bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric granulomatous arthritis: An international registry
Authors: Rosé Carlos D. , Wouters Carine H. , Meiorin Silvia , Doyle Trudy M. , Davey Michael P. , Rosenbaum James T. , Martin Tammy M.
Published: September 2006

Objective

Blau syndrome and its sporadic counterpart, early‐onset sarcoidosis, share an identical phenotype featuring the classic triad of arthritis, dermatitis, and uveitis and are associated with mutations of CARD15 in 50–90% of cases. We chose the term “pediatric granulomatous arthritis” to refer to both. An international registry was established in the spring of 2005 to define the phenotype spectrum and establish the mutation frequency and variants.

Methods

Histologically confirmed granuloma and arthritis were required for inclusion. Probands and relatives were genotyped for CARD15. Deidentified clinical information was collected.

Results

One year after the inception of the registry, 61 individuals from 22 pedigrees had been entered. Seven pedigrees with 19 individuals (8 affected, 11 unaffected) had clinical disease that was atypical, and none of the individuals in those pedigrees showed mutations. There were 9 classic simplex pediatric granulomatous arthritis pedigrees including 19 individuals (9 affected, 10 unaffected) and 6 classic multiplex pedigrees with 22 individuals (17 affected, 5 unaffected). Cutaneous presentation was the most common. Arthritis was polyarticular in 96% of patients. Isolated eye disease was never the presenting symptom, but significant/severe visual impairment was observed in 41% of patients. Eye disease was bilateral in 21 of 22 patients and was complicated by glaucoma in 6 of 22 patients and by cataracts in 50% of patients. Skin biopsy was the best diagnostic approach (because of accuracy and low invasiveness).

Conclusion

In this series, the first combining familial and sporadic pedigrees and, to our knowledge, the largest, we further defined the phenotype and showed that all affected classic (and no nonclassic) pedigrees carry a mutation and that there is no asymptomatic carriage. If these data are confirmed, mutation analysis rather than tissue sampling may prove to be the most efficient diagnostic procedure.
Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis
Authors: Dervieux Thierry , Greenstein Neal , Kremer Joel
Published: September 2006

Objective

To evaluate the contribution of metabolites (methotrexate [MTX] and folate polyglutamate [PG] levels) and pharmacogenetic biomarkers in the folate pathway to the effects of MTX in patients with rheumatoid arthritis not previously treated with this antifolate.

Methods

Forty‐eight MTX‐naive adult patients were enrolled in a prospective longitudinal study. MTX therapy was initiated at 7.5 mg/week and was increased every 4–6 weeks until a therapeutic response was achieved. Response was assessed using the Disease Activity Score in 28 joints (DAS28). Red blood cell (RBC) MTX and folate PG levels were measured with 9 common polymorphisms in the folate pathway. Statistical analyses consisted of generalized linear models and multivariate regressions.

Results

After 6 months of therapy, the median weekly MTX dosage was 17.5 mg and the median decrease in the DAS28 was 2.0. There was a large interpatient variability in RBC MTXPG levels (median 35 nmoles/liter [interquartile range 28–51] at month 6). Patients with a lesser decrease in the DAS28 (fewer improvements) had lower RBC MTXPG levels (P < 0.05) despite the higher MTX dose administered (P < 0.05). RBC folate PG levels decreased significantly during treatment, and a lesser decrease in RBC folate PGs was associated with a lesser decrease in the DAS28 (P < 0.05). Primary side effects were gastrointestinal and neurologic in nature. Risk genotypes associated with toxicity were in γ‐glutamyl hydrolase (−401CC), 5‐aminoimidazole‐4‐carboxamide ribonucleotide transformylase (347GG), methylenetetrahydrofolate reductase (1298AC/CC), methionine synthase (2756AA), and methionine synthase reductase (66GG).

