bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multispecificity of Drug Transporters: Probing Inhibitor Selectivity for the Human Drug Efflux Transporters ABCB1 and ABCG2
Authors: Cramer Joerg , Kopp Stephan , Bates Susan E. , Chiba Peter , Ecker Gerhard F. 
Published: November 2007

AbstractMultidrug resistance transporters P‐glycoprotein/ABCB1 and ABCG2 limit the effect of a large number of cytostatic and cytotoxic drugs by energy‐dependent efflux. In experimental models, pump inhibitors reestablish sensitivity towards these drugs. Both transporters demonstrate remarkably broad and partly overlapping substrate specificity. Propafenone analogues are inhibitors of a large number of drug efflux pumps including P‐glycoprotein and ABCG2 as well as the microbial pumps. Here the two human ABC transporters ABCB1 and ABCG2 have been studied with respect to interaction with this class of compounds. Data indicate that within the same chemical scaffold, selectivity indices span three orders of magnitude. Compounds with the highest selectivity indices contain a non‐ionizable nitrogen atom. Qualitative and quantitative pharmacophore models indicate that hydrophobicity, the number of rotatable bonds, and the number of H‐bond acceptors are key features for both activity and selectivity.
Metabolite Identification via LC‐SPE‐NMR‐MS of the In vitro Biooxidation Products of a Lead mGlu5 Allosteric Antagonist and Impact on the Improvement of Metabolic Stability in the Series
Authors: Ceccarelli Simona M. , Schlotterbeck Götz , Boissin Patrick , Binder Martin , Buettelmann Bernd , Hanlon Steven , Jaeschke Georg , Kolczewski Sabine , Kupfer Ernst , Peters Jens‐Uwe , Porter Richard H. P. , Prinssen Eric P. , Rueher Marianne , Ruf Iris , Spooren Will , Stämpfli Andreas , Vieira Eric 
Published: November 2007

AbstractDetailed information on the metabolic fate of lead compounds can be a powerful tool for an informed approach to the stabilization of metabolically labile compounds in the lead optimization phase. The combination of high performance liquid chromatography (HPLC) with nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) has been used to give comprehensive structural data on metabolites of novel drugs in development. Recently, increased automation and the embedding of on‐line solid‐phase extraction (SPE) into a integrated LC‐SPE‐NMR‐MS system have improved enormously the detection limits of this approach. The new technology platform allows the analysis of complex mixtures from microsome incubations, combining low material requirements with relatively high throughput. Such characteristics make it possible to thoroughly characterize metabolites of selected compounds at earlier phases along the path to lead identification and clinical candidate selection, thus providing outstanding guidance in the process of eliminating undesired metabolism and detecting active or potentially toxic metabolites. Such an approach was applied at the lead identification stage of a backup program on metabotropic glutamate receptor 5 (mGlu5) allosteric inhibition. The major metabolites of a lead 5‐aminothiazole‐4‐carboxylic acid amide 1 were synthesized and screened, revealing significant in vitro activity and possible involvement in the overall pharmacodynamic behavior of 1. The information collected on the metabolism of the highly active compound 1 was pivotal to the synthesis of related compounds with improved microsomal stability.
Obesity and mortality in men with locally advanced prostate cancer
Authors: Efstathiou Jason A. , Bae Kyounghwa , Shipley William U. , Hanks Gerald E. , Pilepich Miljenko V. , Sandler Howard M. , Smith Matthew R. 
Published: November 2007

