bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolites in safety testing: metabolite identification strategies in discovery and development
Authors: Nedderman Angus N. R. 
Published: July 2009

AbstractThe publication of the FDA MIST guidelines in 2008, together with the acknowledged importance of metabolism data for the progression of novel compounds through drug discovery and drug development, has resulted in a renewed focus on the metabolite identification strategies utilised throughout the pharmaceutical industry. With the plethora of existing and emerging technologies available to the metabolite identification scientist, it is argued that increased diligence should be applied to metabolism studies in the early stages of both drug discovery and drug development, in order to more routinely impact chemical design and to comply with the concepts of the MIST guidance without re‐positioning the definitive radiolabelled studies from there typical place in late development.Furthermore, these strategic elements should be augmented by a broad and thorough understanding of the impact of the derived metabolism data, most notably considerations of absolute abundance, structure and pharmacological activity, such that they can be put into proper context as part of a holistic safety strategy.The combination of these approaches should ensure a metabolite identification strategy that successfully applies the principles of the MIST guidance throughout the discovery/development continuum and thereby provides appropriate confidence in support of human safety. Copyright © 2009 John Wiley & Sons, Ltd.
Reproductive toxicity and pharmacokinetics of di‐n‐butyl phthalate (DBP) following dietary exposure of pregnant rats
Authors: Struve Melanie F. , Gaido Kevin W. , Hensley Janan B. , Lehmann Kim P. , Ross Susan M. , Sochaski Mark A. , Willson Gabrielle A. , Dorman David C. 
Published: July 2009

AbstractMost rodent developmental toxicity studies of dibutylphthalate (DBP) have relied on bolus gavage dosing. This study characterized the developmental toxicity of dietary DBP. Pregnant CD rats were given nominal doses of 0, 100, or 500 mg DBP/kg/day in diet (actual intake 0, 112, and 582 mg/kg/day) from gestational day (GD) 12 through the morning of GD 19. Rats were killed 4 or 24 hr thereafter. DBP dietary exposure resulted in significant dose‐dependent reductions in testicular mRNA concentration of scavenger receptor class B, member 1; steroidogenic acute regulatory protein; cytochrome P450, family 11, subfamily a, polypeptide 1; and cytochrome P450 family 17, subfamily a, polypeptide 1. These effects were most pronounced 4 hr after the end of exposure. Testicular testosterone was reduced 24 hr post‐exposure in both DBP dose groups and 4 hr after termination of the 500‐mg DBP/kg/day exposure. Maternal exposure to 500 mg DBP/kg/day induced a significant reduction in male offspring's anogenital distance indicating in utero disruption of androgen function. Leydig cell aggregates, increased cord diameters, and multinucleated gonocytes were present in DBP‐treated rats. Monobutyl phthalate, the developmentally toxic metabolite of DBP, and its glucuronide conjugate were found in maternal and fetal plasma, amniotic fluid, and maternal urine. Our results, when compared to previously conducted gavage studies, indicate that approximately equal doses of oral DBP exposure of pregnant rats, from diet or gavage, result in similar responses in male offspring.Birth Defects Res (Part B), 86:345–354, 2009. © 2009 Wiley‐Liss, Inc.
New luminol chemiluminescence reaction using diperiodatoargentate as oxidate for the determination of amikacin sulfate
Authors: Yang Chunyan , Zhang Zhujun , Wang Jinli 
Published: July 2009

AbstractA new chemiluminescence (CL) reaction between luminol and diperiodatoargentate {K2 [Ag (H2IO6) (OH) 2]} was observed in alkaline medium. The CL intensity could be greatly enhanced by amikacin sulfate. Therefore a new CL method for the determination of amikacin sulfate was built by combining with flow injection technology. A possible mechanism of the CL reaction was proposed via the investigation of the CL kinetic characteristics, the CL spectrum and the UV absorption spectra of some related substance. The concentration range of linear response was 5.1 × 10−8 to 5.1 × 10−6 mol L−1 with a detection limit of 1.9 × 10−8 mol L−1 (3σ). The proposed method had good reproducibility with a relative standard deviation of 2.8% (n = 7) for 5.1 × 10−7 mol L−1 of amikacin sulfate. It was successfully applied to determine amikacin sulfate in serum. Copyright © 2009 John Wiley & Sons, Ltd.
Factors influencing antibody stability at solid–liquid interfaces in a high shear environment
Authors: Biddlecombe James G. , Smith Graeme , Uddin Shahid , Mulot Sandrine , Spencer David , Gee Chris , Fish Brendan C. , Bracewell Daniel G. 
Published: July 2009

