bluuebunny/crossref_metadata_2025 huggingface dataset:
Aromaticity: Molecular‐Orbital Picture of an Intuitive Concept
Authors: Pierrefixe Simon C. A. H. , Bickelhaupt F. Matthias
Published: June 2007

Geometry is one of the primary and most direct indicators of aromaticity and antiaromaticity: a regular structure with delocalized double bonds (e.g., benzene) is symptomatic of aromaticity, whereas a distorted geometry with localized double bonds (e.g., 1,3‐cyclobutadiene) is characteristic of antiaromaticity. Here, we present a molecular‐orbital (MO) model of aromaticity that explains, in terms of simple orbital‐overlap arguments, why this is so. Our MO model is based on accurate Kohn–Sham DFT analyses of the bonding in benzene, 1,3‐cyclobutadiene, cyclohexane, and cyclobutane, and how the bonding mechanism is affected if these molecules undergo geometrical deformations between regular, delocalized ring structures, and distorted ones with localized double bonds. We show that the propensity of the π electrons is always, that is, in both the aromatic and antiaromatic molecules, to localize the double bonds, against the delocalizing force of the σ electrons. More importantly, we show that the π electrons nevertheless decide about the localization or delocalization of the double bonds. A key component of our model for uncovering and resolving this seemingly contradictory situation is to analyze the bonding in the various model systems in terms of two interpenetrating fragments that preserve, in good approximation, their geometry along the localization/delocalization modes.
One‐Step Synthesis of Highly Water‐Soluble Magnetite Colloidal Nanocrystals
Authors: Ge Jianping , Hu Yongxing , Biasini Maurizio , Dong Chungli , Guo Jinghua , Beyermann Ward P. , Yin Yadong
Published: June 2007

A high‐temperature solution‐phase hydrolysis approach has been developed for the synthesis of colloidal magnetite nanocrystals with well‐controlled size and size distribution, high crystallinity, and high water solubility. The synthesis was accomplished by the hydrolysis and reduction of iron(III) cations in diethylene glycol with a rapidly injected solution of sodium hydroxide at an elevated temperature. The high reaction temperature allows for control over size and size distribution and yields highly crystalline products. The superior water solubility is achieved by using a polyelectrolyte, that is, poly(acrylic acid) as the capping agent, the carboxylate groups of which partially bind to the nanocrystal surface and partially extend into the surrounding water. The direct synthesis of water‐soluble nanocrystals eliminates the need for additional surface modification steps which are usually required for treating hydrophobic nanocrystals produced in nonpolar solvents through the widely recognized pyrolysis route. The abundant carboxylate groups on the nanocrystal surface allow further modifications, such as bioconjugation, as demonstrated by linking cysteamine to the particle surface. The monodisperse, highly water‐soluble, superparamagnetic, and biocompatible magnetite nanocrystals should find immediate important biomedical applications.
Characterisation of a Novel Growth Hormone Variant Comprising a Thioether Link between Cys182 and Cys189
Authors: Datola Antonio , Richert Sophie , Bierau Horst , Agugiaro David , Izzo Anna , Rossi Mara , Cregut David , Diemer Hélène , Schaeffer Christine , Van Dorsselaer Alain , Giartosio Carlo Emanuele , Jone Carl
Published: June 2007

A novel variant of recombinant human growth hormone (r‐hGH), isolated from biopharmaceutical preparations produced in E. coli, was identified and characterised. This variant contains a nonreducible thioether bridge near the C terminus between Cys182 and Cys189 and was characterised using various analytical techniques. As previous work by Cunningham and Wells (1993) highlighted the involvement of several residues in this part of the sequence in the binding and affinity of the molecule to its receptor, the presence of this modified intramolecular link may have important implications with regard to the biological behaviour of the molecule. Furthermore, as the conversion of a disulfide into a thioether was previously reported for a therapeutic monoclonal antibody (Tous et al., 2005), this may imply that disulfide bridges located in this part of the molecule have a generic susceptibility to thioether formation. This in turn is relevant to the biopharmaceutical industry for monitoring the integrity of disulfide bridges near the protein C terminus. The present study exhibits a state of the art physicochemical investigation for the unequivocal elucidation of a novel structure involving peptide mapping with mass spectrometry and de novo peptide sequencing. Changes in the higher order structure of the molecule were highlighted by near UV circular dichroism and molecular modelling.
Validation of the 6thedition AJCC pancreatic cancer staging system
Authors: Bilimoria Karl Y. , Bentrem David J. , Ko Clifford Y. , Ritchey Jamie , Stewart Andrew K. , Winchester David P. , Talamonti Mark S.
Published: June 2007

BACKGROUND

With the development of stage‐specific treatments for pancreatic cancer, controversies exist concerning optimal clinical and pathologic staging. The most recent edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 6thEdition included some notable modifications. In anticipation of the 7thedition's publication, the authors evaluated the predictive ability of the current pancreatic adenocarcinoma staging system.

METHODS

By using the National Cancer Data Base (1992–1998), 121,713 patients were identified with pancreatic adenocarcinoma. All patients were restaged by AJCC 6thedition guidelines. Stage‐specific overall survival was estimated by using the Kaplan‐Meier method and compared with log‐rank tests. Concordance indices were calculated to evaluate the discriminatory power of the staging system. Cox modeling was used to determine the relative impact of T, N, and M classification on survival.

