bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of response of U.S. veterans to treatment for the hepatitis C virus
Authors: Backus Lisa I. , Boothroyd Derek B. , Phillips Barbara R. , Mole Larry A.
Published: June 2007

The currently recommended treatment for hepatitis C virus (HCV) infection is pegylated interferon alfa (PEG-INF) and ribavirin, which can be difficult to tolerate. More information about predicting sustained virologic response (SVR) may allow more informed treatment decisions to be made. This retrospective observational cohort study identified predictors of SVR to PEG-INF and ribavirin in routine medical practice at 121 Department of Veterans Affairs facilities. Among 5,944 patients infected with HCV genotypes 1, 2, or 3 who had been treated with PEG-INF and ribavirin, SVR rates were 20%, 52%, and 43%, respectively, and discontinuation rates were 68% (prior to 48 weeks), 34% (24 weeks), and 41% (24 weeks), respectively. In multivariate analysis, significant predictors of decreased likelihood of genotype 1 patients having an SVR were being African American, clinical liver disease, diabetes, low cholesterol, low hemoglobin, low platelet count, and treatment at a low-volume facility. Predictors of increased likelihood of genotype 1 patients having an SVR were low-level HCV viremia, elevated ALT quotient, and receiving PEG-INF 2A (rather than 2B). For genotype 2 patients, increasing body mass index, prior use of interferon, and low platelet count were negative predictors; only low-level HCV viremia was a positive predictor. For genotype 3 patients, only receiving PEG-INF 2A affected the likelihood of an SVR; its effect was positive.

Conclusion:

Among patients for whom HCV treatment is initiated during routine medical care, multiple factors including form of PEG-INF received affect the SVR rate for genotype 1 patients. Few of these factors affect the rate for genotype 2 patients, and even fewer do so for genotype 3 patients. (HEPATOLOGY 2007.)
Assembly and budding of a hepatitis B virus is mediated by a novel type of intracellular vesicles
Authors: Mhamdi Mouna , Funk Anneke , Hohenberg Heinz , Will Hans , Sirma Hüseyin
Published: June 2007

Formation of enveloped viruses involves assembly and budding at cellular membranes. In this study, we elucidated the morphogenesis of hepadnaviruses on the ultrastructural and biochemical level using duck hepatitis B virus (DHBV) as a model system. Formation of virus progeny initiates at the endoplasmic reticulum (ER) and is conserved both in vitro and in vivo. The morphogenesis proceeds via membrane-surrounded vesicles containing both virions and subviral particles, indicating a common morphogenetic pathway. The virus particle–containing vesicles (VCVs) are generated and maintained by reorganization of endomembranes accompanied by a striking disorganization of the rough ER (rER). VCVs are novel organelles with unique identity and properties of ER, intermediate compartment, endosomes, and multivesicular bodies. VCVs are dynamic structures whose size and shape are regulated by both membrane fusion and fission.

Conclusion:

Our data indicate a strong reorganization of endomembranes during DHBV infection, resulting in the biogenesis of novel organelles serving as multifunctional platforms for assembly and budding of virus progeny. (HEPATOLOGY 2007.)
FIB-4
Authors: Vallet-Pichard Anaïs , Mallet Vincent , Nalpas Bertrand , Verkarre Virginie , Nalpas Antoine , Dhalluin-Venier Valérie , Fontaine Hélène , Pol Stanislas
Published: June 2007

To optimize the management of patients with chronic hepatitis C virus (HCV) infection, noninvasive tests to determine the degree of hepatic fibrosis have been developed. The aims of this study were (1) to validate a simple, inexpensive, noninvasive test called FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age, in a series of 847 liver biopsies performed in HCV-monoinfected patients; and (2) to compare the results of 780 FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected patients. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93), respectively. An FIB-4 index <1.45 had a negative predictive value of 94.7% to exclude severe fibrosis with a sensitivity of 74.3%. An FIB-4 index higher than 3.25 had a positive predictive value to confirm the existence of a significant fibrosis (F3-F4) of 82.1% with a specificity of 98.2%. Using these ranges, 72.8% of the 847 liver biopsies were correctly classified. The FIB-4 index was strongly correlated to the FibroTest results for a score <1.45 or >3.25 (κ = 0.561,

P

< 0.01). A FIB-4 value <1.45 or >3.25 (64.6% of the cases) was concordant with FibroTest results in 92.1% and 76%, respectively.

Conclusion:

For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and inexpensive method for assessing liver fibrosis and proved to be concordant with FibroTest results. (HEPATOLOGY 2007.)
Hepatitis C virus protein expression causes calcium-mediated mitochondrial bioenergetic dysfunction and nitro-oxidative stress
Authors: Piccoli Claudia , Scrima Rosella , Quarato Giovanni , D'Aprile Annamaria , Ripoli Maria , Lecce Lucia , Boffoli Domenico , Moradpour Darius , Capitanio Nazzareno
Published: June 2007

Hepatitis C virus (HCV) infection induces a state of oxidative stress that is more pronounced than that in many other inflammatory diseases. In this study we used well-characterized cell lines inducibly expressing the entire HCV open-reading frame to investigate the impact of viral protein expression on cell bioenergetics. It was shown that HCV protein expression has a profound effect on cell oxidative metabolism, with specific inhibition of complex I activity, depression of mitochondrial membrane potential and oxidative phosphorylation coupling efficiency, increased production of reactive oxygen and nitrogen species, as well as loss of the Pasteur effect. Importantly, all these effects were causally related to mitochondrial calcium overload, as inhibition of mitochondrial calcium uptake completely reversed the observed bioenergetic alterations.

