bluuebunny/crossref_metadata_2025 huggingface dataset:
Tribochemische Synthese von Hydriden durch Hochenergie‐Kugelvermahlung
Authors: Felderhoff M. , Pommerin A. , Mamatha M. , Bogdanović B. , Schüth F.
Published: May 2007

Durch Hochenergievermahlen unter Wasserstoffdruck werden hochreaktive Metallhydride und Wasserstoffspeichermaterialien innerhalb von kürzester Zeit synthetisiert. Zur Reaktionskontrolle dieser Synthesen wird ein Telemetriesystem vorgestellt, das die Beobachtung von Druck und Temperatur während des Mahlprozesses erlaubt.
Metallorganische Koordinationspolymere zur adsorptiven Trennung von Propan/Propen‐Gemischen
Authors: Wagener A. , Schindler M. , Rudolphi F. , Ernst S.
Published: May 2007

Die Trennung von Propan/Propen‐Gemischen erfolgt nach dem Stand der Technik durch Tieftemperaturrektifikation. Eine Alternative zu diesem kosten‐ und energieintensiven Prozess ist die Trennung der beiden Gase durch Adsorption an (mikroporösen) Feststoffen. Im vorliegenden Beitrag wird über experimentelle Untersuchungen zur Adsorption von Propan und Propen bzw. eines Gemisches aus beiden Komponenten an metallorganischen Koordinationspolymeren (sog. MOF, metal organic frameworks) berichtet.
Hydroraffinationskatalysatoren in der Erdölverarbeitung – Stand und Perspektiven
Authors: Reschetilowski W.
Published: May 2007

Die Hydroraffination (Hydrotreating) hat sich in den vergangenen Jahrzehnten zu einem der wichtigsten katalytischen Verfahren in der Erdölverarbeitung entwickelt. Insbesondere ist die Herstellung schwefelfreier Kraftstoffe von großer Bedeutung für den Umweltschutz, da bei ihrer Verbrennung ein verkehrsbedingtes Auftreten von SO2‐Emissionen und eine schnelle Desaktivierung von Abgaskatalysatoren ausgeschlossen sind. In diesem Beitrag werden die wichtigsten Vertreter der Hydroraffinationskatalysatoren – von den Herstellungsmethoden über die Struktur und die Oberflächenchemie bis zum Wirkungsmechanismus – beschrieben. Ein besonderes Augenmerk wird auf die klassischen sulfidischen CoMo/Al2O3‐ sowie NiMo/Al2O3‐Katalysatoren zur katalytischen Hydrodesulfurierung (HDS) gerichtet, aber auch neue Katalysatorentwicklungen auf diesem Gebiet werden kurz beleuchtet.
Mikrostrukturreaktoren für die heterogene Katalyse
Authors: Klemm E. , Döring H. , Geißelmann A. , Schirrmeister S.
Published: May 2007

Seit Anfang der 90er Jahre des letzten Jahrhunderts ist eine große Vielzahl heterogen katalysierter Reaktionen, vor allem Gasphasenreaktionen, in Labor‐Mikrostrukturreaktoren durchgeführt und deren prinzipielle Eignung und Potenziale in der heterogenen Katalyse nachgewiesen worden. Seit Beginn dieses Jahrhunderts steht die Übertragung der Mikrotechnologie vom Labor‐ in den Produktionsmaßstab im Vordergrund. Diese Übersicht widmet sich daher insbesondere den technischen Konzepten und den wirtschaftlichen Aspekten. Heterogen katalysierte Gasphasen‐ und Flüssigphasenprozesse werden dabei getrennt voneinander diskutiert. Die Präparation von Wandkatalysatoren ist in beiden Fällen eine entscheidende Schlüsseltechnologie, der ein eigener Abschnitt gewidmet wird. Abschließend erfolgt eine Bewertung des Entwicklungsstands.
Die oberflächenchemische Modifikation von Kohlenstoff‐Nanoröhren für die Anwendung in der heterogenen Katalyse
Authors: Xia W. , Naumann d'Alnoncourt R. , Muhler M.
Published: May 2007

Aufgrund ihrer einzigartigen Strukturen und Eigenschaften sind Kohlenstoff‐Nanoröhren (carbon nanotubes, CNTs) für die heterogene Katalyse von großem Interesse. Um Kohlenstoff‐Nanoröhren als Katalysator oder Trägermaterial einsetzen zu können, ist es nötig, deren Oberfläche und Morphologie geeignet zu verändern. In diesem Beitrag wird die Modifizierung von Kohlenstoff‐Fasern verschiedener Größe beschrieben, ausgehend von Nanoröhren bis hin zu Mikrofasern. Es wird die Rolle von Oberflächengruppen bei der Präparation von geträgerten Palladiumkatalysatoren durch chemische Gasphasenabscheidung erläutert, und es wird gezeigt, wie sich durch Verzweigungen die spezifische Oberfläche von Kohlenstoff‐Nanoröhren erhöhen lässt. Die Entwicklung von hierarchisch strukturierten Kohlenstoff‐Nanoröhren‐Kompositmaterialen wird detailliert beschrieben.
Heterogene Katalyse in überkritischen Medien – 1. Kohlendioxid
Authors: Kruse A. , Vogel H.
Published: May 2007

