bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarker‐based phase I dose‐escalation, pharmacokinetic, and pharmacodynamic study of oral apricoxib in combination with erlotinib in advanced nonsmall cell lung cancer
Authors: Reckamp Karen , Gitlitz Barbara , Chen Lin‐Chi , Patel Ravi , Milne Ginger , Syto Mary , Jezior Deborah , Zaknoen Sara 
Published: October 2010

AbstractBACKGROUND:Apricoxib, a novel once‐daily selective cyclooxygenase‐2 inhibitor, was investigated in combination with erlotinib for recurrent stage IIIB/IV nonsmall cell lung cancer to determine the maximum tolerated dose, dose‐limiting toxicity, and recommended phase II dose (RP2D) based on changes in urinary prostaglandin E2 metabolite (PGE‐M).METHODS:Patients received escalating doses of apricoxib (100, 200, and 400 mg/day) in combination with erlotinib 150 mg/day until disease progression or unacceptable toxicity. Urinary PGE‐M was used to assess biologic activity and inform the optimal biologic dose.RESULTS:Twenty patients were treated (3 at 100 mg; 3 at 200 mg; 14 at 400 mg apricoxib) with a median of 4 cycles (range, 2‐14 cycles); 8 patients (40%) received prior EGFR‐directed therapies. No dose‐limiting toxicity was observed. Study drug‐related adverse events (AEs) included diarrhea, rash, dry skin, anemia, fatigue, and increased serum creatinine; 4 patients had grade ≥3 drug‐related AEs (diarrhea, perforated duodenal ulcer, hypophosphatemia, and deep vein thrombosis). The RP2D was 400 mg/day based on safety, biologic activity based on decreases in urinary PGE‐M, and pharmacokinetics. One patient had a partial response, and 11 had stable disease. Stable disease was observed in patients who had received prior EGFR inhibitor therapy but was greater in patients not previously treated with an EGFR inhibitor. Seventeen patients had elevated urinary PGE‐M at baseline, and 14 (70%) had a decrease from baseline, which was associated with disease control.CONCLUSIONS:Apricoxib plus erlotinib was well tolerated and yielded a 60% disease control rate. A phase II trial is currently investigating 400 mg/day apricoxib plus 150 mg/day erlotinib in patients selected based on change in urinary PGE‐M. Cancer 2011. © 2010 American Cancer Society.
Association of multi‐drug resistance gene polymorphisms with pancreatic cancer outcome
Authors: Tanaka Motofumi , Okazaki Taro , Suzuki Hideo , Abbruzzese James L. , Li Donghui 
Published: October 2010

AbstractBACKGROUND:The purpose of this study was to identify single nucleotide polymorphisms (SNPs) of multidrug resistance genes that are associated with clinical outcome in patients with potentially resectable pancreatic adenocarcinoma who were treated with preoperative gemcitabine‐based chemoradiotherapy at M. D. Anderson Cancer Center.METHODS:We selected 8 SNPs of 7 drug resistance genes, including MDR1 (ABCB1), MRP1‐5 (ABCC1‐5), and BCRP (ABCG2), reported to be important in mediating drug resistance. Genotype was determined by the Taqman method. The associations of genotype with tumor response to therapy and overall survival (OS) were evaluated using log‐rank test, Cox regression, and logistic regression models.RESULTS:MRP5 A‐2G AA genotype showed significant association with OS (log‐rank P = .010). The hazard ratio (95% confidence interval) was 1.65 (1.11‐2.45) after adjusting for clinical predictors. The MRP2 G40A GG genotype had a weak association with reduced OS (log‐rank P = .097). A combined effect of the two genotypes on OS was observed. Patients with none of the adverse genotypes had a median survival time (MST) of 34.0 months, and those with 1‐2 deleterious alleles had a significantly lower MST of 20.7 months (log‐rank P = .006). MRP2 G40A GG genotype was also significantly associated with poor histological response to chemoradiotherapy (P = .028).CONCLUSIONS:These observations suggest a potential role of polymorphic variants of drug resistance genes in predicting therapeutic efficacy and survival of patients with potentially resectable pancreatic cancer. Cancer 2011. © 2010 American Cancer Society.
Prognostic model for survival in patients with early stage cervical cancer
Authors: Biewenga Petra , van der Velden Jacobus , Mol Ben Willem J. , Stalpers Lukas J. A. , Schilthuis Marten S. , van der Steeg Jan Willem , Burger Matthé P. M. , Buist Marrije R. 
Published: October 2010

