bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in head and neck cancer incidence in relation to smoking prevalence
Authors: Sturgis Erich M. , Cinciripini Paul M.
Published: August 2007

The trends in head and neck cancer incidence and smoking prevalence are reviewed, discussing where such trends parallel but also how and why they may not. In the U.S., public health efforts at tobacco control and education have successfully reduced the prevalence of cigarette smoking, resulting in a lower incidence of head and neck cancer. Vigilance at preventing tobacco use and encouraging cessation should continue, and expanded efforts should target particular ethnic and socioeconomic groups. However, an unfortunate stagnation has been observed in oropharyngeal cancer incidence and likely reflects a rising attribution of this disease to oncogenic human papillomavirus, in particular type 16 (HPV‐16). For the foreseeable future, this trend in oropharyngeal cancer incidence may continue, but with time the effects of vaccination of the adolescent and young adult female population should result in a lower viral prevalence and hopefully a reduced incidence of oropharyngeal cancer. To hasten the reduction of HPV‐16 prevalence in the population, widespread vaccination of adolescent and young adult males should also be considered. Cancer 2007. © 2007 American Cancer Society.
Upper tract transitional cell carcinoma: Finding a way forward
Authors: Clark Peter E.
Published: August 2007

The author discusses an article in this issue of Cancer by Novara and colleagues, who presented the results from a multicenter, international, retrospective study that adds to the body of literature divining predictors of disease‐specific survival for patients with transitional cell carcinoma of the upper urinary tract who undergo radical prostatectomy.
Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy
Authors: Goldstein Neal S. , Decker David , Severson Dawn , Schell Scott , Vicini Frank , Margolis Jeffrey , Dekhne Nayana S.
Published: August 2007

BACKGROUND.

The molecular classification system categorizes invasive breast carcinomas according to their key driving biomarkers. In the current study, the authors evaluated whether response to neoadjuvant chemotherapy was correlated with the molecular classification groups.

METHODS.

Using immunohistochemistry, the molecular classification group (luminal‐A, luminal‐B, HER‐2–variant, HER‐2–classic, and basal phenotype) was retrospectively determined in 68 breast cancer patients who received neoadjuvant treatment.

RESULTS.

A total of 28 carcinoma patients (41.2%) achieved a compete pathologic response (CPR), including 2 of 15 patients classified as having luminal‐A (13.3%), 4 of 16 patients classified as having luminal‐B (25.0%), 10 of 12 patients classified as having HER‐2–classic (83.3%), none of the 4 patients classified as having HER‐2–variant, and 12 of 21 patients classified as having basal phenotype (57.1%) neoplasms. The CPR rate among patients with the HER‐2–classic and basal neoplasms was 67% (22 of 33 neoplasms), compared with 17.1% (6 of 35 neoplasms) in the non‐HER‐2–classic/basal combined group (P < .001). Eleven carcinomas were initially diagnosed as invasive lobular carcinomas (pleomorphic and classic), 4 of which were luminal‐A, 4 of which were luminal‐B, 2 of which were HER‐2–classic, and 1 of which was basal. On review, only 3 of these 11 cases remained classified as classic lobular carcinoma, all of which were classified as luminal‐A, and none of these patients achieved a CPR. Four of the other 8 patients achieved a CPR.

CONCLUSIONS.

The molecular classification system is useful for identifying carcinoma patients who are most likely and those who are least likely to achieve a CPR. In the current study, all the morphologically classic lobular carcinomas were classified as luminal‐A neoplasms, which may explain the low rate of CPR reported. Cancer 2007. © 2007 American Cancer Society.
A higher radiotherapy dose is associated with more durable palliation and longer survival in patients with metastatic melanoma
Authors: Olivier Kenneth R. , Schild Steven E. , Morris Christopher G. , Brown Paul D. , Markovic Svetomir N.
Published: August 2007

BACKGROUND.

Oncologists are often reluctant to recommend radiotherapy (RT) to palliate metastatic melanoma due to a perception that this tumor is “radioresistant.” The Mayo Clinic experience was analyzed to determine the efficacy of palliative RT.

METHODS.

Eighty‐four consecutive patients with 114 lesions that were not metastatic to the central nervous system (CNS) were evaluated for the response of the presenting symptom, the duration of response, and survival after RT. The median dose delivered was 30 grays (Gy) and the median biologic effective dose (BED) was 39.0 Gy10. Performance status was not uniformly available for all patients.

RESULTS.

Complete resolution of the presenting symptom occurred in 10 lesions (9%). Of the lesions treated, there was partial improvement in 86 (75%), no change in 12 (11%), and worsening in 6 (5%) lesions. The median survival was 3.8 months and freedom from disease progression (FFP) for individual lesions was 6 months. Patients treated with >30 Gy had significantly longer FFP compared with patients given ≤30 Gy (P = .01). In addition, patients treated with >30 Gy had a significantly longer survival than those given a lesser dose (median of 2 months vs 8 months; P < .0001). Similarly, patients receiving a BED >39.0 Gy10 also were found to have longer FFP (P = .03) and survival (median of 2 months vs 8 months; P < .0001) compared with those receiving a BED ≤39.0 Gy10. The dose per fraction, number of previous therapies, and location of the lesions did not appear to impact the effectiveness of RT.

CONCLUSIONS.

