bluuebunny/crossref_metadata_2025 huggingface dataset:
Von der kovalenten Bindung zur Struktur des Wassermoleküls. Ein Beispiel für kooperatives Lernen in der Sekundarstufe I
Authors: Markic Silvija , Kienast Stephan , Eilks Ingo
Published: May 2004

IN VERSCHIEDENEN VERÖFFENTLICHUNGEN haben wir in den letzten drei Jahren diskutiert, pragmatischer und schülerorientierter mit der Vermittlung des Teilchenkonzepts im Chemieunterricht der Sekundarstufe I umzugehen. Hierbei haben wir vorgeschlagen, schrittweise ein in sich konsistentes und auf jeder Stufe anschlussfähiges Konzept zu vermitteln, das aus einem einfachen Teilchenkonzept, einem Atom‐ und Atombaukonzept und einem Konzept von der Struktur der kovalent aufgebauten Verbindungen bestehen könnte. In diesem Beitrag wird beschrieben, wie nach der Einführung der ersten beiden Konzepte der letzte Schritt hin zum Elektronenpaarabstoßungskonzept in verschiedenen Formen des kooperativen Lernens von den Schülerinnen und Schülern erarbeitet werden kann.
Otto Ruff und Alfred Wohl. Professoren der 1904 gegründeten Königlichen Technischen Hochschule zu Danzig
Authors: Sokolowska Teresa , Piosik Romuald
Published: May 2004

NEBEN ZAHLREICHEN berühmten Wissenschaftlern, die an der Technischen Hochschule (Abb. 1) tätig waren, sind auch die Professoren Otto Ruff und Alfred Wohl zu nennen. In diesem Beitrag wird über die wissenschaftlichen Leistungen dieser beiden berichtet.
Untersuchung des Fortbildungsverhaltens und der Fortbildungswünsche von Chemielehrerinnen und Chemielehrern
Authors: Daus Jessica , Pietzner Verena , Höner Kerstin , Scheuer Rupert , Melle Insa , Neu Christoph , Schmidt Stefanie , Bader Hans Joachim
Published: May 2004

DIE ANALYSE DES Fortbildungsverhaltens und der Fortbildungswünsche von Chemielehrerinnen und ‐lehrern war Gegenstand einer im Jahr 2002 durchgeführten und vom Fonds der Chemischen Industrie geförderten empirischen Untersuchung der drei Chemielehrerfortbildungszentren Braunschweig, Dortmund und Frankfurt. In diesem Artikel werden die zentralen Ergebnisse der mittels Fragebögen und Interviews erhobenen Daten von über 2.000 Chemielehrerinnen und ‐ lehrern vorgestellt.
Rac‐induced increase of phosphorylation of myosin regulatory light chain in HeLa cells
Authors: Brzeska Hanna , Szczepanowska Joanna , Matsumura Fumio , Korn Edward D.
Published: May 2004

The pathways by which activation of the small GTP‐binding protein Rac causes cytoskeletal changes are not fully understood but are likely to involve both assembly of new actin filaments and reorganization of actin filaments driven by the actin‐dependent ATPase activity of myosin II. Here we show that expression of active RacQ61 in growing HeLa cells, in addition to inducing ruffling, substantially enhances the level of phosphorylation of serine‐19 of the myosin II regulatory light chain (MLC), which would increase actomyosin II ATPase and motor activities. Phosphorylated myosin was localized to RacQ61‐induced ruffles and stress fibers. RacQ61‐induced phosphorylation of MLC was reduced by a maximum of about 38% by an inhibitor (Tat‐PAK) of p21‐activated kinase (PAK), about 35% by an inhibitor (Y‐27632) of Rho kinase, 51% by Tat‐PAK plus Y‐27632, and 10% by an inhibitor (ML7) of myosin light chain kinase. Staurosporine, a non‐specific inhibitor of serine/threonine kinases, reduced RacQ61‐induced phosphorylation of MLC by about 58%, at the maximum concentration that did not kill cells. Since Rac activates PAK and PAK can phosphorylate MLC, these data strongly suggest that PAK is responsible for a significant fraction of RacQ61‐induced MLC phosphorylation. To our knowledge, this is the first evidence that active Rac causes phosphorylation of MLC in cells, thus implicating activation of the ATPase activity of actomyosin II as one of the ways by which Rac may induce cytoskeletal changes. Cell Motil. Cytoskeleton 58:186–199, 2004. Published 2004 Wiley‐Liss, Inc.
Use of information resources by patients with cancer and their companions
Authors: Basch Ethan M. , Thaler Howard T. , Shi Weiji , Yakren Sofia , Schrag Deborah
Published: May 2004

BACKGROUND

Use of the Internet is common among patients with cancer and their companions. However, little is known about patterns of use of print or telephone‐based resources amidst growing Internet utilization, nor is it known whether different types of information are sought from electronic compared with print media. It is not clear as to whether patients and their companions differ in their patterns of content seeking.

METHODS

A survey was developed to evaluate the use of electronic and nonelectronic informational resources by patients and their companions. During a 10‐week period, this questionnaire was administered to 443 outpatients and 124 paired companions attending an urban academic cancer center.

