bluuebunny/crossref_metadata_2025 huggingface dataset:
Very Large Supramolecular Capsules Based on Hydrogen Bonding
Authors: Atwood Jerry L. , Barbour Leonard J. , Jerga Agoston
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Molecular Recognition and Self‐Assembly Between Amines and Alcohols (Supraminols)
Authors: Saladino Raffaele , Hanessian Stephen
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Biphasic Synthesis
Authors: Dyson P. J.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Two‐Step Synthesis of Carbohydrates by Selective Aldol Reactions
Authors: Northrup Alan B. , MacMillan David W. C.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Divalent Silicon, Germanium, and Tin Compounds with Element—Heteroatom Bonds
Authors: Zemlyanskii N. N. , Borisova I. V. , Nechaev M. S. , Khrustalev V. N. , Lunin V. V. , Antipin M. Yu. , Ustynyuk Yu. A.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Catalytic Olefination of Carbonyl Compounds. A New Versatile Method for the Synthesis of Alkenes
Authors: Nenajdenko V. G. , Korotchenko V. N. , Shastin A. V. , Balenkova E. S.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Novel Group‐Transfer Radical Reactions with Organotelluriums
Authors: Yamago Shigeru
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Catalytic C—C Bond Formation via Capture of Hydrogenation Intermediates
Authors: Jang Hye‐Young , Krische Michael J.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Organolanthanoid‐Catalyzed Hydroamination
Authors: Hong Sukwon , Marks Tobin J.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
The Chemistry of Vicinal Tricarbonyls and Related Systems
Authors: Wasserman Harry H. , Parr Jonathan
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Rotaxanes Containing Quaternary Azaaromatic Moieties
Authors: Sliwa Wanda , Bachowska Barbara
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
A Challenge for Green Chemistry: Designing Molecules that Readily Dissolve in Carbon Dioxide
Authors: Beckman E. J.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
The Design of Drugs that Target Tumor Hypoxia.
Authors: Denny William A.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
The Synthesis of N‐Ribosyl Transferase Inhibitors Based on a Transition State Blueprint.
Authors: Evans Gary B.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Bimetallic Figure‐Eight Octaphyrins Split into Four‐Pyrrolic Macrocycles
Authors: Latos‐Grazynski Lechoslaw
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Structural Determinations by Circular Dichroism Spectra Analysis Using Coupled Oscillator Methods: An Update of the Applications of the DeVoe Polarizability Model
Authors: Superchi Stefano , Giorgio Egidio , Rosini Carlo
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Validation and adaptation of a nomogram for predicting the survival of patients with extremity soft tissue sarcoma using a three‐grade system
Authors: Mariani Luigi , Miceli Rosalba , Kattan Michael W. , Brennan Murray F. , Colecchia Maurizio , Fiore Marco , Casali Paolo G. , Gronchi Alessandro
Published: December 2004

BACKGROUND

A nomogram for predicting long term tumor‐specific death in patients with soft tissue sarcoma (STS) was developed at the Memorial Sloan‐Kettering Cancer Center (MSKCC).

METHODS

To assess the performance of the MSKCC nomogram, 642 consecutive patients with extremity STS who underwent surgery over a 20‐year span at a single referral center were analyzed. Nomogram predictions were based on tumor size, depth, site, patient age, histologic subtype, and grade. The latter, at variance with the system in use at the MSKCC, was classified as Grade 1–3 according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system. The statistical approach used for nomogram performance assessment was that of “validation by calibration” proposed by Van Houwelingen.

RESULTS

Graphic comparison of observed and predicted sarcoma‐specific survival curves showed that predictions by the nomogram were quite accurate, within 10% of actual survival for all prognostic strata. Statistical analysis showed that such predictions could be improved by employing approximately 25% shrinkage to achieve good calibration. The contribution of histologic grade was highly significant in both univariate analysis (P < 0.001) and multivariate analysis (P < 0.001), and a survival trend across the 3 grade categories was observed. Based on those findings, a nomogram that included the FNCLCC histologic grade classification was produced.

CONCLUSIONS

Results of the current study confirmed that the MSKCC nomogram is a valuable tool for individual prognostic assessment. A nomogram that included the FNCLCC histologic grade classification was proposed and was validated internally. Cancer 2005. © 2004 American Cancer Society.
Weekly docetaxel is safe and effective in the treatment of advanced‐stage acquired immunodeficiency syndrome‐related Kaposi sarcoma
Authors: Lim Soon Thye , Tupule Anil , Espina Byron M. , Levine Alexandra M.
Published: December 2004

BACKGROUND

Intravenous paclitaxel, 100 mg/m2, given over 3 hours every 2 weeks is associated with a response rate of 59% in patients with recurrent or refractory acquired immunodeficiency syndrome (AIDS)‐related Kaposi sarcoma (KS). However, this regimen is associated with significant myelosuppression, and the inconvenience of a 3‐hour infusion. Moreover, no effective therapies have been defined for use after treatment failure with this agent. A Phase II trial was conducted with weekly docetaxel in patients with advanced‐stage KS to assess safety and antitumor activity.

METHODS

Docetaxel was administered at a dose of 25 mg/m2 intravenously over 15–30 minutes weekly for 8 weeks. Thereafter, if the patient experienced stable disease or better response, treatment doses were given every other week until complete disease remission, disease progression, or unacceptable toxicity occurred.