AbstractBACKGROUND:In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment.METHODS:A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease‐specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2‐IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic.RESULTS:The 5‐year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5‐year DSS showed a good discriminative capacity (AUC, 0.85).CONCLUSIONS:In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high‐risk early cervical cancer patients, both to stratify and to include patients. Cancer 2011. © 2010 American Cancer Society.
Diabetes as a disease of endoplasmic reticulum stress
Authors: Thomas Sally E. , Dalton Lucy E. , Daly Marie‐Louise , Malzer Elke , Marciniak Stefan J. 
Published: October 2010

AbstractEndoplasmic reticulum (ER) stress is an integral part of life for all professional secretory cells, but it has been studied to greatest depth in the pancreatic β‐cell. This reflects both the crucial role played by ER stress in the pathogenesis of diabetes and also the exquisite vulnerability of these cells to ER dysfunction. The adaptive cellular response to ER stress, the unfolded protein response, comprises mechanisms to both regulate new protein translation and a transcriptional program to allow adaptation to the stress. The core of this response is a triad of stress‐sensing proteins: protein kinase R‐like endoplasmic reticulum kinase (PERK), inositol‐requiring enzyme 1 (IRE1) and activating transcription factor 6. All three regulate portions of the transcriptional unfolded protein response, while PERK also attenuates protein synthesis during ER stress and IRE1 interacts directly with the c‐Jun amino‐terminal kinase stress kinase pathway. In this review we shall discuss these processes in detail, with emphasis given to their impact on diabetes and how recent findings indicate that ER stress may be responsible for the loss of β‐cell mass in the disease. Copyright © 2010 John Wiley & Sons, Ltd.
Synthetic and Electrochemical Studies of [2Fe2S] Complexes Containing a 4‐Amino‐1,2‐dithiolane‐4‐carboxylic Acid Moiety
Authors: Apfel Ulf‐Peter , Kowol Christian R. , Morera Enrico , Görls Helmar , Lucente Gino , Keppler Bernhard K. , Weigand Wolfgang 
Published: October 2010

AbstractIn the search for novel [FeFe] hydrogenase model systems several di‐ and tripeptides containing an 4‐amino‐1,2‐dithiolane‐4‐carboxylic acid (Adt) moiety orN‐phenylsulfonyl‐Adt‐OMe were treated with Fe3(CO)12. The resulting [FeFe] complexes were characterized by1H and13C NMR spectroscopy, mass spectrometry and elemental analysis. All complexes were investigated by cyclic voltammetry, and their ability to catalyze the reduction of protons to dihydrogen, as a function of acid concentration, was studied in different solvents.
Density Functional Theory Studies of [Fe(O)2L]2+: What is the Role of the Spectator Ligand L with Different Coordination Numbers?
Authors: Tong Glenna So Ming , Che Chi‐Ming 
Published: October 2010

AbstractDensity functional theory (DFT) studies were carried out on [Fe(O)2(L)]n+ [L = qpy (1), simple amines (2), and tpy (3); qpy = 2,2′:6′,2″:6″,2″′:6″′,2″″‐quinquepyridine and tpy = terpyridine; n = 1 or 2] to study how the coordination number of the spectator ligand L affects the geometries and electronic structures of the complexes. It was found that qpy can act as both a tridentate and pentadentate ligand resulting in [Fe(O)2(qpy)]2+ (12+) having a trigonal bipyramidal (TBP) geometry in the former case, and a pentagonal bipyramidal (PBP) geometry in the latter case. The difference in coordination geometries has a significant impact on the electronic structures of 12+. With a TBP geometry, 12+ adopts a [FeV(O)2(qpy)+·]2+ formalism where a d3 quartet FeV ion ferromagnetically and antiferromagnetically couples to the qpy cation radical to give close‐lying triplet and quintet states (within ca. 0.2 eV). With a PBP geometry, the FeV ion in 12+ also formally has three unpaired electrons (a d3 quartet) with the fourth unpaired electron localized on a single oxido ligand to give a quintet state. The unoccupied orbital of 12+ in PBP geometry is lower lying in energy and has higher oxido character than when the complex has TBP geometry. Thus, based on the MO energies and oxido character of the unoccupied orbital, 12+ with PBP geometry is proposed to be a more reactive oxidant than 12+ with TBP geometry. On the other hand, 12+ with TBP geometry has a similar electronic structure to heme Cpd I, and it is possible that these two compounds have similar oxygen atom transfer reaction mechanisms. By varying the ligand coordination number using different spectator ligands L, the dioxido‐iron complex [Fe(O)2(L)]2+ can change from a high‐spin triplet when L = tpy, to a low‐spin singlet when L = simple amines, to a quasi‐degenerate triplet and quintet state when L = qpy.
Anomeric Effect of the Nitrogen Atom in the Isocyano and Urea Groups
Authors: Ichikawa Yoshiyasu , Watanabe Hitomi , Kotsuki Hiyoshizo , Nakano Keiji 
Published: October 2010

