bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total Synthesis of the Cyclodepsipeptide Apratoxin A and Its Analogues and Assessment of Their Biological Activities
Authors: Ma Dawei , Zou Bin , Cai Guorong , Hu Xiaoyi , Liu Jun O. 
Published: July 2006

AbstractA novel total synthesis of apratoxin A is described, with key steps including the assembly of its ketide segment through a D‐proline‐catalyzed direct aldol reaction and Oppolzer's anti aldol reaction and the preparation of its thiazoline unit in a biomimetic synthesis. An oxazoline analogue of apratoxin A has also been elaborated by a similar approach. This compound has a potency against HeLa cell proliferation only slightly lower than that of apratoxin A, whilst a C(40)‐demethylated oxazoline analogue of apratoxin A displays a much lower cytotoxicity and the C(37)‐epimer and C(37) demethylation product of this new analogue are inactive. These results suggest that the two methyl groups at C(37) and C(40) and the stereochemistry at C(37) are essential for the potent cellular activity of the oxazoline analogue of apratoxin A. Further biological analysis revealed that both synthetic apratoxin A and its oxazoline analogue inhibited cell proliferation by causing cell cycle arrest in the G1 phase.
Automated Protein–Ligand Crystallography for Structure‐Based Drug Design
Authors: Mooij Wijnand T. M. , Hartshorn Michael J. , Tickle Ian J. , Sharff Andrew J. , Verdonk Marcel L. , Jhoti Harren 
Published: July 2006

AbstractAn approach to automate protein–ligand crystallography is presented, with the aim of increasing the number of structures available to structure‐based drug design. The methods we propose deal with the automatic interpretation of diffraction data for targets with known protein structures, and provide easy access to the results. Central to the system is a novel procedure that fully automates the placement of ligands into electron density maps. Automation provides an objective way to structure solution, whereas manual placement can be rather subjective, especially for data of low to medium resolution. Ligands are placed by docking into electron density, whilst taking care of protein–ligand interactions. The ligand fitting procedure has been validated on both public domain and in‐house examples. Some of the latter deal with cocktails of low‐molecular weight compounds, as used in fragment‐based drug discovery by crystallography. For such library‐screening experiments we show that the method can automatically identify which of the compounds from a cocktail is bound.
Rational Design of Aziridine‐Containing Cysteine Protease Inhibitors with Improved Potency: Studies on Inhibition Mechanism
Authors: Vicik Radim , Helten Holger , Schirmeister Tanja , Engels Bernd 
Published: July 2006

AbstractTo enable a rational design of improved cysteine protease inhibitors, the present work investigates trends in the inhibition potency of aziridine derivatives with a substituted nitrogen center. To predict the influence of electron‐withdrawing substituents, quantum chemical computations of the ring opening of N‐formylated, N‐methylated, and N‐unsubstituted aziridines with thiolate were performed. They revealed that the N‐formyl group leads to a strong decrease of the reaction barrier and a considerable increase in exothermicity due to stabilization of the transition state. In contrast, a nucleophilic attack at the carbonyl carbon atom is characterized by very low reaction barriers, suggesting a reversible reaction, thus providing the theoretical background for the reversible inhibition of cysteine proteases by peptidyl aldehydes. Reactions of aziridine building blocks (diethyl aziridine‐2,3‐dicarboxylate 1, diethyl 1‐formyl aziridine‐2,3‐dicarboxylate 2) with a model thiolate in aqueous solution which were followed by NMR spectroscopy and mass spectrometry, showed the N‐formylated compound 2 to readily undergo a ring‐opening reaction. In contrast, the reaction of 1 with the thiolate is much slower. Enzyme assays with the cysteine protease cathepsin L showed 2 to be a 5000‐fold better enzyme inhibitor than 1. Dialysis assays clearly proved irreversible inhibition. These experiments, together with the results obtained with the model thiolate, indicate that the main inhibition mechanism of the N‐formylated aziridine 2 is the ring‐opening reaction rather than the reversible attack of the active site cysteine residue at the carbonyl carbon atom.
Influence of tumor type, disease status, and patient age on self‐reported interest regarding participation in cancer clinical trials
Authors: Markman Maurie , Petersen Judith , Montgomery Robert 
Published: July 2006

