerated delinquents.
Antioxidant activity and hepatoprotective potential of agaro-oligosaccharides in vitro and in vivo
Authors: Chen Haimin , Yan Xiaojun , Zhu Peng , Lin Jing
Published: December 2006

Background

Agaro-oligosaccharides derived from red seaweed polysaccharide have been reported to possess antioxidant activity. In order to assess the live protective effects of agar-oligosaccharides, we did both in vitro and in vivo studies based on own-made agaro-oligosaccharides, and the structural information of this oligosaccharide was also determined.

Method

Structure of agaro-oligosaccharides prepared with acid hydrolysis on agar was confirmed by matrix-assisted ultraviolet laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and NMR. The antioxidant effect of agaro-oligosaccharides on intracellular reactive oxygen species (ROS) was assessed by 2', 7'-dichlorofluorescin diacetate. Carbon tetrachloride was used to induce liver injury, some index including SOD, GSH-Px, MDA, AST, ALT were examined to determine the hepatoprotective effect of agaro-oligosaccharides.

Results

Agaro-oligosaccharides we got were composed of odd polymerizations with molecular weights ranged from 500 to 2500. Results from intracellular test indicated that agaro-oligosaccharides could significantly scavenge the level of oxidants in the hepatocytes, more beneficially, also associated with the improvement of cell viability In vivo studies of the antioxidant effects on tissue peroxidative damage induced by carbon tetrachloride in rat model indicated that agaro-oligosaccharides could elevate the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and decrease the level of malondialdehyde (MDA), glutamate oxaloacetate transaminase (AST), glutamic pyruvic transaminase (ALT) significantly. At 400 mg/kg, MDA level reduced 44 % and 21 % in liver and heart, SOD and GSH-Px increased to highest in liver and serum, while ALT level decreased 22.16 % in serum.

Conclusion

Overall, the results of the present study indicate that agaro-oligosaccharides can exert their in vitro and in vivo hepatoprotective effect through scavenging oxidative damage induced by ROS.
Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma
Authors: Liu Gentao , Yuan Xiangpeng , Zeng Zhaohui , Tunici Patrizia , Ng Hiushan , Abdulkadir Iman R , Lu Lizhi , Irvin Dwain , Black Keith L , Yu John S
Published: December 2006

Background

Recently, a small population of cancer stem cells in adult and pediatric brain tumors has been identified. Some evidence has suggested that CD133 is a marker for a subset of leukemia and glioblastoma cancer stem cells. Especially, CD133 positive cells isolated from human glioblastoma may initiate tumors and represent novel targets for therapeutics. The gene expression and the drug resistance property of CD133 positive cancer stem cells, however, are still unknown.

Results

In this study, by FACS analysis we determined the percentage of CD133 positive cells in three primary cultured cell lines established from glioblastoma patients 10.2%, 69.7% and 27.5%, respectively. We also determined the average mRNA levels of markers associated with neural precursors. For example, CD90, CD44, CXCR4, Nestin, Msi1 and MELK mRNA on CD133 positive cells increased to 15.6, 5.7, 337.8, 21.4, 84 and 1351 times, respectively, compared to autologous CD133 negative cells derived from cell line No. 66. Additionally, CD133 positive cells express higher levels of BCRP1 and MGMT mRNA, as well as higher mRNA levels of genes that inhibit apoptosis. Furthermore, CD133 positive cells were significantly resistant to chemotherapeutic agents including temozolomide, carboplatin, paclitaxel (Taxol) and etoposide (VP16) compared to autologous CD133 negative cells. Finally, CD133 expression was significantly higher in recurrent GBM tissue obtained from five patients as compared to their respective newly diagnosed tumors.

Conclusion

Our study for the first time provided evidence that CD133 positive cancer stem cells display strong capability on tumor's resistance to chemotherapy. This resistance is probably contributed by the CD133 positive cell with higher expression of on BCRP1 and MGMT, as well as the anti-apoptosis protein and inhibitors of apoptosis protein families. Future treatment should target this small population of CD133 positive cancer stem cells in tumors to improve the survival of brain tumor patients.
Surface‐Modified LPD Nanoparticles for Tumor Targeting
Authors: LI SHYH‐DAR , HUANG LEAF
Published: December 2006