Überkritische Fluide haben in den letzten Jahren großes Interesse als Reaktionsmedien gefunden. Die Eigenschaften von überkritischen Fluiden liegen zwischen denen von Gasen und Flüssigkeiten. Die Dichten sind zwar geringer als in der flüssigen Phase, aber deutlich höher als in der Gasphase. Dies macht überkritische Fluide zu hervorragenden Lösungsmitteln für eine Vielzahl von Stoffen. Das gute Lösungsvermögen besteht nur im bzw. nahe dem überkritischen Bereich; Reaktionsprodukte lassen sich beispielsweise einfach durch Verminderung von Temperatur und Druck abtrennen. Dies kann zur Prozessintensivierung genutzt werden, da aufwendige Trennprozesse wie Destillationen vermieden werden.
Paddle‐Wheel Zinc Carboxylate Clusters as Building Units for Metal‐Organic Frameworks
Authors: Vagin S. , Ott A. K. , Rieger B.
Published: May 2007

Growth of interest to a field of materials chemistry such as the metal‐organic frameworks (MOFs) demands the comprehensible surveying of new results, and the reviews systematizing and highlighting one or another trend in the MOF research appear periodically. Structural peculiarities of coordination polymers constructed by zinc paddle‐wheel clusters and the investigation of their microporosity are reviewed in detail to emphasize those features of the materials, which are interesting both for the pure and applied chemists.
Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development
Authors: Schlitzer Martin
Published: May 2007

Since ancient times, humankind has had to struggle against the persistent onslaught of pathogenic microorganisms. Nowadays, malaria is still the most important infectious disease worldwide. Considerable success in gaining control over malaria was achieved in the 1950s and 60s through landscaping measures, vector control with the insecticide DDT, and the widespread administration of chloroquine, the most important antimalarial agent ever. In the late 1960s, the final victory over malaria was believed to be within reach. However, the parasites could not be eradicated because they developed resistance against the most widely used and affordable drugs of that time. Today, cases of malaria infections are on the rise and have reached record numbers. This review gives a short description of the malaria disease, briefly addresses the history of antimalarial drug development, and focuses on drugs currently available for malaria therapy. The present knowledge regarding their mode of action and the mechanisms of resistance are explained, as are the attempts made by numerous research groups to overcome the resistance problem within classes of existing drugs and in some novel classes. Finally, this review covers all classes of antimalarials for which at least one drug candidate is in clinical development. Antimalarial agents that are solely in early development stages will be addressed in a separate review.
Paclitaxel And Docetaxel Resistance: Molecular Mechanisms and Development of New Generation Taxanes
Authors: Galletti Elena , Magnani Matteo , Renzulli Michela L. , Botta Maurizio
Published: May 2007

Taxanes represent one of the most promising classes of anticancer agents. Unfortunately, their clinical success has been limited by the insurgence of cellular resistance, mainly mediated by the expression of the MDR phenotype or by microtubule alterations. However, the remarkable relevance of paclitaxel and docetaxel in clinical oncology stimulated intensive efforts in the last decade to identify new derivatives endowed with improved activities towards resistant tumor cells, resulting in a huge number of novel natural and synthetic taxanes. Among them, several structurally different derivatives were found to exhibit a promising behavior against the MDR phenotype in terms of either MDR inhibiting properties, or enhanced cytotoxicity compared to parental drugs, or both. On the other hand, only in more recent years have the first taxanes retaining activity against resistant cancer cells bearing alterations of the tubulin/microtubule system emerged. This review describes the main molecular mechanisms of resistance to paclitaxel and docetaxel identified so far, focusing on the advances achieved in the development of new taxanes potentially useful for the treatment of resistant tumors.
Recent Developments in Ghrelin Receptor Ligands
Authors: Moulin Aline , Ryan Joanne , Martinez Jean , Fehrentz Jean‐Alain
Published: May 2007

The 28‐amino acid peptide ghrelin is a neuroendocrine hormone synthesized primarily in the stomach. It stimulates growth hormone secretion and appetite, thus promoting food intake and body‐weight gain. The pharmacological properties of this peptide are mediated by the growth hormone secretagogue receptor type 1a (GHS‐R1a). Given its wide spectrum of biological activities, it is evident that the discovery of ghrelin and its receptor has opened up many perspectives in the fields of neuroendocrine and metabolic research and has had an influence on such fields of internal medicine as gastroenterology, oncology, and cardiology. It is therefore increasingly likely that synthetic, peptidyl, and nonpeptidyl GHS‐R1a ligands, acting as agonists, partial agonists, antagonists, or inverse agonists, could have both clinical and therapeutic potential. This review summarizes the various types of GHS‐R1a ligands that have been described in the literature and discusses the recent progress made in this research area.
Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia
Authors: Shanafelt Tait D. , Lin Thomas , Geyer Susan M. , Zent Clive S. , Leung Nelson , Kabat Brian , Bowen Deborah , Grever Michael R. , Byrd John C. , Kay Neil E.
Published: May 2007

BACKGROUND.

The prevalence of chronic lymphocytic leukemia (CLL) increases with age. Although chemoimmunotherapy (CIT) has dramatically improved response rates in patients with CLL, some CIT regimens are not well tolerated by many patients ≥70 years of age.

METHODS.

Sixty‐four previously untreated patients with CLL and serum creatinine <1.5 times the upper limit of normal who met National Cancer Institute (NCI) 96‐WG criteria for treatment received pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2). The authors measured performance status at study entry and used age, weight, and baseline creatinine to calculate creatinine clearance (CrCl).

RESULTS.

