bluuebunny/crossref_metadata_2025 huggingface dataset:
In Situ Synthesis of Ti5Si3 Matrix Nanocomposites Reinforced with Nanoparticles by High‐Energy Mechanical Alloying
Authors: Li Chuang , Gu Dongdong , Shen Yifu , Meng Guangbin , Li Yufang
Published: March 2011

In the present work, in situ TiN/Ti5Si3 nanocomposite powder was prepared by high‐energy mechanical alloying of a Ti and Si3N4 powder mixture via the following route: 9Ti + Si3N4 = Ti5Si3 + 4TiN. Constitution phases and microstructural features of the milled powders at different milling times were studied by XRD, SEM, and TEM. The operative formation mechanisms behind the microstructural developments were disclosed. It showed that the original Si3N4 and Ti constituents demonstrated two different reaction mechanisms during milling, i.e., a progressive mechanism of Si3N4 (≤20 h) and a speedy mechanism of Ti (≤10 h). The morphologies of the milled composite powders experienced a successive change: pre‐refining – coarsening – re‐refining on increasing the applied milling time. The variation of the operative mechanisms was ascribed to the existence/exhaustion of the ductile Ti constituent in the milling system due to the nonoccurrence/initiation of the in situ reaction. The 20 h milled powder was the typical nanocomposites featured by the nanocrystalline Ti5Si3 matrix reinforced with in situ TiN nanoparticles. The grain sizes of the in situ formed Ti5Si3 and TiN phases were generally ≤15 nm, exhibiting coherent interfacial structure between reinforcement and matrix.
Atomic Layer Deposition of Conductive Coatings on Cotton, Paper, and Synthetic Fibers: Conductivity Analysis and Functional Chemical Sensing Using “All‐Fiber” Capacitors
Authors: Jur Jesse. S. , Sweet William J. , Oldham Christopher J. , Parsons Gregory N.
Published: March 2011

Conductive coatings on complex fibrous systems are attracting interest for new electronic and other functional systems. Obtaining a quantitative conductivity value for complex surface coatings is often difficult. This work describes a procedure to quantify the effective electrical conductivity of conductive coatings on non‐conductive fibrous networks. By applying a normal force orthogonal to the current and field direction, fiber/fiber contact is improved and consistent conductance values can be measured. Nylon fibers coated with an electroless silver plating shows effective conductivity up to 1950 S cm−1, and quartz fibers coated with tungsten by atomic layer deposition (ALD) show values up to ∼1150 S cm−1. Cotton fibers and paper coated with a range of ZnO film thicknesses by ALD show effective conductivity of up to 24 S cm−1 under applied normal force, and conductivity scaled as expected with film coating thickness. Furthermore, we use the conductive coatings to produce an “all‐fiber” metal–insulator–metal capacitor that functions as a liquid chemical sensor. The ability to reliably analyze the effective conductivity of coatings on complex fiber systems will be important to design and improve performance of similar devices and other electronic textiles structures.
Uniform π‐System Alignment in Thin Films of Template‐Grown Dicarbonitrile‐Oligophenyls
Authors: Klappenberger Florian , Kühne Dirk , Marschall Matthias , Neppl Stefan , Krenner Wolfgang , Nefedov Alexei , Strunskus Thomas , Fink Karin , Wöll Christof , Klyatskaya Svetlana , Fuhr Olaf , Ruben Mario , Barth Johannes V.
Published: March 2011

The ordering and conformational properties of dicarbonitrile‐para‐oligophenyls are studied with complementary methods, namely X‐ray structure analysis, low‐temperature scanning tunneling microscopy, and near‐edge X‐ray absorption fine‐structure spectroscopy. The packing of the functionalized variants differs from their technologically interesting para‐oligophenyl counterparts, both in the bulk crystal phase and in thin films grown by organic molecular beam epitaxy (OMBE) under ultra‐high vacuum conditions on the Ag(111) surface. In the crystal phase, the conformation depends on the number n of phenyl rings, exhibiting an intriguing screw‐like structure in the case of n = 4 at room temperature as well as at 180 K. For OMBE‐grown thin films, the whole series acquires the same type of conformation, characterized by alternately twisted phenyl rings, similar to the pure oligophenyl species. However, for all tested molecules, the orientation of the molecular reference plane is uniform within the entire film and coincides with the surface plane. This contrasts with the herringbone ordering adopted by the phenyl backbones without the carbonitrile groups. Our results demonstrate how the functionalization of moieties with extended conjugated electron systems can help to improve the structural homogeneity in technologically relevant organic thin films.
Collective Motion of Conducting Filaments in Pt/n‐Type TiO2/p‐Type NiO/Pt Stacked Resistance Switching Memory
Authors: Kim Kyung Min , Song Seul Ji , Kim Gun Hwan , Seok Jun Yeong , Lee Min Hwan , Yoon Jung Ho , Park Jucheol , Hwang Cheol Seong
Published: March 2011