Conclusion

: Expression of HCV proteins causes deregulation of mitochondrial calcium homeostasis. This event occurs upstream of further mitochondrial dysfunction, leading to alterations in the bioenergetic balance and nitro-oxidative stress. These observations provide new insights into the pathogenesis of hepatitis C and may offer new opportunities for therapeutic intervention. (HEPATOLOGY 2007.)
Use of mixed bivariate distributions for deriving inter‐station correlation coefficients of rain rate
Authors: Ha Eunho , Yoo Chulsang
Published: June 2007

Even though rain rate is notorious for its spatial and temporal intermittency, its effect on the second‐order statistics of rain rate, especially the inter‐station correlation coefficients, has not been intensively evaluated before. This study has derived and compared the inter‐station correlation coefficient of rain rate for three cases of data: (1) only the positive measurements at both locations; (2) the positive measurements at either one or both locations; (3) all the measurements including zero measurement at both locations. For these three cases, the inter‐station correlation coefficients are analytically derived by applying the mixed bivariate log‐normal distribution. As an application example, the model parameters are estimated using the rain rate data collected at the Geum River basin, Korea, and the resulting inter‐station correlation coefficients are evaluated and compared with those estimated by applying the Gaussian distribution. We could find that highly biased inter‐station correlation coefficients are unavoidable when simply estimating them under the assumption of Gaussian distribution, or even when using the log‐transformed rain rate data. Copyright © 2007 John Wiley & Sons, Ltd.
Hybrid nanofibrous membranes of PLGA/chitosan fabricated via an electrospinning array
Authors: Duan Bin , Wu Lili , Yuan Xiaoyan , Hu Zhen , Li Xiulan , Zhang Yang , Yao Kangde , Wang Min
Published: June 2007

Hybrid nanofibrous membranes of poly(lactic‐co‐glycolic acid) (PLGA) and chitosan with different chitosan amounts (32.3, 62.7, and 86.5%) were fabricated via a specially designed electrospinning setup consisting of two sets of separate syringe pumps and power supplies. After soaking in chloroform overnight to dissolve PLGA, the amount of chitosan in the hybrid membranes was determined. The structure, mechanical properties, water uptake, and cytocompatibilities of the nanofibrous membranes were investigated by scanning electron microscopy, tensile testing, incubation in phosphate buffer solution, and human embryo skin fibroblasts culturing. Results showed that the chitosan amount in PLGA/chitosan membranes could be well controlled by adjusting the number of syringe for electrospinning of PLGA or chitosan, respectively. Because of the introduction of chitosan, which is a naturally hydrophilic polymer, the hybrid PLGA/chitosan membranes after chitosan crosslinking exhibited good mechanical and water absorption properties. The cytocompatibility of hybrid PLGA/chitosan membranes was better than that of the electrospun PLGA membrane. The electrospun hybrid nanofibrous membranes of PLGA and chitosan appear to be promising for skin tissue engineering. The concept of using an electrospinning array to form multicomponent nanofibrous membranes will lead to the creation of novel scaffolds for tissue engineering applications. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Biocompatibility and antibacterial activity of plasma sprayed titania coating grafting collagen and gentamicin
Authors: Li Baoe , Liu Xuanyong , Cao Cong , Ding Chuanxian
Published: June 2007

In this article, the plasma sprayed titania coatings were treated by grafting pure and gentamicin loaded collagen to improve the biocompatibility and antibacterial activity. The biocompatibility of the titania coating grafting collagen was evaluated by in vitro cell culturing test. The release rate of gentamicin from collagen was measured in tris‐HCl buffer using UV spectrophotometer, and the antibacterial activity of the titania coating with gentamicin against Staphylococcus aureus was examined using the zone of inhibition test. The results showed that collagen was successfully grafted on the surface of titania coatings treated by sulfuric acid. The in vitro cell culturing test revealed that collagen significantly improved the cell adhesion and proliferation on the surface of titania coatings. The gentamicin loaded in collagen matrix could retain a sustained release in tris‐HCl for 30 days, which was efficient to protect against the postoperative infection caused by S. aureus. The results indicated that the plasma sprayed titania coating grafting collagen and gentamicin would have the antibacterial activity together with the biocompatibility, which might be beneficial for the long term stability and surgical success rate of implants. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Preparation and characterization of nano‐hydroxyapatite/chitosan/konjac glucomannan composite
Authors: Zhou Gang , Li Yubao , Zhang Li , Zuo Yi , Jansen John A.
Published: June 2007

Nano‐hydroxyapatite (n‐HA)/chitosan (CS)/konjac glucomannan (KGM) composite was prepared by coprecipitation method and investigated by thermal gravitivity/differentiate thermal analysis, Fourier transform infrared spectroscopy, X‐ray diffraction, inductively coupled plasma emission spectroscopy, scanning electron microscopy, and energy dispersive X‐ray analyzer. The analyses showed that the three phases of n‐HA, CS, and KGM combined closely to each other. Further, in vitro tests were conducted to investigate the degradation and bioactivity of the composite. During immersion in simulated body fluid (SBF), pores appeared and a new substance containing Ca and P formed on the surface of the composite. Also, the concentration of Ca and P in SBF changed and weight loss of the composite was observed during time. The composite revealed a high degradation in SBF. Evidently, the new composite has a potential to be used as a carrier of implantable drug delivery system. The biodegradation rate and route could be different from CS and KGM, which will provide an opportunity to control the degradation rate or drug releasing rate by simply adjusting the ratio of CS and KGM. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Epigenetic and genetic mechanisms contribute to telomerase inhibition by EGCG
Authors: Berletch Joel B. , Liu Canhui , Love William K. , Andrews Lucy G. , Katiyar Santosh K. , Tollefsbol Trygve O.
Published: June 2007