AbstractThere is limited information available regarding the reasons cancer patients decide to enter clinical trials. To explore this issue, aggregate responses to the question, “Are you interested in learning about clinical trials for your condition?” obtained from >115,000 cancer patients (or their families) who entered data into 1 of several proprietary decision‐support programs embedded within approximately 100 well‐established cancer‐related Internet sites were analyzed. The percentage of patients (or their families) who expressed interest in learning about clinical trials ranged from as low as 21% (endometrial and cervix cancer patients >80 years of age; n = 178) to as high as 85% (recurrent ovarian cancer patients, age 51–60; n = 842). Patients >80 years of age, regardless of sex, tumor type, or status of disease, were considerably less likely to be interested in clinical trial information than younger individuals. Whereas there were no differences between males and females in their desire to obtain information, patients with self‐declared more “serious conditions” (e.g., metastatic breast cancer, recurrent prostate cancer), and those with specific cancers having a widely recognized poor prognosis (e.g., nonsmall cell lung cancer), were more likely to request study information. In the current evaluation of a large database of individuals who elected to participate in 1 of several cancer‐related decision‐support programs, major differences in self‐expressed interest in obtaining information regarding clinical trials was observed. Particularly notable was the reduced desire to gather such information among the very elderly, and the increased interest by patients with the most serious cancer‐related conditions. Cancer 2006. © 2006 American Cancer Society.
A randomized trial to improve early detection and prevention practices among siblings of melanoma patients
Authors: Geller Alan C. , Emmons Karen M. , Brooks Daniel R. , Powers Catherine , Zhang Zi , Koh Howard K. , Heeren Timothy , Sober Arthur J. , Li Frederick , Gilchrest Barbara A. 
Published: July 2006

AbstractBACKGROUND.Identifying high‐risk individuals for melanoma education and risk reduction may be a viable strategy to curb the incidence of melanoma, which has risen precipitously in the past 50 years. The first‐degree relatives of melanoma patients represent a risk group who may experience a ‘teachable moment’ for enhanced education and risk reduction.METHODS.We report a randomized trial testing an intervention that provided personalized telephone counseling and individually tailored materials to siblings of recently‐diagnosed melanoma patients. The purpose of this study was to test whether an intervention could lead to improvements in siblings' skin cancer risk reduction practices. Intervention condition participants received the following: 1) an initial motivational and goal‐setting telephone intervention session delivered by the health educator; 2) three sets of computer‐generated materials specifically tailored to individual responses from the baseline survey; 3) three telephone counseling sessions with the health educator, timed to follow receipt of the mailed materials; and 4) linkages to free screening programs. Families in the usual care arm received the suggestion from the physician that patients diagnosed with melanoma notify the family members about their diagnosis and encourage the family members to be screened.RESULTS.494 siblings were recruited to the study and 403 siblings remained in the study through at least 6 months. At 12 months, intervention siblings were more likely to examine all moles, including those on the back (OR, 1.76; 95% CI, 1.06–2.91). Compared with baseline, the number of participants in both groups that had received a skin cancer examination more than doubled, with no differences between groups. At 12 months, two‐thirds of siblings in both groups reported routine use of sunscreen, but there were no differences in change over baseline between the two groups.CONCLUSIONS.This study is the one of the first, to our knowledge, to address skin cancer risk‐reduction strategies in a sample of individuals who have a recent family diagnosis of melanoma. Diagnosis of melanoma in a family member provides an important opportunity to intervene with others in that family. The components of the intervention may provide a useful foundation for future efforts to target the more than half million siblings at risk for melanoma, a lethal but preventable disease. Cancer 2006. © 2006 American Cancer Society.
What motivates men age ≥ 50 years to participate in a screening program for melanoma?
Authors: Janda Monika , Youl Philippa H. , Lowe John B. , Baade Peter D. , Elwood Mark , Ring Ian T. , Aitken Joanne F. 
Published: July 2006