Eighteen of 64 (28%) patients were ages ≥70 years. Although individuals ages ≥70 years were more likely to have delayed treatment cycles (28% vs 7%; P = .03), there were no significant differences in the number of cycles administered, need for dose reductions, or grade 3–4 hematologic, infectious, or other toxicities. No significant differences in overall response rate, complete response rate, or progression‐free survival were observed by age. Twenty‐five (39%) patients had a CrCl < 70 mL/min (range, 34–67). Although individuals with CrCl < 70 were more likely to require dose reduction (24% vs 5%; P = .05), there were no significant differences in the number of cycles administered or grade 3–4 hematologic, infectious, or other toxicities. No significant difference in overall response rate, complete response rate, or progression‐free survival were observed between patients with CrCl ≥ 70 mL/min and those with CrCl < 70 mL/min.

CONCLUSIONS.

In this clinical trial, the PCR regimen was well tolerated by older patients and individuals with CrCl ≤ 70. The efficacy of PCR was not significantly affected by age or renal function. These findings suggest PCR may be a good therapeutic option for older patients and those with modestly decreased renal function. Cancer 2007; 109:2291–8. © 2007 American Cancer Society.
Prostate cancer‐specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high‐risk factors
Authors: D'Amico Anthony V. , Chen Ming‐Hui , Catalona William J. , Sun Leon , Roehl Kimberly A. , Moul Judd W.
Published: May 2007

BACKGROUND.

Estimates of prostate cancer‐specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with ≥1 high‐risk factors.

METHODS.

The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high‐risk factors: a prostate‐specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of ≥7, a PSA level of ≥10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high‐risk factors were associated with time to PCSM.

RESULTS.

Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P ≤ .001). The solitary presence of a PSA velocity >2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0–59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4–105 [P = .02]) when compared with men with any other single high‐risk factor.

CONCLUSIONS.

Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high‐risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high‐risk PC. Cancer 2007. © 2007 American Cancer Society.
Molecularly targeted therapy for malignant glioma
Authors: Sathornsumetee Sith , Reardon David A. , Desjardins Annick , Quinn Jennifer A. , Vredenburgh James J. , Rich Jeremy N.
Published: May 2007

Malignant gliomas are relatively uncommon but lethal cancers. Despite recent research efforts in cancer therapy, the prognosis of patients with malignant gliomas has remained dismal. Understanding the molecular pathogenesis of glioma may lead to a rational development of new therapies. Despite the genetic heterogeneity of malignant gliomas, common aberrations in the signaling elements of the growth and survival pathways are found. New treatments have emerged to target molecules in these signaling pathways with the goal to increase specific efficacy and minimize toxicity. Monoclonal antibodies and low molecular‐weight kinase inhibitors are the most common classes of agents in targeted cancer treatment. Most clinical trials of these agents as monotherapies have failed to demonstrate survival benefit in unselected malignant glioma patient populations. Several mechanisms of treatment failure have been demonstrated. In response, multitargeted kinase inhibitors and combinations of single‐targeted kinase inhibitors have been developed to overcome therapeutic resistance. In addition, multimodality combinations of targeted agents with radiation, chemotherapy, or immunotherapy/vaccines may enhance treatment efficacy. Future development of these agents will require advances in discovery and validation of new molecular targets, improvement of therapeutic delivery, and identification of correlative biomarkers. Novel clinical trial designs and endpoints may increase the efficiency of new drug evaluation. In this review, the authors discussed the current understanding of molecular pathogenesis and the development of molecularly targeted therapies in malignant glioma. Cancer 2007. © 2007 American Cancer Society.
Characteristics of pediatric chemotherapy medication errors in a national error reporting database
Authors: Rinke Michael L. , Shore Andrew D. , Morlock Laura , Hicks Rodney W. , Miller Marlene R.
Published: May 2007

BACKGROUND.

Little is known regarding chemotherapy medication errors in pediatrics despite studies suggesting high rates of overall pediatric medication errors. In this study, the authors examined patterns in pediatric chemotherapy errors.

METHODS.

The authors queried the United States Pharmacopeia MEDMARX database, a national, voluntary, Internet‐accessible error reporting system, for all error reports from 1999 through 2004 that involved chemotherapy medications and patients aged <18 years.

RESULTS.

Of the 310 pediatric chemotherapy error reports, 85% reached the patient, and 15.6% required additional patient monitoring or therapeutic intervention. Forty‐eight percent of errors originated in the administering phase of medication delivery, and 30% originated in the drug‐dispensing phase. Of the 387 medications cited, 39.5% were antimetabolites, 14.0% were alkylating agents, 9.3% were anthracyclines, and 9.3% were topoisomerase inhibitors. The most commonly involved chemotherapeutic agents were methotrexate (15.3%), cytarabine (12.1%), and etoposide (8.3%). The most common error types were improper dose/quantity (22.9% of 327 cited error types), wrong time (22.6%), omission error (14.1%), and wrong administration technique/wrong route (12.2%). The most common error causes were performance deficit (41.3% of 547 cited error causes), equipment and medication delivery devices (12.4%), communication (8.8%), knowledge deficit (6.8%), and written order errors (5.5%). Four of the 5 most serious errors occurred at community hospitals.

CONCLUSIONS.

Pediatric chemotherapy errors often reached the patient, potentially were harmful, and differed in quality between outpatient and inpatient areas. This study indicated which chemotherapeutic agents most often were involved in errors and that administering errors were common. Investigation is needed regarding targeted medication administration safeguards for these high‐risk medications. Cancer 2007. © 2007 American Cancer Society.
Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid
Authors: Lee Ju‐Han , Lee Eung‐Seok , Kim Young‐Sik
Published: May 2007

BACKGROUND.

