bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of c‐Jun as a critical mediator for the intracrine 24 kDa FGF‐2 isoform‐induced cell proliferation
Authors: Hortala Marylis , Estival Agnes , Pradayrol Lucien , Susini Christiane , Clemente François
Published: December 2004

Tumor cells frequently synthesize an N‐terminally extended the FGF‐2 isoform of 24 kDa devoid of signal peptide but that contains a functional nuclear localization sequence (NLS). Although the signaling pathways elicited by secreted FGF‐2 are well described, the molecular mechanisms involved in the growth promoting action of nuclearized 24 kDa FGF‐2 remain unknown. The cancer cell line AR4‐2J was engineered to stably express only the 24 kDa FGF‐2 isoform and cDNA microarrays were used to identify targets implicated in the intracrine‐induced cell proliferation. Levels of 27 transcripts were found either upregulated or downregulated compared to control cells. Among the 18 upregulated genes was c‐jun, which is often involved in cell proliferation. Real‐time PCR and Western blot analyses confirmed c‐jun induction at both mRNA and protein levels. The c‐jun antisense oligonucleotide strategy pointed out the involvement of c‐Jun in the 24 kDa FGF‐2‐induced cell proliferation. The mitogenic effect was found to depend on ERK pathway and not on phosphoinositide 3‐kinase, p38 MAPK, c‐Jun NH2‐terminal kinase signal transducers. In addition, the MEK inhibitor PD98059 reduced the 24 kDa FGF‐2‐dependent c‐Jun level. These data show that intracrine FGF‐2‐mediated regulation of cell growth involves ERK activation and consequent c‐Jun expression. Thus, despite its incapacity to be secreted, the intracellular‐localized 24 kDa FGF‐2 can activate a growth‐related signaling pathway normally elicited by cell surface receptors. © 2004 Wiley‐Liss, Inc.
Exosomes: A new delivery system for tumor antigens in cancer immunotherapy
Authors: Cho Jung‐Ah , Yeo Dong‐jun , Son Hye‐Youn , Kim Hyun‐Wha , Jung Dae‐Sun , Ko Jae‐Kyun , Koh Jason Soonju , Kim Yong‐Nyun , Kim Chul‐Woo
Published: December 2004

Exosomes are small membrane vesicles that are released into the extracellular environment during fusion of multivesicular bodies with plasma membrane. Exosomes are secreted by various cell types including hematopoietic cells, normal epithelial cells and even some tumor cells. They are known to carry MHC class I, various costimulatory molecules and some tetraspanins. Recent studies have shown the potential of using native exosomes as immunologic stimulants. Here, we demonstrate a novel means of using exosomes engineered to express a specific tumor antigen to generate an immune response against tumors. We expressed a target tumor antigen, human MUC1 (hMUC1), in 2 MHC type‐distinct mouse cell lines, CT26 and TA3HA. Analysis of exosomes purified from these cells revealed that exosomes contained the target MUC1 antigen on their surfaces as well as other well‐described exosomal proteins, including Hsc70 and MHC class I molecules. In addition, both autologous and allogenic exosomes were able to stimulate the activation of immune cells and suppress hMUC1‐expressing tumor growth in a MUC1‐specific and dose‐related manner. Therefore, these data suggest that exosomes can be engineered from tumor cell lines to deliver a target immunogen capable of inducing an effective immune response and that they may represent a new cell‐free tumor vaccine. © 2004 Wiley‐Liss, Inc.
Reproductive and hormonal factors and risk of brain tumors in adult females
Authors: Hatch Elizabeth E. , Linet Martha S. , Zhang Jianying , Fine Howard A. , Shapiro William R. , Selker Robert G. , Black Peter M. , Inskip Peter D.
Published: December 2004

Causes of brain tumors are largely unknown, and there is an urgent need to identify possible risk factors. Several observations point to a possible role of reproductive hormones, but few epidemiologic studies have examined whether reproductive factors, such as age at menarche and parity, are associated with brain tumor risk. We conducted a multi‐center case‐control study of newly diagnosed glioma (n = 212) and meningioma (n = 151) and frequency‐matched controls (n = 436) in women from hospitals in Phoenix, Arizona; Boston, Massachusetts; and Pittsburgh, Pennsylvania between 1994 and 1998. Research nurses interviewed patients regarding potential risk factors for brain tumors, including reproductive factors and hormone use. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Risk of glioma increased with older age at menarche [OR = 1.90 (95% CI = 1.09–3.32) for age at menarche ≥14 vs. <12 years]. Early age at first birth was associated with reduced risk of glioma [OR = 0.43 (95% CI = 0.23–0.83) for a first birth before age 20 vs. nulliparity], but there was little effect of number of births. Exogenous hormone use was also associated with a lower risk of glioma, but risks did not vary systematically according to duration of use or age at first use. Possibly owing to low statistical power, there were few noteworthy associations between meningioma and reproductive factors, other than a nonsignificant (p = 0.09) trend of increasing risk with increasing age at menopause. The findings suggest that hormonal exposures early in life may be associated with risk of glioma, but the evidence is inconsistent and does not point clearly to a specific causal or protective hypothesis. © 2004 Wiley‐Liss, Inc.
Mammaglobin a in breast cancer: Existence of multiple molecular forms
Authors: O'Brien Neil A. , O'Donovan Norma , Ryan Bríd , Hill Arnold D.K. , McDermott Enda , O'Higgins Niall , Duffy Michael J.
Published: December 2004