RESULTS

Twelve patients were accrued—9 had > 25 mucocutaneous lesions, 1 had lymphedema, and 2 had visceral involvement. Ten patients (83%) had previous systemic chemotherapy, including 4 who received previous paclitaxel. Treatment was well tolerated, with no Grade 4 toxicity of any type. Grade 3 neutropenia occurred in 33% of patients but no patient had neutropenic fever. Five patients (42%) achieved a partial response, including 1 who had previously failed to respond to paclitaxel. The median time to disease progression was 26 months (range, 5–53 months). With a median follow‐up period of 45 months, the median survival point had not been reached.

CONCLUSIONS

Weekly docetaxel is safe, with reasonable antitumor activity in patients with advanced‐stage, recurrent, or refractory AIDS‐related KS. Cancer 2005. © 2004 American Cancer Society.
Determining the Gibbs Energy of Ion Transfer Across Water–Organic Liquid Interfaces with Three‐Phase Electrodes
Authors: Scholz Fritz , Gulaboski Rubin
Published: December 2004

Ions can be transferred between immiscible liquid phases across a common interface, with the help of a three‐electrode potentiostat, when one phase is an organic droplet attached to a solid electrode and containing a redox probe. This novel approach has been used in studies to determine the Gibbs energy of anion and cation transfer, ranging from simple inorganic and organic ions to the ionic forms of drugs and small peptides. This method of studying ion transfer has the following advantages: 1) no base electrolytes are necessary in the organic phase; 2) the aqueous phase contains only the salt to be studied; 3) a three‐electrode potentiostat is used; 4) organic solvents such as n‐octanol and chiral liquids such as D‐ and l‐2‐octanol can be used; 5) the range of accessible Gibbs energies of transfer is wider than in the classic 4‐electrode experiments; 6) the volume of the organic phase can be very small, for example, 1 μL or less; 7) the experiments can be performed routinely and fast. Herein, the basic principle is outlined, as well as a summary of the results obtained to date, and a discussion on the theoretical treatments concerning the kinetic regime of the three‐phase electrodes with immobilized droplets.
A pilot study of psychodynamic psychotherapy for adult survivors of childhood sexual abuse
Authors: Price Jennifer L. , Hilsenroth Mark J. , Callahan Kelley L. , Petretic‐Jackson Patricia A. , Bonge Dennis
Published: December 2004

Clinical samples of child sexual abuse survivors report a variety of psychiatric symptoms and interpersonal difficulties. The treatment outcome literature for this population is often incomplete due to numerous methodological constraints. The purpose of this study was to evaluate the effectiveness of an open trial of individual short‐term, psychodynamic psychotherapy with a naturalistic sample of adult survivors of childhood sexual abuse. Sexual abuse survivors demonstrated significant improvement in symptomatic distress, level of functioning and dynamic personality variables according to self‐report measures and clinical rating scales. Abuse survivors developed positive therapeutic alliances, which remained high throughout the course of treatment, and comparable to the non‐abused clinical sample. Sexual abuse survivors' response to treatment was similar to that of non‐abused patients, with the potential for greater change in feelings about the self. These findings demonstrate that psychodynamic psychotherapy may be useful for childhood sexual abuse survivors presenting with depressive symptoms and interpersonal difficulties. Copyright © 2004 John Wiley & Sons, Ltd.
VBR video transmission with isochronous and asynchronous transfer mode over wireless 1394
Authors: Takazawa Tomoaki , Utsunomiya Yoriko , Komoriya Yota , Bandai Masaki , Sasase Iwao
Published: December 2004

We propose a VBR video transmission scheme with isochronous and asynchronous transfer mode over Wireless 1394. In the proposed scheme, to decrease the idle bandwidth in the isochronous area, a video station which uses the isochronous transfer mode is assigned bandwidth equivalent to the average rate of the video stream. Video data over the average rate are transmitted in asynchronous transfer mode, and video stations have higher transmission priority than data stations in asynchronous transfer mode. By computer simulations, we show that the proposed scheme can improve the channel utilization performance and the waiting time performance, and that it is effective for VBR video transmission. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 88(4): 64–74, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10233
New pulse compression filter to realize minimum S/N loss with zero range side lobe
Authors: Shinonaga Mitsuyoshi , Yajima Shinichi , Nishimoto Shinkichi
Published: December 2004

Pulse compression processing of chirped signals can be treated as a matched filter reception process. However, generation of range side lobes is unavoidable. If a window function is used for suppression of these range side lobes, S/N loss occurs due to signal loss. Although it is possible to derive a window function realizing a desired characteristic such as side lobe‐free conditions by means of a convergence operation, it is not known whether the S/N loss is minimized because the requirement for S/N loss minimization is not taken into account. In the present paper, a method is presented for calculation of the window function and the pulse compression filter satisfying both the S/N loss minimum condition and the side lobe‐free condition. Simulation confirms that the derived pulse compression filter has a lower S/N loss than that in the method with a conventional window function and has a higher range resolution. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 88(4): 1–9, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20192
Lipase‐Promoted Access to Phenolic Herbertane‐Type Sesquiterpenes: (+)‐1,14‐Herbertenediol, (−)‐α‐Herbertenol, (−)‐Herbertenediol and Their Enantiomers
Authors: Acherar Samir , Audran Gérard , Fotiadu Frédéric , Monti Honoré
Published: December 2004

