bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing allosteric peptide ligands targeting a globular protein
Authors: Selz Karen A. , Samoylova Tatiana I. , Samoylov Alexandre M. , Vodyanoy Vitaly J. , Mandell Arnold J. 
Published: September 2006

AbstractPatented signal analytic algorithms applied to hydrophobically transformed, numerical amino acid sequences have previously been used to design short, protein‐targeted,LorDretro‐inverso peptides. These peptides have demonstrated allosteric and/or indirect agonist effects on a variety of G‐protein and tyrosine kinase coupled membrane receptors with 30% to over 80% hit rates. Here we extend these approaches to a globular protein target. We designed eight peptide ligands targeting an ELISA antibody responsive protein, β‐galactosidase, βGAL. Three of the eight 14mer peptides allosterically activated βGAL with ELISA methodology. Using Bayesian statistics, this 38% hit rate would have occurred 2 × 10−9by chance. These peptides demonstrated binding site competitive or noncompetitive interactions, suggesting allosteric site multiplicity with respect to their βGAL binding‐mediated ELISA signal. Kinetic studies demonstrated the temperature dependence of the βGAL peptide binding functions. Using the van't Hoff relation, we found evidence for enthalpy–entropy compensation. This relation is often found for hydrophobic interactions in aqueous media, and is consistent with the postulated hydrophobic series encoding underlying our protein‐targeted, peptide design methods. It appears that our algorithmic, hydrophobic autocovariance eigenvector template approach to the design of allosteric peptides targeting membrane receptors may also be applicable to the design of peptide ligands targeting nonmembrane involved globular proteins. © 2006 Wiley Periodicals, Inc. Biopolymers 85: 38–59, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Blood progenitor cell separation from clinical leukapheresis product by magnetic nanoparticle binding and magnetophoresis
Authors: Jing Ying , Moore Lee R. , Williams P. Stephen , Chalmers Jeffrey J. , Farag Sherif S. , Bolwell Brian , Zborowski Maciej 
Published: September 2006

AbstractPositive selection of CD34+ blood progenitor cells from circulation has been reported to improve patient recovery in applications of autologous transplantation. Current magnetic separation methods rely on cell capture and release on solid supports rather than sorting from flowing suspensions, which limits the range of therapeutic applications and the process scale up. We tested CD34+ cell immunomagnetic labeling and isolation from fresh leukocyte fraction of peripheral blood (leukapheresis) using the continuous quadrupole magnetic flow sorter (QMS), consisting of a flow channel (SHOT, Greenville, IN) and a quadrupole magnet with a maximum field intensity (Bo) of 1.42 T and a mean force field strength (Sm) of 1.45 × 108 TA/m2. Both the sample magnetophoretic mobility (m) and the inlet and outlet flow patterns highly affect the QMS performance. Seven commercial progenitor cell labeling reagent combinations were quantitatively evaluated by measuring magnetophoretic mobility of a high CD34 expression cell line, KG‐1a, using the cell tracking velocimeter (CTV). The CD34 Progenitor Cell Isolation Kit™ (Miltenyi Biotec, Bergisch Gladbach, Germany) showed the strongest labeling of KG‐1a cells and was selected for progenitor cell enrichment from 11 fresh and 11 cryopreserved clinical leukapheresis samples derived from different donors. The CD34+ cells were isolated with a purity of 60–96%, a recovery of 18–60%, an enrichment rate of 12–169, and a throughput of (1.7–9.3) × 104 cells/s. The results also showed a highly regular dependence of the QMS performance on the flow conditions that agreed with the theoretical predictions based on the CD34+ cell magnetophoretic mobility. Biotechnol. Bioeng. 2007;96:1139–1154. © 2006 Wiley Periodicals, Inc.
Systematic Regulation of the Enzymatic Activity of Phenylacetaldoxime Dehydratase by Exogenous Ligands
Authors: Kobayashi Katsuaki , Kubo Minoru , Yoshioka Shiro , Kitagawa Teizo , Kato Yasuo , Asano Yasuhisa , Aono Shigetoshi 
Published: September 2006