RESULTS

For all patients, there was 5‐year survival discrimination by stage (P< .0001). For patients who underwent pancreatectomy, stage predicted 5‐year survival: stage IA, 31.4%; IB, 27.2%; IIA, 15.7%; IIB, 7.7%; III, 6.8%; IV, 2.8% (P< .0001). The concordance index for the staging system was 0.631 for all patients, 0.613 for those who underwent pancreatectomy, and 0.596 for patients who did not undergo resection. In patients who underwent pancreatectomy, tumor size, nodal status, and distant metastases were independent predictors of survival (P< .0001).

CONCLUSIONS

This is the first large‐scale validation of the pancreatic cancer staging system. AJCC 6thedition staging guidelines are accurate with respect to survival. Further investigation is needed to integrate new molecular and biochemical markers into the staging scheme. Cancer 2007; 110:738–44. © 2007 American Cancer Society.
Enabling service adaptability with versatile anycast
Authors: Szymaniak Michal , Pierre Guillaume , Simons‐Nikolova Mariana , van Steen Maarten
Published: June 2007

We present versatile anycast, which allows a service running on a varying collection of nodes scattered over a wide‐area network to present itself to the clients as one running on a single node. Providing a single logical address enables the client‐side software to preserve the traditional service access model based on single access points. At the same time, the dynamic composition of anycast groups implemented by versatile anycast enables the server‐side service infrastructure to evolve and adapt to changing network conditions. We implement versatile anycast using Mobile IPv6, which decouples the logical addresses of mobile nodes from their physical location. We exploit that decoupling to implement logical
service addresses that are not bound to any physical nodes, and employ standard MIPv6 mechanisms to dynamically map each such address onto individual service nodes. Our solution enables a service to transparently hand off clients among the service nodes at the network level while preserving optimal routing between the clients and the service nodes. We demonstrate that the overhead of versatile anycasting is very low. In particular, the client‐perceived handoff time is shown to be a linear function of the latencies among the client and the service nodes participating in the handoff. Copyright © 2007 John Wiley & Sons, Ltd.
Role of direct immunofluorescence on Tzanck smears in pemphigus vulgaris
Authors: Aithal Vijay , Kini Usha , Jayaseelan Elizabeth
Published: June 2007

The Tzanck smear is a simple, sensitive, and rapid test to diagnose pemphigus vulgaris (PV), a life threatening autoimmune blistering disorder. The presence of acantholytic cells in cytology is indicative of but not specific for PV. Hence, a direct Immunofluorescence (DIF) test to demonstrate immunoglobulin deposits on the acantholytic cells would make the Tzanck test more specific, in addition to being a rapid test. Twenty untreated patients with PV confirmed histopathologically were enrolled to evaluate the efficacy of using DIF technique using IgG on Tzanck smear samples. The DIF smears were compared with DIF on skin biopsies in the same patient. This prospective pilot study approved by the institutional ethics committee was carried out in a tertiary health care hospital in a developing country. Of the 15 patients presenting within 3 mo of onset of the illness, 40% (n = 6) showed DIF positivity on Tzanck smear, when compared with 46.67% (n = 7) on skin biopsy. On the other hand, of the five patients presenting beyond 3 mo of their illness, only 20% (n = 2) showed positivity on Tzanck, when compared with all 100% (n = 5) on skin biopsy. The study, thus, suggests that DIF on skin biopsy is comparable to biopsy in diagnosing early PV. This preliminary study proposes that the use of DIF on Tzanck smear is a simple, rapid, painless, and user‐friendly out‐patient procedure for the diagnosis of early PV, even for relatively inaccessible lesions in the oral cavity and flexural regions. This methodology would be of great help in outlying and rural facilities lacking proper histological equipment, thus avoiding the need for a surgical or punch biopsy or heavy investment in laboratory equipment and expertise. Probable reasons for DIF negativity on Tzanck smears are also discussed. Diagn. Cytopathol. 2007;35:403–407. © 2007 Wiley‐Liss, Inc.
Primary pure squamous cell carcinoma of the breast diagnosed by fine‐needle aspiration cytology: A case study using liquid‐based cytology
Authors: Vera‐Alvarez J. , García‐Prats M. D. , Marigil‐Gómez M. , Abascal‐Agorreta M. , López‐López J. I. , Ramón‐Cajal J. M.
Published: June 2007

Pure primary squamous cell carcinoma (SCC) is an extremely rare type of breast tumor. We report one of such cases in a 32‐year‐old woman, diagnosed by fine‐needle aspiration cytology (FNAC). Aspiration smears were characterized by squamous cells, both isolated and in aggregates, at various stages of maturation. The tumor was excised, and the histologic sections confirmed the cytologic diagnosis. Pure primary SCC of the breast has a distinctive cytomorphologic appearance, and diagnosis of this tumor by FNAC is possible. For its diagnosis, the exclusion of SCC of local cutaneous structures and metastasis of distant squamous carcinoma are mandatory. Diagn. Cytopathol. 2007;35:429–432. © 2007 Wiley‐Liss, Inc.
Fine needle aspiration cytology of unsuspected metastatic hurthle cell carcinoma of the thyroid and its pitfalls: A report of two cases
Authors: Lallu Sharda , Naran Sarla , Bethwaite Peter
Published: June 2007

