bluuebunny/crossref_metadata_2025 huggingface dataset:
Properties and pervaporation separation of hydroxyl‐terminated polybutadiene‐based polyurethane/poly(methyl metharcylate) interpenetrating networks membranes
Authors: Tsai Mei‐Hui , Huang Shih‐Liang , Chang Po‐Hsueh , Chen Chiou‐Jey
Published: September 2007

Hydroxyl‐terminated polybutadiene (HTPB), 4,4′‐dicyclohexyl methane diiscyanate (H12MDI), and 1,4‐butane diol are used to synthesize polyurethane (PU) solutions by two‐stage process. Interpenetrating networks (IPNs) of HTPB‐based PU and poly(methyl methacrylate) (PMMA) with HTPB/MMA (wt/wt % ratio) = 2.0, 1.5, 1.0, 1.5, 0.8, and 0.6, which are designated as IPN1 to IPN5, respectively, are synthesized by sequential polymerization technique. Thermal properties, tensile strength, and contact angle of membranes increase with the increase of MMA content, while the elongation of membranes show the reverse trend. Characterization of membranes are investigated by CC/CO absorption ratio and infrared absorption frequency shiftment. These PU and IPN membranes are used for the separation of ethanol/water and isopropanol/water solution by pervaporation test. IPN3 membrane possesses the largest pervaporation permeability and the separation factor. The pervaporation results of ethanol/water feed has the same trend as that of isopropyl alcohol (IPA)/water solution. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Novel binder system for ultraviolet‐curable coatings based on tobacco seed (Nicotiana rustica) oil derivatives as a renewable resource
Authors: Patel Kalpesh I. , Parmar Randhirsinh J. , Parmar Jayant S.
Published: September 2007

Several coatings have been developed to reduce volatile organic component emissions, such as water‐borne coatings, high‐solid coatings, powder coatings, and radiation‐curable coatings. Ultraviolet‐curable coatings are one such boon to paint industries, not only reducing volatile organic components but also increasing productivity. Most polymers industrially produced nowadays are based on petroleum, which is a limited resource. Developing new procedures for making polymers based on natural renewable resources is a resounding theme for this decade and the future also. In response to both these needs, we have investigated the use of tobacco seed (Nicotiana rustica) oil in the synthesis of radiation‐curable coatings. In this work, the alcoholysis of oil in various ratios with polyhydroxyl compounds was performed to prepare novel polyols, and these different polyols were reacted further with excess polyisocyanate to produce isocyanate‐terminated prepolymers. The prepolymer were further reacted with hydroxyethyl methacrylate to produce urethane acrylate oligomers. The radiation‐curable coating compositions were than prepared by the mixing of these oligomers with different reactive diluents, photoinitiators, and activators. These coating compositions were studied for their various physical and film characteristics, and certain coating compositions from tobacco seed oil were found to show very excellent overall coating properties. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Synthesis, QSAR and Calcium Channel Antagonist Activity of New 1,4‐Dihydropyridine Derivatives Containing 1‐Methyl‐4,5‐dichloroimidazolyl Substituents
Authors: Hosseini Maryam , Miri Ramin , Amini Mohsen , Mirkhani Hossein , Hemmateenejad Bahram , Ghodsi Shahram , Alipour Eskandar , Shafiee Abbas
Published: September 2007

A group of dialkyl and diarylester analogues of nifedipine, in which the ortho‐nitrophenyl group at position 4 was replaced by a 1‐methyl‐4,5‐dichloroimidazolyl substituent, were synthesized and evaluated as calcium‐channel antagonists using the high K+ concentration of guinea‐pig ileum longitudinal smooth muscle. The structure of all compounds was confirmed by IR, 1H‐NMR, and mass spectra. The calcium‐channel antagonist activity of compounds 10a–f demonstrated that compound 10b was the most active and 10f the least active one. With unsymmetrical diesters 12a–k, the most active compound was the ethyl, phenethyl derivative. Structural parameters on the calcium‐channel antagonist activity were evaluated by QSAR analysis and a linear correlation was found between the –log IC50 values of these compounds and their constitutional and topological properties.
Tunable Bacterial Agglutination and Motility Inhibition by Self‐Assembled Glyco‐Nanoribbons
Authors: Lim Yong‐beom , Park Somi , Lee Eunji , Ryu Ja‐Hyoung , Yoon You‐Rim , Kim Tae‐Hyun , Lee Myongsoo
Published: September 2007

We explored a method of controlling bacterial motility and agglutination by using self‐assembled carbohydrate‐coated β‐sheet nanoribbons. To this aim, we synthesized triblock peptides that consist of a carbohydrate, a polyethylene glycol (PEG) spacer, and a β‐sheet‐forming peptide. An investigation into the effect of PEG‐spacer length on the self‐assembly of the triblock peptides showed that the PEG should be of sufficiently length to stabilize the β‐sheet nanoribbon structure. It was found that the stabilization of the nanoribbon led to stronger activity in bacterial motility inhibition and agglutination, thus suggesting that antibacterial activity can be controlled by the stabilization strategy. Furthermore, another level of control over bacterial motility and agglutination was attained by co‐assembly of bacteria‐specific and ‐nonspecific supramolecular building blocks. The nanoribbon specifically detected bacteria after the encapsulation of a fluorescent probe. Moreover, the detection sensitivity was enhanced by the formation of bacterial clusters. All these results suggest that the carbohydrate‐coated β‐sheet nanoribbons can be developed as promising agents for pathogen capture, inactivation, and detection, and that the activity can be controlled at will.
Effects of water deprivation on the pharmacokinetics of theophylline and one of its metabolites, 1,3‐dimethyluric acid, after intravenous and oral administration of aminophylline to rats
Authors: Choi Hye D. , Kang Hee E. , Chung Hye J. , Bae Soo K. , Shin Karen N. , Lee Myung G.
Published: September 2007

