bluuebunny/crossref_metadata_2025 huggingface dataset:
A Boundary element method based on cauchy integrals for some linear quadratic boundary control problems on a circle
Authors: Chen Goong , Chen Chiang‐Pu , Aronov Irina
Published: July 2010

For certain types of elliptic boundary control problems, the boundary element method has considerable advantage over the traditional finite element or finite difference methods because of the reduction of dimensionality in computations. In this paper we examine a variant of such boundary integral methods based on Cauchy integrals. The cost functional here contains only finitely many quadratic terms related to sensory data at those finite interior points. We see that the numerical efficiency of this approach hinges largely on the complexity of the inverse of a certain boundary integral operator. In the case of a circle, such an inverse is readily obtainable and entire computations require only a small effort to yield useful numerical information about the optimal control. Other general situations are also discussed.
A Hierarchical approach to optimized control of water distribution systems: Part II. Lower‐level algorithm
Authors: Coulbeck B. , Brdys M. , Orr C. H. , Rance J. P.
Published: July 2010

Consideration is given to the lower level of a hierarchical optimization structure for evaluating optimized control schedules for common types of water distribution systems. The structure is presented in Part I. The lower‐level optimization problem involves independent optimization of a number of generalized pump stations. This requires minimization of individual pump station consumed power. An algorithm for the pump station power minimization is proposed and its convergence and optimality properties are investigated. The algorithm is tested over a range of physical data. Typical results are presented, which include comparisons with an alternative solution method.
Optimal shape design and unilateral boundary value problems: Part I
Authors: Haslinger J. , Neittaanmäki P. , Tiihonen T. , Kaarna A.
Published: July 2010

In the first part we give a general existence theorem and a regularization method for an optimal control problem where the control is a domain in R″ and where the system is governed by a state relation which includes differential equations as well as inequalities. In the second part applications for optimal shape design problems governed by the Dirichlet‐Signorini boundary value problem are presented. Several numerical examples are included.
Feedback controllers for stochastic‐parameter systems: Relations among various stabilizability conditions
Authors: Yaz Engin
Published: July 2010

In this work we consider various feedback controllers designed for linear stochastic‐parameter discrete‐time systems. These controllers are derived by use of different system models (true system model and its deterministic equivalent) and different performance criteria (infinite horizon and finite moving horizon) to stabilize the same class of systems. It is shown that sufficient conditions for almost‐sure and mean‐square stabilizability by these controllers are closely related.
A Boundary value technique for solving singularly perturbed, fixed end‐point optimal control problems
Authors: Kadalbajoo Mohan K. , Singh Arindama
Published: July 2010

A method is proposed to solve fixed end‐point, linear optimal control problems with quadratic cost and singularly perturbed state. After translating the problem into a two‐point boundary value problem, we choose two points t1, t2 ϵ [t0, tf] and let τ = (t‐t0)/ϵ and σ = (tf‐t)/ϵ. The τ‐scaled, original and σ‐scaled boundary value problems are then solved on the intervals [t0, t1], [t1, t2] and [t2, tf] respectively. A test example is solved to illustrate the method.
Adsorption of aqueous Hg (II) by a novel poly(aniline‐co‐o‐aminophenol)/mesoporous silica SBA‐15 composite
Authors: Tang Rong , Li Qin , Cui Hao , Zhang Ya , Zhai Jianping
Published: July 2010

A novel poly(aniline‐co‐o‐aminophenol) (PAOA)/mesoporous silica SBA‐15 nanocomposite was synthesized and investigated for adsorption of Hg (II) from aqueous solutions of wide pH range. A chemical oxidation method was employed for polymerization of aniline and o‐aminophenol on an ordered SBA‐15 template to obtain a significantly enlarged BET surface area of the adsorbent. Efficiency study revealed that the PAOA/SBA‐15 could reach a maximum Hg (II) adsorption capacity of over 400 mg/g. Kinetic study showed that the Hg (II) adsorption by the PAOA/SBA‐15 fitted a pseudo‐second‐order kinetic model, indicating that the mercury adsorption process was predominantly controlled by chemical process. The results of this study also proved that the adsorbed Hg (II) could be effectively desorbed from the PAOA/SBA‐15 in 0.1M HCl and 5% sulfocarbonide solutions. Associated adsorption mechanism was also investigated by means of Fourier transform infrared (FTIR) and X‐ray photoelectron spectroscopy (XPS) techniques. Copyright © 2010 John Wiley & Sons, Ltd.
Ausflug in die Vergangenheit: Chinin und andere Chinaalkaloide 2. Teil: Die Aufklärung des räumlichen Baus der Chinolin‐Chinaalkaloide
Authors: Eiden Fritz
Published: July 2010

Schon im frühen 19. Jahrhundert wurden die wichtigsten Chinaalkaloide isoliert. Zum Nachweis und zur Konstitutionsaufklärung des Chinolinanteils der Alkaloide brauchte man mehr als fünf Jahrzehnte und erst um die Jahrhundertwende kam man der Chinuclidingruppe auf die Spur. 1907 schließlich konnte das Problem der Verknüpfung der Chinolin‐ mit der Chinuclidingruppe gelöst und so die Konstitution der Chinaalkaloide endgültig geklärt werden. Doch damit war das Ziel der mühsamen Wanderung noch lange nicht erreicht: Für die Analyse der Raumstruktur von Chinin, Cinchonin und ihrer Stereoisomeren wurden weitere vierzig Jahre benötigt.
The comparison of the behaviors of polymer/clay nanocomposites based on high density polyethylene and polypropylene in exposure of electron‐irradiation
Authors: Mohaddespour Ahmad , Ahmadi Seyed Javad , Abolghasemi Hossein
Published: July 2010