We discuss two cases of unsuspected metastatic thyroid carcinoma of Hurthle cell type, presenting as subcutaneous masses in the occipital scalp and supra‐acetabular region of the right ilium; clinically suspected to be a lipoma and a vascular tumour, respectively. These two cases were initially investigated by fine‐needle aspiration cytology. In case 1, a definitive diagnosis of metastatic Hurthle cell carcinoma was made based on cell block preparation and positive immunohistochemical stains for thyroglobulin and thyroid transcription factor‐1. Case 2 was reported as suggesting an oncocytic process, metastatic Hurthle cell lesion. The filter preparations from both cases showed compact sheets and individual large polygonal cells with voluminous granular cytoplasm, eccentric nuclei with minimal atypia and bland chromatin. Scattered haemosiderin‐laden macrophages and cystic debris were also identified in both cases. These cases are of interest as the bland cytologic features may lead to an erroneous benign diagnosis. Immunohistochemistry aids the definitive diagnosis of metastatic Hurthle cell carcinoma of thyroid especially when the presence of a previous thyroid lesion is not communicated to the laboratory. Diagn. Cytopathol. 2007;35:439–443. © 2007 Wiley‐Liss, Inc.
Fine‐needle aspiration cytologic features of four special types of breast cancers: Mucinous, medullary, apocrine, and papillary
Authors: Haji Bahiyah E. , Das Dilip K. , Al‐Ayadhy Bushra , Pathan Shahed K. , George Sara G. , Mallik Mrinmay K. , Abdeen Suad M.
Published: June 2007

Recognition of special types of breast cancers by fine‐needle aspiration (FNA) cytology may have prognostic implications but some difficulties still exist in the ability of cytopathologists to determine the tumor subtypes. Detailed cytomorphological features were studied in the four special and unusual types of breast cancer cases (8 cases of mucinous, 9 medullary, 9 apocrime, and 11 papillary) and compared between themselves and with those of 32 duct cell carcinomas, not otherwise specified (NOS). Papillary carcinomas were also compared with 10 benign papillary lesions. The significance of the differences was determined using Fishers' Exact Test of Probability. In mucinous carcinoma, the frequency of signet ring cells (62.5%), and background pools of mucin (87.5%) were significantly higher than those of duct cell carcinoma (NOS), medullary carcinoma, apocrine carcinoma, and papillary carcinoma (P = 0.0408 to < 0.0001). In medullary carcinomas, lymphomononuclear cell infiltration (100.0%) was observed in significantly higher number of cases than in papillary, mucinous, and apocrine types (P < 0.0001). Further, moderate to marked nuclear pleomorphism (100.0%) and nuclear irregularity (77.8%) was significantly higher than those of mucinous carcinoma and papillary carcinoma (P = 0.0294 to <0.0003). Abnormal apocrine cells and papillary formation, characterizing all the apocrine carcinomas and papillary carcinomas, respectively, were present in significantly lower number in other variants and in duct cell carcinoma (NOS) (P = 0.0002 to <0.0001). Glycogen vacuoles (63.6%) were observed in a significantly higher number of papillary carcinoma as compared to duct cell carcinoma (NOS), apocrine, and medullary carcinomas (P = 0.0047 to 0.0022). The significant parameters differentiating papillary carcinoma and benign papillary lesions were loose cohesive clusters (P = 0.001) and acinar formation by neoplastic cells (P = 0.0237). Histopathology reports available in 36 cases, confirmed the cytodiagnosis of carcinoma in all 35 cases and the benign lesion in one case. Cytological subtyping was confirmed in 13 of 16 special types of carcinomas and all the 15 duct cell carcinoma (NOS). Thus, special and unusual variants of duct cell carcinomas like mucinous, medullary, apocrine, and papillary have specific cytomorphological features, which differentiate them from one another and from duct cell carcinoma (NOS). However, differentiating features between papillary carcinoma and benign papillary lesions were very few in this study. Diagn. Cytopathol. 2007;35:408–416. © 2007 Wiley‐Liss, Inc.
Fine‐needle aspiration biopsy findings in sclerosing polycystic adenosis of the parotid gland
Authors: Etit Demet , Pilch Ben Z. , Osgood Rebecca , Faquin William C.
Published: June 2007

Sclerosing polycystic adenosis (SPA) is a recently described, rare lesion of the salivary gland analogous to fibrocystic disease of the breast. Recognition of this benign entity is important since the differential diagnosis includes other more common benign and malignant salivary gland neoplasms, particularly mucoepidermoid carcinoma and tumors with cystic and oncocytic features. While the histomorphology of SPA is well documented, there is only one other cytologic description of SPA in the English‐language literature. Here we describe the fine‐needle aspiration biopsy findings in a case of SPA of the parotid gland in an 84‐year‐old woman. The aspirate was characterized by flat cohesive sheets of epithelial cells with moderate amounts of finely granular oncocytic cytoplasm and enlarged round nuclei with indistinct nucleoli. Some epithelial groups formed glandular structures with lumens, and the background contained small amounts of delicate mucoproteinaceous material. Occasional markedly vacuolated cells were present as well as many cells with apocrine change manifested by well‐defined apical snouting. Familiarity with the cytomorphologic features of SPA, including its characteristic apocrine changes, is important for distinguishing it from other more clinically significant salivary gland lesions. Diagn. Cytopathol. 2007;35:444–447. © 2007 Wiley‐Liss, Inc.
RIP2 mediates LPS‐induced p38 and IκBα signaling including IL‐12 p40 expression in human monocyte‐derived dendritic cells
Authors: Usluoglu Nurguel , Pavlovic Jovan , Moelling Karin , Radziwill Gerald
Published: June 2007

