bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of Hypoxia-Inducible Factor 2α Restores p53 Activity via Hdm2 and Reverses Chemoresistance of Renal Carcinoma Cells
Authors: Roberts Andrew M. , Watson Ian R. , Evans Andrew J. , Foster David A. , Irwin Meredith S. , Ohh Michael 
Published: November 2009

Abstract
p53 mutations are rarely detected in clear cell renal cell carcinoma (CCRCC), but, paradoxically, these tumors remain highly resistant to chemotherapy and death receptor–induced death. Here, we show that the accumulation of hypoxia-inducible factor 2α (HIF2α), a critical oncogenic event in CCRCC following the loss of von Hippel-Lindau (VHL) tumor suppressor protein, leads to Hdm2-mediated suppression of p53. Primary CCRCC specimens exhibiting strong hypoxic signatures show increased levels of activated nuclear phospho-Hdm2(Ser166), which is concomitant with low p53 expression. The abrogation of Hdm2-p53 interaction using the small-molecule Hdm2 inhibitor nutlin-3 or the downregulation of HIF2α via HIF2α-specific short hairpin RNA or wild-type VHL reconstitution restores p53 function and reverses the resistance of CCRCC cells to Fas-mediated and chemotherapy-induced cell death. These findings unveil a mechanistic link between HIF2α and p53 and provide a rationale for combining Hdm2 antagonists with chemotherapy for the treatment of CCRCC. [Cancer Res 2009;69(23):9056–64]
Etude de l’influence du couplage acoustique source-conduit vocal sur F° des voyelles orales
Authors: Guérin B. , Boë L.J. 
Published: November 2009

Abstract
With the aid of a two-mass model of the vocal source loaded by the input impedance of the vocal tract, we first study theoretically, then by simulation, the effects of source-vocal tract coupling on the intrinsic frequencies F₀ of the French oral vowels. We explain the correlation which exists between F₀ and the frequency of the first formant as well as the results from the experiment described by Ishizaka and Flanagan [1972]. In conclusion, we show that the acoustic coupling cannot explain the different values of F₀, intrinsic in the vowels, but on the contrary, a physiological coupling has to compensate for the effects of acoustic coupling to explain the characteristics revealed in natural speech.
Effect of Viscoelasticity in Fountain Flow of Polyethylene Melts
Authors: Mitsoulis E. 
Published: November 2009

Abstract
Fountain flow is the phenomenon of deceleration and outward motion of fluid particles as they approach a slower moving interface. Numerical simulations have been undertaken for the flow of viscoelastic fluids, obeying an integral constitutive equation of the K-BKZ type, capable of describing the behavior of polymer melts. Two polyethylene melts are considered, a branched LDPE and a linear HDPE. Their rheology is well captured by the integral model. The flow simulations are performed for planar and axisymmetric geometries and show the shape and extent of the free surface, as well as the stresses and pressures in the system. The semicircle is a good rough approximation for the free surface of fountain flow, but detailed computations show the effect of elasticity on the free surface, which is non-monotonic for the LDPE as the elasticity level (or apparent shear rate) increases. The less elastic HDPE shows a monotonic decrease in the extent of the flow front as elasticity increases. In all cases, the excess pressure losses (front pressure correction) increase with increasing flow rate. The effect of a nonzero second normal stress difference is to extend the flow front and increase the pressure losses.
Stereoacuity After Refractive Lens Exchange With AcrySof ReSTOR Intraocular Lens Implantation
Authors: Ferrer-Blasco Teresa , Montés-Micó Robert , Cerviño Alejandro , Alfonso José F. , González-Méijome José M. 
Published: November 2009

Purpose:
To evaluate stereoacuity before and after refractive lens exchange (RLE) with AcrySof ReSTOR intraocular lens (IOL) implantation.

Methods:

Stereoacuity was measured using the Titmus stereotest at 40 cm under photopic conditions (85 cd/m
2
) before and after RLE with bilateral AcrySof ReSTOR Natural (SN60D3 model) implantation in 30 hyperopic eyes of presbyopes with low astigmatism (⩽1.00 diopter [D]). Stereoacuity measurements after implantation were compared with those found before surgery.

Results:

Stereoacuity was unchanged after RLE with pseudoaccommodative IOL implantation. In this population of non-cataractous hyperopes with excellent preoperative stereoacuity (46.42±1.36 sec arc), 95% maintained the same level of stereoacuity (48.67±1.13 sec arc) after surgery (
P
=.223). Further calculations predict that this ability to discriminate objects in depth extends to approximately 2 m. Beyond this distance, depth discrimination does not help the visual system.