Numerous studies have investigated the clinical significance of BRAF mutation in papillary thyroid carcinoma (PTC). However, there have been conflicting data on the usefulness of BRAF mutation as a prognostic marker of PTC. To address this controversy, the frequency of the BRAF mutation and the associations between BRAF mutation and clinicopathologic parameters in PTC were evaluated by meta‐analysis.

METHODS.

The relevant published studies were reviewed according to the defined selection criteria. The effect sizes of outcome parameters were estimated by odds ratio or weighted mean difference.

RESULTS.

The current meta‐analysis included 12 studies with a total of 1168 patients. The frequency of the BRAF mutation was 49%. The BRAF mutation was associated with histologic subtype, the presence of extrathyroidal extension, and higher clinical stage, but not with age, sex, race, or tumor size.

CONCLUSIONS.

The effect of the BRAF mutation on the poor prognosis of PTC patients was evident from the current meta‐analysis. The detection of the BRAF mutation may be used as an important prognostic marker of patients with PTC. Cancer 2007. © 2007 American Cancer Society.
Timing of biochemical failure and distant metastatic disease for low‐, intermediate‐, and high‐risk prostate cancer after radiotherapy
Authors: Morgan Peter B. , Hanlon Alexandra L. , Horwitz Eric M. , Buyyounouski Mark K. , Uzzo Robert G. , Pollack Alan
Published: May 2007

BACKGROUND.

The relation of prostate cancer risk‐group stratification and the timing of biochemical failure (BF) and distant metastasis (DM) is not well defined. The authors hypothesized that early failures due to subclinical micrometastasis at presentation could be differentiated from late failures due to local persistence.

METHODS.

A total of 1833 men with clinically localized prostate cancer treated with 3D‐conformal radiotherapy with or without short‐term androgen deprivation were retrospectively analyzed. By using American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (Nadir+2) definitions (developed at the ASTRO‐RTOG [Radiation Therapy Oncology Group] consensus meeting, Phoenix, Arizona, January 21, 2005), the interval hazard rates of BF and DM were determined for men with low‐risk, intermediate‐risk, and high‐risk disease.

RESULTS.

Median follow‐up was 67 months. Multivariate analysis showed that increasing risk group was independently associated with higher ASTRO BF (P < .0001) and Nadir+2 BF (P < .0001). The preponderance (87%) of ASTRO BF occurred ≤4 years after radiotherapy, whereas Nadir+2 BF was more evenly spread over Years 1–12, with 43% at >4 years. The hazard of Nadir+2 BF persisted in Years 8–12 in all risk groups. The interval hazard function for DM appeared to be biphasic (early peak followed by a drop and late increase) for intermediate‐risk and high‐risk patients, but no distinct early wave was evident for low‐risk patients.

CONCLUSIONS.

Because of backdating, ASTRO BF underestimates late BF. Local persistence of disease is suggested by delayed Nadir+2 BF and subsequent late DM in every risk group. The paucity of early DM among those with low‐risk tumors supports the hypothesis that occult micrometastases contributed to the early wave. Cancer 2007. © 2007 American Cancer Society.
Promoter methylation as a common mechanism for inactivating E‐cadherin in human salivary gland adenoid cystic carcinoma
Authors: Zhang Chun‐Ye , Mao Li , Li Lei , Tian Zhen , Zhou Xiao‐Jian , Zhang Zhi‐Yuan , Li Jiang
Published: May 2007

BACKGROUND.

The role of promoter methylation in the inactivation of E‐cadherin (E‐cad) in salivary gland adenoid cystic carcinoma (ACC) is unknown. The objective of this study was to determine the role and potential clinical implications of promoter methylation of E‐cad in salivary gland ACC.

METHODS.

The promoter methylation status of E‐cad was determined by using methylation‐specific polymerase chain reaction (PCR) analysis in 60 primary salivary gland ACC tissues and 3 ACC cell lines. The level of E‐cad protein expression was determined by immunohistochemical analysis of each tumor. E‐cad protein and messenger RNA (mRNA) expression levels were examined by immunohistochemical analysis and reverse transcriptase‐PCR in 3 ACC cell lines. Associations between molecular alterations and patients' clinicopathologic characteristics were analyzed statistically. E‐cad mRNA expression was examined in a 5‐azacytidine‐treated ACC‐2 cell line.

RESULTS.

Promoter methylation of E‐cad was detected in 34 of 60 tumors (57%). Of those 34 tumors, 18 tumors (53%) showed no E‐cad protein expression, whereas only 5 of the remaining 26 tumors (19%) without E‐cad promoter methylation showed no E‐cad protein expression (P = .01). Tumors that had E‐cad promoter methylation had a significantly higher histologic grade (P = .01) and more perineural invasion (P = .02) compared with tumors that did not have methylation. All 3 ACC cell lines exhibited E‐cad promoter methylation and a lack of E‐cad mRNA and protein expression, whereas 5‐azacytidine restoredE‐cad mRNA expression in the ACC‐2 cell line.

CONCLUSIONS.

E‐cad frequently is inactivated in salivary gland ACC through promoter methylation, and E‐cad promoter methylation may play a role in tumor cell differentiation and perineural invasion. Cancer 2007. © 2007 American Cancer Society.
Prognostic significance of CD100 expression in soft tissue sarcoma
Authors: Ch'ng EweSeng , Tomita Yasuhiko , Zhang Binglin , He Juxiang , Hoshida Yoshihiko , Qiu Ying , Morii Eiichi , Nakamichi Itsuko , Hamada Ken‐ichiro , Ueda Takafumi , Aozasa Katsuyuki
Published: May 2007

BACKGROUND.