IL‐12, the critical factor for the generation of the Th1 type immune response, is produced by dendritic cells (DC) upon stimulation with LPS. Different signal pathways mediate LPS‐induced expression of IL‐12 and involve PI3K, MAPK and the transcription factor NF‐κB. Here, we show that the kinase Raf is involved in the expression of IL‐12 in human DC stimulated by LPS. We demonstrate that Raf regulates the expression of the IL‐12 subunit p40 not via the kinase MEK, the major effector of Raf in growth factor‐dependent signaling, but via the receptor‐interacting protein 2 (RIP2) using specific inhibitors for MAPK pathways. RIP2 is a kinase participating in LPS/Toll‐like receptor 4 signaling. Knockdown of RIP2 by siRNA inhibited LPS‐dependent expression of IL‐12 p40. In addition, knockdown of RIP2 reduced phosphorylation of p38 MAPK, ERK and IκBα, which are known upstream regulators of IL‐12 production. Thus, in human DC LPS stimulates a signal cascade that involves the Raf‐dependent activation of RIP2 leading to expression of IL‐12 p40.
Peptide‐activated double‐negative T cells can prevent autoimmune type‐1 diabetes development
Authors: Ford Megan S. , Chen Wenhao , Wong Sophie , Li Carmen , Vanama Ramesh , Elford Alisha R. , Asa Sylvia L. , Ohashi Pamela S. , Zhang Li
Published: June 2007

Autoimmune diseases may develop because of defective maturation, activation, differentiation and function of regulatory T cells. Previous studies have shown that exposure to donor antigen activates peripheral TCRαβ+CD3+CD4–CD8–NK1.1–, double‐negative (DN) T cells, which specifically suppress anti‐donor T cells and enhance survival of skin and heart grafts from allogeneic and xenogeneic donors. However, the role of DN T cells in preventing T cell‐mediated autoimmune disease is unknown. Here, we analyzed the ability of DN T cells to recognize peptides expressed on self MHC and to suppress peptide‐reactive CD8+ T cells, using the P14 mouse model that expresses a transgenic TCR specific for gp33 peptide presented on self MHC class I‐Db. We found that injection of gp33 peptide resulted in increased DN and decreased CD8+ T cell numbers in the lymph nodes when compared to untreated mice. Injection of gp33, but not TCR‐non‐specific AV peptide, increased expression of T cell activation markers on DN T cells. Moreover, gp33‐activated DN T cells suppressed proliferation of syngeneic CD8+ T cells via killing activated CD8+ T cells in an antigen‐specific fashion in vitro. Furthermore, transferring gp33‐activated DN T cells inhibited the development of autoimmune diabetes, suggesting that DN T cells may provide a novel therapy for T cell‐mediated autoimmune diseases.
Chemokine receptor expression defines heterogeneity in the earliest thymic migrants
Authors: Jenkinson William E. , Rossi Simona W. , Parnell Sonia M. , Agace William W. , Takahama Yousuke , Jenkinson Eric J. , Anderson Graham
Published: June 2007

Chemokine signaling has been implicated in directing colonization of the fetal thymus by hematopoietic precursors. However, the patterns of expression of the chemokine receptors responsible for directing thymic colonization by the earliest thymic migrants remain unknown. We have identified heterogeneity within the earliest thymus seeding cells based on chemokine receptor expression. By analyzing the first wave of progenitors to colonize the thymus at E12 of gestation, we show that multiple chemokine receptors are expressed by T‐lymphoid precursors present within perithymic mesenchyme, while expression of chemokine ligands is limited to CCL21, CCL25 and CXCL12, which are located in distinct epithelial and mesenchymal compartments of the thymic/parathyroid anlagen. Collectively, these results identify multiple populations of T‐lymphoid precursors colonizing the fetal thymus and provide evidence for several potential pathways mediating migration of precursors into the embryonic thymus.
Synthesis, Characterization, and Electrochemical and Electrical Properties of Novel Pentaerythritol‐Bridged Cofacial Bismetallophthalocyanines and Their Water‐Soluble Derivatives
Authors: Özer Metin , Altındal Ahmet , Özkaya Ali Rıza , Salih Bekir , Bulut Mustafa , Bekaroğlu Özer
Published: June 2007

Novel cofacial bismetallophthalocyanines and theirwater‐soluble derivatives were prepared. The precursor4,4′‐(2‐phenyl‐1,3‐dioxane‐5,5‐diyl)bis(methylene)bis(oxy)diphthalonitrile3was obtained by the reaction of [5‐(hydroxymethyl)‐2‐phenyl‐1,3‐dioxan‐5‐yl] methanol1and 4‐nitrophthalonitrile2with K2CO3in DMF at 50 °C. Cyclotetramerization was achieved by heating the homogenized mixture of the precursor, bisphthalonitrile, and Zn(OAc)2·2H2O or Co(OAc)2·4H2O at 300 °C, which was followed by catalytic hydrogenation of the resulting product with Pd/C(10 %) in DMF. The target water‐soluble phthalocyanines were acquired from boiling suspensions of the compounds bearing eight OH side groups in aqueous KOH (20 %) solution. The structure of the target compounds was confirmed by elemental analysis, FTIR, UV/Vis,1H NMR, ICP‐MS, and MALDI‐TOF spectroscopic methods. The electrochemical and spectroelectrochemical measurements suggested the formation of various mixed‐valent oxidation and reduction species, as a result of the strong intramolecular interactions between the two cofacial phthalocyanine units in the compounds. Impedance spectroscopy, dc conductivity, and thermopower measurements were performed using spin‐coated films of these compounds as a function of temperature (290–440 K) and frequency (40–105Hz). Dc conductivity showed typical Arrhenius behavior for all compounds. At low temperatures, a curved line was observed for the complex plane plots of impedance for all phthalocyanines. These curved lines transformed into a full semicircle with increasing temperature. The dependency of frequency exponentson temperature suggested hopping‐type conduction. A positive Seebeck coefficient was observed for all compounds, which indicates that the compounds behave as ap‐type semiconductor. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Cleavage of CO by Mo[N(R)Ar]3 Complexes
Authors: Christian Gemma , Stranger Robert , Yates Brian F. , Cummins Christopher C.
Published: June 2007