An enantioselective synthesis of (+)‐1,14‐herbertenediol, and a formal enantioselective synthesis of (−)‐α‐herbertenol and (−)‐herbertenediol, employing a lipase‐promoted and a key stereoselective alkylation of a cyclopentane unit based methodology, are described. Molecular mechanics considerations that could account for the major role played by the substitution pattern of the benzene nucleus in the herbertane framework in comparison with those of the cuparane framework are described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Domino Cyclization/Electrocyclization/Elimination Reactions of Arylacetonitriles with N,N′‐Bis(1‐naphthyl)oxaldiimidoyl Dichlorides: Efficient Synthesis of Fluorescent 15H‐Benzo[h]benzo[6,7]indolo[3,2‐b]quinolines
Authors: Anders Joachim T. , Langer Peter
Published: December 2004

15H‐Benzo[h]benzo[6,7]indolo[3,2‐b]quinolines were prepared by domino cyclization/electrocyclization/elimination reactions of nitriles with N,N′‐bis(1‐naphthyl)oxaldiimidoyl dichlorides. The products can be regarded as hexacyclic δ‐carbolines and are novel fluorescent dyes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Powerful N‐Monoalkylation of Linear Tetraamines via Bisaminal Intermediates
Authors: Claudon Géraldine , Le Bris Nathalie , Bernard Hélène , Handel Henri
Published: December 2004

The bisaminals obtained through the condensation of two linear tetraamines with glyoxal or pyruvic aldehyde were selectively alkylated with bromo‐ or α,ψ‐dibromoalkanes in good yields at one of the secondary amino functions to give rise to N‐monoalkylated tetraamines or linear octaamines. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Photochemistry of the Phototoxic Drug Lomefloxacin: Paths Observed in the Presence of Amines or NaOH and from the Methyl Ester
Authors: Fasani Elisa , Mella Mariella , Albini Angelo
Published: December 2004

The photochemistry of the fluoroquinolone drug lomefloxacin has been examined in aqueous solution in the presence of aliphatic amines (0.01 and 0.2 M) as well as 0.01 M NaOH; a fairly efficient decomposition (Φ = 0.2 to 0.4) takes place. Under the above conditions the product distribution is the same and differs from that previously observed in neutral and acidic aqueous solution. Five products have been characterized, all of them resulting from reductive elimination of the fluorine in the 8‐position and some alteration of the piperazine side‐chain. All of the products are rationalized as resulting from the heterolytic cleavage of the C8−F bond in triplet lomefloxacin to give the corresponding triplet aryl cation. Due to the multiplicity, the C8 site has a carbene rather than a localized cation character. Under these conditions — the amino group in the 4′‐position is free — the main process is formal hydride transfer from the 3′‐position and the minor one attack of the 4′‐amino group at the C6−F bond. In accordance with this rationalization, the methyl ester of lomefloxacin exhibits a closely analogous photochemistry under neutral conditions. The cationic intermediate may be involved in the observed phototoxicity of the drug, via an oxygen‐independent path. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
An Expeditious Asymmetric Synthesis of Polyfunctional 1,7‐Dioxaspiro[5.5]undecanes
Authors: Gerber‐Lemaire Sandrine , Vogel Pierre
Published: December 2004

Quick access to polyfunctional spiroketal (3R)‐4[(2S,6R,8R,10S)‐4,4‐bis(ethylthio)‐10‐hydroxy‐8‐(2‐hydroxyethyl)‐1,7‐dioxaspiro[5.5]undec‐2‐yl]butane‐1,3‐diol [(+)‐19] is now available through the stereoselective functionalization of enantiomerically pure protected tetrol (4R,4′R,6R,6′R)1,1′‐methylenebis[4‐[(benzyloxy)methoxy]‐6‐[(triethylsilyl)oxy]cyclohept‐1‐ene [(−)‐9], derived from 2,2′‐methylenedifuran. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Structural Analysis of a Novel Polysaccharide of the Lipopolysaccharide‐Deficient Extremophile Gram‐Negative Bacterium Thermus thermophilus HB8
Authors: Silipo Alba , Molinaro Antonio , De Castro Cristina , Ferrara Renata , Romano Ida , Nicolaus Barbara , Lanzetta Rosa , Parrilli Michelangelo
Published: December 2004

A novel polysaccharide was isolated from the extremophile Gram‐negative bacterium Thermus thermophilus HB8. Its structural characterization employed compositional and methylation analyses, and 2D 1H and 13C NMR spectroscopy. Various chemical degradations (methanolysis and Smith degradation) were also carried out in order to depolymerise this complex macromolecule, and subsequent chemical and spectroscopic analyses were also carried out on the obtained fragments. All the data suggested a novel polymeric structure that consists of a disaccharide repeating unit to which a branching trisaccharide chain is linked, although not stoichiometrically. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Selective Potentiometric Measurement of Physiologically Significant Thiols
Authors: Gracheva Svetlana , Digga Alkmini , Livingstone Callum , Davis James
Published: December 2004