The ends of human chromosomes are protected from the degradation associated with cell division by 15–20 kb long segments of hexameric repeats of 5′‐TTAGGG‐3′ termed telomeres. In normal cells telomeres lose up to 300 bp of DNA per cell division that ultimately leads to senescence; however, most cancer cells bypass this lifespan restriction through the expression of telomerase. hTERT, the catalytic subunit essential for the proper function of telomerase, has been shown to be expressed in approximately 90% of all cancers. In this study we investigated the hTERT inhibiting effects of (−)‐epigallocatechin‐3‐gallate (EGCG), the major polyphenol found in green tea catechins, in MCF‐7 breast cancers cells and HL60 promyelocytic leukemia cells. Exposure to EGCG reduced cellular proliferation and induced apoptosis in both MCF‐7 and HL60 cells in vitro, although hTERT mRNA expression was decreased only in MCF‐7 cells when treated with EGCG. Furthermore, down‐regulation of hTERT gene expression in MCF‐7 cells appeared to be largely due to epigenetic alterations. Treatment of MCF‐7 cells with EGCG resulted in a time‐dependent decrease in hTERT promoter methylation and ablated histone H3 Lys9 acetylation. In conjunction with demethylation, further analysis showed an increase in hTERT repressor E2F‐1 binding at the promoter. From these findings, we propose that EGCG is effective in causing cell death in both MCF‐7 and HL60 cancer cell lines and may work through different pathways involving both anti‐oxidant effects and epigenetic modulation. J. Cell. Biochem. 103: 509–519, 2008. © 2007 Wiley‐Liss, Inc.
PKD, PKD2, and p38 MAPK mediate Hsp27 serine‐82 phosphorylation induced by neurotensin in pancreatic cancer PANC‐1 cells
Authors: Yuan Jingzhen , Rozengurt Enrique
Published: June 2007

It is widely recognized that Hsp27 is a downstream substrate of the p38 MAPK cascade whereas the role of PKD family members in mediating receptor‐stimulated Hsp27 Ser‐82 phosphorylation has not been evaluated. Here, we show that neurotensin induced a rapid and striking increase in Hsp27 Ser‐82 phosphorylation in PANC‐1 cells, which was closely correlated with stimulation of activation loop phosphorylation of PKDs and p38 MAPK Thr180/Tyr182 phosphorylation. Treatment of PANC‐1 cells with either the selective PKC inhibitor GF‐I or the p38 MAPK inhibitor SB202190 partially reduced neurotensin‐induced Hsp27 Ser‐82 phosphorylation. However, treatment of the cells with a combination of GF‐I and SB202190 virtually abolished neurotensin‐induced Hsp27 Ser‐82 phosphorylation. Overexpression of PKD in stably transfected PANC‐1 cells increased the magnitude and prolonged the duration of Hsp27 Ser‐82 phosphorylation in response to neurotensin. Either PKD or PKD2 gene silencing utilizing siRNAs targeting distinct PKD or PKD2 sequences reduced neurotensin‐stimulated Hsp27 Ser‐82 phosphorylation, but cotransfection of siRNAs targeting both, PKD and PKD2, markedly decreased neurotensin‐induced Hsp27 Ser‐82 phosphorylation. Knockdown of PKD and PKD2 abolished Hsp27 phosphorylation in cells treated with SB202190. Thus, neurotensin induces Hsp27 Ser‐82 phosphorylation through p38 MAPK‐ and PKC/PKD‐dependent pathways in PANC‐1 cells. Our results demonstrate, for the first time, that neurotensin induces a striking increase in Hsp27 phosphorylation on Ser‐82 in PANC‐1 cells through convergent p38 MAPK, PKD, and PKD2 signaling. J. Cell. Biochem. 103: 648–662, 2008. © 2007 Wiley‐Liss, Inc.
Analytical excited state forces for the time‐dependent density‐functional tight‐binding method
Authors: Heringer D. , Niehaus T. A. , Wanko M. , Frauenheim TH.
Published: June 2007

An analytical formulation for the geometrical derivatives of excitation energies within the time‐dependent density‐functional tight‐binding (TD‐DFTB) method is presented. The derivation is based on the auxiliary functional approach proposed in [Furche and Ahlrichs, J Chem Phys 2002, 117, 7433]. To validate the quality of the potential energy surfaces provided by the method, adiabatic excitation energies, excited state geometries, and harmonic vibrational frequencies were calculated for a test set of molecules in excited states of different symmetry and multiplicity. According to the results, the TD‐DFTB scheme surpasses the performance of configuration interaction singles and the random phase approximation but has a lower quality than ab initio time‐dependent density‐functional theory. As a consequence of the special form of the approximations made in TD‐DFTB, the scaling exponent of the method can be reduced to three, similar to the ground state. The low scaling prefactor and the satisfactory accuracy of the method makes TD‐DFTB especially suitable for molecular dynamics simulations of dozens of atoms as well as for the computation of luminescence spectra of systems containing hundreds of atoms. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Hartree–Fock exchange fitting basis sets for H to Rn †
Authors: Weigend Florian
Published: June 2007