AbstractBACKGROUND.The screening behavior and screening outcomes of men age ≥50 years was investigated within a randomized controlled trial of a community‐based intervention of screening for melanoma, consisting of a community education program, an education program for medical practitioners, and the provision of dedicated skin‐screening clinics.METHODS.Data from cross‐sectional telephone surveys before (559 completed interviews), at the end (591 completed interview), and at 2 years after the intervention (445 completed interviews) were analyzed. In addition, the authors analyzed data from skin‐screening clinics within the intervention program (3355 men age ≥50 years participated).RESULTS.During the intervention period men age ≥50 years increased both their screening behavior and intention to screen. Those men age ≥50 years who reported a past history of removal of a mole as well as other risk factors for skin cancer and positive attitudes toward screening were more likely to participate in skin screening across time. Men age ≥50 years accounted for 20.5% of all skin‐screening clinic attendees, 31.3% of those referred for a suspicious lesion, 48.5% of melanomas, and 45% of all keratinocyte carcinomas diagnosed within the screening program, respectively.CONCLUSIONS.The intervention program successfully motivated men age ≥50 years to attend screening for skin cancer, resulting in the highest yield of skin cancer within this subgroup of the population. Messages addressing skin cancer risk factors and attitudes toward skin cancer and screening could be used to target a screening program for melanoma toward men age ≥50 years. Cancer 2006. © 2006 American Cancer Society.
Combinational antitumor effect of siRNA against midkine and paclitaxel on growth of human prostate cancer xenografts
Authors: Takei Yoshifumi , Kadomatsu Kenji , Goto Tatsunori , Muramatsu Takashi 
Published: July 2006

AbstractBACKGROUND.Midkine (MK) is a heparin‐binding growth factor that promotes the growth, migration, and survival of various cells. Its overexpression has been observed in many human malignancies, making it an attractive therapeutic target.METHODS.We established a human midkine blockade system involving RNA interference.RESULTS.The synthetic small interfering RNA (siRNA) targeting human midkine almost completely inhibited the secretion of midkine by a human prostate cancer cell line, PC‐3, and consequently suppressed the proliferation and anchorage‐independent growth of the transfected cells. The midkine siRNA, together with atelocollagen, significantly suppressed the growth of PC‐3 tumors, which had been subcutaneously xenografted. These inhibitory effects of midkine siRNA were augmented by combinational treatment with a chemotherapeutic, paclitaxel (PTX), both in vitro and in vivo. The dose of PTX (12 mg/kg) used for the combinational treatment did not cause leukopenia or liver damage, which are often reported as serious adverse effects of PTX. The effect of the combination on tumor growth was comparable with that of PTX alone at higher doses that have exhibited severe adverse effects. Midkine siRNA suppressed mainly cell proliferation and slightly angiogenesis, whereas PTX enhanced apoptosis and slightly suppressed angiogenesis. The combination treatment was particularly effective for suppression of angiogenesis; consequently, it had striking effects on all aspects (proliferation, apoptosis, and angiogenesis).CONCLUSIONS.We established a novel and safe cancer therapy strategy involving midkine siRNA combined with PTX, with less adverse effects. Cancer 2006. © 2006 American Cancer Society.
Influence of Electric Field on the Phase Transitions of the Hexagonal Cylinder Phase of Diblock Copolymers
Authors: Li Xin , Jiang Ying , Li Yinchang , Liang Haojun 
Published: July 2006

AbstractWe have used the cell dynamic simulations (CDS) method to study the evolution of asymmetric and symmetric diblock copolymers under electric fields. For symmetric diblock copolymers, long‐range‐ordered lamellar phases form readily under electric fields. For asymmetric diblock copolymers, sphere‐to‐cylinder phase transitions occur rapidly when strong electric fields are applied, but it takes longer for the system to form hexagonal cylinder structures. The results of these simulations suggest that the sphere phase is stable under weak electric fields, but a threshold electric intensity exists for the sphere‐to‐cylinder phase transition. In addition, we also studied the kinetic pathways of the transition of the lamellar phase to the hexagonal cylinder phase of the asymmetric diblock copolymers under electric fields. Hexagonal cylinder structures form when the lamellar phase is subjected to a sudden temperature jump. The scattering functions suggest that the hexagonal cylinder structures are very regular and possess very few flaws.
Novel Thallium(III) Solid‐Contact Ion‐Selective Electrode with Electropolymerized Transducer
Authors: Kharitonov Sergey V. , Zarembo Yana V. , Zarembo Viktor I. 
Published: July 2006