Existing serum‐based markers for breast cancer all lack organ specificity. Mammaglobin A (MGA) is a 93 amino acid protein expressed almost exclusively in breast tissue. The aim of our study was to investigate the different forms of MGA protein in fibroadenomas and breast carcinomas. MGA protein was measured by Western blotting in 132 breast cancers, 29 fibroadenomas and 14 nonbreast tissues. MGA protein in breast tissue was found to exist in 2 main forms. These forms migrated with approximate molecular masses of 18 and 25 kDa. Both forms of MGA were detected more frequently in breast carcinomas compared to fibroadenomas. The high molecular weight form of MGA but not the low molecular weight form was found more frequently in hormone receptor‐positive than in receptor‐negative cancers. Furthermore, an inverse relationship was found between the high molecular weight form of MGA and both tumour grade and proliferation index. No significant correlation was found between the MGA proteins and either tumor size or nodal status. Our results show that MGA protein exists in 2 main forms in breast tissue. As the high molecular weight form correlated positively with hormone receptors and negatively with tumor grade and proliferation rate, its presence is likely to be associated with a favourable prognosis for breast cancer. As expression of MGA is almost breast specific, it is a promising marker for breast cancer. Its most immediate use is likely to be in detecting micrometastases from breast cancer. © 2004 Wiley‐Liss, Inc.
Anti‐proliferative and proapoptotic effects of (−)‐epigallocatechin‐3‐gallate on human melanoma: Possible implications for the chemoprevention of melanoma
Authors: Nihal Minakshi , Ahmad Nihal , Mukhtar Hasan , Wood Gary S.
Published: December 2004

Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer‐related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A‐375 amelanotic malignant melanoma and Hs‐294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin‐3‐gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose‐dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki‐67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC‐1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti‐apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases ‐3, ‐7 and ‐9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose‐dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki‐cyclin‐cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma. © 2004 Wiley‐Liss, Inc.
Prescription drug use and risk of acute myeloid leukemia by French‐American‐British subtype: Results from a Los Angeles County case‐control study
Authors: Pogoda Janice M. , Katz Jonathan , McKean‐Cowdin Roberta , Nichols Peter W. , Ross Ronald K. , Preston‐Martin Susan
Published: December 2004

Chemotherapy is a well‐established risk factor for acute myeloid leukemia (AML) but little is known about other prescription drugs and AML risk. We report data from a population‐based Los Angeles County study in which 299 matched case‐control pairs had complete data on prescription drug use and 88% of cases were subtyped according to the French‐American‐British (FAB) criteria. Cases were diagnosed between 1987 and 1994. Prescription nonsteroidal anti‐inflammatory drug (NSAID) use for at least 4 weeks in the 2 to 10 years before diagnosis was associated with decreased risk (odds ratio = 0.5, 95% confidence interval = 0.3, 1.0; p = 0.04) with dose‐response most evident for FAB subtype M2 (OR = 0.6, CI: 0.1, 2.9 for duration ≤6 months; OR = 0.2, CI: 0.0, 1.6 for >6 months). For subtype M4, ORs increased with increasing duration of benzodiazepine use in the 2 to 10 years before diagnosis (OR = 1.5, CI: 0.3, 9.0 for ≤6 months vs. OR = 5.0, CI: 0.6, 42.8 for >6 months). These results suggest that prescription drugs other than chemotherapy may have FAB subtype‐specific effects on AML risk. © 2004 Wiley‐Liss, Inc.
Bortezomib is an efficient agent in plasma cell leukemias
Authors: Esparís‐Ogando Azucena , Alegre Adrián , Aguado Beatriz , Mateo Gema , Gutiérrez Norma , Bladé Joan , Schenkein David , Pandiella Atanasio , San Miguel Jesús F.
Published: December 2004

Plasma cell leukemia (PCL) represents the most aggressive form of monoclonal gammopathy for which new treatment approaches are needed. Here we report the effect of Bortezomib on cells from 4 patients with PCL, as well as the in vivo efficacy on a patient with secondary PCL. Bortezomib reduced PCL numbers and was more efficient in cell growth inhibition than dexamethasone or doxorubicin. Treatment with Bortezomib induced procaspase‐3 and poly(ADP‐ribose) polymerase cleavage and decreased the amount of extracellular signal regulated kinase (Erk1/2) and phospho‐Erk1/2. However, Bortezomib did not substantially affect the levels of the Erk1/2 upstream activating kinase (MEK1), p27 or p21. Finally, we had the opportunity to use Bortezomib in a heavily pretreated patient with overt secondary PCL and severe anemia and thrombocytopenia. Following Bortezomib treatment, circulating plasma cells disappeared; what is more striking, the peripheral blood counts returned to normal, becoming transfusion‐independent. These data support the inclusion of Bortezomib in the therapeutic armamentarium of PCL. © 2005 Wiley‐Liss, Inc.
c‐myc‐induced hepatocarcinogenesis in the absence of IGF‐I receptor
Authors: Cadoret Axelle , Desbois‐Mouthon Christèle , Wendum Dominique , Leneuve Patricia , Perret Christine , Tronche François , Housset Chantal , Holzenberger Martin
Published: December 2004