Abstract:  We have developed a tumor‐targeted LPD formulation (liposome‐polycation‐DNA complex) for siRNA. With surface modification, the targeted, PEGylated LPD increased the delivery efficiency by four‐fold and the gene‐silencing effect by two‐ to three‐fold. Downregulation of survivin in human lung cancer cells by targeted LPD induced 90% of apoptosis and sensitized the cells to cisplatin by four‐fold. PEGylated LPD formulation also significantly improved the tumor localization of siRNA in the NCI‐H460 human lung cancer xenograft model. The tumor appeared to be the major uptake organ for siRNA formulated in surface‐modified LPD. Our encouraging results indicate that surface‐modified LPD may be a potent carrier for RNAi‐based tumor therapy.
Atelocollagen‐Mediated Systemic DDS for Nucleic Acid Medicines
Authors: HANAI KOJI , TAKESHITA FUMITAKA , HONMA KIMI , NAGAHARA SHUNJI , MAEDA MIHO , MINAKUCHI YOSHIKO , SANO AKIHIKO , OCHIYA TAKAHIRO
Published: December 2006

Abstract: The goal of our research is to provide a practical platform for drug delivery in oligonucleotide therapy. We report here the efficacy of an atelocollagen‐mediated oligonucleotide delivery system applied to systemic siRNA and antisense oligonucleotide treatments in animal disease models. Atelocollagen and oligonucleotides formed a complex of nanosized particles, which was highly stable against nucleases. The complex allowed oligonucleotides to be delivered efficiently into several organs and tissues via intravenous administration. In a tumor metastasis model, the complex successfully delivered siRNA to metastasized tumors in bone tissue and inhibited their growth. We also demonstrated that a single intravenous treatment of the antisense oligodeoxynucleotide complex suppressed ear dermatitis in a contact hypersensitivity model. These results indicate the strong potential of the atelocollagen‐mediated drug delivery system for practical therapeutic technology.
Therapeutic Modulation of DMD Splicing by Blocking Exonic Splicing Enhancer Sites with Antisense Oligonucleotides
Authors: AARTSMA‐RUS A. , JANSON A.A.M. , HEEMSKERK J.A. , DE WINTER C.L. , VAN OMMEN G.‐J.B. , VAN DEUTEKOM J.C.T.
Published: December 2006

Abstract:  Antisense oligonucleotides (AONs) can be used to correct the disrupted reading frame of Duchenne muscular dystophy patients (DMD). We have a collection of 121 AONs, of which 79 are effective in inducing the specific skipping of 38 out of the 79 different DMD exons. All AONs are located within exons and were hypothesized to act by steric hindrance of serine‐arginine rich (SR) protein binding to exonic splicing enhancer (ESE) sites. Indeed, retrospective in silico analysis of effective versus ineffective AONs revealed that the efficacy of AONs is correlated to the presence of putative ESE sites (as predicted by the ESEfinder and RESCUE‐ESE software). ESE predicting software programs are thus valuable tools for the optimization of exon‐internal antisense target sequences.
Selective Epoxidation of Cyclohexene by a Square-planar Ru Complex Immobilized into Mesoporous Silicate FSM-16
Authors: Okumura Takeshi , Takagi Hideki , Funahashi Yasuhiro , Ozawa Tomohiro , Fukushima Yoshiaki , Jitsukawa Koichro , Masuda Hideki
Published: December 2006

The Ru complex, [RuII(babp)(dmso)2] (1) (H2babp = 6,6′-bis(benzoylamino)-2,2′-bipyridine), was immobilized into mesoporous silicate FSM-16. The heterogeneous catalyst demonstrated a more selective epoxidation compared with the homogeneous 1.
Transformations of N-Allyl-N-(phenylethynyl)arenesulfonamides into 2,2-Disubstituted 4-Pentenenitriles through Aza-Claisen Rearrangement that Follows Carbomagnesiation
Authors: Yasui Hiroto , Yorimitsu Hideki , Oshima Koichiro
Published: December 2006

Treatment of N-allyl-N-(phenylethynyl)arenesulfonamides with Grignard reagents under copper catalysis resulted in carbomagnesiation across the alkynyl parts. The carbomagnesiations yielded 2-magnesio-3-aza-1,5-hexadienes, which underwent the aza-Claisen rearrangement upon heating. The rearrangement followed by elimination of the arenesulfonyl groups provided 2,2-disubstituted 4-pentenenitriles.
Chiral Scandium-catalyzed Highly Stereoselective Ring-opening of meso-Epoxides with Thiols
Authors: Ogawa Chikako , Wang Naiwei , Kobayashi Shu
Published: December 2006

