bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covalent Linkage Mediates Communication between ACP and TE Domains in Modular Polyketide Synthases
Authors: Tran Lucky , Tosin Manuela , Spencer Jonathan B. , Leadlay Peter F. , Weissman Kira J. 
Published: March 2008

AbstractPolyketide natural products such as erythromycin A and epothilone are assembled on multienzyme polyketide synthases (PKSs), which consist of modular sets of protein domains. Within these type I systems, the fidelity of biosynthesis depends on the programmed interaction among the multiple domains within each module, centered around the acyl carrier protein (ACP). A detailed understanding of interdomain communication will therefore be vital for attempts to reprogram these pathways by genetic engineering. We report here that the interaction between a representative ACP domain and its downstream thioesterase (TE) is mediated largely by covalent tethering through a short “linker” region, with only a minor energetic contribution from protein–protein molecular recognition. This finding helps explain in part the empirical observation that TE domains can function out of their normal context in engineered assembly lines, and supports the view that overall PKS architecture may dictate at least a subset of interdomain interactions.
When did Louis Pasteur present his memoir on the discovery of molecular chirality to the Académie des sciences? Analysis of a discrepancy
Authors: Gal Joseph 
Published: March 2008

AbstractLouis Pasteur presented his historic memoir on the discovery of molecular chirality to the Académie des sciences in Paris on May 22nd, 1848. The literature, however, nearly completely ignores this date, widely claiming instead May 15th, 1848, which first surfaced in 1922 in Pasteur's collected works edited by his grandson Louis Pasteur Vallery‐Radot. On May 21st, 1848, i.e., one day before Pasteur's presentation in Paris, his mother died in Arbois, eastern France. Informed at an unknown point in time that she was “very ill,” Pasteur left for Arbois only after his presentation. Biographies of Pasteur by his son‐in‐law René Vallery‐Radot or the grandson, and Pasteur's collected correspondence edited by the grandson are incomprehensibly laconic or silent about the historic presentation. While no definite conclusions are possible, the evidence strongly suggests a deliberate alteration of the record by the biographer relatives, presumably for fear of adverse public judgment of Pasteur for a real or perceived insensitivity to a grave family medical emergency. Such fear would have been in accord with their hagiographic portrayal of Pasteur, and the findings raise questions concerning the extent of their zeal in protecting his “demigod” image. Universal recognition of the true date of Pasteur's announcement of molecular chirality is long overdue. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Significance of HER2 and C‐MYC oncogene amplifications in breast cancer in atomic bomb survivors
Authors: Miura Shiro , Nakashima Masahiro , Ito Masahiro , Kondo Hisayoshi , Meirmanov Serik , Hayashi Tomayoshi , Soda Midori , Matsuo Takeshi , Sekine Ichiro 
Published: March 2008

AbstractBACKGROUND.It has been postulated that radiation induces breast cancers in atomic bomb (A‐bomb) survivors. Oncogene amplification is an important mechanism during breast carcinogenesis and also serves as an indicator of genomic instability (GIN). The objective of this study was to clarify the association of oncogene amplification in breast cancer in A‐bomb survivors with radiation exposure.METHODS.In total, 593 breast cancers were identified in A‐bomb survivors from 1968 to 1999, and the association between breast cancer incidence and A‐bomb radiation exposure was evaluated. Invasive ductal cancers from 67 survivors and 30 nonsurvivors were analyzed for amplification of the HER2 and C‐MYC genes by fluorescence in situ hybridization, and expression levels of hormone receptors were analyzed by immunostaining.RESULTS.The incidence rate increased significantly as exposure distance decreased from the hypocenter (hazard ratio per 1‐km decrement, 1.47; 95% confidence interval [95% CI], 1.30–1.66). The incidence of HER2 and C‐MYC amplification was increased significantly in the order of the control group, the distal group (P = .0238), and the proximal group (P = .0128). Multivariate analyses revealed that distance was a risk factor for the coamplification of C‐MYC and HER2 in breast cancer in survivors (odds ratio per 1‐km increment, 0.17; 95% CI, 0.01–0.63). The histologic grade of breast cancers became significantly higher in the order of the control group, the distal group, and the proximal group and was associated with oncogene amplifications.CONCLUSIONS.The current results suggested that A‐bomb radiation may affect the development of oncogene amplification by inducing GIN and may be associated with a higher histologic grade in breast cancer among A‐bomb survivors. Cancer 2008. © 2008 American Cancer Society.
Telomere length and telomerase subunits as diagnostic and prognostic biomarkers in Barrett carcinoma
Authors: Gertler Ralf , Doll Dietrich , Maak Matthias , Feith Marcus , Rosenberg Robert 
Published: March 2008

