bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcatheter arterial chemoembolization or chemoinfusion for unresectable intrahepatic cholangiocarcinoma
Authors: Kim Jin Hyoung , Yoon Hyun‐Ki , Sung Kyu‐Bo , Ko Gi‐Young , Gwon Dong Il , Shin Ji Hoon , Song Ho‐Young
Published: August 2008

BACKGROUND.

The role of transcatheter arterial chemoembolization (TACE) or transcatheter arterial chemoinfusion (TACI) for unresectable intrahepatic cholangiocarcinoma (ICC) has recently been questioned. The aim of the study was to evaluate the clinical efficacy of TACE or TACI in patients with unresectable ICC and to identify prognostic factors associated with clinical success.

METHODS.

From 1997 to 2007, 49 patients with unresectable ICC were treated with TACE (n = 124) or transcatheter arterial chemoinfusion (TACI) (n = 96). Tumor response was evaluated based on computed tomography scans obtained 1 month to 3 months after TACE or TACI. Factors associated with clinical success were evaluated using multivariate logistic regression analysis. Factors associated with the survival period were evaluated using multivariate Cox regression analysis.

RESULTS.

After treatment, 27 (55%) of the patients showed radiographic response. Multivariate analysis confirmed that tumor vascularity (odds ratio [OR], 31.2; P = .002) was the only independent factor associated with radiographic response. The median and mean survival periods in our study patients were 12 and 24 months. Multivariate Cox regression analyses showed that tumor size (OR, 2.64; P = .048), tumor vascularity (OR, 13.5; P < .001), and the Child‐Pugh class (OR, 3.65; P = .014) were the independent factors associated with the length of the survival period.

CONCLUSIONS.

Hepatic intra‐arterial chemotherapy is well tolerated and may be effective to prolong survival of patients with unresectable ICC. Tumor vascularity is significantly associated with radiographic response. Large tumor size, tumor hypovascularity, and Child‐Pugh class B were poor prognostic factors for determining the patient survival period. Cancer 2008. © 2008 American Cancer Society.
Molecular Logic Operations Based on Surfactant Nanoaggregates
Authors: Qian Junhong , Xu Yufang , Qian Xuhong , Zhang Shenyi
Published: August 2008

Two molecular logic gates, FS1 and FS2, which display a UV and fluorescence behavior that is dependent on the pH value and the sodium dodecyl sulfate (SDS) surfactant concentration, are demonstrated based on the intramolecular charge‐transfer mechanism. They are constructed according to the inorganic salts that induce transformation from premicelle to micelle. The absorption band of FS1 at 480 nm is significantly enhanced only when both SDS and Na2SO4 are the input at high concentrations, in accordance with an AND logic gate. The OR logic function can be realized in a 3.5 mM SDS/FS2 aqueous solution with SDS and Na2SO4 as inputs along with the emission intensity as output. Furthermore, half addition and half subtraction can be incorporated in FS1. This is facilitated by the surfactant, due to its versatility.
Rare Earth and Alkaline Earth Metal Complexes with Me2Si‐Bridged Cyclopentadienyl‐Imidazolin‐2‐Imine Ligands and Their Use as Constrained‐Geometry Hydroamination Catalysts
Authors: Panda Tarun K. , Hrib Cristian G. , Jones Peter G. , Jenter Jelena , Roesky Peter W. , Tamm Matthias
Published: August 2008

The imidazolin‐2‐imino‐functionalized tetramethylcyclopentadiene, 3‐H, has been prepared by the reaction of two equivalents of 1,3‐diisopropyl‐4,5‐dimethylimidazolin‐2‐imine (1) with 5‐(chlorodimethylsilyl)‐1,2,3,4‐tetramethyl‐1,3‐cyclopentadiene (2). The reactions of 3‐H with the trimethylsilylmethyl (neosilyl) [Ln(CH2SiMe3)3(THF)2] (Ln = Sc, Y, Lu) complexes afford tetramethylsilane and the constrained‐geometry [(η5:η1‐3)Ln(CH2SiMe3)2] (Ln = Sc, 4a; Ln = Y, 4b; Ln = Lu, 4c) complexes, whereas the analogousbis(trimethylsilyl)amido (HMDS) calcium complex, [(η5:η1‐3)Ca(HMDS)(THF)] (5), can be obtained from 3‐H and [Ca(HMDS)2(THF)2] with loss of hexamethyldisilazane, (Me3Si)2NH. The molecular structures of 4a–4c and 5 have been established by X‐ray diffraction analyses, which confirm in all cases the formation of complexes with a chelating Me2Si‐bridged cyclopentadienyl‐imidazolin‐2‐imine ligand. The presence of short Ln–N and Ca–N bonds is indicative of the strong electron‐donating capacity of the imidazolin‐2‐imino nitrogen atom, which is based on the ability of the imidazolium ring to effectively stabilize a positive charge. The rare earth metal complexes 4a–4c can be used as efficient catalysts for the hydroamination/cyclization reaction of terminal aminoalkenes and aminoalkynes.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
New Stack Design of Micro‐tubular SOFCs for Portable Power Sources
Authors: Suzuki T. , Funahashi Y. , Yamaguchi T. , Fujishiro Y. , Awano M.
Published: August 2008