It has been reported that the expressions of hepatic microsomal cytochrome P450 (CYP) 1A1/2, 2B1/2 and 3A1/2 were not changed in rats with water deprivation for 72 h (rat model of dehydration) compared with the controls. It has been also reported that 1,3‐dimethyluric acid (1,3‐DMU) was formed from theophylline via CYP1A1/2 in rats. Hence, it could be expected that the formation of 1,3‐DMU could be comparable between the two groups of rats. As expected, after both intravenous and oral administration of theophylline at a dose of 5 mg/kg to the rat model of dehydration, the AUC of 1,3‐DMU was comparable to the controls. After both intravenous and oral administration of theophylline to the rat model of dehydration, the Clr of both theophylline and 1,3‐DMU was significantly slower than the controls. This could be due to significantly smaller urinary excretions of both theophylline and 1,3‐DMU since the AUC of both theophylline and 1,3‐DMU were comparable between the two groups of rats. The smaller urinary excretion of both theophylline and 1,3‐DMU could be due to urine flow rate‐dependent timed‐interval renal clearance of both theophylline and 1,3‐DMU in rats. Copyright © 2007 John Wiley & Sons, Ltd.
Statistical Surveillance of Epidemics: Peak Detection of Influenza in Sweden
Authors: Bock David , Andersson Eva , Frisén Marianne
Published: September 2007

A statistical surveillance system gives a signal as soon as data give enough evidence of an important event. We consider on‐line surveillance systems for detecting changes in influenza incidence. One important feature of the influenza cycle is the start of the influenza season, and another one is the change to a decline (the peak). In this report we discuss statistical methods for on‐line peak detection. One motive for doing this is the need for health resource planning. Surveillance systems were adapted for Swedish data on laboratory verified diagnoses of influenza. In Sweden, the parameters of the influenza cycles vary too much from year to year for parametric methods to be useful. We suggest a non‐parametric method based on the monotonicity properties of the increase and decline around a peak. A Monte Carlo study indicated that this method has useful stochastic properties. The method was applied to Swedish data on laboratory verified diagnoses of influenza for seven periods. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Adjusting Nonresponse Bias at Subdomain Levels using Multiple Response Phases
Authors: Oleson Jacob J. , He Chong Z.
Published: September 2007

When a sampling unit doesn't respond to a survey it is termed unit nonresponse. Unit nonresponse may have a dramatic affect on estimation results of interest. Using only those who responded to the survey to calculate the estimate may bias the estimate, known as nonresponse bias. Many approaches have been created in order to account for nonresponse. One such approach is to resample those nonrespondents in a second response “phase” (or more). We build a Bayesian hierarchical model that uses information from multiple response “phases” to estimate the phase specific response rates fromIsubdomains. This information is simultaneously used to estimate the success rates in thoseIsubdomains. Conditional success rates are then estimated for the first phase respondents, second phase respondents, and nonrespondents (the third response phase). A relationship between these three sets of conditional success rates is incorporated into the model. This is done through a spatially dependent structure. The 1998 Missouri Turkey Hunting Survey is used to illustrate this methodology. The success rate estimates from nonrespondents have a significant impact on the overall success rate. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Health-related quality of life among patients with adenocarcinoma of the gastro-oesophageal junction treated by gastrectomy or oesophagectomy
Authors: Barbour A P , Lagergren P , Hughes R , Alderson D , Barham C P , Blazeby J M
Published: September 2007

Background

Tumours of the gastro-oesophageal junction may be resected by total gastrectomy (TG) or transthoracic oesophagectomy (TTO). This study compared health-related quality of life (HRQL) following these procedures.

Methods

Prospective clinical and HRQL data (European Organization for Research and Treatment of Cancer QLQ-C30) were collected from 63 consecutive patients (20 TG and 43 TTO) before and 6 months after surgery for Siewert type I–III gastro-oesophageal tumours.

Results

Questionnaire response rates exceeded 90 per cent. Patients were similar with respect to disease stage, treatment-related mortality and survival, but those selected for TTO were younger with less co-morbidity than those undergoing TG. These differences were reflected in baseline HRQL scores, which were better in patients selected for TTO. Six months after surgery, however, HRQL showed a greater deterioration after TTO than after TG in terms of role and social function, global quality of life and fatigue. Symptom scores for pain and diarrhoea increased in both groups.

Conclusion

TTO had a greater negative impact on HRQL than TG for tumours of the gastro-oesophageal junction.
Optimising production cost and end‐product quality when raw material quality is varying
Authors: Måge Ingrid , Næs Tormod
Published: September 2007

This paper deals with the optimisation of production processes in a situation where the raw material varies. The objective is to minimise production costs for a given raw material quality, with restrictions on the end‐product quality. Three important issues are addressed. First, we discuss the collection of data for response surface modelling. In full‐scale production processes it is very difficult to perform large experiments. We show that merging smaller designed experiments can be a good alternative. Second, we illustrate the use of an approach for combining data obtained using an experimental design with spectroscopic raw material measurements in a joint regression model. Finally, we discuss some issues related to robustness and sensitivity in optimisation. We also show how this optimisation can be used as a tool when purchasing raw materials. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis, DNA‐Binding, Cleavage, and Cytotoxic Activity of New 1,7‐Dioxa‐4,10‐diazacyclododecane Artificial Receptors Containing Bisguanidinoethyl or Diaminoethyl Double Side Arms
Authors: Sheng Xin , Lu Xiao‐Min , Chen Yue‐Ting , Lu Guo‐Yuan , Zhang Jing‐Jing , Shao Ying , Liu Fang , Xu Qiang
Published: September 2007