AbstractA rotating disk shear device was used to study the effect of interfacial shear on the structural integrity of human monoclonal antibodies of IgG4 isotype. Factors associated with the solution conditions (pH, ionic strength, surfactant concentration, temperature) and the interface (surface roughness) were studied for their effect on the rate of IgG4 monomer loss under high shear conditions. The structural integrity of the IgG4 was probed after exposure to interfacial shear effects by SDS‐PAGE, IEF, dynamic light scattering, and peptide mapping by LC‐MS. This analysis revealed that the main denaturation pathway of IgG4 exposed to these effects was the formation of large insoluble aggregates. Soluble aggregation, breakdown in primary structure, and chemical modifications were not detected. The dominant factors found to affect the rate of IgG4 monomer loss under interfacial shear conditions were found to be pH and the nanometer‐scale surface roughness associated with the solid‐liquid interface. Interestingly, temperature was not found to be a significant factor in the range tested (15–45°C). The addition of surfactant was found to have a significant stabilizing effect at concentrations up to 0.02% (w/v). Implications of these findings for the bioprocessing of this class of therapeutic protein are briefly discussed. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Determination of the lactate threshold and maximal blood lactate steady state intensity in aged rats
Authors: Cunha Rafael Rodrigues , de Carvalho Cunha Verusca Najara , Segundo Paulo Russo , Moreira Sérgio Rodrigues , Kokubun Eduardo , Campbell Carmen Sílvia Grubert , Jacó de Oliveira Ricardo , Simões Herbert Gustavo 
Published: July 2009

AbstractThe reliability of the lactate threshold (LT) determined in aged rats and its validity to identify an exercise intensity corresponding to the maximal blood lactate steady state (MLSS) were analyzed. Eighteen male aged Wistar rats (∼365 days) were submitted to two incremental swimming tests until exhaustion, consisting of an initial load corresponding to 1% of body mass (BM) and increments of 1% BM at each 3‐min with blood lactate ([lac]) measurements. The LT was determined by visual inspection (LTV) as well by applying a polynomial function on the [lac]/workload ratio (LTP) by considering the vertices of the curve. For the MLSS, twelve animals were submitted, on different days, to 3–4 exercise sessions of 30‐min with workload corresponding to 4, 5 or 6% BM. The MLSS was considered the highest exercise intensity at which the [lac] variation was not higher than 0.07 mM.min−1 during the last 20‐min. No differences were observed for the test‐retest results (4.9 ± 0.7 and 5.0 ± 0.8 %BM for LTv; and 6.0 ± 0.6 and 5.8 ± 0.6 %BM for LTp) that did not differ from the MLSS (5.4 ± 0.5 %BM). The LT identified for aged rats in swimming, both by visual inspection and polynomial function, was reliable and did not differ from the MLSS. Copyright © 2009 John Wiley & Sons, Ltd.
A multi‐access method for BPL based on orthogonal pulse division multiplexing, barker‐code‐based spectrum spreading and orthogonal frequency division multiplexing
Authors: Zhang Hong Xin , Lu Ying Hua , Nie Rong 
Published: July 2009

AbstractA highly efficient multi‐access scheme of broadband power line (BPL) communication, named as OFDM‐BPS‐OPDMA, is proposed based on the Orthogonal Pulse Division Multiplexing Access (OPDMA), Barker‐code‐based Spectrum Spreading (BSS) and Orthogonal Frequency Division Multiplexing (OFDM) method. The orthogonal pulses are generated by using the eigenvectors of Hermitian matrix. At the same time, a specific pulse will be allocated to every user of the communication system. The transmitting data are first modulated by OFDM. Then, it is processed with OPDMA and BSS. Finally, the data is sent to the power line channel. On the receiving side, the data is processed with BSS demodulation, OPDMA demodulation and OFDM demodulation, and the receiving data for each user is acquired. Because of the orthogonality between these pulses, the multi‐user interference could be eliminated; when BSS is used, the waveform restoration is enhanced. Meanwhile, with the help of OFDM, the multi‐path interference is mitigated. Particularly, all users can share the resources of time and spectrum without interfering with others, and get excellent reliability in the concerned scheme. When OFDM is used, the sub‐carriers may be allocated dynamically, and the legal radio frequency band could be shunned by sharing the common bandwidth with other communication systems. Copyright © 2009 John Wiley & Sons, Ltd.
Stress‐induced laboratory eating behavior in obese women with binge eating disorder
Authors: Laessle Reinhold G. , Schulz Simone 
Published: July 2009

