bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐prostate specific membrane antigen designer T cells for prostate cancer therapy
Authors: Ma Qiangzhong , Safar Mazin , Holmes Eric , Wang Yawen , Boynton Alton L. , Junghans Richard P. 
Published: March 2004

AbstractBackgroundDesigner T cells are T lymphocytes engineered toward specific antibody‐type membrane antigens through chimeric immunoglobulin‐T‐cell receptor (IgTCR) genes that have been used for adoptive cellular immunotherapy. We have extended this approach to prostate specific membrane antigen (PSMA) as a means to attack prostate cancer.MethodsA chimeric anti‐PSMA IgTCR gene was constructed based on an anti‐PSMA monoclonal antibody, 3D8. Both T‐cell lines and primary cultured human T lymphocytes were transduced with the chimeric anti‐PSMA IgTCR construct and were analyzed for IgTCR expression, specific activation by PSMA, cytotoxicity against PSMA‐expressing tumor cells in vitro, and retardation of tumor growth in an animal model.ResultsThe IgTCR was incorporated into the TCR–CD3 complex and formed a functional chimeric complex. The IgTCR‐modified T cells were specifically activated through the chimeric receptor with PSMA as measured by IL‐2 production and increased CD25 expression and specifically lysed the PSMA‐expressing prostate cancer cells in vitro as well as retarded tumor growth in an animal model.ConclusionsThe anti‐PSMA designer T cells exhibit an antibody‐type specificity that can recognize PSMA expressing tumor cells in a MHC‐independent fashion, resulting in T‐cell activation, target cell lysis in vitro and inhibition of tumor growth in vivo. © 2004 Wiley‐Liss, Inc.
Anti‐tumor effects and lack of side effects in mice of an immunotoxin directed against human and mouse prostate‐specific membrane antigen
Authors: Huang Xianming , Bennett Mary , Thorpe Philip E. 
Published: March 2004

AbstractBackgroundProstate‐specific membrane antigen (PSMA) is a transmembrane protein that is largely restricted to prostatic epithelial cells in humans and is strongly upregulated on prostatic carcinoma cells. It is also expressed on the endothelium of tumor vasculature in humans, but not on the vasculature of normal tissues. Expression of low levels of PSMA has also been found on non‐vascular cells in several normal tissues, most prominently on the brain and kidney in humans. PSMA is an excellent candidate for targeting prostate cancer or targeting tumor vasculature of various solid tumors. The high potential clinical benefit of these agents has prompted the search for an animal model in which to assess the efficacy and safety of anti‐PSMA monoclonal antibody (mAb)‐based therapies.MethodsA rat monoclonal antibody, E6 that recognizes both mouse and human PSMA was generated using conventional hybridoma techniques. The antibody was characterized by enzyme‐linked immunosorbent assay (ELISA), Western blot, and immunohistochemistry. An immunotoxin composed of E6, antibody and deglycosylated ricin A‐chain (dgA) was prepared chemically. The anti‐tumor effects of the immunotoxin were determined in vitro and in mice bearing subcutaneous LnCaP human prostate tumors, which express PSMA on the tumor cell surface.ResultsE6 recognizes the extracellular domain of both human and mouse PSMA in ELISA, immunoblot and by immunohistochemistry. E6 strongly stained the vascular endothelium of tumors from humans but not from mice. E6 stained proximal tubules in mouse and human kidneys, and neurons in the mouse and human hippocampus but, unlike the human, did not detectably stain epithelial cells in mouse prostate or small intestine. An E6‐dgA immunoconjugate strongly inhibited the growth of LnCaP tumor xenografts without causing apparent toxicity to the mice. Histological observation indicated that the anti‐tumor effects were mediated through direct cytotoxic effects on the tumor cells.ConclusionsWe have generated and characterized a rat mAb (E6) that reacts specifically with both human and mouse PSMA and have demonstrated that an immunotoxin constructed from E6 is safe and effective against human prostatic carcinoma cells growing subcutaneously in nude mice. © 2004 Wiley‐Liss, Inc.
Identification of polycomb group protein enhancer of zeste homolog 2 (EZH2)‐derived peptides immunogenic in HLA‐A24+ prostate cancer patients
Authors: Ogata Rika , Matsueda Satoko , Yao Akihisa , Noguchi Masanori , Itoh Kyogo , Harada Mamoru 
Published: March 2004