RT was found to provide effective palliation of non‐CNS metastasis from malignant melanoma and should be considered for symptomatic patients. RT doses >30 Gy and a BED >39.0 Gy10 were found to be associated with longer palliation. Cancer 2007. © 2007 American Cancer Society.
Increasing incidence and continued dismal outcome of primary central nervous system lymphoma in Norway 1989–2003
Authors: Haldorsen Ingfrid S. , Krossnes Bård K. , Aarseth Jan H. , Scheie David , Johannesen Tom B. , Mella Olav , Espeland Ansgar
Published: August 2007

BACKGROUND.

The incidence of primary central nervous system lymphoma (PCNSL) appears to be increasing in some countries, whereas it is stable in others. Many reports the last decades have suggested that there have been improvements in the treatment of PCNSL. The objective of this study was to analyze time trends in the incidence, clinical features, histologic diagnosis, treatment, and outcome of nonacquired immunodeficiency syndrome (non‐AIDS) PCNSL in Norway from 1989 to 2003.

METHODS.

Patients were identified by a chart review of all patients who had a recorded diagnosis of PCNSL from 1989 to 2003 in The Norwegian Cancer Registry. The histologic and cytologic material from each patient was re‐examined by pathologists. Time trends were analyzed according to year of diagnosis grouped into 3 5‐year periods: 1989–1993, 1994–1998, and 1999–2003.

RESULTS.

There were 98 patients who had confirmed, newly diagnosed non‐AIDS PCNSL in Norway from 1989 to 2003. The incidence rate increased during the consecutive 5‐year periods from 0.89 per million during 1989 to 1993, to 1.74 per million during 1994 to 1998, and to 1.82 per million during 1999 to 2003 (P = .013). Diagnostic delay and overall survival did not improve with time. Survival decreased from 1999 to 2003 compared with survival from 1994 to 1998, which was explained in part by reduced performance status and fewer patients receiving combined chemotherapy and radiotherapy during 1999 to 2003. In multivariate analysis, age ≤50 years, a good performance status, and active treatment (especially combined chemotherapy and radiotherapy) significantly improved survival.

CONCLUSIONS.

The incidence of PCNSL is increasing in Norway. Despite diagnostic and therapeutic advances over the last decades, neither a reduction in diagnostic delay nor any improvement in overall survival with time was observed. The search for improved understanding of etiology and treatment should be intensified. Cancer 2007. © 2007 American Cancer Society.
GPFlow: an intuitive environment for web‐based scientific workflow
Authors: Rygg Asbjørn , Roe Paul , Wong On , Sumitomo Jiro
Published: August 2007

Increasingly scientists are using collections of software tools in their research. These tools are typically used in concert, often necessitating laborious and error‐prone manual data reformatting and transfer. We present an intuitive workflow environment to support scientists with their research. The workflow, GPFlow, wraps legacy tools, presenting a high level, interactive web‐based front end to scientists. The workflow backend is realized by a commercial grade workflow engine (Windows Workflow Foundation). The workflow model is inspired by spreadsheets and is novel in its support for an intuitive method of interaction enabling experimentation as required by many scientists, e.g. bioinformaticians. We apply GPFlow to two bioinformatics experiments and demonstrate its flexibility and simplicity. Copyright © 2007 John Wiley & Sons, Ltd.
Query capabilities of the Karma provenance framework
Authors: Simmhan Yogesh L. , Plale Beth , Gannon Dennis
Published: August 2007

Provenance metadata in e‐Science captures the derivation history of data products generated from scientific workflows. Provenance forms a glue linking workflow execution with associated data products, and finds use in determining the quality of derived data, tracking resource usage, and for verifying and validating scientific experiments. In this article, we discuss the scope of provenance collected in the Karma provenance framework used in the LEAD Cyberinfrastructure project, distinguishing provenance metadata from generic annotations. We further describe our approaches to querying for different forms of provenance in Karma in the context of queries in the first provenance challenge. We use an incremental, building‐block method to construct provenance queries based on the fundamental querying capabilities provided by the Karma service centered on the provenance data model. This has the advantage of keeping the Karma service generic and simple, and yet supports a wide range of queries. Karma successfully answers all but one challenge query. Copyright © 2007 John Wiley & Sons, Ltd.
Bias field induced impedance relaxation of TlGaSe2 semiconducting layered crystal at room temperature
Authors: Okutan M. , Azak F. , Şahin P. , Çavdarlı M. , Erdem Z. , Şentürk E.
Published: August 2007

Complex Impedance Spectroscopy has been employed for the study of absorption kinetics at TlGaSe2 layered crystal under Bias voltage at room temperature. Two relaxations mechanisms have been observed. The crystal has “slow” and “fast” relaxation mechanisms in low and high frequency region, respectively. The complex impedance spectra were fitted by the superposition of two Cole‐Cole types of relaxations. The fast relaxation in the higher frequency region may be due to dipolar relaxation and the slow relaxation in the low frequency region may be due to Maxwell‐Wagner type relaxation. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crystal growth and spectral analysis of Dy3+ and Er3+ doped KPb2Cl5 as a mid‐infrared laser crystal
Authors: Wang Yan , Li Jianfu , Tu Chaoyang , You Zhenyu , Zhu Zhaojie , Wu Baichang
Published: August 2007