The effect of irradiation on thermal and mechanical properties of high density polyethylene (HDPE) and polypropylene (PP)/clay nanocomposites in the presence of polyethylene glycol (PEG) and polypropylene glycol (PPG) for enhancing the clay dispersion into the polymer matrices is considered. The morphology studies show that clay layers satisfactorily expand in the presence of compatibilizers. The irradiation improves the mechanical properties of HDPE nanocomposites at 500 kGy, but it decreases the tensile strength of PP nanocomposites. The addition of PEG markedly ameliorates the mechanical properties of HDPE nanocomposites at 500 kGy, while this improvement is not deduced for PP nanocomposites. The thermogravimetric analysis data show that the irradiation increases the thermal stability of HDPE nanocomposites at the clay content of 5 wt% with and without compatibilizer. The thermal stability of PP nanocomposites descends with the irradiation dose, and the presence of PPG into the PP matrix intensifies this reduction. POLYM. COMPOS., 2010. © 2009 Society of Plastics Engineers
Inferential closed‐loop control of particle size and molecular weight distribution in emulsion polymerization of styrene
Authors: Vafa Ehsan , Shahrokhi Mohammad , Abedini Hossein
Published: July 2010

In this work, simultaneous inferential control of particle size distribution (PSD) and molecular weight distribution (MWD) in a semi‐batch emulsion polymerization reactor of styrene has been addressed. Using a comprehensive dynamic model for PSD and MWD predictions and performing a sensitivity analysis, it has been revealed that free surfactant and chain transfer agent (CTA) concentrations in the reactor are the most suitable candidates for inferential control of PSD and MWD, respectively. To control concentrations of these species in the reactor, their inlet feed flow rates are used as manipulated variables. It is assumed that the concentration of CTA is measured infrequently and therefore an open‐looped observer, based on the reaction calorimetry, has been designed to estimate the CTA concentration. The infrequent measurements of CTA concentration are used to correct its estimation. As the online measuring of the ionic free surfactant concentration is also difficult, solution conductivity which is a good indication of free surfactant concentration is used for control purposes. Simulation results show that the performance of the proposed control scheme is satisfactory even in the presence of model mismatch. POLYM. ENG. SCI., 2010. © 2010 Society of Plastics Engineers
Improved mechanical properties of poly(ethylene terephthalate) nanocomposite fibers
Authors: Litchfield David W. , Baird Donald G. , Rim Peter B. , Chen Chen
Published: July 2010

Improvements in Young's modulus and strength (tenacity) of poly(ethylene terephthalate) (PET) fibers were obtained by drawing unoriented nanocomposite filaments containing low concentrations (<3 wt%) of various organically modified montmorillonites (MMTs) in a second step at temperatures above the glass transition. Prior to melt spinning, solid‐state polymerization was used to rebuild lost molecular weight, due to MMT‐induced degradation, to a level suitable for producing high strength fibers. Greater improvements in mechanical properties occurred when the MMT stacks were intercalated with PET. A nominal 1 wt% loading of dimethyl‐dehydrogenated tallow quaternary ammonium surface modified MMT in drawn PET fiber showed a 28% and 63% increase in Young's modulus and strength, respectively. Relative to an unfilled PET fiber, these results surpassed the upper bound of the rule of mixtures estimate and suggested that both the type of surface modification and concentration of MMT affect the degree of PET orientation and crystallinity. Furthermore, drawability above Tg and elongation at break increased upon the addition of organically modified MMT to unoriented PET fibers, which was a key distinction of this work from others examining similar systems. POLYM. ENG. SCI., 2010. © 2010 Society of Plastics Engineers
Effect of side chain length on the glass transition of copolymers from styrene with n‐alkyl citraconimides and with n‐alkyl itaconimides
Authors: Cowie J. M. G. , Reid V. M. C. , Mcewen I. J.
Published: July 2010

Equimolar copolymers of styrene with a series of N‐n‐alkyl citraconimides where the alkyl group varies from methyl to octadecyl were synthesised and the dependence of the glass transition on the length of the alkyl chain examined. Over the series N‐methyl to N‐n‐octadecyl only a smooth monotonic decrease in the value of the glass transition temperature Tg was found. Any increase in Tg at high alkyl chain lengths that might arise from ordering effects was not detected. However, by viewing the copolymer structure as comprising a main chain unit and a series of methylene side chain units of varying length, then plotting the data according to the Gordon‐Taylor equation, a deviation from linearity is revealed that may be interpreted as due to incipient crystallisation of the longer side chains.

A similar examination of a series of copolymers of styrene with N‐n‐alkyl itaconimides proved impracticable due to the inability to prepare isomerically pure itaconimide monomers. Comparisons of the citraconimide series were thus drawn with literature data on copolymers of styrene with N‐alkyl maleimides.
Non‐Gaussian effects in styrene‐butadiene rubber
Authors: Doherty William O. S. , Leè Kim L. , Treloar Leslie R. G.
Published: July 2010

Simultaneous measurements of stress and birefringence were made on a vulcanized styrene‐butadiene rubber (SBR) at 0°, 15° and 25°C. The stress‐strain curves at all temperatures showed a strong upward deviation from the Gaussian statistical theory at high extensions which became more pronounced with decreasing temperature due to the increasing extension to break. The birefringence, however, was substantially of the form predicted by the Gaussian theory. Comparison studies on natural rubber under similar conditions of experiment showed birefringence and hysteresis effects which could be interpreted on the basis of strain‐induced crystallisation (as revealed by X‐rays). Such effects were completely absent in the SBR samples which also showed no evidence of crystallisation on X‐ray examination in the stretched state. It is concluded that the upturn in stress‐strain curve in both materials is primarily due to the limited extensibility of the network, as treated in the non‐Gaussian statistical theory, and that crystallisation, when present, plays only a subsidiary role.
Insights in Molecular Structure of Organosilicon Plasma Polymer Produced by Means of Atmospheric Pressure Dielectric Barrier Discharge Process
Authors: Bour Jérôme , Charles Laurence , Petersen Julien , Michel Marc , Bardon Julien , Ruch David
Published: July 2010