The reaction of benzoquinone with reduced thiol species has been investigated using potentiometric techniques. The specificity of this reaction for thiol functionality has been briefly assessed and the nature of the electrode response has been elucidated. The system has been characterized in terms of selectivity, sensitivity and the efficacy of using the system for the quantification of thiol containing pharmaceuticals has been demonstrated. The simplicity of the detection methodology is shown to markedly contrast alternative thiol detection strategies. The transfer of the technology to a mass production format through the adoption of screen print electrode formats has been achieved and the efficacy of the approach demonstrated. Recovery experiments using captopril and penicillamine in tissue culture as a model analyte system were performed.
Efficacy of a rapamycin analog (CCI‐779) and IFN‐γ in tuberous sclerosis mouse models
Authors: Lee Laifong , Sudentas Paul , Donohue Brian , Asrican Kirsten , Worku Aelaf , Walker Victoria , Sun Yanping , Schmidt Karl , Albert Mitchell S. , El‐Hashemite Nisreen , Lader Alan S. , Onda Hiroaki , Zhang Hongbing , Kwiatkowski David J. , Dabora Sandra L.
Published: December 2004

Tuberous sclerosis complex (TSC) is a familial tumor disorder for which there is no effective medical therapy. Disease‐causing mutations in the TSC1 or TSC2 gene lead to increased mammalian target of rapamycin (mTOR) kinase activity in the conserved mTOR signaling pathway, which regulates nutrient uptake, cell growth, and protein translation. The normal function of TSC1 and TSC2 gene products is to form a complex that reduces mTOR kinase activity. Thus, mTOR kinase inhibition may be a useful targeted therapeutic approach. Elevated interferon‐gamma (IFN‐γ) expression is associated with decreased severity of kidney tumors in TSC patients and mouse models; therefore, IFN‐γ also has therapeutic potential. We studied cohorts of Tsc2+/− mice and a novel mouse model of Tsc2‐null tumors in order to evaluate the efficacy of targeted therapy for TSC. We found that treatment with either an mTOR kinase inhibitor (CCI‐779, a rapamycin analog) or with IFN‐γ reduced the severity of TSC‐related disease without significant toxicity. These results constitute definitive preclinical data that justify proceeding with clinical trials using these agents in selected patients with TSC and related disorders. © 2004 Wiley‐Liss, Inc.
Sequence of oligodendrocyte development in the human fetal telencephalon
Authors: Jakovcevski Igor , Zecevic Nada
Published: December 2004

Oligodendrocytes (OL), cells that myelinate axons in the CNS, differentiate from early to late oligodendrocyte progenitor cells (OPC) to become mature OL. Unlike the case in the rodent brain, myelin formation starts prenatally in the human brain, but the sequence of OL development and the onset of myelination are not well understood. We studied the human fetal forebrain at midgestation (17–23 gestational weeks, g.w.) using OL lineage‐specific antibodies and mRNA probes. Early OPC were present in a gradient from the subventricular zone to the cortical plate. Their close apposition to radial glia fibers suggests a possible role of these fibers in OPC migration. Late OPC reached peak density in the subplate layer, whereas multipolar cells with the morphology of mature OL were restricted to the emerging white matter. At 20 g.w., myelinated axons were observed in the diencephalon, but not in the telencephalon, consistent with caudal‐to‐rostral progression of myelination. Interestingly, in organotypic slice cultures of the same gestational ages, the subventricular zone contained a considerably greater number of the mature OL cells, suggesting the presence of inhibitory signals in vivo. Overall, in addition to considerable similarities with rodents, important differences in temporal and spatial distribution and regulatory signals for OL differentiation exist in the human brain. © 2004 Wiley‐Liss, Inc.
ATP binding cassette transporter ABC1 is required for the release of interleukin‐1β by P2X7‐stimulated and lipopolysaccharide‐primed mouse Schwann cells
Authors: Marty Vincent , Médina Chantal , Combe Chantal , Parnet Patricia , Amédée Thierry
Published: December 2004

Schwann cells are best known as myelinating glial cells of the peripheral nervous system, but they also participate actively in the sphere of immunity by producing pro‐inflammatory cytokines, such as interleukin‐1β (IL‐1β). In a previous study, we demonstrated that posttranslational processing of IL‐1β by immune‐challenged Schwann cells required the P2X7 receptor. Remarkably, the release of IL‐1β was not associated with cell death, indicating the involvement of an active mechanism. ATP binding cassette (ABC) transporters are known to transport leaderless secretory proteins, such as IL‐1β; therefore, we investigated whether such transporters were at work in Schwann cells. Mouse Schwann cells expressed ABC1 transporter mRNA and displayed the functional protein. Glybenclamide and diisothiocyanato‐stilbene‐disulfonic acid (DIDS), two blockers of chloride fluxes that drive the export activity of ABC1 transporters, inhibited IL‐1β release without altering its intracellular processing. Enhancing chloride efflux potentiated the release of IL‐1β, while decreasing it led to a strong reduction in its release. Because the stimulation of the P2X7 receptor also activates a chloride conductance, we investigated the possibility of a sole anionic pathway mobilized by the P2X7 receptor and ABC1. Glybenclamide and DIDS had no significant effects on the P2X7‐activated chloride current suggesting therefore the existence of two different pathways. In summary, ABC1 transporters are required for the release of IL‐1β by mouse Schwann cells. Being associated together with chloride conductance, P2X7 receptors and ABC1 transporters delineate a subtle and complex regulation of IL‐1β production in mammalian Schwann cells. Furthermore, ABC1 transporters could be a target of therapeutic interest for regulating IL‐1β activity in neuroinflammation disorders. GLIA, 2004. © 2004 Wiley‐Liss, Inc.
Constitutive nuclear localization of activated caspase 3 in subpopulations of the astroglial family of cells
Authors: Noyan‐Ashraf Mohammad Hossein , Brandizzi Federica , Juurlink Bernhard H.J.
Published: December 2004