Micro‐tubular solid oxide fuel cells (SOFCs) have high thermal stability and higher volumetric power density, which are considered to be ideal features for portable power sources and auxiliary power units for automobile. Here, we report a new stack design using anode supported micro‐tubular SOFCs with 2 mm diameter using Gd doped CeO2 (GDC) electrolyte, NiO‐GDC anode and (La, Sr)(Co, Fe)O3 (LSCF)‐GDC cathode. The new stack consists of three bundles with five tubular cells, sealing layers and interconnects and fuel manifolds. The performance of the stack whose volume is 1 cm3 was shown to be 2.8 V OCV and maximum power output of 1.5 W at 500 °C, applying air only by natural convection. The results also showed strong dependence of the fuel flow rates on the stack performance, which was correlated to the gas diffusion limitation.
Head and neck mucosal melanoma: Experience with 42 patients, with emphasis on the role of postoperative radiotherapy
Authors: Meleti Marco , Leemans C. René , de Bree Remco , Vescovi Paolo , Sesenna Enrico , van der Waal Isaäc
Published: August 2008

Background.

Treatment of head and neck mucosal melanoma remains a challenge. Surgery has traditionally been the main therapeutic approach. The role of postoperative radiotherapy has never been clearly established.

Methods.

The experience with a group of 42 patients (16 males, 26 females) with a primary head and neck mucosal melanoma is reported.

Results.

Eleven of 19 patients (57.9%) receiving surgery alone developed a regional lymphatic metastasis. For patients receiving postoperative radiotherapy (19 patients), regional metastatic spread occurred in 4 patients (21%). Percentages of local failure were 57.9% (11/19) and 26.3% (5/19) for patients treated with surgery alone and for those treated with surgery and radiotherapy, respectively. Distant metastases occurred in 10 of 19 patients (52.6%) receiving surgery alone and in 9 of 19 patients (47.3%) receiving both therapies.

Conclusions.

The present evaluation confirms a poor prognosis for patients with head and neck mucosal melanoma, independent of the treatment modality. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy
Authors: Rodriguez Cristina P. , Adelstein David J. , Rybicki Lisa A. , Saxton Jerrold P. , Lorenz Robert R. , Wood Benjamin G. , Strome Marshall , Esclamado Ramon M. , Lavertu Pierre , Carroll Marjorie A.
Published: August 2008

Background.

Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success.

Methods.

Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure.

Results.

The 5‐year Kaplan–Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1‐2 versus T3‐4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control.

Conclusion.

Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3‐4 tumors, it was infrequent and surgical salvage was effective. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
E‐cadherin loss and ΔNp73L expression in oral squamous cell carcinomas showing aggressive behavior
Authors: Foschini Maria P. , Cocchi Roberto , Morandi Luca , Marucci Gianluca , Pennesi Maria G. , Righi Alberto , Tosi Anna L. , de Biase Dario , Pession Annalisa , Montebugnoli Lucio
Published: August 2008

Background.

This article sought to investigate the existence of parameters useful for predicting lymph node metastases in cases of surgically resected oral squamous cell carcinomas (OSCCs).

Methods.

Fifty‐eight cases were studied for E‐cadherin and the truncated dominant‐negative isoform of p63 (ΔNp63) with immunohistochemistry. In addition, the p63 gene expression profile was evaluated by reverse transcriptase‐polymerase chain reaction (RT‐PCR) to disclose the presence of the truncated variant ΔNp73L.

Results.

E‐cadherin expression was the most powerful parameter related to the presence of lymph node metastases at presentation. Twenty‐four of 38 (63%) cases showing low E‐cadherin expression had lymph node metastases at presentation compared with 5 of 20 (25%) (p <.01) cases showing high E‐cadherin expression. The high predictive value was also maintained when a low expression of E‐cadherin was associated with immunohistochemical high expression of ΔNp63. The association between low E‐cadherin expression and ΔNp73L (as seen with reverse transcriptase‐polymerase chain reaction) was highly predictive for developing lymph node metastases, especially in small tumors (T1\T2). When this association occurred, metastases developed in 62.5% of cases during the follow‐up compared with 16.1% in those which did not show low E‐cadherin expression and presence of ΔNp73L.

Conclusion.

This study shows that low E‐cadherin expression is useful for predicting lymph node metastases in cases of OSCC. The predictive value is enhanced when low E‐cadherin positivity is associated with ΔNp63 and ΔNp73L expression. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Fc receptor‐like 1–5 molecules are similarly expressed in progressive and indolent clinical subtypes of B‐cell chronic lymphocytic leukemia
Authors: Kazemi Tohid , Asgarian‐Omran Hossein , Hojjat‐Farsangi Mohammad , Shabani Mahdi , Memarian Ali , Sharifian Ramazan Ali , Razavi Seyed Mohsen , Jeddi‐Tehrani Mahmood , Rabbani Hodjatallah , Shokri Fazel
Published: August 2008