RESULTS

In this cohort, 64% of patients and 76% of companions were computer owners, with home Internet access indicated by 58% and 68%, respectively. Use of the Internet to obtain cancer‐related information was reported by 44% of patients and 60% of companions. Print resources were used by 79% of patients and 83% of companions, with telephone resources used by 22% and 23%, respectively. The majority of Internet users also read print content (85%), whereas one‐half of print users did not access data electronically (52%). Topic areas sought via print and the Internet were similar, with the exception of nutrition‐related information, which was more commonly sought in print texts. There was a high rate of concordance between patient and companion use of both electronic and nonelectronic resources.

CONCLUSIONS

Despite recent publicity and scrutiny focusing on the quality of Internet health care content, print products remain the most common source of information sought by patients with cancer. Future investigation should focus on the quality of print products used by patients. Cancer 2004. © 2004 American Cancer Society.
Fludarabine and mitoxantrone for patients with chronic lymphocytic leukemia
Authors: Tsimberidou Apostolia M. , Keating Michael J. , Giles Francis J. , Wierda William G. , Ferrajoli Alessandra , Lerner Susan , Beran Miloslav , Andreeff Michael , Kantarjian Hagop M. , O'Brien Susan
Published: May 2004

BACKGROUND

The objective of the current study was to assess the efficacy of combination therapy with fludarabine and mitoxantrone in patients with B‐cell chronic lymphocytic leukemia (CLL).

METHODS

Eighty‐eight patients were treated with fludarabine 30 mg/m2 intravenously daily for 3 days and mitoxantrone 10 mg/m2 on Day 1 (FN). Patients were divided into four groups based on expected response to single‐agent fludarabine. These four groups included previously untreated patients, patients who previously were treated with alkylating agents, patients who were successfully treated with alkylating agents and fludarabine but who developed recurrent disease, and patients whose disease was refractory to fludarabine with or without alkylating agents.

RESULTS

The overall response rate was 66%. The response rates were 83% in previously untreated patients, 87% in patients previously treated with alkylating agents, 50% in patients whose disease was not refractory to fludarabine at the start of therapy, and 25% in patients whose disease was refractory to fludarabine. The complete remission (CR) rate was 20% for previously untreated patients, which was not significantly different from the CR rate for a group of historical control patients who were treated with single‐agent fludarabine. The median follow‐up was 8 years for surviving patients. The median progression free survival was 24 months for all patients and 34 months for previously untreated patients. The median overall survival was 40 months, and the median survival of previously untreated patients was 88 months. The most common toxicities were myelosuppression and infection. Eleven patients (12.5%) developed a second malignancy after a median of 62 months.

CONCLUSIONS

The FN regimen did not have a significant advantage over fludarabine alone in the treatment of patients with CLL. Cancer 2004. © 2004 American Cancer Society.
Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma
Authors: Shelley Hwang E. , Nyante Sarah J. , Yi Chen Yunn , Moore Dan , DeVries Sandy , Korkola James E. , Esserman Laura J. , Waldman Frederic M.
Published: May 2004

BACKGROUND

Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor‐product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array‐based comparative genomic hybridization (CGH).

METHODS

Twenty‐four samples from the University of California–San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer–amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and ILC were compared.

RESULTS

A substantial proportion of the genome was altered in samples of both LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole‐arm changes. Smaller regions of gain and loss were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score.

CONCLUSIONS

LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma. Cancer 2004. © 2004 American Cancer Society.
Weekly combination chemotherapy with docetaxel and gemcitabine as first‐line treatment for elderly patients and patients with poor performance status who have extensive‐stage small cell lung carcinoma
Authors: Hainsworth John D. , Carrell Donna , Drengler Ronald L. , Scroggin Carroll , Greco F. Anthony
Published: May 2004

BACKGROUND

The goal of the current study was to evaluate the feasibility, toxicity, and efficacy of a novel combination of weekly docetaxel and gemcitabine for elderly patients and patients with poor performance status who had advanced‐stage small cell lung carcinoma (SCLC).

METHODS

Previously untreated patients with advanced‐stage SCLC were eligible for the current clinical trial. In addition, patients were required to be age > 65 years or to have poor performance status (Eastern Cooperative Oncology Group 2). All patients received 800 mg/m2 gemcitabine and 30 mg/m2 docetaxel intravenously on Days 1, 8, and 15. Courses were repeated at 28‐day intervals.

RESULTS

Forty patients were enrolled in the current multicenter, community‐based trial. Nine patients (23%) had partial responses to treatment. The median survival for the entire group was 4 months. Fourteen percent of patients were alive at 1 year. Myelosuppression was mild to moderate, with no episodes of neutropenia and fever. Grade 3/4 fatigue (25%) was the only common nonhematologic toxicity.

CONCLUSIONS

Although relatively well tolerated, the weekly regimen of gemcitabine and docetaxel possessed only modest activity in this group of patients with unfavorable prognosis. The regimen offered no potential advantages over standard treatment approaches and is not recommended for further development. Cancer 2004. © 2004 American Cancer Society.
Preoperative induction of CPT‐11 and cisplatin chemotherapy followed by chemoradiotherapy in patients with locoregional carcinoma of the esophagus or gastroesophageal junction
Authors: Ajani Jaffer A. , Walsh Garrett , Komaki Ritsuko , Morris Jeff , Swisher Stephen G. , Putnam Joe B. , Lynch Patrick M. , Wu Tsung‐Teh , Smythe Roy , Vaporciyan Ara , Faust Josephine , Cohen Deborah S. , Nivers Rebecca , Roth Jack A.
Published: May 2004

BACKGROUND

Patients with localized esophageal carcinoma often develop locoregional and distant disease recurrence. The current study investigated the outcome of a new chemotherapy combination as induction therapy before chemoradiotherapy.