Novel 1,7‐dioxa‐4,10‐diazacyclododecane artificial receptors with two pendant aminoethyl (3) or guanidinoethyl (4) side arms have been synthesized. Spectroscopy, including fluorescence and CD spectroscopy, of the interactions of 3, 4, and their copper(II) complexes with calf thymus DNA indicated that the DNA binding affinity of these compounds follows the order Cu2+–4>Cu2+–3>4>3, and the binding constants of Cu2+–3 are Cu2+–4 are 7.2×104 and 8.7×104 M−1, respectively. Assessment by agarose gel electrophoresis of the plasmid pUC 19 DNA cleavage activity in the presence of the receptors showed that the complexes Cu2+–3 and Cu2+–4 exhibit powerful supercoiled DNA cleavage efficiency. Kinetic data of DNA cleavage promoted by Cu2+–3 and Cu2+–4 under physiological conditions fit to a saturation kinetic profile with kmax values of 0.865 and 0.596 h−1, respectively, which give about 108‐fold rate acceleration over uncatalyzed supercoiled DNA. This acceleration is due to efficient cooperative catalysis of the copper(II) center and the functional (diamino or bisguanidinium) groups. In‐vitro cytotoxic activities toward murine melanoma B16 cells and human leukemia HL‐60 cells were also examined: Cu2+–4 shows the highest activity with IC50 values of 1.62×10−4 and 1.19×10−5 M, respectively.
Sodium Chains as Core Nanowires for Gelation of Organic Solvents from a Functionalized Nicotinic Acid and Its Sodium Salt
Authors: Bardelang David , Camerel Franck , Hotze Anna C. G. , Kariuki Benson , Paik Biswajit , Schmutz Marc , Ziessel Raymond , Hannon Michael J.
Published: September 2007

A new metallo‐organic gelator formed from an admixture of a substituted nicotinic acid and its sodium salt is described. The nicotinic acid is substituted in the 6‐position by an acetal functionality. The crystal structure of the 1:1 mixture revealed that the sodium atoms are aligned in infinite chains with the two organic units hydrogen bonded together to create potentially trinucleating ligands that encase the metal core, which leads to tube‐like structures. These one‐dimensional crystals were found to spontaneously gelify dichloromethane and provide pyridine gels with high thermal resistance. Gel formation was investigated by several analytical techniques, which included differential scanning calorimetry, TEM, freeze fracture electron microscopy (FFEM), IR spectroscopy and X‐ray diffraction, and was found to be induced by the swelling of the one‐dimensional material. FFEM and powder X‐ray diffraction have revealed that the sodium chains are associated in a highly compacted state into a layered structure inside the gel. Doping these robust gels with dyes by diffusion, such as xylene cyanol, methyl yellow and bromo thymol blue, is feasible without destruction of the gels.
A New Generation of Metal String Complexes: Structure, Magnetism, Spectroscopy, Theoretical Analysis, and Single Molecular Conductance of an Unusual Mixed‐Valence Linear [Ni5]8+ Complex
Authors: Liu Isiah Po‐Chun , Bénard Marc , Hasanov Hasan , Chen I‐Wen Peter , Tseng Wei‐Hsiang , Fu Ming‐Dung , Rohmer Marie‐Madeleine , Chen Chun‐hsien , Lee Gene‐Hsiang , Peng Shie‐Ming
Published: September 2007

Two new linear pentanickel complexes [Ni5(bna)4(Cl)2][PF6]2 (1) and [Ni5(bna)4(Cl)2][PF6]4 (2; bna=binaphthyridylamide), were synthesized and structurally characterized. A derivative of 1, [Ni5(bna)4(NCS)2][NCS]2 (3), was also isolated for the purpose of the conductance experiments carried out in comparison with [Ni5(tpda)4(NCS)2] (4; tpda=tripyridyldiamide). The metal framework of complex 2 is a standard [Ni5]10+ core, isoelectronic with that of [Ni5(tpda)4Cl2] (5). Also as in 5, complex 2 has an antiferromagnetic ground state (J=−15.86 cm−1) resulting from a coupling between the terminal nickel atoms, both in high‐spin sate (S=1). Complex 1 displays the first characterized linear nickel framework in which the usual sequence of NiII atoms has been reduced by two electrons. Each dinickel unit attached to the naphthyridyl moieties is assumed to undergo a one‐electron reduction, whereas the central nickel formally remains NiII. DFT calculations suggest that the metal framework of the mixed‐valence complex 1 should be described as intermediate between a localized picture corresponding to NiII‐NiI‐NiII‐NiI‐NiII and a fully delocalized model represented as (Ni2)3+‐NiII‐(Ni2)3+. Assuming the latter model, the ground state of 1 results from an antiferromagnetic coupling (J=−34.03 cm−1) between the two (Ni2)3+ fragments, considered each as a single magnetic centre (S=3/2). An intervalence charge‐transfer band is observed in the NIR spectrum of 1 at 1186 nm, suggesting, in accordance with DFT calculations, that 1 should be assigned to Robin–Day class II of mixed‐valent complexes. Scanning tunnelling microscopy (STM) methodology was used to assess the conductance of single molecules of 3 and 4. Compound 3 was found ≈40 % more conductive than 4, a result that could be assigned to the electron mobility induced by mixed‐valency in the naphthyridyl fragments.
Supramolecular Circular Helicates Formed by Destabilisation of Supramolecular Dimers
Authors: Hamblin Jacqueline , Tuna Floriana , Bunce Siona , Childs Laura J. , Jackson Alexander , Errington William , Alcock Nathaniel W. , Nierengarten Helene , Van Dorsselaer Alain , Leize‐Wagner Emmanuelle , Hannon Michael J.
Published: September 2007