AbstractThe anomeric effect associated with the nitrogen atom in the isocyano group was investigated by using 1H NMR spectroscopic analysis of an anomeric pair of xylopyranosyl isocyanides 8 and 7. We found that β‐anomer 7 prefers to exist in the 1C4 conformation in which the nitrogen atom in the isocyano group adopts an axial orientation. This observation, coupled with the results of X‐ray crystallographic analysis establishes that the nitrogen atom in the isocyano group displays the anomeric effect. Furthermore, xylopyranosyl isocyanides 8 and 7 were transformed into the corresponding xylopyranosyl ureas 10 and 11. In the case of the urea group, a normal sterically determined preference is observed in which the bulky urea substituents at the pyranose anomeric position occupy the equatorial position.
Palladium‐Catalyzed Reactions of 3‐Substituted Methylenecyclopropanes
Authors: Shao Li‐Xiong , Li Jia , Wang Bao‐Yu , Shi Min 
Published: October 2010

AbstractPd‐catalyzed reactions of 3‐substituted methylenecyclopropanes (MCPs), in which the substituents can be either hydroxymethyl or formyl, have been thoroughly investigated in the presence or absence of an acid source. It was found that the Pd‐catalyzed reactions of methylenecyclopropylcarbinols (Z)‐1 in the presence of acetic acid, acetic acid 2‐methylene‐but‐3‐enyl esters 4 can be formed in moderate yields. It was also found that Pd alone can catalyze the isomerization of methylenecyclopropylcarbinols (E)‐1 in the absence of an acid source to form pent‐4‐enals 3. The Pd‐catalyzed reactions of methylenecyclopropanecarbaldehydes 5 were also carried out in the presence of acetic acid. It was found that when (E)‐5 was used as the substrate, the isomerized product, penta‐2,4‐dienal 6, could be obtained in good to high yields, whereas the use of (Z)‐5 gave 2‐(3‐formylpenta‐2,4‐dienylidene)cyclopropanecarbaldehyde 7 in moderate to good yields. Plausible mechanisms for all these transformations have been discussed on the basis of the obtained results and control experiments.
trans‐Tetrahydrofurans by OH‐Assisted Ru‐Catalyzed Isomerization of 2‐Butene‐1,4‐diols
Authors: Fehr Charles , Magpantay Iris , Saudan Lionel , Sommer Horst 
Published: October 2010

AbstractWe herein report a general method for the synthesis of 1,2‐annulated trans‐tetrahydrofurans by the OH‐assisted Ru‐catalyzed isomerization of (Z)‐2‐butene‐1,4‐diols (using Chaudret's catalyst), followed by reduction of the incipient lactol (using Et3SiH and Amberlyst 15). Alternatively, the lactol can be oxidized to the corresponding lactone (using Ikariya's catalyst). It was shown by labeling experiments that an addition/elimination pathway is (at least to some extent) operative for the isomerization reaction.
Optimization of cyclical electrical field flow fractionation
Authors: Srinivas Merugu , Sant Himanshu J. , Gale Bruce K. 
Published: October 2010

AbstractCyclical electrical field flow fractionation (CyElFFF) is a variation on electrical field flow fractionation (ElFFF) where cyclical electrical fields are used instead of steady DC fields to increase the effective field experienced by particles in the flow channel. Even though the effective field increases more than 20‐fold compared to normal ElFFF, the retention and resolution in CyElFFF has not been shown to be better than in ElFFF. In this paper we report how one can optimize operational parameters in CyElFFF to obtain good retention and resolution in CyElFFF. The effects of offset voltage, frequency, flowrate, concentration of particles and sample size on retention, resolution and retained peak/void peak ratio have been observed. The results obtained from these experiments were analyzed and suggestions have been made to improve both retention and resolution. A 4‐fold improvement in retention without a significant increase in band broadening is reported.
Physical interpretation of the Lr parameter in the theory for the gel electrophoresis of partially denatured DNA
Authors: Sean David , Slater Gary W. 
Published: October 2010