AbstractBACKGROUND.Greater body mass index (BMI) is associated with shorter time to prostate‐specific antigen (PSA) failure following radical prostatectomy and radiation therapy (RT). Whether BMI is associated with prostate cancer‐specific mortality (PCSM) was investigated in a large randomized trial of men treated with RT and androgen deprivation therapy (ADT) for locally advanced prostate cancer.METHODS.Between 1987 and 1992, 945 eligible men with locally advanced prostate cancer were enrolled in a phase 3 trial (RTOG 85‐31) and randomized to RT and immediate goserelin or RT alone followed by goserelin at recurrence. Height and weight data were available at baseline for 788 (83%) subjects. Cox regression analyses were performed to evaluate the relations between BMI and all‐cause mortality, PCSM, and nonprostate cancer mortality. Covariates included age, race, treatment arm, history of prostatectomy, nodal involvement, Gleason score, clinical stage, and BMI.RESULTS.The 5‐year PCSM rate for men with BMI <25 kg/m2was 6.5%, compared with 13.1% and 12.2% in men with BMI ≥25 to <30 and BMI ≥30, respectively (Gray'sP= .005). In multivariate analyses, greater BMI was significantly associated with higher PCSM (for BMI ≥25 to <30, hazard ratio [HR] 1.52, 95% confidence interval [CI], 1.02–2.27,P= .04; for BMI ≥30, HR 1.64, 95% CI, 1.01–2.66,P= .04). BMI was not associated with nonprostate cancer or all‐cause mortality.CONCLUSIONS.Greater baseline BMI is independently associated with higher PCSM in men with locally advanced prostate cancer. Further studies are warranted to evaluate the mechanism(s) for increased cancer‐specific mortality and to assess whether weight loss after prostate cancer diagnosis alters disease course. Cancer 2007. © 2007 American Cancer Society.
Randomized clinical trial of a family intervention for prostate cancer patients and their spouses
Authors: Northouse Laurel L. , Mood Darlene W. , Schafenacker Ann , Montie James E. , Sandler Howard M. , Forman Jeffrey D. , Hussain Maha , Pienta Kenneth J. , Smith David C. , Kershaw Trace 
Published: November 2007

AbstractBACKGROUND.Few intervention studies have been conducted to help couples manage the effects of prostate cancer and maintain their quality of life. The objective of this study was to determine whether a family‐based intervention could improve appraisal variables (appraisal of illness or caregiving, uncertainty, hopelessness), coping resources (coping strategies, self‐efficacy, communication), symptom distress, and quality of life in men with prostate cancer and their spouses.METHODS.For this clinical trial, 263 patient‐spouse dyads were stratified by research site, phase of illness, and treatment; then, they were randomized to the control group (standard care) or the experimental group (standard care plus a 5‐session family intervention). The intervention targeted couples' communication, hope, coping, uncertainty, and symptom management. The final sample consisted of 235 couples: 123 couples in the control group and 112 couples in the experimental group. Data collection occurred at baseline before randomization and at 4 months, 8 months, and 12 months.RESULTS.At 4‐month follow‐up, intervention patients reported less uncertainty and better communication with spouses than control patients, but they reported no other effects. Intervention spouses reported higher quality of life, more self‐efficacy, better communication, and less negative appraisal of caregiving, uncertainty, hopelessness, and symptom distress at 4 months compared with controls, and some effects were sustained to 8 months and 12 months.CONCLUSIONS.Men with prostate cancer and their spouses reported positive outcomes from a family intervention that offered them information and support. Programs of care need to be extended to spouses who likely will experience multiple benefits from intervention. Cancer 2007. © 2007 American Cancer Society.
Hypermethylation of the somatostatin promoter is a common, early event in human esophageal carcinogenesis
Authors: Jin Zhe , Mori Yuriko , Hamilton James P. , Olaru Alexandru , Sato Fumiaki , Yang Jian , Ito Tetsuo , Kan Takatsugu , Agarwal Rachana , Meltzer Stephen J. 
Published: November 2007

