bluuebunny/crossref_metadata_2025_split huggingface dataset:
NMR‐derived folate‐bound structure of dihydrofolate reductase 1 from the halophile Haloferax volcanii
Authors: Boroujerdi Arezue F. B. , Young John K. 
Published: September 2008

AbstractFolate binds to dihydrofolate reductase (DHFR) to form a binary complex whose structure maintains the overall configuration of the enzyme; however, some significant changes are evident when a comparison is made to the enzyme. The structure of DHFR1 from the halophilic Halopherax volcanii was solved in its folate‐bound form using nuclear magnetic resonance spectroscopy. NOE data obtained from the 15N‐NOESY‐HSQC and 13C‐NOESY‐HSQC experiments of the triply labeled (1H, 13C, and 15N) binary complex were used as input for the structure calculation with the Crystallography and Nuclear Magnetic Resonance System program. The resulting family of structures was compared with the enzyme solved by both nuclear magnetic resonance and X‐ray crystallography and also to the mesophilic folate‐bound enzyme from Escherichia coli. The binary complex exhibited less convergence of structure in the α2‐helix and differences in the hinge residues D39 and A94. In comparison to the previously reported mesophilic binary complex solved by X‐ray crystallography, the halophilic binary complex reported here does not agree with the convergence of the M20 loop to a single structure. The corresponding L21 loop of the halophilic binary complex family of structures solved by nuclear magnetic resonance indicates variability in this region. © 2008 Wiley Periodicals, Inc. Biopolymers 91: 140–144, 2009.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Biophysical characterization of DNA aptamer interactions with vascular endothelial growth factor
Authors: Potty Ajish S. R. , Kourentzi Katerina , Fang Han , Jackson George W. , Zhang Xing , Legge Glen B. , Willson Richard C. 
Published: September 2008

AbstractThe binding of a DNA aptamer (5′‐CCGTCTTCCAGACAAGAGTGCAGGG‐3′) to recombinant human vascular endothelial growth factor (VEGF165) was characterized using surface plasmon resonance (SPR), fluorescence anisotropy and isothermal titration calorimetry (ITC). Results from both fluorescence anisotropy and ITC indicated that a single aptamer molecule binds to each VEGF homodimer, unlike other VEGF inhibitors that exhibit 2(ligand):1(VEGF homodimer) stoichiometry. In addition, ITC revealed that the association of the aptamer to VEGF at 20°C is enthalpically driven, with an unfavorable entropy contribution. SPR kinetic studies, with careful control of possible mass transfer effects, demonstrated that the aptamer binds to VEGF with an association rate constant kon = 4.79 ± 0.03 × 104 M−1 s−1 and a dissociation rate constant koff = 5.21 ± 0.02 × 10−4 s−1 at 25°C. Key recognition hot‐spots were determined by a combination of aptamer sequence substitutions, truncations, and extensions. Most single‐nucleotide substitutions, particularly within an mfold‐predicted stem, suppress binding, whereas those within a predicted loop have a minimal effect. The 5′‐end of the aptamer plays a key role in VEGF recognition, as a single‐nucleotide truncation abolished VEGF binding. Conversely, an 11‐fold increase in the association rate (and affinity) is observed with a single cytosine nucleotide extension, due to pairing of the 3′‐GGG with 5′‐CCC in the extended aptamer. Our approach effectively maps the secondary structural elements in the free aptamer, which present the unpaired interface for high affinity VEGF recognition. These data demonstrate that a directed binding analysis can be used in concert with library screening to characterize and improve aptamer/ligand recognition. © 2008 Wiley Periodicals, Inc. Biopolymers 91: 145–156, 2009.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
A role for neoadjuvant gemcitabine plus cisplatin in muscle‐invasive urothelial carcinoma of the bladder
Authors: Dash Atreya , Pettus Joseph A. , Herr Harry W. , Bochner Bernard H. , Dalbagni Guido , Donat S. Machele , Russo Paul , Boyle Mary G. , Milowsky Matthew I. , Bajorin Dean F. 
Published: September 2008