This paper reports crystal growth and optical characteristics of dysprosium (Dy3+) and erbium (Er3+) doped mid‐infrared laser crystal ternary‐potassium‐lead‐chloride (KPb2Cl5). Two transparent crystals with good optical quality have been grown successfully by using the Bridgman technique,the largest crystal size reaches up to ∅︁10×60mm2. Measurements of X‐ray diffraction(XRD) and absorption spectra were carried out. Based on Judd‐Ofelt theory, the intensity parameters Ωt(t=2,4,6), the experimental and theoretical oscillator strengths have been obtained.The intensity parameters Ωt(t=2,4,6) of Er3+:KPb2Cl5 were calculated to be Ω2=5.10×10‐20 cm2, Ω4=1.25×10‐20 cm2, Ω6=0.83×10‐20 cm2, and the values for Dy3+:KPb2Cl5 were calculated to be Ω2=6.26×10‐20 cm2, Ω4=2.45×10‐20 cm2, Ω6=0.04×10‐20 cm2 respectively. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth and optical absorption studies on potassium dihydrogen phosphate single crystals
Authors: Raj C. Justin , Krishnan S. , Dinakaran S. , Uthrakumar R. , Das S. Jerome
Published: August 2007

Growth of bulk nonlinear optical (NLO) single crystals gained new significance with the advent of solid‐state laser sources for opto‐electronic applications. An optically transparent crystal of potassium dihydrogen phosphate (KDP) has been grown from aqueous solution along (001) plane with the aid of modified growth assembly of Sankaranarayanan‐Ramasamy (SR) Method. The evaporation rate was controlled and single crystals of 5 mm diameter and 60 mm length with a growth rate 5 mm per day have been grown successfully. The improved transparency of grown crystal was investigated using DRS UV transmittance spectral analysis and the presence of functional groups in the grown crystal is confirmed using FTIR analysis. (© 2007 WILEY ‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Studies on electrical conduction behavior of La1‐3xCaxBaxSrxMnO3 synthesized by chemical route
Authors: Mandal K. D. , Rai A. K. , Parkash Om.
Published: August 2007

In the manganite La1‐xMxMnO3 (M = Ca, Ba, Sr) the doping concentration introduces a mixed valency (Mn3+, Mn4+) which governs the magnetic and electrical properties of the compound. The perovskite oxides La1‐3xCaxBaxSrxMnO3 (x = 0.00, 0.05, 0.10) were prepared by chemical method. Single‐phase formation is confirmed by XRD studies. The electrical behavior of compositions with x = 0.00, 0.05 and 0.10 in the system La1‐3xCaxBaxSrxMnO3 was studied in the temperature range 300‐420 K. It is observed that conductivity decreases with increasing temperature as well as dopants concentration. Metallic behavior of these compositions decreases with increasing dopants concentration (x). The microstructures of these samples have been characterized using scanning electron microscopy (SEM). (© 2007 WILEY ‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Numerical investigation of induction heating and heat transfer in a SiC growth system
Authors: Chen X. J. , Liu L. J. , Tezuka H. , Usuki Y. , Kakimoto K.
Published: August 2007

A global simulation model is applied for a silicon carbide growth system heated by induction coils. A finite‐volume method (FVM) and a global model are applied to solve the equations for electromagnetic field, conductive and radiative heat transfer. The growth rate is predicted by Hertz‐Knudsen equation and one‐dimensional mass transfer equation. Further, simulations for five different coil positions are carried out to investigate the effects of coil position on temperature distribution in the furnace. The numerical results reveal that the variation of temperature in the radial direction along the substrate surface and the temperature difference between the powder and substrate are greatly affected by the coil position. The predicted growth rate along the substrate surface for five coil positions is also studied. Finally, a reasonable range of coil positions maintaining a balance between large‐diameter crystal, high growth rate, temperature limitation of material and lower electrical power consumption is obtained. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Intermediate products in solid‐state reactions of gadolinium oxide and ammonium dihydrogen phosphate
Authors: Uztetik Morkan A. , Morkan İ. , Demirözü‐Şenol S. , Güler H.
Published: August 2007

The solid‐state reactions of Gd2O3 with NH4H2PO4 using various molar ratios (3:6, 2:8, 1:6 and 1:8) of the reactants were investigated at different temperatures (350‐1100°C) to observe the intermediate compounds. Analysis of the X‐ray powder diffraction patterns of the products obtained at 350°C; for the compositions of 2:8, 1:6 and 1:8 molar ratios revealed the formation of a new compound, NH4GdHP3O10 which was reported previously for Nd, Ho and Er. At higher temperatures, gadolinium tripolyphosphate was obtained for all of the molar ratios. On the other hand, the IR data of the products also confirmed the proposed reaction pathways. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
UV‐visible emission of (O2‐ ‐ F+) centres in KBr
Authors: Zehani F. , Sebais M.
Published: August 2007

Single crystals of KBr containing the (O2‐ ‐ F+) color centres and elaborated in atmospheric air by the Czochralski method are studied. The measure of the UV‐visible emission spectra at 78 K present several emission bands situated between 340 and 800 nm. The photoluminescence excitation shows that these emissions are attributed to O‐2 and (O2‐ ‐ F+) centres. This study show the new emission bands of (O2‐ ‐ F+) centres which are situated in the UV‐visible spectral domain. The comparison between the emission spectra before and after the thermal treatment of samples shows clearly the transformation of O‐2 centers at high temperature to (O2‐ ‐ F+) centres. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Exploring responsible property investing: a survey of American executives
Authors: Pivo Gary
Published: August 2007

Property is an important part of modern economies with significant social and environmental consequences. As a result, practitioners and scholars have begun focusing on the social responsibility and sustainability of property investors. This paper expands that work by examining Responsible Property Investing among investment organizations in the United States. Responsible Property Investing is defined as efforts that go beyond compliance with minimum legal requirements to better manage the environmental, social, and governance issues associated with property investing. A survey of senior American executives finds that most organizations are going beyond compliance, implementing management strategies and investing in properties that are consistent with Responsible Property Investment principles. Most executives also place their organization beyond compliance in a Responsible Property Investing stage model. Business concerns are the leading drivers and impediments. Among the various types of organizations studied, pension funds, foundations and endowments lag behind others in implementing Responsible Property Investing. Copyright © 2007 John Wiley & Sons, Ltd and ERP Environment.
Distinct signaling mechanisms activate the target of rapamycin in response to different B‐cell stimuli
Authors: Donahue Amber C. , Fruman David A.
Published: August 2007