Fc receptor‐like (FCRL) 1–5 molecules are exclusively expressed in B‐cells and have recently been considered as potential targets for immunotherapy of B‐cell malignancies. In this study, the expression pattern of FCRL1–5 molecules was investigated in Iranian patients with B‐cell chronic lymphocytic leukemia (B‐CLL). Our RT‐PCR results have demonstrated that all FCRL molecules, except FCRL4, were expressed in the vast majority of the patients with B‐CLL. However, comparison of the relative mRNA expression levels of FCRL between B‐CLL (n = 86) and elderly normal subjects (n = 10) revealed significantly lower expression levels of FCRL1 (p < 0.0001), FCRL3 (p = 0.01) and FCRL4 (p = 0.002), but not FCRL2 or FCRL5, in cases with B‐CLL. No significant differences were observed between the indolent and progressive subtypes of patients with B‐CLL. Comparison between the mutated and unmutated subtypes revealed a significantly higher expression level of FCRL3 (p = 0.017) in patients with mutated CLL. Surface and intracytoplasmic expression of FCRL1, 2, 4 and 5 in leukemic cells of 12 patients by flow cytometry revealed similar results to those obtained by RT‐PCR with a few exceptions. Thus, while FCRL4 was expressed in only 2 samples at intracytoplasmic level, FCRL1 and 2 were expressed in the majority of samples, both at surface and intracytoplasm. FCRL5 protein was also detected in 10 samples, but surface expression was confirmed in only 2. Analysis of B‐cells from 5 normal subjects by flow cytometry revealed higher expression levels of FCRL molecules compared to CLL. Our results indicate differential expression of FCRL molecules in B‐CLL and suggest the potential implication of FCRL1 and 2 for immunotherapeutic interventions. © 2008 Wiley‐Liss, Inc.
Clean synthesis of methyl N‐phenyl carbamate over ZnO‐TiO2 catalyst
Authors: Li Fang , Wang Yanji , Xue Wei , Zhao Xinqiang
Published: August 2008

BACKGROUND: Methyl N‐phenyl carbamate (MPC) is an intermediate for the preparation of methylene diphenyl diisocyanate (MDI), which is an important monomer for polyurethane synthesis. The synthesis of MPC by the reaction of aniline and dimethyl carbonate (DMC) is becoming more and more attractive. However, most of the catalysts used in MPC synthesis are homogeneous and not environment‐friendly. Therefore, it is important and necessary to develop a new kind of oxide catalyst, that is not only friendly to the environment, but also exhibits higher activity and longer service time.

RESULTS: A new heterogeneous catalyst, ZnO‐TiO2, was prepared for MPC synthesis. ZnO‐TiO2 catalyst with a molar ratio Ti/Zn = 2 and calcined at 673 K exhibited good catalytic activity: aniline conversion was 96.9% and MPC yield 66.7%.

CONCLUSION: ZnO‐TiO2 exhibits better catalytic activity than ZnO or TiO2 alone, which may result from the formation of ZnTiO3 and Zn2TiO4. Compared with ZnTiO3, Zn2TiO4 has better selectivity for MPC synthesis. Lewis acid sites with weaker acid strength favour MPC synthesis. The catalyst activity can be recovered almost completely by calcination. Copyright © 2008 Society of Chemical Industry
Supercritical antisolvent micronisation of synthetic all‐trans‐β‐carotene with tetrahydrofuran as solvent and carbon dioxide as antisolvent
Authors: Tavares Cardoso Miguel A , Antunes Sofia , van Keulen Frederik , Ferreira Bruno S , Geraldes Augusto , Cabral Joaquim MS , Palavra António MF
Published: August 2008

BACKGROUND: Supercritical antisolvent (SAS) micronisation of synthetic trans‐β‐carotene was studied using tetrahydrofuran (THF) as solvent and supercritical carbon dioxide (CO2) as antisolvent, with the objective of increasing its bioavailability and facilitating its dispersion in oil and emulsion formulations as a result of its smaller particle size. The micronised powder was analysed by scanning electron microscopy and high‐performance liquid chromatography. Micronisation experiments were performed in order to evaluate the effects of temperature (308.15–333.15 K), pressure (6.5–13 MPa) and concentration of the liquid solution (6–9 g L−1). The effect of the supercritical CO2/THF flow ratio in the range between 4 and 44 (on a mass basis) was also analysed. Determinations of equilibrium concentrations of β‐carotene in the CO2/THF mixture were also performed.

RESULTS: The particle size obtained ranged from 1 to 500 µm, with mean particle diameters around 100 µm. Three types of morphology were found in the precipitated powder: crystalline with superficial pores and leaf‐like appearance; crystalline with regular shapes and blade‐like edges; and crystalline without superficial pores and leaf‐like apearance. The Peng–Robinson equation of state was used to calculate the density of the CO2/THF binary mixture, and the solubility of β‐carotene in this mixture was correlated with its density.

CONCLUSION: The use of the SAS technique to micronise β‐carotene proved to be efficient, and the absence of degradation in the micronised powder allows the industrial application of this technique. Copyright © 2008 Society of Chemical Industry
Improvement of performance in label‐free quantitative proteome analysis with monolithic electrospray ionization emitter
Authors: Wang Fangjun , Ye Mingliang , Dong Jing , Tian Ruijun , Hu Lianghai , Han Guanghui , Jiang Xinning , Wu Ren'an , Zou Hanfa
Published: August 2008

The postcolumn void volume, which is introduced by the connecting tubing and void ESI emitter in the nanoflow LC coupled with MS/MS system (μLC‐MS/MS), is harmful for the analysis of peptides in shotgun proteome analysis. A new type of porous C12 monolithic ESI emitter was prepared to eliminate the disruption and mixing effects occurring in the connecting tubing and void emitter. It was demonstrated that the porous hydrophobic monolith inside the emitter played a key role in retaining the good peak profile, and the average peak capacity of the whole separation system increased 12.8% in contrast to commercially available void emitter. Then, the porous C12 monolithic emitter was applied in label‐free quantitative proteome analysis of two standard protein mixtures that were spiked into the tryptic digest of mouse livers extract. Compared to commercially available void ESI emitter, the number of proteins with reliable results in quantification increased greatly. And the relative quantities of the four standard proteins were all determined with the relative error ⪇6.8%. However, quantitative information of only three standard proteins could be obtained when void emitter was used.
Soil quality indices for evaluation of long‐term land use and soil management practices in semi‐arid sub‐tropical India
Authors: Masto R. E. , Chhonkar P. K. , Purakayastha T. J. , Patra A. K. , Singh D.
Published: August 2008