AbstractBACKGROUND.The promoter of somatostatin (SST), a primary inhibitor of gastrin‐stimulated gastric acid secretion, is hypermethylated in 80% of human colon cancers. The aim of the current study was to investigate whether and at what stage promoter hypermethylation of SST is involved in human esophageal carcinogenesis.METHODS.SST promoter hypermethylation was examined by real‐time methylation‐specific polymerase chain reaction (PCR) (MSP) in 260 human esophageal tissue specimens. Real‐time reverse‐transcriptase PCR and MSP were also performed on esophageal cancer cell lines before and after treatment with 5‐aza‐2′‐deoxycytidine (5‐Aza‐dC).RESULTS.SST hypermethylation showed highly discriminative receiver‐operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) from normal esophagus (NE) (P < .01). Both SST methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett metaplasia without dysplasia or EAC (BE), low‐grade and high‐grade (HGD) dysplasia occurring in BE, EAC, and ESCC than in NE (P < .01). SST hypermethylation frequency was significantly lower in NE (9%) than in BE (70%), HGD (71.4%), or EAC (71.6%), whereas 14 (53.8%) of 26 ESCCs exhibited SST hypermethylation. There was a significant relation between SST hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Demethylation of KYSE220 ESCC and OE33 EAC cells with 5‐Aza‐dC reduced SST methylation and increased SST mRNA expression. SST mRNA levels in native unmethylated EACs were significantly higher than in native methylated EACs (P < .05).CONCLUSIONS.SST promoter hypermethylation is a common event in human esophageal carcinomas and is related to early neoplastic progression in Barrett esophagus. Cancer 2008. © 2007 American Cancer Society.
Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B‐cell chronic lymphocytic leukemia
Authors: Del Poeta Giovanni , Del Principe Maria Ilaria , Buccisano Francesco , Maurillo Luca , Capelli Giovanni , Luciano Fabrizio , Perrotti Alessio Pio , Degan Massimo , Venditti Adriano , de Fabritiis Paolo , Gattei Valter , Amadori Sergio 
Published: November 2007

AbstractBACKGROUND.Rituximab in sequential combination with fludarabine (Flu) allowed patients with B‐cell chronic lymphocytic leukemia (B‐CLL) to achieve higher remission rates and longer response duration. Based on their recent experience in indolent non‐Hodgkin lymphomas, in this study, the authors attempted to demonstrate whether consolidation/maintenance therapy with rituximab could prolong the response duration in this patient population.METHODS.This Phase II study was based on a consolidation/maintenance therapy with rituximab for patients in complete remission (CR) or partial remission (PR) who were positive for minimal residual disease (MRD), as determined by flow cytometry. Seventy‐five symptomatic, untreated patients with B‐CLL received 6 monthly cycles of Flu (25 mg/m2 for 5 days) followed by 4 weekly doses of rituximab (375 mg/m2). Then, 28 patients who were positive for MRD were consolidated with 4 monthly cycles of rituximab (375 mg/m2) followed by 12 monthly low doses of rituximab (150 mg/m2).RESULTS.Based on National Cancer Institute criteria, 61 of 75 patients (81%) achieved a CR, 10 of 75 patients (13%) had a PR, and 4 of 75 patients (5%) had either no response or disease progression. MRD‐positive patients in CR or PR who received consolidation therapy (n = 28 patients) had a significantly longer response duration (87% vs 32% at 5 years; P = .001) compared with a subset of patients who did not receive consolidation therapy (n = 18 patients). All patients experienced a long progression‐free survival from the end of induction treatment (73% at 5 years). It was noteworthy that, within the subset of ZAP‐70‐positive patients, MRD‐positive, consolidated patients (n = 12 patients) had a significantly longer response duration (69% vs 0% at 2.6 years; P = .007) compared with MRD‐positive, unconsolidated patients (n = 11 patients).CONCLUSIONS.The addition of a consolidation and maintenance therapy withrituximab prolonged response duration significantly in patients with MRD‐positive B‐CLL. Cancer 2008. © 2007 American Cancer Society.
Bcl‐6 predicts improved prognosis in primary central nervous system lymphoma
Authors: Levy Oren , DeAngelis Lisa M. , Filippa Daniel A. , Panageas Katherine S. , Abrey Lauren E. 
Published: November 2007