Phosphoinositide 3‐kinase (PI3K) and the mammalian target of rapamycin (mTOR), a downstream kinase, are both required for proliferation of splenic B cells. However, the functions of PI3K and mTOR in response to different stimuli and among B cell subsets have not been fully elucidated. We used flow cytometry and magnetic cell sorting to examine the requirement for PI3K and mTOR in responses of splenic B cell subsets to BCR and LPS stimulation. BCR‐mediated phosphorylation of Akt and Erk is sensitive to the PI3K catalytic inhibitor wortmannin in both marginal zone (MZ) and follicular (FO) cells. BCR‐mediated mTOR activation in both subsets is inhibited by wortmannin, though less strongly in MZ cells. In contrast, LPS‐induced mTOR signaling is strikingly resistant to wortmannin in both subsets. Similarly, functional responses to LPS are partially wortmannin resistant yet sensitive to mTOR inhibition by rapamycin. We also observed mitogen‐independent mTOR activity that is regulated by nutrient availability, and is significantly elevated in MZ cells relative to FO cells. These data define both similarities and differences in PI3K/mTOR signaling mechanisms in MZ and FO cells, and suggest that mTOR signaling can occur in the absence of PI3K activation to promote B cell responses to LPS.
Memory phenotype CD8+ T cells with innate function selectively develop in the absence of active Itk
Authors: Hu Jianfang , Sahu Nisebita , Walsh Elizabeth , August Avery
Published: August 2007

T cells with a memory‐like phenotype and possessing innate immune function have been previously identified as CD8+CD44hi cells. These cells rapidly secrete IFN‐γ upon stimulation with IL‐12/IL‐18 and are involved in innate responses to infection with Listeria monocytogenes. The signals regulating these cells are unclear. The Tec kinase Itk regulates T cell activation and we report here that a majority of the CD8+ T cells in Itk null mice have a phenotype of CD44hi similar to memory‐like innate T cells. These cells are observed in mice carrying an Itk mutant lacking the kinase domain, indicating that active Tec kinase signaling suppresses their presence. These cells carry preformed message for and are able to rapidly produce IFN‐γ upon stimulation in vitro with IL‐12/IL‐18, and endow Itk null mice the ability to effectively respond to infection with L. monocytogenes or exposure to lipopolysaccharides by secretion of IFN‐γ. Transfer of these cells rescues the ability of IFN‐γ null mice to reduce bacterial burden following L. monocytogenes infection, indicating that these cells are functional CD8+CD44hi T cells previously detected in vivo. These results indicate that active signals from Tec kinases regulate the development of memory‐like CD8+ T cells with innate function.
Back to the beginning – the quest for thymic epithelial stem cells
Authors: Swann Jeremy B. , Boehm Thomas
Published: August 2007

Stem cell‐based therapies hold much promise for the rejuvenation of aged or damaged tissues; however, before such cells can be used therapeutically, they must first be accurately identified. In this issue of the European Journal of Immunology it is reported that MTS24, a marker previously associated with progenitor cells of the thymic epithelium, fails to accurately identify epithelial cell populations with the ability to reconstitute a functional thymus. This finding demonstrates that much progress needs to be made before thymic epithelial stem cells can be harnessed for clinical benefit.

See accompanying article: http://dx.doi.org/10.1002/eji.200737275
Organometallic and Classical Coordination Sites in Highly Preorganized Pyrazolate‐Based Hybrid Systems: The Mn/Ni Case
Authors: Zhang Huaxin , Dechert Sebastian , Linseis Michael , Winter Rainer F. , Meyer Franc
Published: August 2007

A series of unsymmetric heterodinuclear Mn/Ni complexes is reported in which an organometallic CpMn(CO)2 fragment and a classical Werner‐type nickel(II) subunit are arranged in close proximity by means of a bridging pyrazolate. The two metalloligand scaffolds (1 and 2) employed differ in the chelate size of the tripodal tetradentate {N4} binding site for nickel. Molecular structures have been determined for (1‐H)Ni(NO3) (3), (2‐H)Ni(NO3) (4), and (2‐H)Ni(OAc) (5). Comparison with the molecular structures of the related Mn/Mn, Mn/Co, and Mn/Zn systems confirms that structural flexibility is greater for the complexes based on ligand 2 due to the longer chelate arms. According to IR and UV/Vis spectroelectrochemistry, oxidation of the heterobimetallic systems is highly localized at the organometallic manganese site. Structural and spectroscopic features as well as trends for the redox potentials of the MnI/MnII couple suggest that ligand variations at the nickel(II) Werner‐type subunit exert only a small influence on the properties of the organometallic part. In contrast, reduction occurs at the nickel site and is strongly dependent on the anion present. The effects at the organometallic CpMn(CO)2 subunit upon reduction of the proximate nickel ion are most pronounced for 5. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Methylation of a Terdentate Schiff Base Ligand NNO‐Coordinated to Palladium with Nitromethane
Authors: Arnaiz Ana M. , Carbayo Arancha , Cuevas José V. , Diez Virginia , García‐Herbosa Gabriel , González Roberto , Martínez Abigail , Muñoz Asunción
Published: August 2007