AbstractPhenylacetaldoxime dehydratase from Bacillus sp. OxB‐1 (OxdB) contains a heme that acts as the active site for the dehydration reaction of aldoxime. Ferrous heme is the active form, in which the heme is five coordinate with His282 as a proximal ligand. In this work, we evaluated the functional role of the proximal ligand for the catalytic properties of the enzyme by “the cavity mutant technique”. The H282G mutant of OxdB lost enzymatic activity, although the heme, which was five coordinate with a water molecule (or OH−) as an axial ligand, existed in the protein matrix. The enzymatic activity was rescued by imidazole or pyridine derivatives that acted as the exogenous proximal ligand. By changing the electron‐donation ability of the exogenous ligand with different substituents, the enzymatic activity could be regulated systematically. The stronger the electron‐donation ability of the exogenous ligand, the higher was the restored enzymatic activity. Interestingly, H282G OxdB with 2‐methyl imidazole showed a higher activity than the wild‐type enzyme. Kinetic analyses revealed that the proximal His regulated not only the affinity of substrate binding to the heme but also the elimination of the OH group from the substrate.
Evidence for a sliding‐resistance at the tip of the trypanosome flagellum
Authors: Woolley David , Gadelha Catarina , Gull Keith 
Published: September 2006

AbstractMotility in trypanosomes is achieved through the undulating behaviour of a single “9 + 2” flagellum; normally the flagellar waves begin at the flagellar tip and propagate towards the base. For flagella in general, however, propagation is from base‐to‐tip and it is believed that bend formation, and sustained regular oscillation, depend upon a localised resistance to inter‐doublet sliding ‐ which is normally conferred by structures at the flagellar base, typically the basal body. We therefore predicted that in trypanosomes there must be a resistive structure at the flagellar tip. Electron micrographs of Crithidia deanei, Herpetomonas megaseliae, Trypanosoma brucei and Leishmania major have confirmed that such attachments are present. Thus, it can be assumed that in trypanosomes microtubule sliding at the flagellar tip is resisted sufficiently to permit bend formation. Cell Motil. Cytoskeleton 2006. © 2006 Wiley‐Liss, Inc.
Dynein light chain family in Tetrahymena thermophila
Authors: Wilkes David E. , Rajagopalan Vidyalakshmi , Chan Clarence W. C. , Kniazeva Ekaterina , Wiedeman Alice E. , Asai David J. 
Published: September 2006

AbstractDyneins are large protein complexes that produce directed movement on microtubules. In situ, dyneins comprise combinations of heavy, intermediate, light‐intermediate, and light chains. The light chains regulate the locations and activities of dyneins but their functions are not completely understood. We have searched the recently sequenced Tetrahymena thermophila macronuclear genome to describe the entire family of dynein light chains expressed in this organism. We identified fourteen genes encoding putative dynein light chains and seven genes encoding light chain‐like proteins. RNA‐directed PCR revealed that all 21 genes were expressed. Quantitative real time reverse transcription PCR showed that many of these genes were upregulated after deciliation, indicating that these proteins are present in cilia. Using the nomenclature developed in Chlamydomonas, Tetrahymena expresses two isoforms each of LC2, LC4, LC7, and Tctex1, three isoforms of p28, and six LC8/LC8‐like isoforms. Tetrahymena also expresses two LC3‐like genes. No Tetrahymena orthologue was found for Chlamydomonas LC5 or LC6. This study provides a complete description of the different genes and isoforms of the dynein light chains that are expressed in Tetrahymena, a model organism in which the targeted manipulation of genes is straightforward. Cell Motil. Cytoskeleton 2006. © 2006 Wiley‐Liss, Inc.
L‐Amino acid load to enhance PET differentiation between tumor and inflammation: an in vitro study on 18F‐FET uptake
Authors: Laïque S. , Egrise D. , Monclus M. , Schmitz F. , Garcia C. , Lemaire C. , Luxen A. , Goldman S. 
Published: September 2006

AbstractLabeled amino acids (AA) are tumor tracers for use in nuclear medecine. O‐(2‐[18F]fluoroethyl)‐L‐tyrosine (FET) is transported by the L‐system, known to function as an exchanger. In vitro utilization of FET, after a preload or prior to an afterload of non radioactive L‐amino acids, was evaluated in order to measure the potential effects of AA content on the distinction between tumor and inflammatory lesions. Cellular uptake of FET was studied on rat osteosarcoma cells (ROS 17/2.8) and human leukocytes, initially loaded with nonradioactive L‐tyrosine or L‐methionine. FET efflux was evaluated from cells loaded with nonradioactive L‐phenylalanine after tracer uptake. ROS 17/2.8 showed a higher sensitivity to preload and afterload effects on cellular FET content as compared with the leukocytes. We conclude that preload with L‐tyrosine, prior to the administration of FET, may be a potential procedure to improve PET differentiation between tumor and inflammatory lesions. Copyright © 2006 John Wiley & Sons, Ltd.
Prostate‐specific antigen recurrence and mortality after conventional dose radiation therapy in select men with low‐risk prostate cancer
Authors: Petit Joshua H. , Chen Ming‐Hui , Loffredo Marian , Sussman Brenda , Renshaw Andrew A. , D'Amico Anthony V. 
Published: September 2006