Conclusion

RBC MTXPG levels are a useful means by which to monitor therapy. The genetic associations presented generate hypotheses, and confirmation in independent cohorts is warranted.
Variability in the efficacy of interferon‐α in Erdheim‐Chester disease by patient and site of involvement: Results in eight patients
Authors: Haroche Julien , Amoura Zahir , Trad Salim G. , Wechsler Bertrand , Cluzel Philippe , Grenier Philippe A. , Piette Jean‐Charles
Published: September 2006

Objective

Erdheim‐Chester disease (ECD) is a rare, non‐Langerhans form of histiocytosis of unknown origin, characterized by infiltration of tissues by spumous histiocytes. ECD features heterogeneous systemic manifestations, and the general prognosis remains poor despite various treatment options.

Methods

We treated 8 patients with multisystemic ECD with subcutaneous interferon‐α (IFNα) at a dosage of 3–9 × 106 units 3 times weekly, for a median duration of 23 months (range 1–46 months).

Results

Treatment was generally well tolerated, and side effects remained limited to fever following injections. Treatment was discontinued in 1 patient, because of severe depression. During treatment, some manifestations of ECD disappeared (i.e., xanthelasma, exophthalmos, papilledema, and intracranial hypertension). The efficacy of IFNα on cardiovascular ECD was variable, however. Treatment resulted in partial regression of “coated aorta” in some cases and clear failure in others; 2 patients died. The level of C‐reactive protein diminished sharply in 5 patients.

Conclusion

IFNα might be a valuable first‐line therapy for prolonged treatment of ECD. However, the efficacy of IFNα varies among patients and according to the sites of disease involvement, and symptoms may fail to respond to treatment, especially in patients with severe multisystemic forms of ECD with central nervous system and cardiovascular involvement.
An Environmentally Benign Process for the Hydrogenation of Ketones with Homogeneous Iron Catalysts
Authors: Enthaler Stephan , Hagemann Bernhard , Erre Giulia , Junge Kathrin , Beller Matthias
Published: September 2006

Iron complexes generated in situ catalyze homogeneously the transfer hydrogenation of aliphatic and aromatic ketones by utilizing 2‐propanol as a hydrogen donor in the presence of base. The influence of different reaction parameters on the catalytic activity is investigated in detail by applying a three‐component catalyst system composed of an iron salt, 2,2′:6′,2′′‐terpyridine, and PPh3. The scope and limitations of the described catalyst is shown in the reduction of 11 different ketones. In most cases, high conversion and excellent chemoselectivity are obtained. Mechanistic studies indicate a monohydride reaction pathway for the homogeneous iron catalyst.
Ring‐Closing Olefin Metathesis for the Synthesis of Benzene Derivatives
Authors: Yoshida Kazuhiro , Kawagoe Fumihiro , Iwadate Noriyuki , Takahashi Hidetoshi , Imamoto Tsuneo
Published: September 2006

Benzene derivatives were synthesized in excellent yield from 1,4,7‐trien‐3‐ols by tandem ruthenium‐catalyzed ring‐closing olefin metathesis (RCM)/dehydration. The method was extended to the tandem RCM/oxidation process to obtain phenol and aniline derivatives. This method displays many advantages over aromatic‐substitution‐based classical routes.
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

Patented 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

Positive 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

Phenylacetaldoxime 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.
Cover Picture: Dramatic Enhancement of Enone Epoxidation Rates in Nonionic Microemulsions (Chem. Eur. J. 29/2006)
Authors: Wielpütz Thomas , Sottmann Thomas , Strey Reinhard , Schmidt Friederike , Berkessel Albrecht
Published: September 2006

Microemulsions are used by A. Berkessel et al. on pp. 7565 ff. in epoxidation reactions to investigate how these would accelerate the reactions. The model epoxidation reactions involved α,β‐unsaturated enones and alkaline hydrogen peroxide in different nonionic microemulsions, both in the presence and absence of a phase‐transfer agent (PTA).
Evidence for a sliding‐resistance at the tip of the trypanosome flagellum
Authors: Woolley David , Gadelha Catarina , Gull Keith
Published: September 2006

Motility 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

Dyneins 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

Labeled 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

BACKGROUND.