AbstractA solid‐contact ion‐selective electrode for thallium(III) based on its complex with new complexone N,N′‐dioctylethylenediamine‐N,N′‐disuccinic acid ([Tl(DOEDDSA)]−) into a polymeric membrane is described. The ion‐to‐electron transducer used as the solid contact electrode was polyaniline which was electrochemically polymerized on a Pt wire. The plasticized poly(vinyl chloride) membrane incorporate ion‐associate of [Tl(DOEDDSA)]− with N,N,N‐trihexadecyl‐N‐methylammonium cation as electroactive material for ionometric sensor controls. The best performance in terms of slope (56±2 mV per decade) and response time (15 s) is displayed. The sensor shows a Nernstian response for [Tl(DOEDDSA)]− ions over a wide concentration range of 6.4×10−7 to 10−2 M, with a detection limit of thallium complexonate 8.2×10−8 M. The sensor can be used for more than three months without any considerable divergence in potentials. The selectivity is also good towards the most common univalent and divalent anions and the signal is constant in the pH range 4.7–9.0. An application to thallium determination in a mineral sample proved to be a success, and it was employed as an indicator electrode in direct potentiometry.
Response Mechanisms and New Approaches with Solid‐State Ion‐Selective Electrodes: A Powerful Multitechnique Materials Characterization Approach
Authors: De Marco Roland , Jiang Zhong‐Tao , Becker Thomas , Clarke Graeme , Murgatroyd Gareth , Prince K. 
Published: July 2006

AbstractIn modern materials science, there is a plethora of characterization techniques of materials that can provide valuable insights into the fundamental chemical physics of solid‐state devices such as chalcogenide glass ion‐selective electrodes (ISEs). In this paper, electrochemical impedance spectroscopy (EIS), X‐ray photoelectron spectrometry (XPS) and secondary ion mass spectrometry (SIMS) have been used in the elucidation of the mechanistic chemistry of the cadmium chalcogenide glass ISE. Furthermore, in situ synchrotron radiation‐grazing incidence X‐ray diffraction (SR‐GIXRD), in situ EIS/SR‐GIXRD, along with small angle neutron scattering (SANS), can be used to unravel the complex relationship between the nanostructure, bulk electrical conductivity and concomitant electrochemical reactivity of an iron chalcogenide glass ISE. Significantly, exciting preliminary modified atomic force microscopy (AFM) data – utilizing AFM cantilevers with attached microparticles of the copper sensing material jalpaite – demonstrate the tremendous potential of selective force ISE‐AFM in the imaging of important molecular structures such as the copper ion channels of cell membranes in fish gills and/or phytoplankton.
Comparison of Different Contactless Conductivity Detectors for the Determination of Small Inorganic Ions by Capillary Electrophoresis
Authors: Kubáň Pavel , Evenhuis Christopher J. , Macka Mirek , Haddad Paul R. , Hauser Peter C. 
Published: July 2006

AbstractThe analytical performance parameters of four different contactless conductivity detectors for capillary electrophoresis were determined. These detectors were designed either with a miniature cell for versatility, with high voltage excitation for high sensitivity or with a battery power supply for field application. One of the units is commercially available. The plate numbers and reproducibility of peak areas (typically about 2%) were very similar, indicating that these parameters are generally limited by the separation and injection procedures rather than the detectors. The linear dynamic ranges are better than 2 orders of magnitude for all detectors and the correlation coefficients were also almost identical. Significant differences were found with regard to the detection limits. For the detector with a miniature cell, which lacks an in‐cell amplifier, the detection limit was typically 1.5 μM for the inorganic ions tested (K+, Ca2+, Na+, Mg2+, Li+, Cl−, NO3− and SO42−), while with the other 3 detectors this parameter was as low as about 0.1 μM. The use of buffer solutions with relatively high background conductivity was found to lead to detection limits which were up to one order of magnitude higher. The extent of deterioration of this parameter with buffer conductivity was found to be related to the excitation voltage and was most pronounced for the high voltage detector.
All Solid‐State pH Electrode Based on Titanium Nitride Sensitive Film
Authors: Wang Yan , Yuan Hongyan , Lu Xulin , Zhou Zaide , Xiao Dan 
Published: July 2006