AbstractPartial strand melting of dsDNA during gel electrophoresis typically results in an abrupt reduction of mobility. Several DNA analysis technologies are based on this phenomenon. Inspired by the de Gennes' theory for the reptation of branched polymers in gels, Lerman et al. (Ann. Rev. Biophys. Bioeng. 1984, 13, 399–423) proposed a mathematical expression to predict this reduced mobility. The latter contains only two parameters: the average number of denatured bases p̄ (which can be obtained using a theory for DNA melting) and a constant Lr. However, there is confusion in the literature regarding the physical interpretation of Lr and little is known about its dependence upon experimental parameters. The purpose of this short communication is to derive an explicit equation for the parameter Lr from the de Gennes theory of reptation. Our derivation shines light on the meaning of Lr, clarifies the scope of the underlying approximations, and makes predictions about the dependence of Lr upon the gel pore size and the persistence length of ssDNA.
Interaction of uranyl with Se(IV) and Se(VI) in aqueous acid solutions by means of capillary electrophoresis
Authors: Sladkov Vladimir 
Published: October 2010

AbstractThe uranyl–selenium(IV) and uranyl–selenium(VI) interactions were studied by CE in aqueous acid solutions, containing U(VI) and Se(IV) or Se(VI) at different concentrations, at pH 1.5, 2.0 and 2.5. The method proposed in this paper allows one with the use of CE data on metal ion mobilities at different pHs to establish the ligand species interacting with metal ion and complex species formed. In the case of Se(VI) a selenate, as demonstrated, interacts with uranyl ions, in the case of Se(IV) this is a hydroselenite. It was also shown that the equilibria for the U(VI)–Se(VI) and U(VI)–Se(IV) systems can be established from CE data. The formation of UO2SeO4, UO2(SeO4), UO2HSeO and UO2(HSeO3)2 species is demonstrated. The stability constant values were measured at different ionic strengths (from 0.02 to 0.2 mol/L). The logarithms of the stability constant values (β°) extrapolated to ionic strength 0 by the specific ion interaction theory (SIT) are found to be log β°1=2.93±0.06 for UO2SeO4 formation, log β°2=4.030.18 for UO2(SeO4) formation, log β°1=3.270.15 for UO2HSeO formation and log β°2=5.510.11 for UO2(HSeO3)2 at 25°C. The results for the first constant values for each of systems are consistent with the published values. For UO2(SeO4) formation, a new constant stability value is given. The existence of UO2(HSeO3)2 complex species is demonstrated and its constant stability value is given for the first time.
Modularity in the mammalian dentition: mice and monkeys share a common dental genetic architecture
Authors: Hlusko Leslea J. , Sage Richard D. , Mahaney Michael C. 
Published: October 2010

AbstractThe concept of modularity provides a useful tool for exploring the relationship between genotype and phenotype. Here, we use quantitative genetics to identify modularity within the mammalian dentition, connecting the genetics of organogenesis to the genetics of population‐level variation for a phenotype well represented in the fossil record. We estimated the correlations between dental traits owing to the shared additive effects of genes (pleiotropy) and compared the pleiotropic relationships among homologous traits in two evolutionary distant taxa—mice and baboons. We find that in both mice and baboons, who shared a common ancestor >65 Ma, incisor size variation is genetically independent of molar size variation. Furthermore, baboon premolars show independent genetic variation from incisors, suggesting that a modular genetic architecture separates incisors from these posterior teeth as well. Such genetic independence between modules provides an explanation for the extensive diversity of incisor size variation seen throughout mammalian evolution—variation uncorrelated with equivalent levels of postcanine tooth size variation. The modularity identified here is supported by the odontogenic homeobox code proposed for the patterning of the rodent dentition. The baboon postcanine pattern of incomplete pleiotropy is also consistent with predictions from the morphogenetic field model.J. Exp. Zool. (Mol. Dev. Evol.) 316:21–49, 2011. © 2010 Wiley‐Liss, Inc.
Genetic inactivation of ERK1 and ERK2 in chondrocytes promotes bone growth and enlarges the spinal canal
Authors: Sebastian Arjun , Matsushita Takehiko , Kawanami Aya , Mackem Susan , Landreth Gary E. , Murakami Shunichi 
Published: October 2010