METHODS

Forty‐three patients with resectable carcinoma of the esophagus or gastroesophageal junction were enrolled. Most of the tumors were endoscopic ultrasonography (EUS) EUST3 (84%) and EUSN1 (63%). The patients received ≤ 2 6‐week cycles of CPT‐11 and cisplatin followed by chemoradiotherapy (45 grays with 5‐fluorouracil and paclitaxel). Five to six weeks after chemoradiotherapy, the patients underwent staging and surgery. The feasibility, curative resection rates, overall and disease‐free survival rates, rate of significant pathologic response, and patterns of disease recurrence were assessed.

RESULTS

Of the 43 patients, 39 (91%) underwent an R0 resection. Two patients (5%) died after surgery. A pathologic complete response (pathCR) was observed in 11 (28%) of the 39 patients (or 26% of the 43 patients). In addition, 16 patients (41% of 39 patients or 37% of 43 patients) had < 10% viable tumor in the surgical specimen (pathPR). A comparison of endoscopic ultrasonograpy T and N classifications with surgical T and N classifications demonstrated significant down‐staging (P < 0.01). The median survival period of all 43 patients was 22.1 months. Patients who had achieved a pathCR or pathPR had a longer median survival (25.6 months) than those who achieved less than a pathPR (18.5 months; P = 0.52). None of the clinical parameters examined were found to correlate with survival or pathologic response.

CONCLUSIONS

CPT‐11–based induction chemotherapy resulted in substantial pathCR and pathPR rates, both of which lead to a favorable survival outcome. The three‐step strategy needs to be developed further, with the investigation of targeted therapies with chemotherapy and radiotherapy. Cancer 2004. © 2004 American Cancer Society.
Erythropoietin is effective in improving the anemia induced by imatinib mesylate therapy in patients with chronic myeloid leukemia in chronic phase
Authors: Cortes Jorge , O'Brien Susan , Quintas Alfonso , Giles Francis , Shan Jianquin , Rios Mary Beth , Talpaz Moshe , Kantarjian Hagop
Published: May 2004

BACKGROUND

Myelosuppression occurs in up to 50% of patients with chronic myeloid leukemia (CML) who are treated with imatinib and ≥ Grade 3 myelosuppression is reported in approximately 10% of patients.

METHODS

The authors investigated the prognostic significance of anemia occurring during therapy with imatinib in patients with CML in chronic phase.

RESULTS

Of 338 patients treated with imatinib (150 patients after interferon failure and 188 patients with newly diagnosed CML), 230 (68%) developed anemia. In a multivariate analysis, factors associated with an increased probability of developing anemia were a starting hemoglobin level < 12 g/dL, age ≥ 60 years, female gender, higher imatinib dose, and intermediate or high Sokal risk group. Of these 230 patients, 102 patients received treatment with 40,000 U of recombinant human erythropoietin administered subcutaneously once weekly. An increase in the hemoglobin level of ≥ 2 g/dL was achieved in 69 patients (68%) and 22 patients (22%) had an increase of 1–1.9 g/dL. Patients who developed anemia had a trend toward a lower probability of complete cytogenetic remission compared with patients without anemia (68% vs. 77%;P= 0.14), as well as a trend for inferior survival. Patients with anemia and other manifestations of myelosuppression were found to have a significantly worse outcome than those with isolated anemia.

CONCLUSIONS

The authors concluded that erythropoietin is safe and effective in patients in chronic‐phase CML who develop anemia with imatinib therapy. Cancer 2004. © 2004 American Cancer Society.
Expression of cell cycle proteins in T1a and T1b urothelial bladder carcinoma and their value in predicting tumor progression
Authors: Mhawech Paulette , Greloz Vincent , Oppikofer Chantal , Szalay‐Quinodoz Idliko , Herrmann Francois
Published: May 2004

BACKGROUND

Cell cycle proteins are important markers in predicting tumor behavior in urothelial carcinoma of the bladder. The objectives of this study were 1) to determine the expression levels of some of those markers in a series of patients with bladder carcinoma, 2) to define their value in distinguishing T1a (minimally invasive) from T1b (invasive) tumors, and 3) to evaluate their use as predictive factors in the progression of T1a and T1b tumors.

METHODS

Tumor specimens from 101 patients were included (22 Ta specimens, 34 T1a specimens, 15 T1b specimens, and 30 T2 specimens). A tissue microarray from the 101 paraffin embedded tissue blocks was constructed. Immunohistochemistry for p16, p27, p21, p53, cyclin D1, and Ki‐67 were performed. To evaluate T1a and T1b tumor progression, clinical and follow‐up data were available for all 49 patients.

RESULTS

Cyclin D1 and p27 were the only markers that showed a significant association with tumor stage and tumor grade (cyclin D1: P = 0.002 and P > 0.00, respectively; p27: P = 0.024 and P = 0.031, respectively). The results indicated that a combination of p21 (odds ratio, 5.7; 95% confidence interval [95% CI], 1.3–24.8 [P = 0.022]) and p16 (odds ratio, 3.7; 95% CI, 0.8–16.5 [P = 0.081]) may have potential use in distinguishing T1b tumors from T1a tumors. Finally, none of the markers examined were found to have predictive value for T1a and T1b tumor progression.