The reaction of MoL3 [L = NH2 and N(tBu)Ar] with CO was explored using DFT in order to rationalize why CO cleavage is not observed experimentally for this system in contrast to the corresponding N2 reaction which results in spontaneous cleavage of the N–N bond. The binding of CO to MoL3 was found to be both kinetically and thermodynamically favored over the binding of N2, with the formation of the encounter complex, L3Mo–CO, calculated to be without barrier and exothermic. While the overall reaction to form the C–MoL3 and O–MoL3 products was calculated to be energetically favorable, both the encounter complex and intermediate dimer, L3Mo–CO–MoL3, were found to be lower in energy than the products, with the final C–O cleavage step calculated to be endothermic by 169 kJ mol–1 and 163 kJ mol–1 for L = NH2 and N(tBu)Ar, respectively. The unfavorable CO cleavage step can be attributed to the fact that Mo does not possess the optimum d‐electron configuration to sufficiently stabilise the carbide and oxide products relative to the CO‐bridged intermediate dimer.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of (–)‐(S)‐Norlaudanosine, (+)‐(R)‐O,O‐Dimethylcoclaurine, and (+)‐(R)‐Salsolidine by Alkylation of an α‐Aminonitrile
Authors: Werner Frank , Blank Nancy , Opatz Till
Published: June 2007

A short asymmetric synthesis of 1‐substituted 1,2,3,4‐tetrahydroisoquinoline alkaloids by deprotonation of an unprotected α‐aminonitrile and alkylation of the resulting carbanion followed by spontaneous elimination of HCN and asymmetric reduction is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of the Germination Stimulant 3‐Methyl‐2H‐furo[2,3‐c]pyran‐2‐one and Analogous Compounds from Carbohydrates
Authors: Goddard‐Borger Ethan D. , Ghisalberti Emilio L. , Stick Robert V.
Published: June 2007

An efficacious synthetic route to the recently identified, potent germination stimulant 3‐methyl‐2H‐furo[2,3‐c]pyran‐2‐one and analogous compounds, using carbohydrate substrates, is described. D‐Xylose and D‐glucuronic acid γ‐lactone were used in the preparation of the parent heterocycle and its 5‐methoxycarbonyl analogue, respectively. These compounds were elaborated using various methods to furnish the natural product and a suite of its analogues. The germination stimulant was thus prepared on a multi‐gram scale in nine steps from inexpensive, commercially available 1,2‐O‐isopropylidene‐D‐xylofuranose in an overall yield of 30 %, vastly improving upon the only method published to date.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Taylor–Aris dispersion in temperature gradient focusing
Authors: Huber David E. , Santiago Juan G.
Published: June 2007

Microfluidic temperature gradient focusing (TGF) uses an axial temperature gradient to induce a gradient in electrophoretic flux within a microchannel. When balanced with an opposing fluid flow, charged analytes simultaneously focus and separate according to their electrophoretic mobilities. We present a theoretical and experimental study of dispersion in TGF. We model the system using generalized dispersion analysis that yields a 1‐D convection‐diffusion equation that contains dispersion terms particular to TGF. We consider analytical solutions for the model under uniform temperature gradient conditions. Using a custom TGF experimental setup, we compare focusing measurements with the theoretical predictions. We find that the theory well represents the focusing behavior for flows within the Taylor–Aris dispersion regime.
Quantification of CpG methylation at the 5′‐region of XIST by pyrosequencing from human serum
Authors: Song Min‐Ae , Park Jung‐Hoon , Jeong Kyoung‐Sin , Park Dong Soo , Kang Myung Seo , Lee Suman
Published: June 2007

Aberrant methylation of X (inactive)‐specific transcript (XIST) is common in serum derived from human prostate and testicular germ cell tumors. The direct quantification of XIST methylation is urgently required for clinical application because human serum contains both normal and cancer‐originated XIST DNA. We directly quantitated the methylation percentage of three CpG sites (+947, +956, +971) from the 5′‐region of XIST by pyrosequencing. The average methylation percentages at three CpG sites were 88% (±5.8) at CpG1, 98% (±3.4) at CpG2, and 92% (±5.6) at CpG3 from normal male (N = 19). From prostate cancer‐derived sera, the average methylation percentage of XIST was 65% (±8.3) at CpG1, 82% (±10.9) at CpG2, and 74% (±4.4) at CpG3, which is lower than the normal XY serum DNA, but greater than normal XX serums. The methylation status of XIST also correlated with its gene expression in B‐lymphoblastoid and prostate cancer cell lines. This method is sensitive for quantifying the small percentage change in the methylation status of XIST, and may be used for early diagnosis and monitoring of cancer in men using serum.
A robust high‐resolution finite volume scheme for the simulation of long waves over complex domains
Authors: Delis A. I. , Kazolea M. , Kampanis N. A.
Published: June 2007

The propagation, runup and rundown of long surface waves are numerically investigated, initially in one dimension, using a well‐balanced high‐resolution finite volume scheme. A conservative form of the nonlinear shallow water equations with source terms is solved numerically using a high‐resolution Godunov‐type explicit scheme coupled with Roe's approximate Riemann solver. The scheme is also extended to handle two‐dimensional complex domains. The numerical difficulties related to the presence of the topography source terms in the model equations along with the appearance of the wet/dry fronts are properly treated and extended. The resulting numerical
model accurately describes breaking waves as bores or hydraulic jumps and conserves volume across flow discontinuities. Numerical results show very good agreement with previously presented analytical or asymptotic solutions as well as with experimental benchmark data. Copyright © 2007 John Wiley & Sons, Ltd.
A numerical model for the transport of salinity in estuaries
Authors: Navarrina F. , Colominas I. , Casteleiro M. , Cueto‐Felgueroso L. , Gómez H. , Fe J. , Soage A.
Published: June 2007