AbstractBACKGROUND.Neoadjuvant cisplatin‐based chemotherapy improves survival in muscle‐invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) considered the standard regimen. Gemcitabine plus cisplatin (GC) has similar efficacy and less toxicity than MVAC in metastatic disease, but is untested as neoadjuvant treatment.METHODS.The authors retrospectively evaluated patients with muscle‐invasive urothelial carcinoma who received neoadjuvant GC before radical cystectomy between November 2000 and December 2006 at Memorial Sloan‐Kettering Cancer Center. Post‐therapy pathological downstaging to either residual disease at cystectomy (pT0) or no residual muscle‐invasion (<pT2, ie, pT0, pTIS, pT1), chemotherapy delivery, and disease‐free survival were the endpoints of interest. For comparison, similar endpoints were assessed in a historical cohort treated with neoadjuvant MVAC.RESULTS.Four cycles of neoadjuvant GC were given over 12 weeks (n = 42). Thirty‐nine (93%) of 42 patients received 4 cycles, with a median 91% drug delivery for cisplatin and 90% for gemcitabine. The pT0 proportion was 26% (95% confidence interval [CI], 14‐42), and no residual muscle‐invasive disease proportion (<pT2) was 36% (95% CI, 21‐52); pT0 was achieved in 28% (95% CI, 16‐42) and <pT2 in 35% (95% CI, 23‐49) of 54 MVAC‐treated patients. All 15 GC patients achieving <pT2 pathologic stage remained disease‐free at a median follow‐up of 30 months.CONCLUSIONS.Neoadjuvant GC is feasible and allows for timely drug delivery. The proportion of GC‐treated patients whose primary tumors were downstaged, with prolonged disease‐free survival and minimal or no residual disease, was similar to MVAC‐treated patients. Cancer 2008. © 2008 American Cancer Society.
A randomized phase II trial of adjuvant chemotherapy with uracil/tegafur and gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer
Authors: Yoshitomi Hideyuki , Togawa Akira , Kimura Fumio , Ito Hiroshi , Shimizu Hiroaki , Yoshidome Hiroyuki , Otsuka Masayuki , Kato Atsushi , Nozawa Satoshi , Furukawa Katsunori , Miyazaki Masaru ,   Pancreatic Cancer Chemotherapy Program of the Chiba University Department of General Surgery Affiliated Hospital Group
Published: September 2008

AbstractBACKGROUND.There have been few randomized studies of adjuvant chemotherapy using gemcitabine (GEM) in patients with resected pancreatic cancer.METHODS.Patients with invasive ductal pancreatic cancer who underwent radical surgery were enrolled and assigned to receive uracil/tegafur (UFT) and GEM together (GU) or GEM alone (G). GEM was administrated at a dosage of 1 g/m2 intravenously weekly 3 of 4 weeks and UFT at a dosage of 200 mg/day orally continuously. Eligibility included resection status 0 or 1, and no previous chemo‐ or/and radiation therapy. The primary endpoint was disease‐free survival (DFS), and secondary endpoints included overall survival (OS) and toxicity.RESULTS.Between 2002 and 2005, 100 patients were randomized into the 2 arms of the trial (50 patients to GU and 50 to G). One patient in the G group was found to be ineligible. Baseline characteristics were well balanced between the 2 groups. With a median observation period of 21 months, the 1‐ and 3‐year DFS rates were 50.0% and 17.7% in the GU group and 49.0% and 21.6% in the G group, respectively. The median OS was 21.2 months in the GU group and 29.8 months in the G group. Toxicity was minor and acceptable, less than grade 4 in both groups.CONCLUSIONS.Postoperative GEM‐based adjuvant chemotherapy was safe and well tolerated. However, addition of UFT with GEM did not improve DFS as compared with GEM alone. Further clinical trial resources for adjuvant chemotherapy should address other combinations and novel agents. Cancer 2008. © 2008 American Cancer Society.
Functional maturation of lamina propria dendritic cells by activation of NKT cells mediates the abrogation of oral tolerance
Authors: Chang Jae‐Hoon , Lee Jung‐Mi , Youn Hyun‐Jun , Lee Kyoo‐A , Chung Yeonseok , Lee Ah‐Young , Kweon Mi‐Na , Kim Ho‐Youn , Taniguchi Masaru , Kang Chang‐Yuil 
Published: September 2008