AbstractBackgroundAntigens overexpressed in metastatic prostate cancer are appropriate targets in anti‐cancer immunotherapy, and one candidate is the polycomb group protein enhancer of zeste homolog 2 (EZH2).MethodsEleven EZH2‐derived peptides were prepared based on the HLA‐A24 binding motif. These peptide candidates were screened first by their ability to be recognized by immunoglobulin G (IgG), and then by their ability to induce peptide‐specific cytotoxic T lymphocytes (CTLs).ResultsIgGs reactive to three EZH2 peptides (EZH2‐243 to ‐252, EZH2‐291 to ‐299, and EZH2‐735 to ‐;742) were detected in the plasma of almost half of prostate cancer patients. Among them, the EZH2‐291 to ‐299 and EZH2‐735 to ‐742 peptides effectively induced HLA‐A24‐restricted and prostate cancer‐reactive CTLs from prostate cancer patients. The cytotoxicity was mainly dependent on EZH2 peptide‐specific and CD8+ T cells.ConclusionsThese EZH2‐291 to ‐299 and EZH2‐735 to ‐742 peptides could be promising candidates for peptide‐based immunotherapy for HLA‐A24+ prostate cancer patients with metastases. © 2004 Wiley‐Liss, Inc.
PC‐3 cells with enhanced androgen receptor signaling: A model for clonal selection in prostate cancer
Authors: Buchanan Grant , Craft Paul S. , Yang Miao , Cheong Albert , Prescott Jennifer , Jia Li , Coetzee Gerhard A. , Tilley Wayne D. 
Published: March 2004

AbstractBackgroundTwo sublines of the human prostate cancer cell line, PC‐3, which is widely used as a model of prostate cancer progression, have been reported: PC‐3AR− that do not express androgen receptor (AR), and PC‐3AR+ that have measurable AR RNA but little protein.MethodsWe assayed the geneotype, karyotype, AR expression, and physical characteristics of the two PC‐3 sublines, and compared their ability to elicit a transactivation response from ectopic AR in the presence and absence of specific AR coregulators.ResultsPC‐3AR− and PC‐3AR+ cells are genotypically and karyotypically similar, but exhibit salient differences in their morphology, growth rate, and expression of AR RNA. Whereas endogenous AR expression in PC‐3AR+ cells does not result in sufficient protein to confer androgen responsiveness in culture, ectopic AR consistently elicited a much greater transactivation response in PC‐3AR+ than in PC‐3AR− cells, without altered sensitivity to activation by native ligand or AR coregulators including GRIP1, BRCA1, and Zac1. Moreover, phenotypic differences of AR variants implicated in prostate cancer susceptibility and progression were only observed in PC‐3AR+ cells. Higher levels of known AR coregulator proteins detected in PC‐3AR+ compared with PC‐3AR− cells likely contribute to these differences.ConclusionsThese studies provide new evidence that the androgen‐signaling axis can be sensitized in prostate cancer cells, and have important implications for the analysis and interpretation of AR structure and function in in vitro cell systems. © 2004 Wiley‐Liss, Inc.
Retinoic acid slows progression and promotes apoptosis of spontaneous prostate cancer
Authors: Huss Wendy J. , Lai Lihua , Barrios Roberto J. , Hirschi Karen K. , Greenberg Norman M. 
Published: March 2004