Most of polymers resulting from plasma polymerization exhibit a structure, which is very complex and different from those synthesized by conventional polymerization methods. The molecular structure of such plasma polymers is difficult to assess, but its characterization is a crucial issue. Mass spectrometry (MS) seems to be a promising analytical approach to get this molecular information. The chemical structure of a ppHMDSO (plasma polymer HexaMethylDiSiloxane) film, deposited by means of atmospheric pressure dielectric barrier discharge process, has first been characterized by means of FTIR spectroscopy. Additional insights in the polymer structure were provided by mass spectrometric techniques. MALDI‐TOF‐MS and ESI‐Q‐TOF‐MS analyses were carried out to obtain information on high molecular weight oligomers and/or small polymers collected in the THF soluble fraction of a ppHMDSO film. Although uncertainty still remains about the detected species, it could be concluded they were copolymers such as poly(dimethylsiloxane‐co‐methylsiloxane) or poly(dimethylsiloxane‐co‐SiO2) with a number of monomers up to 20, and some structures could be proposed for the end groups.

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The three‐dimensional structure of the first EGF‐like module of human factor IX: Comparison with EGF and TGF‐α
Authors: Baron M. , Norman D.G. , Harvey T.S. , Campbell I.D. , Handford P.A. , Mayhew M. , Brownlee G.G. , Tse A.G.D.
Published: July 2010

The three‐dimensional structure of the first epidermal growth factor (EGF)‐like module from human factor IX has been determined in solution using two‐dimensional nuclear magnetic resonance (in the absence of calcium and at pH 4.5). The structure was found to resemble closely that of EGF and the homologous transforming growth factor‐α (TGF‐α). Residues 60–65 form an antiparallel β‐sheet with residues 68–73. In the C‐terminal subdomain a type II β‐turn is found between residues 74 and 77 and a five‐residue turn is found between residues 79 and 83. Glu 78 and Leu 84 pair in an antiparallel β‐sheet conformation. In the N‐terminal region a loop is found between residues 50 and 55 such that the side chains of both are positioned above the face of the β‐sheet. Residues 56–60 form a turn that leads into the first strand of the β‐sheet. Whereas the global fold closely resembles that of EGF, the N‐terminal residues of the module (46–49) do not form a β‐strand but are ill‐defined in the structure, probably due to the local flexibility of this region. The structure is discussed with reference to recent site‐directed mutagenesis data, which have identified certain conserved residues as ligands for calcium.
Sequence and expression of the gene for N10‐formyltetrahydrofolate synthetase from Clostridium cylindrosporum
Authors: Rankin Carolyn A. , Haslam Gale C. , Himes Richard H.
Published: July 2010

Sau3 A and Hind III restriction fragments of Clostridium cylindrosporum genomic DNA were used to isolate clones containing 80% of the N10‐H4folate synthetase gene in a 5′ fragment and the remaining 20% of the gene in the 3′ fragment. These fragments were joined at a common SnaB I restriction site and expressed in Escherichia coli at a level equivalent to what is normally found in C. cylindrosporum. Sequence comparisons show a large degree of homology with genes from two other clostridial species, including a thermophile. Certain conserved sequences found in the three clostridial proteins and in the N10‐H4folate synthetase portion of eukaryotic Cl‐H4folate synthases may represent consensus sequences for nucleotide and H4folate binding.
Crevice‐forming mutants of bovine pancreatic trypsin inhibitor: Stability changes and new hydrophobic surface
Authors: Kim Key‐Sun , Tao Feng , Fuchs James , Woodward Clare , Danishefsky Avis T. , Housset Dominique , Wlodawer Alexander
Published: July 2010

Four mutants of bovine pancreatic trypsin inhibitor (BPTI) with replacements in the rigid core result in the creation of deep crevices on the surface of the protein. Other than crevices at the site of the mutation, few other differences are observed in the crystal structures of wild‐type BPTI and the mutants F22A, Y23A, N43G, and F45A. These mutants are highly destabilized relative to wild type (WT). The differences between WT and mutants in the free energy change associated with cooperative folding/unfolding, ΔΔG0(WT→mut), have been measured by calorimetry, and they are in good agreement with ΔΔG0(WT→mut) values from hydrogen exchange rates. For F22A the change in free energy difference is about 1.7 kcal/mol at 25 °C; for the other three mutants it is in the range of 5–7 kcal/mol at 25 °C. The experimental ΔΔG0(WT→mut) values of F22A, Y23A, and F45A are reasonably well accounted for as the sum of two terms: the difference in transfer free energy change, and a contribution from exposure to solvent of new surface (Eriksson, A.E., et al., 1992, Science 255, 178–183), if the recently corrected transfer free energies and surface hydrophobicities (De Young, L. & Dill, K., 1990, J. Phys. Chem. 94, 801–809; Sharp, K.A., et al., 1991a, Science 252, 106–109) are used and only nonpolar surface is taken into account. In N43G, three protein–protein hydrogen bonds are replaced by protein–water hydrogen bonds. The value of ΔΔG0(WT→mut) computed from model transfer free energies and surface hydrophobicities is 4.0 kcal/mol less than observed, consistent with reports that one hydrogen bond contributes about 1.3 kcal/mol of stabilizing free energy (Shirley, B.A., et al., 1992, Biochemistry 31, 725–732).
Crystal structure of recombinant human triosephosphate isomerase at 2.8 Å resolution. Triosephosphate isomerase‐related human genetic disorders and comparison with the trypanosomal enzyme
Authors: Mande Shekhar C. , Hol Wim G.J. , Mainfroid Véronique , Goraj Karine , Martial Joseph A. , Kalk Kor H.
Published: July 2010