AbstractObjective:To compare the microstructural eating behavior of obese patients with and without binge eating disorder (BED) after stress induction in laboratory.Method:Forty‐eight obese women were investigated. Seventeen were assigned to the group of BED. Group (BED vs. non‐BED) by condition (stress vs. no stress) interaction effect on feeding variables, measured by a universal eating monitor, was tested. Stress was induced by the trier social stress test (TSST) and chocolate pudding served as laboratory food.Results:From the nonstress to the stress condition, patients with BED, when compared with non‐BED had a greater increase in average eating rate (p < .01) and a corresponding greater increase in the frequency of spoonfuls (p < .02). The BED group also showed a different change in acceleration/deceleration from the nonstress to the stress condition compared to the non‐BED group (p < .04).Discussion:Obese individuals with BED appear to exhibit a different response to stress than obese non‐BED individuals and individuals with bulimia nervosa. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009
Bis(terdentate) Pyrazole/Pyridine Ligands: Synthesis, Crystal Structures and Magnetic Properties of Bridged Binuclear and Tetranuclear Copper(II) Complexes
Authors: Kumar Singh Akhilesh , van der Vlugt Jarl Ivar , Demeshko Serhiy , Dechert Sebastian , Meyer Franc 
Published: July 2009

AbstractA new binucleating bis(terdentate) ligand, 3,5‐[3‐bis(2‐pyridyl)pyrazole‐1‐ylmethyl]pyrazole (HL2), was synthesized. Reaction of the deprotonated ligand L2 with hydrated CuII salts gives (μ‐pyrazolato)(μ‐hydroxido)‐bridged binuclear and tetranuclear complexes [L2Cu2(μ‐OH)(ClO4)(MeCN)](ClO4) (2), [L2Cu2(dmf)2(μ3‐OH)]2(ClO4)4·4dmf (3·4dmf) and [L2L′Cu2](ClO4)2 [4; HL′ = 3‐(2‐pyridyl)pyrazole]. In these complexes, both μ‐OH and μ3‐OH bridges were observed. This contrasts the situation for a dicopper(II) complex of the related bis(terdentate) ligand 3,5‐bis[6(2,2′‐dipyridyl)]pyrazole (HL1), {L1Cu2(OMe)(MeOH)[κ1‐O‐(NO3)]}{[Cu2(NO3)2(μ‐OMe)2]}0.5·MeOH (1·MeOH), where the shorter and more rigid ligand side arms enforce a larger Cu···Cu separation and the formation of a MeO–HOMe moiety within the bimetallic pocket. Molecular structures of all complexes were elucidated by X‐ray crystallography. Variable‐temperature magnetic susceptibility measurements (295–2 K) for powdered samples of complexes 2–4 reveal strong antiferromagnetic coupling between two copper centres. The magnitude of the coupling is discussed in view of the structural features. During the preparation of complex 4, partial ligand hydrolysis was also observed, but this strongly depends on the reaction conditions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Role of Coordinated Water and Hydrogen‐Bonding Interactions in Stabilizing Monophenoxido‐Bridged Triangular CuIIMII­CuII Compounds (M = Cu, Co, Ni, or Fe) Derived from N,N′‐Ethylenebis(3‐meth­oxysalicylaldimine): Syntheses, Structures, and Magnetic Properties
Authors: Majumder Samit , Koner Rajesh , Lemoine Pascale , Nayak Malabika , Ghosh Meenakshi , Hazra Susanta , Lucas C. Robert , Mohanta Sasankasekhar 
Published: July 2009