In a study examining for apoptosis in spontaneously hypertensive rats (SHR), we observed the constitutive presence of activated caspase 3 in Bergmann glia. We then examined stroke‐prone SHR as well as the normotensive strains Wistar, Wistar Kyoto, and Sprague‐Dawley. In all these strains, we found that Bergmann glia expressed activated caspase 3 in nuclei. Furthermore, subpopulations of astrocytes in the granular layer of the cerebellar cortex, in the hippocampus, and spinal cord gray matter, particularly in the dorsal part of the dorsal horns, expressed nuclear activated caspase 3. This distribution corresponds to the distribution of astrocytes that express the glutamate transporter GLAST. We conclude that Bergmann glia and a subpopulation of astrocytes throughout the CNS express activated caspase 3 in nuclei to fulfill a yet‐to‐be defined non‐apoptotic function. GLIA. © 2004 Wiley‐Liss, Inc.
Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a Greek population
Authors: Papaconstantinou Ioannis , Theodoropoulos George , Gazouli Maria , Panoussopoulos Dimitris , Mantzaris Gerassimos J. , Felekouras Evangelos , Bramis John
Published: December 2004

Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example since patients with longstanding IBD are at increased risk for development of colorectal cancer (CRC). Therefore, genetic factors predisposing to or implicated in the chronic inflammatory process in IBD may simultaneously predispose to CRC. Recently CARD15/NOD2 has been associated with IBD, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the CARD15/NOD2 gene, which appear with significantly higher frequency in patients with IBD. In this report, we have examined the frequency of the 3 major mutations R702W, G908R and 3020insC of the CARD2/NOD2 gene in a series of 104 consecutive Greek patients with sporadic colorectal cancer and 100 healthy individuals. The frequency of all the mutations was significantly elevated compared to the control population (R702W, OR=5.00, p=0.023; G908R, OR=2.78, p=0.025; 3020insC, OR=2.44, p=0.017). Patients with advanced stage tumors were more frequently carriers of at least 1 variant in the CARD15/NOD2 gene (p=0.009). Our results suggest that CARD2/NOD2 may be a genetic factor that predispose to sporadic colorectal cancer. © 2005 Wiley‐Liss, Inc.
Nuclear or cytoplasmic expression of survivin: What is the significance?
Authors: Li Fengzhi , Yang Jie , Ramnath Nithya , Javle Milind M. , Tan Dongfeng
Published: December 2004

Growing evidence suggests that survivin expression in cancer cell nuclei may represent an important prognostic marker to predict disease outcome for cancer patients. Current reports in this research area, however, are inconsistent and propose opposing conclusions regarding the significance and prognostic value of survivin nuclear expression. The aim of our study is to review and discuss the data reported in the original publications. We have also provided new experimental data to support our view regarding the possible reasons for the observed inconsistencies in the literature. This would alert researchers to pay attention to potential pitfalls in the determination of nuclear or cytoplasmic expression of survivin for the future. © 2004 Wiley‐Liss, Inc.
p16INK4a promoter methylation and protein expression in breast fibroadenoma and carcinoma
Authors: Vinci Angela Di , Perdelli Luisa , Banelli Barbara , Salvi Sandra , Casciano Ida , Gelvi Ilaria , Allemanni Giorgio , Margallo Edoardo , Gatteschi Beatrice , Romani Massimo
Published: December 2004

The potential role of p16INK4a methylation in breast cancer is controversial whereas there are no data on fibroadenoma. To assess if inactivation of p16INK4a by promoter hypermethylation occurs in this hyperproliferative benign breast lesion or, on the contrary, it is strictly related to the carcinogenic process, we have tested the different histological components of 15 cases of fibroadenoma and the intraductal and infiltrating components of 15 cases of carcinoma and their adjacent non‐tumoral epithelium. All samples were obtained by laser‐assisted microdissection. The relationship between promoter methylation status, immunohistochemical protein expression and ki67 proliferative activity was evaluated for each lesion. Our data demonstrate that hypermethylation of p16INK4a promoter is a common event occurring at similar frequency in all the different histological areas of the benign and malignant breast lesions taken into exam. Conversely, protein p16 expression, although heterogeneously distributed within the section, is considerably higher in breast carcinoma as compared to fibroadenoma in both tumoral and non‐tumoral epithelia and stroma. The protein localization was almost exclusively nuclear in fibroadenoma and non‐tumoral epithelia whereas, in carcinoma, the staining was both nuclear and cytoplasmic or cytoplasmic alone. Furthermore, in a subset of fibroadenoma with higher proliferative activity, p16 protein expression was substantially decreased as compared to those showing lower proliferation. We did not observe this association in carcinomas. Our data demonstrate that the hypermethylation of the p16INK4a promoter is not specifically associated with malignancy and that, on the contrary, the overexpression of p16 and its cytoplasmic sequestration is a feature of breast carcinoma. © 2004 Wiley‐Liss, Inc.
Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid
Authors: Camphausen Kevin , Cerna David , Scott Tamalee , Sproull Mary , Burgan William E. , Cerra Michael A. , Fine Howard , Tofilon Philip J.
Published: December 2004