Numerous tumours, including hepatocarcinomas, produce IGFs, and some depend on these growth factors in a paracrine or autocrine fashion. We have shown that c‐myc‐induced experimental hepatocarcinogenesis is associated with enhanced production of IGF‐II. To assess the role of the IGF‐I receptor (IGF‐IR) in hepatocarcinogenesis, we generated conditional mutant mice that overexpressed c‐myc and were knocked out for IGF‐IR specifically in the liver. We compared these mice with littermate controls that also overexpressed c‐myc but had wild‐type IGF‐IR alleles. We found that the pretumoral phase, induced by early c‐myc expression and characterised by increased cell proliferation, was largely unaffected by the lack of IGF‐IR. To our further surprise, hepatocellular carcinomas (HCCs) lacking IGF‐IR readily developed and progressed at the same rate as control HCCs. At 9 months, all c‐myc transgenic mice displayed well‐differentiated multifocal tumours, regardless of whether their livers—and their tumours—were able to produce IGF‐IR. Levels of IRS‐1 and IRS‐2 were elevated in all tumours in the presence or absence of IGF‐IR, suggesting that the signalling pathway downstream of IGF‐IR is activated via IGF‐IR‐independent mechanisms in HCC. In conclusion, the deregulation of IGF signalling pathways, which often occurs during liver tumorigenesis, does not necessarily require IGF‐IRs, and hepatic IGF‐IR alone may not play a determinant role in c‐myc‐induced hepatocarcinogenesis. © 2004 Wiley‐Liss, Inc.
Improving outcomes for poorly responding clients: The use of clinical support tools and feedback to clients
Authors: Harmon Cory , Hawkins Eric J. , Lambert Michael J. , Slade Karstin , Whipple Jason S.
Published: December 2004

We present two methods of enhancing outcome and preventing treatment failure in psychotherapy. The first involves providing therapists with a decision tree and several assessment measures for clients who are not having a positive response to psychotherapy. The organization of the decision tree and the selection of measures were based on results from psychotherapy outcome studies. The second method involves providing clients with feedback on their progress throughout the course of treatment. Both methods of providing feedback enhanced treatment outcomes and representative studies are reviewed. Use of these methods is recommended for application in routine practice. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Implementation of a feedback system in a managed care environment: What are patients teaching us?
Authors: Brown George S. , Jones Edward R.
Published: December 2004

Lessons about patient treatment response from a large‐scale outcomes management project are summarized. More than 7,000 clinicians contributed outcome data. Overall, the data demonstrated that patients who have clinical levels of psychological distress and impairment showed a relatively rapid response to treatment. Furthermore, although it appears that the duration and intensity of treatment vary widely from case to case, clinicians and patients make sound judgments as to how much and what kind of treatment is appropriate. Results supported the conclusion that the most effective method to manage costs is to ensure that each patient receive effective care. There are large and stable differences in the effectiveness of clinicians, and outcomes can be improved by referring patients to effective clinicians. The data also suggested that patients who had a poor initial response to treatment eventually had positive outcomes, provided that they remained engaged in treatment. This finding suggests that outcomes can be improved by identifying at‐risk patients and proactively keeping them engaged in treatment. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Effect of the promoter and support on the catalytic activity of PdCeO2‐supported catalysts for CH4 combustion
Authors: Pecchi G , Reyes P , Zamora R , López T , Gómez R
Published: December 2004

A series of palladium–ceria‐supported catalysts prepared by the sol–gel method are characterized and their catalytic results are reported. It was found that the addition of ceria to alumina produces a highly dispersed catalyst when compared with their zirconia counterparts. However, the catalytic activity of the ceria zirconia series is higher, essentially due to the larger particle size of palladium. This result can be attributed to the structure‐sensitive reaction of the combustion of methane. Copyright © 2004 Society of Chemical Industry
Extremal solutions for nonlinear second order differential inclusions
Authors: Douka P. , Papageorgiou N. S.
Published: December 2004

We consider a nonlinear second order differential inclusion driven by the scalar p‐Laplacian and with nonlinear multivalued boundary conditions. Assuming the existence of an ordered pair of upper‐lower solutions and using truncation and penalization techniques together with Zorn's lemma, we show that the problem has extremal solutions in the order interval formed by the upper und lower solutions. We present some special cases of interest and show that our method applies also to the periodic problem. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hurwitz spaces of quadruple coverings of elliptic curves and the modulispace of abelian threefolds 𝒜3(1, 1, 4)
Authors: Kanev Vassil
Published: December 2004

We prove that the moduli space 𝒜3(1, 1, 4) of polarized abelian threefolds with polarization of type (1, 1, 4) is unirational. By a result of Birkenhake and Lange this implies the unirationality of the isomorphic moduli space 𝒜3(1, 4, 4). The result is based on the study the Hurwitz space ℋ︁4,n(Y) of quadruple coverings of an elliptic curve Y simply branched in n ≥ 2 points. We prove the unirationality of its codimension one subvariety ℋ︁04,A(Y) which parametrizes quadruple coverings π : X → Y with Tschirnhausen modules isomorphic to A–1, where A ∈ Picn/2Y, and for which π* : J(Y) → J(X) is injective. This is an analog of the result of Arbarello and Cornalba that the Hurwitz space ℋ︁4,n(ℙ1) is unirational. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Elliptic problems for the Dolbeault complex
Authors: Kytmanov A. , Myslivets S. , Schulze B.‐W. , Tarkhanov N.
Published: December 2004

The inhomogeneous$ \overline \partial $‐equation is an inexhaustible source of locally unsolvable equations, subelliptic estimates and other phenomena in partial differential equations. Loosely speaking, for the analysis on complex manifolds with boundary nonelliptic problems are typical rather than elliptic ones. Using explicit integral representations we assign a Fredholm complex to the Dolbeault complex over an arbitrary bounded domain in ℂn. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Wavelet bases and entropy numbers in weighted function spaces
Authors: Haroske Dorothee D. , Triebel Hans
Published: December 2004

The aim of this paper is twofold. First we prove that inhomogeneous wavelets of Daubechies type are unconditional Schauder bases in weighted function spaces of Bspq and Fspq type. Secondly we use these results to estimate entropy numbers of compact embeddings between these spaces. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Vorticity–vector potential formulations of the Stokes equations in the half‐space
Authors: Boulmezaoud Tahar Zamène , Medjden Mohamed
Published: December 2004

The main objective of this paper is to propose two vorticity–vector potential formulations of the Stokes problem in the half space of ℝ3. Weighted spaces are used for describing the behaviour at large distances.