AbstractBACKGROUND.Maintenance of telomeres has been identified as an essential regulator of proliferative capacity and genomic integrity in malignant tumors. The authors evaluated telomere length and telomerase subunits, hTR and hTERT, as prognostic markers in patients with Barrett carcinoma.METHODS.Telomere length was measured by Southern blot analysis and hTR expression and hTERT expression by real‐time polymerase chain reaction in both cancer tissue and adjacent noncancerous Barrett mucosa in resection specimens from 46 patients with Barrett carcinoma (International Union Against Cancer [UICC] stages I‐III). The median follow‐up time of the surviving patients was 79 months.RESULTS.Cancer tissue expressed more hTERT‐mRNA than noncancerous mucosa (P< .05). Telomere lengths in cancer tissue and in noncancerous mucosa increased with higher pT category (P= .08 andP= .05, respectively). Twenty‐one patients who died of tumor recurrence showed significantly longer telomeres in cancer tissue compared with 25 patients without tumor‐related deaths (P< .05). Telomere length in both cancer tissue and in noncancerous mucosa and the telomere‐length ratio cancer:noncancerous tissue were correlated with overall survival. In multivariate analysis, the telomere‐length ratio proved to be an independent prognostic parameter (P< .02; relative risk of death 3.4; confidence interval, 1.3–8.9). Ten patients with telomere‐length ratios >1.17 had a significantly poorer overall survival compared with 36 patients with telomere‐length ratios ≤1.17 with 5‐year survival rates of 0% and 60%, respectively (P< .02).CONCLUSIONS.Telomere length and telomerase subunits were identified as diagnostic and prognostic biomarkers for Barrett carcinoma. Genetic alterations found in adjacent noncancerous mucosa suggested a “field effect” in Barrett carcinoma. Cancer 2008. © 2008 American Cancer Society.
Histologic response of dose‐intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high‐risk soft tissue sarcomas
Authors: Ryan Christopher W. , Montag Anthony G. , Hosenpud Janet R. , Samuels Brian , Hayden James B. , Hung Arthur Y. , Mansoor Atiya , Peabody Terrance D. , Mundt Arno J. , Undevia Samir 
Published: March 2008

AbstractBACKGROUND.The authors studied a dose‐intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high‐risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95% pathologic necrosis.METHODS.Twenty‐five patients with intermediate‐grade or high‐grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted).RESULTS.Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty‐one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide‐induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of ≥95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21–59%). Estimates of 2‐year overall and disease‐free survival were 84% (95% CI, 66–100%) and 62% (95% CI, 37–86%), respectively.CONCLUSIONS.A high rate of ≥95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity. Cancer 2008. ©2008 American Cancer Society.
Spatial patterning of cholinergic amacrine cells in the mouse retina
Authors: Whitney Irene E. , Keeley Patrick W. , Raven Mary A. , Reese Benjamin E. 
Published: March 2008

AbstractMosaic of cholinergic amacrine cells (green, labeled for choline acetyltransferase) in the ganglion cell layer of the mouse retina. The somal patterning of the mosaic is degraded due to the presence of blood vessels (white, labeled for PNA) and fascicles of optic axon (magenta, labeled for neurofilaments). Also shown are the retinal astrocytes (blue, labeled for glial fibrillary acidic protein). J. Comp. Neurol. 508:1‐12, 2008. © 2008 Wiley‐Liss, Inc.
Fe1−yO Nanoparticles: Organometallic Synthesis and Magnetic Properties
Authors: Glaria Arnaud , Kahn Myrtil L. , Lecante Pierre , Barbara Bernard , Chaudret Bruno 
Published: March 2008