For elements H to Rn (except Lanthanides), a series of auxiliary basis sets fitting exchange and also Coulomb potentials in Hartree–Fock treatments (RI‐JK‐HF) is presented. A large set of small molecules representing nearly each element in all its common oxidation states was used to assess the quality of these auxiliary bases. For orbital basis sets of triple zeta valence and quadruple zeta valence quality, errors in total energies arising from the RI‐JK approximation are below ∼1 meV per atom in molecular compounds. Accuracy of RI‐JK‐approximated HF wave functions is sufficient for being used for post‐HF treatments like Møller–Plesset perturbation theory, MP2. Compared to nonapproximated treatments, RI‐JK‐HF leads to large computational savings for quadruple zeta valence orbital bases and, in case of small to midsize systems, to significant savings for triple zeta valence bases. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Searching for globally optimal functional forms for interatomic potentials using genetic programming with parallel tempering
Authors: Slepoy A. , Peters M. D. , Thompson A. P.
Published: June 2007

Molecular dynamics and other molecular simulation methods rely on a potential energy function, based only on the relative coordinates of the atomic nuclei. Such a function, called a force field, approximately represents the electronic structure interactions of a condensed matter system. Developing such approximate functions and fitting their parameters remains an arduous, time‐consuming process, relying on expert physical intuition. To address this problem, a functional programming methodology was developed that may enable automated discovery of entirely new force‐field functional forms, while simultaneously fitting parameter values. The method uses a combination of genetic programming, Metropolis Monte Carlo importance sampling and parallel tempering, to efficiently search a large space of candidate functional forms and parameters.

The methodology was tested using a nontrivial problem with a well‐defined globally optimal solution: a small set of atomic configurations was generated and the energy of each configuration was calculated using the Lennard‐Jones pair potential. Starting with a population of random functions, our fully automated, massively parallel implementation of the method reproducibly discovered the original Lennard‐Jones pair potential by searching for several hours on 100 processors, sampling only a minuscule portion of the total search space. This result indicates that, with further improvement, the method may be suitable for unsupervised development of more accurate force fields with completely new functional forms. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
On searching in, sampling of, and dynamically moving through conformational space of biomolecular systems: A review
Authors: Christen Markus , van Gunsteren Wilfred F.
Published: June 2007

Methods to search for low‐energy conformations, to generate a Boltzmann‐weighted ensemble of configurations, or to generate classical‐dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems. After having chosen the degrees of freedom and method to generate molecular configurations, the efficiency of the search or sampling can be enhanced in various ways: (i) efficient calculation of the energy function and forces, (ii) application of a plethora of search enhancement techniques, (iii) use of a biasing potential energy term, and (iv) guiding the sampling using a reaction or transition pathway. The overview of the available methods should help the reader to choose the combination that is most suitable for the biomolecular system, degrees of freedom, interaction function, and molecular or thermodynamic properties of interest. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Efficiency of numerical basis sets for predicting the binding energies of hydrogen bonded complexes: Evidence of small basis set superposition error compared to Gaussian basis sets
Authors: Inada Yasuji , Orita Hideo
Published: June 2007

Binding energies of selected hydrogen bonded complexes have been calculated within the framework of density functional theory (DFT) method to discuss the efficiency of numerical basis sets implemented in the DFT code DMol3 in comparison with Gaussian basis sets. The corrections of basis set superposition error (BSSE) are evaluated by means of counterpoise method. Two kinds of different numerical basis sets in size are examined; the size of the one is comparable to Gaussian double zeta plus polarization function basis set (DNP), and that of the other is comparable to triple zeta plus double polarization functions basis set (TNDP). We have confirmed that the magnitudes of BSSE in these numerical basis sets are comparative to or smaller than those in Gaussian basis sets whose sizes are much larger than the corresponding numerical basis sets; the BSSE corrections in DNP are less than those in the Gaussian 6‐311+G(3df,2pd) basis set, and those in TNDP are comparable to those in the substantially large scale Gaussian basis set aug‐cc‐pVTZ. The differences in counterpoise corrected binding energies between calculated using DNP and calculated using aug‐cc‐pVTZ are less than 9 kJ/mol for all of the complexes studied in the present work. The present results have shown that the cost effectiveness in the numerical basis sets in DMol3 is superior to that in Gaussian basis sets in terms of accuracy per computational cost. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Extensive theoretical study on the low‐lying electronic states of silicon monofluoride cation including spin‐orbit coupling
Authors: Liu Kun , Bian Wensheng
Published: June 2007

Ab initio calculations on the low‐lying electronic states of SiF+ are performed using the internally contracted multireference configuration interaction method with the Davidson correction and entirely uncontracted aug‐cc‐pV5Z basis set. The effects of spin‐orbit coupling are accounted for by the state interaction approach with the full Breit–Pauli Hamiltonian. The entire 23 Ω states generated from the 12 valence Λ–S states, which correlate with the first dissociation channel are studied for the first time. Good agreement is found between the calculated results and the available experimental data. The spin‐orbit coupling effects on the potential energy curves and spectroscopic properties are studied. Various curve crossings are revealed, which could lead to the predissociation of the a3Π, A1Π, and (2)3Σ+ states and the predissociation pathways are analyzed based upon the calculated spin‐orbit matrix elements. The calculated ionization potentials of the ground‐state SiF to a few states of SiF+ are in good agreement with the available experimental measurements. Moreover, the transition dipole moments of the dipole‐allowed transitions and the transition properties for the A3Π0+–X1Σ and B3Π1–X1Σ transitions are predicted, including the Franck–Condon factors and the radiative lifetimes. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Efficient bond function basis set for π‐π interaction energies
Authors: Ding Yun , Mei Ye , Zhang John Z. H. , Tao Fu‐Ming
Published: June 2007

