bluuebunny/crossref_metadata_2025 huggingface dataset:
Biotransformation of glycerol into 1,3‐propanediol
Authors: Willke Thomas , Vorlop Klaus
Published: August 2008

Today, glycerol is mainly a by‐product of fat splitting and biodiesel production. Further growth of the biodiesel market would result in a fall in the price of glycerol. Particularly glycerol‐water from rapeseed oil methyl ester production, for example, would be an interesting raw material if it could be utilised in fermentation without further pretreatment. Under anaerobic conditions, bacteria can transform glycerol into 1,3‐propanediol (PDO), which can be used as a monomer in the chemical industry. PDO can be produced biotechnologically from glycerol with the aid of bacteria. Another way would be the utilization of glucose instead of glycerol, which would provide independence from the fluctuating glycerol market. However, under certain conditions, the classic technique based on glycerol can be quite interesting with regard to technical and economic aspects: A concerted, extensive search for new microorganisms (screening) and improved process design (fed‐batch with pH‐controlled substrate dosage) allowed the product concentrations, which were relatively low at a maximum of 70–80 g/L as a result of product inhibition, to be raised to more than 100 g/L. An additional advantage of the new technique and the newly isolated strains is the utilisation of low‐priced crude glycerol or glycerol‐water. This is a factor which should not be underestimated and has a direct effect on the product costs. Further on, the use of immobilised cells compared to freely suspended cells enables an increase of productivity from about 2 up to 30 g /Lh.
1‐Oxoniaadamantane
Authors: Etzkorn Markus , Aniszfeld Robert , Li Tiejun , Buchholz Herwig , Rasul Golam , Prakash G. K. Surya , Olah George A.
Published: August 2008

The missing member of the heteroadamantane series, 1‐oxoniaadamantane (4a), was prepared by the ionization of suitable bicyclic precursors under strongly acidic conditions. The ion 4a was characterized by 1H and 13C NMR spectroscopy. The X‐ray crystal structure of ion 4a was also obtained with a CB11H6Cl6 counter anion. DFT calculations were performed on 1‐elementaadamantane cations for comparison. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Electrocatalytic Oxidation and Voltammetric Determination of Nitrite on Hydrophobic Ionic Liquid‐Carbon Nanotube Gel‐Chitosan Composite Modified Electrodes
Authors: Xiao Fei , Liu Liqin , Li Jun , Zeng Junjie , Zeng Baizhao
Published: August 2008

A novel room temperature ionic liquid (i.e., 1‐octyl‐3‐methylimidazolium hexafluorophosphate, OMIMPF6)‐multiwall carbon nanotube (MWNT) gel‐chitosan (Chi) composite modified glassy carbon electrode (GCE) was fabricated and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), infrared spectroscopy (IR), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). The OMIMPF6‐MWNT gel‐Chi composite showed good conductivity, stability, and extraction effect due to the synergic action of OMIMPF6, MWNT, and Chi. Furthermore, it was found that the OMIMPF6‐MWNT gel‐Chi composite had strong electrocatalytic effect on the oxidation of nitrite and at the OMIMPF6‐MWNT gel‐Chi/GCE nitrite could produce a very sensitive anodic peak. Under optimized conditions, the peak current was linear to nitrite concentration from 2.0×10−8 to 6.0×10−5 M. The detection limit was 1.0×10−8 M. The electrode also exhibited acceptable stability, repeatability and selectivity. It was used successfully for the determination of nitrite in soil, sewage and sausage samples.
A Selective and Sensitive Method for Simultaneous Determination of Traces of Paracetamol and p‐Aminophenol in Pharmaceuticals Using Carbon Ionic Liquid Electrode
Authors: Safavi Afsaneh , Maleki Norouz , Moradlou Omran
Published: August 2008

A reliable and simple electrochemical method has been proposed for the simultaneous determination of paracetamol (PAR) and p‐aminophenol (PAP) in pharmaceutical formulations. The oxidation and reduction peak potentials in cyclic voltammetry (CV) for PAR on carbon ionic liquid electrode (CILE) were occurred at 370 and 225 mV vs. Ag/AgCl, respectively at pH 7.0, while those for PAP on CILE appeared at 128 mV and 68 mV, respectively at the scan rate of 0.05 V s−1. In comparison to the conventional carbon paste electrode, the apparent reversibility and kinetics of the electrochemical reactions of PAR and PAP were significantly improved on CILE. In differential pulse voltammetric technique, the peak potentials for PAR and PAP appeared at 345 and 130 mV, respectively, with the peak separation of 215 mV, sufficient for their simultaneous determination in samples containing these two species. The proposed method was used for simultaneous determination of PAR and PAP in tablets. PAR and PAP can be determined in the ranges of 2.0×10−6–2.2×10−3 M and 3.0×10−7–1.0×10−3 M, with the detection limits of 5.0×10−7 and 1.0×10−7 M (calculated by 3σ), respectively. The relative standard deviations for the determination of PAR and PAP were less than 2%.
Iridium Oxide Film Electrodes for Anodic Stripping Voltammetry
Authors: Hull Ewa , Piech Robert , Kubiak Władysław W.
Published: August 2008