AbstractBACKGROUNDAll‐trans retinoic acid (ATRA) promotes terminal differentiation in epithelial cells and anti‐angiogenesis and thus, may have beneficial effects in an intervention therapy for prostate cancer.METHODSWe used the autochthonous spontaneous transgenic adenocarcinoma of the mouse prostate (TRAMP) model system to test the ability of ATRA to prevent initiation and progression of prostate cancer in a pre‐clinical setting.RESULTSInitial studies demonstrated that exposure of TRAMP‐derived C2N prostate tumor cells to ATRA in vitro decreased total viable cell numbers with a concomitant decrease in the fraction of cells in S phase. When TRAMP mice were treated in vivo with ATRA for either 6 or 8 weeks at low, medium, or high dose, mice on average presented with lower grade and more differentiated tumors. However, ATRA therapy conferred no significant protection on incidence of tumors or frequency of metastasis at any dose. Nevertheless, we were able to observe a significant decrease in the expression of synaptophysin, a marker of neuroendocrine differentiation, in tumors of mice receiving the highest dose of ATRA. As well, expression of the cell cycle inhibitor p21 was found to be elevated only in well‐differentiated tumors of mice, treated with ATRA while expression of p27, was found to be elevated only in the poorly differentiated tumors.CONCLUSIONSCollectively, our in vitro and in vivo data demonstrates that ATRA was able to slow prostate tumor cell proliferation, induce apoptosis, and block the emergence of the neuroendocrine phenotype. Furthermore, our study suggests the differential regulation of p21 and p27 as a molecular mechanism whereby ATRA intervention therapy can inhibit the natural history of spontaneous prostate cancer. © 2004 Wiley‐Liss, Inc.
Evaluation of local structure alphabets based on residue burial
Authors: Karchin Rachel , Cline Melissa , Karplus Kevin 
Published: March 2004

AbstractResidue burial, which describes a protein residue's exposure to solvent and neighboring atoms, is key to protein structure prediction, modeling, and analysis. We assessed 21 alphabets representing residue burial, according to their predictability from amino acid sequence, conservation in structural alignments, and utility in one fold‐recognition scenario. This follows upon our previous work in assessing nine representations of backbone geometry.1 The alphabet found to be most effective overall has seven states and is based on a count of Cβ atoms within a 14 Å‐radius sphere centered at the Cβ of a residue of interest. When incorporated into a hidden Markov model (HMM), this alphabet gave us a 38% performance boost in fold recognition and 23% in alignment quality. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Automatic target selection for structural genomics on eukaryotes
Authors: Liu Jinfeng , Hegyi Hedi , Acton Thomas B. , Montelione Gaetano T. , Rost Burkhard 
Published: March 2004

AbstractA central goal of structural genomics is to experimentally determine representative structures for all protein families. At least 14 structural genomics pilot projects are currently investigating the feasibility of high‐throughput structure determination; the National Institutes of Health funded nine of these in the United States. Initiatives differ in the particular subset of “all families” on which they focus. At the NorthEast Structural Genomics consortium (NESG), we target eukaryotic protein domain families. The automatic target selection procedure has three aims: 1) identify all protein domain families from currently five entirely sequenced eukaryotic target organisms based on their sequence homology, 2) discard those families that can be modeled on the basis of structural information already present in the PDB, and 3) target representatives of the remaining families for structure determination. To guarantee that all members of one family share a common foldlike region, we had to begin by dissecting proteins into structural domain‐like regions before clustering. Our hierarchical approach, CHOP, utilizing homology to PrISM, Pfam‐A, and SWISS‐PROT chopped the 103,796 eukaryotic proteins/ORFs into 247,222 fragments. Of these fragments, 122,999 appeared suitable targets that were grouped into >27,000 singletons and >18,000 multifragment clusters. Thus, our results suggested that it might be necessary to determine >40,000 structures to minimally cover the subset of five eukaryotic proteomes. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
X‐ray structural and simulation analysis of a protein mutant: The value of a combined approach
Authors: Mattos Carla , Cohen Justin D. , Green David F. , Tidor Bruce , Karplus Martin 
Published: March 2004

AbstractThe effect of the mutation Arg 96 to His on the stability of bacteriophage T4 lysozyme has been previously studied by calorimetric experiments, X‐ray crystallography, and free energy simulation techniques. The experimental and calculated values for the difference between the free energy of denaturation of the mutant and the wild type are in reasonable agreement. However, the two approaches led to different explanations for the loss in stability. To analyze the differences, a series of refinements based on the crystallographic data were performed, a number of aspects of the simulations were reexamined, and continuum electrostatic calculations were done to complement the latter. The results of those comparisons provide a better understanding of the origin of the free energy difference in this mutant. Furthermore, they show the importance of the combined use of simulations and crystallography for interpreting the effects of mutations on the energetics of the system. Proteins 2004. © 2004 Wiley‐Liss, Inc.
The determinants of carboxyl pKa values in turkey ovomucoid third domain
Authors: Li Hui , Robertson Andrew D. , Jensen Jan H. 
Published: March 2004