CONCLUSIONS

The expression of cyclin D1 and p27 was associated with the most important prognostic factors (tumor stage and grade). The combination of p21 and p16 may have value in distinguishing T1b tumors from T1a tumors, although this finding must be evaluated in much larger series. Finally, none of the markers studied appeared to have predictive value for disease progression in patients with T1a and T1b urothelial bladder tumors. Cancer 2004. © 2004 American Cancer Society.
DFT Calculations on the C−Cl/Si−H Exchange Catalyzed by P,N‐Chelated PtII Complexes
Authors: Sturmayr Dietmar , Schubert Ulrich
Published: May 2004

The mechanism of the previously reported C−Cl/Si−H exchange reaction between HxCCl4−x (x = 0−3) and HSiMe2Ph catalyzed by [PtMeCl(Ph2PCH2CH2NMe2‐κ2P,N)] [PtMeCl(P∩N)] was investigated by DFT calculations. The energetically less‐favored isomer of [PtMeCl(P∩N)], with Cl and P being cis, was identified to be the actual catalytic species. The catalytic reaction proceeds by oxidative addition of the silane, de‐coordination of the nitrogen atom of the P,N‐chelating ligand, reductive elimination of the chlorosilane and oxidative addition of the C−Cl bond of HxCCl4−x. The final step is the reductive elimination of the C−H bond with concomitant re‐coordination of the nitrogen atom of the P,N‐chelating ligand. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Characterization and Applications of a Bismuth Bulk Electrode
Authors: Pauliukaitė Rasa , Hočevar Samo B. , Ogorevc Božidar , Wang Joseph
Published: May 2004

A bismuth bulk electrode (BiBE), a new solid‐state electrode, is presented. The polycrystalline metal bismuth disk‐shaped electrode was examined for its anodic stripping voltammetry performance, which was found to be well comparable to that achieved with the bismuth or mercury film electrodes. Useful potential windows of the BiBE in aqueous solutions of pH 1 to 13 were found to range from approximately −1.7 to −0.1 V, depending on pH, where either hydrogen evolution or anodic dissolution of metallic bismuth limit the electrochemical inertness of the BiBE. Employing cyclic voltammetry (CV), the cathodic behavior of the BiBE was examined by testing inorganic (cadmium(II) ions) and organic (2‐nitrophenol) model compounds; a CV quasi‐reversible behavior was recorded in the case of the Cd(II)‐Cd(0) couple. The characteristics of the BiBE under anodic conditions, i.e., at bismuth surface coated with a thin conductive Bi2O3 film, was examined by testing two well‐established redox systems, potassium hexacyanoferate(III) and ruthenium(III) hexaaminechloride; a nearly reversible behavior was recorded in the latter case. Based on the presented preliminary results, BiBE can be considered as an interesting alternative to common solid and (toxic) mercury electrodes for possible use in electrochemical studies and electroanalytical applications.
Genomic aberrations in carcinomas of the uterine corpus
Authors: Micci Francesca , Teixeira Manuel R. , Haugom Lisbeth , Kristensen Gunnar , Abeler Vera M. , Heim Sverre
Published: May 2004

Endometrial carcinoma, the most common invasive neoplasm of the female genital tract, occurs either in a hormone‐related, less virulent form (type I) or in a hormone‐independent, more aggressive form (type II). Another cancer of the uterine corpus is carcinosarcoma, a biphasic or mixed epithelial–mesenchymal tumor, now classified as metaplastic carcinoma. We examined by karyotyping and comparative genomic hybridization a consecutive series of 67 endometrial carcinomas and 15 carcinosarcomas and compared the cytogenetic features of the different carcinoma subtypes. All three subtypes of uterine carcinoma had in common a nonrandom gain of material from 1q and 8q but differed from one another in other respects. Endometrial carcinomas of type I mostly presented gains from chromosome arms 1q and 8q and losses from Xp, 9p, 9q, 17p, 19p, and 19q, whereas endometrial carcinomas of type II showed a more complex imbalance picture, with gains from chromosome arms 1q, 2p, 3q, 5p, 6p, 7p, 8q, 10q, and 20q and losses from Xq, 5q, and 17p. The carcinosarcomas mostly showed gains of or from 1q, 5p, 8q, and 12q but losses from 9q, that is, they were much more similar to endometrial carcinomas in their pattern of acquired genomic changes than to sarcomas of the uterine corpus. It was also possible to identify different copy number changes among the different grades of type I carcinomas, between serous papillary and clear‐cell carcinomas of type II, as well as between homologous and heterologous carcinosarcomas. Specifically, type I adenocarcinomas that were highly differentiated mostly showed gains from 1q and 10p; those that were moderately differentiated showed gains from 1q, 7p, 7q, and 10q as well as losses from Xp, 9p, 9q, 17p, 19p, and 19q; whereas those poorly differentiated showed gains from 1q, 2p, 2q, 3q, 6p, 8q, and 20q but losses from Xp, Xq, 5q, 9p, 9q, 17p, and 17q. The serous papillary carcinomas showed gains from 1q, 2p, 2q, 3q, 5p, 6p, 6q, 7p, 8q, 18q, 20p, and 20q but losses from 17p, whereas the clear‐cell carcinomas showed gains from 3q, 7p, 8q, 10q, 16p, and 20q but losses from 6q. Finally, the homologous carcinosarcomas presented gains from 1p, 1q, 8q, 12q, and 17q as well as losses from 9q and 13q, whereas the heterologous tumors showed gains from 1q, 8p, and 8q. The reproducibility of the observed correlations between karyotypic aberration patterns and histological differentiation was underscored by the fact that those carcinosarcomas whose epithelial component resembled type I endometrial carcinomas also exhibiting a type I aberration profile, whereas carcinosarcomas with a type II carcinoma differentiation had karyotypic abnormalities similar to those of type II endometrial carcinomas. © 2004 Wiley‐Liss, Inc.
HNPCC mutation MLH1 P648S makes the functional protein unstable, and homozygosity predisposes to mild neurofibromatosis type 1
Authors: Raevaara Tiina E. , Gerdes Anne‐Marie , Lönnqvist Karin E. , Tybjærg‐Hansen Anne , Abdel‐Rahman Wael M. , Kariola Reetta , Peltomäki Päivi , Nyström‐Lahti Minna
Published: May 2004