The crystal structure of recombinant human triosephosphate isomerase (hTIM) has been determined complexed with the transition‐state analogue 2‐phosphoglycolate at a resolution of 2.8 Å. After refinement, the R‐factor is 16.7% with good geometry. The asymmetric unit contains 1 complete dimer of 53,000 Da, with only 1 of the subunits binding the inhibitor. The so‐called flexible loop, comprising residues 168‐174, is in its “closed” conformation in the subunit that binds the inhibitor, and in the “open” conformation in the other subunit. The tips of the loop in these 2 conformations differ up to 7 Å in position. The RMS difference between hTIM and the enzyme of Trypanosoma brucei, the causative agent of sleeping sickness, is 1.12 Å for 487 Cα positions with 53% sequence identity. Significant sequence differences between the human and parasite enzymes occur at about 13 Å from the phosphate binding site. The chicken and human enzymes have an RMS difference of 0.69 Å for 484 equivalent residues and about 90% sequence identity. Complementary mutations ensure a great similarity in the packing of side chains in the core of the β‐barrels of these 2 enzymes. Three point mutations in hTIM have been correlated with severe genetic disorders ranging from hemolytic disorder to neuromuscular impairment. Knowledge of the structure of the human enzyme provides insight into the probable effect of 2 of these mutations, Glu 104 to Asp and Phe 240 to Ile, on the enzyme. The third mutation reported to be responsible for a genetic disorder, Gly 122 to Arg, is however difficult to explain. This residue is far away from both catalytic centers in the dimer, as well as from the dimer interface, and seems unlikely to affect stability or activity. Inspection of the 3‐dimensional structure of trypanosomal triosephosphate isomerase, which has a methionine at position 122, only increased the mystery of the effects of the Gly to Arg mutation in the human enzyme.
Hydrogen bonding motifs of protein side chains: Descriptions of binding of arginine and amide groups
Authors: Shimoni Liat , Glusker Jenny P.
Published: July 2010

The modes of hydrogen bonding of arginine, asparagine, and glutamine side chains and of urea have been examined in small‐molecule crystal structures in the Cambridge Structural Database and in crystal structures of protein‐nucleic acid and protein‐protein complexes. Analysis of the hydrogen bonding patterns of each by graph‐set theory shows three patterns of rings (R) with one or two hydrogen bond acceptors and two donors and with eight, nine, or six atoms in the ring, designated R2 2(8), R2 2(9), and R1 2(6). These three patterns are found for arginine‐like groups and for urea, whereas only the first two patterns Rl(8) and R2(9) are found for asparagine‐ and glutamine‐like groups. In each case, the entire system is planar within 0.7 Å or less. On the other hand, in macromolecular crystal structures, the hydrogen bonding patterns in protein‐nucleic acid complexes between the nucleic acid base and the protein are all R2 2(9), whereas hydrogen bonding between Watson‐Crick‐like pairs of nucleic acid bases is R2 2(8). These two hydrogen bonding arrangements [R2 2(9) and R2 2(8)] are predetermined by the nature of the groups available for hydrogen bonding. The third motif identified, R1 2(6), involves hydrogen bonds that are less linear than in the other two motifs and is found in proteins.
Crystals of the neurotrophins
Authors: Robinson Robert C. , Stuart David I. , Yvonne Jones E. , Radziejewski Czeslaw
Published: July 2010

The neurotrophins show a high degree of amino acid sequence homology, share similar solution properties, and display distinct but parallel functionalities. Here we report the crystallization and preliminary X‐ray characterization of three neurotrophins: brain‐derived neurotrophin, neurotrophin 3, and the heterodimer between brain‐derived neurotrophin and neurotrophin 4. These findings are related to other published crystal parameters for neurotrophins, leading to the observation that, although crystal packing is highly variant, neurotrophins share common solubilities with respect to crystal growth.
N‐terminally tagged prion protein supports prion propagation in transgenic mice
Authors: Telling Glenn C. , Tremblay Patrick , Torchia Marilyn , Dearmond Stephen J. , Cohen Fred E. , Prusiner Stanley B.
Published: July 2010

The eight amino acid sequence, Asp‐Tyr‐Lys‐Asp‐Asp‐Asp‐Asp‐Lys, representing the FLAG peptide, was inserted after codons 22 or 88 of the mouse (Mo) prion protein (PrP) gene. Inclusion of the FLAG sequence at these locations interfered neither with the cellular processing of PrPc nor its conversion into PrPSc. Inclusion of the FLAG epitope at residue 22 but not at residue 88 facilitated immunodetection of tagged PrP by anti‐FLAG monoclonal antibodies (mAbs). Inoculation of transgenic (Tg) mice expressing N‐terminally tagged MoPrP with Mo prions resulted in abbreviated incubation times, indicating that the FLAG sequence was not deleterious to prion propagation. Immunopurification of FLAG‐tagged MoPrPc in the brains of Tg mice was achieved using the calcium‐dependent anti‐FLAG M1 mAb and non‐denaturing procedures. Although the function of PrPc remains unknown, our studies demonstrate that some modifications of PrPc do not inhibit the one biological activity that can be measured, i.e., conversion into PrPSc. Tagged PrP molecules may prove useful in the development of improved assays for prions as well as structural studies of the PrP isoforms.
Mutational analysis of human DNase I at the DNA binding interface: Implications for DNA recognition, catalysis, and metal ion dependence
Authors: Pan Clark Q. , Uumer Jana S. , Herzka Andrea , Lazarus Robert A.
Published: July 2010