Systematic study has been carried out to investigate the accuracy of mid‐bond functions in describing π‐π interactions in benzene dimer. Potential energy curves are calculated for the sandwich, T‐shaped, and parallel‐displaced configurations of benzene dimer by adding bond functions in MP2 (second‐order Møller–Plesset perturbation theory) calculations with a wide range of split‐valence and augmented, correlation‐consistent basis sizes. At MP2 level, the largest basis set used with a bond function (denoted aug‐cc‐pVDZf‐6s6p4d2f) differs by only ∼0.1 kcal/mol relative to the result obtained from the standard aug‐cc‐pVQZ basis calculation (without the bond function). The calculated potential energy curves from the bond function basis aug‐cc‐pVDZf‐6s6p4d2f and the larger standard basis aug‐cc‐pVTZ are in excellent agreement with each other for all three configurations. The number of bond function basis aug‐cc‐pVDZf‐6s6p4d2f is 526 compared to 828 of aug‐cc‐pVTZ and 1512 of aug‐cc‐pVQZ. Current study shows that bond functions can be effectively employed to give accurate description of π‐π interactions with the addition of only a minimal number of bond functions. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
On the chromatic spectrum of acyclic decompositions of graphs
Authors: Jamison Robert E. , Mendelsohn Eric
Published: June 2007

If G is any graph, a G‐decomposition of a host graph H = (V, E) is a partition of the edge set of H into subgraphs of H which are isomorphic to G. The chromatic index of a G‐decomposition is the minimum number of colors required to color the parts of the decomposition so that two parts which share a node get different colors. The G‐spectrum of H is the set of all chromatic indices taken on by G‐decompositions of H. If both S and T are trees, then the S‐spectrum of T consists of a single value which can be computed in polynomial time. On the other hand, for any fixed tree S, not a single edge, there is a unicyclic host whose S‐spectrum has two values, and if the host is allowed to be arbitrary, the S‐spectrum can take on arbitrarily many values. Moreover, deciding if an integer k is in the S‐spectrum of a general bipartite graph is NP‐hard. We show that if G has c > 1 components, then there is a host H whose G‐spectrum contains both 3 and 2c + 1. If G is a forest, then there is a tree T whose G‐spectrum contains both 2 and 2c. Furthermore, we determine the complete spectra of both paths and cycles with respect to matchings. © 2007 Wiley Periodicals, Inc. J Graph Theory 56: 83–104, 2007
GC‐MS analysis of multiply derivatized opioids in urine
Authors: Chen Bud‐Gen , Wang Sheng‐Meng , Liu Ray H.
Published: June 2007

Opiates such as hydrocodone, hydromorphone, oxycodone, noroxycodone, and oxymorphone reportedly may interfere with the analysis of morphine and codeine. The analysis of these compounds themselves also is an important issue. Thus, double derivatization approaches utilizing methoxyamine and hydroxylamine to first form oxime products with keto‐opiates, followed by the derivatization with trimethylsilyl (TMS) or propionyl groups, have been developed for the simultaneous analysis of these compounds. However, these studies have not included all compounds of interest and resulted in inadequate chromatographic resolution or significant intensity cross‐contribution between the ions designating the analyte and its deuterated internal standard for certain compounds. By exploring three‐step derivatization approaches with the combination of various derivatization groups and orders, this study concluded that application of methoxyimino/propionyl/TMS groups, in the order listed, facilitated the simultaneous analysis of eight opiates (morphine, 6‐acetylmorphine, hydromorphone, oxymorphone, codeine, hydrocodone, oxycodone and noroxycodone) in urine samples, achieving satisfactory limits of quantitation and detection. In addition, the adapted approach resulted in two usable products for morphine and codeine providing alternatives, should interferences render any of these products non‐usable. Copyright © 2007 John Wiley & Sons, Ltd.
Impaired SDF1/CXCR4 signaling in glial progenitors derived from SOD1G93A mice
Authors: Luo Yongquan , Xue Haipeng , Pardo Andrea C. , Mattson Mark P. , Rao Mahendra S. , Maragakis Nicholas J.
Published: June 2007