Valproic acid (VA) is a well‐tolerated drug used to treat seizure disorders and has recently been shown to inhibit histone deacetylase (HDAC). Because HDAC modulates chromatin structure and gene expression, parameters considered to influence radioresponse, we investigated the effects of VA on the radiosensitivity of human brain tumor cells grown in vitro and in vivo. The human brain tumor cell lines SF539 and U251 were used in our study. Histone hyperacetylation served as an indicator of HDAC inhibition. The effects of VA on tumor cell radiosensitivity in vitro were assessed using a clonogenic survival assay and γH2AX expression was determined as a measure of radiation‐induced DNA double strand breaks. The effect of VA on the in vivo radioresponse of brain tumor cells was evaluated according to tumor growth delay analysis carried out on U251 xenografts. Irradiation at the time of maximum VA‐induced histone hyperacetylation resulted in significant increases in the radiosensitivity of both SF539 and U251 cells. The radiosensitization was accompanied by a prolonged expression of γH2AX. VA administration to mice resulted in a clearly detectable level of histone hyperacetylation in U251 xenografts. Irradiation of U251 tumors in mice treated with VA resulted in an increase in radiation‐induced tumor growth delay. Valproic acid enhanced the radiosensitivity of both SF539 and U251 cell lines in vitro and U251 xenografts in vivo, which correlated with the induction of histone hyperacetylation. Moreover, the VA‐mediated increase in radiation‐induced cell killing seemed to involve the inhibition of DNA DSB repair. © 2004 Wiley‐Liss, Inc.
Morpholino antisense oligomer targeting human midkine: Its application for cancer therapy
Authors: Takei Yoshifumi , Kadomatsu Kenji , Yuasa Kanako , Sato Waichi , Muramatsu Takashi
Published: December 2004

Overexpression of a heparin‐binding growth factor, midkine (MK), has been observed in many malignancies, making it an attractive therapeutic target. We used morpholino antisense oligomers to downregulate human MK expression in human prostate (PC‐3) and colon carcinoma (SW620) cells, and determined the practical advantages of this anticancer therapeutic. Morpholino antisense oligomers directed against MK caused a dramatic and sequence‐specific decrease of the target protein level, resulting in the inhibition of growth and anchorage‐independent growth of the transfected cells. Furthermore, MK morpholino antisense oligomers exhibited a significant anticancer effect in the PC‐3‐ and SW620‐xenograft models. In comparison with phosphorothioate‐modified oligodeoxynucleotide, morpholino oligomers showed 2 major advantages, stability and non‐toxicity. MALDI‐TOF mass spectrometric analysis showed that morpholino antisense oligomers were completely stable in the presence of serum nuclease(s). Serological examinations demonstrated no toxicity of MK morpholino antisense oligomers. Our study indicates that inhibition of MK expression by morpholino antisense oligomer is a promising novel and safe therapeutic strategy for cancers. © 2004 Wiley‐Liss, Inc.
Enhancing growth human endothelial cells on Arg‐Gly‐Asp (RGD) embedded poly (ε‐caprolactone) (PCL) surface with nanometer scale of surface disturbance
Authors: Chung Tze‐Wen , Yang Min‐Gia , Liu Der‐Zen , Chen Wen‐Pin , Pan Chin‐I , Wang Shoei‐Shen
Published: December 2004

To explore the application of PCL for the engineering of soft tissues, the PCL surface was first embedded in an amphiphilic moiety and then grafted with RGD peptide to enhance the growth rate of human endothelial cells (HUVEC) on the surface. To graft cell‐adhesive peptide RGD on the PCL surface, the PCL surface was first etched by the selected solvent with only nanometer‐scale of surface disturbance, and simultaneously embedded with DSPE‐PEG [di‐stearoyl‐phosphatidyl‐ethanolamine‐methoxy‐poly (ethylene glycol)] moiety. Then the PCL‐PEG surface was photochemically grafted by GRGD to form PCL‐PEG‐RGD surface. PCL and the modified surfaces were characterized by surface morphology, surface disturbance, contact angles, ATR‐FTIR functional group analysis, and the growth rate of HUVEC. The surface disturbances of PCL and the modified surfaces were examined by atomic force microscope (AFM) and presented by the topography and a roughness parameter, Ra. The Ra values were 16.4 ± 3.0, 34.8 ± 1.6, and 12.8 ± 0.3 nm (n = 3) for PCL, PCL‐PEG, and PCL‐PEG‐RGD surfaces, respectively. The topographies of the surfaces and Ra values indicated that the PCL modified technique developed by this study resulted in only nanometer scale of surface disturbance. In addition to reducing surface disturbances, reducing contact angle from 73.7° ± 0.4 (n = 3) for the PCL surface to 56.9° ± 4.0 (n = 3) for the PCL‐PEG surface, and the ATR‐FTIR transmission spectra at 1660 cm−1 for shoulder of amine I of PCL‐PEG‐RGD surface both confirmed the successful modification of PCL surfaces. HUVECs adhered well and grew on the PCL‐PEG‐RGD surface after 36 h incubation, whereas other surfaces did not support growth. Moreover, the viability for the relative growth rate of HUVECs on the PCL‐PEG‐RGD surface analyzed by MTT assay showed 8.5 times greater growth than that of the unmodified one. In conclusion, a PCL‐PEG‐RGD surface for enhancing the growth rate of HUVECs has been prepared by a new technique that caused only a nanometer‐scale of surface disturbance. This technique and the PCL‐PEG‐RGD surface could be further applied to engineer soft tissues. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 213–219, 2005
Simulation of a compositional model for multiphase flow in porous media
Authors: Chen Zhangxin , Huan Guanren , Wang Hemei
Published: December 2004