The desymmetrization of meso-epoxides with thiols proceeded smoothly in dichloromethane or dichloroethane in the presence of a catalytic amount of a chiral scandium complex consisting of Sc(OTf)3 and chiral bipyridine 1, to afford the corresponding sulfides in high yields with high enantioselectivities.
Iron(III) Chloride-catalyzed Reductive Etherification of Carbonyl Compounds with Alcohols
Authors: Iwanami Katsuyuki , Yano Kentaro , Oriyama Takeshi
Published: December 2006

A facile reductive etherification of carbonyl compounds can be performed by the reaction with alcohols and triethylsilane catalyzed by iron(III) chloride. The corresponding alkyl ethers are obtained in good to excellent yields under mild reaction conditions.
Incidence and Economic Burden of Osteoporosis-Related Fractures in the United States, 2005–2025
Authors: Burge Russel , Dawson-Hughes Bess , Solomon Daniel H , Wong John B , King Alison , Tosteson Anna
Published: December 2006

This study predicts the burden of incident osteoporosis-related fractures and costs in the United States, by sex, age group, race/ethnicity, and fracture type, from 2005 to 2025. Total fractures were >2 million, costing nearly $17 billion in 2005. Men account for >25% of the burden. Rapid growth in the disease burden is projected among nonwhite populations.

Introduction: The aging of the U.S. population will likely lead to greater prevalence of osteoporosis. Policy makers require precise projections of the disease burden by demographic subgroups and skeletal sites to effectively target osteoporosis intervention and treatment programs.

Materials and Methods: A state transition Markov decision model was used to estimate total incident fractures and costs by age, sex, race/ethnicity, and skeletal site for the U.S. population ≥50 years of age for 2005–2025.

Results: More than 2 million incident fractures at a cost of $17 billion are predicted for 2005. Total costs including prevalent fractures are more than $19 billion. Men account for 29% of fractures and 25% of costs. Total incident fractures by skeletal site were vertebral (27%), wrist (19%), hip (14%), pelvic (7%), and other (33%). Total costs by fracture type were vertebral (6%), hip (72%), wrist (3%), pelvic (5%), and other (14%). By 2025, annual fractures and costs are projected to rise by almost 50%. The most rapid growth is estimated for people 65–74 years of age, with an increase >87%. An increase of nearly 175% is projected for Hispanic and other subpopulations.

Conclusions: Osteoporosis prevention, treatment, and education efforts should address all skeletal sites, not just hip and vertebral, and appropriate attention is warranted for men and diverse race/ethnicity subgroups.
Demonstration of Choline Acetyltransferase of a Peripheral Type in the Rat Heart
Authors: Yasuhara Osamu , Matsuo Akinori , Bellier Jean-Pierre , Aimi Yoshinari
Published: December 2006

Cholinergic innervation of the heart has been analyzed using cholinergic markers including acetylcholinesterase, choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT). In the present study we demonstrate putative cholinergic nerves in the rat heart using an antibody to ChAT of a peripheral type (pChAT), which is the product of a splice variant of ChAT mRNA and preferentially localized to peripheral cholinergic nerves. Expression of mRNAs for pChAT and the conventional form of ChAT (cChAT) were verified in the rat atrium by RT-PCR. Localization of both protein products in the atrium was confirmed by Western blotting. Virtually all neurons and small intensely fluorescent cells in the intrinsic cardiac ganglia were stained immunohistochemically for pChAT. The density of pChAT-positive fibers was very high in the conducting system, high in both atria, the right atrium in particular, and low in the ventricular walls. pChAT and VAChT immunoreactivities were closely associated in some fibers and fiber bundles in the ventricular walls. These results indicate that intrinsic cardiac neurons homogeneously express both pChAT and cChAT. Furthermore, innervation of the ventricular walls by pChAT- and VAChT-positive fibers provides morphological evidence for a significant role of cholinergic mechanisms in ventricular functions.
Topochemical investigation on phenolic deposits in the vessels of afzelia (Afzelia spp.) and merbau (Intsia spp.) heartwood
Authors: Koch Gerald , Richter Hans-Georg , Schmitt Uwe
Published: December 2006