The effect of changes in the angles at the connection points of linear/circular helicates is explored as a route to control the nuclearity and architecture of metallo‐supramolecular arrays. This effect is probed by changing the geometry of the metal centre used to assemble bis‐pyridylimine ligands that contain a 1,3‐bis(aminomethyl) benzene spacer group. Tetrahedral metal ions favour linear dimers, whereas octahedral nickel(II) predominantly gives a triangular circular helicate. Five‐coordinate copper(II) falls in the middle of these extremes and results in the formation of solvent‐dependent mixtures of dimer and trimer. The trinuclear, triangular, circular helicate structures, which result from coordination to copper(II) and nickel(II), are structurally characterised by X‐ray crystallography and reveal that the units can aggregate into hexagonal arrays that contain anion‐filled tube‐like channels in the solid state.
The Role of Lipid‐lowering Therapy in Preventing Coronary Heart Disease in Patients with Type 2 Diabetes
Authors: Karalis Dean G.
Published: September 2007

Coronary heart disease is the most common cause of death among diabetic patients. The increased risk of coronary heart disease in type 2 diabetes is due, in part, to lipid abnormalities often present in the diabetic patient. Diabetic dyslipidemia is characterized by elevated triglycerides, low high‐density lipoprotein cholesterol (HDL‐C) and an increased preponderance of small, dense low‐density lipoprotein cholesterol (LDL‐C) particles. Current guidelines for the prevention of coronary heart disease in diabetic patients identify elevated LDL‐C as the primary target of lipid‐lowering therapy, and recommend statins as the first‐line treatment for diabetic dyslipidemia. This review evaluates the large statin trials that have included diabetic patients, and discusses the role of combination therapy in managing dyslipidemia in diabetic patients. Copyright © 2007 Wiley Periodicals, Inc.
Homology Modeling of NR2B Modulatory Domain of NMDA Receptor and Analysis of Ifenprodil Binding
Authors: Marinelli Luciana , Cosconati Sandro , Steinbrecher Thomas , Limongelli Vittorio , Bertamino Alessia , Novellino Ettore , Case David A.
Published: September 2007

NMDA receptors are glutamate‐gated ion channels (iGluRs) that are involved in several important physiological functions such as neuronal development, synaptic plasticity, learning, and memory. Among iGluRs, NMDA receptors have been perhaps the most actively investigated for their role in chronic neurodegeneration such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Recent studies have shown that the NTD of subunit NR2B modulates ion channel gating through the binding of allosteric modulators such as the prototypical compound ifenprodil. In the present paper, the construction of a three‐dimensional model for the NR2B modulatory domain is described and docking calculations allow, for the first time, definition of the ifenprodil binding pose at an atomic level and fully explain all the available structure–activity relationships. Moreover, in an attempt to add further insight into the ifenprodil mechanism of action, as it is not completely clear if it binds and stabilizes an open or a closed conformation of the NR2B modulatory domain, a matter, which is fundamental for the rational design of NMDA antagonists, MD simulations followed by an MM‐PBSA analysis were performed. These calculations reveal that the closed conformation of the R1‐R2 domain, rather than the open, constitutes the high affinity binding site for ifenprodil and that a profound stabilization of the closed conformation upon ifenprodil binding occurs. Thus, for a rational design and/or for virtual screening experiments, the closed conformation of the R1‐R2 domain should be taken into account and our 3D model can provide valuable hints for the design of NR2B‐selective antagonists.
Synthesis of Conformationally Constrained Glutamic Acid Homologues and Investigation of Their Pharmacological Profiles
Authors: Conti Paola , Pinto Andrea , Tamborini Lucia , Grazioso Giovanni , De Sarro Giovambattista , Bräuner‐Osborne Hans , Szabo Geza , Gábor Hársing László , De Micheli Carlo
Published: September 2007

Homologation of the glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. We investigated the effects of a further increase in the distance between the amino acid moiety and the distal carboxylate group of model compounds (±)‐1 and (±)‐2 on their activity/selectivity profiles. We therefore synthesized new derivatives (±)‐3–(±)‐6, which are homologues of glutamic acid containing three additional carbon units. Moreover, because the potency of NMDA antagonists can be markedly increased by replacing the distal carboxylate with the bioisosteric phosphonate group, we also prepared the corresponding phosphonate derivatives (±)‐7–(±)‐10. All new compounds were submitted to binding assays with iGluRs, and derivatives (±)‐3–(±)‐6 were also tested in second messenger assays at representative mGluR subtypes. All the applied structural modifications were detrimental to the interaction with NMDA receptors. Conversely, structural variation of the nonselective mGluR ligand (±)‐2 led to derivative (±)‐5, which behaved as a selective group I metabotropic receptor antagonist. Notably, upon i.c.v. administration in DBA/2 mice, amino acid (±)‐5 produced a significant protection against audiogenic seizures, whereas it was inactive after i.p. administration.
The hazards of intermediate endpoints
Authors: Beer Tomasz M. , Ryan Christopher W.
Published: September 2007

Progression‐free survival in men with advanced prostate cancer is a composite endpoint that has been neither standardized nor validated as a measure of clinical benefit in advanced prostate cancer. The absence of a progression‐free survival benefit in this randomized trial of atrasentan leaves the authors uncertain with regard to the potential value of this agent in prostate cancer.
Phase 1 study of tipifarnib in combination with imatinib for patients with chronic myelogenous leukemia in chronic phase after imatinib failure
Authors: Cortes Jorge , Quintás‐Cardama Alfonso , Garcia‐Manero Guillermo , O'Brien Susan , Jones Dan , Faderl Stefan , Ebarb Theresa , Giles Francis , Thomas Deborah , Kantarjian Hagop
Published: September 2007

BACKGROUND.