Heterozygous germ‐line mutations in DNA mismatch repair (MMR) genes predispose individuals to hereditary nonpolyposis colorectal cancer (HNPCC), whereas with homozygous MMR gene mutations children are diagnosed at an early age with de novo neurofibromatosis type 1 (NF1) and/or hematological malignancies. Here, we describe a mutation, MLH1 P648S, which was found in a typical HNPCC family, with one homozygous child displaying mild features of NF1 and no hematological cancers. To evaluate the pathogenicity of the mutation, we studied both the expression and the function of the mutated protein. It generally has been assumed that the predisposing mutations prevent the production of a functional protein. The mutated MLH1 P648S protein was found to be unstable but still functional in mismatch repair, suggesting that the cancer susceptibility in the family and possibly also the mild disease phenotype in the homozygous individual are linked to shortage of the functional protein. © 2004 Wiley‐Liss, Inc.
Maximum‐likelihood estimation of haplotype frequencies in nuclear families
Authors: Becker Tim , Knapp Michael
Published: May 2004

The importance of haplotype analysis in the context of association fine mapping of disease genes has grown steadily over the last years. Since experimental methods to determine haplotypes on a large scale are not available, phase has to be inferred statistically. For individual genotype data, several reconstruction techniques and many implementations of the expectation‐maximization (EM) algorithm for haplotype frequency estimation exist. Recent research work has shown that incorporating available genotype information of related individuals largely increases the precision of haplotype frequency estimates. We, therefore, implemented a highly flexible program written in C, called FAMHAP, which calculates maximum likelihood estimates (MLEs) of haplotype frequencies from general nuclear families with an arbitrary number of children via the EM‐algorithm for up to 20 SNPs. For more loci, we have implemented a locus‐iterative mode of the EM‐algorithm, which gives reliable approximations of the MLEs for up to 63 SNP loci, or less when multi‐allelic markers are incorporated into the analysis. Missing genotypes can be handled as well. The program is able to distinguish cases (haplotypes transmitted to the first affected child of a family) from pseudo‐controls (non‐transmitted haplotypes with respect to the child). We tested the performance of FAMHAP and the accuracy of the obtained haplotype frequencies on a variety of simulated data sets. The implementation proved to work well when many markers were considered and no significant differences between the estimates obtained with the usual EM‐algorithm and those obtained in its locus‐iterative mode were observed. We conclude from the simulations that the accuracy of haplotype frequency estimation and reconstruction in nuclear families is very reliable in general and robust against missing genotypes. © 2004 Wiley‐Liss, Inc.
Response of heterograft heart valve biomaterials to moderate cyclic loading
Authors: Sun Wei , Sacks Michael , Fulchiero Gregory , Lovekamp Joshua , Vyavahare Naren , Scott Michael
Published: May 2004

We have recently demonstrated that noncalcific tissue damage can lead to significant collagen degradation in clinically explanted bioprosthetic heart valves (BHVs). In the present study we quantified the early response of glutaraldehyde treated bovine pericardium (GLBP) to cyclic tensile loading to begin to elucidate the mechanisms of noncalcific tissue degeneration in BHV biomaterials. GLBP specimens were cycled at 30 Hz to a maximum uniaxial strain of 16% (corresponding to approximately 1‐MPa peak stress), with the loading direction parallel to the preferred collagen fiber (PD) direction. After 30 × 106 cycles, specimens were subjected to biaxial mechanical testing, then cycled until 65 × 106 cycles. The results indicated a permanent change in the unloaded tissue dimensions of +7.1% strain in the PD direction and −7.7% strain in the cross fiber direction (XD) after 65 × 106 cycles and an increase of the collagen crimp period from 40.6 to 45.2 μm by 65 × 106 cycles (p = 0.05). Fourier transform IR spectroscopy analysis indicated that cyclic fatigue of GLBP leads to both collagen conformational changes and early denaturation. Furthermore, no significant changes in areal strain were found under 1‐MPa equibiaxial stress, indicating that cyclic loading changed the collagen fiber orientation but not the overall tissue compliance. These observations suggest that while deterioration of collagen begins immediately, fiber straightening and reorientation dominates the changes in the mechanical behavior up to 65 × 106 cycles. The present study underscores the complexity of the response of biologically derived biomaterials to cyclic mechanical loading. Improved understanding of these phenomena can potentially guide the development of novel chemical treatment methods that seek to improve BHV durability by minimizing these degenerative processes. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 658–669, 2004
A molecular modeling study of the effect of surface chemistry on the adsorption of a fibronectin fragment spanning the 7–10th type III repeats
Authors: Wilson Kerry , Stuart Steven J. , Garcia Andrés , Latour Robert A.
Published: May 2004