The new iridium oxide film electrode, applied for the determination of lead(II), cadmium(II) and copper(II) traces using differential pulse anodic stripping voltammetry (DP ASV) is presented. The electrode display an interesting stripping voltammetric performance which compares with electrodes commonly used in voltammetry. The deposited film is known as anodically electrodeposited iridium oxide film (AEIROF). The AEIROF electrode is characterized by long‐term stability (more than 40 days) and very good reproducibility of the analytical signals in this time (≤12% for 0.5 μM of lead). The regeneration of iridium film is very simple in a time shorter than 60 seconds. The effects of various factors such as: thickness of AEIROF film, preconcentration potential and time, supporting electrolyte composition, potential interferences are optimized. The detection limit for AEIROF film electrode based on glassy carbon for an accumulation time of 30 s is as low as 7 nM for lead(II). The repeatability of the method at a concentration level of the lead(II) as low as 0.5 μM, expressed as RSD is 2.5% (n=10). The proposed method was successfully applied and validated by studying certified reference material CTA‐OTL‐1. Such an attractive use of ‘mercury–free’ ‐ environmentally friendly electrodes offers great promise to measure trace metals.
A Mediator‐Free Bienzyme Amperometric Biosensor Based on Horseradish Peroxidase and Glucose Oxidase Immobilized on Carbon Nanotube Modified Electrode
Authors: Yao Yan‐Li , Shiu Kwok‐Keung
Published: August 2008

Multiwalled carbon nanotube (CNT) modified glassy carbon electrode immobilized with horseradish peroxidase (HRP) in Nafion coating showed direct electron transfer between HRP enzyme and the CNT‐modified electrode. A mediator‐free bienzyme glucose biosensor based on horseradish peroxidase and glucose oxidase was constructed. The bienzyme biosensor exhibited a high sensitivity for glucose detection at zero applied potential.
Improved Voltammetric Response of L‐Tyrosine on Multiwalled Carbon Nanotubes‐Ionic Liquid Composite Coated Glassy Electrodes in the Presence of Cupric Ion
Authors: Liu Liqin , Zhao Faqiong , Xiao Fei , Zeng Baizhao
Published: August 2008

L‐Tyrosine can exhibit a small anodic peak on multiwalled carbon nanotubes (MWCNTs) coated glassy carbon electrodes (GCE). At pH 5.5 its peak potential is 0.70 V (vs. SCE). When an ionic liquid (i.e., 1‐octyl‐3‐methylimidazolium hexafluorophosphate, [omim][PF6]) is introduced on the MWCNT coat, the peak becomes bigger. Furthermore, in the presence of Cu2+ ion the anodic peak of L‐tyrosine increases further due to the formation of Cu2+‐L‐tyrosine complex, while the peak potential keeps unchanged. Therefore, a sensitive voltammetry based on the oxidation of Cu2+‐L‐tyrosine complex on MWCNTs‐[omim][PF6] composite coated electrode is developed for L‐tyrosine. Under the optimized conditions, the anodic peak current is linear to L‐tyrosine concentration in the range of 1×10−8–5×10−6 M, and the detection limit is 8×10−9 M. The modified electrode shows good reproducibility and stability. In addition, the voltammetric behavior of other amino acids is explored. It is found that among them tryptophan (Trp) and histidine (His) can also produce sensitive anodic peak under same experimental conditions, and their detection limits are 4×10−9 M and 4×10−6 M, respectively.
Damage detection of a steel–concrete composite frame by a multilevel approach: Experimental measurements and modal identification
Authors: Chellini Giuseppe , De Roeck Guido , Nardini Luca , Salvatore Walter
Published: August 2008

Structural Health Monitoring (SHM) and Experimental Modal Analysis (EMA) have revealed to be really efficient tools for the damage detection of structures and structural elements in many engineering fields (Shock Vib. Dig. 1998; 30(2):91–105; Philos. Trans. R. Soc. A 2007; 365(1851):303–315; Mech. Syst. Signal Process. 2003; 17(1):133–142; Philos. Trans. R. Soc.: Math. Phys. Eng. Sci. 2001; 359(1778): 131–149; Struct. Control Health Monit. 2006; 14:1083–1100; Mech. Syst. Signal Process. 2004; 17(1): 83–89). Unfortunately the great variety of morphologies, construction materials and structural schemes makes these techniques not easily applicable to buildings, due to inherent problems related to the location and the extent of damage, the sensitivity of the dynamic response to damage, the choice of damage indexes to be used, the sensors' location, etc.

On the other hand, the modern seismic capacity design of buildings in earthquake‐prone areas tends to locate dissipative zones in well‐determined portions of structures (CEN, European Committee for Standardization, EN 1998‐1. Eurocode 8: Design of Structures for Earthquake Resistance. Part 1: General Rules, Seismic Actions and Rules for Buildings, European Community, Brussels, Belgium, 2005); thus, the application of vibration‐based damage detection techniques to earthquake‐resistant structures seems to be very promising even if nowadays there are only few studies on these arguments.

The present paper reports the experiences of a vibration‐based damage identification study applied to a steel–concrete composite frame structure, suitably designed to be high ductile according to Eurocode 8 and localizing the seismic energy dissipation in the beam‐to‐column joints. The structure was subjected to series of pseudo‐dynamic (PsD) and cyclic tests with increasing peak ground acceleration at the European Laboratory for Structural Assessment of Joint Research Centre at Ispra (VA, Italy). The damaging phenomena, caused by PsD tests, were assessed and quantified by means of a multi‐level vibration‐based approach suitably designed in order to evaluate the changes in the global dynamic structural response and to experimentally estimate the reduction in joint stiffness. Copyright © 2008 John Wiley & Sons, Ltd.
Experimental performance evaluation of an equipment isolation using MR dampers
Authors: Fan Yu‐Cheng , Loh Chin‐Hsiung , Yang Jann N. , Lin Pei‐Yang
Published: August 2008