The tolerability and efficacy of the combination of tipifarnib, an orally bioavailable nonpeptidomimetic farnesyl transferase inhibitor, and imatinib was investigated in patients with chronic myelogenous leukemia in chronic phase who had failed imatinib.

METHODS.

Twenty‐six patients (13 [50%] with Abl kinase domain mutations) were treated. The initial dose level was tipifarnib at a dose of 300 mg twice daily and imatinib at a dose of 300 mg daily. Therapy was escalated following a ‘3 + 3’ phase 1 design and the maximum tolerated dose was defined as tipifarnib at a dose of 400 mg twice daily and imatinib at a dose of 400 mg daily. Therapy was administered for a median of 26 weeks (range, 3–150 weeks).

RESULTS.

Adverse events included diarrhea in 21 patients (81%) and nausea in 18 patients (69%), but were generally grade 2 or less (using the revised National Cancer Institute Common Toxicity Criteria). Grade 3–4 neutropenia and thrombocytopenia occurred in 11 patients (42%) and 8 patients (31%), respectively. Sixteen patients discontinued therapy (5 due to toxicity and 11 due to lack of response or disease progression). Hematologic responses were attained by 17 (68%) of 25 assessable patients. Nine patients (36%) also achieved a cytogenetic response (3 complete responses, 4 partial responses, and 2 minimal responses), including 4 patients harboring mutant Bcr‐Abl tyrosine kinases. One patient bearing the highly imatinib‐resistant T315I mutant achieved a partial cytogenetic response. The median response duration was 3 months (range, 2–30+ months).

CONCLUSIONS.

The combination of tipifarnib and imatinib is well tolerated and has activity against several Abl kinase domain mutants. Combinations of tipifarnib with more potent tyrosine kinase inhibitors warrant further investigation. © 2007 American Cancer Society.
Biologic significance of receptor‐binding cancer antigen expressed on SiSo cells (RCAS1) as a pivotal regulator of tumor growth through angiogenesis in human uterine cancer
Authors: Sonoda Kenzo , Miyamoto Shingo , Yamazaki Ayano , Kobayashi Hiroaki , Nakashima Manabu , Mekada Eisuke , Wake Norio
Published: September 2007

BACKGROUND.

The expression of receptor‐binding cancer antigen expressed on SiSo cells (RCAS1) is related significantly to the overall survival of patients with various cancers. RCAS1 reportedly induces apoptotic cell death in peripheral lymphocytes, which may contribute to the escape of tumor cells from immune surveillance. RCAS1 expression also has been related to tumor invasiveness and size in uterine cervical cancer. To clarify whether RCAS1 exacerbates tumor progression, the authors investigated the association between RCAS1 expression and tumor growth potential.

METHODS.

The authors constructed small interfering ribonucleic acid (RNA) (siRNA) to target RCAS1. After transfection of siRNA and the RCAS1‐encoding gene, growth of tumor cells was assessed in vitro and in vivo. The correlation between RCAS1 expression and angiogenesis was investigated in the transfected cells and in inoculated tumors from nude mice. In addition, the same association was investigated immunohistochemically with tissue samples from patients with uterine cervical cancer.

RESULTS.

Knockdown of RCAS1 expression by siRNA significantly suppressed the in vivo growth of SiSo and HOUA tumor cells (P < .005); however, in vitro cell growth was not affected significantly. Enhanced RCAS1 expression significantly promoted in vivo growth, but not in vitro growth, of tumors derived from COS‐7 cells (P = .0039). Introduction of the RCAS1‐encoding gene increased expression of vascular endothelial growth factor (VEGF). In uterine cervical cancer, RCAS1 expression was associated significantly with VEGF expression (P = .0407) and with microvessel density (P = .0108).

CONCLUSIONS.

RCAS1 may be a pivotal regulator of tumor growth through angiogenesis. Continued exploration of the biologic function of RCAS1 may allow the development of novel therapeutic strategies for uterine cancer. Cancer 2007. © 2007 American Cancer Society.
PEG‐IFN‐α‐2b therapy in BCR‐ABL–negative myeloproliferative disorders
Authors: Jabbour Elias , Kantarjian Hagop , Cortes Jorge , Thomas Deborah , Garcia‐Manero Guillermo , Ferrajoli Alessandra , Faderl Stefan , Richie Mary Ann , Beran Miloslav , Giles Francis , Verstovsek Srdan
Published: September 2007

BACKGROUND.

Interferon‐alpha (IFN‐α) has shown significant activity in the treatment of BCR‐ABL–negative myeloproliferative disorders (MPDs), particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG‐IFN‐α‐2b is a pegylated IFN‐α‐2b with a significant advantage over nonpegylated form in that it is administered once a week.

METHODS.

Thirty‐eight patients with BCR‐ABL–negative MPDs were treated with PEG‐IFN‐α‐2b, given subcutaneously weekly, at the starting dose of 3 μg/kg/wk for the first 14 patients and then 2 μg/kg/wk for the next 24 patients, with intent to treat patients as long as they benefited from the therapy.