Human deoxyribonuclease I (DNase I), an enzyme used to treat cystic fibrosis patients, has been systematically analyzed by site‐directed mutagenesis of residues at the DNA binding interface. Crystal structures of bovine DNase I complexed with two different oligonucleotides have implicated the participation of over 20 amino acids in catalysis or DNA recognition. These residues have been classified into four groups based on the characterization of over 80 human DNase I variants. Mutations at any of the four catalytic amino acids His 134, His 252, Glu 78, and Asp 212 drastically reduced the hydrolytic activity of DNase I. Replacing the three putative divalent metal ion‐coordinating residues Glu 39, Asp 168, or Asp 251 led to inactive variants. Amino acids Gin 9, Arg 41, Tyr 76, Arg 111, Asn 170, Tyr 175, and Tyr 211 were also critical for activity, presumably because of their close proximity to the active site, while more peripheral DNA interactions stemming from 13 other positions were of minimal significance. The relative importance of these 27 positions is consistent with evolutionary relationships among DNase I across different species, DNase I‐like proteins, and bacterial sphingomyelinases, suggesting a fingerprint for a family of DNase I‐like proteins. Furthermore, we found no evidence for a second active site that had been previously implicated in Mn2+‐dependent DNA degradation. Finally, we correlated our mutational analysis of human DNase I to that of bovine DNase I with respect to their specific activity and dependence on divalent metal ions.
Tetramer‐dimer equilibrium of oxyhemoglobin mutants determined from auto‐oxidation rates
Authors: Griffon Nathalie , Baudbin Véronique , Dieryck Wilfrid , Dumoulin Antoine , Pagnier Josée , Poyart Claude , Marden Michael C.
Published: July 2010

One of the main difficulties with blood substitutes based on hemoglobin (Hb) solutions is the auto‐oxidation of the hemes, a problem aggravated by the dimerization of Hb tetramers. We have employed a method to study the oxyHb tetramer‐dimer equilibrium based on the rate of auto‐oxidation as a function of protein concentration. The 16‐fold difference in dimer and tetramer auto‐oxidation rates (in 20 mM phosphate buffer at pH 7.0, 37°C) was exploited to determine the fraction dimer. The results show a transition of the auto‐oxidation rate from low to high protein concentrations, allowing the determination of the tetramer‐dimer dissociation coefficient K4,2 = [Dimer]2/[Tetramer]. A 14‐fold increase in K4,2 was observed for addition of 10 mM of the allosteric effector inositol hexaphosphate (IHP). Recombinant hemoglobins (rHb) were genetically engineered to obtain Hb with a lower oxygen affinity than native Hb (Hb A). The rHb α2β2 [(C7) F41Y/(G4) N102Y] shows a fivefold increase in K4,2 at pH 7.0, 37°C. An atmosphere of pure oxygen is necessary in this case to insure fully oxygenated Hb. When this condition is satisfied, this method provides an efficient technique to characterize both the tetramer‐dimer equilibrium and the auto‐oxidation rates of various oxyHb. For low oxygen affinity Hb equilibrated under air, the presence of deoxy subunits accelerates the auto‐oxidation. Although a full analysis is complicated, the auto‐oxidation studies for air equilibrated samples are more relevant to the development of a blood substitute based on Hb solutions. The double mutants, rHb α2β2 [(C7) F41Y/(G4) N102A] and rHb α2β2 [(C7) F41Y/(E10) K66T], show a lower oxygen affinity and a higher rate of oxidation than Hb A. Simulations of the auto‐oxidation rate versus Hb concentration indicate that very high protein concentrations are required to observe the tetramer auto‐oxidation rate. Because the dimers oxidize much more rapidly, even a small fraction dimer will influence the observed oxidation rate.
High throughput protein characterization by automated reverse‐phase chromatography/electrospray tandem mass spectrometry
Authors: Ducret Axel , Oostveen Inge Van , Eng Jimmy K. , Yates John R. , Aebersold Ruedi
Published: July 2010

We describe an integrated workstation for the automated, high‐throughput, and conclusive identification of proteins by reverse‐phase chromatography electrospray ionization tandem mass spectrometry. The instrumentation consists of a refrigerated autosampler, a submicrobore reverse‐phase liquid chromatograph, and an electrospray triple quadrupole mass spectrometer. For protein identification, enzymatic digests of either homogeneous polypeptides or simple protein mixtures were generated and loaded into the autosampler. Samples were sequentially injected every 32 min. Ions of eluting peptides were automatically selected by the mass spectrometer and subjected to collision‐induced dissociation. Following each run, the resulting tandem mass spectra were automatically analyzed by SEQUEST, a program that correlates uninterpreted peptide fragmentation patterns with amino acid sequences contained in databases. Protein identification was established by SEQUEST_SUMMARY a program that combines the SEQUEST scores of peptides originating from the same protein and ranks the cumulative results in a short summary.