Critical non‐structural equipments, including life‐saving equipment in hospitals, circuit breakers, computers, high technology instrumentations, etc., are vulnerable to strong earthquakes, and the failure of these equipments may result in a heavy economic loss. In this connection, innovative control systems and strategies are needed for their seismic protections. This paper presents the performance evaluation of passive and semi‐active control in the equipment isolation system for earthquake protection. Through shaking table tests of a 3‐story steel frame with equipment on the first floor, a magnetorheological (MR)‐damper together with a sliding friction pendulum isolation system is placed between the equipment and floor to reduce the vibration of the equipment. Various control algorithms are used for this semi‐active control studies, including the decentralized sliding mode control (DSMC) and LQR control. The passive‐on and passive‐off control of MR damper is used as a reference for the discussion on the control effectiveness. Copyright © 2008 John Wiley & Sons, Ltd.
The fault is not in her parents but in her insula—A neurobiological hypothesis of anorexia nervosa
Authors: Nunn Ken , Frampton Ian , Gordon Isky , Lask Bryan
Published: August 2008

The reported abnormalities of brain function in anorexia nervosa (AN) include impairment of neural circuits involving cortical (orbito‐frontal, somatosensory and parietal) and sub‐cortical (amygdala, hippocampus, thalamus, hypothalamus and striatum) structures. The insular cortex serves an integrative function for all the structures relevant to the features of AN and as such may be central to this impairment. We hypothesise that a rate limiting dysfunction of neural circuitry integrated by the insula can account for the clinical phenomena of AN. Such dysfunction could account for the known psychopathology, neuroimaging abnormalities and neuropsychological deficits. Proposals to test this hypothesis are made. Copyright © 2008 John Wiley & Sons, Ltd and Eating Disorders Association.
Comparison of antioxidants to prevent oxidation of sulphur flavour compound in sunflower oil
Authors: Leclercq Ségolène , Milo Christian , Reineccius Gary A.
Published: August 2008

The objective of this study was to compare the effectiveness of various antioxidants in slowing sulphur flavour compound oxidation in oil matrix. A model aroma compound mixture was prepared in sunflower oil and stored for 8 weeks. Six systems were studied, in which samples contained: 0.01% δ‐tocopherol; 0.05% rosemary extract or a mixture of 0.02% (ratio 1:1) δ‐tocopherol and ascorbyl palmitate; or of butylated hydroxy anisole (BHA) and butylated hydroxy toluene (BHT); and lastly with no antioxidant added, with low‐Oxygen level or with ambient air oxygen level. Aroma volatiles were analysed by static headspace–GC–FID to determine stability over time. The effect of each antioxidant system on their stability was generally compound‐dependent: BHA/BHT and systems containing tocopherol did not provide any significant protection (p > 0.05) to furfuryl mercaptan (FMCP), dimethyl sulphide (DMS) and propane thiol (1‐PSH), but did protect 2‐butanethiol (2‐BSH) over 8 weeks of storage. In contrast, adding rosemary extract did not improve the stability of 2‐BSH but substantially protected the three other compounds. Overall, less reactive sulphur compounds were better protected by the presence of antioxidants. While all antioxidants systems reduced oxidation of the oil matrix over time, they were not as effective in reducing the losses of flavour compounds. Copyright © 2008 John Wiley & Sons, Ltd.
Morphology of secretory structures and essential oil composition in Mentha cervina L. from Portugal
Authors: Rodrigues Leandra , Monteiro Patrícia , Póvoa Orlanda , Teixeira Generosa , Moldão Margarida , Figueiredo Ana Cristina , Monteiro Ana
Published: August 2008

Mentha cervina L. is an aromatic plant that is traditionally used in the Alentejo region of Portugal to flavour food dishes and for the medicinal properties of the essential oil produced in its glandular trichomes. The morphology and distribution of the secretory structures of 20 populations was studied by light and scanning electron microscopy and revealed a great similarity in the type and distribution of glandular and non‐glandular trichomes. In addition, two populations were surveyed at different stages of their life cycles. This showed that both maximum trichome density and maximum filling capacity of the glandular trichomes are attained early on. The GC and GC–MS chemical analyses showed that pulegone (62–80%), isomenthone (3–18%) and limonene (3–7%) are the main components of M. cervina essential oils. Cluster analysis of the identified essential oil components revealed a major chemical consistency between the 20 populations evaluated. Copyright © 2008 John Wiley & Sons, Ltd.
Volatile constituents from the rhizomes of Curcuma haritha Mangaly and Sabu from southern India
Authors: Raj Gopan , Baby Sabulal , Dan Mathew , Thaha Abdul Rasheed Muhammed , Sethuraman Mathur Gopalakrishnan , George Varughese
Published: August 2008

Volatile oil from the rhizomes of Curcuma haritha Mangaly and Sabu from the Western Ghats, southern India, was isolated by hydrodistillation and characterized by a combination of GC–FID, GC–MS, co‐GC, database and literature search, linear retention indices, prep. TLC, IR, NMR and MS. Refractive index, specific rotation and specific gravity of C. haritha rhizome oil were measured. Fifty constituents, comprising 99.9% of C. haritha rhizome oil, were identified, of which monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons and oxygenated sesquiterpenes constituted 7.7%, 72.0%, 1.9% and 18.2%, respectively. Camphor (36.0%), 1,8‐cineole (13.9%), isoborneol (10.6%), camphene (5.7%) and linalool (4.7%) were the major monoterpenes, while curdione (6.9%), furanogermenone (3.3%) and germacrone (2.8%) were the major sesquiterpenoids in C. haritha rhizome oil. Camphor and curdione were quantified by external standardization. Copyright © 2008 John Wiley & Sons, Ltd.
Numerical investigation of hemodynamics at an end‐to‐side junction with a laterally diffused bypass graft
Authors: Kim Yong Hyun , Lee Joon Sang
Published: August 2008