CD100, a class IV semaphorin, promotes angiogenesis, invasive growth, proliferation, and antiapoptosis of cancer cells in vitro. The expression of CD100 in soft tissue sarcoma (STS) and its correlation with clinicopathologic factors and prognostic significance were evaluated.

METHODS.

Expression levels of CD100 in patients with localized STS were evaluated immunohistochemically on paraffin‐embedded sections from 81 patients, including 47 men and 34 women with a median age of 54 years. Staining intensity was categorized into weaker than (level 1) or equal to that of lymphocytes with a rate of <10% stained tumor cells (level 2) or >10% stained tumor cells (level 3). Ki‐67 staining was performed in parallel.

RESULTS.

Forty‐two tumors (52%) had level 1 CD100 expression, 18 tumors (22%) had level 2 CD100 expression, and 21 tumors (26%) had level 3 CD100 expression. Tumors that had level 2 and 3 CD100 expression were correlated significantly with higher mitotic count, cellularity, ratio of necrosis, and Ki‐67 labeling index (LI) compared with tumors that had level 1 CD100 expression. There was no correlation between CD100 expression and other characteristics. Among the 3 levels of CD100 expression, higher expression levels were correlated with poorer overall and disease‐free survival. Multivariate analysis revealed that CD100 expression (levels 1 and 2 vs level 3) and tumor size (≤5 cm vs >5 cm) were independent prognosticators for overall survival (P< .05 for both), and CD100 expression (levels 1 and 2 vs level 3) was an independent prognosticator for disease‐free survival (P< .05).

CONCLUSIONS.

The results from this study indicated the demonstrated prognostic significance of CD100 expression in STS. Cancer 2007. © 2007 American Cancer Society.
Merkel cell carcinoma: Critical review with guidelines for multidisciplinary management
Authors: Bichakjian Christopher K. , Lowe Lori , Lao Christopher D. , Sandler Howard M. , Bradford Carol R. , Johnson Timothy M. , Wong Sandra L.
Published: May 2007

Merkel cell carcinoma (MCC) is a relatively rare cutaneous malignancy that occurs predominantly in the older white population. The incidence of MCC appears to have tripled during the past 20 years; an increase that is likely to continue because of the growing number of older Americans. The pathogenesis of MCC remains largely unknown. However, ultraviolet radiation and immunosuppression are likely to play a significant pathogenetic role. Many questions currently remain unanswered regarding the biologic behavior and optimal treatment of MCC. Large, prospective, randomized studies are not available and are unlikely to be performed because of the rarity of the disease. The objective of this review was to provide a comprehensive reference for MCC based on a critical evaluation of the current data. The authors investigated the importance of sentinel lymph node biopsy as a staging tool for MCC to assess the status of the regional lymph node basin and to determine the need for additional therapy to the lymph node basin. In an attempt to standardize prospective data collection with the intention to define prognostic indicators, the authors also present histopathologic profiles for primary MCC and sentinel lymph nodes. The controversies regarding the appropriate surgical approach to primary MCC, the use of adjuvant radiation therapy, and the effectiveness of adjuvant chemotherapy were examined critically. Finally, the authors have provided treatment guidelines based on the available evidence and their multidisciplinary experience. Cancer 2007. © 2007 American Cancer Society.
Unsteady free convection–radiation flow over a vertical wall embedded in a porous medium
Authors: Zueco Joaquín
Published: May 2007

A numerical solution for the transient two‐dimensional free convection flow of viscous dissipative fluid over an infinite vertical plate through a porous medium bounded, taking into account the thermal radiation, is analysed. The fluid is grey, and acts as a radiation emitting and absorbing (but non‐scattering) medium. The influence of the non‐dimensional parameters such as the Forchheimer coefficient (Fo), the permeability parameter (P), the Eckert number (Ec) and the radiation parameter (R) on the velocity, temperature, Nusselt number and on the time taken to reach the steady state is studied. The possibility of non‐Darcy flow is also analysed. The numerical method employed, network simulation method, is based on an electro‐thermal analogy and permits the direct visualization and evolution of the local and/or integrated transport variables (velocities, temperatures and fluxes) at any point or section of the medium. The numerical solutions of this work have been compared with the existing information in the literature with good agreement. Copyright
© 2007 John Wiley & Sons, Ltd.
A framework for performance analysis of Co‐Array Fortran
Authors: Mohr Bernd , DeRose Luiz , Vetter Jeffrey
Published: May 2007

Co‐Array Fortran (CAF) is a parallel programming extension to Fortran that provides a straightforward mechanism for representing distributed memory communication and, in particular, one‐sided communication. Although this integration of communication primitives with the language improves programmer productivity, this new level of abstraction makes the analysis of CAF performance mode difficult. This situation is due, in part, to a lack of tools for the analysis of CAF applications. In this paper, we present an extension to the KOJAK toolkit based on a source‐to‐source translator that supports performance instrumentation, data collection, trace generation, and performance visualization of CAF applications. We illustrate this approach with a performance visualization of a CAF version of the Halo kernel benchmark using the VAMPIR event trace visualization tool. Copyright © 2007 John Wiley & Sons, Ltd.
Segregation of Inorganic Ions at Surfaces of Polar Nonaqueous Liquids
Authors: Cwiklik Lukasz , Andersson Gunther , Dang Liem X. , Jungwirth Pavel
Published: May 2007

