bluuebunny/crossref_metadata_2025_split huggingface dataset:
p38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel vascular disrupting agent combretastatin A4
Authors: Quan Haitian , Xu Yongping , Lou Liguang 
Published: December 2007

AbstractCombretastatin A4 (CA4) is a novel vascular disrupting agent that has promising clinical efficacy because of its ability to inhibit microtubule assembly and subsequently disrupt tumor blood flow. In this study, we demonstrate that mitogen‐activated protein kinases (MAPKs) are critically involved in the cytotoxicity of CA4. CA4 stimulates both extracellular signal‐regulated kinases (ERK1/2) and p38 MAPK in the BEL‐7402 hepatocellular carcinoma cell line in a time‐ and dose‐dependent manner. This stimulation is a result of CA4‐induced microtubule disassembly, which is a reversible process. Reversibility of microtubule disassembly is evidenced by the ability of disassembled microtubules to reassemble just a few hours after CA4 treatment. p38 MAPK, but not ERK1/2, contributes to this microtubule reassembly following CA4 exposure, and only inhibition of p38 MAPK, but not ERK1/2, synergistically enhances CA4‐induced G2/M cell cycle arrest. Consistent with this, p38 MAPK inhibitors such as SB203580 and SB202190 also synergistically enhance the cytotoxicity of CA4 in cells where p38 MAPK is activated by CA4. This enhancement appears to be specific for CA4 because the cytotoxicity of other microtubule‐targeted agents such as paclitaxel, vinorelbine and colchicine was not affected by p38 MAPK inhibitors. These data indicate that p38 MAPK is a potential anticancer target and that the combination of CA4 with p38 MAPK inhibitors may be a novel and promising strategy for cancer therapy. © 2007 Wiley‐Liss, Inc.
Familial clustering of cancer at human papillomavirus‐associated sites according to the Swedish Family‐Cancer Database
Authors: Hussain Shehnaz K. , Sundquist Jan , Hemminki Kari 
Published: December 2007

AbstractFamilial aggregation of cervical cancer has been demonstrated previously, however aggregation of other human papillomavirus‐associated anogenital, upper aerodigestive tract and skin cancers has not been fully characterized. The Swedish Family‐Cancer Database, which contains reliable data on cancer incidence and nuclear family linkages for all residents of Sweden between 1958 and 2004, was used to calculate standardized incidence ratios (SIR) and 95% confidence intervals for offspring site‐specific cancer risks according to site‐specific cancer in sibling and parental probands. Offspring cancer risk was significantly increased when either a sibling or parent was affected at the same site for penile squamous cell carcinoma (SCC, SIR = 7.54), cervical adenocarcinoma (AC, SIR = 2.31), vulvar SCC (SIR = 2.27), skin SCC (SIR = 2.14), rectal AC (SIR = 1.86), in situ cervical SCC (SIR = 1.80), invasive cervical SCC (SIR = 1.77) and upper aerodigestive tract SCC (SIR = 1.57). Significant aggregation on the order of 2‐fold between anogenital cancers at different sites or histologies was also observed. In situ cervical SCC risk in offspring was strongly influenced by siblings affected with oropharyngeal SCC (SIR = 3.17) and tonsillar SCC (SIR = 1.84). Familial skin SCC was largely unassociated with anogenital or upper aerodigestive tract cancer risk in offspring. These data suggest that common host factors exist among individuals affected with anogenital and upper aerodigestive tract cancers. © 2007 Wiley‐Liss, Inc.
Risks of cancer among a cohort of 23,935 men and women with osteoporosis
Authors: McGlynn Katherine A. , Gridley Gloria , Mellemkjaer Lene , Brinton Louise A. , Anderson Kenneth C. , Caporaso Neil E. , Landgren Ola , Olsen Jorgen H. 
Published: December 2007