Land use changes and soil management can potentially alter soil quality. A study was conducted to assess the long‐term (>20 years) effects of perennial trees (PT), vegetable crops (VC), rice–wheat (RW) system, sewage‐irrigated fields (SF), maize–wheat (MW) system and uncultivated soils (US) on soil quality. Soil physical quality parameters were significantly affected only in the SF system when compared with the US soil, particularly for bulk density (BD 1·51 Mg m−3 in SF vs. 1·34 in US). Among chemical parameters, electrical conductivity was high in SF, and soil nutrients (N, P, K, S, Zn, Fe, Cu and Mn) were well above the critical limits of deficiency in all the systems. Soil parameters were integrated into soil quality indices (SQIs) by unscreened transformation and principal component analysis (PCA). SQI observed under each system were compared with the US to assess the degree of degradation. Mean SQI differences showed that PT (+16·02 per cent), VC (+4·80 per cent), RW (+10·04 per cent), and MW (+11·30 per cent) are aggrading, whereas SF (−2·06 per cent) is degrading with respect to the reference soil (US). Adoption of MW system proved to be better than traditional RW; and in general agricultural crops have a significant advantage than VC, in terms of maintaining soil quality. Sewage irrigation is not a sustainable practice and long‐term use may degrade the soil. Among the SQIs, PCA with nonlinear scoring function (NLSF) based SQI was effective in judging land degradation due to soil quality changes as affected by long‐term land use and soil management practices. Copyright © 2008 John Wiley & Sons, Ltd.
Slow and fast light: Controlling the speed of light using semiconductor waveguides
Authors: Mørk J. , Öhman F. , van der Poel M. , Chen Y. , Lunnemann P. , Yvind K.
Published: August 2008

We give an overview of slow‐ and fast‐light effects in semiconductor active waveguides. Experimental and theoretical results are presented, emphasizing the physics of these phenomena and the limitations imposed by the carrier dynamical processes.
Uniform Chitosan Microspheres for Potential Application to Colon‐Specific Drug Delivery
Authors: Choy Young Bin , Cheng Felice , Choi Hyungsoo , Kim Kyekyoon (Kevin)
Published: August 2008

Uniform chitosan microspheres have been fabricated and weakly crosslinked for potential applications in colon‐specific drug delivery. The effects of microsphere size, crosslinking density and electrostatic interactions between the drug and chitosan on drug release were studied, employing model drugs of different acidities. When the drug was basic, all chitosan spheres exhibited 100% release within 30 min. As the acidity of the drug increased, the release slowed down and depended on the crosslinking density and microsphere size. The release of weakly acidic drug was most suppressed for large spheres (35–38 µm), while the small spheres (23–25 µm) with higher crosslinking exhibited the most retention of highly acidic drug, indicating that they are a promising candidate for colon‐specific delivery.

magnified image
Localized Yielding Around Crack Tips of Double‐Network Gels
Authors: Tanaka Yoshimi , Kawauchi Yasunori , Kurokawa Takayuki , Furukawa Hidemitsu , Okajima Takaharu , Gong Jian Ping
Published: August 2008

Double‐network (DN) gels, a type of interpenetrating polymer network (IPN) consisting of rigid and flexible polymer components, exhibit two outstanding mechanical behaviors: yielding deformation of the entire specimen in tensile tests and quite high fracture energy in tearing tests. In this study, atomic force microscope (AFM) measurements were conducted on DN gels to determine the local Young's moduli immediately below the fracture surfaces Ef and below the usual molded surfaces Em, and compare the local modulus with bulk Young's moduli measured before and after the yielding deformation, denoted as Eh and Es, respectively. Em and Eh are around 0.1 MPa; Ef and Es, around 0.01 MPa, one order lower than the former two moduli. The order relation indicates that yielding deformation occurred locally around the crack tip of the DN gel during fracture. This supports the basic assumption of phenomenological models recently proposed to explain high fracture energy of DN gels. (H. R. Brown, Macromolecules 2007, 40, 3815–3818; Y. Tanaka, Europhys. Lett. 2007, 78, 56005).

magnified image
Reversible and Highly Selective Fluorescent Sensor for Mercury(II) Based on a Water‐Soluble Poly(para‐phenylene)s Containing Thymine and Sulfonate Moieties
Authors: Lv Jing , Ouyang Canbin , Yin Xiaodong , Zheng Haiyan , Zuo Zicheng , Xu Jialiang , Liu Huibiao , Li Yuliang
Published: August 2008

A novel water‐soluble poly(para‐phenylene) derivative with pendant thymine and sulfonate units (PBTS) has been prepared and its metal ion sensing properties have been investigated. PBTS exhibited a reversible and selective fluorescence quenching behavior toward Hg2+ ions as compared to Ag+, Ni2+, Mg2+, Ca2+, Hg2+, Co2+, Cd2+, Cu2+, Pb2+, Ba2+, Fe3+, and Zn2+ ions in aqueous solution. The fluorescence quenching resulted from the interpolymeric π‐stacking aggregation which was induced by the specific thymine–Hg–thymine interaction.