In this
paper, a numerical model for the simulation of the hydrodynamics and of the evolution of the salinity in shallow water estuaries is presented. This tool is intended to predict the possible effects of Civil Engineering public works and other human actions (dredging, building of docks, spillages, etc.) on the marine habitat, and to evaluate their environmental impact in areas with high productivity of fish and of seafood. The prediction of these effects is essential in the decision making about the different options that could be implemented.

The mathematical model consists of two coupled systems of differential equations: the shallow water hydrodynamic equations (that describe the evolution of the depth and of the velocity field) and the shallow water advective–diffusive transport equation (that describes the evolution of the salinity level).

Some important issues that must be taken into account are the effects of the tides (including that the seabed could be exposed), the volume of fresh water provided by the rivers and the effects of the winds. Thus, different types of boundary conditions are considered.

The numerical model proposed for solving this problem is a second‐order Taylor–Galerkin finite element formulation.

The proposed approach is applied to a real case: the analysis of the possible effects of dredging Los Lombos del Ulla, a formation of sandbanks in the Arousa Estuary (Galicia, Spain).

A number of simulations have been carried out to compare the actual salinity level with the predicted situation if the different dredging options were executed. Some of the obtained results are presented and discussed. Copyright © 2007 John Wiley & Sons, Ltd.
Role of the inclination of an inverted‐V upper plate on the heat and flow behavior of trapped gases in a modified Rayleigh–Bénard cavity
Authors: Ridouane El Hassan , Campo Antonio , Chang Jane Y.
Published: June 2007

Thermal buoyant air inside a modified Rayleigh–Bénard (RB) cavity bounded by a lower flat plate and an inverted‐V upper plate has been investigated numerically using the finite‐volume method. The second‐order‐accurate QUICK and SIMPLE schemes were used for the discretization of the convective terms and the pressure–velocity coupling in the set of conservation equations, respectively. The problem under study is controlled by two parameters: (1) the Rayleigh number ranging from
103 to
106 and (2) the relative height of the vertical sidewalls d. In reference to the latter, it varies from one limiting case corresponding to the standard RB cavity (a rectangle with
d = 1) to another limiting case represented by an isosceles triangular cavity where
d = 0. The numerical results for the velocity and temperature fields are presented in terms of streamlines, isotherms, local and mean heat fluxes. An additional effort was devoted to determine the critical Ra values characterizing the transition from symmetrical to asymmetrical buoyant airflow responsive to incremental changes in Ra. For purposes of engineering design, a general correlation equation for the Nusselt number in terms of the pertinent Ra and d was constructed using nonlinear multiple regression theory. Copyright © 2007 John Wiley & Sons, Ltd.
Introducing unsteady non‐uniform source terms into the lattice Boltzmann model
Authors: Cheng Yongguang , Li Jinping
Published: June 2007

Taking body forces into account is not new for the lattice Boltzmann method, yet most of the existing approaches can only treat steady and uniform body forces. To manage situations with time‐ and space‐dependent body forces or source terms, this paper proposes a new approach through theoretical derivation and numerical verification. The method by attaching an extra term to the lattice Boltzmann equation is still used, but the expression of the extra term is modified. It is the modified extra term that achieves the particularity of the new approach. This approach can not only introduce unsteady and non‐uniform body forces into momentum equations, but is also able to add an arbitrary source term to the continuity equation. Both the macroscopic equations from multi‐scale analysis and the simulated results of typical examples show that the accuracy with second‐order convergence can be guaranteed within incompressible limit. Copyright © 2007 John Wiley & Sons, Ltd.
Application of a second‐order Runge–Kutta discontinuous Galerkin scheme for the shallow water equations with source terms
Authors: Kesserwani G. , Ghostine R. , Vazquez J. , Ghenaim A. , Mosé R.
Published: June 2007

The present work addresses the numerical prediction of discontinuous shallow water flows by the application of a second‐order Runge–Kutta discontinuous Galerkin scheme (RKDG2). The unsteady flow of water in a one‐dimensional approach is described by the Saint Venant's model which incorporates source terms in practical applications. Therefore, the RKDG2 scheme is reformulated with a simple way to integrate source terms. Further, an adequate boundary conditions handling, by the theory of characteristics, was overviewed to be adapted to the external points of the mesh, as well as to some points of local invalidity of the Saint Venant's model. To validate the proposed technique, steady and transient test problems (all having a reference solution) were considered and computed by means of the overall method. The results were illustrated jointly with the reference solution and the results carried out by a traditional second‐order finite volume (FV2) scheme implemented with the same techniques as the RKDG2. The proposed method has proven its practical consideration when solving discontinuous shallow water flow involving: non‐prismatic channels, various cross‐sections, smoothly varying bed topography and internal boundary conditions. Copyright © 2007 John Wiley & Sons, Ltd.
Numerical simulation of minimum B‐jumps at abrupt drops
Authors: Tokyay Nuray Denli , Altan‐Sakarya A. Burcu , Eski Elvan
Published: June 2007