Intimal hyperplasia (IH) at arterial bypass graft is a major factor responsible for graft failure. Several techniques are used to explain IH formation at the end‐to‐side anastomosis junction. Abnormal hemodynamics contributing to the development of disease at the junction is the one of most common theories. This study describes a means of modifying the area of bypass graft at the junction part. This procedure, called the laterally diffused bypass graft (LDBG), is able to alter the hemodynamics in the end‐to‐side anastomosis. The LDBG model, due to an expansion of the outer curvature in the graft, reduces the velocity on the artery bed, side and top junction walls. The recirculation with velocity vectors on the host artery is significantly altered near the heel region on the host artery. Wall shear stress is decreased by up to 34% on the floor of artery centerline at the peak systole and by 61.9% on the top junction of artery during the systole deceleration. Corresponding time‐averaged wall shear stresses are found to decrease by 40.5%. Secondary flow is observed to be decreased significantly at the distal junction. Copyright © 2008 John Wiley & Sons, Ltd.
Tectonic environments of ancient civilizations in the eastern hemisphere
Authors: Force Eric R.
Published: August 2008

The map distribution of ancient civilizations shows a remarkable correspondence with tectonic boundaries related to the southern margin of the Eurasian plate. Quantification of this observation shows that the association is indeed significant, and both historical records and archaeoseismological work show that these civilizations commonly suffered earthquake damage. Close association of ancient civilizations with tectonic activity seems to be a pattern of some kind. In the hope that dividing the civilizations into subsets might clarify the meaning of this relation, primary and derivative civilizations were compared. Derivative civilizations prove to be far more closely related to the tectonic boundaries. Similarly, the civilizations that endured the longest (and that have been described as most static) are systematically the farthest from plate boundaries. It is still unclear how the relation actually worked in ancient cultures, i.e., what aspects of tectonism promoted complexity. Linkages to water and other resources, trade (broadly construed), and societal response seem likely. Volcanism appears not to be involved. © 2008 Wiley Periodicals, Inc.
Late Pleistocene and Early Holocene lake‐level fluctuations in the Lahontan Basin, Nevada: Implications for the distribution of archaeological sites
Authors: Adams Kenneth D. , Goebel Ted , Graf Kelly , Smith Geoffrey M. , Camp Anna J. , Briggs Richard W. , Rhode David
Published: August 2008

The Great Basin of the western U.S. contains a rich record of Late Pleistocene and Holocene lake‐level fluctuations as well as an extensive record of human occupation during the same time frame. We compare spatial‐temporal relationships between these records in the Lahontan basin to consider whether lake‐level fluctuations across the Pleistocene‐Holocene transition controlled distribution of archaeological sites. We use the reasonably well‐dated archaeological record from caves and rockshelters as well as results from new pedestrian surveys to investigate this problem. Although lake levels probably reached maximum elevations of about 1230–1235 m in the different subbasins of Lahontan during the Younger Dryas (YD) period, the duration that the lakes occupied the highest levels was brief. Paleoindian and Early Archaic archaeological sites are concentrated on somewhat lower and slightly younger shorelines (_1220–1225 m) that also date from the Younger Dryas period. This study suggests that Paleoindians often concentrated their activities adjacent to large lakes and wetland resources soon after they first entered the Great Basin. © 2008 Wiley Periodicals, Inc.
Activating NK cell receptor ligands are differentially expressed during progression to cervical cancer
Authors: Textor Sonja , Dürst Matthias , Jansen Lars , Accardi Rosita , Tommasino Massimo , Trunk Marcus J. , Porgador Angel , Watzl Carsten , Gissmann Lutz , Cerwenka Adelheid
Published: August 2008

Human papillomavirus‐induced cervical carcinomas often show impaired expression of MHC class I molecules resulting in the inability of tumor cells to directly present viral peptides to cytotoxic T lymphocytes. Loss of MHC class I expression combined with the expression of activating NK cell receptor ligands renders tumor cells potentially susceptible to NK cell attack. Thus, in this study, we analyzed the expression of activating NK cell receptor ligands, NK cell accumulation and activation status in situ in normal ectocervical tissue (NCT), cervical intraepithelial neoplasia (CIN) and squamous cervical carcinoma (CxCa). We observed that expression of the DNAM‐1 ligand CD155 was frequently upregulated in CxCa, but not in CIN. The NKG2D ligand MICA was upregulated in fewer CxCa biopsies. In contrast, another NKG2D ligand ULBP2 was preferentially expressed in differentiated epithelial cells of NCT. Increased numbers of NK cells were detected in CIN as compared to NCT and CxCa. Expression of activating NK cell receptor ligands combined with loss of MHC class I was not correlated with enhanced NK cell accumulation or activation status. Furthermore, we demonstrate that cervical cancer cell lines are killed by the NK cell line, NKL, in a NKG2D‐ and DNAM‐1‐dependent manner in vitro. Since a significant number of CxCa biopsies showed low MHC class I expression combined with high expression of one or more of the tested activating NK cell receptor ligands, we conclude that CxCa might be a promising target for NK cell‐based adoptive immunotherapy. © 2008 Wiley‐Liss, Inc.
MLH1 −93G>A promoter polymorphism and risk of mismatch repair deficient colorectal cancer
Authors: Allan James M. , Shorto Jennifer , Adlard Julian , Bury Jonathan , Coggins Ron , George Rina , Katory Mark , Quirke Philip , Richman Susan , Scott Daniel , Scott Kathryn , Seymour Matthew , Travis Lois B. , Worrillow Lisa J. , Bishop D. Timothy , Cox Angela ,   on behalf of the UK NCRI Colorectal Clinical Studies Group and the Colorectal Cancer Study Group
Published: August 2008