Conclusions:
Refractive lens exchange with AcrySof ReSTOR IOL implantation does not affect the binocular ability of the human eye regarding depth perception, the best evidence of binocular function in hyperopic individuals.

[
J Refract Surg
. 2009;25:1000–1004.]
Palladium‐catalyzed arylation of arylglyoxals with arylboronic acids
Authors: Zhang Qiang , Xu Chun‐Mei , Chen Jiu‐Xi , Xu Xiao‐Ling , Ding Jin‐Chang , Wu Hua‐Yue 
Published: November 2009

AbstractA palladium‐catalyzed coupling‐type reaction of arylglyoxals with arylboronic acids was achieved by use of trimesitylphosphine as the ligand and K2CO3 as base in toluene, providing symmetrical and unsymmetrical benzil derivatives with yields ranging from moderate to excellent. Of particular mention, the rigorous exclusion of air and moisture is not required in these transformations. Copyright © 2009 John Wiley & Sons, Ltd.
Aerobic batch cultivation in micro bioreactor with integrated electrochemical sensor array
Authors: van Leeuwen Michiel , Krommenhoek Erik E. , Heijnen Joseph J. , Gardeniers Han , van der Wielen Luuk A. M. , van Gulik Walter M. 
Published: November 2009

AbstractAerobic batch cultivations of Candida utilis were carried out in two micro bioreactors with a working volume of 100 μL operated in parallel. The dimensions of the micro bioreactors were similar as the wells in a 96‐well microtiter plate, to preserve compatibility with the current high‐throughput cultivation systems. Each micro bioreactor was equipped with an electrochemical sensor array for the online measurement of temperature, pH, dissolved oxygen, and viable biomass concentration. Furthermore, the CO2 production rate was obtained from the online measurement of cumulative CO2 production during the cultivation. The online data obtained by the sensor array and the CO2 production measurements appeared to be very reproducible for all batch cultivations performed and were highly comparable to measurement results obtained during a similar aerobic batch cultivation carried out in a conventional 4L bench‐scale bioreactor. Although the sensor chip certainly needs further improvement on some points, this work clearly shows the applicability of electrochemical sensor arrays for the monitoring of parallel micro‐scale fermentations, e.g. using the 96‐well microtiterplate format. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Microparticle‐mediated gene delivery for the enhanced expression of a 19‐kDa fragment of merozoite surface protein 1 of Plasmodium falciparum
Authors: Liu Shan , Danquah Michael K. , Forde Gareth M. , Ma Charles , Wang Lina , Coppel Ross 
Published: November 2009

AbstractThe 19 kDa carboxyl‐terminal fragment of merozoite surface protein 1 (MSP119) is a major component of the invasion‐inhibitory response in individual immunity to malaria. A novel ultrasonic atomization approach for the formulation of biodegradable poly(lactic‐co‐glycolic acid) (PLGA) microparticles of malaria DNA vaccines encoding MSP119 is presented here. After condensing the plasmid DNA (pDNA) molecules with a cationic polymer polyethylenimine (PEI), a 40 kHz ultrasonic atomization frequency was used to formulate PLGA microparticles at a flow rate of 18 mL h−1. High levels of gene expression and moderate cytotoxicity in COS‐7 cells were achieved with the condensed pDNA at a nitrogen to phosphate (N/P) ratio of 20, thus demonstrating enhanced cellular uptake and expression of the transgene. The ability of the microparticles to convey pDNA was examined by characterizing the formulated microparticles. The microparticles displayed Z‐average hydrodynamic diameters of 1.50–2.10 μm and zeta potentials of 17.8–23.2 mV. The encapsulation efficiencies were between 78 and 83%, and 76 and 85% of the embedded malaria pDNA molecules were released under physiological conditions in vitro. These results indicate that PLGA‐mediated microparticles can be employed as potential gene delivery systems to antigen‐presenting cells in the prevention of malaria. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES)
Authors: Haeusler Julia , Ranft Andreas , Boelling Tobias , Gosheger Georg , Braun‐Munzinger Gabriele , Vieth Volker , Burdach Stefan , van den Berg Henk , Juergens Heribert , Dirksen Uta 
Published: November 2009