A numerical simulation of minimum B‐jumps in horizontal rectangular channels having an abrupt drop is given. Gradually varied, steady, supercritical flow is assumed as the initial condition. An unsteady flow is created by increasing the downstream depth. One‐dimensional, unsteady Saint‐Venant equations are solved by using the MacCormack and the dissipative two–four explicit finite difference schemes. The steady flow solution is obtained by treating the time variable as an iteration parameter and letting the solution converge to the steady state. The abrupt drop is treated as an interior boundary and solved by the method of characteristics. The results are compared with experimental and analytical studies. Copyright © 2007 John Wiley & Sons, Ltd.
AN examination of short QQQ option trades
Authors: Simon David P.
Published: June 2007

This study shows that unconditional QQQ option selling strategies from January 2001 through November 2004 are generally significantly profitable after transactions costs. However, when straddle and strangle sales are combined with purchases of out of the money puts, few of the strategies are significantly profitable. Profits improve when the QQQ Volatility Index is high relative to time series volatility forecasts, but only when actual volatility is forecast to be moderate. Active delta‐hedging reduces profitability, whereas stop loss/take profit orders enhance profitability. Overall, QQQ short volatility trades appear to be less compelling than what others have found with S&P options. © 2007 Wiley Periodicals, Inc. Jrl Fut Mark 27:739–770, 2007
Mild cognitive impairment: coping with an uncertain label
Authors: Joosten‐Weyn Banningh Liesbeth , Vernooij‐Dassen Myrra , Rikkert Marcel Olde , Teunisse Jan‐Pieter
Published: June 2007

Background

The recently introduced diagnostic label of Mild Cognitive Impairment (MCI) identifies patients with a cognitive decline that is more pronounced than is usual for a person's age and educational level but does not notably interfere with activities of daily living (ADL). The natural course of the syndrome is uncertain although MCI sufferers have a higher risk of developing dementia.

Objectives

To investigate how patients fulfilling MCI criteria experience and cope with their cognitive decline with the secondary aim to derive key themes for a prospective MCI support‐group programme.

Methods

The grounded theory approach.

Results

Analysis of guided interviews with eight MCI patients revealed four common themes. Changes related to cognitive abilities, mobility, affect, vitality and somatic complaints. Attributions were numerous and concerned aetiologies such as personality traits and overload of information. Consequences were all negative and concerned the patients themselves such as anxiety and loss of self‐confidence, others such as feelings of irritation and anger towards others or activities like abandoning leisure activities. Patients applied emotion‐oriented, problem‐focused and avoidant coping strategies.

Conclusion

MCI patients encounter stress‐inducing practical, social and psychological difficulties. Based on the current preliminary findings, the key themes for an MCI support‐group programme should include the provision of information about the syndrome's causes, course, concomitant symptoms, attributions, social consequences, and available treatments. The impact of receiving an MCI label warrants further investigation. Copyright © 2007 John Wiley & Sons, Ltd.
Transforming growth factor-β1 suppresses hepatitis B virus replication primarily through transcriptional inhibition of pregenomic RNA
Authors: Chou Yu-Chi , Chen Mong-Liang , Hu Cheng-Po , Chen Ya-Ling , Chong Chin-Liew , Tsai Yue-Lin , Liu Tzu-Ling , Jeng King-Song , Chang Chungming
Published: June 2007

Transforming growth factor–beta1 (TGF-β1) is a pleiotropic cytokine with pivotal roles in the regulation of cellular functions and immune responses. In this study, we found that TGF-β1 was able to effectively suppress hepatitis B virus (HBV) replication. In the presence of TGF-β1, the level of viral replicative intermediates was dramatically decreased, both in actively dividing cells and in confluent cells. At the same time, the levels of viral transcripts, core protein, and nucleocapsid were significantly diminished by TGF-β1 treatment. Interestingly, the inhibitory activity of TGF-β1 was associated with preferential reduction of the level of pregenomic RNA compared with pre-C mRNA. Further analysis indicated that TGF-β1 might exert its antiviral effect primarily through reducing expression of the HBV core protein by transcriptional regulation instead of posttranscriptional modification.

Conclusion:

TGF-β1 may play a dual role in HBV infection, in the suppression of immune responses against viral infection and in the direct inhibition of viral replication, resulting in minimization of liver damage in patients with chronic hepatitis. (Hepatology 2007.)
Surface properties and implantation site affect the capsular fibrotic overgrowth
Authors: Bakeine G.J. , Bertolotti A. , Latina M. , Congiu T. , Prati U. , Roveda L. , Trotta F. , Tormen M. , Fabrizio E. Di , Carlini G. , Facoetti A. , Nano R.
Published: June 2007

Transplantation of encapsulated pancreatic islets is a promising approach for the treatment of type 1 diabetes. Large‐scale application of this technique, however, is hampered by insufficient biocompatibility of the capsules. In this study, we have evaluated the biocompatibility of a new synthetic material with six different chemical groups on their surface (amino, carboxy‐sulfate, carboxylate, hydroxylate, sulfate, and PMMA) used for the fabrication of the microcapsules. Eight Lewis rats were inoculated with a suspension of empty capsules made for each candidate material in the retroperitoneal ileopsoas muscle and renal subcapsular space. Four weeks later kidney and muscle containing the capsules were explanted, paraffin embedded, sectioned and stained with Sirius Red and Masson's Trichrome for histological analysis. The amount of fibrosis was also ultrastructurally evaluated with scanning electron microscopy. The samples were then subjected to digitalized quantitative analysis using specific software to determine the degree of fibrotic overgrowth. The quantification of collagen deposition, calculated in proximity of the microcapsules, was expressed as a percentage of the total area and can be considered a good index for the biocompatibility, an essential prerequisite for functional pancreatic islet transplantation. The results show that subcapsular renal space is the best implantation site and the positive surface charge induces a more intense collagen synthesis. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Parabiosis and transplantation models show no evidence of circulating dermal fibroblast progenitors in bleomycin‐induced skin fibrosis
Authors: Boban Ivana , Barisic‐Dujmovic Tatjana , Clark Stephen H.
Published: June 2007