Filamentary resistance switching (RS) is one of the more obvious and useful phenomena in the family of RS mechanisms. In filamentary RS, the long reset switching time and substantially large power consumption are the critical obstacles for microelectronic applications. In this study, an innovative solution to overcome this reset problem is suggested by stacking n‐type TiO2 and p‐type NiO films. Interestingly, in this stacked structure, the region where filament rupture and rejuvenation occurs could be arbitrarily controlled to be at any location between the interface with the metal electrode and the TiO2/NiO interface by using an appropriate switching sequence. This collective motion behavior of conducting filaments can be practically used to reduce reset switching time from ∼100 μs to ∼150 ns, with an extremely high off/on resistance ratio of ∼106.
Doping of Organic Semiconductors Using Molybdenum Trioxide: a Quantitative Time‐Dependent Electrical and Spectroscopic Study
Authors: Gwinner Michael C. , Pietro Riccardo Di , Vaynzof Yana , Greenberg Kathryn J. , Ho Peter K. H. , Friend Richard H. , Sirringhaus Henning
Published: March 2011

Doping of organic semiconductors (OSCs) with transition metal oxides such as molybdenum trioxide (MoO3) has been used as a powerful method to overcome common issues such as contact resistance and low conductivity, which are limiting factors in organic optoelectronic devices. In this study, the mechanism and efficiency of MoO3‐induced p‐type doping in OSCs are investigated by means of simultaneous electrical and spectroscopic measurements on lateral diodes. It is demonstrated that energetic changes in the MoO3 energy levels outside vacuum can limit charge‐transfer doping and device performance. It is shown and investigated that these changes crucially depend on the OSC. The time evolution of important OSC parameters such as induced charge density, doping concentration and efficiency, conductivity and mobility, is deduced. Moreover, the energetic and chemical changes in MoO3 are investigated via ultraviolet and x‐ray photoemission spectroscopy. Combining these experiments, important conclusions are drawn on the time‐dependence and stability of MoO3‐doping of OSCs, as well as on the processing conditions and device architectures suitable for high‐performance devices.
Functional Materials for Rechargeable Batteries
Authors: Cheng Fangyi , Liang Jing , Tao Zhanliang , Chen Jun
Published: March 2011

There is an ever‐growing demand for rechargeable batteries with reversible and efficient electrochemical energy storage and conversion. Rechargeable batteries cover applications in many fields, which include portable electronic consumer devices, electric vehicles, and large‐scale electricity storage in smart or intelligent grids. The performance of rechargeable batteries depends essentially on the thermodynamics and kinetics of the electrochemical reactions involved in the components (i.e., the anode, cathode, electrolyte, and separator) of the cells. During the past decade, extensive efforts have been dedicated to developing advanced batteries with large capacity, high energy and power density, high safety, long cycle life, fast response, and low cost. Here, recent progress in functional materials applied in the currently prevailing rechargeable lithium‐ion, nickel‐metal hydride, lead acid, vanadium redox flow, and sodium‐sulfur batteries is reviewed. The focus is on research activities toward the ionic, atomic, or molecular diffusion and transport; electron transfer; surface/interface structure optimization; the regulation of the electrochemical reactions; and the key materials and devices for rechargeable batteries.
On the Effect of the Amorphous Silicon Microstructure on the Grain Size of Solid Phase Crystallized Polycrystalline Silicon
Authors: Sharma Kashish , Branca Annalisa , Illiberi Andrea , Tichelaar Frans D. , Creatore Mariadriana , van de Sanden Mauritius C. M.
Published: March 2011

In this paper the effect of the microstructure of remote plasma‐deposited amorphous silicon films on the grain size development in polycrystalline silicon upon solid‐phase crystallization is reported. The hydrogenated amorphous silicon films are deposited at different microstructure parameter values R* (which represents the distribution of SiHx bonds in amorphous silicon), at constant hydrogen content. Amorphous silicon films undergo a phase transformation during solid‐phase crystallization and the process results in fully (poly‐)crystallized films. An increase in amorphous film structural disorder (i.e., an increase in R*), leads to the development of larger grain sizes (in the range of 700–1100 nm). When the microstructure parameter is reduced, the grain size ranges between 100 and 450 nm. These results point to the microstructure parameter having a key role in controlling the grain size of the polycrystalline silicon films and thus the performance of polycrystalline silicon solar cells.
A mild and clean synthesis of alkyl azides from alkyl halides mediated by poly(4‐vinylpyridine)‐supported sodium azide under nonaqueous conditions
Authors: Karimi Zarchi Mohammad Ali , Escandari Zohreh
Published: March 2011