AbstractBACKGROUND:The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES) was investigated.METHODS:We analyzed 120 patients registered into the European Ewing Tumor Working Initiative of National Groups (EURO‐E.W.I.N.G. 99) trial at the trial center of Muenster from 1998 to 2006. Median age was 16.2 years. Local treatment of the primary tumor was surgery in 26 of 120 patients, surgery and radiotherapy in 21 patients, and definitive radiotherapy in 40 patients. For treatment of metastases, 6 of 120 patients received surgery; 9 patients, surgery and radiotherapy; and 33 patients, definitive radiotherapy. Forty‐seven (39%) patients had local treatment of both the primary tumor and metastases, 41 (34%) patients of either the primary tumor or metastases, and 32 (27%) received no local therapy.RESULTS:Event‐free survival (EFS) at 3 years was 0.24 (95% CI, 0.16‐0.33). Univariate analyses demonstrated the impact of local therapy given to the primary tumor: 3‐year EFS was 0.25 with surgery, 0.47 with surgery and radiotherapy, 0.23 with radiotherapy, and 0.13 when no local therapy was administered (P < .001). Three‐year EFS in PDMES was also influenced by the local treatment: surgery, 0.33; surgery and radiotherapy, 0.56; radiotherapy, 0.35; no local therapy, 0.16 (P = .003). Three‐year EFS was 0.39 in patients who received local treatment of both primary tumor and PDMES, compared with 0.17 in patients with any local treatment of either primary tumor or PDMES and 0.14 in patients with no local therapy (P < .001). Multivariate analysis showed absence of local treatment to be the major risk factor (HR = 2.21; P = .027; n = 20).CONCLUSIONS:Local therapy of involved sites is important for patients with PDMES and should complement systemic treatment whenever possible. Cancer 2010. © 2010 American Cancer Society.
A phase 2 study of platinum and gemcitabine in patients with advanced salivary gland cancer
Authors: Laurie Scott A. , Siu Lillian L. , Winquist Eric , Maksymiuk Andrew , Harnett Erica L. , Walsh Wendy , Tu Dongsheng , Parulekar Wendy R. 
Published: November 2009

AbstractBACKGROUND:Salivary gland cancers are rare, histologically diverse, and varied in their biologic behavior and responsiveness to systemic therapy. To the authors' knowledge, there currently is no standard chemotherapy for these tumors, but cisplatin‐based regimens are often used. This phase 2 trial evaluated the combination of gemcitabine with cisplatin (carboplatin in those with protocol‐defined contraindications to cisplatin).METHODS:Fit, consenting adult patients had advanced, metastatic, or locoregionally recurrent salivary gland cancer (any histologic subtype) that was not suitable for radiation or surgery. Therapy was comprised of gemcitabine at a dose of 1000 mg/m2 administered intravenously on Days 1 and 8, and cisplatin at a dose of 70 mg/m2 on Day 2, of a 21‐day cycle. If carboplatin was substituted, it was administered on Day 1, targeted to an area under the concentration‐time curve of 5 mg/mL/s. Response was assessed every 2 cycles according to Response Evaluation Criteria In Solid Tumors. Patients received up to 6 cycles. The primary endpoint was objective response. A 2‐stage design was used, with a response rate of 45% required to declare the regimen active.RESULTS:Thirty‐three eligible patients were enrolled, of whom 30 were response evaluable. Eight objective responses were observed (1 complete and 7 partial) for a response rate of 24% (95% confidence interval, 11‐42%), with responses observed in all histologic subtypes. Toxicity was within that expected for this combination.CONCLUSIONS:This regimen did not meet the predefined criteria to be declared active in advanced salivary gland cancers. Enrollment of patients with these rare cancers into well‐designed clinical trials remains an urgent priority. Cancer 2010. © 2010 American Cancer Society.
Observation of Protein Domain Motions by Neutron Spectroscopy
Authors: Monkenbusch Michael , Richter Dieter , Biehl Ralf 
Published: November 2009

AbstractHigh‐resolution inelastic neutron scattering, which is available with neutron spin‐echo spectroscopy (NSE) is introduced as a tool for the analysis of biomolecule ﬂexibility. Coherent scattering in a range where it is sensitive to length scales of nanometers and covering a time range from picoseconds to several 100 ns makes the motion of larger subdomains within proteins visible. We show that and how the internal domain motion within a protein in solution can be measured. Comparison with displacement patterns from normal mode analysis provides further insight into the nature of the geometry of the motions that lead to the oberved dynamic signature. The NSE experiment on alcohol dehydrogenase (ADH) is used as example to illustrate the general principles of the method.
An efficient strategy overcoming the bottleneck in Candida parapsilosis catalyzing stereoinversion from (R)‐1‐phenyl‐1, 2‐ethanediol to the corresponding counterpart
Authors: Hu Qingsen , Xu Yan , Nie Yao 
Published: November 2009