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

The 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

Genetic 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

In 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

The 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

The 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

The 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

The 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

To 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

The 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.
Investigations of the Morphogenesis of Filamentous Microorganisms
Authors: Kelly S. , Grimm L. H. , Jonas R. , Hempel D. C. , Krull R.
Published: September 2006

Several biotechnological production processes are based on the cultivation of filamentous microorganisms like the fungus Aspergillus niger. The morphological development plays an important role for transport phenomena and the related productivity. The description of filamentous morphogenesis of A. niger as a model organism, given here, is structured in three morphological growth processes, a very fast conidial aggregation, followed by a second slower aggregation step promoted by germination and hyphal tip growth, and the growth of pellets as the last process.
Integrated Enzymatic Synthesis and Adsorption of Isomaltose in a Multiphase Fluidized Bed Reactor
Authors: Ergezinger M. , Bohnet M. , Berensmeier S. , Bucholz K.
Published: September 2006

Dextransucrase catalyzes the formation of dextran, but also of numerous oligosaccharides from sucrose and different acceptors, if appropriate conditions are chosen. A process on a technical scale with immobilized enzyme was established to produce isomaltose, a disaccharide of industrial interest. Isomaltose is also a reactant for dextransucrase and has to be quickly taken out of the reaction solution. This was realized by integrated adsorption of isomaltose on zeolites. In the case of biotransformation the reactor works with a fluidized bed of immobilized enzyme and the in situ separation is realized with a suspension flow of adsorbent. This process was investigated experimentally and theoretically. With a design model consisting of hydrodynamics, kinetics of enzymatic synthesis, and thermodynamics of adsorption, a comparison was made between experimental and calculated data.
Apparent Delay of Product Secretion by Product Adsorption in Aspergillus niger
Authors: Emmler M. , Jungebloud A. , Göcke Y. , Cordes C. , Horn H. , Hempel D. C.
Published: September 2006

Optimization and modeling of cultivation processes for the production of heterologous and homologous proteins requires a comprehensive characterization of product formation. Methods have been developed for the experimental investigation of mass transport, substrate turnover and product formation in biopellets of the fungus Aspergillus niger for the production of glucoamylase (GAM). GAM production in A. niger was chosen as a model system, its advantage being its potential for complex, posttranslational protein modifications.
Travelling‐wave multipath simulation of two‐conductor HF signalling over indoor power‐line networks and RMS‐delay‐spread dependence
Authors: Papaleonidopoulos Ioannis C. , Karagiannopoulos Constantinos G. , Theodorou Nickolas J.
Published: September 2006

An efficient, travelling‐wave based multipath‐simulation technique is presented, suitable for the estimation of Power‐Line Communication channels' response in terms of both transfer function and power delay profile. The cable transmission parameters are thereupon requisite, as well as the vicinal network topology. The algorithm applies directly to narrowband single‐phase HF signalling over cabling compliant with the two‐conductor transmission‐line model. Experimental verification throughout the 1.6–30 MHz band on the basis of the quantitative path‐incorporation criterion proposed, reveals resultant amplitude‐response accuracy of no less than 5 dB. Dependency of the RMS delay spread on the multitude of network's impedance‐mismatch points, the overall network length, as well as the carrier frequency, is in addition investigated. Quite clear functional interrelations ensue thereupon, whereat proper analytical descriptions are proposed. Applicability of the multipath approach introduced is indicated for narrowband and wideband channel capacity estimations, and relevant hints towards the treatment of multiconductor line structures are suggested. Copyright © 2006 AEIT
Performance of FFH/BFSK AGC receiver over a Nakagami‐fading channel with partial‐band jamming
Authors: Zhu Li‐ping , Yao Yan , Zhu Yi‐Sheng , Dong Shi‐Wei
Published: September 2006

The bit error rate (BER) performance of a noncoherent fast frequency‐hopped binary orthogonal frequency‐shift‐keying (FFH/BFSK) spread spectrum (SS) receiver with adaptive gain control (AGC) is investigated in the presence of partial‐band jamming (PBJ) and additive white Gaussian noise (AWGN) over frequency nonselective slow Nakagami‐fading channels. Exact BER expressions in a onefold integral is derived. The effects of arbitrarily values of fading parameter and diversity level on system performance are considered. Numerical results compare the worst‐case BER performance of the AGC receiver with that of the product combining (PC) receiver. Copyright © 2006 AEIT
Discounting in economic evaluations: stepping forward towards optimal decision rules
Authors: Gravelle Hugh , Brouwer Werner , Niessen Louis , Postma Maarten , Rutten Frans
Published: September 2006