On propose deux formulations de type vorticité–potentiel vecteur du problème de Stokes dans le demi‐espace de ℝ3. Les espaces de Sobolev avec poids sont utilisés pour décrire le comportement des fonctions à l'infini. Copyright © 2004 John Wiley & Sons, Ltd.
Piperidone derivative from Dalbergia sympathetica
Authors: Shanmugam Nagarajan N. , Priya Rao R , Narayanan Manoj C. , Gopalakrishnan Sethuraman M.
Published: December 2004

An alcoholic extract of Dalbergia sympathetica, on column chromatography, yielded a compound which analyzed for C6H11NO3 (M+ 145). The IR spectrum of the compound showed the presence of carbonyl and hydroxyl groups. PMR, 13C and DEPT NMR spectral studies of the compound showed the presence of one N‐methyl, two methine and two methylene groups. A quaternary carbon signal at δ 172.88 ppm was assigned to C‐2 carbonyl of the compound. From all the above observations and also from the HMQC 2D NMR spectrum, the compound was identified as 3, 6‐dihydroxy‐N‐methyl‐2‐piperidone. This is the first report of the natural occurrence of this compound from plant sources. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis and complete 1H, 13C and 15N NMR assignment of substituted isoxazolo[3,4‐d]pyridazin‐7(6H)‐ones
Authors: Dal Piaz V. , Graziano A. , Haider N. , Holzer W.
Published: December 2004

The synthesis and complete assignment of all hydrogen, carbon and nitrogen NMR signals of several new isoxazolo[3,4‐d]pyridazin‐7(6H)‐ones is reported. The spectroscopic characterization is extended to previously described analogues. Copyright © 2004 John Wiley & Sons, Ltd.
195Pt, 1H and 31P PGSE diffusion studies on platinum complexes
Authors: Nama Devendrababu , Anil Kumar P. G. , Pregosin Paul S.
Published: December 2004

The first example of the use of 195Pt PGSE diffusion data (D values) to recognize the solvent dependence of aggregation of the hexachloroplatinate dianion in Na2PtCl6 (1) and in H2PtCl6 (2) is reported. In water, the ions are separated; however, in methanol the D values suggest ion pairing and/or aggregation. Additional 1H and 31P diffusion data for organometallic Pt complexes trans‐PtX(Aryl)(L)2 (where L = PEt3 or PPh3) and Pt(C7H4O2)(L1)(L2) (where L1 and L2 = a variety of ligand types) reveal that phenyl phosphines afford relatively large hydrodynamic radii rh. The presence of a substituent on the aryl ligand of PtX(Aryl)(L)2 does not markedly affect the D values, whereas a substituent of similar size added to a PPh3 group in Pt(C7H4O2)(L1)(L2) markedly changes both D and rh values. There is only a small concentration dependence of the D values in PtX(Aryl)(L)2 on changing from 2 to 10 mM. Copyright © 2004 John Wiley & Sons, Ltd.
Excitability differences in lower‐limb motor axons during and after ischemia
Authors: Krishnan Arun V. , Lin Cindy S.‐Y. , Kiernan Matthew C.
Published: December 2004

Neuropathic diseases typically begin distally and spread proximally. Irrespective of the etiology, pathological investigations often indicate changes consistent with ischemia. In the present study, threshold tracking was used to investigate length‐dependent differences in ischemic susceptibility of lower‐limb axons in 6 healthy volunteers, with ischemia induced by a sphygmomanometer cuff inflated to 200 mm Hg and maintained for 13 minutes. Following stimulation of the peroneal nerve at the fibula neck, compound muscle action potentials were recorded proximally from tibialis anterior (TA) and distally from extensor digitorum brevis (EDB). During ischemia, excitability changes were consistent with nerve depolarization, with a greater reduction in threshold in EDB than TA. This reduction in threshold was associated with an increase in refractoriness, decrease in superexcitability, and prolongation of strength–duration time constant, consistent with axonal depolarization. With release of ischemia, reversal of these changes was associated with an increase in threshold, greater in EDB than TA, indicating axonal hyperpolarization. The rate of recovery of threshold was similar proximally and distally, arguing against a gradient in Na+/K+ pump function along the peroneal nerve. The greater changes in threshold in EDB during and after ischemia suggest an increased susceptibility of more distal axons to ischemia and are likely to contribute to the length‐dependent development of neuropathy. Muscle Nerve, 2005
Ab initio prediction of the three‐dimensional structure of a de novo designed protein: A double‐blind case study
Authors: Klepeis John L. , Wei Yinan , Hecht Michael H. , Floudas Christodoulos A.
Published: December 2004

Ab initio structure prediction and de novo protein design are two problems at the forefront of research in the fields of structural biology and chemistry. The goal of ab initio structure prediction of proteins is to correctly characterize the 3D structure of a protein using only the amino acid sequence as input. De novo protein design involves the production of novel protein sequences that adopt a desired fold. In this work, the results of a double‐blind study are presented in which a new ab initio method was successfully used to predict the 3D structure of a protein designed through an experimental approach using binary patterned combinatorial libraries of de novo sequences. The predicted structure, which was produced before the experimental structure was known and without consideration of the design goals, and the final NMR analysis both characterize this protein as a 4‐helix bundle. The similarity of these structures is evidenced by both small RMSD values between the coordinates of the two structures and a detailed analysis of the helical packing. Proteins 2005. © 2004 Wiley‐Liss, Inc.
Water dynamics simulation as a tool for probing proton transfer pathways in a heptahelical membrane protein
Authors: Kandt Christian , Gerwert Klaus , Schlitter Jürgen
Published: December 2004