Rare inherited mutations in the mutL homolog 1 (MLH1) DNA mismatch repair gene can confer an increased susceptibility to colorectal cancer (CRC) with high penetrance where disease frequently develops in the proximal colon. The core promoter of MLH1 contains a common single nucleotide polymorphism (SNP) (−93G>A, dbSNP ID:rs1800734) located in a region essential for maximum transcriptional activity. We used logistic regression analysis to examine the association between this variant and risk of CRC in patients in the United Kingdom. All statistical tests were 2 sided. In an analysis of 1,518 patients with CRC, homozygosity for the MLH1 −93A variant was associated with a significantly increased 3‐fold risk of CRC negative for MLH1 protein by immunohistochemistry (odds ratio (OR): AA vs GG = 3.30, 95% CI 1.46–7.47, n = 1392, p = 0.004, MLH1 negative vs MLH1 positive CRC) and with a 68% excess of proximal CRC (OR: AA vs GG=1.68, 95% confidence interval (CI) 1.00–2.83, n = 1,518, p = 0.05, proximal vs distal CRC). These findings suggest that the MLH1 −93G>A polymorphism defines a low penetrance risk allele for CRC. © 2008 Wiley‐Liss, Inc.
Angiostatic activity of obtustatin as α1β1 integrin inhibitor in experimental melanoma growth
Authors: Brown Meghan C. , Staniszewska Izabela , Del Valle Luis , Tuszynski George P. , Marcinkiewicz Cezary
Published: August 2008

The presented results show the effect of targeting of collagen receptor, α1β1 integrin expressed on the endothelial cells on the development of experimental melanoma and pathological angiogenesis. Obtustatin, a snake venom KTS‐disintegrin, was applied as a specific inhibitor of this integrin. This low molecular weight peptide revealed a potent therapeutic effect on melanoma progression in 2 animal systems, mouse and quail. Its oncostatic effect was related to the inhibition of angiogenesis. Obtustatin inhibited the neovascularization ratio on the CAM embryo of quail, which was pathologically induced by the developing tumor. The i.v. administration of obtustatin completely blocked cancer growth of MV3 human melanoma in nude mice. In B16F10 syngeneic mouse model treatment with the disintegrin revealed a lower effect, although the development of the tumor was significantly reduced for both dosages. The mechanism of obtustatin action is related to the blocking of microvascular endothelial cell proliferation, which undergoes apoptosis in caspase‐dependent manner. Summarizing, we present studies of low molecular weight disintegrin, obtustatin as a potential therapeutic compound for treatment of melanoma that contain a high level of vascularization. © 2008 Wiley‐Liss, Inc.
Selenite induces topoisomerase I and II‐DNA complexes in K562 leukemia cells
Authors: López‐Lázaro Miguel , Willmore Elaine , Elliott Sarah L. , Austin Caroline A.
Published: August 2008

The essential trace element selenium is one of the most promising cancer chemopreventive agents. Data from preclinical studies have revealed that selenite, an inorganic form of selenium, may also be useful in cancer chemotherapy. DNA topoisomerases (topos) are the target of several useful anticancer drugs. These drugs induce DNA complexes with either topo I or topo II; then cellular processing coverts these topo‐DNA complexes into permanent DNA strand breaks that ultimately lead to cell death. Previous reports have revealed that selenite can induce apoptosis in cancer cells selectively and that selenite‐induced apoptosis is preceded by the formation of DNA strand breaks. In vitro experiments have shown that selenite induces topo II‐DNA complexes, which seem to be involved in selenite‐induced apoptosis. Using the cell‐based assay TARDIS, here we show that selenite induces topo II‐DNA complexes (topo IIα and topo IIβ) in K562 leukemia cells; these complexes appeared in a time‐dependent manner and correlated with the induction of apoptosis. Cells lacking topo IIβ were resistant to selenite‐induced cell growth inhibition, suggesting that this isoenzyme is a target for selenite. We report for the first time that selenite induces topo I‐DNA complexes in K562 cells; the levels of these complexes were high at short exposure times and seem to appear before the induction of apoptosis. Overall, our results show that selenite induces topo‐DNA complexes in cells with both topo I and II, and support previous data that suggest that this agent has potential for the treatment of cancer. © 2008 Wiley‐Liss, Inc.
Antiproliferative effects of AVN944, a novel inosine 5‐monophosphate dehydrogenase inhibitor, in prostate cancer cells
Authors: Floryk Daniel , Thompson Timothy C.
Published: August 2008

Inosine 5‐monophosphate dehydrogenase II, a key enzyme in the de novo synthesis of purine nucleotides, is expressed in prostate tumors and prostate cancer cells. AVN944 is a new, specific, noncompetitive IMPDH inhibitor. In this study, we investigated the effects of IMPDH inhibitor AVN944 on LNCaP, CWR22Rv1, DU145 and PC‐3 human prostate cancer cells. AVN944 inhibited proliferation of these 4 prostate cancer cell lines and was associated with cell cycle G1 arrest of LNCaP cells and S‐phase block of androgen‐independent CWR22Rv1, DU145 and PC‐3 cells. AVN944 induced caspase‐dependentand caspase‐independent cell death in LNCaP, CWR22Rv1, and DU145 cells. AVN944 induced expression of p53‐target proteins Bok, Bax and Noxa in androgen‐responsive cell lines and suppressed expression of survivin in prostate cancer cells regardless of their androgen sensitivity. AVN944 also induced differentiation of androgen‐independent prostate cancer cells as indicated by morphological changes and increased expression of genes coding for prostasomal proteins, keratins and other proteins, including tumor suppressor genes MIG‐6 and NDRG1. AVN944‐differentiated androgen‐independent DU145 and PC‐3 cells are sensitized to TRAIL‐induced apoptosis as demonstrated by induction of caspases and PARP cleavage. In summary, AVN944 inhibited the growth of human prostate cancer cells by inducing cell cycle arrest, cell death as well as differentiation. AVN944 is a novel, promising therapeutic agent that might be combined with other agents for treatment of human prostate cancer. © 2008 Wiley‐Liss, Inc.
KAI1/CD82 is a novel target of estrogen receptor‐mediated gene repression and downregulated in primary human breast cancer
Authors: Christgen Matthias , Bruchhardt Henriette , Ballmaier Matthias , Krech Till , Länger Florian , Kreipe Hans , Lehmann Ulrich
Published: August 2008