AbstractActivating mutations in FGFR3 cause the most common forms of human dwarfism: achondroplasia and thanatophoric dysplasia. In mouse models of achondroplasia, recent studies have implicated the ERK MAPK pathway, a pathway activated by FGFR3, in creating reduced bone growth. Our recent studies have indicated that increased Fgfr3 and ERK MAPK signaling in chondrocytes also causes premature synchondrosis closure in the cranial base and vertebrae, accounting for the sometimes fatal stenosis of the foramen magnum and spinal canal in achondroplasia. Conversely, whether the decrease—or inactivation—of ERK1 and ERK2 promotes bone growth and delays synchondrosis closure remains to be investigated. In this study, we inactivated ERK2 in the chondrocytes of ERK1‐null mice using the Col2a1‐Cre and Col2a1‐CreER transgenes. We found that the genetic inactivation of ERK1 and ERK2 in chondrocytes enhances the growth of cartilaginous skeletal elements. We also found that the postnatal inactivation of ERK1 and ERK2 in chondrocytes delays synchondrosis closure and enlarges the spinal canal. These observations make ERK1 and ERK2 an attractive target for the treatment of achondroplasia and other FGFR3‐related skeletal syndromes. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:375–379, 2011
Erratum: Chemical composition of cabbage (Brassica oleracea L. var. capitata) grown on acid sulfate soils
Authors: Fältmarsch Rasmus , Österholm Peter 
Published: October 2010

AbstractThe purpose of this study was to investigate the influence of soil geochemistry on the concentrations of Ca, K, Mg, P, Co, Ni, Zn, Mn, Cu, and Fe in cabbage (Brassica oleracea L. var. capitata) grown on acid sulfate (AS) soils in Western Finland. A total of 11 topsoil (0–20 cm) and corresponding cabbage samples and three whole‐soil profiles (≈ 0–260 cm) were collected on three agricultural fields. The concentrations of Co and Zn in cabbage were correlated with the NH4Ac‐extractable (easily available) concentrations in the topsoil, indicating that the uptake of these elements in cabbage is largely governed by soil geochemistry. Yet, the concentrations of Co and Zn in cabbage were not in general elevated relative to that of Finnish average values, although some AS soils showed enriched concentrations of these metals in the soil and cabbage. Significant geochemical differences (e.g., oxidation depth, organic‐matter and S content, pH) were observed among the studied AS soils, while, on the other hand, the concentrations of Ca, K, Mg, P, Ni, Mn, Cu, and Fe in cabbage were relatively similar. The hydroxylamine‐extractable concentrations of these elements in the topsoil were not correlated to those in cabbage, suggesting that uptake is not governed by the oxide‐bound fraction of these elements in the soil. Similarly, the easily available concentrations of Ca, P, Ni, Mn, Cu, and Fe in the topsoil were not correlated to those in cabbage, indicating that uptake is independent of the easily available concentrations in the soil. Hence, it is suggested that cabbage can regulate and thus optimize its concentrations of Ca, P, Ni, Mn, Cu, and Fe. Oxidation depth affected neither the easily available concentrations of Co, Ni, Zn, and Mn in the topsoil nor the concentrations in cabbage. However, the subsoil with a lower oxidation depth, which is to a smaller extent affected by leaching, may partly be enriched in these metals. Nevertheless, these showed no increased concentrations in cabbage. Based on these findings, it is suggested that the large amounts of metals mobilized in AS soils are easily lost to drains, subsequently contaminating nearby waterways and estuaries whereas they are only partly enriched in cabbage and other previously studied crops (oat).
Public perception of landscape restoration along a degraded urban streamside
Authors: Özgüner H. , Eraslan Ş. , Yilmaz S. 
Published: October 2010

AbstractRestoration of degraded lands in urban areas increases the ecologic, aesthetic and economic value of these areas and contributes to quality of life in cities. This study explores public attitudes towards restoration of a derelict urban streamside corridor. Data for this study were collected using a social survey among users and neighbourhood residents of the Çayboyu area in Isparta, Turkey. The survey compared the previous and present situation of the survey site in order to reveal the influence of stream restorations on public perception and use of derelict urban landscapes. The results identified a dramatic change in public perceptions between the previous and present situation of the area. Following the restoration works, the Çayboyu area has become one of the most popular and intensively used green spaces in the city. The survey results suggest that restoration of derelict lands increases the value of such areas for people and enhances their uses for recreational purposes in urban areas. Therefore, it is vital that urban planners and local authorities should encourage restoration of derelict and unused urban areas and preserve them as green spaces to meet the amenity needs of urban people. Copyright © 2010 John Wiley & Sons, Ltd.