AbstractLow hormone levels among persons with osteoporosis may decrease risk of some cancers. Other osteoporosis risk factors, such as smoking and alcohol consumption, however, may increase risk. As these deleterious factors are more often associated with osteoporosis diagnosed prior to age 70 years, cancer risk may be higher in these younger persons than in the general population. To examine this hypothesis, a cohort study of 23,935 persons with osteoporosis was conducted in Denmark. Patients hospitalized with osteoporosis between 1978 and 1993 were identified in the Danish Inpatient Register. Linkage to the Danish Cancer Registry identified all cancer outcomes through 2003. Standardized incidence ratios (SIR) and 95% confidence intervals (95%CI) were calculated to compare cancer incidence in the cohort with that in the general population. Persons diagnosed prior to age 70 years were at increased cancer risk (women: SIR = 1.11, 95%CI = 1.04–1.19; men: SIR = 1.31, 95%CI = 1.13–1.50) due, in part, to increased risks of cancers of the buccal cavity, esophagus, liver, pancreas and lung. Persons diagnosed at ages 70 and older were at decreased risk (women: SIR = 0.91, 95%CI = 0.87–0.96; men: SIR = 0.89, 0.77–1.01) due, in part, to decreased risks of breast, endometrial, colon, rectal and brain cancers in women and prostate cancer in men. These results suggest that risk factors associated with earlier onset osteoporosis may be associated with increased risk of cancer. Conversely, factors associated with later onset osteoporosis may be related to a decreased risk of cancer. © 2007 Wiley‐Liss, Inc.
The use of doxycycline as a protectant against sulphur mustard in HaCaT cells
Authors: Lindsay Christopher D. , Gentilhomme Edgar , Mathieu Jacques D. 
Published: December 2007

AbstractAs part of an ongoing programme on medical countermeasures against the chemical warfare agent sulphur mustard (HD) and set against the background of the involvement of matrix metalloproteinases (MMPs) in the pathology of HD‐induced vesication processes, the potentially beneficial effects of doxycycline on cell attachment was determined in confluent HaCaT cell cultures exposed to HD. Doxycycline was found to inhibit to a significant extent the tendency of HD‐exposed cells to detach from the growth substrate, however, analysis of the metabolic activity of the adherent cells indicated that doxycycline treatment did not maintain cell viability. It was confirmed that apoptosis was the predominant mode of HD‐induced cell death. The results suggested that doxycycline and other MMP inhibitors may have a role to play in therapeutic intervention against HD exposure, but only as part of a combination therapy. The specific value of protease inhibitors in this capacity remains to be determined. Copyright © 2007 John Wiley & Sons, Ltd., and © Crown Copyright 2007, reproduced with the permission of the Controller of HMSO.
A Gibbs free energy correlation for automated docking of carbohydrates
Authors: Hill Anthony D. , Reilly Peter J. 
Published: December 2007

AbstractThermodynamic information can be inferred from static atomic configurations. To model the thermodynamics of carbohydrate binding to proteins accurately, a large binding data set has been assembled from the literature. The data set contains information from 262 unique protein–carbohydrate crystal structures for which experimental binding information is known. Hydrogen atoms were added to the structures and training conformations were generated with the automated docking program AutoDock 3.06, resulting in a training set of 225,920 all‐atom conformations. In all, 288 formulations of the AutoDock 3.0 free energy model were trained against the data set, testing each of four alternate methods of computing the van der Waals, solvation, and hydrogen‐bonding energetic components. The van der Waals parameters from AutoDock 1 produced the lowest errors, and an entropic model derived from statistical mechanics produced the only models with five physically and statistically significant coefficients. Eight models predict the Gibbs free energy of binding with an error of less than 40% of the error of any similar models previously published. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Parameterization of Ca+2–protein interactions for molecular dynamics simulations
Authors: Project Elad , Nachliel Esther , Gutman Menachem 
Published: December 2007

AbstractMolecular dynamics simulations of Ca+2 ions near protein were performed with three force fields: GROMOS96, OPLS‐AA, and CHARMM22. The simulations reveal major, force‐field dependent, inconsistencies in the interaction between the Ca+2 ions with the protein. The variations are attributed to the nonbonded parameterizations of the Ca+2‐carboxylates interactions. The simulations results were compared to experimental data, using the Ca+2‐HCOO− equilibrium as a model. The OPLS‐AA force field grossly overestimates the binding affinity of the Ca+2 ions to the carboxylate whereas the GROMOS96 and CHARMM22 force fields underestimate the stability of the complex. Optimization of the Lennard‐Jones parameters for the Ca+2‐carboxylate interactions were carried out, yielding new parameters which reproduce experimental data. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Theoretical study on the OH + CH3NHC(O)OCH3 reaction
Authors: Zhang Hui , Zhang Gui‐Ling , Liu Jing‐Yao , Liu Bo , Yu Xiao‐Yang , Li Ze‐Sheng 
Published: December 2007