AbstractThe syntheses, structures, and magnetic properties of the trinuclear triangular compounds [{CuIIL1}2CuII(H2O)2](ClO4)2·H2O (1) and [{CuIIL1}2MII(H2O)2](ClO4)2 {M = Ni (2), Co (3), Fe (4)} derived from N,N′‐ethylenebis(3‐methoxysalicylaldimine) (H2L1) are described. Compound 1 crystallizes in the monoclinic P21/n space group, while the crystal system for the isomorphous compounds 2–4 is monoclinic P21/c. In the cations of these compounds, two copper(II) ions occupy the salen type N2O2 cavity of two [L1]2– ligands, while one phenoxido and one methoxy oxygen atom of each of these two [CuIIL1] moieties coordinate to a central metal ion, which results in the formation of the trinuclear CuII2MII systems in which the two pairs of central···terminal metal ions are monophenoxido‐bridged. In addition, to the two phenoxido bridges, the central metal ion is coordinated to two methoxy and two water oxygen atoms. The coordinated water molecules are strongly hydrogen bonded to the phenoxido and methoxy oxygen atoms. The presence of the coordinated water molecules and the interaction of these water molecules with the phenoxido and methoxy oxygen atoms are proposed to be the governing factors for the stabilization of the rare example of the monophenoxido‐bridged CuII3 compound 1 and of the first examples of the monophenoxido‐bridged CuII2MII compounds 2–4. The three metal ions define an isosceles triangle. The phenoxido bridge angles in these compounds are significantly obtuse and vary between 121.10(12)° and 129.84(13)°. On the other hand, the trinuclear cores are highly twisted as evidenced from the range of the dihedral angles (58.5–143.7°) between the basal planes of the terminal and the central metal ions. The variable‐temperature (2–300 K) magnetic susceptibilities of compounds 1–4 have been measured. The magnetic data for 1 have been analyzed by using a model of two exchange integrals for the two pairs of adjacent metal ions, while one J value is considered for the other three complexes. The exchange integrals obtained are: CuII3 compound 1: J1 = –97.6 cm–1, J2 = –89.5 cm–1; CuII2NiII compound 2: J = –25.4 cm–1; CuII2CoII compound 3: J = –9.0 cm–1; CuII2FeII compound 4: J = –6.5 cm–1. These moderate to weak antiferromagnetic interactions in 1–4 are related to the twisting of the trinuclear cores. The relative order of the exchange integrals can been understood from the nature of the magnetic orbitals. The structural and magnetic results have been compared with previously reported related compounds.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Syntheses, Structures and Magnetic Properties of Heterobridged Dinuclear and Cubane‐Type Tetranuclear Complexes of Nickel(II) Derived from a Schiff Base Ligand
Authors: Hazra Susanta , Koner Rajesh , Lemoine Pascale , Sañudo E. Carolina , Mohanta Sasankasekhar 
Published: July 2009

AbstractSyntheses, structures and magnetic properties of a heterobridged μ‐phenoxido‐μ1,1‐NCO dinickel(II) compound [NiII2(HL)3(μ‐NCO)]·2H2O (1) and a heterobridged bis(μ3‐phenoxido)bis(μ3‐alkoxido)tetranickel(II) system, [NiII4(L)2(HL)2(SeCN)2(H2O)2]·C3H7NO·4H2O (2), containing a cubane‐type NiII4O4 core, derived from the tetradentate Schiff base compartmental ligand N‐(2‐hydroxyethyl)‐3‐methoxysalicylaldimine (H2L) were described. Compounds 1 and 2 crystallize in triclinic P$\bar {1}$ and monoclinic P21/c systems, respectively. Compound 2, in which the Ni4O4 cubane core is composed of two μ3‐phenoxido and two μ3‐alkoxido moieties, represents the sole example of this type. The variable‐temperature (2–300 K) magnetic susceptibilities and magnetizations of these two compounds were measured. The interaction between the metal centres in dinuclear compound 1 is weak ferromagnetic, resulting in an ST = 2 ground state at 2 K. The overall interaction observed in 2 is weak ferromagnetic, leading to an unusual ST = 3 ground state. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Scale‐up of Oldenlandia affinis suspension cultures in photobioreactors for cyclotide production
Authors: Seydel Peter , Walter Christian , Dörnenburg Heike 
Published: July 2009

AbstractCyclotides are a family of backbone‐cyclized cystine‐knot‐containing macrocyclic peptides from plants that possess extremely interesting biological activities. Suspension cultures of Oldenlandia affinis, a model plant containing cyclotides, were scaled‐up from shake flask to photobioreactor operation in order to produce these plant peptides under controlled conditions. Cell growth was highly dependent on inoculation culture; cell density as well as culture age had an effect on the growth rates and thus affected the kalata B1 productivity of the bioprocess.In a 25 l scale bioreactor the maximum doubling time was about 1.12 days compared to 2.24 days in shake flasks. The accumulation of kalata B1 of 0.09 mg g−1 DW and 0.07–0.10 mg g−1 DW respectively, however, was on a similar level during the corresponding stationary growth phases in both bioreactor and flask processes.An adjustment of cell culture growth via culture preparation and inoculum density to high cyclotide accumulation results in an estimated output during the most productive retardation phase of about 21 mg kalata B1 per day in the 25 l system. This makes the biotechnological cyclotide synthesis under GMP conditions a competitive production tool compared to field cultivation, chemical, and recombinant synthesis in drug discovery for structure analysis and bioactivity assays.
Photobioreactor for cultivation and real‐time, in‐situ measurement of O2 and CO2 exchange rates, growth dynamics, and of chlorophyll fluorescence emission of photoautotrophic microorganisms
Authors: Červený Jan , Šetlík Ivan , Trtílek Martin , Nedbal Ladislav 
Published: July 2009