Alkyl halides were efficiently converted to their corresponding alkyl azides under mild nonaqueous conditions with a polymer‐supported azide as a new polymeric reagent at room temperature at high yields and purities. All of the byproducts were removed by filtration, and pure products were obtained by the evaporation of the solvent. The spent polymeric reagent could usually be removed quantitatively and regenerated. The regenerated polymeric reagent could be reused several times. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Grafting of molecularly imprinted polymers from the surface of Fe3O4 nanoparticles containing double bond via suspension polymerization in aqueous environment: A selective sorbent for theophylline
Authors: Luo Xubiao , Deng Fang , Luo Shenglian , Tu Xinman , Yang Lixia
Published: March 2011

Molecularly imprinted polymers (MIPs) were grafted from the surface of Fe3O4 nanoparticles containing double bond via suspension polymerization in aqueous environment, and the leakage of Fe3O4 nanoparticles from MIPs was overcome in this study. The effect of different cross‐linker on adsorption capacity of the resultant magnetic MIPs was investigated using pure trimethylolpropane trimethacrylate (TRIM) or the mixture of TRIM and divinylbenzene (DVB) as cross‐linker. Both magnetic MIPs exhibited higher adsorption capacity for the template theophylline than the corresponding non‐imprinted polymer, and Freundlich model fitted reasonably well for theophylline adsorption on both magnetic MIPs. In addition, both magnetic MIPs exhibited good recognition properties for the template theophylline versus caffeine, and the selectivity of magnetic MIPs using pure TRIM as cross‐linker (mag‐MIP‐TRIM) was much higher than those using the mixture of TRIM and DVB as cross‐linker (mag‐MIP‐TRIM and DVB). The adsorption dynamics of theophylline on both magnetic MIPs fitted well with the first‐order kinetic model, but the adsorption equilibrium on mag‐MIP‐TRIM and DVB reached faster than that on mag‐MIP‐TRIM. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Reversible phosphorylation regulation of NADPH‐linked polyol dehydrogenase in the freeze‐avoiding gall moth, Epiblema scudderiana: role in glycerol metabolism
Authors: Holden Helen A. , Storey Kenneth B.
Published: March 2011

Larvae of the goldenrod gall moth, Epiblema scudderiana, use a freeze avoidance strategy of cold hardiness to survive the winter. A key metabolic adaption that supports subzero survival is the accumulation of large amounts of glycerol as a colligative antifreeze. Production of glycerol relies on polyol dehydrogenase (PDH) which catalyzes the NADPH‐dependent conversion of glyceraldehyde into glycerol. Kinetic analysis of PDH from E. scudderiana revealed significant changes in properties as a result of subzero temperature acclimation; the Km for glyceraldehyde in 5°C‐acclimated larvae was 7.0 mM and doubled in − 15°C‐exposed larvae. This change suggested that PDH is regulated by a state‐dependent covalent modification. Indeed, high and low Km forms could be interconverted by incubating larval extracts in vitro under conditions that stimulated either endogenous protein kinases or protein phosphatases. Protein kinase incubations doubled the Km glyceraldehyde of the 5°C enzyme, whereas protein phosphatase incubations decreased the Km of the − 15°C enzyme by about 50%. PDH was purified by ion exchange and affinity chromatography steps and then subjected to electrophoresis. Staining with ProQ Diamond phosphoprotein stain showed a much higher phosphate content of PDH from − 15°C‐acclimated larvae, a result that was further confirmed by immunoblotting that showed a much greater phosphoserine content on the − 15°C enzyme. These experiments established that PDH is regulated by state‐dependent reversible phosphorylation in E. scudderiana and suggest that this regulatory mechanism makes a significant contribution to controlling the synthesis, maintenance, and degradation of glycerol pools over the winter months. © 2011 Wiley Periodicals, Inc.
Conjugate Additions to Alkylidene Bis(Sulfoxides)
Authors: Brebion Franck , Vincent Guillaume , Chelli Saloua , Kwasnieski Ophélie , Najera Francisco , Delouvrié Bénédicte , Marek Ilan , Derat Etienne , Goddard Jean‐Philippe , Malacria Max , Fensterbank Louis
Published: March 2011