In this article, we consider the simulation of a compositional model for three‐dimensional, three‐phase, multicomponent flow in a porous medium. This model consists of Darcy's law for volumetric flow velocities, mass conservation for hydrocarbon components, thermodynamic equilibrium for mass interchange between phases, and an equation of state for saturations. A discretization scheme based on the block‐centered finite difference method for pressures and compositions is developed. Numerical results are reported for the benchmark problem of the third comparative solution project (CSP) organized by the society of petroleum engineers (SPE). © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005.
On a finite element method for a compressible viscous flow in a MOCVD reactor
Authors: Duque Jairo
Published: December 2004

We propose a stable finite element method for approximating the flow of a chemically reacting gas mixture in an MOCVD (metal‐organic chemical vapor deposition) reactor. The flow is governed by the full compressible Navier‐Stokes equations extended by transport equations for the chemical species, the energy equations and the equation of state, together with boundary conditions providing information on the reactor geometry and experimental conditions. The equations form a semilinear system with a constraint for which the corresponding pressure term is not the Lagrangian multiplier. An application of our method to a real world model of growth of GaAs shows the consistency with experimental data. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Modelling of Swelling Phenomena in Charged Hydrated Porous Media
Authors: Acartürk Ayhan , Ehlers Wolfgang , Abbas Ibrahim
Published: December 2004

Biological tissues like articular cartilage and geomaterials like clay have a multicomponent microstructure. The charged solid is saturated by a viscous fluid, which itself is composed of several components: the liquid solvent and the dissolved ions, namely, water, anions and cations. These charged multiphase materials exhibit a swelling behaviour under varying chemical conditions.

The model describing such materials combines electrochemical and mechanical effects like osmosis and electrostatics within a macroscopic formulation. Starting from the Theory of Porous Media (TPM), a four component model is presented, wherein all constituents are materially incompressible and mass exchanges are excluded. This isothermal model leads to a set of equations which consists of three primary variables: the solid displacement uS, the pore‐pressure p and the molar ion concentration cm, since the ion concentrations always depend on each other because of the electroneutrality condition.

For the numerical treatment, the weak formulations of governing equations are implemented in the FE tool PANDAS, wherein Taylor‐Hood elements are used for the spatial discretization. Finally, a simulation of a 3‐d swelling experiment is shown. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optimization of piezoelectric fiber distribution in composite smart materials
Authors: Bohn Niels , Gabbert Ulrich
Published: December 2004

A new approach to obtain macroscopic properties of fiber‐matrix composite materials is given by the optimization of the fiber distribution for a given pair of materials. The optimization was carried out by Evolution Strategies using an interface to the finite‐element‐software ANSYS. To cover the effects of varied micro level parameters, a homogenization algorithm was included in the optimization process. Two applications verify the correct implementation of the software. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Numerical investigation of microstructure evolution in metal forming processes
Authors: Bontcheva Nikolina , Petzov Georgi , Iankov Roumen
Published: December 2004

Grain size evolution and phase transformation during metal forming processes is investigated numerically by means of the Finite element method. Appropriate microstructure models are involved into the FEM code MSC.MARC. Material characteristics obtained by means of own experiments are used. Hot closed die forging and rod rolling are considered. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Macroscopic finite element analyses of discretematerials based on directly evaluated micro‐macro transitions
Authors: Dettmar Joachim , Miehe Christian
Published: December 2004

We consider a homogenized macro‐continuum with locally attached microstructure of granules and derive specific micromacro transitions by a consistent transfer of discrete micro‐variables to field variables on a continuous macrostructure. Displacements and rotational constraints are imposed on the granules on the defined boundary frame of the microstructure. The constraints for linear displacements and uniform tractions on the surface yield upper and lower bound characteristics for periodic boundary conditions with regard to the aggregate stiffness. Secondly, we perform two‐scale analyses where we link simulations on the macro‐ and the microscales. Therein, coupled boundary‐value problems are solved on both scales. The macroscopic homogeneous problem is solved by a finite element method where the material model is implemented using the directly evaluated micro‐macro transitions on the basis of the discrete microstructures. Finally, a model problem is investigated to clarify the proposed method. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A unified approach for elasto‐plastic FEM simulations, incorporating adaptive spatial and time discretization
Authors: Eckert Steffen , Gross Dietmar
Published: December 2004

In FEM calculations the discretization should be chosen in a way, that further mesh refinement does not change the results. Otherwise the discretization error might yield unphysically stiff material behavior. If elasto‐plasticity is considered, a second type of error due to the time discretization of the evolution equations has to be taken into account. Due to the non‐linearity of the underlying initial boundary value problem, large time increments often result in non‐converging solutions during equilibrium iteration.