AbstractA detailed knowledge about the dynamics of phytoplanktonic photosynthesis and respiration is crucial for the determination of primary productivity in open oceans as well as for biotechnological applications. The dynamics are best studied in photobioreactors that are able to simulate natural conditions in such, that light can be modulated not only diurnally but also mimicking effects of solar elevation angle from sunrise to sunset, variable cloudiness, light modulation in refractory sun flecks due to water waves, or light intermittence due to turbulent flow in dense suspensions. In addition, high performance photobioreactors ought to be able to monitor in real time photosynthetic and respiratory activities as well as culture growth. Here, we demonstrate performance of a newly designed bench‐top laboratory photobioreactor that meets these needs, with a study of green alga Scenedesmus quadricauda. The algal suspension was exposed to simulated daily variations of total photosynthetic active irradiance and spectral profile, with a larger proportion of red photons in the morning and evening hours. The instrument monitored automatically the culture growth by measuring the optical densities at 735 nm and 680 nm and by measuring steady state and maximal chlorophyll fluorescence emission yields. The photochemical yields were estimated from chlorophyll fluorescence data. These widely used but rather indirect yield estimates were confronted with direct measurements of oxygen evolution and consumption quantum yields. The CO2 fluxes in and out of the culture media as well as the dissolved CO2 in algal suspension were also recorded. The experiments demonstrated potential of the new photobioreactor to reveal minute modulations in gas exchange rates as well as to yield data for calculation of photon requirement of oxygen evolution in the suspension volume that is key technological parameter for planning of large scale photobioreactors as well as key optimization parameter for strain selection.
Damping analysis of primary and auxiliary control of HVDC systems
Authors: Yu Tao , Tong Jia‐peng , Chan Ka Wing 
Published: July 2009

AbstractIt is well documented that an inappropriate HVDC controller will cause dynamic instability in an AC/DC system. In order to have a better analysis on the mechanism of this phenomenon, this paper proposes a generic theoretical equation of electric damping coefficient of a HVDC link using the complex torque coefficient (CTC) method for quantitatively analysis of the damping characteristics of different types of HVDC control systems. Furthermore, a theoretical design methodology will also be established to improve the performances of the HVDC primary and auxiliary control systems with an application example. Copyright © 2009 John Wiley & Sons, Ltd.
Evaluation of clinical biomaterial surface effects on T lymphocyte activation
Authors: Rodriguez Analiz , Anderson James M. 
Published: July 2009

AbstractPrevious in vitro studies in our laboratory have shown that lymphocytes can influence macrophage adhesion and fusion on biomaterial surfaces. However, few studies have evaluated how material adherent macrophages can influence lymphocyte behavior, specifically T cells. In this study, we cultured human peripheral blood mononuclear cells from healthy donors on three synthetic nonbiodegradable biomedical polymers: elasthane 80A (PEU), silicone rubber (SR), or polyethylene terephthalate (PET) and tissue culture polystyrene (TCPS). Upregulation of T cell surface activation markers (CD69 and CD25), lymphocyte proliferation, and interleukin‐2 (IL‐2) and interferon‐γ (IFNγ) concentrations were evaluated by flow cytometry, carboxy‐fluorescein diacetate, succinimydyl ester (CFSE) incorporation, and multiplex cytokine immunoassay, respectively, to assess T cell activation. Following 3 and 7 days of culture, CD4+ helper T cells from cultures of any of the material groups did not express the activation markers CD69 and CD25 and lymphocyte proliferation was not present. IL‐2 and IFNγ levels were produced, but dependent on donor. These data indicate that T cells are not activated in response to clinically relevant synthetic biomaterials. The data also suggest that lymphocyte subsets exclusive of T cells are the source of the lymphokines, IL‐2 and IFN‐γ, in certain donors. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Response of rat osteoblasts to polycaprolactone/chitosan blend porous scaffolds
Authors: Wu Hua , Wan Ying , Dalai Siqin , Zhang Rui 
Published: July 2009

AbstractNovel porous polycaprolactone/chitosan blend scaffolds were fabricated via a particle‐leaching technique using hexafluoro‐2‐propanol as a shared solvent and salt particles as porogen. By selecting optimized processing conditions, numerous blend scaffolds were already built with well‐controlled porous structures and approximately similar pore parameters. The interactions between these scaffolds and the rat osteoblasts were further investigated by measuring the adhesion, proliferation, and morphologies of cells as well as the corresponding alkaline phosphatase activity during various culture periods in vitro. Data collected from different measurements reflected that by incorporating an appropriate amount of chitosan component, the resultant blend scaffolds could improve the adhesion and growth of osteoblasts and exert a significant impact on the osteoblastic phenotype. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010