The proton transfer pathway in a heptahelical membrane protein, the light‐driven proton pump bacteriorhodopsin (BR), is probed by a combined approach of structural analysis of recent X‐ray models and molecular dynamics (MD) simulations that provide the diffusion pathways of internal and external water molecules. Analyzing the hydrogen‐bond contact frequencies of the water molecules with protein groups, the complete proton pathway through the protein is probed. Beside the well‐known proton binding sites in the protein interior—the protonated Schiff base, Asp85 and Asp96, and the H5O complex stabilized by Glu204 and Glu194—the proton release and uptake pathways to the protein surfaces are described in great detail. Further residues were identified, by mutation of which the proposed pathways can be verified. In addition the diffusion pathway of water 502 from Lys216 to Asp96 is shown to cover the positions of the intruding waters 503 and 504 in the N‐intermediate. The transiently established water chain in the N‐state provides a proton pathway from Asp96 to the Schiff base in the M‐ to N‐transition in a Grotthus‐like mechanism, as concluded earlier from time‐resolved Fourier transform infrared experiments [le Coutre et al., Proc Nat Acad Sci USA 1995;92:4962–4966]. Proteins 2005. © 2004 Wiley‐Liss, Inc.
Synthesis of spiroketal enol ethers related to tonghaosu and their insecticidal activities
Authors: Chen Li , Xu Han‐Hong , Hu Tai‐Shan , Wu Yu‐Lin
Published: December 2004

This paper describes the syntheses and biological activities of a number of spiroketal enol ethers which are analogues of the plant extract tonghaosu. The insecticidal potential of this spiroketal system is assessed. Copyright © 2005 Society of Chemical Industry
Protein open‐access liquid chromatography/mass spectrometry
Authors: White Wendy L. , Wagner Craig D. , Hall John T. , Chaney Erin E. , George Bindu , Hofmann Karen , Miller Luke A. D. , Williams Jon D.
Published: December 2004

Each year increasing numbers of proteins are submitted for routine characterization by liquid chromatography/mass spectrometry (LC/MS). This paper reports a solution that transforms routine LC/MS analysis of proteins into a fully automated process that significantly reduces analyst intervention. The solution developed, protein open‐access (OA) LC/MS, consists of web‐enabled sample submission and registration, automated data processing, data interpretation, and report generation. Sample submissions and results are recorded in a LIMS that utilizes an Oracle database. The protein sequence is captured during the sample submission process, stored in the database, and utilized to determine the theoretical protein molecular weight. This calculated mass is used to set the parameters for transformation of the mass‐to‐charge spectra to the mass domain and evaluate the presence or absence of the desired protein. Three protein OA‐LC/MS instruments have been deployed in our facility to support protein characterization, purification, and modification efforts. Copyright © 2004 John Wiley & Sons, Ltd.
Oxidized carbon nanotubes as matrix for matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometric analysis of biomolecules
Authors: Ren Shi‐fang , Guo Yin‐long
Published: December 2004

Oxidized carbon nanotubes (CNTs), which can form a stable homogeneous suspension in water close to a solution phase, were synthesized and used for matrix‐assisted desorption/ionization mass spectrometric (MALDI‐MS) analysis of biomolecules. Infrared (IR) spectra, transmission electron microscopy (TEM) and particle size analysis were used for the characterization of the oxidized CNTs. The results indicate that the physical structure of the CNTs was not damaged, but carboxylate groups were introduced onto the surface of the CNTs. In addition, impurities including amorphous carbon, which is one of the main reasons for ion source contamination, were destroyed by the oxidization. The carboxyl groups on the oxidized surface of the CNTs can not only provide an additional proton source, but can also increase the surface polarity and solubility of the CNTs, making it easier to manipulate which is important for MALDI analysis of some biomolecules, especially larger peptides and proteins. The oxidized CNTs were successfully applied to the analysis of neutral oligosaccharides, peptides, and insulin, and thus promise to be an efficient matrix for MALDI‐MS analysis of biomolecules. Copyright © 2004 John Wiley & Sons, Ltd.
Using a simple high‐performance liquid chromatography separation and fraction collection methodology to achieve compound‐specific isotopic analysis for dissolved organic compounds
Authors: Marschner Mark , Middlestead Paul , Clark Ian D.
Published: December 2004

A new application for the quantitative and isotopic analyses of dissolved inorganic and dissolved organic carbon compounds has been developed. Dissolved organic matter (DOM) in natural water samples can be separated on a high‐performance liquid chromatography (HPLC) column and collected as fractions. Each discrete fraction can then be analyzed using the technique of St‐Jean (Rapid Commun. Mass Spectrom. 2003; 17: 419–428) with a total inorganic carbon/total organic carbon (TIC/TOC) analyzer interfaced with a continuous‐flow isotope ratio mass spectrometer. Experimental data using short‐chain fatty acid standards (formic, acetic, and propionic acids) show that fraction recoveries of 100% are possible and that sample integrity is maintained. 13C‐isotopic analyses of products prior to and subsequent to extraction and collection show no isotopic effects associated with the methodology, and errors are well within the accepted analytical uncertainty of the IRMS. Comparison of data from pure standards and organic‐rich natural waters shows that quantitative analyses still need to be done with standards that more closely imitate the matrices of the samples, in order to acquire an appropriate calibration curve. Injections of organic‐rich matrices on the HPLC column did not affect fraction recovery, nor did they create high background of partially retained organic compounds slowly released from the HPLC column, and hence 13C‐isotopic results are relatively unaffected. The specific limitation on this methodology is the required use of carbon‐free carrier solvents due to potential memory effects associated with the TIC/TOC analyzer. Further developments of this application could make routine compound‐specific isotopic analyses (CSIA) for a wider range of organic materials possible. Copyright © 2004 John Wiley & Sons, Ltd.
Effects of reduced endogenous 5‐HT on the in vivo binding of the serotonin transporter radioligand 11C‐DASB in healthy humans
Authors: Talbot Peter S. , Frankle W. Gordon , Hwang Dah‐Ren , Huang Yiyun , Suckow Raymond F. , Slifstein Mark , Abi‐Dargham Anissa , Laruelle Marc
Published: December 2004