Mutations in the superoxide dismutase 1 (SOD1) gene are associated with familial amyotrophic lateral sclerosis (ALS), and the SOD1G93A transgenic mouse has been widely used as one animal model for studies of this neurodegenerative disorder. Recently, several reports have shown that abnormalities in neuronal development in other models of neurodegeneration occur much earlier than previously thought. To study the role of mutant SOD1 in glial progenitor biology, we immortalized glial restricted precursors (GRIPs) derived from mouse E11.5 neural tubes of wild‐type and SOD1G93A mutant mice. Immunocytochemistry using cell lineage markers shows that these cell lines can be maintained as glial progenitors, because they continue to express A2B5, with very low levels of glial fibrillary acidic protein (astrocyte), βIII‐tubulin (neuron), and undetected GalC (oligodendrocyte) markers. RT‐PCR and immunoblot analyses indicate that the chemokine receptor CXCR4 is reduced in SOD1G93A GRIPs. Subsequently, SOD1G93A GRIPs are unable to respond to SDF1α to activate ERK1/2 enzymes and the transcription factor CREB. This may be one pathway leading to a reduction in SOD1G93A cell migration. These data indicate that the abnormalities in SOD1G93A glial progenitor expression of CXCR4 and its mediated signaling and function occur during spinal cord development and highlight nonneuronal (glial) abnormalities in this ALS model. © 2007 Wiley‐Liss, Inc.
Gender‐specific in vivo measurement of the structural and mechanical properties of the human patellar tendon
Authors: Onambélé Gladys N.L. , Burgess Katherine , Pearson Stephen J.
Published: June 2007

Human patellar tendon stress (σ), strain (ε), stiffness (K), and tensile or Young's modulus (E), are determined in vivo through voluntary isometric contractions monitored with B‐mode ultrasonography. The limitations in previous studies are: (1) they have generally not accounted for the fact that the distal attachment of the patellar tendon (the tibial tuberosity) also displaces; thus, they have underestimated ε (and, hence, injury risk) while overestimating K; (2) no gender effect has been studied despite the fact that females are seen to have higher incidences of tendon‐related injuries. The current investigation therefore aimed to determine the gender specific values of σ, ε, K, and E of the patellar tendon while also accounting for distal displacement of the patellar tendon. Healthy young males (aged 23.1 ± 1.3 years, n = 10) and females (aged 21.3 ±0.9 years, n = 10) were tested. The maximal ε of the young males was ∼5–10% higher than that reported in earlier literature. Average female versus male values for ε, σ, K, and E, taken at the same force level as the males for comparison purposes, were respectively 10.6 ± 1.0 versus 9.0 ± 1.0%, 36.9 ± 1.4 versus 28.9 ± 0.9 MPa, 1053 ± 108 versus 1652 ± 216 N · mm−1, and 0.61 ± 0.08 versus 0.68 ± 0.10 GPa (p < 0.05). There are gender differences in tendon structural and mechanical properties. The current methodology may be useful in a clinical context where early prediction of injury risk and/or monitoring of reconstructed tendon needs to be an accurate, objective, and reliable method if optimal functionality is to be achieved. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1635–1642, 2007
Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP‐43 in skeletal muscle following denervation in a rat model
Authors: Ma Jianjun , Shen Jian , Garrett Jeffrey P. , Lee Cassandra A. , Li Zhongyu , Elsaidi Gamal A. , Ritting Andrew , Hick Jeffrey , Tan Kim H. , Smith Thomas L. , Smith Beth P. , Koman L. Andrew
Published: June 2007

Neuromuscular junction destabilization following nerve injury contributes to irreversible functional impairment. Myogenic Regulatory Factors (MRF's) including myoblast determination factor (MyoD), MRF‐4, Myogenin, and myogenic factors‐5 (myf‐5), and Growth‐associated protein 43 KDa (GAP43) regulate gene expression of nicotinic acetylcholine receptor (nAChR) subunits (alpha, beta, delta, gamma, and epsilon). We hypothesized that nerve injury induces altered gene expression of MRF's, nAChRs, and GAP‐43 in the skeletal muscle which destabilize neuromuscular junctions. The tibial nerve was transected in 42 juvenile male Sprague‐Dawley rats. Denervated and contralateral control gastrocnemius m. mRNA for nAChR subunits, MRF's, and GAP‐43 were determined by real time reverse transcription polymerase chain reaction (real time RT‐PCR). After transection, muscle mass decreased for 1 year with a nadir of 75% at 3 months. Alpha, gamma, and epsilon subunit genes increased by 3 and peaked at 7 days before returning to control levels (P < 0.05). Beta subunits and GAP‐43 tended to increase. Delta subunits peaked at 3 days returning to control levels by 30 days. By one month, most of the nAChR subunits had returned to control levels. Alpha, beta, gamma, and delta subunit expression remained significantly lower than control up to 1 year later (P < 0.05). MRF4, Myogenin, and MyoD expression paralleled that of alpha, gamma, and epsilon nAChR subunits (P < 0.05). Gene expression of nAChR alpha, gamma, delta and epsilon subunits was biphasic in the first month after nerve injury, similar to that of MRF's. nAChR subunits and MRF's may play a critical role in neuromuscular junction stability. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1498–1505, 2007
Role of parathyroid hormone in the mechanosensitivity of fracture healing
Authors: Gardner Michael J. , van der Meulen Marjolein C.H. , Carson Joshua , Zelken Jonathan , Ricciardi Benjamin F. , Wright Timothy M. , Lane Joseph M. , Bostrom Mathias P.
Published: June 2007