AbstractWe previously showed that although systemic administration of α‐galactosylceramide (αGalCer) or agonistic anti‐CD40 induced functional maturation of dendritic cells (DC) in mesenteric lymph nodes, only the former treatment succeeded in breaking the induction of oral tolerance. In this study, we looked for the essential factor responsible for the disruption of oral tolerance. We found that lamina propria (LP)‐DC was responsible for the oral OVA presentation and that Peyer's patch was not essential for the induction of oral tolerance. Therefore, we investigated the role of LP‐DC. Treatment with αGalCer but not with anti‐CD40 induced the full maturation of LP‐DC at an early time point. This functional activation of LP‐DC was mediated by strong activation of NKT cells that reside abundantly in the small intestinal lamina propria (SI‐LP) and interferon‐γ partially contributed to the LP‐DC activation. LP‐DC isolated from αGalCer‐treated OVA‐fed mice induced the differentiation of naïve CD4+ T cells into Th1 and Th2 and was associated with the reduced Foxp3+ population. In contrast, LP‐DC isolated from anti‐CD40‐treated OVA‐fed mice failed to generate Th cell differentiation but induced more Foxp3+ CD4+ T cells. Our results demonstrate that triggered by NKT cells in SI‐LP, functional maturation of Ag‐capturing DC from SI‐LP is necessary for the abrogation of oral tolerance induction.
Th memory for interleukin‐17 expression is stable in vivo
Authors: Lexberg Maria H. , Taubner Annegret , Förster Anna , Albrecht Inka , Richter Anne , Kamradt Thomas , Radbruch Andreas , Chang Hyun‐Dong 
Published: September 2008

AbstractBased on the memory for the re‐expression of certain cytokine genes, different subsets of Th cells have been defined. In Th type 1 (Th1) and Th2 memory lymphocytes, the genes for the cytokines interferon‐γ and interleukin (IL)‐4 are imprinted for expression upon restimulation by the expression of the transcription factors T‐bet and GATA‐3, respectively, and epigenetic modification of the cytokine genes. In Th17 cells, IL‐17 expression is dependent on the transcription factors RORγt and RORα. Here, we analyze the stability and plasticity of IL‐17 memory in Th17 cells. We have developed a cytometric IL‐17 secretion assay for the isolation of viable Th cells secreting IL‐17. For Th17 cells generated in vitro, IL‐17 expression itself is dependent on continued TGF‐β/IL‐6 or IL‐23 signaling and is blocked by interferon‐γ and IL‐4 signaling. In response to IL‐12 and IL‐4, in vitro generated Th17 cells are converted into Th1 or Th2 cells, respectively. Th17 cells isolated ex vivo, however, maintain their IL‐17 memory upon subsequent in vitro culture, even in the absence of IL‐23. Their cytokine memory is not regulated by IL‐12 or IL‐4. Th17 cells generated in vivo are a stable and distinct lineage of Th cell differentiation.
Frequency dependence of viscoelastic properties of medical grade silicones
Authors: Mahomed A. , Chidi N. M. , Hukins D. W. L. , Kukureka S. N. , Shepherd D. E. T. 
Published: September 2008

AbstractCylinders of medical grade silicone elastomers, (29 mm in diameter and 13 mm thick), immersed in physiological saline solution at 37°C, were investigated by dynamic mechanical analysis (DMA). A sinusoidal cyclic compression of 40 ± 5 N was applied over a frequency range, f, of 0.02–100 Hz. Values of the storage, E′, and loss, E″, moduli for the cylinders were found to depend on f; the dependence of E′ or E″ on the logarithm (base 10) of f was represented by a third‐order polynomial. Above about 0.3 Hz, the cylindrical specimens appeared to be undergoing the onset of a transition from the rubbery to the glassy state. There was no significant difference between results obtained at 37 and 23°C; pretreatment of specimens in physiological saline at 37°C for 24 h and 29 days had no appreciable effect on the results. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Stability of carbon‐centered radicals: Effect of functional groups on the energetics of addition of molecular oxygen
Authors: Wright James S. , Shadnia Hooman , Chepelev Leonid L. 
Published: September 2008

AbstractIn this paper we examine a series of hydrocarbons with structural features which cause a weakening of the CH bond. We use theoretical calculations to explore whether the carbon‐centered radicals R• which are created after breaking the bond can be stabilized enough so that they resist the addition of molecular oxygen, i.e. where the reaction R• + O2 → ROO• becomes energetically unfavorable. Calculations using a B3LYP‐based method provide accurate bond dissociation enthalpies (BDEs) for RH and ROO• bonds, as well as Gibbs free energy changes for the addition reaction. The data show strong correlations between ROO• and RH BDEs for a wide variety of structures. They also show an equally strong correlation between the ROO• BDE and the unpaired spin density at the site of addition. Using these data we examine the major functional group categories proposed in several experimental studies, and assess their relative importance. Finally, we combine effects to try to optimize resistance to the addition of molecular oxygen, an important factor in designing carbon‐based antioxidants. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
The inverse methodology of parameter estimation for model adjustment, design, simulation, control and optimization of fluid catalytic cracking (FCC) risers
Authors: Souza J. A. , Vargas J. V. C. , von Meien O. F. , Martignoni W. P. , Ordonez J. C. 
Published: September 2008