To test the hypothesis of an extra‐dermal origin of dermal fibroblasts, parabiosis, and transplantation models were developed utilizing a collagen promoter green fluorescent protein (GFP) reporter transgene expressed in dermal fibroblasts. Parabiotic pairs were treated with bleomycin to induce the skin fibrosis that was evaluated for a dense deposition of collagen and inflammatory cell infiltrates in the thickened dermis in comparison with parabiotic pairs treated with saline. Although, in all cases, repeated injection of bleomycin for 4 weeks induced skin fibrosis, only a few GFP positive cells were detected in skin samples from some of the treated non‐transgenic mice. Unexpectedly, similar results were observed in saline treated controls. Furthermore, bone marrow chimeras were created in which non‐transgenic recipient mice received injections of bone marrow cell preparations isolated from pOBCol3.6GFP transgenic mice. After bone marrow chimerism had been successfully established, fibrotic lesions in the skin were induced by local bleomycin injections. Donor GFP expressing cells were observed in the skin from all recipient mice. However, no difference in the presence of GFP expressing cells was observed between non‐treated mice or mice treated with bleomycin or saline. A large number of GFP expressing cells were observed in the lung preparations from all chimeric mice. Mac‐3 antibody immunostaining confirmed a macrophage phenotype for these GFP expressing cells suggesting the expression of the pOBCol3.6GFP transgene in a non‐collagen producing cell. Based on these observations, we found no evidence of circulating dermal fibroblast progenitors that participate in the development of bleomycin‐induced skin fibrosis. J. Cell. Physiol. 214:230–237, 2008. © 2007 Wiley‐Liss, Inc.
Syndecan‐1 interaction with the LG4/5 domain in laminin‐332 is essential for keratinocyte migration
Authors: Bachy Sophie , Letourneur François , Rousselle Patricia
Published: June 2007

Laminin 5/laminin 332 (LN332) is an adhesion substrate for epithelial cells. After secretion of LN332, a regulated cleavage occurs at the carboxy‐terminus of its alpha3 subunit, which releases a tandem of two globular modules named LG4/5. We show that the presence of the LG4/5 domain in precursor LN332 decreases its integrin‐mediated cell adhesion properties in comparison with mature LN332. Whereas cell adhesion to the recombinant LG4/5 fragment relies solely on the heparan sulfate proteoglycan (HSPG) receptor syndecan‐1, we reveal that both syndecan‐1 and the alpha3beta1 integrin bind to precursor LN332. We further demonstrate that syndecan‐1 mediated cell adhesion to the LG4/5 fragment and pre‐LN332 allows the formation of fascin‐containing protrusions, depending on the GTPases Rac and Cdc42 activation. Reducing syndecan‐1 expression in normal keratinocytes prevents cell protrusions on pre‐LN332 with subsequent failure of the peripheral localization of the alpha3beta1 integrin. We finally show that cell migration on pre‐LN332 requires syndecan‐1. Therefore, the LG4/5 domain in precursor LN332 appears to trigger intracellular signaling events, which participate in keratinocyte motility. J. Cell. Physiol. 214:238–249, 2008. © 2007 Wiley‐Liss, Inc.
PI3‐K/Akt‐dependent activation of cAMP‐response element‐binding (CREB) protein in Jurkat T leukemia cells treated with TRAIL
Authors: Caravatta Luciana , Sancilio Silvia , di Giacomo Viviana , Rana Rosalba , Cataldi Amelia , Di Pietro Roberta
Published: June 2007

We recently demonstrated the activation of phosphatidylinositol 3‐kinase (PI3‐K/Akt) survival pathway in Jurkat T leukemia cells known for their sensitivity to the tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL)/Apo2L cytotoxic action. The present investigation was done to elucidate the role of cAMP‐response element‐binding (CREB) protein in this system. Jurkat T cells were treated with 100–1,000 ng/ml TRAIL for time intervals up to 24 h in the presence or absence of selective pharmacologic inhibitors of PI3‐K/Akt (LY294002) or p38 MAPK (SB253580) pathways. Upon TRAIL treatment, a dose‐dependent increase in the percentage of apoptotic cells as well as in caspase‐3 activity was observed. A further enhancement of apoptotic cell death was obtained with the use of CREB1 siRNA technology, as demonstrated by flow cytometry. Western blot analysis showed a high constitutive level of CREB phosphorylation at Ser133 in Jurkat T cells under normal serum culture conditions. Under low serum culture conditions, an early (within 1 h) and transient increase in CREB phosphorylation was detected in response to both TRAIL doses and reduced upon pre‐treatment with LY294002 or SB253580, demonstrating the PI3‐K/Akt‐ and p38 MAPK‐dependency of this effect. The parallel analysis in immune fluorescence demonstrated the nuclear translocation of the phosphorylated form upon treatment with 100 ng/ml TRAIL, whereas the immune labeling was mainly detectable in the cytoplasm compartment upon the higher more cytotoxic dose. These results let us hypothesize that CREB activation can be an important player in the complex cross‐talk among pro‐ and anti‐apoptotic pathways in this peculiar cell model. J. Cell. Physiol. 214:192–200, 2008. © 2007 Wiley‐Liss, Inc.