The mechanical environment at a fracture site can influence the course of healing. Intermittent parathyroid hormone (PTH) has been shown to accelerate fracture healing. Intact bone models show that mechanical loading and PTH have a synergistic beneficial effect on osteogenesis. We hypothesized that PTH and mechanical loading would have a similar synergistic effect on fracture healing. Eighty mice underwent surgical osteotomy and intramedullary nailing of the tibia. The mice were divided into four groups: one underwent daily loading, one received daily subcutaneous PTH injections (30 µg/kg/day), one received both loading and PTH, and a control group received sham loading and vehicle injection. Daily loading was applied to the ends of the tibia with an external loading device for 2 weeks. Fracture healing was assessed by microcomputed tomography, histology, and biomechanical testing. The group with both loading and PTH had increased osteoblast and osteoclast activity and was the only group with a significantly larger callus mineral density and bone volume fraction. The PTH only group had significantly more osteoid in the callus compared to the control group, indicating enhanced early osteoblast activity. This group also had a significantly higher bone mineral content and total bone volume compared to controls. The group that received loading as the only intervention had significantly greater osteoclast activity versus controls. The contribution of loading and PTH administration to the fracture healing cascade indicates a synergistic effect. This finding may be of potential clinical utility when weight bearing is utilized to stimulate lower extremity fracture healing. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1474–1480, 2007
Oxysterols enhance osteoblast differentiation in vitro and bone healing in vivo
Authors: Aghaloo Tara L. , Amantea Christopher M. , Cowan Catherine M. , Richardson Jennifer A. , Wu Ben M. , Parhami Farhad , Tetradis Sotirios
Published: June 2007

Oxysterols, naturally occurring cholesterol oxidation products, can induce osteoblast differentiation. Here, we investigated short‐term 22(S)‐hydroxycholesterol + 20(S)‐hydroxycholesterol (SS) exposure on osteoblastic differentiation of marrow stromal cells. We further explored oxysterol ability to promote bone healing in vivo. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA expression, mineralization, and Runx2 DNA binding activity. To explore the effects of osteogenic oxysterols in vivo, we utilized the critical‐sized rat calvarial defect model. Poly(lactic‐co‐glycolic acid) (PLGA) scaffolds alone or coated with 140 ng (low dose) or 1400 ng (high dose) oxysterol cocktail were implanted into the defects. Rats were sacrificed at 6 weeks and examined by three‐dimensional (3D) microcomputed tomography (microCT). Bone volume (BV), total volume (TV), and BV/TV ratio were measured. Culture exposure to SS for 10 min significantly increased ALP activity after 4 days, while 2 h exposure significantly increased mineralization after 14 days. Four‐hour SS treatment increased OCN mRNA measured after 8 days and nuclear protein binding to an OSE2 site measured after 4 days. The calvarial defects showed slight bone healing in the control group. However, scaffolds adsorbed with low or high‐dose oxysterol cocktail significantly enhanced bone formation. Histologic examination confirmed bone formation in the defect sites grafted with oxysterol‐adsorbed scaffolds, compared to mostly fibrous tissue in control sites. Our results suggest that brief exposure to osteogenic oxysterols triggered events leading to osteoblastic cell differentiation and function in vitro and bone formation in vivo. These results identify oxysterols as potential agents in local and systemic enhancement of bone formation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1488–1497, 2007
No effects of in vivo micro‐CT radiation on structural parameters and bone marrow cells in proximal tibia of wistar rats detected after eight weekly scans
Authors: Brouwers Julienne E.M. , van Rietbergen Bert , Huiskes Rik
Published: June 2007

Recently developed in vivo animal high‐resolution micro‐CT scanners offer the possibility to monitor longitudinal changes in bone microstructure of small rodents, but may impose high radiation doses that could damage bone tissue. The goal of this study was to determine the effects on the bone of 8 weeks of in vivo scanning of the proximal tibia in female Wistar rats. Eight weekly CT scans were made of the right proximal tibia of nine female, 30‐week‐old, retired‐breeder, Wistar rats. Two weeks after the last weekly scan, a final scan was made. The left leg was only scanned during first and final measurements and served as a control. A two‐way ANOVA with repeated measures was performed on the first and last measurements of left and right tibiae for six bone structural parameters. Bone marrow cells were flushed out and tested for cell viability. No significant difference was found between left and right for any of the bone structural parameters (p > 0.05). Structure model index and trabecular separation significantly changed as a result of aging, while none of the other parameters did. No significant difference was found between left and right in absolute and percentage number of cell viability. We did not find any indication that the applied scanning regime, in combination with the particular settings used, would affect the results of in vivo bone structural measurements in long‐term studies using aged, female Wistar rats. However, careful consideration should be made when determining the number of scans, particularly when a different experimental design is used. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1325–1332, 2007
Hearth bread baking quality of durum wheat varying in protein composition and physical dough properties
Authors: Edwards Nancy M , Preston Ken R , Paulley F Garth , Gianibelli M Cristina , McCaig Tom N , Clarke John M , Ames Nancy P , Dexter James E
Published: June 2007