AbstractBACKGROUND: A simple model is required to produce a fast computational code that is sufficiently precise to be used for the design, simulation, control and optimization of fluid catalytic cracking (FCC) risers. This work experimentally validates and adjusts a simplified FCC riser model using available experimental data, and proposes utilization of the inverse problem of the parameter estimation method to fit any existing kinetic model to a specific feedstock/catalyst set for general application.RESULTS: The model adjustment procedure was repeated for nine different experimental sets and the best fitting parameters were obtained statistically. The fitting parameters were utilized to predict the riser output conditions for the other 18 data sets. The numerical results are in good quantitative and qualitative agreement with the experimental data. The model was then utilized to simulate an industrial FCC riser, predicting concentrations and temperature profiles from the bottom to the top of the riser.CONCLUSIONS: The results suggest that the simplified model, combined with the proposed inverse methodology could produce accurate results for any feedstock/catalyst set, once the kinetic model is known for a particular feedstock/catalyst set. Therefore, a low computational time and accurate tool is made available for simulation, control, design and optimization of FCC risers. Copyright © 2008 Society of Chemical Industry
Reproducible MRI measurement of adipose tissue volumes in genetic and dietary rodent obesity models
Authors: Johnson David H. , Flask Chris A. , Ernsberger Paul R. , Wong Wilbur C.K. , Wilson David L. 
Published: September 2008

AbstractPurposeTo develop ratio MRI [lipid/(lipid+water)] methods for assessing lipid depots and compare measurement variability with biological differences among lean controls (spontaneously hypertensive rats [SHRs]), dietary obese rats (SHR‐DOs), and genetic/dietary obese rats (SHROBs).Materials and MethodsImages with and without chemical shift‐selective (CHESS) water suppression were processed using a semiautomatic method that accounts for relaxometry, chemical shift, receive coil sensitivity, and partial volume.ResultsPartial volume correction improved results by 10% to 15%. Over six operators, volume variation was reduced to 1.9 mL from 30.6 mL for single‐image‐analysis with intensity inhomogeneity. For three acquisitions on the same animal, volume reproducibility was <1%. SHROBs had six times more visceral and eight times more subcutaneous adipose tissue than SHRs. SHR‐DOs had enlarged visceral depots (three times larger than those in SHRs). SHROBs had significantly more subcutaneous adipose tissue, indicating a strong genetic component to this fat depot. Liver ratios in SHR‐DO and SHROB were higher than in SHR, indicating elevated fat content. Among SHROBs, evidence suggested a phenotype SHROB* having elevated liver ratios and visceral adipose tissue volumes.ConclusionEffects of diet and genetics on obesity were significantly larger than variations due to image acquisition and analysis, indicating that these methods can be used to assess accumulation/depletion of lipid depots in animal models of obesity. J. Magn. Reson. Imaging 2008;28:915–927. © 2008 Wiley‐Liss, Inc.
Traumatic extra‐axial hemorrhage: Correlation of postmortem MSCT, MRI, and forensic‐pathological findings
Authors: Añon Javier , Remonda Luca , Spreng Adrian , Scheurer Eva , Schroth Gerhard , Boesch Chris , Thali Michael , Dirnhofer Richard , Yen Kathrin 
Published: September 2008

AbstractPurposeTo evaluate the diagnostic accuracy of in situ postmortem multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) in the detection of primary traumatic extra‐axial hemorrhage.Materials and MethodsThirty forensic neurotrauma cases and 10 nontraumatic controls who underwent both in situ postmortem cranial MSCT and MR imaging before autopsy were retrospectively reviewed. Both imaging modalities were analyzed in view of their accuracy, sensitivity, and specificity concerning the detection of extra‐axial hemorrhage. Statistical significance was calculated using the McNemar test. κ values for interobserver agreement were calculated for extra‐axial hemorrhage types and to quantify the agreement between both modalities as well as MRI, CT, and forensics, respectively.ResultsAnalysis of the detection of hemorrhagic localizations showed an accuracy, sensitivity, and specificity of 89%, 82%, and 92% using CT, and 90%, 83%, and 94% using MRI, respectively. MRI was more sensitive than CT in the detection of subarachnoid hemorrhagic localizations (P = 0.001), whereas no significant difference resulted from the detection of epidural and subdural hemorrhagic findings (P = 0.248 and P = 0.104, respectively). Interobserver agreement for all extra‐axial hemorrhage types was substantial (CT κ = 0.76; MRI κ = 0.77). The agreement of both modalitites was almost perfect (readers 1 and 2 κ = 0.88).ConclusionCT and MRI are of comparable potential as forensic diagnostic tools for traumatic extra‐axial hemorrhage. Not only of forensic, but also of clinical interest is the observation that most thin blood layers escape the radiological evaluation. J. Magn. Reson. Imaging 2008;28:823–836. © 2008 Wiley‐Liss, Inc.
Maturational changes in diffusion anisotropy in the rat corpus callosum: Comparison with quantitative histological evaluation
Authors: Jito Junya , Nakasu Satoshi , Ito Ryuta , Fukami Tadateru , Morikawa Shigehiro , Inubushi Toshiro 
Published: September 2008