The reaction of the complex [Pd(κ3‐NN′O)CH3] [NN′O = 2‐Py‐CH=N‐(o‐C6H4)O–] (1a) with nitromethane affords a mixture of 2a and 2b. In this reaction methylation of the ligand takes place. These complexes display exchange equilibrium in solution. The methylation reaction is proposed to occur through nucleophilic attack of the nitronate anion on the iminic carbon atom. DFT calculations are presented in order to support a part of the mechanism and these calculations show that the participation of water in the migration of a proton is important. The crystal structure of the derivative productafter spontaneous release of methane (3) is presented as well. Attempts to extend the reaction to other nitroalkanes resulted in a mixture of complexes that was not easy to characterize. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Phospha‐ and Arsaalkenes RE=C(NMe2)2 (E = P, As) as Novel Phosphinidene‐ and Arsinidene‐Transfer Reagents
Authors: Weber Lothar
Published: August 2007

Phosphinidenes (phosphanylidenes) (RP) are electronically and coordinatively unsaturated phosphorus compounds, which, as six‐electron species, are formally analogous to the more familiar carbenes and nitrenes. In contrast to carbenes (CR2), the extremely reactive phosphinidenes cannot be isolated without decomposition. Thus, our knowledge on phosphinidenes is mainly limited to trapping reactions and quantum‐chemical calculations. There are a number of synthetic methods for phosphinidenes available, for example photolysis or thermolysis of cyclic phosphanes and oligophosphanes, dehalogenation of organodihalophosphanes, liberation of dinitrogen from organodiazidophosphanes, or decomposition of phosphoranylidene‐σ4‐phosphoranes (arylP=PMe3). A plethora of information is available on the generation of highly reactive terminal phosphinidene complexes [RPW(CO)5] and their chemistry. Many of these methods suffer from comparatively harsh conditions (strong base, heat, etc.) which limit their preparative use. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Straightforward Synthesis of Donor‐Stabilised Phosphenium Adducts from Imidazolium‐2‐carboxylate and Their Electronic Properties
Authors: Azouri Michèle , Andrieu Jacques , Picquet Michel , Richard Philippe , Hanquet Bernard , Tkatchenko Igor
Published: August 2007

Cationic imidazolium‐2‐phosphanes were obtained by the addition of a chlorophosphane (R2PCl, R = Ph, iPr or Cy) to 1,3‐dimethylimidazolium‐2‐carboxylate without the need for a purification step. An additional anion exchange reaction with KPF6 led to the corresponding halide‐free ligands in excellent yields. The molecular structure of one of them was examined both in the solid state and in solution. The lone pair of electrons on the phosphorus atom is not delocalised to the imidazolium fragment and thus remains available for further metal coordination. As such compounds can be described as phosphenium cations stabilised by a N‐heterocarbene donor base, the electronic properties of the Lewis acceptor phosphorus centre was evaluated upon nickel tricarbonyl coordination, and the properties are surprisingly similar to those found for phosphites. The stronger π‐acceptor character of these imidazolium‐2‐phosphanes relative to that of neutral tertiary phosphanes can thus explain the higher catalytic activities observed with the corresponding rhodium complexes in styrene hydroformylation reactions. Additionally, a preliminary study of platinum coordination chemistry indicated that the steric demand of 1,3‐dimethylimidazolium‐2‐phosphanes is comparable to mixed arylalkylphosphanes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Evidence for Ligand‐Centered Reactivity of a 17e Radical Cationic 2H‐Azaphosphirene Complex
Authors: Helten Holger , Neumann Christoph , Espinosa Arturo , Jones Peter G. , Nieger Martin , Streubel Rainer
Published: August 2007

Reactions of 2H‐azaphosphirene complex1with electron‐rich nitrile derivatives2a–ein the presence of substoichiometric amounts of ferrocenium hexafluorophosphate yielded regioselectively 2H‐1,4,2‐diazaphosphole complexes3a–eunder mild conditions. The dependence of the reaction on the amount of ferrocenium hexafluorophosphate is discussed. In the reactions of1with electron‐poor nitrile derivatives HCN (2f), EtOC(O)CN (2g), and C6F5CN (2h), byproducts possessing a P–F bond are formed, which indicates that the hexafluorophosphate anion is involved in the reaction course. Apart from NMR spectroscopic (3a–f) and X‐ray data (3b,3d–e), a detailed DFT study is included that provides first insight into the reaction pathway.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Calorimetry of edible oils: Isothermal freezing curve for assessing extra‐virgin olive oil storage history
Authors: Angiuli Marco , Ferrari Carlo , Righetti Maria Cristina , Tombari Elpidio , Salvetti Giuseppe
Published: August 2007

The calorimetric method described here investigates the solid‐liquid phase transitions in a Tuscan extra‐virgin olive oil in order to evaluate the changes induced by light exposition. The parameters of the freezing and the melting curves show high sensitivity to oil quality degradation, in agreement with the data from routine tests at disposal. Possible applications of the method are discussed.
Oxidative Nucleophilic Substitution (SNOx) of the Benzylic Position as a Tunable Synthesis of Tetrahydroisoquinoline Natural Alkaloid Analogues
Authors: Aubry Sylvain , Pellet‐Rostaing Stéphane , Lemaire Marc
Published: August 2007