RESULTS.

Median age was 54 years. Patient diagnoses were: 13 (34%) ET; 11 (29%) primary myelofibrosis (PMF); 5 (13%) BCR‐ABL–negative chronic myeloid leukemia (CML); 4 (10.5%) hypereosinophilic syndrome (HES); 4 (10.5%) PV; and 1 (3%) unclassified myeloproliferative disease (uMPD). Recorded grade 3–4 toxicities were related to fatigue, myelosuppression, and musculoskeletal pain. Ten (26%) patients stopped treatment because of toxicity. Thirteen (34%) patients achieved a complete remission, and 4 (11%) achieved a partial response. Only 1 patient with PMF responded. Median time to response was 5 months. Median duration of response was 20 months. Three patients had a sustained response for >24 months.

CONCLUSIONS.

PEG‐IFN‐α‐2b, with proper dose modifications, is effective in controlling disease in a significant proportion of BCR‐ABL–negative MPD patients, particularly ET and PV. However, toxicities encountered with PEG‐IFN‐α‐2b therapy are similar to those obtained with conventional IFN‐α, thus limiting the duration of therapy. Cancer 2007. © 2007 American Cancer Society.
PASSing the provenance challenge
Authors: Holland David A. , Seltzer Margo I. , Braun Uri , Muniswamy‐Reddy Kiran‐Kumar
Published: September 2007

Provenance‐aware storage systems (PASS) are a new class of storage system treating provenance as a first‐class object, providing automatic collection, storage, and management of provenance as well as query capabilities. We developed the first PASS prototype between 2005 and 2006, targeting scientific end users. Prior to undertaking the provenance challenge, we had focused on provenance collection and storage, without much emphasis on a query model or language. The challenge forced us to (quickly) develop a query model and infrastructure implementing this model. We present a brief overview of the PASS prototype and a discussion of the evolution of the query model that we developed for the challenge. Copyright © 2007 John Wiley & Sons, Ltd.
Analysis of Al2O3 Atomic Layer Deposition on ZrO2 Nanoparticles in a Rotary Reactor
Authors: McCormick J. A. , Rice K. P. , Paul D. F. , Weimer A. W. , George S. M.
Published: September 2007

Al2O3 atomic layer deposition (ALD) is analyzed on ZrO2 nanoparticles in a rotary reactor. This rotary reactor allows for static exposures and efficiently utilizes the reactants for ALD on high surface area nanoparticles. The Al2O3 ALD is performed using exposures to Al(CH3)3 and H2O reactants. The pressure transients during these exposures are examined using a sequence of reactant micropulses. These micropulses are less than the required exposures for the ALD surface chemistry to reach completion. The pressure transients during identical sequential Al(CH3)3 and H2O micropulses change as the surface chemistry progresses to completion. These pressure transients allow the required saturation reactant exposure to be determined to maximize reactant usage. The ZrO2 nanoparticles are coated using various numbers of Al(CH3)3 and H2O reactant exposures. The Al2O3 ALD‐coated ZrO2 nanoparticles are subsequently analyzed using a number of techniques including scanning electron microscopy (SEM), transmission electron microscopy (TEM), Auger electron spectroscopy (AES), scanning AES (SAES), and X‐ray photoelectron spectroscopy (XPS). The TEM images reveal very conformal Al2O3 ALD on the ZrO2 nanoparticles. The Al2O3 ALD thicknesses versus number of Al(CH3)3 and H2O reactant exposures yielded an Al2O3 ALD growth rate of 2.0 Å per reactant cycle. The AES and XPS results are consistent with an Al2O3 ALD film that completely and conformally covered the underlying ZrO2 nanoparticle. The SAES measurements show that the Al2O3 ALD films are continuous and homogeneous on the ZrO2 nanoparticles. These results demonstrate that a rotary reactor can successfully perform ALD with high reactant efficiency on high surface area nanoparticles.
CVD and Powders: A Great Potential to Create New Materials
Authors: Caussat B. , Vahlas C.
Published: September 2007

Powders play a major role in modern industrial activity, a role further increased by the development of nanomaterials and especially of nanoparticles. In this Editorial, Guest Editors Brigitte Caussat and Constantin Vahlas give an overview of the role played by CVD in the synthesis and functionalization of powder materials and introduce the papers in this Special Issue reporting on the current state of the art.
Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects
Authors: Loomes Kathleen M. , Stevens Stacey A. , O'Brien Megan L. , Gonzalez Dorian M. , Ryan Matthew J. , Segalov Michelle , Dormans Nicholas J. , Mimoto Mizuho S. , Gibson Joshua D. , Sewell William , Schaffer Alyssa A. , Nah Hyun‐Duck , Rappaport Eric F. , Pratt Stephen C. , Dunwoodie Sally L. , Kusumi Kenro
Published: September 2007

Mutations in the Notch1 receptor and delta‐like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3‐Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3‐Notch1 double heterozygous animals exhibited localized, segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant reduction of mandibular height and elongation of maxillary hard palate. Examination of somite‐stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray‐based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch‐regulated segmental or craniofacial development. Thus, Dll3‐Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders. Developmental Dynamics 236:2943–2951, 2007. © 2007 Wiley‐Liss, Inc.
Endoplasmic reticulum stress induced by tunicamycin disables germ layer formation in Xenopus laevis embryos
Authors: Yuan Li , Cao Ying , Knöchel Walter
Published: September 2007