AbstractBACKGROUND: Microbial stereoinversion has been widely used for the biosynthesis of numerous chiral compounds. However, little work has been done to improve the efficiency of microbial stereoinversion. This study investigated the bottleneck in the deracemization of 1‐phenyl‐1,2‐ethanediol (PED), and then the efficiency and the sustainability of biocatalyst was improved significantly by using a strategy.RESULTS: When (S)‐PED concentration exceeded 17.5 g L−1, it strongly inhibited deracemization. Furthermore, the deficiency of NADPH regeneration also limited such reaction. To overcome these limitations, extractive biocatalysis was developed using adsorbent resin NKII combined with xylose addition for cofactor regeneration. Compared with the initial reaction condition, which only afforded (S)‐PED with 35% optical purity after the first batch reaction at 30 g L−1 substrate concentration, the cells in the new system could be reused three times and the optical purity remained at a high level of 95%.CONCLUSION: Product inhibition and coenzyme regeneration had a significant effect on catalytic activity of Candida parapsilosis. By using a resin and D‐xylose, the efficiency and reusability of whole‐cell catalyst can be considerably improved, which would be helpful for effective synthesis of high value chiral intermediates. Copyright © 2009 Society of Chemical Industry
A comprehensive study of lipase production byYarrowia lipolyticaCECT 1240 (ATCC 18942): from shake flask to continuous bioreactor
Authors: Deive Francisco J. , Sanromán M. Angeles , Longo Maria A. 
Published: November 2009

AbstractBACKGROUND:Lipases are commercially important enzymes, and the development and optimization of their production processes are of great interest. The diversity of behaviours between strains stresses the need for research on this topic, especially when bioreactor culture is considered. The study of a continuous operating mode is especially attractive, since very scarce information is available on its application to microbial lipases production.RESULTS:Lipase production in submerged cultures ofYarrowia lipolyticaCECT 1240 (ATCC 18 942) has been investigated. Significant lipolytic activity (over 700 U dm−3), mostly extracellular and membrane‐bound, was obtained in shake flasks using medium supplemented with olive oil. The culture was carried out in air‐lift and stirred tank bench‐scale bioreactors and the latter was selected. The influence of aeration and agitation rates was assessed in batch cultures, and agitation from 400–700 rpm and low aeration rates (i.e. 0.2 vvm) are recommended. Batch, fed‐batch and continuous operation were investigated, and regular enzyme production (up to 600 U dm−3) was achieved with the latter.CONCLUSION:Lipase production by the selected strain was successfully carried out in shake flasks and bench‐scale bioreactors. After studying batch, fed‐batch and continuous processes, continuous culture in a stirred tank bioreactor was found best in terms of regular enzyme production, exceptionally good operational stability and good fitting of the results to mathematical models. Copyright © 2009 Society of Chemical Industry
SPECT/CT for preoperative sentinel node localization
Authors: Vermeeren Lenka , van der Ploeg Iris M.C. , Olmos Renato A. Valdés , Meinhardt Willem , Klop W. Martin C. , Kroon Bin B.R. , Nieweg Omgo E. 
Published: November 2009

AbstractThe value of SPECT/CT for detection and localization of sentinel nodes is reviewed. SPECT/CT depicts extra sentinel nodes and identifies non‐nodal tracer accumulation. SPECT/CT is indicated in patients with complex lymphatic drainage as often present in patients with head, neck and scapular melanoma, breast cancer patients with extra‐axillary sentinel nodes and patients with tumors draining to pelvic nodes. SPECT/CT also clarifies the drainage pattern of inconclusive conventional images (non‐visualization or unclear location of the nodes). J. Surg. Oncol. 2010;101:184–190. © 2009 Wiley‐Liss, Inc.
Recent Progress in Polyphosphoesters: From Controlled Synthesis to Biomedical Applications
Authors: Wang Yu‐Cai , Yuan You‐Yong , Du Jin‐Zhi , Yang Xian‐Zhu , Wang Jun 
Published: November 2009

AbstractPolyphosphoesters (PPEs) with repeating phosphoester bonds in the backbone are structurally versatile, biocompatible, and biodegradable through hydrolysis as well as enzymatic digestion under physiological conditions. They are appealing for biological applications because of their potential functionality, biocompatibility, and similarity to biomacromolecules such as nucleic acids. The expanding scope of PPEs in materials science, especially as biomaterials, is described in this review. We mainly focus on controlled synthetic methods of PPEs, which provide access to novel and complex polymer structures, especially for block copolymers. The hydrolytic and enzymatic degradation of PPEs, thermoresponsive PPEs, and biomedical applications have also been discussed.magnified image
Reproducibility of tract‐specific magnetization transfer and diffusion tensor imaging in the cervical spinal cord at 3 tesla
Authors: Smith Seth A. , Jones Craig K. , Gifford Aliya , Belegu Visar , Chodkowski BettyAnn , Farrell Jonathan A. D. , Landman Bennett A. , Reich Daniel S. , Calabresi Peter A. , McDonald John W. , van Zijl Peter C.M. 
Published: November 2009