AbstractBACKGROUND.Prostate‐specific antigen (PSA) recurrence, prostate cancer‐specific mortality (PCSM), and all‐cause mortality (ACM) were evaluated for men age >70 years receiving conventional dose external beam radiation therapy (RT).METHODS.Between January 1, 1989, and December 1, 2002, 358 men were treated with RT for localized prostate cancer at a Harvard Medical School Affiliate in Fall River, MA. Median age was 71.2 (range, 43.2–83.5) years and patients were followed for a median of 4.0 (range, 0.2–13.5) years.RESULTS.Univariable analysis demonstrated that increasing pretreatment PSA velocity was significantly associated with increasing pretreatment PSA (P < .0001), Gleason score (P = .0002), and shorter post‐RT PSA doubling time (P = .0007) but not with clinical T‐category (P = .09) or percent positive biopsies (P = .08). For the select cohort of men age >70 years with low‐risk disease and a pretreatment PSA velocity ≤1.0 ng/mL per year, all deaths observed to date have been from nonprostate cancer etiologies. Whereas PSA recurrence in this group reached 43.3% by 7 years, due to the advanced age of the cohort and less aggressive biology, competing causes of mortality predominated as the cause of death despite PSA failure.CONCLUSIONS.In men age >70 years with low‐risk prostate cancer and pretreatment PSA velocity ≤1.0 ng/mL/year, prostate cancer death was not observed despite a modest PSA recurrence rate. Cancer 2006. © 2006 American Cancer Society.
P2PGrid: integrating P2P networks into the Grid environment
Authors: Cao Jiannong , Liu Fred Bojin , Xu Cheng‐Zhong 
Published: September 2006

AbstractThe current Grid architecture suffers from high complexity, inefficiency in leveraging common PC capabilities, and the single point of failure problem originated from Grid's client–server mode of interaction. In this paper, we propose an approach to solve the problems by incorporating peer‐to‐peer (P2P) networks with the Grid environment. A two‐layer integration model is proposed, which consists of a Grid layer and an underlying P2P layer that can be accessed from but is not limited to the Grid layer. A prototype implementation of the model, called P2PGrid, has been developed and experimented with example applications built on the platform. The results show that the complexity for common PCs to participate in the Grid can be greatly reduced, the resource aggregation efficiency has been increased, and the single point of failure problem can be solved by using P2P mode of communication in the Grid environment. Copyright © 2006 John Wiley & Sons, Ltd.
Using parallelization and hardware concurrency to improve the performance of a genetic algorithm
Authors: Tirumalai Vijay , Ricks Kenneth G. , Woodbury Keith A. 
Published: September 2006

AbstractGenetic algorithms (GAs) are powerful tools for solving many problems requiring the search of a solution space having both local and global optima. The main drawback for GAs is the long execution time normally required for convergence to a solution. This paper discusses three different techniques that can be applied to GAs to improve overall execution time. A serial software implementation of a GA designed to solve a task scheduling problem is used as the basis for this research. The execution time of this implementation is then improved by exploiting the natural parallelism present in the algorithm using a multiprocessor. Additional performance improvements are provided by implementing the original serial software GA in dedicated reconfigurable hardware using a pipelined architecture. Finally, an advanced hardware implementation is presented in which both pipelining and duplicated hardware modules are used to provide additional concurrency leading to further performance improvements. Copyright © 2006 John Wiley & Sons, Ltd.
A distributed packed storage for large dense parallel in‐core calculations
Authors: Baboulin Marc , Giraud Luc , Gratton Serge , Langou Julien 
Published: September 2006