AbstractThe multiple‐channel reactions OH + CH3NHC(O)OCH3 → products are investigated by direct dynamics method. The optimized geometries, frequencies, and minimum energy path are all obtained at the MP2/6‐311+G(d,p) level, and energetic information is further refined by the BMC‐CCSD (single‐point) method. The rate constants for every reaction channels, R1, R2, R3, and R4, are calculated by canonical variational transition state theory with small‐curvature tunneling correction over the temperature range 200–1000 K. The total rate constants are in good agreement with the available experimental data and the two‐parameter expression k(T) = 3.95 × 10−12 exp(15.41/T) cm3 molecule−1 s−1 over the temperature range 200–1000 K is given. Our calculations indicate that hydrogen abstraction channels R1 and R2 are the major channels due to the smaller barrier height among four channels considered, and the other two channels to yield CH3NC(O)OCH3 + H2O and CH3NHC(O)(OH)OCH3 + H2O are minor channels over the whole temperature range. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Liquid–liquid extraction of biomolecules: an overview and update of the main techniques
Authors: Mazzola Priscila G , Lopes Andre M , Hasmann Francislene A , Jozala Angela F , Penna Thereza CV , Magalhaes Perola O , Rangel‐Yagui Carlota O , Pessoa Jr Adalberto 
Published: December 2007

AbstractTwo‐phase systems can be exploited in separation science for the extraction/purification of desired biomolecules. This article reviews recent experimental work on the use of aqueous two‐phase polymer systems, two‐phase aqueous micellar systems and reversed micellar systems for the extraction/purification of biomolecules. The experimental partitioning behavior of different biomolecules is reviewed and new results with nisin and lipopolysaccharides are presented. An extensive description of each system is presented, based on the biomolecules behavior and the tools employed to improve their extraction and purification. Copyright © 2007 Society of Chemical Industry
Impact of effective alkali and sulfide profiling on Eucalyptus globulus kraft pulping. Selectivity of the impregnation phase and its effect on final pulping results
Authors: Santiago Ana S , Pascoal Neto C , Vilela Carla 
Published: December 2007

AbstractBACKGROUND: Eucalyptus globulus is an important wood source for paper production and, in the last few years, great efforts have been made to assess its chemical specificities and improve the kraft pulping efficiency. Despite the existence of several works concerning mostly the kinetics of E. globulus kraft pulping there is a lack of systematic studies on the initial phase of pulping as well as on the impact of effective alkali (EA) charge profiling on the kraft pulping performance of this species. The aim of the present work is to assess the effect of initial effective alkali and sulfide charges on the lignin and carbohydrates removal on the impregnation phase and to investigate the effect of EA splitting charge on the whole E. globulus pulping process efficiency.RESULTS: When the EA charge at impregnation phase increases, the amount of dissolved wood increases until it reaches a constant value of about 20%. Maximum polysaccharide removal at impregnation phase was about 10% of total wood weight. Glucose removal during impregnation was attributed to the degradation and/or dissolution of E. globulus glucans. For EA charges at impregnation phase higher than ∼15%, xylan retention on wood was roughly constant. Despite the differences found at impregnation phase on the amount of dissolved wood and lignin removal, it was demonstrated that these differences are almost completely attenuated until the end of the kraft pulping process.CONCLUSION: In the case of E. globulus, for a constant effective alkali charge, alkali profiling does not affect the whole kraft pulping performance. Copyright © 2007 Society of Chemical Industry
Fabrication of macroporous hydrogel membranes using photolithography for enzyme immobilization
Authors: Choi Dongkil , Lee Woojin , Lee Yeol , Kim Dae‐Nyun , Park Jinwon , Koh Won‐Gun 
Published: December 2007

AbstractBACKGROUND: The main problem when immobilizing enzyme inside hydrogel is the activity loss of the trapped enzymes due to the limitation on diffusion. In this study, macroporous poly(ethylene glycol) (PEG) hydrogel membrane was fabricated using photolithography to enhance the activity of immobilized enzyme.RESULT: Photopolymerization through the designed photomask produced crosslinked hydrogel with tunnel‐like macropores which were completely opened from top to bottom of the hydrogel membranes. Arrays of pores with 50 µm and 100 µm diameters were successfully created in the hydrogel membranes, and the pore density could be controlled by changing the photomask design. An activity study demonstrated that there was an enhancement of more than 50% in glucose oxidase activity in the macroporous membrane in comparison to the nonporous membrane. The activity of immobilized enzyme could be further enhanced by increasing the pore density of the hydrogel membranes or by using a higher molecular weight PEG.CONCLUSION: Increased enzymatic activity was observed in macroporous hydrogel membranes compared with nonporous hydrogel membranes due to the higher surface to volume ratio provided by the macroporous structure. Compared with other methods of obtaining porous hydrogel, the proposed method is much simpler and can minimize the deactivation of enzyme. Copyright © 2007 Society of Chemical Industry
Global sensitivity analysis for the determination of parameter importance in the chromatographic purification of polyclonal antibodies
Authors: Chhatre Sunil , Francis Richard , Newcombe Anthony R , Zhou Yuhong , Titchener‐Hooker Nigel , King Josh , Keshavarz‐Moore Eli 
Published: December 2007