AbstractDamage to specific white matter tracts within the spinal cord can often result in the particular neurological syndromes that characterize myelopathies such as traumatic spinal cord injury. Noninvasive visualization of these tracts with imaging techniques that are sensitive to microstructural integrity is an important clinical goal. Diffusion tensor imaging (DTI)‐ and magnetization transfer (MT)‐derived quantities have shown promise in assessing tissue health in the central nervous system. In this paper, we demonstrate that DTI of the cervical spinal cord can reliably discriminate sensory (dorsal) and motor (lateral) columns. From data derived from nine healthy volunteers, two raters quantified column‐specific parallel (λ||) and perpendicular (λ⟂) diffusivity, fractional anisotropy (FA), mean diffusivity (MD), and MT‐weighted signal intensity relative to cerebrospinal fluid (MTCSF) over two time‐points separated by more than 1 week. Cross‐sectional means and standard deviations of these measures in the lateral and dorsal columns were as follows: λ||: 2.13 ± 0.14 and 2.14 ± 0.11 μm2/ms; λ⟂: 0.67 ± 0.16 and 0.61 ± 0.09 μm2/ms; MD: 1.15 ± 0.15 and 1.12 ± 0.08 μm2/ms; FA: 0.68 ± 0.06 and 0.68 ± 0.05; MTCSF: 0.52 ± 0.05 and 0.50 ± 0.05. We examined the variability and interrater and test‐retest reliability for each metric. These column‐specific MR measurements are expected to enhance understanding of the intimate structure‐function relationship in the cervical spinal cord and may be useful for the assessment of disease progression. Copyright © 2009 John Wiley & Sons, Ltd.
Review of perinatal management of arthrogryposis at a large UK teaching hospital serving a multiethnic population
Authors: Navti O. B. , Kinning E. , Vasudevan P. , Barrow M. , Porter H. , Howarth E. , Konje J. , Khare M. 
Published: November 2009

AbstractObjectiveTo review the prevalence and perinatal management of cases of arthrogryposis delivering at our hospital over a 6‐year period.MethodsThis was a retrospective review of cases of arthrogryposis managed at a UK teaching hospital. Cases were identified from the regional congenital anomalies register and departmental databases. Case notes were reviewed and analysed.ResultsFrom 2002 to 2007, there were 27 cases of arthrogryposis. Sixteen (59.3%) were Caucasians, 7(25.9%) Asians and 4(14.8%) Afro‐Caribbean; 17(63%) were nulliparous. In eight (29.6%) cases, there was a family history of congenital anomalies. Three had previously affected siblings and in three cases the parents were affected with arthrogryposis. Five (18.5%) were from consanguineous families. Eighteen (66.7%) cases were diagnosed prenatally at a mean gestational age of 21 weeks. Twelve (57%) were delivered by caesarean section. There were 18 live births. Sixteen (59%) cases were reviewed by clinical geneticist. Following detailed review and investigation including post‐mortems, 20 (74%) of our cases had a formal diagnosis or likely cause identified.ConclusionsSuspected cases of arthrogryposis require multi‐disciplinary management to optimise the possibility of making a diagnosis and providing parents with accurate information to enable them to make informed choices regarding the pregnancy and providing information regarding likelihood of recurrence. Copyright © 2009 John Wiley & Sons, Ltd.
‘Sulfo‐click’ for ligation as well as for site‐specific conjugation with peptides, fluorophores, and metal chelators
Authors: Rijkers Dirk T. S. , Merkx Remco , Yim Cheng‐Bin , Brouwer Arwin J. , Liskamp Rob M. J. 
Published: November 2009

AbstractThe ‘sulfo‐click’ reaction, which is a chemoselective amidation reaction involving the reaction of an aminoethane sulfonyl azide with a thio acid, encompasses a new approach for ligation and conjugation. Detailed protocols are provided for decorating biologically active peptides or dendrimers with biophysical tags, fluorescent probes, metal chelators, and small peptides by using this reaction as a novel, metal‐free ‘sulfo‐click’ approach. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.