The cell‐surface glycoprotein KAI1 suppresses tumor growth and metastasis in various animal models. Downregulation of KAI1 has been implicated in the progression of cancer. However, the mechanisms of KAI1 inactivation are poorly understood. This is the first study that investigates expression and regulation of KAI1 in human breast cancer. KAI1 expression was analyzed on custom‐made tissue microarrays comprising 209 well‐characterized breast cancers and normal mammary gland tissue. Strong KAI1 immunoreactivity was observed throughout the normal mammary gland epithelium. In breast cancer tissue, KAI1 immunoreactivity was lost in 161/209 (77%) cases. Strikingly, KAI1 was preferentially lost in estrogen receptor (ER)‐positive breast cancers (p < 0.001). This was validated by real‐time RT‐PCR analyses showing a 7.5‐fold downregulation of KAI1 mRNA in ER‐positive relative to ER‐negative tumors (p = 0.028). Notably, this was also corroborated by Affymetrix microarray expression data of an independent cohort of 49 breast cancers. Class comparison analysis identified KAI1 as downregulated in ER‐positive tumors. Subsequently, human breast cancer cell lines were employed to test a potential role of ER‐activity in the downregulation of KAI1, as suggested by our expression analyses. Exposure of ER‐positive breast cancer cells to fulvestrant, a clinically approved ER‐antagonist that reverses ER‐mediated gene repression, induced a significant upregulation of KAI1 and inhibited cell proliferation as well as migration. In summary, we demonstrate for the first time that KAI1 is a target of ER‐mediated gene‐repression, and thus, it is downregulated in ER‐positive breast cancer. Importantly, KAI1 might be reinducible by endocrine therapy with ER‐antagonists in patients suffering from ER‐positive breast cancer. © 2008 Wiley‐Liss, Inc.
Tissue culture‐based breast cancer biomarker discovery platform
Authors: Kulasingam Vathany , Diamandis Eleftherios P.
Published: August 2008

Current cancer biomarkers suffer from low diagnostic sensitivity and specificity and have not yet made a major impact on reducing cancer burden. Proteomic methods based on mass spectrometry have matured significantly over the past few years and hold promise to deliver candidate markers for diagnosis, prognosis or monitoring therapeutic response. Because of the complex nature of biological fluids such as plasma, biomarker discovery efforts using proteomics have not as yet delivered any novel tumor markers. Recently, there has been a rise in the number of publications utilizing a cell culture‐based model of cancer to identify novel candidate tumor markers. The secretome of cancer cell lines constitutes an important class of proteins that can act locally and systemically in the body. Secreted proteins, in addition to serving as serological markers, play a central role in physiology and pathophysiology. In this review, we focus on the proteomics of breast cancer and the different strategies to mine for biomarkers, with particular emphasis on a cell culture‐based model developed in our laboratory. © 2008 Wiley‐Liss, Inc.
Differential subcellular localisation of the tumour suppressor protein LIMD1 in breast cancer correlates with patient survival
Authors: Spendlove Ian , Al‐Attar Ahmad , Watherstone Oliver , Webb Thomas M. , Ellis Ian O. , Longmore Gregory D. , Sharp Tyson V.
Published: August 2008

The tumour suppressor gene (TSG) LIM domain containing protein 1 (LIMD1) has been associated with transformation of epithelial cells of the lung and its expression is downregulated in all lung tumour samples tested compared to normal lung matched controls. In the first study of its kind we used an anti‐LIMD1 specific monoclonal antibody to investigate expression/localisation of the LIMD1 protein in a well‐characterised tissue microarray of breast cancers and normal adjacent epithelia. Comparison of tumour with adjacent normal and distant normal tissue demonstrated that LIMD1 expression is moderate to high compared to tumour. There was also a significant correlation with histological grade (p = 0.0001), tumour size (p = 0.013) and tumour type (p = 0.004) indicating an association with aggressive disease. Cytoplasmic LIMD1 expression was seen in 99.3% of cases, with 43.1% showing both nuclear and cytoplasmic localisation. Absence/loss of nuclear staining showed a strong correlation with patient survival and was indicative of poor prognosis (p = 0.033). There was no association with lymph node status and other clinicopathological parameters. Nuclear staining was more pronounced in better prognosis tumours and normal tissue. This study demonstrates that LIMD1 represents a novel prognostic marker for breast cancer. Combined with the fact that LIMD1 expression is downregulated in lung cancers this clearly indicates that LIMD1 may represent a critical TSG, the function of which is deregulated via overall loss of expression and/or relocalisation within the cell during tumour development. The possible functions of LIMD1 localisation within the nucleus and cytoplasm and its relationship to tumour prognosis are discussed. © 2008 Wiley‐Liss, Inc.
Optical contrast agents and imaging systems for detection and diagnosis of cancer
Authors: Pierce Mark C. , Javier David J. , Richards‐Kortum Rebecca
Published: August 2008