AbstractA computational methodology for protein pKa predictions, based on ab initio quantum mechanical treatment of part of the protein and linear Poisson–Boltzmann equation treatment of the bulk solvent, is presented. The method is used to predict and interpret the pKa values of the five carboxyl residues (Asp7, Glu10, Glu19, Asp27, and Glu43) in the serine protease inhibitor turkey ovomucoid third domain. All the predicted pKa values are within 0.5 pH units of experiment, with a root‐mean‐square deviation of 0.31 pH units. We show that the decreased pKa values observed for some of the residues are primarily due to hydrogen bonds to the carboxyl oxygens. Hydrogen bonds involving amide protons are shown to be particularly important, and the effect of hydrogen bonding is shown to be nonadditive. Hydrophobic effects are also shown to be important in raising the pKa. Interactions with charged residues are shown to have relatively little effect on the carboxyl pKa values in this protein, in general agreement with experiment. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
The architecture of the binding site in redox protein complexes: Implications for fast dissociation
Authors: Crowley Peter B. , Carrondo Maria Arménia 
Published: March 2004

AbstractInterprotein electron transfer is characterized by protein interactions on the millisecond time scale. Such transient encounters are ensured by extremely high rates of complex dissociation. Computational analysis of the available crystal structures of redox protein complexes reveals features of the binding site that favor fast dissociation. In particular, the complex interface is shown to have low geometric complementarity and poor packing. These features are consistent with the necessity for fast dissociation since the absence of close packing facilitates solvation of the interface and disruption of the complex. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Accurate and efficient description of protein vibrational dynamics: Comparing molecular dynamics and Gaussian models
Authors: Micheletti Cristian , Carloni Paolo , Maritan Amos 
Published: March 2004

AbstractCurrent all‐atom potential based molecular dynamics (MD) allows the identification of a protein's functional motions on a wide‐range of timescales, up to few tens of nanoseconds. However, functional, large‐scale motions of proteins may occur on a timescale currently not accessible by all‐atom potential based MD. To avoid the massive computational effort required by this approach, several simplified schemes have been introduced. One of the most satisfactory is the Gaussian network approach based on the energy expansion in terms of the deviation of the protein backbone from its native configuration. Here, we consider an extension of this model that captures in a more realistic way the distribution of native interactions due to the introduction of effective side‐chain centroids. Since their location is entirely determined by the protein backbone, the model is amenable to the same exact and computationally efficient treatment as previous simpler models. The ability of the model to describe the correlated motion of protein residues in thermodynamic equilibrium is established through a series of successful comparisons with an extensive (14 ns) MD simulation based on the AMBER potential of HIV‐1 protease in complex with a peptide substrate. Thus, the model presented here emerges as a powerful tool to provide preliminary, fast yet accurate characterizations of protein near‐native motion. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Photoluminescence of one‐dimensional electron gases in cleaved‐edge overgrowth quantum wires
Authors: Kristukat C. , Gonñi A. R. , Bichler M. , Wegscheider W. , Abstreiter G. , Thomsen C. 
Published: March 2004

AbstractWe carried out micro‐photoluminescence studies of doped multiple quantum wire structures grown by the cleaved‐edge overgrowth technique in the GaAs/AlGaAs material system. The wires are defined in a quantum well whose potential is modulated by adjacent alternating negatively and positively charged layers. We observed strong band gap renormalization effects in the quantum wires indicating that they are densely populated. The measured recombination energies are in good agreement with a simple quantum mechanical calculation. Nevertheless, the design of the sample appears to be not suitable for light scattering studies of the one dimensional (1D) electron gas, for the 1D confinement strongly depends on photoexcitation. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Impurity‐related magnetism in the diluted magnetic semiconductors Pb1−xSnxTe:Yb
Authors: Skipetrov E. , Zvereva E. , Skipetrova L. , Kovalev B. , Volkova O. , Golubev A. , Slyn'ko E. 
Published: March 2004

AbstractThe effect of ytterbium impurity on the magnetic and galvanomagnetic properties of new diluted magnetic semiconductors Pb1−xSnxTe:Yb was investigated. Impurity‐related Curie–Weiss paramagnetism was revealed. The concentration of magnetic centers and the ytterbium impurity‐band occupancy as a function of impurity content were determined. The results are discussed assuming the formation of a ytterbium‐induced level under the valence‐band top and a variation of the magnetic centers concentration due to changing of the mutual arrangement of the valence band, impurity level and Fermi‐level position. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Lattice dynamics and phase transition in LaBGeO5
Authors: Smirnov M. B. , Menschikova A. V. , Kratochvilova‐Hruba I. , Zikmund Z. 
Published: March 2004