AbstractBACKGROUND: The financial and technical challenges currently being faced by the pharmaceutical industry have prompted the development of computer models that rapidly evaluate manufacturing strategies for commercial‐scale drug production. The utility of a model is enhanced by the application of sensitivity analysis techniques (SA), which seek to quantify the relative importance of different input variables. Among several SA methods available, global sensitivity analysis (GSA) provides a powerful means of ranking inputs based on the contribution that each makes towards the variance of a model. To demonstrate the value of the approach, this paper describes the application of GSA to a mathematical model of the synthetic adsorbent‐based chromatographic capture of antibodies from ovine serum, a strategy being considered by Protherics UK Limited for production of an FDA‐approved rattlesnake anti‐venom.RESULTS: Results indicated that the binding capacity of the adsorbent for the antibody molecules was the most significant factor influencing their recovery, followed closely by the flowrate at which the ovine serum was applied to the column and then finally the antibody concentration in the feedstock. Together, these accounted for almost 94% of the model variance and hence suggest that these would be the key variables to focus upon during process development.CONCLUSION: Such data illustrate how GSA enables development studies to be concentrated upon those factors which exert the greatest influence on manufacturing performance. Ultimately, this reduces the size of the design space, making it easier to optimize a process and identify the most suitable operating conditions for large‐scale drug production. Copyright © 2007 Society of Chemical Industry
Removal of sulfur inorganic compounds by a biofilm of sulfate reducing and sulfide oxidizing bacteria in a down‐flow fluidized bed reactor
Authors: Celis‐García Lourdes B , González‐Blanco Gehovana , Meraz Mónica 
Published: December 2007

AbstractBACKGROUND: Biological sulfate removal is a process based on the biological sulfur cycle that consists of two steps: (1) production of sulfide by sulfate reduction; and (2) biological or physico‐chemical sulfide oxidation to elemental sulfur (S0). The objective of this work was to transform soluble sulfur (sulfate) into insoluble sulfur (elemental sulfur) coupling sulfate reduction and sulfide oxidation in one reactor. To accomplish this, a 2.3 L down‐flow fluidized bed reactor was used. Lactate was supplied as electron donor, sulfate and oxygen (air) were the electron acceptors.RESULTS: After 55 days of batch operation a biofilm with sulfate reducing and sulfide oxidizing activities was developed over a plastic support. Continuous operation for 90 days at a down‐flow superficial velocity of 7.7 m h−1 and 30 °C, showed that sulfate reduction amounted to 72–77% and carbon removal to 20–31%. Under low aeration rates (2.3 L d−1) 50% of the sulfate was transformed to elemental sulfur, when aeration increased to 5.4 L d−1 elemental sulfur recovery was only 30% and sulfide in the effluent amounted to 27% of the sulfur fed.CONCLUSION: It was possible to obtain elemental sulfur through a coupled anaerobic/aerobic process in one reactor using lactate, sulfate and oxygen (air) as substrates. The development of a biofilm with sulfate reducing and sulfide oxidizing activities was the key of the process. Copyright © 2007 Society of Chemical Industry
Sorption capacity of a new generation granular activated carbon—Bio‐Sep® bead—and its use in a suspended growth bioreactor
Authors: Lal Manmohan S , Thoma Gregory J , Karim Khursheed 
Published: December 2007