Maintenance of endoplasmic reticulum (ER) homeostasis is essential for correct protein targeting and secretion. ER stress caused by accumulation of unfolded or misfolded proteins leads to disruption of cellular functions. We have investigated the effect of ER stress on Xenopus embryogenesis. ER stress induced by tunicamycin (TM) treatment of embryos resulted in defects affecting germ layer formation. We observed up‐regulation of ER stress response genes, enhanced cytoplasmic splicing of xXBP1 RNA, and increased rate of apoptosis. In animal cap assays, TM treatment inhibited mesoderm formation induced by overexpression of activin/nodal RNA but did not affect mesoderm formation induced by functional activin protein, suggesting that dysfunction of ER caused a failure in activin/nodal processing and/or secretion. The observation that activin protein renders mesoderm formation under ER stress strengthens the role of activin/nodal for mesoderm induction. The results underline the functional significance of ER homeostasis in germ layer formation during Xenopus embryogenesis. Developmental Dynamics 236:2844–2851, 2007 © 2007 Wiley‐Liss, Inc.
Is your “gene of interest” interesting?
Authors: Kiefer Julie C.
Published: September 2007

Has a large‐scale screen turned up a potential gene‐of‐interest that you know nothing about? Your computer is a portal to a wealth of information that can save you valuable time and resources. Freely available data can help to determine whether a particular gene is worthy of further research, and what direction that research should take. Presented here are approaches to mining the Internet, including searching popular model organism databases. The primer covers two typical scenarios: the gene of interest is well characterized, or mostly uncharacterized. Also featured are interviews with Monte Westerfield, PhD, Director of the Zebrafish Information Network (ZFIN) online database, and Principal Investigator of the Human Protein Reference Database (HPRD) project, Akhilesh Pandey, MD, PhD. Developmental Dynamics 236:2962–2969, 2007. © 2007 Wiley‐Liss, Inc.
Expression of the murine retinol dehydrogenase 10 (Rdh10) gene correlates with many sites of retinoid signalling during embryogenesis and organ differentiation
Authors: Cammas Laura , Romand Raymond , Fraulob Valérie , Mura Carole , Dollé Pascal
Published: September 2007

Retinoic acid acts as a signalling molecule regulating many developmental events in vertebrates. As this molecule directly influences gene expression by activating nuclear receptors, its patterns of synthesis have to be tightly regulated, and it is well established that at least three retinaldehyde dehydrogenases (RALDHs) are involved in such tissue‐specific synthesis. Whereas embryos from oviparous species can obtain retinaldehyde by metabolizing carotenoids stored in the yolk, placental embryos rely on retinol transferred from the maternal circulation. Here, we show that the gene encoding one of the murine retinol dehydrogenases, Rdh10, is expressed according to complex profiles both during early embryogenesis and organ differentiation. Many of its expression sites correlate with regions of active retinoid signalling and Raldh gene expression, especially with Raldh2 in the early presomitic and somitic mesoderm, retrocardiac and posterior branchial arch region, or later in the pleural mesothelium and kidney cortical region. Rdh10 also shows cell‐type and/or regional specificity during development of the palate, teeth, and olfactory system. During limb bud development, it may participate in retinoic acid production in proximal/posterior cells, and eventually in interdigital mesenchyme. These data implicate the retinol to retinaldehyde conversion as the first step in the tissue‐specific regulation of retinoic acid synthesis, at least in mammalian embryos. Developmental Dynamics 236:2899–2908, 2007. © 2007 Wiley‐Liss, Inc.
Regiospecific ortho‐Aromatic Hydroxylation via Cyclonickelation Using Hydrogen Peroxide and Other Oxygen Donors: Synthesis of Metalloazosalophens (Eur. J. Inorg. Chem. 27/2007)
Authors: Pattanayak Poulami , Lal Pratihar Jahar , Patra Debprasad , Burrows Andrew , Mohan Mary , Chattopadhyay Surajit
Published: September 2007

The cover picture shows the reaction sequence of an NiII‐assisted regiospecific ortho‐aromatic hydroxylation. Sequential events of orthonickelation, oxygen insertion into the Ni–C bond induced by H2O2 and demetallation have been demonstrated to be involved in the aromatic hydroxylation in 2‐(arylazo)aniline. The H2O2‐induced O insertion into the Ni–C bond led to the formation of metalloazosalophen analogues of metallosalophens for the first time. Details are discussed in the article by S. Chattopadhyay et al. on p. 4263 ff.
Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis
Authors: Nieuwenhuizen Willem F. , Duivenvoorden Ilse , Voshol Peter J. , Rensen Patrick C. N. , van Duyvenvoorde Wim , Romijn Johannes A. , Emeis Jef J. , Havekes Louis M.
Published: September 2007