magnified image
Functionalization of Multi‐Walled Carbon Nanotubes by Thermo‐Grafting with α‐Methylstyrene‐Containing Copolymers
Authors: Jiang Shan , Deng Jianping , Yang Wantai
Published: August 2008

The present article reports on a strategy for the functionalization of multi‐walled carbon nanotubes (MWCNTs) by grafting with various polymer chains. Copolymers consisting of α‐methylstyrene (AMS) and a second monomer, that is glycidyl methacrylate (GMA) or styrene (St), were synthesized in advance. The copolymers were heated in the presence of MWCNTs in solution, decomposition of the AMS sequences occurred, providing macroradicals, which further attacked the double bonds on the MWCNT surfaces. Grafting of the copolymer chains onto the surface of the MWCNTs was thus achieved, as demonstrated by FT‐IR, XPS and Raman technologies. The resulting poly(AMS‐co‐GMA)‐g‐MWCNTs could be uniformly dispersed in N,N‐dimethylformamide (DMF) and acetone, and the poly(AMS‐co‐St)‐g‐MWCNTs also could be uniformly dispersed in DMF.

magnified image
Parameterization of tropospheric delay correction for mobile GNSS positioning: a case study of a cold front passage
Authors: Eresmaa R. , Nordman M. , Poutanen M. , Syrjärinne J. , Luntama J. ‐ P. , Järvinen H.
Published: August 2008

Numerical weather prediction (NWP) model output can be used for derivation of tropospheric delay correction in order to decrease positioning errors of Global Navigation Satellite System (GNSS) applications. In precise geodetic positioning it is possible to make use of corrections that are derived separately for all GNSS signal paths. Due to the large amounts of data, this approach is considered impractical from real‐time mobile positioning point of view. This article introduces several parameterization schemes that provide a zenith‐ and azimuth‐angle‐dependent description of tropospheric delay correction at a single observation site. These parameterization schemes are compared in a case study of a cold front passage. Inclusion of zenith‐angle dependency in the parameterization, instead of applying a prescribed mapping function, is found to be crucially important for accuracy. Parameterization can be further improved by applying a horizontal delay gradient and by separating the total tropospheric delay into hydrostatic and wet components. It is concluded that any increase of sophistication in the parameterization results in an increased parameterization accuracy. Copyright © 2008 Royal Meteorological Society
Mechanisms and sequelae of E‐cadherin silencing in hereditary diffuse gastric cancer
Authors: Barber M , Murrell A , Ito Y , Maia A‐T , Hyland S , Oliveira C , Save V , Carneiro F , Paterson AL , Grehan N , Dwerryhouse S , Lao‐Sirieix P , Caldas C , Fitzgerald RC
Published: August 2008

Around 25–40% of cases of hereditary diffuse gastric cancer (HDGC) are caused by heterozygous E‐cadherin (CDH1) germline mutations. The mechanisms for loss of the second allele still remain unclear. The aims of this study were to elucidate mechanisms for somatic inactivation of the wild‐type CDH1 allele and to seek evidence for cadherin switching. Archival tumour material was analysed from 16 patients with CDH1 germline mutations and seven patients fulfilling HDGC criteria without CDH1 germline mutations. The 16 CDH1 exons were sequenced. E‐cadherin promoter methylation was analysed by bisulphite sequencing and pyrosequencing and allele specificity was determined using polymorphic loci. Loss of heterozygosity was analysed using microsatellite markers. Cadherin expression levels were determined by real‐time RT–PCR and immunohistochemistry. Six of 16 individuals with germline mutations had at least one second hit mechanism. Two exonic mutations (exon 9 truncating, exon 3 missense) and four intronic mutations which may affect splicing were identified. Tumours from 4/16 individuals had promoter hypermethylation that was restricted to the A allele haplotype in three cases. E‐cadherin loss (mRNA and protein) generally correlated with identification of a second hit. In cases without germline E‐cadherin mutations there was no evidence for somatic mutation or significant promoter methylation. P‐cadherin (>25% cells) was expressed in 7/13 (54%) and 4/5 (80%) with and without germline CDH1 mutations, respectively, independent of complete E‐cadherin loss. Overall, inactivation of the second CDH1 allele occurs by mutation and methylation events. Methylation is commonly allele‐specific and is uncommon without germline mutations. P‐cadherin over‐expression commonly occurs in individuals with diffuse type gastric cancer. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Comparative expression of Hedgehog ligands at different stages of prostate carcinoma progression
Authors: Azoulay S , Terry S , Chimingqi M , Sirab N , Faucon H , Diez de Medina S Gil , Moutereau S , Maillé P , Soyeux P , Abbou C , Salomon L , Vacherot F , de La Taille A , Loric S , Allory Y
Published: August 2008