AbstractBACKGROUND: A new generation granular activated carbon—Bio‐Sep® beads—consist of 25% polymer (Nomex) and 75% powdered activated carbon. The porous structure and high surface area of these beads make them suitable for sorbent in adsorption columns, and for immobilization media in bioreactors. The aim of this study was to study the sorption characteristics of Bio‐Sep® beads for methyl t‐butyl ether (MTBE) and t‐butyl alcohol (TBA), and to demonstrate the advantage of their usage in a suspended growth bioreactor.RESULTS: The maximum uptake capacity of Bio‐Sep® beads for MTBE and TBA, in the studied concentration range (10–100 mg L−1), was observed to be 9.73 and 6.23 mg g−1, respectively. A 52 h desorption experiment resulted in 13.6–42.2% MTBE and 33–53% TBA desorption corresponding to the initial solid phase concentrations of 1.68–9.73 mg g−1 and 1.41–6.23 mg g−1, respectively. The sorption of TBA on the Bio‐Sep® beads was significantly hindered by the presence of MTBE. The addition of 10 g Bio‐Sep® beads (dry weight) in a suspended growth bioreactor was able to eliminate the inhibitory effect of 150 mg L−1 MTBE.CONCLUSIONS: At an equilibrium aqueous phase concentration (Ce) of 1 mg L−1, the solid phase concentration (qe) on Bio‐Sep® beads were observed as 1.44 and 0.47 mg g−1 for MTBE and TBA, respectively. The results obtained in this study indicate that Bio‐Sep® beads have reasonable sorption and desorption characteristics, which can be successfully exploited for the removal/degradation of toxic organic pollutants in high rate bioreactors. Copyright © 2007 Society of Chemical Industry
Processing of soybean (Glycine max) extracts in aqueous two‐phase systems as a first step for the potential recovery of recombinant proteins
Authors: Aguilar Oscar , Rito‐Palomares Marco 
Published: December 2007

AbstractBACKGROUND: The potential use of plants as production systems to establish bioprocesses has been established over the past decade. However, the lack of efficient initial concentration and separation procedures affect the generic acceptance of plants as economically viable systems. In this context the use of aqueous two‐phase systems (ATPS) can provide strategies to facilitate the adoption of plants as a base for bioprocesses. Among the crops, soybeans (Glycine max) represent an attractive alternative since potentially they can produce high levels of recombinant protein. In this paper the processing of fractionated soybean extracts using ATPS is evaluated as a first step to recover recombinant proteins expressed in plants, using β‐glucuronidase (GUS; E.C. 3.2.1.31) as a model protein.RESULTS: The evaluation of the effect of system parameters provided the conditions under which the contaminant proteins from fractionated soybean extracts and GUS concentrated in opposite phases. A PEG 600/phosphate system comprising 14.5% (w/w) polyethylene‐glycol (PEG), 17.5% (w/w) phosphate, a volume ratio (Vr) equal to 1.0, and a system pH of 7.0 resulted in the potential 83% recovery of GUS from the complex mixture and an increase in purity of 4.5‐fold after ATPS.CONCLUSIONS: The findings reported here demonstrate the potential of ATPS to process fractionated soybean extract as a first step to isolate and purify a recombinant protein expressed in soybeans. The proposed approach can simplify the way in which recombinant proteins expressed in plants can be recovered. Copyright © 2007 Society of Chemical Industry
Practical approach to protein recovery by countercurrent distribution in aqueous two‐phase systems
Authors: Hernandez‐Mireles Ileana , Benavides Jorge , Rito‐Palomares Marco 
Published: December 2007

AbstractBACKGROUND: The development of efficient processes that will rapidly deliver new biological products to the market is a key goal in biochemical engineering. The establishment of purification processes that permit the recovery of closely related products is essential. The recovery and purification of these types of products is not a trivial task. The current approach exploiting chromatography techniques demands practical alternatives to address the technical and economic constraints. The potential application of countercurrent distribution in aqueous two‐phase systems (CCD‐ATPS) for the purification of related proteins is an alternative of great potential worth considering.RESULTS: The evaluation of the potential application of CCD‐ATPS for the recovery of proteins provided conditions under which three model proteins (i.e. bovine serum albumin (BSA), ovalbumin and α‐lactoalbumin) of similar isoelectric point but different molecular size can be separated. Process conditions PEG 1000 13% (w/w), phosphate 14% (w/w) at pH 7.0 and volume ratio of 1.0 resulted, after 32 transfers in CCD, in three distinguishable peaks that corresponded to each of the selected proteins.CONCLUSIONS: The findings reported here demonstrate a practical strategy that serves as a first step to establishing initial conditions to further exploit the separation of closely related proteins. Copyright © 2007 Society of Chemical Industry