The workstation's performance was demonstrated by the unattended identification of 90 proteins from the yeast Saccharomyces cerevisiae, which were separated by high‐resolution two‐dimensional PAGE. The system was found to be very robust and identification was reliably and conclusively established for proteins if quantities exceeding 1‐5 pmol were applied to the gel. The level of automation, the throughput, and the reliability of the results suggest that this system will be useful for the many projects that require the characterization of large numbers of proteins.
Context‐dependent protein stabilization by methionine‐to‐leucine substitution shown in T4 lysozyme
Authors: Lipscomb Leigh Ann , Gassner Nadine C. , Snow Sheila D. , Eldridge Aimee M. , Baase Walter A. , Drew Devin L. , Matthews Brain W.
Published: July 2010

The substitution of methionines with leucines within the interior of a protein is expected to increase stability both because of a more favorable solvent transfer term as well as the reduced entropic cost of holding a leucine side chain in a defined position. Together, these two terms are expected to contribute about 1.4 kcal/mol to protein stability for each Met → Leu substitution when fully buried. At the same time, this expected beneficial effect may be offset by steric factors due to differences in the shape of leucine and methionine. To investigate the interplay between these factors, all methionines in T4 lysozyme except at the amino‐terminus were individually replaced with leucine. Of these mutants, M106L and M120L have stabilities 0.5 kcal/mol higher than wild‐type T4 lysozyme, while M6L is significantly destabilized (‐2.8 kcal/mol). M102L, described previously, is also destabilized (‐0.9 kcal/mol). Based on this limited sample it appears that methionine‐to‐leucine substitutions can increase protein stability but only in a situation where the methionine side chain is fully or partially buried, yet allows the introduction of the leucine without concomitant steric interference. The variants, together with methionine‐to‐lysine substitutions at the same sites, follow the general pattern that substitutions at rigid, internal sites tend to be most destabilizing, whereas replacements at more solvent‐exposed sites are better tolerated.
Bipolar androgen therapy: The rationale for rapid cycling of supraphysiologic androgen/ablation in men with castration resistant prostate cancer
Authors: Denmeade Samuel R. , Isaacs John T.
Published: July 2010

Androgen ablation is highly effective palliative therapy for metastatic prostate cancer but eventually all men relapse. New findings demonstrating that androgen receptor (AR) expression continues in androgen ablated patients has resulted in the classification “Castration Resistant Prostate Cancer” (CRPC) and has led to the development of new second‐line “anti‐ligand” hormonal agents. In this background is the paradoxical observation that the growth of some AR‐expressing “androgen sensitive” human prostate cancer cells can be inhibited by supraphysiologic levels of androgens. This response may be due to effects of high‐dose androgen on inhibiting re‐licensing of DNA in cells expressing high levels of AR. It may also be due to recently described effects of androgen in inducing double strand DNA breaks. Based on available preclinical data described in this review demonstrating the effects of supraphysiologic levels of testosterone on inhibition of growth of CRPC xenografts, we initiated a clinical trial in men with CRPC testing the effect of monthly treatments with an intramuscular (IM) depot injection of testosterone. This IM formulation achieves supraphysiologic levels of testosterone that cannot be achieved with standard testosterone gel‐based applications. The supraphysiologic testosterone level is followed by a rapid drop to castrate levels of testosterone with each cycle of therapy. This “bipolar androgen therapy” will not allow time for prostate cancer cells to adapt their AR expression in response to environmental conditions. The goal is to determine if a clinical response can be achieved through this non‐adaptive rapid cycling approach in men with CRPC. Prostate 70: 1600–1607, 2010. © 2010 Wiley‐Liss, Inc.
Livin‐α promotes cell proliferation by regulating G1‐S cell cycle transition in prostate cancer
Authors: Ye Lin , Song Xishuang , Li Sheng , Yang Deyong , Zhang Jianing , Che Xiangyu , Chen Xiaochi , Wang Jianbo , Zhang Zhiwei
Published: July 2010

BACKGROUND

Prostate cancer is the third most common cancer and the second leading cause of cancer death for males in US. Livin has recently been described as a cancer‐associated member of inhibitor of apoptosis proteins family, highly expressed in prostate cancer. Livin gene encodes two splicing variants, termed Livin‐α and Livin‐β. We hypothesized that deregulation of proliferation could be due in part to Livin expression.

METHODS

Pathological analysis of Livin was performed in 20 prostate cancer tissues and 5 benign prostatic hyperplasia tissues. The expression of Livin isoforms was also investigated by Western blot in prostate cancer cell lines LNCaP and PC3. The role of Livin‐α in vitro was further studied. Using Livin‐α knockdown and overexpression models, cell cycle analysis, Ki‐67 immunocytostaining, and MTT assay were performed respectively.

RESULTS

Livin expression positive ratio was shown to be 5.4%, 23.6%, 52.4%, 73.4% in benign prostatic hyperplasia, low, medium, and high grade of prostate cancer respectively, and Livin was positively correlated with clinical pathological grades of prostate cancer. Livin‐α was expressed in both LNCaP and PC3; meanwhile; Livin‐β was only detected in the PC3. Livin‐α siRNA not only resulted in G1‐S cell cycle arrest, but also strongly correlated with the descended proliferation index and survival rate in LNCaP. In comparison, overexpression of Livin‐α resulted in an accelerated S phase entry combined with elevated proliferation index and survival in LNCaP.

CONCLUSIONS

Livin‐α may promote cell proliferation by regulating G1‐S cell cycle transition and possibly play an important part in initiation of prostate cancer. Prostate 71: 42–51, 2011. © 2010 Wiley‐Liss, Inc.
Liposomal imatinib–mitoxantrone combination: Formulation development and therapeutic evaluation in an animal model of prostate cancer
Authors: Pinto Ana Catarina , Moreira João Nuno , Simões Sérgio
Published: July 2010

BACKGROUND

Mitoxantrone plus prednisone is a palliative treatment for hormone‐refractory prostate cancer (HRPC) but without survival benefit. Imatinib has shown activity against HRPC but only in the preclinical setting. Our previous in vitro cytotoxicity screening study established that their free combination act additively to inhibit proliferation of PC‐3 cells. We aim to develop a liposomal imatinib–mitoxantrone (LIM) formulation with improved in vivo therapeutic activity.