Molecular imaging has rapidly emerged as a discipline with the potential to impact fundamental biomedical research and clinical practice. Within this field, optical imaging offers several unique capabilities, based on the ability of cells and tissues to effect quantifiable changes in the properties of visible and near‐infrared light. Beyond endogenous optical properties, the development of molecularly targeted contrast agents enables disease‐specific morphologic and biochemical processes to be labeled with unique optical signatures. Optical imaging systems can then provide real‐time visualization of pathophysiology at spatial scales from the subcellular to whole organ levels. In this article, we review fundamental techniques and recent developments in optical molecular imaging, emphasizing laboratory and clinical systems that aim to visualize the microscopic and macroscopic hallmarks of cancer. © 2008 Wiley‐Liss, Inc.
Development of nanofiber‐covered stents using electrospinning: In vitro and acute phase in vivo experiments
Authors: Kuraishi Keita , Iwata Hiroo , Nakano Shigeyuki , Kubota Shinichiro , Tonami Hiroyuki , Toda Mitsuaki , Toma Naoki , Matsushima Satoshi , Hamada Kazuhide , Ogawa Satoru , Taki Waro
Published: August 2008

There are some technical difficulties in treating for a broad necked aneurysm and a higher incidence of recurrence. Because of these drawbacks, more innovative techniques for superior endovascular reconstructive treatment are required. We developed a novel covered stent employing electrospinning to deposit fine polyurethane (PU) fibers onto stents. An in vitro water leak test was designed and applied prior to animal testing to estimate the performance of covered stents and to determine the appropriate amount of PU fibers on a stent. Two tenths of a milligram of PU fibers proved to be sufficient to prevent water leakage. Then, the efficacy of the covered stents to that of bare stents was compared using 10 rabbits in which model aneurysms had been formed at the right common carotid artery by the elastase method. Angiographic evaluation on day 1 posttreatment (acute phase) revealed complete occlusion of the aneurysms and the patency of the parent arteries in animals treated with covered stents. At 10 days poststenting (subacute phase), the aneurysm neck was completely covered with neointimal layer as shown by scanning electron microscopic examination. The PU‐covered stent holds promise as a device for treating cerebral aneurysms. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Inkjet printing of bioadhesives
Authors: Doraiswamy Anand , Dunaway Timothy M. , Wilker Jonathan J. , Narayan Roger J.
Published: August 2008

Over the past century, synthetic adhesives have largely displaced their natural counterparts in medical applications. However, rising concerns over the environmental and toxicological effects of the solvents, monomers, and additives used in synthetic adhesives have recently led the scientific community to seek natural substitutes. Marine mussel adhesive protein is a formaldehyde‐free natural adhesive that demonstrates excellent adhesion to several classes of materials, including glasses, metals, metal oxides, and polymers. In this study, we have demonstrated computer aided design (CAD) patterning of various biological adhesives using piezoelectric inkjet technology. A MEMS‐based piezoelectric actuator was used to control the flow of the mussel adhesive protein solution through the ink jet nozzles. Fourier transform infrared spectroscopy (FTIR), microscopy, and adhesion studies were performed to examine the chemical, structural, and functional properties of these patterns, respectively. FTIR revealed the piezoelectric inkjet technology technique to be nondestructive. Atomic force microscopy was used to determine the extent of chelation caused by Fe(III). The adhesive strength in these materials was correlated with the extent of chelation by Fe(III). Piezoelectric inkjet printing of naturally‐derived biological adhesives may overcome several problems associated with conventional tissue bonding materials. This technique may significantly improve wound repair in next generation eye repair, fracture fixation, wound closure, and drug delivery devices. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Response of HEK293 and CHO cells overexpressing fusiogenic syncytin‐1 to mitochondrion‐mediated apoptosis induced by antimycin A
Authors: Knerr Ina , Söder Stephan , Licha Elke , Aigner Thomas , Rascher Wolfgang
Published: August 2008

Apoptosis is essential for the regulation of cellular homeostasis in the placenta and is also involved in the pathophysiology of pregnancy‐related diseases such as pre‐eclampsia and intrauterine growth restriction (IUGR). Syncytin‐1, a fusiogenic glycoprotein of endogenous‐retroviral origin expressed in human trophoblasts, facilitates placental syncytium formation and is found reduced in pre‐eclamptic placentas. We focus here on the mitochondrial apoptotic pathway and investigate whether the overexpression of syncytin‐1 in HEK293‐52 (human embryonic kidney cells) and CHO‐52 cells influences the apoptotic response to the mitochondrial inhibitor antimycin A (AA). After the induction of apoptosis by 5 µM AA and incubation for up to 36 h in the absence of serum, the mean apoptotic rate was reduced by 15–30% in syncytin‐1 transfected cells compared with mock‐transfectants. After 12 h of challenge with AA we found lower cytochrome c levels in the cytoplasmic protein fraction and higher amounts in the mitochondrial fraction in syncytin‐1 transfectants compared with mock‐transfectants. We observed a decreased Mitotracker Red staining of mitochondria following AA challenge for 24 h in mock‐treated CHO cells, in particular, compared with syncytin‐1 transfectants. Moreover, we found a reduced activation of caspase 9 in syncytin‐1 transfected HEK293‐52 cells after 48 h of apoptotic challenge compared to mock‐transfectants. However, a high expression of anti‐apoptotic Bcl‐xL was found in both cell types. Using syncytin‐1 transfected HEK293‐52 cells and CHO‐52 cells, we provide initial evidence that syncytin‐1 may exert its anti‐apoptotic function at the mitochondrial level. A reduced release of cytochrome c followed by a diminished activation of caspase 9 is a possible mechanism. J. Cell. Biochem. 105: 766–775, 2008. © 2008 Wiley‐Liss, Inc.
Continuous lipase‐catalyzed synthesis of hexyl laurate in a packed‐bed reactor: optimization of the reaction conditions in a solvent‐free system
Authors: Ju Hen‐Yi , Yang Cheng‐Kang , Yen Yue‐Horng , Shieh Chwen‐Jen
Published: August 2008

BACKGROUND: Hexyl laurate has been applied widely in cosmetic industries and is synthesized by chemical methods with problems of cost, environmental pollution, and by‐products. In this study, Lipozyme® IM77 (from Rhizomucor miehei) was used to catalyze the direct‐esterification of hexanol and lauric acid in a solvent‐free system by utilizing a continuous packed‐bed reactor, wherein the aforementioned difficulties could be overcome. Response surface methodology (RSM) and three‐level‐three‐factor Box‐Behnken design were employed to evaluate the effects of synthesis parameters, such as reaction temperature (45–65 °C), mixture flow rate (0.25–0.75 mL min−1) and concentration of lauric acid (100–300 mmol L−1) on the production rate (µmol min−1) of hexyl laurate by direct esterification.