AbstractNon‐stoichiometric wüstite particles (Fe1−yO) are synthesized using the controlled room‐temperature hydrolysis of the organometallic precursor {Fe[N(SiMe3)2]2}. Particles stabilized by hexadecylamine with a diameter of ∼5 nm are obtained. For such small nanoparticles, a distorted crystallographic structure is evidenced by wide‐angle X‐ray scattering at room temperature and reported for the first time. The study of the magnetic properties indicates that these particles are composed of an antiferromagnetic core surrounded by a ferromagnetic shell. According to the Néel theory, we demonstrate that this shell consists of 1.5 % of Fe3+ ions ferromagnetically coupled with Fe2+ ions.
Expression and activity of P‐glycoprotein (MDR1/ABCB1) in peripheral blood mononuclear cells from patients with anorexia nervosa compared with healthy controls
Authors: Storch Caroline Henrike , Nikendei Christoph , Schild Sandra , Haefeli Walter Emil , Weiss Johanna , Herzog Wolfgang 
Published: March 2008

AbstractObjective:Pharmacotherapeutic strategies for treatment of anorexia nervosa (AN) are characterized by limited success. Some drugs used (antipsychotics, selective serotonin reuptake inhibitors) are transported by P‐glycoprotein (P‐gp), a transporter with major impact on pharmacokinetics of substrate drugs. Biochemical alterations seen in AN patients could lead to increased expression and/or activity of P‐gp and therefore to diminished access of drugs to the brain. The aim of our study was to investigate expression and activity levels of P‐gp in peripheral blood mononuclear cells (PBMCs) in AN patients.Method:PBMCs of 16 AN patients and 16 controls were isolated. Activity of P‐gp was determined by flow cytometry and expression was quantified by reverse‐transcriptase‐real‐time‐polymerase‐chain‐reaction.Results:Neither a significant difference in P‐gp expression (AN: 0.00154 ± 0.00088 [MDR1/β2 mg], control: 0.00244 ± 0.0013 [MDR1/β2 mg], p = .138) nor a difference in P‐gp activity (rhodamine123 ratio AN: 1.79 ± 0.73, control: 2.03 ± 0.42, p = .20) between AN patients and healthy controls could be detected. In contrast to previous studies, expression and activity of P‐gp correlated significantly (p = .0031).Conclusion:Failure in pharmacotherapy with P‐gp substrates in AN patients are probably neither caused by different P‐gp expression nor activity levels. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008
F‐Amphiphilic 1,2,3‐Triazoles by Unexpected Intramolecular Cyclisation of Vinyl Azides
Authors: Mayot Estelle , Lemière Pascal , Gérardin‐Charbonnier Christine 
Published: March 2008

AbstractA series of fluoroalkylated 1,2,3‐triazoles have been synthetised in significant yields through unexpected intramolecular cyclisations of vinyl azides bearing electron‐withdrawing groups. The mechanism proposed in this study implies the participation of a catalytic amount of azide ions in the cyclisations of the vinyl azides to triazoles. The study includes the alkylation of these compounds with various alkylating agents and the evaluation of the surface activities of the ionic derivatives.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis and Reactivity of Silylformylation Products Derived from Alkynes
Authors: Aronica Laura Antonella , Caporusso Anna Maria , Salvadori Piero 
Published: March 2008