The National Institute for Clinical Excellence has recently changed its guidelines on discounting costs and effects in economic evaluations. In common with most other regulatory bodies it now requires that health effects should be discounted at the same rate as costs. We show that the guideline leads to sub‐optimal decisions because it fails to account for the changing value of health. NICE (and other regulatory bodies) should either use differential discounting or stipulate how the changing value of health should otherwise be dealt with. We also show how binding health service budget constraints should be incorporated in evaluations. Copyright © 2006 John Wiley & Sons, Ltd.
A comparison of patient and population values for health states in varicose veins patients
Authors: Ratcliffe Julie , Brazier John , Palfreyman Simon , Michaels Jonathan
Published: September 2006

Cost utility analyses typically incorporate preferences based upon the mean values for health states generated from a sample of the general population. The main argument for using general population values rests upon the premise that in a publicly funded health care system the main objective of the health care system is a societal one, namely to maximise health subject to equity concerns. Alternatively, it can be argued that patients themselves should be asked to value their own health state given that they have first hand experience of the state being valued. This paper investigates the relationship between patient and general population values within the context of a randomised controlled trial to compare alternative treatments for varicose veins. It was found that patients' own health valuations tended to be higher than those of the general population sample. The results from this study have important implications for economic evaluation. The incremental QALY gain for patients receiving treatment for moderate varicose veins would be almost halved if patients' own values were used to estimate QALYs in contrast to the general population values. The results also suggest that the variant of elicitation technique may be more important than the source of those values in revealing discrepancies. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of octanol:water partition coefficients of organophosphorus compounds on biodistribution and percutaneous toxicity
Authors: Czerwinski Steven E. , Skvorak John P. , Maxwell Donald M. , Lenz David E. , Baskin Steven I.
Published: September 2006

Knowledge of partition coefficient (log P) data can play a critical role in understanding the pharmacokinetic and pharmacodistributive properties of toxic organophosphorus (OP) compounds. Using a recently published gas chromatographic method, the octanol:water log P values for the compounds tabun (GA), sarin (GB), cyclosarin (GF), and O‐ethyl‐S‐(2‐diisopropylaminoethyl) methylphosphonothiolate (VX) were determined to be 0.384 ± 0.033, 0.299 ± 0.016, 1.038 ± 0.055, and 0.675 ± 0.070, respectively. Based on these data, the log P value of the fluorophosphonate fragment, common to GB, soman (GD), and GF, was determined to be −2.256 ± 0.273. The predictive value for absorption and distribution of the determined log P values was compared to measured values. The time to onset of local fasciculations (47.3, 29.0, 8.8, 8.5, and 6.3 min, respectively) in guinea pigs exposed percutaneously to equilethal doses of GA, VX, GF, GB, or GD was used as an indicator of dermal penetration. There was a good correlation (r = 0.95) between the measured log P value and the rate of onset of local fasciculations. Assuming a direct correspondence, equilibrium tissue:blood log P may be estimated from octanol:water log P. Comparison of the estimated and directly measured tissue:blood log P revealed a correlation of 0.8 for GD in liver, muscle, and adipose tissue. Our results demonstrate the use of log P data to both predict absorption and determine the distribution of OP compounds in tissues. This facilitates further estimates of in vivo OP effects from in vitro experiments. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:241–246, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20140
Influence of ethanol on methanol‐induced oxidative stress and neurobehavioral deficits
Authors: Sandhir Rajat , Kaur Kamaljit
Published: September 2006