RESULTS: The production rate was affected significantly by the mixture flow rate and lauric acid concentration. On the basis of ridge‐max analysis, the optimum synthesis conditions for hexyl laurate were as follows: 81.58 ± 1.76 µmol min−1 at 55 °C, 0.5 mL min−1 flow rate and 0.3 mol L−1 lauric acid.

CONCLUSION: The lipase‐catalyzed synthesis of hexyl laurate by Lipozyme® IM‐77 in a continuous packed‐bed bioreactor and solvent‐free system was successfully developed; optimization of the reaction parameters was obtained by Box–Behnken design and RSM. Copyright © 2008 Society of Chemical Industry
Reuterin production by Lactobacillus reuteri NRRL B‐14171 immobilized in alginate
Authors: Zamudio‐Jaramillo Miguel A. , Hernandez‐Mendoza Adrian , Robles Victor J. , Mendoza‐Garcia Patricia G. , Espinosa‐de‐los‐Monteros José Joel , Garcia Hugo S.
Published: August 2008

BACKGROUND: Lactobacillus reuteri NRRL B‐14171 was immobilized in spherical calcium alginate beads to study reuterin production.

RESULTS: In relation to free cells (82 mmol L−1), the immobilized cells showed a sharp increase in reaction rate and achieved similar conversions with a reduction in the required biomass. Tests for mass transfer limitations on the reaction rate indicated that neither intraparticle nor external constraints were present. Effectiveness factors near 1 were estimated.

CONCLUSION: Immobilization induced increased production of reuterin in Lactobacillus reuteri and is a feasible option for increasing process productivity. Copyright © 2008 Society of Chemical Industry
Biological removal of 17α‐ethinylestradiol (EE2) in an aerated nitrifying fixed bed reactor during ammonium starvation
Authors: Forrez Ilse , Carballa Marta , Boon Nico , Verstraete Willy
Published: August 2008

BACKGROUND: Conventional wastewater treatment plants (WWTPs) tend to partially remove recalcitrant chemicals, such as pharmaceuticals. Among these, the synthetic estrogen 17α‐ethinylestradiol (EE2) is of great environmental concern. In this work a continuously aerated submerged fixed bed bioreactor was used for the biological removal of EE2 at µg L−1 levels.

RESULTS: Removal efficiencies higher than 96% were obtained at a hydraulic retention time (HRT) of 4.3 days and a volumetric loading rate (Bv) of 11 µg EE2 L−1 d−1. Increasing the Bv up to 40 and 143 µg EE2 L−1 d−1 led to slightly lower removal efficiencies, 81 and 74%, respectively. Nitrification was confirmed to be the main biological mechanism involved in EE2 removal. Most interestingly, the elimination of EE2 was not affected by the absence of ammonium in the feed, suggesting that ammonia‐oxidizing bacteria (AOB) were able to maintain their population density and their activity, even after several months of starvation.

CONCLUSION: The concept of an aerated submerged fixed bed bioreactor, capable of removing estrogens in a sustainable and biological way, shows great potential as an effluent polishing step for existing WWTPs. Copyright © 2008 Society of Chemical Industry
Surface modification of rubber (Hevea brasiliensis) leaves for the adsorption of copper ions: kinetic, thermodynamic and binding mechanisms
Authors: Ngah Wan Saime Wan , Hanafiah Megat Ahmad Kamal Megat
Published: August 2008

BACKGROUND: This research describes the adsorption of copper ions from aqueous solutions following the modification of rubber (Hevea brasiliensis) leaves with formaldehyde solution. The main objectives of this research were to identify the binding mechanisms of copper ions on the chemically modified rubber leaves by spectroscopic techniques and to investigate the effects of several important physicochemical parameters such as pH, copper concentration, contact time, adsorbent dose and temperature on copper removal.

RESULTS: Based on a kinetic study, the pseudo‐second‐order model was found to fit the experimental results well, while the Boyd kinetic model indicated that the rate‐determining step was due to film diffusion. Adsorption isotherms were modelled by the Langmuir and Freundlich isotherm equations, with the former providing a better fit for the data. Based on the Langmuir model, the maximum adsorption capacities of Cu(II) ions at 300, 310 and 320 K were 8.36, 8.61 and 8.71 mg g−1, respectively. Thermodynamic parameters such as the Gibbs free energy (ΔG°), enthalpy (ΔH°) and entropy changes (ΔS°) were calculated. The adsorption process was spontaneous as the values of ΔG° were negative, and endothermic as higher adsorption capacities were recorded at higher temperatures. More than 80% of copper ions bound on the adsorbent were able to be desorbed using 0.02 mol L−1 HCl, HNO3 and EDTA solutions. Besides ion exchange, surface complexation could also play a major role in copper binding.

CONCLUSION: Due to its relative abundance and satisfactory adsorption capacity, the modified rubber leaves can be considered as a good low‐cost adsorbent for removing copper ions from dilute aqueous solutions. Copyright © 2008 Society of Chemical Industry