Although it is well documented that proteins adsorb onto biomaterial surfaces, relatively little is quantitatively understood about the effects of adsorption on protein orientation and conformation. Because this is the primary determining factor of protein bioactivity, the ability to accurately predict a protein's orientation and conformation following adsorption will be essential for the rational design of biomaterial surfaces to control biological responses. Force field‐based computational chemistry methods provide an excellent means to theoretically address this issue, with the nontrivial requirement that the force field must be tailored to appropriately represent protein adsorption behavior. Accordingly, we have modified an existing force field (CHARMm) based on semiempirical quantum‐mechanical peptide adsorption data to enable it to simulate protein adsorption behavior in an implicit aqueous environment. This modified force field was then applied to predict the adsorption behavior of the 7–10 type III repeats of fibronectin on functionalized surfaces. Predicted changes in adsorption energy and adsorption‐induced conformation as a function of surface chemistry were found to correlate well with experimentally observed trends for these same systems. This work represents a first attempt towards the development of a molecular mechanics force field that is specifically parameterized to accurately simulate protein adsorption to biomaterial surfaces. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 686–698, 2004
Genetics and cell biology of lysophosphatidic acid receptor‐mediated signaling during cortical neurogenesis
Authors: Kingsbury M.A. , Rehen S.K. , Ye X. , Chun J.
Published: May 2004

Lysophosphatidic acid (LPA) is a small lysophospholipid that signals through G‐protein coupled receptors (GPCRs) to mediate diverse cellular responses. Two LPA receptors, LPA1 and LPA2, show gene expression profiles in mouse embryonic cerebral cortex, suggesting roles for LPA signaling in cerebral cortical development. Here, we review loss‐of‐function and gain‐of‐function models that have been used to examine LPA signaling. Genetic deletion of lpa1 or both lpa1 and lpa2 in mice results in 50–65% neonatal lethality, but not obvious cortical phenotypes in survivors, suggesting that compensatory signaling systems exist for regulating cortical development. A gain‐of‐function model, approached by increasing receptor activation through exogenous delivery of LPA, shows that LPA signaling regulates cerebral cortical growth and anatomy by affecting proliferation, differentiation and cell survival during embryonic development. © 2004 Wiley‐Liss, Inc.
ERM proteins of the lens
Authors: Bagchi M. , Katar M. , Lo W.‐K. , Yost R. , Hill C. , Maisel H.
Published: May 2004

Ezrin and radixin and protein 4.1 were detected in the lens of the eye. These proteins were mainly present in the young elongating cortical fiber cells and localized to the plasma membranes. Moesin was not detected. Ezrin, radixin, and protein 4.1 provide another means whereby actin is linked to the plasma membrane in addition to the known adherens junctions in the lens. © 2004 Wiley‐Liss, Inc.
Induction of osteoblast differentiation indices by statins in MC3T3‐E1 cells
Authors: Maeda Toyonobu , Matsunuma Ayako , Kurahashi Izuru , Yanagawa Toru , Yoshida Hiroshi , Horiuchi Noboru
Published: May 2004

Statins inhibit 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, which catalyzes conversion of HMG‐CoA to mevalonate, a rate‐limiting step in cholesterol synthesis. The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Simvastatin at 10−7 M markedly increased mRNA expression for bone morphogenetic protein‐2 (BMP‐2), vascular endothelial growth factor (VEGF), alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin (OCN) in nontransformed osteoblastic cells (MC3T3‐E1), while suppressing gene expression for collagenase‐1, and collagenase‐3. Extracellular accumulation of proteins such as VEGF, OCN, collagenase‐digestive proteins, and noncollagenous proteins was increased in the cells treated with 10−7 M simvastatin, or 10−8 M cerivastatin. In the culture of MC3T3‐E1 cells, statins stimulated mineralization; pretreating MC3T3‐E1 cells with mevalonate, or geranylgeranyl pyrophosphate (a mevalonate metabolite) abolished statin‐induced mineralization. Statins stimulate osteoblast differentiation in vitro, and may hold promise drugs for the treatment of osteoporosis in the future. © 2004 Wiley‐Liss, Inc.
Blocking anti‐apoptosis as a strategy for cancer chemotherapy: NF‐κB as a target
Authors: Monks N.R. , Biswas D.K. , Pardee A.B.
Published: May 2004

Critical processes underlying cancers must be better understood to develop strategies for treatment and prevention. A chemotherapeutic strategy is proposed that is based upon re‐establishment, with a drug, of nullified programmed cell death (apoptosis) in cancer cells, which to survive have mutated to block apoptosis. A chemotherapy that is specific against tumors implanted in mice demonstrated the feasibility of this principle. This therapy is specific because it affects a process unique to cancer cells. It also has the advantage of killing these cells, in contrast to reversibly blocking their proliferation. The anti‐apoptotic transcription factor NF‐κB provides a potential therapeutic target in estrogen receptor negative (ER−) breast cancers that over‐express the epidermal growth factor family of receptors (EGFR). Further investigations of the pathways utilize dominant negative protein inhibitory peptide, and small inhibitory RNAs (siRNAs) to block the production of relevant enzymes. © 2004 Wiley‐Liss, Inc.
Preventive effects of a water‐soluble derivative of chroman moiety of vitamin E on lipid hydroperoxide‐induced cell injuries and DNA cleavages through repressions of oxidative stress in the cytoplasm of human keratinocytes
Authors: Huang Zhe , Senoh Yuichiro , Katoh Shinya , Miwa Nobuhiko
Published: May 2004