AbstractThe silylformylation reaction of unsaturated compounds consists of the rhodium‐catalysed addition of a R3Si and a CHO moiety to a carbon–carbon multiple bond. The silylformylation process is applicable to both terminal and internal alkynes and is tolerant towards several functional groups. Many factors can influence the chemoselectivity of the reaction that generally affords β‐silylalkenals with high yields and regioselectivity. The β‐silylalkenals are polyfunctionalised substrates that can be submitted to several chemical transformations and in particular can undergo fluoride‐promoted (TBAF) aryl migration from an aryldimethylsilyl group to the adjacent carbon atom thus generating 2‐(arylmethyl)aldehydes, important industrial precursors of perfumes. This silylformylation‐aryl migration two‐steps sequence can be applied to functionalised alkyne precursors and chemo‐, regio‐ and stereoselectivity of the products can be modulated according to the nature and the position of the functional group. When a good leaving group is present in the ω position of the aliphatic chain of the alkyne cyclisation products are obtained, while α,β‐unsaturated aldehydes are generated from propargyl tosylamides, acetates and benzoates. α‐Silylmethylene‐β‐lactams, prepared from p‐tosylamides according to silylcarbocyclisation reaction, can be transformed into the corresponding arylmethyl‐β‐lactams by means of TBAF‐induced rearrangement that takes place without involving the lactam ring. A plausible mechanism of the rearrangement reaction is reported that suggests the addition of the fluoride ion to the arylsilicon moiety and the consequent migration of the aryl group to the adjacent carbon atom. Both aryl and heteroaryl substituents can migrate without any loss of configuration further enhancing the high synthetic value of this protocol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Polarographic Behavior of Human Plasma Thrombin and Changes in Its Anticoagulation Activity Through Various Conformations
Authors: Singh Niyati , Pitre K. S. 
Published: March 2008

AbstractThrombin plays a pivotal role in the regulation of blood fluidity and therefore constitutes a primary target in the treatment of various hemostatic disorders. For this differential pulse polarography has been developed in an appropriate supporting electrolyte, which produced well‐defined DPP peaks. The average prothrombin time (PT) in citrated plasma samples was determined, which indicated decrease of average PT with rise of thrombin and albumin concentrations, while PT resulted differently (increase) with heparin, thus confirming their role in anticoagulation activity. The PT of thrombin‐heparin and thrombin‐albumin conformations showed sharp increased and steady decreased respectively. Thus, two opposite actions of thrombin, coagulation (thrombin‐albumin) and anticoagulation (thrombin‐heparin) may prove fruitful in clinical approach for thrombotic disorders.
Electrochemical Behavior and Determination of L‐Tyrosine at Single‐walled Carbon Nanotubes Modified Glassy Carbon Electrode
Authors: Yu Xiaozhi , Mai Zhibin , Xiao Yun , Zou Xiaoyong 
Published: March 2008

AbstractBased on single‐walled carbon nanotubes (SWCNTs) modified glassy carbon electrode (GCE/SWCNTs), a novel method was presented for the determination of L‐tyrosine. The GCE/SWCNTs exhibited remarkable catalytic and enhanced effects on the oxidation of L‐tyrosine. In 0.10 mol/L citric acid‐sodium citrate buffer solution, the oxidation potential of L‐tyrosine shifted negatively from +1.23 V at bare GCE to +0.76 V at GCE/SWCNTs. Under the optimized experimental conditions, the linear range of the modified electrode to the concentration of L‐tyrosine was 5.0×10−6–2.0×10−5 mol/L (R1=0.9952) and 2.7×10−5–2.6×10−4 mol/L (R2=0.9998) with a detection limit of 9.3×10−8 mol/L. The kinetic parameters such as α (charge transfer coefficient) and D (diffusion coefficient) were evaluated to be 0.66, 9.82×10−5 cm2 s−1, respectively. And the electrochemical mechanism of L‐tyrosine was also discussed.
Heat release rate and computer fire modelling vs real‐scale fire tests in passenger trains
Authors: Capote Jorge A. , Alvear Daniel , Lázaro Mariano , Espina Pablo 
Published: March 2008