The topochemical distribution of phenolic deposits in the vessels of afzelia (Afzelia spp.) and merbau (Intsia spp.) heartwood was investigated by means of cellular UV microspectrophotometry (UMSP) to characterise the chemical composition and synthesis by pit membrane-associated enzymes. UV absorbance spectra of the deposits attached to the vessel walls of merbau are characterised by a distinct maximum at a wavelength of 368 nm representing the UV absorbance of pure robinetin (C15H10O7). Deposits in the vessels of afzelia display a typical spectrum of kaempferol (C15H10O2) with two distinct maxima at 270 and 350 nm. The pit membranes and pit canals of associated vessel and parenchyma cells are impregnated by these compounds. These results verify the assumption that the synthesis of deposits in afzelia and merbau is regulated by pit membrane-associated enzymes.
Application of scanning UV microspectrophotometry for the topochemical detection of lignin within individual cell walls of brown-rotted Scots pine (Pinus sylvestris L.) sapwood
Authors: Irbe Ilze , Noldt Guna , Koch Gerald , Andersone Ingeborga , Andersons Bruno
Published: December 2006

Brown rotted Scots pine (Pinus sylvestris) sapwood was studied using scanning UV microspectrophotometry. Wood blocks were exposed to the fungus Coniophora puteana (Schum.: Fr.) Karst. (BAM Ebw.15) for 6, 8, 10, 30, and 50 days. No wood weight loss was detected in the initial decay periods. On the other hand, point analyses of lignin distribution in wood cells revealed higher absorbance after 6–10 days of decay, which we interpret as an increase in the absorption coefficient of lignin due to its oxidative modification by the fungus. Uneven wood degradation occurred in the later periods (30 and 50 days), with both significantly decayed and visually sound cells observed. The decayed cells showed a higher absorbance at 280 nm, although the apparently sound cells were also degraded to a lower extent. Degradation of lignin-rich compounds in middle lamellae and cell corners was not observed during fungal attack.
Influence of overexpression of a gibberellin 20-oxidase gene on the kinetics of xylem cell development in hybrid poplar (Populus tremula L. and P. tremuloides Michx.)
Authors: Dünisch Oliver , Fladung Matthias , Nakaba Satoshi , Watanabe Yoko , Funada Ryo
Published: December 2006

Gibberellins (GAs) are important regulators of shoot growth in trees. We studied the kinetics of xylem formation in hybrid poplar (Populus tremulaL.×P. tremuloidesMichx.) in which the key regulatory gene gibberellin acid 20 oxidase (GA20-oxidase) isolated fromArabidopsisis overexpressed. Increments in the height and radius of shoots were registered by high-resolution laser measurements. The anatomical and chemical structure of mature xylem cells was studied by light electron microscopy and UV spectrophotometry. Transgenic plants showed an increase in height growth, but a lower speed of cell elongation during primary growth compared to wild-type plants. During the first year of growth, transgenic plants showed a higher radius increment, an increase in the period of cell expansion of vessels and fibres and their final size, and a higher lignin content of the compound middle lamella between fibres compared to wild-type plants. In contrast, during the third year of growth, only a slight increase in the period of cell expansion of fibre cells was observed in transgenic compared to wild-type plants. Analyses of GA20-oxidase expression in leaves and shoots of 6-month- and 3-year-old plants of three different independent transgenic lines revealed a decrease in its expression only in shoots but not in leaves of the 3-year-old plants. The results indicate that overexpression of the GA20-oxidase gene in young shoots of transgenic poplar predominately affects cell expansion, while no GA20-oxidase expression was observed in shoots of 3-year-old transgenic plants, resulting in wild-type xylem cell development.
Decay resistance of anhydride-modified Corsican pine sapwood exposed to the brown rot fungus Coniophora puteana
Authors: Hill Callum A.S. , Hale Michael D. , Ormondroyd Graham A. , Kwon Jin H. , Forster Simon C.
Published: December 2006

Corsican pine (Pinus nigra) sapwood was chemically modified with acetic or hexanoic anhydride to a variety of weight gains. The modified wood was exposed to the brown rot fungus Coniophora puteana, and the relationship between weight loss due to decay and weight percentage gain, or degree of hydroxyl substitution, was determined in a 16-week exposure test. The effect of exposure time and the strain of C. puteana upon the decay protection threshold of acetylated Corsican pine was also examined.
Extraction of iron compounds from wood from the Vasa
Authors: Almkvist Gunnar , Persson Ingmar
Published: December 2006