Recent studies have revealed the potential involvement of Hedgehog (Hh) signalling in proliferation and invasive behaviour of prostate carcinoma (PCa). The aim of this study was to specify the role of Sonic Hh (Shh), Desert Hh (Dhh) and Indian Hh (Ihh) in the natural history of PCa. Hh ligands expression was compared in primary hormone‐naive PCa (HNPC), hormone‐treated PCa (HTPC) and hormone‐refractory PCa (HRPC), using immunohistochemistry. Shh and Dhh were expressed by both epithelial and stromal cells of prostate tissues. Ihh was only expressed by stromal cells. For the three ligands, mRNA and immunostaining were not correlated. In HNPC, Shh epithelial expression was significantly associated with high Gleason scores (p = 0.03), metastatic lymph nodes (p = 0.004) and Dhh epithelial staining was associated with high pT stages (p = 0.003), seminal vesicle invasion (p = 0.03) and bladder neck invasion (p = 0.0008). Negative Shh staining in stromal cells was associated with high Gleason scores (p = 0.015), high pT stages (p = 0.01) and bladder neck invasion (p = 0.04). Concomitant absence of Shh and Dhh expression in stromal cells was an independent prognostic parameter for biological recurrence on multivariate analysis (p = 0.01). Epithelial expression of Shh and Dhh was increased in HTPC compared to HNPC (p = 0.02 and p = 0.04). Interestingly, in vitro, transcript analysis also showed increased expression of these 2 Hh ligands when androgen‐sensitive LNCaP cells were maintained in androgen‐free medium mimicking hormonal therapy. Epithelial expression of Dhh was increased (p < 0.0001) in HRPC compared to HNPC, while stromal expression of Shh and Dhh was decreased (p < 0.0001). In conclusion, the Hh signalling pathway is associated with pejorative pathological parameters in HNPC and is up‐regulated in epithelial cells of HTPC and HRPC. Moreover, the lack of Hh molecules in stromal cells seems to be associated with invasive and hormone‐refractory behaviours and suggests specific changes in stromal–epithelial crosstalks during PCa progression. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A critical role for TRAIL in resolution of granulomatous experimental autoimmune thyroiditis
Authors: Fang Y , Sharp GC , Yagita H , Braley‐Mullen H
Published: August 2008

Granulomatous experimental autoimmune thyroiditis (G‐EAT) is induced by mouse thyroglobulin (MTG)‐sensitized splenocytes activated in vitro with MTG and IL‐12. Thyroid lesions reach maximal severity 20 days after cell transfer, and usually resolve or progress to fibrosis by day 60 depending on the extent of thyroid damage at day 20. Our previous studies indicated that neutralization of TNF‐α or FasL had no effect on G‐EAT induction, but neutralization of TNF‐α promoted, while neutralization of FasL inhibited, G‐EAT resolution. TNF‐related apoptosis‐inducing ligand (TRAIL) is a member of the TNF superfamily. This study was undertaken to define the role of endogenous TRAIL in G‐EAT development and/or resolution. Neutralization of endogenous TRAIL had little effect on G‐EAT induction, but significantly inhibited G‐EAT resolution and increased thyroid fibrosis. This correlated with higher expression of pro‐inflammatory cytokines and preferential expression of the pro‐apoptotic molecule TRAIL, and anti‐apoptotic molecules FLIP and Bcl‐xL on inflammatory cells in thyroids of anti‐TRAIL‐treated recipients. The results suggest that endogenous TRAIL is not required for G‐EAT development in recipients, but is critical for G‐EAT resolution. Endogenous TRAIL might promote resolution, at least in part, through modulation of the balance between pro‐ and anti‐inflammatory cytokines, and the expression pattern of pro‐ and anti‐apoptotic molecules of thyroid epithelial cells (TECs) and inflammatory cells. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Silica‐filled polypropylene composites: The effect of ethylene diamine dilaurate and maleic anhydride grafted polypropylene on mechanical properties, water absorption, morphology, and thermal properties
Authors: Suryadiansyah  , Ismail H. , Azhari B.
Published: August 2008

The effect of two compatibilizers, i.e. ethylene diamine dilaurate (EDD) and maleic anhydride grafted polypropylene (MAPP) on the mechanical properties, water absorption, morphology, and thermal properties of silica‐filled polypropylene (PP/Sil) composites were studied. The results show that the tensile, impact and flexural strengths (up to 2 php), Young's modulus, and elongation at break (Eb) increased with increasing EDD content. However, increasing MAPP content increases the tensile strength, Young's modulus, impact and flexural strengths, and water absorption resistance. At a similar compatibilizer content, EDD exhibits higher Eb, impact and flexural strengths but lowers tensile strength, Young's modulus, and water absorption resistance compared with MAPP. Scanning electron microscopy study of tensile fractured surfaces exhibits the evidence of better silica‐PP adhesion with MAPP and EDD compared with the similar composites but without compatibilizer. Fourier transform infra red spectra provide an evidence of interaction between EDD or MAPP with PP/Sil composites. Termogravimetry analysis results indicate that the addition of EDD or MAPP slightly increases the thermal stability of PP/Sil composites. Differential scanning calorimetry also indicates that PP/Sil composites with EDD or MAPP have higher heat fusion (ΔHf(com)) and crystallinity (Xcom) than similar composites but without compatibilizer. POLYM. COMPOS., 2008. © 2008 Society of Plastics Engineers
Crystallization behavior and mechanical properties of polypropylene/modified carbon black composites
Authors: Zhu Ping , Chen Jing , Wu Chifei
Published: August 2008

Carbon black (CB) modified with small organic molecules was filled in polypropylene (PP) matrix. The crystallization behavior and mechanical properties of PP/modified CB (MCB) composites were investigated. Compared with the original CB, MCB could be dispersed uniformly in smaller particle sizes in PP matrix, and MCB could act as a more effective nucleating, toughening, and reinforcing agent when it was filled in PP at low concentrations. Further increasing of MCB particles in PP matrix resulted in the decrease of impact and tensile strength of PP/MCB composites. It was inferred from DSC results that the existence of CB vand MCB in PP matrix could result in the decrease of crystallite size and degree of perfection of PP. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers
Preparation and microwave characterization of PTFE/PEEK blends
Authors: Rajani K.V. , Rajesh S. , Murali K.P. , Mohanan P. , Ratheesh R.
Published: August 2008