ChrCrx (6‐hydroxy‐2, 5, 7, 8‐tetramethyl‐chroman‐2‐carboxylic acid) is a water‐soluble analog in which 4′, 8′, 12′‐trimethyltridecyl chain is deleted from an alpha‐tocopherol molecule known as a hydrophobic antioxidant. Cell viability of human skin epidermal keratinocytes HaCaT was lowered by treatment with tert‐butylhydroperoxide (t‐BuOOH) of 50 μM for 48 h, designated as a subacute cytotoxicity, which was prevented by previous administration with ChrCrx in a dose‐dependent manner as estimated by mitochondrial function‐based WST‐1 assay and cell morphological microscopy. In contrast an acute cytotoxicity due to treatment with t‐BuOOH as dense as 200 μM for a period as short as 2 h could be also prevented with ChrCrx that was administered before and after, but was eliminated during, treatment with t‐BuOOH. In contrast α‐tocopherol was not cytoprotective against t‐BuOOH. DNA strand cleavages were induced with t‐BuOOH in the keratinocytes, and could be prevented by ChrCrx more effectively than α‐tocopherol as assayed by TUNEL stain. The intracellular reactive oxygen species (ROS) was accumulated in a manner dependent on periods of t‐BuOOH treatment in the cytoplasm more abundantly rather than the nucleus of keratinocytes, and was markedly diminished by ChrCrx as shown by fluorography using the redox indicator dye. Thus t‐BuOOH‐induced cell injuries and DNA cleavages of the keratinocytes can be prevented at least in part through efficient diminishment of ROS generated in the cytoplasm, to which the preferred distribution of ChrCrx may be advantageous over to the nucleus or membrane owing to its molecular hydrophilicity relative to α‐tocopherol. © 2004 Wiley‐Liss, Inc.
Zinc‐metallothionein genoprotective effect is independent of the glutathione depletion in HaCaT keratinocytes after solar light irradiation
Authors: Jourdan Eric , Marie Jeanne Richard , Régine Steiman , Pascale Guiraud
Published: May 2004

UV radiations are the major environmental factors that induce DNA damage of skin cells either by direct absorption (UVB), or after inducing an oxidative stress (UVA and UVB). Cells maintain a reducing intracellular environment to avoid genomic damage. MTs have been expected not only to control metal homeostasis but also counteract the glutathione (GSH) depletion induced by oxidative stress because of their high thiol content. Induction and redistribution of MTs in cultured human keratinocytes (HaCaT) in response to SSL, is an important cellular defense mechanism against DNA damage. Reduced glutathione (GSH) is another way of cellular protection against UV‐induced oxidative stress. This study which extend our previous finding focused on the relation between intracellular GSH and Zn genoprotective effects after solar irradiation. HaCaT cells, depleted or not in GSH by a chemical treatment were used to compare MTs induction by Northern blot, expression by Western blot and localization using immunocytochemistry. Zn genoprotection experiments after SSL irradiation was carried out by the comet assay. We demonstrated that in absence of GSH, Zn‐MTs could protect DNA after SSL irradiation and that GSH depletion has no effect on MTs induction and localization. Nuclear Zn‐MTs could be responsible for this observed genoprotection in GSH depleted cells. So the GSH/Zn and the MT/Zn systems could be two independent but interacting mechanisms of cellular protection against SSL injury. © 2004 Wiley‐Liss, Inc.
Teaching cancer cells to die
Authors: Zawel Leigh
Published: May 2004

Tumor cells have evolved numerous mechanisms to thwart apoptosis. As our understanding of the machinery which regulates cell‐death evolves, these apoptotic defects have fallen into the crosshairs of cancer drug developers. The issues raised in exploiting these alterations for therapeutic benefit are discussed. © 2004 Wiley‐Liss, Inc.
Cluster distance geometry of polypeptide chains
Authors: Crippen Gordon M.
Published: May 2004

Distance geometry has been a broadly useful tool for dealing with conformational calculations. Customarily each atom is represented as a point, constraints on the distances between some atoms are obtained from experimental or theoretical sources, and then a random sampling of conformations can be calculated that are consistent with the constraints. Although these methods can be applied to small proteins having on the order of 1000 atoms, for some purposes it is advantageous to view the problem at lower resolution. Here distance geometry is generalized to deal with distances between sets of points. In the end, much of the same techniques produce a sampling of different configurations of these sets of points subject to distance constraints, but now the radii of gyration of the different sets play an important role. A simple example is given of how the packing constraints for polypeptide chains combine with loose distance constraints to give good calculated protein conformers at a very low resolution. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1305–1312, 2004
An algorithm for computing nucleic acid base‐pairing probabilities including pseudoknots
Authors: Dirks Robert M. , Pierce Niles A.
Published: May 2004

Given a nucleic acid sequence, a recent algorithm allows the calculation of the partition function over secondary structure space including a class of physically relevant pseudoknots. Here, we present a method for computing base‐pairing probabilities starting from the output of this partition function algorithm. The approach relies on the calculation of recursion probabilities that are computed by backtracking through the partition function algorithm, applying a particular transformation at each step. This transformation is applicable to any partition function algorithm that follows the same basic dynamic programming paradigm. Base‐pairing probabilities are useful for analyzing the equilibrium ensemble properties of natural and engineered nucleic acids, as demonstrated for a human telomerase RNA and a synthetic DNA nanostructure. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1295–1304, 2004
Volatile fatty acid production during anaerobic mesophilic digestion of solid potato waste
Authors: Parawira Wilson , Murto Marika , Read John S , Mattiasson Bo
Published: May 2004