The present study examines the efficacy of ethanol as an antidote in methanol neurotoxicity in terms of its effect on antioxidant defense system and behavior. It was observed that acute methanol exposure (7.5 g/kg body weight) led to an increase in lipid peroxidation in various regions of brain. Ethanol administration (7.5 g/kg body weight), on the other hand, was found to accentuate methanol‐induced lipid peroxidation. Glutathione levels in brain were significantly reduced in methanol‐exposed animals. However, in the coexposed animals, the levels of glutathione were comparable to those observed in controls. The activities of superoxide dismutase and catalase were decreased in the brain following methanol exposure, whereas in methanol‐ and ethanol‐coexposed animals there was no significant effect on these enzymes as compared to methanol‐exposed animals. The activity of acetylcholinesterase was significantly reduced in the methanol‐exposed animals. On the other hand, acetylcholinesterase activity was not affected in the coexposed animals in comparison to methanol‐treated group. Neurobehavioral studies revealed impaired motor and cognitive functions following methanol exposure. In contrast, ethanol exposure ameliorated the behavioral deficits induced by methanol. The findings from the present study suggest the beneficial effect of ethanol on neurobehavioral deficits induced by methanol along with intensification of methanol‐induced oxidative stress. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:247–254, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20141
Low‐carbohydrate diet and oxidative stress in diabetic and nondiabetic rats
Authors: Kamuren Zipporah T. , Sanders Ruth , Watkins John B.
Published: September 2006

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low‐carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low‐carbohydrate diet for 30 days. Elevated glucose, HbA1c, and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low‐carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low‐carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low‐carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and γ‐glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet‐treated diabetic rats. Overall, the low‐carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:259–269, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20142
Influence of copper on the interaction between cytochrome c and sulfite in vitro
Authors: Wang Jinsheng , Guo Dongsheng , Yuan Xiaoying
Published: September 2006

The quantitative influence of copper on the interaction between cytochrome c and sulfite, which is a derivate of sulfur dioxide in the human body, has been studied by fluorescence spectrometry and ultraviolet absorption spectrometry in vitro. The results indicate that copper may intensely combine with protein component and ferroporphyrin component in cytochrome c at the concentration of 0.1 mM, and the respective association constants (KA) are 3.77 × 104 L mol−1 and 9.38 × 103 L mol−1. Sulfite has little interaction with the protein component in cytochrome c (KA = 0.094 L mol−1), at either low concentrations or relatively high concentrations (<0.15 M). However, it can react with the ferroporphyrin component in cytochrome c (KA = 4.297 L mol−1). After copper is added to the sulfite–cytochrome c binary systems, the reaction between sulfite and the protein component in cytochrome c is obviously strengthened at a low concentration (KA = 7.289 L mol−1), while the addition of copper merely has a little effect on the interaction between sulfite and the ferroporphyrin component in cytochrome c. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:255–258, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20143
Characterization of esterase activity in Geobacillus sp. HBB‐4
Authors: Metin Kubilay , Burcu Bakir Ateslier Z. , Basbulbul Gamze , Halil Biyik H.
Published: September 2006

A thermophilic esterase producing bacterium (Bacillus sp. 4), recently isolated from Alangüllü thermal spring in Aydın (Turkey), was analyzed using 16S rRNA and classified as Geobacillus sp. HBB‐4, most closely related to Bacillus sp. BGSC W9A59 (0.70% sequence divergence) which belongs to the newly described genus Geobacillus. The effects of several chemicals on the activity of thermostable esterase from Geobacillus sp. HBB‐4 were examined. Among the various metal ions tested, esterase activity was enhanced by Mn+2 and Ni+2, but was inhibited by Hg+2 and Cu+2, whereas Ca+2, Mg+2 and Co+2 had no effect. In addition, other metal ions studied have caused a slight inhibition on the esterase activity. EDTA partially inhibited the HBB‐4 esterase. The activator metal ions, Mn+2 and Ni+2 have restored partial inhibition of EDTA. The activity of HBB‐4 esterase was inhibited by ionic detergents while non‐ionic detergents activated the enzyme. However, a zwitterionic detergent, CHAPS, has caused a slight inhibition in the enzyme activity. HBB‐4 esterase activity was inhibited at the high concentrations of all the organic solvents tested in the present study. However, 50% final concentration of DMSO increased the enzyme activity about 7%. The HBB‐4 esterase has shown more than about 50% of activity in the presence of ethanol and methanol solutions. These characteristics of the enzyme along with its significant thermostability make the Geobacillus sp. HBB‐4 esterase a potent candidate for future industrial applications. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)