AbstractThe materials and products used in passenger trains may not be the first ignited element, but during the fire development, these materials, especially ceiling linings and wall coverings, contribute significantly to the fire growth. The fire safety requirements in passenger trains consist mainly of bench‐scale tests, with particular focus on the sample geometry, position and fire exposition. When this information is extrapolated to real end use conditions limitations appear.In this paper, a discussion of the use of fire dynamics simulator model and heat release rate experiments in cone calorimeter (bench‐scale test) is presented in order to represent the fire development in a passenger train compartment. For the study, two fire scenarios were selected: (1) the single burning item SBI test (modified) and (2) a passenger train compartment. Initially, the limitations of the assumptions and hypothesis made when producing the model were analyzed and the research team carried out a sensitivity study of the model results considering different grid sizes.In order to validate the model, both bench‐ and full‐scale fire tests were considered based on the results provided by the European research program FIRESTARR. The limitations and uncertainties in the results demonstrate the importance of two basic factors: the incident heat flux in the cone calorimeter tests and the prescribed ignition temperature. Copyright © 2008 John Wiley & Sons, Ltd.
Human survivability in motor vehicle fires
Authors: Digges K. H. , Gann R. G. , Grayson S. J. , Hirschler M. M. , Lyon R. E. , Purser D. A. , Quintiere J. G. , Stephenson R. R. , Tewarson A. 
Published: March 2008

AbstractAutomobile fires are consistently among the largest causes of fire death in the United States (about 500 annually) and the U.S. motor vehicle industry and others have spent a significant amount of money in recent years studying this problem. The authors of this review have analyzed the auto industry reports, the scientific literature, and statistical data, and conclude that measures should be taken to improve survivability in automobile fires. The U.S. Federal Motor Vehicle Safety Standard 302 (FMVSS 302) was introduced almost 40 years ago to measure the flammability of interior materials, but improvements in the crashworthiness of automobiles and their fuel tanks and the increased use of combustible materials have changed the motor vehicle fire scenario significantly. In particular, the primary threat has changed from ignition of a small quantity of combustible interior materials by a lit cigarette, in 1960, to ignition of a large quantity of combustible interior and exterior materials by an impact‐induced fire, at present. The authors therefore suggest that FMVSS 302 is no longer relevant to automobile fire safety and recommend improved standards based on objective criteria for fire safety performance (fireworthiness) at the system/vehicle level as is routinely done for crashworthiness. Copyright © 2008 John Wiley & Sons, Ltd.
Flame retardation and thermal degradation of flame‐retarded polypropylene composites containing melamine phosphate and pentaerythritol phosphate
Authors: Zhou Shun , Wang Zhengzhou , Gui Zhou , Hu Yuan 
Published: March 2008

AbstractThe flame retardation of polypropylene (PP) composites containing melamine phosphate (MP) and pentaerythritol phosphate (PEPA) was characterized by limiting oxygen index (LOI) and UL 94. The morphology of the char obtained from the combustion of the composites was studied by scanning electron microscopy (SEM). The thermal degradation of the composites was investigated using thermogravimetric (TG) analysis and real‐time Fourier transform infrared (RTFTIR) spectroscopy. It has been found that the PP composites containing only MP do not show good flame retardancy even at 40% additive level. Compared with the PP/MP binary composites, all the LOI values of the PP/MP/PEPA ternary composites at the same additive loading increase, and UL 94 ratings of the ternary composites at suitable MP/PEPA ratios are raised to V‐0 from no rating (PP/MP). The TG and RTFTIR studies indicate that the interaction occurs among MP, PEPA and PP. Copyright © 2008 John Wiley & Sons, Ltd.
Spectral/hp penalty least‐squares finite element formulation for unsteady incompressible flows
Authors: Prabhakar V. , Reddy J. N. 
Published: March 2008

AbstractIn this paper, we present spectral/hp penalty least‐squares finite element formulation for the numerical solution of unsteady incompressible Navier–Stokes equations. Pressure is eliminated from Navier–Stokes equations using penalty method, and finite element model is developed in terms of velocity, vorticity and dilatation. High‐order element expansions are used to construct discrete form. Unlike other penalty finite element formulations, equal‐order Gauss integration is used for both viscous and penalty terms of the coefficient matrix. For time integration, space–time decoupled schemes are implemented. Second‐order accuracy of the time integration scheme is established using the method of manufactured solution. Numerical results are presented for impulsively started lid‐driven cavity flow at Reynolds number of 5000 and transient flow over a backward‐facing step. The effect of penalty parameter on the accuracy is investigated thoroughly in this paper and results are presented for a range of penalty parameter. Present formulation produces very accurate results for even very low penalty parameters (10–50). Copyright © 2008 John Wiley & Sons, Ltd.