AbstractBACKGROUND.In systemic non‐Hodgkin lymphoma (NHL), tumors that resemble germinal center B‐cells are less aggressive than tumors that resemble postgerminal center B‐cells. However, the value of B‐cell differentiation markers in primary central nervous system lymphoma (PCNSL) is less clear. The objectives of this study were to characterize the immunophenotypes of PCNSL samples and to determine their utility in predicting clinical outcomes.METHODS.The immunohistochemical staining profile of PCNSL was determined from 66 immunocompetent patients. Then, the authors evaluated whether theexpression of these proteins was associated with progression‐free or overall survival.RESULTS.Only 8% of PCNSL samples were positive for the cluster designation (CD) germinal center marker CD10. Another germinal center marker, bcl‐6, was positive in 47% of samples. Ninety‐four percent of samples expressed significant levels of the postgerminal center marker melanoma‐associated antigen (MUM‐1). In univariate analyses, only bcl‐6 staining had a significant effect on progression‐free survival (median, 20.5 months in bcl‐6‐positive patients vs 10.1 months in bcl‐6‐negative patients; P = .02). There was a nonsignificant trend toward improved overall survival in patients who had bcl‐6 expressing tumors. Older age and poorer performance status, as observed previously, were associated with reduced survival.CONCLUSIONS.Bcl‐6 expression was associated with a better prognosis in patients with PCNSL. Cancer 2008. © 2007 American Cancer Society.
Time‐Resolved Synchrotron Radiation Excited Optical Luminescence: Light‐Emission Properties of Silicon‐Based Nanostructures
Authors: Sham Tsun‐Kong , Rosenberg Richard A. 
Published: November 2007

AbstractThe recent advances in the study of light emission from matter induced by synchrotron radiation: X‐ray excited optical luminescence (XEOL) in the energy domain and time‐resolved X‐ray excited optical luminescence (TRXEOL) are described. The development of these element (absorption edge) selective, synchrotron X‐ray photons in, optical photons out techniques with time gating coincide with advances in third‐generation, insertion device based, synchrotron light sources. Electron bunches circulating in a storage ring emit very bright, widely energy tunable, short light pulses (<100 ps), which are used as the excitation source for investigation of light‐emitting materials. Luminescence from silicon nanostructures (porous silicon, silicon nanowires, and Si–CdSe heterostructures) is used to illustrate the applicability of these techniques and their great potential in future applications.
Multichromophores for Nonlinear Optics: Designing the Material Properties by Electrostatic Interactions
Authors: Terenziani Francesca , D'Avino Gabriele , Painelli Anna 
Published: November 2007

AbstractTo fully exploit the promise of molecular materials for NLO applications, inter‐ and supramolecular interactions must be accounted for. We review our recent work on electrostatic interchromophore interactions in multichromophores for NLO applications. The discussion is based on a bottom‐up modeling strategy: each chromophore is described in terms of an essential state model, validated and parameterized against spectroscopic data for solvated chromophores. The relevant information is then used to build a model for clusters of chromophores interacting through electrostatic forces. Exact NLO responses and spectra calculated within this model fully account for collective and cooperative interchromophore interactions, which can either amplify or suppress NLO responses; supramolecular engineering of multichromophores is a powerful tool for the design of NLO materials. Moreover, new features emerge in multichromophores with no counterpart at the single‐chromophore level, offering new exciting opportunities for applications.
Conformational Relaxation of p‐Phenylenevinylene Trimers in Solution Studied by Picosecond Time‐Resolved Fluorescence
Authors: Di Paolo Roberto E. , Seixas de Melo João , Pina João , Burrows Hugh D. , Morgado Jorge , Maçanita António L. 
Published: November 2007