Synthetic investigations of 1,3‐dichloro‐5,6‐dicyanobenzoquinone‐mediated benzylic oxidation is reported for the synthesis of natural alkaloid analogues. Extensive explorations of the oxidative nucleophilic substitution of the benzylic position of β‐phenylethylamine derivatives and the synthesis of functionalized tetrahydroisoquinolines of ecteinascidin 743 precursors have been carried out. Starting from L‐DOPA, a tunable oxazolidinone group was installed under oxidative benzylic conditions. This derivative 13 was submitted to benzylic oxidation reactions using a wide range of carboxylic acids and subsequent chemical transformations of these compounds were attempted. Moreover, an efficient synthesis of an aromatic ketone derivative 20 was achieved and gave rise to tetrahydroisoquinoline 24 through a direct Pictet–Spengler cyclisation reaction. Subsequently, 24 was transformed into functionalized α‐amino alcohols 31a and 31b, precursors of ecteinascidin 743 analogues. In addition, in order to assess the viability of our synthetic strategy, the reaction of 24 with methyl thioglycolate was performed and the stereoselectivity confirmed by X‐ray analysis of 33a. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Oreacerebrosides: Bioactive Cerebrosides with a Triunsaturated Sphingoid Base from the Sea Star Oreaster reticulatus
Authors: Costantino Valeria , de Rosa Caterina , Fattorusso Ernesto , Imperatore Concetta , Mangoni Alfonso , Irace Carlo , Maffettone Carmen , Capasso Domenica , Malorni Livia , Palumbo Rosanna , Pedone Carlo
Published: August 2007

The sea star Oreaster reticulatus contains, along with the known ophidiacerebrosides C–E, nine new glycosphingolipids named oreacerebrosides A–I. Their structures were elucidated by a combination of spectroscopic methods and chemical degradation. All compounds contain a 4,8,10‐triunsaturated sphingoid base. Oreacerebrosides A–C have a β‐glucopyranoside as the sugar residue, as found in ophidiacerebrosides C–E and in all known compounds of this type; in contrast, oreacerebrosides D–I are the first examples of β‐galactosylceramides containing this unusual sphingoid base. Four representative glycosphingolipids were tested for cytotoxic activity on rat glioma C6 cells and were shown to be mildly cytotoxic; the glucosylceramides were more active than the galactosylceramides. In addition, oreacerebroside I, but not ophidiacerebroside E, was shown to exert proangiogenic activity and was able to increase VEGF‐induced human endothelial cell proliferation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Highly Selective Synthesis of Enantiopure (S,E)‐α,β‐Unsaturated γ‐Amino Esters Through a Sequential Reaction of Ethyl Dibromoacetate with α‐Amino Aldehydes Promoted by Chromium Dichloride
Authors: Concellón José M. , Méjica Carmen
Published: August 2007

A sequential reaction of ethyl dibromoacetate with various enantiopure N,N‐dibenzyl‐ or N‐Boc‐α‐amino aldehydes (derived from natural α‐amino acids), promoted by chromium dichloride, afforded optically active (S,E)‐α,β‐unsaturated γ‐amino esters. The C=C double bond was generated with total or very high E‐selectivity and the (S,E)‐α,β‐unsaturated γ‐amino esters were obtained with complete enantiomeric purity, except from N‐Boc‐phenylalaninal (as determined by chiral HPLC). A mechanism is proposed to explain this transformation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of Pinguisane‐Type Sesquiterpenoids Acutifolone A, Pinguisenol, and Bisacutifolones by a Diels–Alder Dimerization Reaction
Authors: Shiina Junichi , Oikawa Masataka , Nakamura Kensuke , Obata Rika , Nishiyama Shigeru
Published: August 2007

The total synthesis of pinguisane‐type sesquiterpenoids, acutifolone A (1) and pinguisenol (2), has been achieved by using the Mukaiyama aldol reaction as the key step. The intermolecular Diels–Alder reaction of these monomeric natural products successfully led to stereoselective dimerization, leading to bisacutifolones A (3) and B (4). Theoretical calculations revealed that the dimerization reaction proceeded through the most stable transition state. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Novel Approach to Stabilize Unstable Molecular Wires by Simultaneous Rotaxane Formation – Synthesis of Inclusion Complexes of Oligocarbynes with Cyclic Host Molecules
Authors: Sugiyama Jiro , Tomita Ikuyoshi
Published: August 2007

An effective method to stabilize oligocarbynes as a modelfor polycarbyne by the simultaneous complexation withα‐cyclodextrin (α‐CD) is described. 1,12‐Bis(9‐phenanthryl)‐1,3,5,7,9,11‐dodecahexayne possessing one or two α‐CD molecules was prepared by the oxidative coupling reaction of the corresponding triyne in the presence of α‐CD. The resulting rotaxanes proved to be stable enough in comparison with the corresponding free oligoynes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Highly Efficient Direct Alkylation of Activated Methylene by Cycloalkanes
Authors: Zhang Yuhua , Li Chao‐Jun
Published: August 2007

A simple FeCl2‐catalyzed C–C bond formation by direct alkylation of activated methylene by using simple cycloalkanes was developed. Several kinds of alkanes were found to react with phenyl β‐ketone ester and diketone compounds to afford alkylated 1,3‐dicarbonyl compounds in 10–88 % yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Direct Electrochemistry of Hemoglobin Immobilized on Carbon‐Coated Iron Nanoparticles for Amperometric Detection of Hydrogen Peroxide
Authors: Zhang Hai‐Li , Zou Xiao‐Zhi , Lai Guo‐Song , Han De‐Yan , Wang Fang
Published: August 2007