Thirty durum wheat genotypes from ten countries of origin were grown in field plots for two consecutive years. Three of the genotypes were γ‐gliadin 42 types and the remainder were γ‐gliadin 45 types. Among the γ‐gliadin 45 types, six high‐molecular‐weight glutenin subunit (HMW‐GS) patterns were identified: 6 + 8, 7 + 8, 7 + 16, 14 + 15, 20 and 2*, 20. All the γ‐gliadin 42 genotypes contained low amounts of unextractable polymeric protein (UPP) and exhibited low gluten index values and weak gluten properties. The γ‐gliadin 45 genotypes exhibited a wide range of UPP, gluten index and dough strength. HMW‐GS 20 genotypes were generally weak, whereas HMW‐GS 6 + 8 and 7 + 8 genotypes were generally strong. When baked by a lean formulation, long‐fermentation straight‐dough hearth bread process, the durum wheat genotypes exhibited a wide range of baking quality. Loaf volume and bread attributes were strongly correlated with UPP and gluten index. Some of the genotypes exhibited bread attributes and loaf volume equal or slightly superior to those of a high‐quality bread wheat flour. However, even the strongest durum wheat genotypes exhibited inferior fermentation tolerance to the bread wheat flour, as seen by a requirement for lower baking absorption during dough handling and more fragile dough properties when entering the oven. Among the HMW‐GS groups, HMW‐GS 7 + 8 and 6 + 8 exhibited the best and HMW‐GS 20 the poorest baking quality. Farinograph, alveograph and small‐scale extensigraph properties demonstrated that a combination of dough elasticity and extensibility was needed for superior durum wheat baking performance. Copyright © 2007 Society of Chemical Industry
Survival in patients with papillary thyroid cancer is not affected by the use of radioactive isotope
Authors: Podnos Yale D. , Smith David D. , Wagman Lawrence D. , Ellenhorn Joshua D.I.
Published: June 2007

Introduction

Papillary cancer is the most common neoplasm of the thyroid. The mainstay of treatment is thyroidectomy, but most patients are additionally treated with radioactive iodine (RAI). Its utility is controversial. This study seeks to determine whether RAI use affects patient outcome and to identify specific cohorts of patients that benefit from its use.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database is a large‐scale sample of approximately 14% of the US population. It was used to identify patients with papillary carcinoma of the thyroid. Statistical analyses were used to compare prognostic factors such as lymph node status, age, tumor size, and treatment with RAI.

Results

A total of 14,545 patients were identified in SEER as having papillary cancer of the thyroid. Multivariate analysis showed significantly worse outcome in patients with age>45 years, tumor size >2 cm, lymph node disease, and distant metastases. Multivariate analysis failed to show RAI significantly affecting mortality. Survival between those not treated with RAI was similar to those whose treatment included it (P = 0.9176). Subgroup analysis identified patients older than 45 years with primary tumors >2 cm and disease in the lymph nodes with distant metastatic disease as the only group positively affected by RAI.

Conclusions

Despite its widespread use in the treatment of well‐differentiated papillary cancer of the thyroid, RAI only affects a survival advantage in older patients with large primary tumors involving the lymph nodes and with distant spread. Treating other patient groups is costly and offers no improvement in outcome. J. Surg. Oncol. 2007; 96:3–7. © 2007 Wiley‐Liss, Inc.
Photophysics and kinetics of naphthopyran derivatives, Part 5: An analytical model utilizing temperature effects to evaluate ABC(2k,3–5ϕ) kinetic parameters
Authors: Maafi M. , Brown R. G.
Published: June 2007

A theoretical model is established for a photochemical ABC(2k,6ϕ) system in order to characterize the relationship of its absorbance at the photostationary state with temperature. Provided that the thermal processes of the system are not opposing steps, it has been found that depending on the relative magnitude of the system parameters (two rate constants, up to six quantum yields, and two extinction coefficients), several behaviors are predicted by the model. However, from an analytical viewpoint, this mathematical description generates for all cases, six new equations involving kinetic and spectroscopic parameters that are numerically defined by the available experimental data. For the first time, the latter are used to solve the dynamics of several systems. Novel procedures allowing a complete analytical elucidation of ABC(2k,3ϕ) systems (eight unknowns) as well as many other cases belonging to ABC(2k,4–5ϕ) kinetics have been successfully established. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 472–479, 2007
The silver(I)‐catalyzed exchange of coordinated cyanide in hexacyanoferrate(II) by phenylhydrazine in aqueous medium
Authors: Naik R. M. , Tiwari R. K. , Singh P. K. , Yadav S. B. S.
Published: June 2007

The [Ag]+‐catalyzed exchange of coordinated cyanide in [Fe(CN)6]4− by phenylhydrazine (PhNHNH2) has been studied spectrophotometrically at 488 nm by monitoring increase in the absorbance for the formation of cherry red colored complex [Fe(CN)5PhNHNH2]3−. The other reaction conditions were pH 2.80±,0.02, temperature = 30.0 ± 0.1°C, and ionic strength (I) = 0.02 M (KNO3). The reaction was followed as a function of pH, ionic strength, temperature, [Fe(CN)4−6], [PhNHNH2], [Ag+] by varying one variable at a time. The initial rates were evaluated for each variation using the plane mirror method. The initial rates evaluated as a function of [Fe(CN)4−6] clearly indicate that the initial rate increases with the increase in [Fe(CN)4−6] and finally reaches to a limiting value when [Fe(CN)4−6]/[AgNO3] ⩾ 1000. It indicates the formation of a strong adduct between [Fe(CN)6]4− and AgNO3 prior to the abstraction of CN−. The variation in initial rates with [PhNHNH2] also showed limiting values at [Fe(CN)4−6]/[PhNHNH2] ⩾ 8.30. The complex behavior due to pH and [Ag+] variations on the rate has been explained in detail. The composition of the final reaction product [Fe(CN)5PhNHNH2] formed during the course of reaction has been found to be 1:1 using the mole ratio method. The evaluated values of activation parameters for the catalyzed reaction are Ea = 53.85 kJ mol−1, Δ H≠, = 51.33 kJ mol−1, and Δ S≠ = −134.63 J K−1 mol−1, which suggest an interchange dissociative mechanism. A most plausible mechanistic scheme has been proposed based on the experimental observations. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 447–456, 2007