In our approach the time integration error resulting from a second order BDF2 time integration method is calculated and utilized in an automatic step size control. In conjunction with a DAE‐treatment of the initial boundary value problem, it allows in the average considerably larger time steps compared to classical ‘elastic predictor – plastic corrector’ schemes. To reduce the discretization error, adaptive mesh‐refinement based on a Z2‐error‐estimator is performed. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the numerical treatment of multiphasic flow processes in deformable porous media
Authors: Graf Tobias , Ehlers Wolfgang
Published: December 2004

The description of multiphasic flow processes and their interaction with a deformable solid skeleton plays an important role in a big field of engineering applications, as for example in the modelling of partially saturated soil or groundwater contamination. For a numerical simulation of such a material behaviour, a triphasic continuum mechanical model based on a multiphasic formulation embedded in the well‐founded framework of the Theory of Porous Media (TPM) is used. Therein, the single constituents are a materially incompressible elasto‐viscoplastic solid skeleton and materially compressible or incompressible pore‐fluids, e. g., water, oil or air. The numerical treatment is based on the weak formulations of the governing equations, where the primary variables are the displacement of the solid skeleton and the effective pressures or saturations of the pore‐fluids. An initial boundary‐value problem concerning an infiltration problem in a heterogeneous porous material is discussed in detail, where the resulting system of strongly coupled differential‐algebraic equations is solved by the FE tool PANDAS. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Stress And Strain in a Yeast Cell Under High Hydrostatic Pressure
Authors: Hartmann Christoph , Delgado Antonio
Published: December 2004

The mechanical effects of the compression of a yeast cell (Saccharomyces cerevisiae) under high hydrostatic pressure (HHP) are modeled and simulated numerically. The deformation of the cell under pressure deviates strongly from isotropic volume reduction. In the cell wall, von‐Mises stress reaches the critical value upon failure at a pressure load between 415Mpa and 460MPa. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Theory and implementation of orthotropic materials in growing continua
Authors: Himpel Grieta , Kuhl Ellen , Menzel Andreas , Steinmann Paul
Published: December 2004

Most biological tissues show a material behavior which is characterized through a pronounced anisotropy. In particular hard tissues such as bones or soft tissues as muscles are commonly modeled as either transversely isotropic or even orthotropic. In contrast to engineering materials, however, biological tissues possess the ability to adapt, e.g. their density, to the current loading situation. Based on a formulation for growth in isotropic continua, see for instance Kuhl, Menzel & Steinmann [3], and transversely isotropic continua as discussed e.g. in Himpel [2], we attend to a model for the functional adaption of orthotropic biomaterials. The material model has been implemented in a finite element code and is studied by means of a numerical example. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Micro‐Macro Modelling of Piezoelectric Fiber Composites
Authors: Kari Sreedhar , Berger Harald , Gabbert Ulrich
Published: December 2004

The present work deals with the numerical modeling of 1‐3 periodic composites made of piezoceramic (PZT) fibers embedded in a soft non‐piezoelectric matrix. We especially focus on predicting the effective co‐efficients of the periodic transversely isotropic piezoelectric fiber composites using representative volume element method (unit cell method). The results which are obtained from the FEM technique are compared with analytical homogenization method for different volume fractions. The effective co‐efficients are obtained for rectangular and hexagonal arrangement of unidirectional piezoelectric fiber composites. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Large deformation frictional contact formulation based on a velocity description
Authors: Konyukhov Alexander , Schweizerhof Karl
Published: December 2004

The main idea of the velocity description is to describe kinematics of the contact in the specially defined local surface coordinate system which is related to the closest point projection procedure. All necessary operations for the description of the contact problems: kinematics, all differential operations etc. are considered from the geometrical point of view. While exploiting the differential geometry of the contact surfaces a consistent formulation for the contact problem, including friction is obtained. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Strongly Coupled Analysis of Fluid‐Structure Interaction with Free Surface Flow
Authors: Kölke Andreas , Walhorn Elmar , Hübner Björn , Dinkler Dieter
Published: December 2004

For the numerical analysis of interactions of immiscible two‐fluid flows and lightweight elastic structures a discretization method based on stabilized space‐time finite elements is applied. The use of the level set method provides an implicitly given description of the evolving flow domains and useful geometrical information of the moving and topological changing fluid‐fluid interface. Due to the choice of a proper enriched basis within the partition of unity concept, the method is able to capture strong discontinuous solutions in space and time introduced by interfacial jump conditions and different material properties on each side of the moving interface. A numerical example demonstrates the ability of the method to handle complex free surface flow situations and their interplay with elastic bodies. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Simulation of Piezoelectric Smart Lightweight Structures by the Finite Element Method for Acoustic Control
Authors: Lefèvre Jean , Gabbert Ulrich
Published: December 2004

Piezoelectric patches are widely used as distributed actuators and sensors for active vibration control. Active control of sound in this way is mainly interesting in the low frequency range, where passive methods are less effective. To simulate such electromechanical‐acoustical systems a virtual overall model based on the FEM is presented in the paper. Different approaches for model reduction with respect to controller design purposes are discussed. As a simple test example the numerical model of an acoustic box is studied. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)