The production of volatile fatty acids by anaerobic digestion of solid potato waste was investigated using a batch solid waste reactor with a working capacity of 2 dm−3 at 37°C. Solid potato waste was packed into the digester and the organic content of the waste was released by microbial activity by circulating water over the bed, using batch loads of 500 g or 1000 g potato waste. The sequence of appearance of the volatile fatty acids was (acetic, propionic); (n‐butyric); (n‐valeric, iso‐valeric, caproic); (iso‐butyric). After 300 h digestion of potato waste on a small scale, the fermentation products were chiefly (mg g−1 total VFAs): acetic acid (420), butyric acid (310), propionic acid (140) and caproic acid (90), with insignificant amounts of iso‐butyric acid, n‐valeric and iso‐valeric acids. When the load of potato solids was increased, the volatile fatty acid content was similar, but butyric acid constituted 110 mg g−1 and lactic acid 400 mg g−1 of the total volatile fatty acids. The maximum soluble chemical oxygen demand (COD) achieved under the experimental conditions used was 27 and 37 g COD dm−3 at low and high loadings of potato solids, respectively. The total volatile fatty acids reached 19 g dm−3 of leachate at both loads of potato solid waste. Gas production was negligible, indicating that methanogenic activity was effectively inhibited. Copyright © 2004 Society of Chemical Industry
Synthesis of ZSM‐5 from diatomite: a case of zeolite synthesis from a natural material
Authors: Sanhueza Vilma , Kelm Ursula , Cid Ruby , López‐Escobar Leopoldo
Published: May 2004

A highly crystalline ZSM‐5 product was obtained from diatomite, a natural raw material, both with and without the presence of diethanolamine. The synthesis process took 40 h, and was carried out under hydrothermal conditions, at autogenic pressure, and at a temperature of 180 °C. The resulting crystals were identified as ZSM‐5 by X‐ray diffraction and characterized by scanning electron microscopy, infrared spectroscopy, thermal gravimetry and differential thermal analysis. Copyright © 2004 Society of Chemical Industry
Investigation of the specific interfacial area of a palm oil–water system
Authors: Al‐Zuhair Sulaiman , Ramachandran Kadathur B , Hasan Masitah
Published: May 2004

Oil–water dispersions have many important applications in the chemical and oleochemical industries. A measure of the specific interfacial area of the dispersed phase provides a direct indication of the quality of the dispersion. In this study, the specific interfacial area for the palm oil–water system was determined using a microscopic technique. The effects of oil volume fraction, agitation speed and temperature on the specific interfacial area have been determined experimentally and an empirical correlation to predict the total specific interfacial area under different operating conditions is proposed. This correlation can be used in the design of reaction and non‐reaction systems using palm oil–water dispersions. Copyright © 2004 Society of Chemical Industry
Fighting governmental corruption: the New World Bank programme evaluated
Authors: Klein Haarhuis Carolien M. , Leeuw Frans L.
Published: May 2004

Over the past decade, the international donor community has come up with a range of initiatives to curb governmental corruption in developing countries. Top‐down approaches devise administrative and judicial reforms, whereas bottom‐up approaches deal with the process of awareness—raising in civil society. The World Bank currently integrates these top‐down and bottom‐up approaches in a combined anti‐corruption programme. In this paper, the most recent version of this World Bank's training programme is reconstructed and assessed. Several core approaches in the programme, such as the strengthening of civil society and the privatisation of parastatals, turn out to have unintended consequences. The empirical support is largely case‐specific and turns out to be highly conditional. It is concluded that indicators need to be developed to assess the relevance of national anti‐corruption policies to country‐specific governance and anti‐corruption conditions. Copyright © 2004 John Wiley & Sons, Ltd.
International inequality in well‐being
Authors: McGillivray Mark , Pillarisetti J. Ram
Published: May 2004

This paper examines inter‐country inequality in indicators of human well‐being. It is primarily concerned with inequality in two gender‐related, composite indicators of development levels proposed: the Gender‐related Development Index (GDI) and the Gender Empowerment Measure (GEM). A number of inequality indices are calculated using data for the period 1992 to 1998. A special interest of the paper is whether the GDI and GEM tell different stories with respect to inequality than the Human Development Index (HDI) and PPP GDP per capita. Results indicate that the answer to this question with respect to PPP GDP per capita is a qualified yes, being dependent on how this variable is measured. Other results indicate that the GEM and GDI exhibit slightly higher inequality than the HDI. Copyright © 2004 John Wiley & Sons, Ltd.
International trade and economic growth in a global environment
Authors: De Matteis Alessandro
Published: May 2004

The present analysis focuses on one of the central aspects of the current process of globalization, that is the liberalization of trade policy aimed at maximizing the favourable effects that an export expansion can generate on economic growth. It has been considered how the relationship between exports and economic growth changes according to income levels as well as during the various phases of economic growth.

It has been found out that integration with the international economy does not seem to constitute a necessary condition in support of the role that an export expansion can play over growth. On the contrary, it has been found out that an increasing international exposure seems to have some negative effects on economic growth. Copyright © 2004 John Wiley & Sons, Ltd.