AbstractA detailed analysis of the LaBGeO5 single crystal vibration spectra has been carried out. The lattice vibration calculation based on a short‐range model potential function provides the theoretical background of this study. The model function parameters are taken from ab initio quantum mechanic calculations of molecular clusters containing structural fragments. When applied to the lattice dynamics calculations the model satisfactorily reproduces the spectra of IR‐ and Raman‐active modes. The main goal of this lattice dynamics study was to find the proper atomic rearrangement associated with a ferroelectric phase transition. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optical properties of Sm‐chelate containing methyl methacryate solution and its solid polymer matrix
Authors: Liang Hao , Zheng Zhiqiang , Zhang Qijin , Ming Hai , Chen Biao 
Published: March 2004

AbstractFrom optical absorption spectra and using the Judd–Ofelt theory, the phenomenological parameters, Ω2, Ω4, and Ω6 of Sm(DBM)3(TOPO)2 containing methyl methacryate (MMA) solution and solid poly(methyl methacryate) (PMMA) matrix were obtained. The chemical structure of Sm‐chelate accounts for the nearly same Ω2 values in liquid solution and solid polymer matrix. The evaluation of the radiative properties of Sm‐chelate containing PMMA showed that the 4G5/2 → 6H9/2 transition of Sm3+ in polymer matrix is potential to be a laser transition.. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
2003 SOMMA KMS Meeting International Symposium on Magnetic Materials and Applications, Daejeon, Korea, 3–6 December 2003
Authors: Stobiecki Tomasz 
Published: March 2004

AbstractConference Reports are meant to offer an authoritative view on a recently held scientific meeting rather than a comprehensive list of the conference presentations. Authors are invited to describe what they feel were the most interesting contributions.The full Proceedings of the 2003 SOMMA KMS Meeting will be published in phys. stat. sol. (a) and phys. stat. sol. (b) in Spring 2004. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Editorial: phys. stat. sol. (b) 241/5
Authors: Stutzmann Martin 
Published: March 2004

AbstractPhysica status solidi was founded in 1961 by a number of eminent solid state physicists as an attempt to overcome the iron curtain, which then separated East and West, at least in the field of science. Since that time our world has changed quite a bit, and so have the boundary conditions of science publishing. However, one thing has not changed: then as now, the general policy and development of a respectable scientific journal should be determined by a board of independent scientists, who volunteer to assume responsibility for the scientific content of the journal, to assure a fair and critical peer review process for all submitted manuscripts, and, in cases of conflict, to finally decide which papers will be published and which will not.As a matter of fact, an international Board of Editors which consists of scientists coming from different countries and continents, with a good reputation in their respective community, and without any conflict of interest with the Publisher of the journal is, in my opinion, these days more important than ever. As our daily scientific work becomes increasingly specialized, but at the same time also increasingly interdisciplinary, we are more and more forced to trust the quality and reliability of published scientific results in the literature, without really having a chance to come to an independent opinion on our own. This is one of the reasons why the many recent cases of plagiarism, scientific misconduct, or outright fraud have caused such a high level of public awareness. It is quite clear that without a serious peer review there would be an even larger number of such cases in the literature, and that without the responsible action taken by concerned Journal Editors, many of the revealed cases probably would have remained “under the carpet”.It is, therefore, a particular pleasure for me to introduce to you on the following pages the current Editorial Board of physica status solidi (b) in the form of a brief curriculum vitae, a photograph, and an e‐mail address (in case you want to contact our Editors directly!). Of course, since 1961 the Editorial Board of our journal has undergone many changes and will continue to do so, but we always have attempted to maintain a good balance between the different areas of solid state physics, between theory and experiment, and between different countries. And although nothing is perfect, I hope that you will find at least one or two board members, who are known to you through their contributions to the literature in solid state physics.For me, this is the perfect occasion to thank all Members of the Editorial Board, past and present, for their advice, continuing support, and dedication! Vielen herzlichen Dank!