Present paper describes the preparation and characterization of the PTFE / PEEK blends. The surface morphology of different volume percentage of PTFE/PEEK blends is investigated using Scanning Electron Microscopy. The permittivity and loss tangent of the blends up to 40 MHz are studied using a Precision Impedance Analyzer. The variation of permittivity with respect to temperature (τεr) of the composite blends are also measured in the 0–100°C temperature region using a microprocessor controlled hot and cold chamber. The microwave dielectric properties of the polymer blends are studied in the X‐band (8.2–12.4 GHz) region by waveguide cavity perturbation technique using a Vector Network Analyzer. Rectangular cavity resonator is used to measure the complex permittivity of the PTFE/PEEK blends. Different modeling approaches are used to predict the theoretical permittivity of the blends and the results are compared with the experimental values. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers
Tensile properties of LDPE + Boehmite composites
Authors: Brostow Witold , Datashvili Tea , Huang Bernard , Too Jonathan
Published: August 2008

Effect of interfacial interactions on mechanical properties of composites of low‐density polyethylene reinforced with micrometric Boehmite powders were studied in combination with two silane coupling agents vinyltri(2‐methoxyethoxy)‐silane (VTMES)‐SCA 972 and 3‐(trimethoxysilyl)‐propylmethacrylate (3MPS)‐SCA 989. Samples were prepared via melt mixing followed by compression or injection molding. Morphology and mechanical behavior of the composites were investigated as a function of the filler loading. The modulus of the composites increases with increasing contents of micrometric Boehmite particles. Environmental scanning electron microscopy (ESEM) examination reveals formation of fibrous structures upon addition of the treated micro fillers. We presume the fibrillation of the LDPE phase is related to changes of the matrix viscosity. Improvements in mechanical properties are attributed to homogeneous dispersion and good interfacial adhesion between the filler and the matrix, as evidenced by ESEM. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers
Flow cytometry‐assisted purification and proteomic analysis of the corticotropes dense‐core secretory granules
Authors: Gauthier Daniel J. , Sobota Jacqueline A. , Ferraro Francesco , Mains Richard E. , Lazure Claude
Published: August 2008

The field of organellar proteomics has emerged as an attempt to minimize the complexity of the proteomics data obtained from whole cell and tissue extracts while maximizing the resolution on the protein composition of a single subcellular compartment. Standard methods involve lengthy density‐based gradient and/or immunoaffinity purification steps followed by extraction, 1‐DE or 2‐DE, gel staining, in‐gel tryptic digestion, and protein identification by MS. In this paper, we present an alternate approach to purify subcellular organelles containing a fluorescent reporter molecule. The gel‐free procedure involves fluorescence‐assisted sorting of the secretory granules followed by gentle extraction in a buffer compatible with tryptic digestion and MS. Once the subcellular organelle labeled, this procedure can be done in a single day, requires no major modification to any instrumentation and can be readily adapted to the study of other organelles. When applied to corticotrope secretory granules, it led to a much enriched granular fraction from which numerous proteins could be identified through MS.
Laser desorption 7.87 eV postionization mass spectrometry of antibiotics in Staphylococcus epidermidis bacterial biofilms
Authors: Gasper Gerald L. , Carlson Ross , Akhmetov Artem , Moore Jerry F. , Hanley Luke
Published: August 2008

This paper describes the development of laser desorption 7.87 eV vacuum UV (VUV) postionization MS to detect antibiotics within intact bacterial colony biofilms. As >99% of the molecules ejected by laser desorption are neutrals, VUV photoionization of these neutrals can provide significantly increased signal as compared to the detection of directly emitted ions. Postionization with VUV radiation from the molecular fluorine laser single photon ionizes laser desorbed neutrals with ionization potentials below the 7.87 eV photon energy. Antibiotics with structures indicative of sub‐7.87 eV ionization potentials were examined for their ability to be detected by 7.87 eV laser desorption postionization MS. Tetracycline, sulfadiazine, and novobiocin were successfully detected neat as dried films physisorbed on porous silicon oxide substrates. Tetracycline and sulfadiazine were then detected within intact Staphylococcus epidermidis colony biofilms, the former with LOD in the micromolar concentration range.
Molecular dynamics guided study of salt bridge length dependence in both fluorinated and non‐fluorinated parallel dimeric coiled‐coils
Authors: Pendley Scott S. , Yu Yihua B. , Cheatham Thomas E.
Published: August 2008