METHODS

Imatinib and mitoxantrone were simultaneously co‐loaded into DSPC/Chol liposomes by means of a (NH4)2SO4‐generated proton gradient method. The optimized formulation was characterized in terms of mean size diameter, loading parameters and drug retention in human serum. In vivo antitumor activity of developed LIM formulation was evaluated in a nude mice bearing subcutaneous PC‐3 xenograft model.

RESULTS

LIM formulation exhibited maximal encapsulation efficiency (>95%) and enhanced drug retention for both drugs. Additionally, this LIM formulation, administered at a low mitoxantrone dose (0.5 mg/kg), showed a tumor inhibition activity (TGI = 66.7% and 4.0‐fold tumor volume increase) slightly superior to that of liposomal mitoxantrone (LM) at 2 mg/kg (TGI = 53.0% and 4.2‐fold volume increase). Therefore, therapeutic activity of mitoxantrone was significantly improved by co‐loading with imatinib since a four times lower dose was needed to achieve an equivalent growth inhibition effect.

CONCLUSIONS

The loading parameters and drug retention properties of our LIM formulation, combined with its in vivo antitumor activity, make this formulation an excellent strategy to improve the therapeutic index of mitoxantrone and a promising candidate for clinical development in prostate cancer therapy. Prostate 71: 81–90, 2011. © 2010 Wiley‐Liss, Inc.
Systematic investigation on the effect of contact resistance on the performance of a‐IGZO thin‐film transistors with various geometries of electrodes
Authors: Lee Jae Sang , Chang Seongpil , Bouzid Houcine , Koo Sang‐Mo , Lee Sang Yeol
Published: July 2010

We demonstrate the influence of the contact resistance on the electrical properties of a‐IGZO thin‐film transistors (TFTs) with ZrO2 gate insulator grown by rf‐magnetron sputtering at room temperature by adopting various channel widths and lengths. These TFTs have all been processed at room temperature with the same channel W/L ratio (W/L = 5) but different channel widths (50, 150, 250, and 350 µm). As the channel width increases from 50 to 350 µm, the on‐current and field effect mobility increase from 0.7 to 1 mA and 19 to 31 cm2/V s, respectively. However, the subthreshold swing decreases from 0.37 to 0.19 V/decade. These results show that the contact resistance strongly affects the device performances and should be considered in these applications.
Isotope correction of mass spectrometry profiles
Authors: Eibl Günther , Bernardo Katussevani , Koal Therese , Ramsay Steven L. , Weinberger Klaus M. , Graber Armin
Published: July 2010

Isotope correction of a profile is an important step in the analysis of mass spectrometry derived data. The problem is mathematically formulated as a system of linear equations which is general enough to include previous correction methods. For the solution of these equations when applied to the whole profile an efficient algorithm is developed. In experimental tests the resulting algorithm corrected the profile fast and successfully. Copyright © 2008 John Wiley & Sons, Ltd.
Bacterial stimulus perception and signal transduction: Response to osmotic stress
Authors: Krämer Reinhard
Published: July 2010

When exposed to osmotic stress from the environment, bacteria act to maintain cell turgor and hydration by responding both on the level of gene transcription and protein activity. Upon a sudden decrease in external osmolality, internal solutes are released by the action of membrane embedded mechanosensitive channels. In response to an osmotic upshift, the concentration of osmolytes in the cytoplasm is increased both by de novo synthesis and by active uptake. In order to coordinate these processes of osmoregulation, cells are equipped with systems and mechanisms of sensing physical stimuli correlated to changes in the external osmolality (osmosensing), with pathways to transduce these stimuli into useful signals which can be processed in the cell (signal transduction), and mechanisms of regulating proper responses in the cell to recover from the environmental stress and to maintain all necessary physiological functions (osmoregulation). These processes will be described by a number of representative examples, mainly of osmoreactive transport systems with a focus on available data of their molecular mechanism. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 10: 217–229; 2010: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.201000005
Comments and criticism. Point: Belief, understanding, and the teaching of evolution
Authors: Cobern William W.
Published: July 2010

Educators typically think that one teaches evolution to develop students' conceptual understanding of evolution. It is assumed that if students understand evolution they will believe it. From a constructivist perspective it can be argued that understanding and belief, though related, are distinct concepts and that each is a potential goal for instruction. Though there are good reasons why belief should not be an instructional goal, achieving conceptual understanding requires that issues of belief be addressed. The point is that students are not likely to gain much understanding of something that they dismiss outright as unbelievable. What counts as believable for an individual rests on that person's worldview. This article argues that instruction on evolution can profitably begin with a dialogue on what counts as believable based on a study of the cultural history of Darwinism. The purpose of this strategy is to create in the classroom a shared meaning that certain fundamental questions are worth discussing and that the biological principles of evolution can contribute to that discussion.
Chronic toxicity of chlordane to Daphnia magna and Ceriodaphnia dubia: A comparative study
Authors: Manar Rachid , Vasseur Paule , Bessi Hlima
Published: July 2010