We present a short review of recent computational and experimental studies on surfaces of solutions of inorganic salts in polar nonaqueous solvents. These investigations complement our knowledge of aqueous interfaces and show that liquids such as formamide, liquid ammonia, and ethylene glycol can also surface‐segregate large polarizable anions like iodide, albeit less efficiently than water. For liquids whose surfaces are covered with hydrophobic groups (e.g. methanol), the surface‐ion effect all but disappears. Based on the present data a general picture of inorganic‐ion solvation at the solution–vapor interface of polar liquids is outlined.
Song and brain development in canaries raised under different conditions of acoustic and social isolation over two years
Authors: Leitner Stefan , Catchpole Clive K.
Published: May 2007

Early isolation experiments indicate that male songbirds learn their songs during an early sensitive period, although later work has shown that some open‐ended learners modify songs in later years. Recent isolation experiments suggest that in some species song has a stronger genetic basis than previously thought. This study raised domestic canaries under different combinations of acoustic and social isolation and followed song development into the second year. Males raised alone in acoustic isolation developed songs with normal syllables, but larger repertoires and also produced syllables with lower repetition rates when compared to controls. The smallest repertoire occurred in males raised in a peer group. Isolate males had a smaller song control nucleus HVC than controls, but there was no effect on nucleus RA or on brain weight in general. In the second year, after introduction into a large normal colony, isolate and peer group males adjusted their syllable repertoire to normal size. In particular, the isolates reduced their repertoire even though the size of HVC showed a significant increase in volume. However, songs of isolate and peer group males still differ in repetition rate and number of single syllables in the common aviary. In contrast, control males showed low syllable turnover and no significant change in repertoire size. Nor did they show any significant change in the volumes of song control nuclei. It seems that complete isolation affects only some aspects of song and brain development, and later socialization corrects some but not all of these in the second year. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007
Species differences in auditory processing dynamics in songbird auditory telencephalon
Authors: Terleph Thomas A. , Mello Claudio V. , Vicario David S.
Published: May 2007

The caudomedial nidopallium (NCM) of songbirds is a telencephalic area involved in the auditory processing and memorization of complex vocal communication signals. We used pure tone stimuli and multiunit electrophysiological recordings in awake birds to investigate whether the basic properties of song‐responding circuits in NCM differ between canaries and zebra finches, two species whose songs are markedly different in their spectral and temporal organization. We found that the responses in zebra finch NCM are characterized by broad tuning and sustained responses that may facilitate the integration of zebra finch song syllables and call notes that are of long duration and have a broad harmonic structure. In contrast, we found that the responses in canary NCM show narrower tuning and less sustained responses over the time periods analyzed. These characteristics may contribute to enhanced processing of the narrow‐band whistles, rapid trills, and steep frequency modulations that are prominent features of canary song. These species differences are much less pronounced in field L2, the direct thalamorecipient region that represents a preceding station in the central avian auditory pathway. NCM responses did not differ across sexes of either species, but field L2 did show wider tuning in zebra finch females relative to males. In sum, species differences in the response properties of NCM likely reflect selectivity for the acoustic elements of each species' vocal repertoire. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007
Deletion of the Bax gene disrupts sexual behavior and modestly impairs motor function in mice
Authors: Jyotika Jigyasa , McCutcheon Jill , Laroche Julie , Blaustein Jeffrey D. , Forger Nancy G.
Published: May 2007

Cell death is a nearly ubiquitous feature of the developing nervous system, and differential death in males and females contributes to several well studied sex differences in neuron number. Nonetheless, the functional importance of neuronal cell death has been subjected to few direct tests. Bax, a pro‐apoptotic protein, is required for cell death in many neural regions. Deletion of the Bax gene in mice increases neuron number in several areas and eliminates sex differences in cell number in the brain and spinal cord. Here, sexual and motor behaviors were examined in Bax−/− mice and their wild‐type siblings to test the functional consequences of preventing Bax‐dependent cell death. Animals were gonadectomized in adulthood and provided with ovarian hormones or with testosterone for tests of feminine and masculine sexual behaviors, respectively. Wild‐type mice exhibited a sex difference in feminine sexual behavior, with high lordosis scores in females and low scores in males. This sex difference was eliminated by Bax deletion, with very low receptivity exhibited by both male and female Bax−/− mice. Masculine sexual behavior was not sexually dimorphic among wild‐type mice, but mounts and pelvic thrusts were nearly eliminated in Bax−/− mice of both sexes. Motor strength and performance at low speeds on a RotaRod apparatus did not differ by sex or Bax gene status. However, Bax−/− animals exhibited impairments on the RotaRod at higher speeds. Thus, developmental cell death may be required for masculine and feminine sexual behaviors and the fine tuning of motor coordination. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007
Effects of a mutation in the Drosophila porin gene encoding mitochondrial voltage‐dependent anion channel protein on phototransduction
Authors: Lee Sunji , Leung Hung‐Tat , Kim Eunju , Jang Jeyoun , Lee Eunsung , Baek Kwanghee , Pak William L. , Yoon Jaeseung
Published: May 2007