AbstractIn this paper we propose a distributed packed storage format that exploits the symmetry or the triangular structure of a dense matrix. This format stores only half of the matrix while maintaining most of the efficiency compared with a full storage for a wide range of operations. This work has been motivated by the fact that, in contrast to sequential linear algebra libraries (e.g. LAPACK), there is no routine or format that handles packed matrices in the currently available parallel distributed libraries. The proposed algorithms exclusively use the existing ScaLAPACK computational kernels, which proves the generality of the approach, provides easy portability of the code and provides efficient re‐use of existing software. The performance results obtained for the Cholesky factorization show that our packed format performs as good as or better than the ScaLAPACK full storage algorithm for a small number of processors. For a larger number of processors, the ScaLAPACK full storage routine performs slightly better until each processor runs out of memory. Copyright © 2006 John Wiley & Sons, Ltd.
Spectral and Photophysical Studies of Substituted Indigo Derivatives in Their Keto Forms
Authors: de Melo J. Sérgio Seixas , Rondão Raquel , Burrows Hugh D. , Melo Maria J. , Navaratnam Suppiah , Edge Ruth , Voss Gundula 
Published: September 2006

AbstractThe spectral and photophysical properties of indigo derivatives with di‐, tetra‐, and hexa‐substitution in their neutral (keto) form are investigated in solution. The study comprises absorption and emission spectra, together with quantitative measurements of quantum yields of fluorescence (ϕF) and singlet oxygen formation (ϕΔ) and fluorescence lifetimes. The energy difference between the HOMO and LUMO orbitals is dependent on the degree (number of groups) and relative position of substitution. The ϕF and ϕΔ values were found to be very low ≤10−3. Because of the absence of transient triplet–triplet signal, the intersystem crossing yields (ϕT) were estimated by assuming that all the triplet states formed give rise to singlet oxygen formation, that is, ϕΔ≈ϕT . It was then possible from ϕIC=1−ϕF−ϕT to estimate the S1∼∼→S0 internal conversion yields and thus, with the other data, to determine the rate constants for all decay processes. From these, several conclusions are drawn. Firstly, the radiationless rate constants, kNR , clearly dominate over the radiative rate constants, kF , (and processes). Secondly, the main deactivation channel for the compounds in their keto form is the radiationless S1∼∼→S0 internal conversion process. Finally, although the changes are relatively small, internal conversion yield seems to be independent of the overall pattern of substitution. A more detailed investigation of the decay profiles with collection at the blue and red emission of the fluorescence band of indigo and one di‐substituted indigo reveals the decays to be bi‐exponential and that at longer emission wavelengths these appear to be associated with both rise and decay times indicating that two excited species exist, which is consistent with a keto‐excited form giving rise (by fast proton transfer) to the enol‐form of indigo. Evidence is presented which supports the idea that intramolecular (and possibly some intermolecular) proton transfer can explain the high efficiency of internal conversion in indigo.
Solvent and Ligand Effects on the Structures of Iron Halide Cations in the Gas Phase
Authors: Gruene Philipp , Trage Claudia , Schröder Detlef , Schwarz Helmut 
Published: September 2006

AbstractThe effects of the oxidation state, the ligand, and the solvent on structures and energetics of cationic iron complexes are investigated by means of electrospray‐ionization mass spectrometry. Insights into the potential‐energy surfaces of FeX+, FeX2+, and XFe(OCH3)+ ions (X = F, Cl, Br, I) with a variable number of coordinated methanol molecules are obtained by means of collision experiments and complementary thermochemical considerations. It is shown that upon change of the halide ligand, the weakly solvated ions respond differentially to the increasing need for stabilization of the partial charge on the metal center. For example, whereas F2Fe(CH3OH)n+ ions tend to lose mainly HF for n = 1–3, the loss of HBr is not observed at all for Br2Fe(CH3OH)n+. Instead, the iron‐bromide cations undergo reductive loss of atomic bromine. Cl2Fe(CH3OH)n+ bears an intermediate position in that both reduction as well as elimination of HCl can occur. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Suzuki–Miyaura Cross‐Coupling and Ring‐Closing Metathesis: A Strategic Combination for the Synthesis of Cyclophane Derivatives
Authors: Kotha Sambasivarao , Mandal Kalyaneswar 
Published: September 2006

AbstractThe synthesis of cyclophane derivatives through a sequence involving Suzuki–Miyaura cross‐coupling between α,α′‐dibromo‐m‐xylene and arylboronic acid derivatives, alkenylation and ring‐closing metathesis has been achieved. One of the cyclophanes was obtained by tandem isomerization and metathesis. Significant magnetic anisotropic effects on the intra‐annular hydrogen atoms were observed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Cometabolic Degradation of MTBE Using Methane‐Propane‐ and Butane‐Utilizing Enrichment Cultures and Rhodococcus sp. BU3
Authors: Haase K. , Wendlandt K.‐D. , Gräber A. , Stottmeister U. 
Published: September 2006