AbstractTitanium nitride was used as pH‐sensitive material to fabricate all solid‐state pH electrode. The fabrication and the response performance of the pH electrode were described in the paper. The TiN film electrode showed a linear response in the pH range of 2–12 with a near‐Nenstian response (−55 mV/pH). The response time was within 1 min, and the electrode had good reproducibility, stability and low sensitivities for different species. Compared with the glass pH electrode, the electrode exhibited some advantages, for example, without activation, rapid response and high mechanical strength. In addition, the electrode performed excellently in a corrosion medium containing F−(1 M). Electrochemical behaviors of TiN electrode in Britton‐Robinson buffers were studied with Electrochemical Impedance Spectroscopy (EIS).
Dopamine Oxidation at Per(6‐deoxy‐6‐thio)‐α‐Cyclodextrin Monolayer Modified Gold Electrodes
Authors: Majewska Urszula E. , Chmurski Kazimierz , Biesiada Krzysztof , Olszyna Andrzej R. , Bilewicz Renata 
Published: July 2006

AbstractThe gold electrode is functionalized by sequential self‐assembly of a monolayer of the title thiolated cyclodextrin with and without dopamine included in the cavities. The structure of α‐cyclodextrin modified gold electrode is carefully characterized using STM and AFM. Surface complexation of dopamine is examined and its association constant is evaluated. Chemical reactions accompanying the electrode process of dopamine, which interfere in the electrochemical dopamine determination, are described and the conditions to avoid them are proposed. Dopamine incorporated in the α‐cyclodextrin sites anchored to the electrode surface was found to provide electrochemical contact of the electrode with the solution‐resident dopamine. Dopamine present in the α‐cyclodextrin cavities has different properties compared to dopamine in the bulk buffer solution and can act as a mediator for the dopamine molecules diffusing to the electrode. This unique mediation effect leads to improvement of the sensitivity of dopamine determination using the α‐cyclodextrin modified electrode and a procedure for the determination of dopamine in large excess of ascorbate is proposed.
Preparation, Characterization and Analytical Applications of a New and Novel Electrically Conducting Polymer
Authors: D'Eramo F. , Sereno L. E. , Arévalo A. H. 
Published: July 2006

AbstractIn this study, a glassy carbon electrode (GC) was modified with an electropolymerized film of 1‐naphthylamine (1‐NAP) with a subsequent overoxidation treatment in 0.2 M sodium hydroxide solution. This polymer p‐1‐NAPox film coated GC electrode was used for the selective determination of dopamine (DA) in the presence of a triple concentration of ascorbic acid (AA).These studies were performed using cyclic voltammetry and square‐wave voltammetry at physiological pH. p‐1‐NAPox shows an attractive permselectivity, a marked enhancement of the current response and antifouling properties when compared to a bare GC electrode activated in basic media. With a preconcentration time of 3 minutes at open circuit, linear calibration plots were obtained for DA in buffer solution (pH 7.4) over the concentration range from 1×10−6–1×10−4 M with a detection limit of 1.59×10−7 M.
Detrending economic time series: a Bayesian generalization of the Hodrick–Prescott filter
Authors: Trimbur Thomas M. 
Published: July 2006

AbstractThis article develops a new method for detrending time series. It is shown how, in a Bayesian framework, a generalized version of the Hodrick–Prescott filter is obtained by specifying prior densities on the signal‐to‐noise ratio (q) in the underlying unobserved components model. This helps ensure an appropriate degree of smoothness in the estimated trend while allowing for uncertainty in q. The article discusses the important issue of prior elicitation for time series recorded at different frequencies. By combining prior expectations with the likelihood, the Bayesian approach permits detrending in a way that is more consistent with the properties of the series. The method is illustrated with some quarterly and annual US macroeconomic series.  Copyright © 2006 John Wiley & Sons, Ltd.
Random walk hypothesis in exchange rate reconsidered
Authors: Chu Chia‐Shang J. , Lu Hsin‐Min 
Published: July 2006

AbstractAn econometric model for exchange rate based on the behavior of dynamic international asset allocation is considered. The capital movement intensity index is constructed from the adjustment of a fully hedged international portfolio. Including this index as an additional explanatory variable helps to explain the fluctuation of the exchange rate and predict better than the competing random walk model. Supporting empirical evidence is found in Germany–USA, Japan–USA, Singapore–USA and Taiwan–USA exchange markets.  Copyright © 2006 John Wiley & Sons, Ltd.