Mitochondrial porins, also know as VDACs (voltage‐dependent anion channels), play an important role in regulating energy metabolism, apoptosis, and the transport of metabolites across the mitochondrial outer membrane. So far three distinct isoforms of VDAC (VDAC1‐3) have been reported in vertebrates, but their functions remain unknown. The annotation database of the Drosophila melanogaster genome sequence has identified four genes (porin, CG17137, CG17139, and CG17140) encoding different isoforms of VDACs. We identified post‐translational modifications of PORIN that are specific to D. melanogaster eyes. We also identified the P‐element insertion in the porin gene, porinG2294, that is homozygous viable whereas all the porin mutants previously reported are homozygous lethal at the pupal stage. The mutant does not show any defects in fly morphology, survival, and photoreceptor structure. The mutant, however, produces <10% of the normal level of wild‐type (WT) porin transcripts and 16.5% of WT level of the PORIN protein. The P‐element insertion affects only the expression of Class I transcript but not Class II transcript of the porin gene. Unlike in WT, the mutant displays an ERG (electroretinogram) that is not maintained during a prolonged light stimulus. The revertant obtained from remobilization of the P‐element in the mutant produces the WT level of porin transcripts and PORIN protein, and shows a normal ERG response. Our data suggest that the PORIN protein is important in maintaining a photoreceptor response during prolonged stimulation. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007
nAChR‐mediated calcium responses and plasticity in Drosophila Kenyon cells
Authors: Campusano Jorge M. , Su Hailing , Jiang Shaojuan A. , Sicaeros Beatriz , O'Dowd Diane K.
Published: May 2007

In Drosophila, nicotinic acetylcholine receptors (nAChRs) mediate fast excitatory synaptic transmission in mushroom body Kenyon cells, a neuronal population involved in generation of complex behaviors, including responses to drugs of abuse. To determine whether activation of nAChRs can induce cellular changes that contribute to functional plasticity in these neurons, we examined nicotine‐evoked responses in cells cultured from brains of late stage OK107‐GAL4 pupae. Kenyon cells can be identified by expression of green fluorescent protein (GFP+). Nicotine activates α‐bungarotoxin‐sensitive nAChRs, causing a rapid increase in intracellular calcium levels in over 95% of the Kenyon cells. The nicotine‐evoked calcium increase has a voltage‐gated calcium channel (VGCC) dependent component and a VGCC‐independent component that involves calcium influx directly through nAChRs. Thapsigargin treatment reduces the nicotine response consistent with amplification by calcium release from intracellular stores. The response to nicotine is experience‐dependent: a short conditioning pulse of nicotine causes a transient 50% reduction in the magnitude of the response to a test pulse of nicotine when the interpulse interval is 4 h. This cellular plasticity is dependent on activation of the VGCC‐component of the nicotine response and on cAMP‐signaling, but not on protein synthesis. These data demonstrate that activation of nAChRs induces a calcium‐dependent plasticity in Kenyon cells that could contribute to adult behaviors involving information processing in the mushroom bodies including responses to nicotine. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007
Effects of GABA and GABA receptor inhibition on differentiation of mesencephalic precursors into dopaminergic neurons in vitro
Authors: Parga J.A. , Rodriguez‐Pallares J. , Guerra M.J. , Labandeira‐Garcia J.L.
Published: May 2007

Neurotransmitters have been shown to control CNS neurogenesis, and GABA‐mediated signaling is thought to be involved in the regulation of nearly all key developmental stages. Generation of dopaminergic (DA) neurons from stem/precursor cells for cell therapy in Parkinson's disease has become a major focus of research. However, the possible effects of GABA on generation of DA neurons from proliferating neurospheres of mesencephalic precursors have not been studied. In the present study, GABAA, and GABAB receptors were found to be located in DA cells. Treatment of cultures with GABA did not cause significant changes in generation of DA cells from precursors. However, treatment with the GABAA receptor antagonist bicuculline (10−5 M) led to a significant increase in the number DA cells, and treatment with the GABAB receptor antagonist CGP 55845 (10−5 M) to a significant decrease. Simultaneous treatment with bicuculline and CGP 55845 did not induce significant changes. Apoptotic cell death studies and bromodeoxyuridine immunohistochemistry indicated that the aforementioned differences in generation of DA neurons are not due to changes in survival or proliferation of DA cells, but rather to increased or decreased differentiation of mesencephalic precursors towards the DA phenotype. The results suggest that these effects are exerted via GABA receptors located on DA precursors, and are not an indirect consequence of effects on the serotonergic or glial cell population. Administration of GABAA receptor antagonists in the differentiation medium may help to obtain higher rates of DA neurons for potential use in cell therapy for Parkinson's disease. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007
Neural crest cell deficiency of c‐myc causes skull and hearing defects
Authors: Wei Ke , Chen Jiyuan , Akrami Kevan , Galbraith Gary C. , Lopez Ivan A. , Chen Fabian
Published: May 2007

The proto‐oncogene c‐myc has a central role in multiple processes important for embryonic development, including cell proliferation, growth, apoptosis, and differentiation. We have investigated the role of c‐myc in neural crest by using Wnt1‐Cre‐mediated deletion of a conditional mutation of the c‐myc gene. c‐myc deficiency in neural crest resulted in viable adult mice that have defects in coat color, skull frontal bone, and middle ear ossicle development. Physiological hearing studies demonstrated a significant hearing deficit in the mutant mice. In this report, we focus on the craniofacial and hearing defects. To further examine neural crest cells affected by c‐myc deficiency, we fate mapped Wnt1‐Cre expressing neural crest cells using the ROSA26 Cre reporter transgene. The phenotype obtained demonstrates the critical role that c‐myc has in neural crest during craniofacial development as well as in providing a model for examining human congenital skull defects and deafness. genesis 45:382–390, 2007. Published 2007 Wiley‐Liss, Inc.
Highly restricted diversity of TCR delta chains of the amphibian Mexican axolotl (Ambystomamexicanum) in peripheral tissues
Authors: André Sébastien , Kerfourn Fabienne , Affaticati Pierre , Guerci Aline , Ravassard Philippe , Fellah Julien S.
Published: May 2007