Although abnormal serotonin (5‐HT) function is implicated in a range of mental disorders, there is currently no method to directly assess 5‐HT synaptic levels in the living human brain. The in vivo binding of some dopamine (DA) radioligands such as 11C‐raclopride is affected by fluctuations in endogenous DA, thus providing an indirect measure of DA presynaptic activity. Attempts to identify a serotonergic radiotracer with similar properties have proved unsuccessful. Here, we investigated in humans the effects of reduced synaptic 5‐HT on the in vivo binding of the 5‐HT transporter (SERT) radioligand 11C‐DASB, using Positron Emission Tomography (PET) and the rapid tryptophan depletion (RTD) technique. Eight (8) subjects (5M, 3F) were scanned with 11C‐DASB under control and reduced endogenous 5‐HT conditions, in a within‐subject, double‐blind, counterbalanced, crossover design. Regional distribution volumes (VT) were calculated using kinetic modeling and metabolite‐corrected arterial input function. 11C‐DASB specific binding was estimated as binding potential (BP) and specific to nonspecific equilibrium partition coefficient (V), using the cerebellum as reference region. RTD caused small but significant mean reductions in 11C‐DASB VT (−6.1%) and BP (−4.5%) across brain regions, probably explained by a concomitant reduction in 11C‐DASB plasma free fraction (f1) of similar magnitude. No significant change in 11C‐DASB V was observed between control and reduced 5‐HT conditions. Nor was there a significant relationship between the magnitude of tryptophan depletion and change in BP and V across individual subjects. These results suggest that 11C‐DASB in vivo binding is not affected by reductions in endogenous 5‐HT. Synapse 55:164–175, 2005. © 2004 Wiley‐Liss, Inc.
Professionalizing youth development: The role of higher education
Authors: Borden Lynne M. , Craig Deborah L. , Villarruel Francisco A.
Published: December 2004

Certificates, credentials, and degrees offered through institutions of higher education allow youth development professionals to acquire educational experiences that are recognized in a formal manner.
Getting down to business: Defining competencies for entry‐level youth workers
Authors: Astroth Kirk A. , Garza Pam , Taylor Barbara
Published: December 2004

In January 2004, the National Collaboration for Youth approved a list of core competencies needed by entry‐level youth development workers for effective youth development practice. This chapter provides an overview of these competencies, explaining why and how the list was created, outcomes, and recommendations for next steps.
Achieve Boston: A citywide innovation in professional development
Authors: Barbosa Moacir , Gannett Ellen S. , Goldman Jude , Wechsler Samantha , Noam Gil G.
Published: December 2004

Achieve Boston is a broad‐based collaborative effort to improve the overall quality of programs for children and youth by establishing a professional development infrastructure that supports those who work with young people during the out‐of‐school‐time hours.
The intermediary role in youth worker professional development: Successes and challenges
Authors: Johnson Elaine , Rothstein Fran , Gajdosik Jennifer
Published: December 2004

This chapter examines the role of a national network of local and regional intermediary organizations in initiating and sustaining community‐based youth worker professional development systems. This approach is instructive for other intermediaries in establishing training standards, assessing impact, providing organizational supports for youth development workers, and going to scale.
Professional development in national organizations: Insights from Girls Incorporated
Authors: Johnston Nicholson Heather , Houchin Susan , Stegall Brenda
Published: December 2004

The largest national youth organizations have targeted, comprehensive professional development systems. For one of them, Girls Incorporated, its mission “to inspire all girls to be strong, smart, and bold”SM drives sophisticated, evaluated professional development for affiliate staff and trustees.
Synthesis and Characterization of a Molecular Zinc Phosphate Ni(2, 2'‐bipy)3·[ZnCl(H2PO4)3]
Authors: Lin Zhi‐En , Zhang Jie , Zheng Shou‐Tian , Yang Guo‐Yu
Published: December 2004

A new zinc phosphate cluster Ni(2, 2'‐bipy)3 · [ZnCl(H2PO4)3] (1) was obtained by the hydrothermal reaction of ZnO, H3PO4, NiCl2·6H2O, 2, 2'‐bipyridine(2, 2'‐bipy) and H2O in a molar ration of 1 : 1.9 : 0.5 : 1.5 : 126. The structure of 1 is made of [ZnCl(H2PO4)3] clusters that are separated by nickel complexes. The compound is novel in the sense that it is the first zinc phosphate cluster with metal complexes acting as structure‐directing agents. Crystal data: trigonal, space group = R3¯c (no. 167), a = 13.2407(3), c = 74.034(3) Å, V = 11240.5(6) Å3, Z = 12.
Synthesis, Spectral, Cyclic Voltammetric Studies, and Single Crystal X‐Ray Structure Determination of the Planar NiS2P2, NiS2PN, and NiS2PC Chromophores
Authors: Thiruneelakandan R. , Ramalingam K. , Bocelli G. , Righi L.
Published: December 2004

Synthesis, spectral and cyclic voltammetric characterization of [Ni(dedtc)(4‐MP)2](ClO4) (1), [Ni(dedtc)(4‐MP)(NCS)](2), [Ni(dedtc)(PPh3)(NCS)] (3) and [Ni(dedtc)(PPh3)(CN)] (4) (dedtc = diethyldithiocarbamate, 4‐MP = tri(4‐methylphenyl)phosphine, PPh3 = triphenylphophine) are reported. IR spectra of complexes 1‐4 show the characteristic thioureide (C‐N) bands at higher wave numbers compared to that of the parent dithiocarbamate complex [Ni(dedtc)2]. The d‐d transitions are observed in the region 452—482 nm.