The prevalence of dyslipidemia and obesity resulting from excess energy intake and physical inactivity is increasing. The liver plays a pivotal role in the systemic lipid homeostasis. Effective, natural dietary interventions that lower plasma lipids and promote liver health are needed. APOE*3Leiden mice were fed a Western‐type diet, supplemented with different sphingolipids, to determine their effect on plasma lipids and liver steatosis. Hepatic lipid levels and lipid‐related gene expression were also determined. Dietary sphingolipids dose‐dependently lowered both plasma cholesterol (C) and triglycerides (TG) in APOE*3Leiden mice. 1% Phytosphingosine (PS) reduced C and TG by 57 and 58%, respectively. PS (a) decreased the absorption of dietary C and free fatty acid but did not affect the intestinal TG lipolysis, (b) increased hepatic VLDL‐TG production whereas plasma lipolysis was not affected; and (c) increased the hepatic uptake of VLDL remnants. Hepatic mRNA levels indicated enhanced hepatic lipid synthesis and VLDL and LDL uptake. Livers of PS (1%) fed mice were lighter (−22%), less pale, and contained less cholesteryl ester (−61%) and TG (−56%). Furthermore, markers for liver inflammation (SAA) and liver damage (ALAT) were decreased by 74% and 79%, respectively in PS‐fed mice. Sphingolipids lower plasma C and TG and protect the liver from fat‐ and cholesterol‐induced steatosis. In a preliminary small double‐blind cross‐over study with six middle‐aged slightly overweight male volunteers the daily supplementation of one gram of PS to the diet resulted in a −9.8% (p = 0.0074) and – 13.2% (p = 0.0002) reduction of total C and LDL‐C, respectively. The C/HDL‐C ratio was not significantly affected (p = 0.0571). Due to the relatively low pre‐study levels of TG in the human volunteers, and the individual variability of TG levels, the TG lowering in humans was not significant in this first small study, but per individual there was a clear trend in TG lowering.
A novel method for the determination of acid value of vegetable oils
Authors: Li Shu‐Guo , Zhang Hui , Xue Wen‐Tong
Published: September 2007

The voltammetric behavior of naphthoquinone in the presence of free fatty acids (FFA) at the polypyrrole (PPy)‐modified electrode was investigated in an ethanol/1,2‐dichloroethane (3 : 1) solution containing 0.1 M LiClO4. A well‐defined new reduction peak appeared at a more positive potential and was higher than that obtained at the bare Pt electrode. Based on the fact that the new reduction peak current showed a good correlation with the concentration of fatty acids, an electroanalytical method for the acid value (AV) of vegetable oils was developed using the PPy‐modified electrode in linear potential sweep voltammetry. The experimental parameters were optimized to obtain a sensitive voltammetric response in this work. A linear calibration graph was obtained in the concentration range of 5.0×10–6–6×10–3 M for FFA (R = 0.993), with a sensitivity of 2.41×10–2 A L/mol and a detection limit of 1.2×10–6 M (S/N = 3). Each assay of vegetable oil sample took about 80 s. The developed method is applied to the AV determination of six commercial vegetable oils. The results well agreed with those obtained by the titration method. Compared to the conventional titration method, the proposed method is superior in sensitivity and accuracy and requires a small amount of vegetable oil sample, with no pretreatment.
Preliminary chemical characterization of Tunisian monovarietal virgin olive oils and comparison with Sicilian ones
Authors: Baccouri Olfa , Cerretani Lorenzo , Bendini Alessandra , Caboni Maria Fiorenza , Zarrouk Mokhtar , Pirrone Luigi , Miled Douja Daoud Ben
Published: September 2007

Work was carried out on the characterization of monovarietal virgin olive oils (VOO) from Tunisia and Sicily (Italy). The two main Tunisian VOO (cvv. Chétoui of the North and cv. Chemlali grown in the Center and some regions of the South) and three principal Sicilian VOO (cvv. Nocellara del Belice, Biancolilla and Cerasuola) were studied. Moreover, the Chétoui oils were tested in a rain‐fed control and an irrigation regime. All olive samples were picked at three different stages of ripeness. Analyses of major components (fatty acids and triacylglycerols) and minor ones (squalene, tocopherols and phenolic compounds) were carried out. Chétoui oils had a higher level of phenolic compounds followed by Chemlali. Generally, in the Sicilian oils these natural antioxidant contents were lower. These preliminary results indicate that it was possible to classify the Tunisian and Sicilian oils tested in their original growing area based on their chemical composition.
Lipid production by oleaginous Mucorales cultivated on renewable carbon sources
Authors: Papanikolaou Seraphim , Galiotou‐Panayotou Maria , Fakas Stylianos , Komaitis Michael , Aggelis George
Published: September 2007

Mortierella isabellina and Cunninghamella echinulata were cultivated on glucose‐, pectin‐, starch‐ and lactose‐based media. Culture on glucose at two initial C/N ratios favored lipid synthesis in the media with increased C/N. Starch was an adequate substrate for both molds, but lipid (in g/g of biomass) was produced in lower quantities compared with the glucose trial. Pectin was inadequate for C. echinulata whereas growth of M. isabellina was satisfactory (8.4 g/L), followed by moderate lipid production. Growth of C. echinulata on lactose was negligible, while that of M. isabellina was notable (9.5 g/L) although lipid in biomass was only 0.36 g/g. Hydrolytic enzymes (α‐amylase, polygalacturonase and β‐galactosidase) activities of both strains seemed to be low enough to saturate their metabolic capabilities. This seemed a major cause for the lower amount of lipid accumulated during growth on complex media compared with that on glucose. Cellular fatty acids of M. isabellina were oleic, linoleic and palmitic acid, while γ‐linolenic acid (GLA) was produced in low quantities. In C. echinulata grown on glucose, lactose or starch, GLA concentration was notable at the beginning and end of culture. Growth on pectin at the first growth steps was accompanied by the production of saturated fatty acids, the amount of which decreased thereafter.
Synthesis of Spirocyclic Pyridoazepines as Analogues of Galanthamine by Nucleophilic Aromatic Substitution of 3‐Substituted 2‐Chloropyridines
Authors: Vanlaer Sofie , De Borggraeve Wim M. , Compernolle Frans
Published: September 2007

In this report we describe the synthesis of spirocyclic pyridoazepines starting from easily available precursors. The key step of our synthesis is an intramolecular nucleophilic aromatic substitution of the appropriate 3‐substituted 2‐chloropyridines. The final compounds, designed as simplified analogues of the alkaloid galanthamine, showed significant acetylcholinesterase inhibition activity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)