Chronic toxicity of chlordane, an organochlorine insecticide, was assessed on Ceriodaphnia dubia under standardized conditions of testing. Results were compared to Daphnia magna to determine the sensitivity of the two freshwater cladoceran species to this persistent organic pollutant (POP) and to explore the possibility of using the 7‐day C. dubia test as an alternative to the 21‐day D. magna test in chronic toxicity assessment of POPs. The NOEC‐7d value of chlordane on reproduction of C. dubia (2.9 μg/L) was much higher than the NOEC‐21d value of D. magna (0.18 μg/L), attesting that the 7‐day test on C. dubia was less sensitive than the 21‐day reproduction test on D. magna to chlordane. However, extending the period of exposure of C. dubia to chlordane from 7 to 14 days led to a NOEC‐14d value similar to the NOEC‐21d value in D. magna (0.18 μg/L). This study highlights the usefulness of prolonging the exposure time of the reproduction test in C. dubia from 7 to 14 days to increase the performances of the reproduction test on C. dubia for assessing chronic toxicity of POPs. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
The negative inotropic effects of gaseous sulfur dioxide and its derivatives in the isolated perfused rat heart
Authors: Zhang Quanxi , Meng Ziqiang
Published: July 2010

Epidemiological investigations have revealed that sulfur dioxide (SO2) exposure is linked to cardiovascular diseases. The present study was designed to investigate the negative inotropic effects of gaseous SO2 and its derivatives in the isolated perfused rat heart and the possible mechanisms involved in their effects. The results showed that both SO2 and SO2 derivatives elicited a negative inotropic effect in a dose‐dependent manner, and SO2 produced a higher negative effect than SO2 derivatives. The mechanism of SO2‐induced negative inotropic effects at low concentrations was different from that at high concentrations. At low concentrations, the mechanism of SO2‐induced negative inotropic effects might occur through promoting the activities of protein kinase C (PKC), cycloxygenase, and cGMP, while the mechanism of SO2 derivatives‐induced effects might be related to the opening of ATP‐sensitive K+ (KATP) channel and the inhibition of Ca2+ influx via L‐type calcium‐channel. At high concentrations, the mechanisms of SO2 and SO2 derivatives‐induced negative inotropic effects were similar, which might be related to the KATP channel and L‐type calcium‐channel as well as the possible alterations in PKC, cycloxygenase, and cGMP. Further work is needed to determine the relative contribution of each pathway in SO2‐mediated inotropic effect. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
An Operator Theory for a Class of Linear Fractional Programming Problems II
Authors: Lata Manju
Published: July 2010

In a recent paper on the same topic, we studied the problem of modifying the optimal solution to a class of transportation problems with linear fractional objective function when basis preserving rim operators are applied to vary the rim conditions as a linear function of a single parameter. We continue this study in the present paper and study various transformations arising as a result of applying cost and bound operators. As before, we confine to basis preserving operators and develop algorithms for applying any of the cost operators and for finding the maximum limit for δ. A small numerical example is solved at the end to illustrate various results.
Non‐Newtonian Flow due to Noncoaxially Rotations of a Disk and a Fluid at Infinity
Authors: Erdoǧan M. E.
Published: July 2010

The flow produced by a rotating disk in a second‐order fluid which at infinity is itself in a rigid body rotation around another axis of rotation, parallel but not coincident with that of the disk is considered. It is shown that the equations of motion have an exact solution that may be obtained in general numerically. The expressions of the force and the torque exerted by the fluid on the disk are given. A special case in which rotations are with nearly the same angular velocities is discussed.
Genauigkeitsschranken bei gemischter Anwendung von Barriere‐ und Strafmethoden in der konvexen Optimierung
Authors: Grossmann Ch. , Kürcz A. , Schöniger G.
Published: July 2010

Aufbauend auf Genauigkeitsabschätzungen bei Barriere‐ und Strafmethoden werden untere und obere Schranken für den optimalen Zielfunktionswert auch für den Fall angegeben, daß eine gemischte Anwendung von Straf‐ und Barrierefunktionen erfolgt.
On the Laplace Formula and the Meniscus Height for a Capillary Surface
Authors: Finn R.
Published: July 2010

Upper and lower bounds are given for the center and meniscus heights of a symmetric equilibrium capillary surface. The bounds are sensibly identical at small Bond numbers B, and they provide significant information also for intermediate values of B.
Existenzsatz Für Potentialströmungen mit Totwassern um zwei geradlinige Hindernisse
Authors: Hilbig H.
Published: July 2010

Es werden ideale, inkompressible, wirbelfreie, ebene Strömungen um zwei geradlinige Hindernisse, hinter denen sich bis ins Unendliche erstreckende Totwassergebiete ausbilden, betrachtet. Zum Nachweis der Existenz derartiger Strömungen um Hindernisse mit vorgegebenen Längen und vorgegebenem vertikalen Abstand werden Fixpunktgleichungen aufgestellt. Ihre Lösbarkeit folgt mit Hilfe der Theorie des Abbildungsgrades, da in einem Symmetriefall eine Lösung angegeben werden kann.
Optimierung mit Hilfe des Intervall‐Newton‐Verfahrens
Authors: Oelschlägel D. , Süsse H.
Published: July 2010

Das bekannte Intervall‐Newton‐Verfahren wird so modifiziert, daß das Minimum einer streng konvexen Funktion über einem Intervall aus I(R) eingeschlossen wird. Dabei werden auch eingangsbedingte Fehler berücksichtigt. Mit Hilfe dieses Verfahrens wird ein Algorithmus angegeben, der die gleiche Optimierungsaufgabe löst, wobei die Zielfunktion nicht konvex zu sein braucht. Weiterhin wird mit dem angegebenen Verfahren das mehrdimensionale Problem der Minimierung einer streng konvexen Funktion über einem Quader gelöst.