γδ T cells localize at mammalian epithelial surfaces to exert both protective and regulatory roles in response to infections. We have previously characterized the Mexican axolotl (Ambystoma mexicanum) T cell receptor delta (TRD) chain. In this study, TRD repertoires in spleen, liver, intestine and skin from larvae, pre‐adult and adult axolotls were examined and compared to the thymic TRD repertoire. A TRDV transcript without N/D diversity, TRDV1S1‐TRDJ1, dominates the TRD repertoires until sexual maturation. In adult tissues, this canonical transcript is replaced by another dominant TRDV1S1‐TRDJ1 transcript. In the thymus, these two transcripts are detected early in development. Our results suggest that γδ T cells that express the canonical TRDV1S1‐TRDJ1 transcript emerge from the thymus and colonize the peripheral tissues, where they are selectively expanded by recurrent ligands. This particular situation is probably related to the neotenic state and the slow development of the axolotl. In thymectomized axolotls, TRD repertoires appear different from those of normal axolotls, suggesting that extrathymic γδ T cell differentiation could occur. Gene expression analysis showed the importance of the gut in T cell development.
Absence of functional alternative complement pathway alleviates lupus cerebritis
Authors: Alexander Jessy J. , Jacob Alexander , Vezina Paul , Sekine Hideharu , Gilkeson Gary S. , Quigg Richard J.
Published: May 2007

The complement inhibitor, Crry, which blocks both the classical and alternative pathways, alleviates CNS disease in the lupus model, MRL/MpJ‐Tnfrsf6lpr (MRL/lpr) mice. To understand the role of the alternative pathway, we studied mice deficient in a key alternative pathway protein, complement factor B (fB). Immune deposits (IgG and C3) were reduced in the brains of MRL/lpr fB‐deficient (fB–/–MRL/lpr) compared to fB‐sufficient (MRL/lpr) mice, indicating reduced complement activation. Reduced neutrophil infiltration (22% of MRL/lpr mice) and apoptosis (caspase‐3 activity was reduced to 33% of MRL/lpr mice) in these mice indicates that the absence of the alternative pathway was neuroprotective. Furthermore, expression of phospho (p)‐Akt (0.16 ± 0.02 vs. 0.35 ± 0.13, p <0.03) was increased, while expression of p‐PTEN (0.40 ± 0.06 vs. 0.11 ± 0.07, p <0.05) was decreased in fB–/–MRL/lpr mice compared to their MRL/lpr counterparts. The expression of fibronectin, laminin and collagen IV was significantly decreased in fB–/–MRL/lpr mice compared to MRL/lpr mice, indicating that in the lupus setting, tissue integrity was maintained in the absence of the alternative pathway. Absence of fB reduced behavioral alterations in MRL/lpr mice. Our results suggest that in lupus, the alternative pathway may be the key mechanism through which complement activation occurs in brain, and therefore it might serve as a therapeutic target for lupus cerebritis.
Back to the future –defining NK cells and T cells
Authors: Lanier Lewis. L.
Published: May 2007

In this issue of the European Journal of Immunology (EJI), Stewart et al. report about a population of γδ‐T cells expressing an extensive repertoire of NK cell receptors, and the presence of non‐rearranged germline TCRδ transcripts in conventional NK cells. These findings and other recent studies highlight the similarities of NK cells and T cells and the problems in discriminating between these two lineages.

See accompanying article: http://dx.doi.org/10.1002/eji.200737354
Cover Picture: Involvement of nonclassical MHC class Ib molecules in heat shock protein‐mediated anti‐tumor responses – Eur. J. Immunol. 6/2007
Authors: Goyos Ana , Guselnikov Sergey , Chida Asiya S. , Sniderhan Lynn F. , Maggirwar Sanjay B. , Nedelkovska Hristina , Robert Jacques
Published: May 2007

The image of the jumping frog was kindly provided by Jacques Robert and created by his son by Adrien. Anti‐tumor responses, both in vitro and in vivo, are studied using Xenopus laevis by Robert and colleagues (pp. 1494–1501); non‐classical MHC class Ib molecules are shown, by RNA interference, to be important for the gp96‐induced CTL response against class Ia‐negative tumors in Xenopus. The conservation of the class Ia‐unrestricted response from Xenopus to mammals indicates the importance of this anti‐tumor immune mechanism.
Syntheses and Structures of Molybdenum, Tungsten, and Manganese Complexes of a Cyclic Thiourea, [M(CO)5(SC3N2Me4)] (M = Mo, W) and [{CpMn(CO)2}2(μ‐SC3N2Me4)]
Authors: Saito Kazuya , Kawano Yasuro , Shimoi Mamoru
Published: May 2007

Photolysis of [CpMn(CO)3] in the presence of 1,3,4,5‐tetramethylimidazoline‐2‐thione, SC3N2Me4 (1), produced a thione‐bridged dinuclear complex, [{CpMn(CO)2}2(μ‐SC3N2Me4)] (2). Compound 2 shows unprecedented geometry of the Mn–S–Mn framework, featuring a pyramidal sulfur atom and long Mn···Mn distance. Photoreaction of [M(CO)6] (M = Mo, W) with 1 afforded mononuclear complexes [M(CO)5(SC3N2Me4)] [M = Mo (3), W (4)]. In compounds 2–4, the C–S bond of the thione ligand is stretched on coordination because of the polarization of the metal–ligand linkage. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)