A novel method for preparation of hydrogen peroxide biosensor was presented based on immobilization of hemoglobin (Hb) on carbon‐coated iron nanoparticles (CIN). CIN was firstly dispersed in a chitosan solution and cast onto a glassy carbon electrode to form a CIN/chitosan composite film modified electrode. Hb was then immobilized onto the composite film with the cross‐linking of glutaraldehyde. The immobilized Hb displayed a pair of stable and quasireversible redox peaks and excellent electrocatalytic reduction of hydrogen peroxide (H2O2), which leading to an unmediated biosensor for H2O2. The electrocatalytic response exhibited a linear dependence on H2O2 concentration in a wide range from 3.1 μM to 4.0 mM with a detection limit of 1.2 μM (S/N=3). The designed biosensor exhibited acceptable stability, long‐term life and good reproducibility.
Multistrip Western blotting to increase quantitative data output
Authors: Aksamitiene Edita , Hoek Jan B. , Kholodenko Boris , Kiyatkin Anatoly
Published: August 2007

The qualitative and quantitative measurements of protein abundance and protein modification states are essential in understanding their role in diverse cellular processes. Traditional Western blotting technique, though sensitive, is prone to produce substantial errors and is not readily adapted to high‐throughput technologies. We propose a modified immunoblotting procedure, which is based on simultaneous transfer of proteins from multiple gel‐strips onto the same membrane, and is compatible with any conventional gel electrophoresis system. As a result, the data output per single blotting cycle can readily be increased up to ten‐fold. In contrast to the traditional “one protein detection per electrophoresis cycle”, this procedure allows simultaneous monitoring of up to nine different proteins. In addition to maintaining the ability to detect picogram quantities of protein, the modified system substantially improves data accuracy by reducing signal errors by two‐fold. Multistrip Western blotting procedure allows making statistically reliable side‐by‐side comparisons of different or repeated sets of data. Compared to the traditional methods, this approach provides a more economical, reproducible, and effective procedure, facilitating the generation of large amounts of high‐quality quantifiable data.
An optimized procedure for solubilization, reduction, and transfer of human breast cancer membrane‐enriched fraction by 2‐DE
Authors: Ruan Yusong , Wan Mingxi
Published: August 2007

The separation of integral and peripheral membrane proteins is still a challenge, although many achievements have been made in the 2‐DE‐based membrane proteomics. Using a human breast cancer cell line, MCF‐7, we investigated the influences of Tris, reducing reagents, cup loading, and SDS on membrane protein solubilization and separation by 2‐DE. The addition of Tris to the sample solution improved the solubilization of the membrane‐enriched fraction, and the best‐quality gel patterns were obtained at 20 mM Tris. Tributylphosphine (TBP), a reducing agent, was not optimum in the 2‐DE process because it not only decreased the solubilization of hydrophobic proteins but also caused some proteins, such as hsp60, prohibitin, and actin, to be resolved to a string of spots. However, when combined with DTT, TBP could improve the resolution of 2‐DE patterns. Cup loading significantly facilitated the entrance of membrane proteins into IPG strips and over 1000 protein spots with high resolution were visualized. Adopting this strategy, an ATP synthase α chain was resolved into two adjacent spots for the first time in 2‐DE gel patterns through the adding DTT in the middle of the IEF. A high SDS concentration in the equilibration buffer enhanced the transfer and increased the staining intensity of ˜50% of the protein spots in the gels, but also resulted in losses of some spots.
Microscale immunoaffinity SPE and MEKC in fast determination of testosterone in male urine
Authors: Amundsen Lotta K. , Nevanen Tarja K. , Takkinen Kristiina , Rovio Stella , Sirén Heli
Published: August 2007

Conventional methods for the determination of testosterone in body fluids typically suffer from poor recovery, lack of specificity, complex sample pretreatment, or the need for derivatization. Here, a simple, specific, and fast analysis method for testosterone was developed, with a methodology based on testosterone‐specific immunoaffinity SPE (IA‐SPE) and subsequent analysis by partial filling MEKC (PF‐MEKC). An immunosorbent consisting of a recombinant antitestosterone Fab fragment covalently attached to activated Sepharose was prepared. IA‐SPE and PF‐MEKC were set up in hyphenated and off‐line constructions, and the applicability of the two constructions in analysis of testosterone in male urine was investigated. The results obtained with the hyphenated construction proved to be only indicative of the presence of testosterone. The off‐line IA‐SPE and PF–MEKC construction, however, was successfully used in the determination of free testosterone in male urine samples after enzymatic hydrolysis of the glucuronide conjugates. Except for the hydrolysis reaction, no sample pretreatment was required. After hydrolysis, the overall analysis time per sample was only 14 min. The off‐line IA‐SPE and PF‐MEKC method proved to be robust, sensitive (LOQ 35 μg/L), and specific, enabling separation of testosterone from four related steroids. Thus, it provides attractive features when compared to traditional methods for determination of testosterone in male urine.
Protein‐bound glutathione measurement in cultured cells by CZE with LIF detection
Authors: Zinellu Angelo , Sotgia Salvatore , Posadino Anna Maria , Pasciu Valeria , Zinellu Elisabetta , Usai Maria Franca , Scanu Bastianina , Chessa Roberto , Gaspa Leonardo , Tadolini Bruna , Deiana Luca , Carru Ciriaco
Published: August 2007