AbstractPurposeTo determine the main histological components that affect fractional anisotropy (FA) in postnatal development of the rat corpus callosum and compare FA values with histological changes evaluated quantitatively.Materials and MethodsDiffusion tensor image (DTI) data of the rat (postnatal 1–10 weeks) corpus callosum were obtained with a 7.0 T MR scanner. Histological parameters were quantitatively assessed in toluidine blue‐stained semithin sections. Simple and multiple linear regression analyses were performed to investigate relationships between FA values and histological variables.ResultsThe mean FA value (mFA) increased significantly in the early growth stages, whereas the change became smaller after postnatal week 4. Simple regression analysis showed a high correlation between the area of myelin sheath and mFA (r = 0.856; P < 0.01). The area of extracellular space correlated negatively with mFA (r = −0.813; P < 0.01). In a forward stepwise analysis, the area of myelin sheath had the strongest influence on mFA (P < 0.001), followed by the number of unmyelinated axons (P = 0.113). Multiple linear regression analysis revealed that both parameters predicted mFA with a highly significant adjusted correlation coefficient (r2 adj. = 0.738, P < 0.001).ConclusionDuring the early development stage in the rat corpus callosum, the strongest contribution to FA value is the area of myelin sheath. J. Magn. Reson. Imaging 2008;28:847–854. © 2008 Wiley‐Liss, Inc.
Manganese‐enhanced MRI of the rat visual pathway: Acute neural toxicity, contrast enhancement, axon resolution, axonal transport, and clearance of Mn2+
Authors: Thuen Marte , Berry Martin , Pedersen Tina Bugge , Goa Pål Erik , Summerfield Mike , Haraldseth Olav , Sandvig Axel , Brekken Christian 
Published: September 2008

AbstractPurposeTo provide dose‐response data for the safe and effective use of MnCl2 for manganese (Mn2+) ‐enhanced MRI (MEMRI) of the visual pathway.Materials and MethodsRetinal ganglion cell (RGC) toxicity, CNR in MEMRI, axon density resolution for MEMRI, mode of axonal transport and clearance of Mn2+ from the vitreous after ivit were investigated. After 0, 30, 150, 300, 1500, and 3000 nmol ivit MnCl2, neural toxicity was measured by counting surviving RGC back‐filled with FluroGold (FG), CNR of the vitreous body and visual pathway by three‐dimensional (3D) MEMRI, resolution of ON axon density by correlating CNR with axon density, and axonal transport of Mn2+ by studying CNR in 3D MEMRI of the ON after ion of 200 nmol MnCl2.ResultsThere were no changes in RGC density after ivit MnCl2 ≤ 150 nmol, and reductions of 12%, 57%, and 94% occurred after 300, 1500, and 3000 nmol MnCl2. CNR increased in the visual pathway with MnCl2 ≤ 300 nmol, and decreased when the dose was raised further. Minimum detectable ON axon densities were 125,000/mm2. After 200 nmol ion MnCl2, CNR>0 were recorded distally from the ion site, but there was no signal in the retina. At ivit doses >1500 nmol, clearance from the vitreous body was impaired.ConclusionThe optimal dose for MEMRI of the rat visual pathway was found to be 150–300 nmol ivit MnCl2. Higher doses are toxic, causing RGC death, impair active clearance from the vitreous, and loss of Mn2+ enhancement throughout the visual pathway. Mn2+ traffic within RGC axons is mediated mainly by anterograde transport. J. Magn. Reson. Imaging 2008;28:855–865. © 2008 Wiley‐Liss, Inc.