The α‐helical coiled‐coil is one of the most common oligomerization motifs found in both native and engineered proteins. To better understand the stability and dynamics of the coiled‐coil motifs, including those modified by fluorination, several fluorinated and nonfluorinated parallel dimeric coiled‐coil protein structures were designed and modeled. We also attempt to investigate how changing the length and geometry of the important stabilizing salt bridges influences the coiled‐coil protein structure. Molecular dynamics (MD) and free energy simulations with AMBER used a particle mesh Ewald treatment of the electrostatics in explicit TIP3P solvent with balanced force field treatments. Preliminary studies with legacy force fields (ff94, ff96, and ff99) show a profound instability of the coiled‐coil structures in short MD simulation. Significantly, better behavior is evident with the more balanced ff99SB and ff03 protein force fields. Overall, the results suggest that the coiled‐coil structures can readily accommodate the larger acidic arginine or S‐2,7‐diaminoheptanedoic acid mutants in the salt bridge, whereas substitution of the smallerL‐ornithine residue leads to rapid disruption of the coiled‐coil structure on the MD simulation time scale. This structural distortion of the secondary structure allows both the formation of large hydration pockets proximal to the charged groups and within the hydrophobic core. Moreover, the increased structural fluctuations and movement lead to a decrease in the water occupancy lifetimes in the hydration pockets. In contrast, analysis of the hydration in the stable dimeric coiled‐coils shows high occupancy water sites along the backbone residues with no water occupancy in the hydrophobic core, although transitory water interactions with the salt bridge residues are evident. The simulations of the fluorinated coiled‐coils suggest that in some cases fluorination electrostatically stabilizes the intermolecular coiled‐coil salt bridges. Structural analyses also reveal different side chain rotamer preferences for leucine when compared with 5,5,5,5′,5′,5′‐hexafluoroleucine mutants. These observed differences in the side chain rotamer populations suggest differential changes in the side chain conformational entropy upon coiled‐coil formation when the protein is fluorinated. The free energy of hydration of the isolated 5,5,5,5′,5′,5′‐hexafluoroleucine amino acid is calculated to be 1.1 kcal/mol less stable than leucine; this hydrophobic penalty in the monomer may provide a driving force for coiled‐coil dimer formation. Estimation of the ellipticity at 222 nm from a series of snapshots from the MD simulations with DicroCalc shows distinct increases in the ellipticity when the coiled‐coil is fluorinated, which suggests that the helicity in the folded coiled‐coils is greater when fluorinated. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Building alternate protein structures using the elastic network model
Authors: Yang Qingyi , Sharp Kim A.
Published: August 2008

We describe a method for efficiently generating ensembles of alternate, all‐atom protein structures that (a) differ significantly from the starting structure, (b) have good stereochemistry (bonded geometry), and (c) have good steric properties (absence of atomic overlap). The method uses reconstruction from a series of backbone framework structures that are obtained from a modified elastic network model (ENM) by perturbation along low‐frequency normal modes. To ensure good quality backbone frameworks, the single force parameter ENM is modified by introducing two more force parameters to characterize the interaction between the consecutive carbon alphas and those within the same secondary structure domain. The relative stiffness of the three parameters is parameterized to reproduce B‐factors, while maintaining good bonded geometry. After parameterization, violations of experimental CαCα distances and CαCαCα pseudo angles along the backbone are reduced to less than 1%. Simultaneously, the average B‐factor correlation coefficient improves to R = 0.77. Two applications illustrate the potential of the approach. (1) 102,051 protein backbones spanning a conformational space of 15 Å root mean square deviation were generated from 148 nonredundant proteins in the PDB database, and all‐atom models with minimal bonded and nonbonded violations were produced from this ensemble of backbone structures using the SCWRL side chain building program. (2) Improved backbone templates for homology modeling. Fifteen query sequences were each modeled on two targets. For each of the 30 target frameworks, dozens of improved templates could be produced In all cases, improved full atom homology models resulted, of which 50% could be identified blind using the D‐Fire statistical potential. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Turns revisited: A uniform and comprehensive classification of normal, open, and reverse turn families minimizing unassigned random chain portions
Authors: Koch Oliver , Klebe Gerhard
Published: August 2008

Turns are irregular secondary structure elements with a hydrogen bond or a specific Cα‐Cα distance between the first and the last residue. They are up to six residues in length. Here, we present a uniform classification for all normal (COi – NHi+n hydrogen bond), open (a Cαi‐Cαi+n distance up to 10 Å), and reverse (NHi – COi+i hydrogen bond) turn families based on current structural data. Considering the large amount of data evaluated, this classification likely covers quite comprehensively most of the possible conformations of turns. All turn structures of a nonredundant dataset of 1903 protein chains were retrieved using Relibase and clustered using emergent self‐organizing maps. This leads to three normal, four open, and five reverse turn families with several new turn‐types. Based on the amino acid propensities, the achieved separation into normal, open, and reverse turn families seems convincing. In combination with β‐sheet and helix classification on average 96% of the given protein chain can now be successfully classified. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Docking and scoring with alternative side‐chain conformations
Authors: Hartmann Christoph , Antes Iris , Lengauer Thomas
Published: August 2008

We describe a scoring and modeling procedure for docking ligands into protein models that have either modeled or flexible side‐chain conformations. Our methodical contribution comprises a procedure for generating new potentials of mean force for the ROTA scoring function which we have introduced previously for optimizing side‐chain conformations with the tool IRECS. The ROTA potentials are specially trained to tolerate small‐scale positional errors of atoms that are characteristic of (i) side‐chain conformations that are modeled using a sparse rotamer library and (ii) ligand conformations that are generated using a docking program. We generated both rigid and flexible protein models with our side‐chain prediction tool IRECS and docked ligands to proteins using the scoring function ROTA and the docking programs FlexX (for rigid side chains) and FlexE (for flexible side chains). We validated our approach on the forty screening targets of the DUD database. The validation shows that the ROTA potentials are especially well suited for estimating the binding affinity of ligands to proteins. The results also show that our procedure can compensate for the performance decrease in screening that occurs when using protein models with side chains modeled with a rotamer library instead of using X‐ray structures. The average runtime per ligand of our method is 168 seconds on an Opteron V20z, which is fast enough to allow virtual screening of compound libraries for drug candidates. Proteins 2009. © 2008 Wiley‐Liss, Inc.