Protein modification due to S‐glutathio(ny)lation, usually a reversible process in intact cells, arises interest as a possible mode of regulatory events that may potentially modify a large number of cellular processes. However, since less than 1% of the total protein is S‐thiolated in resting cells, high sensitivity methods are required for its evaluation. We set up a new method by CE with LIF detection that allows to measure all forms of intracellular GSH involved in the process. For total and reduced glutathione, cell lysates were rapidly derivatized by 5‐iodoacetoamidofluorescein (5‐IAF), a selective reagent which traps thiol groups, thus minimizing auto‐oxidation. Derivatized samples were separated in a 47 cm×75 μm id capillary by using 7 mmol/L sodium phosphate at pH 11.6. For the evaluation of S‐glutathio(ny)lation, intracellular proteins from cell lysates were precipitated and washed to eliminate free GSH. After protein resuspension with NaOH and reduction treatment with tri‐n‐butylphosphine (TBP), the freed GSH was dried in a vacuum concentrator and directly dissolved in the derivatization mixture. GSH–IAF adduct was detected in a 6 mmol/L sodium phosphate, 3 mmol/L boric acid, and 75 mmol/L N‐methylglucamine run buffer in less than 5 min. The high sensitivity ensured by 5‐IAF use and sample concentration, allowed to quantify GSH at levels as low as 5 nmol/L, value suitable for the evaluation of protein S‐glutathio(ny)lation. The method suitability was checked both in HUVEC and ECV304 cultured cells.
Dynamic modification of poly(methyl methacrylate) chips using poly(vinyl alcohol) for glycosaminoglycan disaccharide isomer separation
Authors: Zhang Yong , Ping Guichen , Kaji Noritada , Tokeshi Manabu , Baba Yoshinobu
Published: August 2007

We describe a microchip electrophoresis (MCE) method for the assay of unsaturated disaccharides of chondroitin sulfates, dermatan sulfates, and hyaluronic acid (HA). Poly(vinyl alcohol) (PVA) could be irreversibly adsorbed onto poly(methyl methacrylate) (PMMA) substrates and this approach was applicable for dynamic coating. The characteristics of the PMMA surface with PVA coating were evaluated in terms of the wettability, EOF, and adsorption of 2‐aminoacridone (AMAC)‐labeled disaccharide. The water contact angle decreased from ˜73° on a pristine PMMA surface to ˜37.5° on a PVA‐coated surface, indicating that the PVA coating increased hydrophilicity. EOF was reduced approximately twofold and was relatively stable. Scanning electron microscopy and fluorescence microscopy images showed that adsorption of AMAC‐labeled disaccharides was dramatically suppressed. Using the PVA coating, baseline separation of two pairs of glycosaminoglycan (GAG) disaccharide isomers, ΔDi‐diSB/ΔDi‐diSD and ΔDi‐0S/ΔDi‐HA, was achieved in Tris‐borate buffer within 130 s by MCE.
Base excision repair pathway is involved in the repair of lesions generated by flavonoid‐enriched fractions of pepper tree (Schinus terebinthifolius, Raddi) stem bark
Authors: Varela‐Barca Francisco Napoleão Túlio , Agnez‐Lima Lucymara Fassarella , de Medeiros Sílvia Regina Batistuzzo
Published: August 2007

Cell‐free and bacterial assays indicate that flavonoid‐enriched fractions and the flavonoids of pepper tree stem bark from Schinus terebinthifolius Raddi have genotoxic rather than antigenotoxic properties. In the present report, we have examined the ability of flavonoid‐enriched fractions to damage plasmid DNA and the repair pathways involved in the recognition of these DNA lesions. High concentrations of two flavonoid‐enriched fractions were able to break phosphodiester bonds in DNA. In addition, studies using bacterial strains deficient in nucleotide excision repair and base excision repair (BER) enzymes indicated that the flavonoid‐enriched fractions generated lesions that were substrates for enzymes belonging to the BER pathway. In addition, in vitro studies indicated that the DNA damage produced by the flavonoid‐enriched fractions was also a substrate for exonuclease III and that the phosphodiester breakage was amplified by copper ions. These results indicate that flavonoids from the pepper tree (Schinus terebinthifolius, Raddi) generate lesions on DNA that are potential targets of FPG and MutY glycosylase from the BER pathway. Chromatographic and spectral analyses helped to support the hypothesis that the flavonoids of the Brazilian pepper tree bark are the main factors involved in the fraction's damage potential. The isolated flavonoids from Fraction II were also tested in vitro and support the oxidative damage potential of these flavonoids. Environ. Mol. Mutagen., 2007. © 2007 Wiley‐Liss, Inc.
Detection of local and global outliers in mapping studies
Authors: Ainsworth L. M. , Dean C. B.
Published: August 2007

In mapping studies, extreme risk areas may arise in proximity to one another in a smooth spatial surface. They may also arise as isolated ‘hotspots’ or ‘lowspots’, which are quite distinct from those of neighbouring sites. In this paper, we develop spatial methods which encompass both types of extreme risks. The former is modelled by a spatially smooth surface using a conditional autoregressive model; the latter is addressed with the addition of a discrete clustering component, which offers the flexibility of accommodating extreme isolated risks and is not limited by spatial smoothness. The autoregressive component incorporates the spatially correlated risk as a baseline surface, acknowledging that environmental activity, often spatially correlated, influences risk responses. The discrete component identifies hotspots/lowspots of activity beyond the spatially correlated baseline risk surface. Both types of extreme risk are important, but isolated extremes may provide insight into areas with potential of being a centre for future spatially correlated extreme risks. Hence these may be particularly important in terms of surveillance. A Bayesian approach to inference is employed and graphical techniques for isolating extremes are illustrated. Model assessment is conducted via cross‐validation posterior predictive checks. Three examples demonstrate the utility of the methods and case studies show the procedures to be useful for pinpointing extreme risks. In addition, sensitivity to priors is investigated. Copyright © 2007 John Wiley & Sons, Ltd.