In 2000, salt precipitates were found on surfaces of the Swedish warship Vasa, accompanied by low pH values, partly as a result of oxidation of accumulated sulfur compounds. One hypothesis is that oxidation of the sulfur compounds was catalysed by the large amounts of diverse iron compounds present in the wood. It is therefore of interest to develop a method to extract the iron compounds and simultaneously neutralise the acids. The iron compounds could be extracted using an aqueous solution of ethylenediimino-bis(2-hydroxy-4-methylphenyl)acetic acid (EDDHMA) or diethylenetriamine penta-acetic acid (DTPA) at alkaline pH, leaving only small amounts of iron compounds. The polyethylene glycol (PEG) used as the conservation agent, salts and other water-soluble compounds were co-extracted. The extraction rate was enhanced by stirring and by higher concentrations of the chelator, but diffusion of compounds through the wood was the most important factor for the overall extraction efficiency. Extraction of iron compounds from deep inside the wood is time-consuming and may take years. The results from this study imply that aqueous extraction with strong chelators at relatively high pH, 9–11, effectively removes iron compounds and neutralises the acids present. Although the results are promising, it is still too early to start major re-conservation of Vasa wood using extraction, as all the effects on the wood are not known, but such studies are in progress.
High-consistency ozonation of hardwood kraft pulp
Authors: Tran Ai Van
Published: December 2006

At present, ozone is one of the main chemicals in elemental chlorine-free (ECF) and totally chlorine-free (TCF) bleaching sequences. High consistency (HC) and medium consistency (MC) technologies are in use. This study shows that HC ozonation of hardwood kraft pulp, as expressed by the overall kappa number encompassing both hexenuronic acid groups and residual lignin, is a two-phase path. The reaction rate of the first phase is two- to three-fold higher than that of the second phase. We propose that the first phase is due to ozonation of both hexenuronic acid groups and residual lignin, whereas the second phase involves only residual lignin. The fiber width and wall thickness were relatively unchanged during ozonation. These results are in contrast to the “shrinking core kinetic model” frequently discussed in the context of HC ozonation. The development of pulp brightness and the decrease in pulp viscosity with the ozonation time are well correlated with the overall kappa number or the kappa number due to residual lignin alone.
Measurement of Helium Generation in AISI 304 Reflector and Blanket Assemblies after Long-term Irradiation in EBR-II
Authors: Garner FA , Oliver BM , Greenwood LR , Porter DL , Allen T
Published: December 2006

Five hexagonal ducts constructed from AISI 304 stainless steel in the annealed state were removed from rows 8–14 of the EBR-II fast reactor after many years of irradiation to study the effect of atomic displacement rate on void swelling. For this objective it was important to assure that the observed differences in void swelling were not strongly influenced by variations in helium/dpa ratio. The two major contributions to helium production arise from the nickel and boron content of the steel. However, the boron content was unspecified and therefore unknown, but it was determined from an unirradiated archive duct by converting a well-defined fraction to helium and then measuring the helium content using isotopic dilution mass spectrometry. The same technique was used to measure the total helium in the irradiated duct specimens. After separating the boron contribution from the total measured helium it was possible to determine the contribution from various fast and thermal neutron interactions with the other major elements in the steel and compare the helium generation with predicted values. One important conclusion of the study is that the range of He/dpa ratios over the five subassemblies was not very large, allowing the observed changes in swelling to be attributed primarily to variations in displacement rate and temperature.
A New Biaxial Tension Test Fixture for Uniaxial Testing Machine—A Validation for Hyperelastic Behavior of Rubber-like Materials
Authors: Brieu M. , Diani J. , Bhatnagar N.
Published: December 2006

A new mechanism for a biaxial tension test is developed for loading an in-plane specimen simultaneously in two principal directions. This mechanism can be adapted to any uniaxial tension test machine and thereby it reduces the cost of conducting tests on expensive machines. It provides a uniform state of equibiaxial tension necessary for procedure characterizing the biaxial loading of any material system and particularly for understanding the hyperelastic behavior law of rubber-like materials for large deformations. The mechanism can also be utilized for evaluating an interaction coefficient of anisotropic or orthotropic materials like reinforced composites that can help in characterizing and predicting failure behavior. As a sample case, the experimental results obtained by this new mechanism are validated with the existing models for two rubber-like materials undergoing hyperelasticity.
The influence of porosity on whisker growth in electroplated tin films
Authors: Winterstein J.P. , Norton M.G.
Published: December 2006