AbstractThe fuel oxygenated methyl tert‐butyl ether (MTBE) is used worldwide to replace leaded organic compounds. Although MTBE is persistent in the environment, chiefly due to its low biodegradability, some microbial cultures are able to mineralize it. This paper reports on the cometabolic degradation of MTBE by methane‐, propane‐ and butane‐utilizing enrichment cultures and the pure Rhodococcus sp. BU3 culture isolated from natural habitats. Three methane‐, three propane‐ and four butane‐utilizing cultures, which degrade MTBE cometabolically, were enriched. In experiments with resting cells at 20 °C, enrichment cultures grown on methane degraded MTBE at a maximum rate of 1.0 mg MTBE/(g biomass · h). Propane‐ and butane‐utilizing enrichment cultures degraded MTBE and the intermediate tert‐butyl alcohol (TBA) cometabolically at temperatures of 20 °C at maximum rates of 7.2 mg MTBE/(g biomass · h) and 5.2 mg MTBE/(g biomass · h), respectively. Propane‐utilizing cultures were also able to degrade MTBE and TBA consecutively after growth on 1‐propanol. However, the MTBE degradation rate after growth on 1‐propanol was lower than on propane. The isolated pure culture BU3 specified as Rhodococcus sp. degraded MTBE at maximum rates of 5.4 mg MTBE/(g biomass · h) when grown on propane and 2.3 mg MTBE/(g biomass · h) when grown on 1‐propanol, respectively. In column systems with recirculation, it is shown that Rhodococcus sp. BU3 degraded 95 mg/L MTBE over a time period of 6 days. The degradation activity of the immobilized bacteria could be regenerated by the addition of growth substrates (propanol or propane). The results of these experiments provide a promising basis for their implementation in an enhanced natural attenuation approach.
Factors Controlling the Activity of Bacteriophage UZ1 against Enterobacter aerogenes Strain BE1 under Simulated Intestinal Conditions
Authors: Verthé K. , Possemiers S. , Vaneechoutte M. , Boon N. , Verstraete W. 
Published: September 2006

AbstractTo study specific bacteriophage‐bacteria interactions under intestinal conditions, a previously developed in vitro model system was used, combining a common pathogenic bacterium Enterobacter aerogenes BE1 and a for this bacterium specific bacteriophage, phage UZ1. As many environmental factors may influence the phage‐bacterium interaction, the model was used in this study to investigate the effect of inoculum size, presence of oxygen, and physiological hindrance. When monocultures of E. aerogenes BE1/gfp with increasing inoculum size were infected with phage UZ1, complete host lysis was observed up to an inoculum size of 7 log [CFU/mL]. However, at 8 log [CFU/mL], growth was observed and phage resistant E. aerogenes BE1/gfp cells were isolated. Under simulated intestinal conditions, infection with phage UZ1 resulted in a significant decrease, up to 3 log, of E. aerogenes BE1/gfp compared to the non‐phage treated control. However, no complete removal of the bacterial host could be achieved after 18 h. At high inoculum size, resistant bacteria were also isolated. However, growth curve analysis showed a reduced fitness of the phage UZ1‐resistant bacteria, limiting their intestinal proliferation. Another factor responsible for differences in the bacteriolytic efficiency was the presence of oxygen. Under anaerobic conditions, the latent period increased from 20 min to more then 3 h and the burst size decreased from 70 to less than 24, compared to aerobic conditions. In conclusion, the major factors responsible for different bacteriolytic efficacy were resistance to phage infection by mutation and limited oxygen availability. Although no complete removal of the pathogen was obtained under anaerobic conditions, the strong host specificity of the phage, the decrease in bacterial concentrations and the reduced fitness of phage‐resistant bacteria indicate the possibility for prophylactic use of the phage to reduce the risk of E. aerogenes BE1 infections.
Bacillus megaterium as a Host for Recombinant Protein Production
Authors: Hollmann R. , Malten M. , Biedendieck R. , Yang Y. , Wang W. , Jahn D. , Deckwer W.‐D. 
Published: September 2006

AbstractThe production of biocatalysts is usually carried out in a few well‐characterized microorganisms like E. coli or, in the case of pharmaceuticals, in animal cell culture. Although well known as an established system, protein production in E. coli is restricted by several intrinsic problems. Studies conducted here show that the Gram‐positive Bacillus megaterium offers many advantages over E. coli as a protein production system. B. megaterium was successfully used in the production of three recombinant proteins.