The CV studies clearly show the presence of reduced electron density on the nickel ions in mixed ligand complexes 1‐4 compared to the parent dithiocarbamate. Single crystal X‐ray structure studies show all the complexes to containplanar NiS2P2, NiS2PN, and NiS2PC chromophores in keeping with the observed diamagnetism. In all the complexes the Ni‐S distances are asymmetric. The thioureide C‐N distance of the complexes 1‐4 are less thanthe C‐N distance observed in the parent [Ni(dedtc)2].
Crystal Structures and Solution Studies of Two Novel Zinc(II) Complexes of a Proton Transfer Compound Obtained from 2, 6‐Pyridinedicarboxylic Acid and 1, 10‐Phenanthroline: Observation of Strong Intermolecular Hydrogen Bonds
Authors: Moghimi Abolghasem , Sheshmani Shabnam , Shokrollahi Ardeshir , Shamsipur Mojtaba , Kickelbick Guido , Aghabozorg Hossein
Published: December 2004

The proton transfer compound LH2, (phenH+)2(pydc2—), has been prepared from 1, 10‐phenanthroline, phen, and 2, 6‐pyridinedicarboxylic acid, (dipicolinic acid), pydcH2. Characterization was performed using solution and solid phase CP/MAS 13C NMR and IR spectroscopy. The reactions of this adduct with ZnSO4·7H2O and Zn(NO3)2·4H2O give the complexes, [Zn(pydc)2][Zn(phen)2(H2O)2]·7H2O (1) and [Zn(phen)3]4(H(Hpydc)2)(NO3)7·26H2O (2), respectively. These complexes were characterized by 1H and 13C NMR spectroscopy and single crystal X‐ray analysis. The complexes crystallize in the triclinic space group P1 with Z = 2. The unit cell dimensions for complex 1 and 2 are: a = 9.9838(9) Å, b = 14.7483(13) Å, c = 14.8365(13) Å and a = 12.640(4) Å, b = 15.855(5) Å, c = 21.830(7) Å, respectively. In complex 1 (pydc2—) and phen, are tri‐ and bidentate ligands, respectively, and an anionic [Zn(pydc)2]2— and cationic [Zn(phen)2(H2O)2]2+ complex are formed simultaneously. In complex 2, three phen participate in complexation leaving hydrogen‐bis(pyridine‐2‐carboxylate), (H(Hpydc)2)— as a supramolecular anion. The fragments (H(Hpydc)2)—, 7 NO3—, and 26 H2O in complex 2 are joined together by extensive and strong H‐bonding; therefore, the structure is composed of [Zn(phen)3]48+, and an anionic hydrogen bond supramolecular assembly with the formula, {(H(Hpydc)2(NO3)7)8—·26H2O}n. The anionic species (H(Hpydc)2)— has a special position at the inversion center, as well as one of the NO3— anions, which is disordered over the inversion center. Most of the hydrogen bonds in complex 2 represent strong H‐bonding. The protonation constants of the building blocks of the pydc‐phen adduct, the equilibrium constants for the reaction of (pydc2—) with phenanthroline and the stoichiometry and stability of the ZnII complex with LH2 on aqueous solution were determined by potentiometric pH titration. The solution study results support self‐association between (pydc2—) and (phenH+) with a stoichiometry for the Zn(II) complex similar to that observed for the isolated crystalline complex.
A New Inorganic‐Organic Hybrid with Zinc Phosphate Layers Pillared by the 4, 4'‐Bipyridine Units
Authors: Lin Zhi‐En , Zhang Jie , Zheng Shou‐Tian , Yang Guo‐Yu
Published: December 2004

A new inorganic‐organic hybrid zinc phosphate with the formula Zn2(4, 4'‐bipy)(HPO4)2 (4, 4'‐bipy = 4, 4'‐bipyridine) has been synthesized under hydrothermal conditions and characterized by single‐crystal X‐ray diffraction, FTIR, ICP analysis, elemental analysis, SEM, powder X‐ray diffraction, thermogravimetric analysis and its fluorescent spectrum. The compound crystallizes in the monoclinic system, space group P21/c (No.14), a = 10.4479(7), b = 8.1694(5), c = 8.9643(5) Å, β = 97.907(2), V = 757.86(8) Å3, Z = 2. The structure consists of ZnO3N and HPO4 tetrahedra by corner‐sharing to generate neutral 4.82‐net sheets, which are pillared through 4, 4'‐bipy ligands to form a 3‐D hybrid framework.
One‐dimensionally linked Chain Crown Ether Complexes. Syntheses and Crystal Structures of Complexes [K(18‐Crown‐6)]2[M(SeCN)4](H2O) (M = Pd, Pt)
Authors: Li Da‐Cheng , Du Mao‐Xi , Dou Jian‐Min , Wang Da‐Qi
Published: December 2004