AbstractTwo p‐phenylenevinylene (PV) trimers, containing 3′‐methylbutyloxyl (in MBOPV3) and 2′‐ethylhexyloxyl (in EHOPV3) side chains, are used as model compounds of PV‐based conjugated polymers (PPV) with the purpose of clarifying the origin of fast (picosecond time) components observed in the fluorescence decays of poly[2‐methoxy‐5‐(2′‐ethylhexyloxy)‐p‐phenylenevinylene] (MEH‐PPV). The fluorescence decays of MBOPV3 and EHOPV3 reveal the presence of similar fast components, which are assigned to excited‐state conformational relaxation of the initial population of non‐planar trimer conformers to lower‐energy, more planar conformers. The rate constant of conformational relaxation kCR is dependent on solvent viscosity and temperature, according to the empirical relationship kCR=aηo−α⋅exp(−αEη/RT), where aηo−α is the frequency factor, ηo is the pre‐exponential coefficient of viscosity, Eη is the activation energy of viscous flow. The empirical parameter α, relating the solvent microscopic friction involved in the conformational change to the macroscopic solvent friction (α=1), depends on the side chain. The fast component in the fluorescence decays of MEH‐PPV polymers (PPVs), is assigned to resonance energy transfer from short to longer polymer segments. The present results call for revising this assignment/interpretation to account for the occurrence of conformational relaxation, concurrently with energy transfer, in PPVs.
Time series prediction model for sequential learning
Authors: Gouko Manabu , Sugaya Yoshihiro , Aso Hirotomo 
Published: November 2007

AbstractAs a time series prediction model for sequential learning considering memory size limitations, this paper proposes the Adaptive and Sequential Learning Network (ASLN) model. The proposed model sequentially memorizes time sequence information given as the input and then performs prediction based on the memory. While effective use of the memory capacity is attempted for changes in the ambient environment, the model can follow up by varying its own memory. The model memorizes the elements contained in the input time series and the information on their transitions. It identifies the elements with a higher frequency of inputs among the time series and memorizes them as priority items. Information on the transitions of the input elements is represented as a state vector and is memorized by a layered neural network. The state vector maintains information on the past input sequence so that expression of the context is possible. A numerical experiment shows that the proposed model can predict a time series while tracking environmental changes. An experiment on learning of a number sequence was performed, using handwritten number patterns containing fluctuations. The prediction capability was verified with an increasing number of patterns. Guidelines are also provided for setting of parameters, which is important when the model memorizes the transition information of the time series. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(12): 129–139, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20406
Robust obstacle detection in general road environment based on road extraction and pose estimation
Authors: Seki Akihito , Okutomi Masatoshi 
Published: November 2007

AbstractThis paper proposes a method of obstacle detection using vehicle‐mounted stereo cameras. There are various objects in the road environment; these can be divided into objects, such as pedestrians, which have the possibility of colliding with the vehicle, and objects, such as road patterns, which do not have such a possibility. In this paper, an obstacle is defined as an object which is located in the space through which the vehicle will travel. In order to decide whether an object is an obstacle from the pattern in the image, it is necessary to estimate the position of the pattern in relation to the road surface. For this purpose, the planar region is determined by dynamically estimating the homography (projection transformation) matrix between the images corresponding to the plane. The pose of the camera with respect to the road is determined. Then the spatial position obtained by stereo measurement is converted to road coordinates, based on the orientation of the road surface. By applying segmentation based on the converted result of stereo measurement, obstacles are detected. On ordinary roads it is required to detect various obstacles, ranging from relatively small obstacles such as pedestrians and bicycles to large obstacles such as cars. The proposed method can detect obstacles without explicit modeling. The effectiveness of the proposed method is demonstrated by experiments using various actual images. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(12): 12–22, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20413
An overview and case study of a statistical regression testing method for software maintenance
Authors: Takagi Tomohiko , Furukawa Zengo , Yamasaki Toshinori 
Published: November 2007

AbstractWe propose a statistical regression testing method for evaluating the reliability of software as part of the software maintenance process. Maintenance procedures take up more than half the time of the software development process; in addition, software reliability is an important factor in determining the dependability of a product. Regression tests are performed in order to conserve or improve software reliability as part of the software maintenance process. However, existing systematic testing methods based on regression tests are not necessarily appropriate for evaluating software reliability. The statistical regression testing method is a means for compensating for the flaws of such existing methods. In this method a model of how the user makes use of the software is defined by means of a Markov chain; this is known as theusage model, and then test cases are generated at random according to a probability distribution based on this usage model. In this paper we perform experiments applying the proposed method to a small‐scale client server program and demonstrate that the proposed method can be implemented. In addition, we clarify the effects and issues that may be anticipated when applying the method and establish how it may be used in practice. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(12): 23–34, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20414