Tin whisker growth has been observed since the 1950s and has become of more interest in the past 15 to 20 years due to the desire to use lead-free solders, pure tin being a good lead-free candidate. In the same time period, failure of satellites and other devices using pure tin solders has been blamed on tin whisker growth. The accepted driving force for whisker growth is compressive stresses in films. This article reports a microstructure-control method of limiting whisker growth through the introduction of pores that permit an alternate means of stress relief.
Effect of Cu addition on interfacial reaction between Sn–9Zn solder and Ag
Authors: Yen Yee-Wen , Jao Chien-Chung , Lee Chiapyng
Published: December 2006

The effect of Cu added eutectic Sn–9Zn solder reacting with the Ag substrate has been investigated in this study. Three Ag–Zn intermetallic compounds (IMCs), ∈–AgZn3, γ–Ag5Zn8, and ζ–AgZn, were formed on the Sn–9Zn/Ag interface at 260 °C. While Cu was gradually added to the Sn–9Zn alloy, microstructures of intermetallic compounds changed dramatically. The intermetallic compound microstructures became loose and Sn and Cu atoms in the Ag-Zn intermetallic compounds increased. If more than 3 wt% of Cu was added to the Sn-9Zn alloy, Ag-Sn intermetallic compounds were formed on the Ag surface and massive spalling of Ag–Zn IMC layers from the Ag surface occurred in a short reaction time.
Introduction to first-principles electronic structure methods: Application to actinide materials
Authors: Klepeis John E.
Published: December 2006

This paper provides an introduction for non-experts to first-principles electronic structure methods that are widely used in condensed-matter physics. Particular emphasis is placed on giving the appropriate background information needed to better appreciate the use of these methods to study actinide and other materials. Specifically, the underlying theory is described in sufficient detail to enable an understanding of the relative strengths and weaknesses of the methods. In addition, the meaning of commonly used terminology is explained, including density functional theory (DFT), local density approximation (LDA), and generalized gradient approximation (GGA), as well as linear muffin-tin orbital (LMTO), linear augmented plane wave (LAPW), and pseudopotential methods. Methodologies that extend the basic theory to address specific limitations are also briefly discussed. Finally, a few illustrative applications are presented, including quantum molecular dynamics (QMD) simulations and studies of surfaces, impurities, and defects. The paper concludes by addressing the current controversy regarding magnetic calculations for actinide materials.
Modeling and experimental study of the interface morphology and growth kinetics of fibrous eutectic solidification
Authors: Yao X.
Published: December 2006

Experimental studies of fibrous eutectic growth in succinonitrile–camphor reveal that models of the stable range of interfibrous spacings must incorporate the dynamic effects and the instability of the growth front of the fibrous phase, which determines the fineness and regularity of the microstructures. An analytical mathematical model for fibrous eutectic growth has been developed and compared with the experimental results. The selected wavelength scales obey , where d0, ls, lt are the capillary, diffusion, and thermal lengths, respectively. While only at a relatively high growth rate or steep temperature gradient, the scaling law λ2V = constant is fulfilled. It is found that the selected band of interfibrous spacings is very narrow. This means that the interfibrous spacing is almost unique at a given growth rate and a fixed temperature gradient. The effects of convection on the interfibrous spacing selection and fibrous phase instability of short wavelength perturbations have also been investigated. These studies reveal that the controlled solidification of a fibrous eutectic produces a very fine and regular microstructure.
Linear growth of Ni2Si thin film on n+/p junction at low temperature
Authors: Jiang Yu-Long , Ru Guo-Ping , Qu Xin-Ping , Li Bing-Zong , Detavernier Christophe , Van Meirhaeghe R.L.
Published: December 2006

Nickel mono-silicide has been considered a promising silicide candidate for sub-90 nm nodes of integrated circuits manufacturing. To form high-quality nickel mono-silicide as source/drain contact electrodes, a two-step low temperature rapid thermal process has been proposed, in which the as-deposited Ni will react with silicon during a low temperature (<310 °C) first anneal. Due to the lower annealing temperature Ni2Si will form after the first anneal. To better control the silicidation process the growth kinetics of Ni2Si thin film fabricated by solid-state reaction of sputtered Ni thin film on n+/p junction at low temperature is investigated in this paper. It is demonstrated that between 260 and 280 °C the thickness of Ni2Si thin film has a linear rather than parabolic dependence on annealing time. The corresponding activation energy for this linear growth is found to be ∼1.35 eV.