18‐crown‐6(18‐C‐6) complexes with K2[M(SeCN)4] (M = Pd, Pt): [K(18‐C‐6)]2[Pd(SeCN)4] (H2O) (1) and [K(18‐C‐6)]2[Pt(SeCN)4](H2O) (2) have been isolated and characterized by elemental analysis, IR spectroscopy and single crystal X‐ray analysis. The complexes crystallize in the monoclinic space group P21/n with cell dimensions: 1: a = 1.1159(3) Å, b = 1.2397(3) Å, c = 1.6003(4) Å, β = 92.798(4)°, V = 2.2111(8) Å3, Z = 2, F(000) = 1140, R1 = 0.0418, wR2 = 0.0932 and 2: a = 1.1167(3) Å, b = 1.2394(3) Å, c = 1.5968(4) Å, β = 92.945(4)°, V = 2.2071(9) Å3, Z = 2, F(000) = 1204, R1 = 0.0341, wR2 = 0.0745. Both complexes form one‐dimensionally linked chains of [K(18‐C‐6)]+ cations and [M(SeCN)4]2— (M = Pd, Pt) anions bridged by K‐O‐K interactions between adjacent [K(18‐C‐6)]+ units.
Syntheses, Crystal Structures and Non‐linear Optical Properties of Cluster Compounds [MoAu2S4(PPh2Py)2] and [WAu2S4(PPh2Py)2]
Authors: Zhou Jian‐Liang , Song Ying‐Lin , Mo Hong‐Bing , Li Yi‐Zhi , Zheng He‐Gen , Xin Xin‐Quan
Published: December 2004

The cluster compounds, [MoAu2S4(PPh2Py)2] (1) and [WAu2S4(PPh2Py)2] (2), were synthesized by the reaction of (NH4)2MS4 (M = Mo, W), H[AuCl4]·4H2O and diphenyl‐2‐pyridyl‐phosphine (PPh2Py) in CH2Cl2 solution. [MoAu2S4(PPh2Py)2] crystallizes in the monoclinic space group P21/c with a = 18.385(2), b =12.304(1), c = 16.904(2) Å, β =110.722(2)°, and Z = 4. [WAu2S4(PPh2Py)2] crystallizes in the triclinic space group P‐1 with a = 9.333 (3), b = 10.628(3), c = 19.566(6) Å, α = 89.26(1), β = 80.87(1), γ = 68.85(1)°, and Z = 2. Single crystal X‐ray analysis showed that these two compounds are isostructural, but belong to different space groups. The Mo (W) atom has a slightly distorted tetrahedral coordination, and the two Au atoms are distorted from trigonal planar, the P—Au—M—Au—P chain is nearly linear. Measurement of the nonlinear optical (NLO) properties using the Z‐scan technique with an 8‐ns pulsed laser at 532 nm showed that 1 and 2 possess NLO absorption and effective self‐focusing effect. The effective α2 and n2 values of cluster 1 are 5.89 × 10—12 m · W—1 and 6.45 × 10—18 m2 · W—1; the effective α2 and n2 values of compound 2 are 4.35 × 10—11 m · W—1 and 3.73 × 10—17 m2 · W—1.
The quasi-genderless heresy: The Dhūtaists and Master Jizhao
Authors: BORETTI VALENTINA
Published: December 2004

This paper looks at the professional alternatives that Buddhism offered to women by analysing the important role played by a female master in the as yet little studied Dhūta movement, a form of ‘heretical’ Chan Buddhism that flourished during the final years of the Jin dynasty and afterwards in the Yuan dynasty. By examining the descriptions of female master Jizhao and male master Puguang, as seen in epitaphs composed by officers-literati and preserved in a Bejing gazetteer dating back to the mid-fourteenth century, this paper aims to highlight some features of the Dhūtaists' discourse of femininity and also to point out the differences vis-à-vis orthodox Chan constructs, in order finally to evaluate whether such a discourse could have an influence on the general definitions and content of gender roles.
Learning the piano: a study of attitudes to parental involvement
Authors: Macmillan Jenny
Published: December 2004

Numerous studies in general education have concluded that parental involvement improves student achievement. Research in music education indicates that parental involvement is beneficial to progress on a musical instrument. However, few music teachers are known to actively encourage it. This paper reports on a detailed qualitative survey that examines teachers', pupils' and parents' attitudes to parental involvement, the extent and nature of that involvement, and pupils' resultant enjoyment and achievement.

The survey found that, while pupils and parents alike welcome parental involvement, some teachers encourage this collaboration and some do not. Teachers who (a) have pedagogical qualifications, (b) have followed specialist courses, and (c) are experienced, prove more likely to encourage parental involvement.
Boys' and girls' constructions of gender through musical composition in the primary school
Authors: Charles Brigitte
Published: December 2004

The purpose of the study is to examine, through interviews and observations, the extent to which 8–10 year old children in a London primary school replicate gendered musical practices and experience gendered musical meanings, and how these may affect their expectations and the specific practices and products of their composition. I also consider how primary school teachers participate in the overarching discourse on gender and music education, by examining their expectations about the nature of girls' and boys' compositions. I analyse my findings in relation to Lucy Green's model of gendered musical meaning and experience. One outcome of the analysis is the development of a concept of ‘female musical subculture’ to interpret girls' and women's participation in the compositional world. Secondly, the findings strongly suggest that in their musical practice, the children in the research are not reproducing ideological assumptions about gendered musical practices, which contradicts how they operate discursively, for their discourse lies within the bounds of gendered musical ideology. Thirdly, the findings also indicate that the teachers are strongly affected by gendered musical ideologies, and have concomitant expectations about the music girls and boys produce.