A general study on the conjugate addition of anionic nucleophiles to alkylidene bis(sulfoxides) is presented. Alkoxides gave high yielding and diastereoselective addition reactions, which could be influenced by solvents and the counteranion. Azides provided an interesting entry into sulfinyl‐substituted triazoles. Organometallics, mainly copper reagents, proved also to be valuable nucleophiles, and complete inversion of the stereoselectivity was achieved in the addition reaction with the latter. Modelizations provide a rationale for the observed diastereoselectivity.
Large‐scale circulation anomalies associated with persistent low temperature over Southern China in January 2008
Authors: Bueh Cholaw , Shi Ning , Xie Zuowei
Published: March 2011

A pre‐existing anticyclonic anomaly over Scandinavia/western Russia played a crucial role in the persistent low temperature event over southern China in January 2008. This anticyclonic anomaly extended eastward along the arctic coast of the Eurasian continent, and then induced the persistent low temperature over southern China. Considering that anticyclonic anomalies over Scandinavia/western Russia rarely extended eastward to central Siberia, the simultaneous presence of this feature along with the vigorous Rossby wave propagation along the African‐Asian jet stream is found to be a fundamental factor in the occurrence of the persistent event. Copyright © 2011 Royal Meteorological Society
Immunohistochemical study of human costotransverse joints: A preliminary investigation
Authors: Dedrick G.S. , Sizer P.S. , Sawyer B.G. , BrismeÈ J.M. , Smith M.P.
Published: March 2011

The human costotransverse joint (CTJ) is the articulation between the posterior tubercle of the ribs with the first through tenth costal facet of the thoracic transverse processes. While the CTJ is well defined anatomically and considered a synovial joint, the human CTJ as a pain generating structure is controversial and not supported from a histological perspective. The objective of the present study was to investigate the histological pain producing properties of CTJ capsule tissue. Ten micron cross‐sections at each level (1–10) were stained with H & E or immunostained with antisera against Substance P (SP), calcitonin‐gene‐related peptide (CGRP), and neuropeptide Y (NPY). Immunoreactivity was confirmed for SP, CGRP, and NPY within the CTJ tissue samples of two unembalmed male cadavers. The presence of previously mentioned neuropeptides suggests that human CTJ is capable of producing pain through somatic and autonomic nervous systems. Therefore, clinicians should consider the CTJ as a differential diagnostic possibility when examining and treating painful thoracic conditions. Clin. Anat. 24:741–747, 2011. © 2011 Wiley‐Liss, Inc.
Approaches to Enzyme and Substrate Design of the Murine Dnmt3a DNA Methyltransferase
Authors: Jurkowska Renata Z. , Siddique Abu Nasar , Jurkowski Tomasz P. , Jeltsch Albert
Published: March 2011

Dnmt3a‐C, the catalytic domain of the Dnmt3a DNA‐(cytosine‐C5)‐methyltransferase, is active in an isolated form but, like the full‐length Dnmt3a, shows only weak DNA methylation activity. To improve this activity by directed evolution, we set up a selection system in which Dnmt3a‐C methylated its own expression plasmid in E. coli, and protected it from cleavage by methylation‐sensitive restriction enzymes. However, despite screening about 400 clones that were selected in three rounds from a random mutagenesis library of 60 000 clones, we were not able to isolate a variant with improved activity, most likely because of a background of uncleaved plasmids and plasmids that had lost the restriction sites. To improve the catalytic activity of Dnmt3a‐C by optimization of the sequence of the DNA substrate, we analyzed its flanking‐sequence preference in detail by bisulfite DNA‐methylation analysis and sequencing of individual clones. Based on the enrichment and depletion of certain bases in the positions flanking >1300 methylated CpG sites, we were able to define a sequence‐preference profile for Dnmt3a‐C from the −6 to the +6 position of the flanking sequence. This revealed preferences for T over a purine at position −2, A over G at −1, a pyrimidine at +1, and A and T over G at +3. We designed one “good” substrate optimized for methylation and one “bad” substrate designed not to be efficiently methylated, and showed that the optimized substrate is methylated >20 times more rapidly at its central CpG site. The optimized Dnmt3a‐C substrate can be applied in enzymatic high‐throughput assays with Dnmt3a‐C (e.g., for inhibitor screening), because the increased activity provides an improved dynamic range and better signal/noise ratio.
Introduction to Peptides and Proteins. By Ülo Langel, Benjamin F. Cravatt, Astrid Gräslund, Gunnar von Heijne, Tiit Land, Sherry Niessen and Matjaž Zorko.
Authors: Görbitz Carl Henrik
Published: March 2011

CRC Press, Boca Raton 2010, XIV+424 pp., hardcover $ 99.95.—ISBN 978‐1‐4200‐6412‐4
Tuning the Regio‐ and Stereoselectivity of CH Activation in n‐Octanes by Cytochrome P450 BM‐3 with Fluorine Substituents: Evidence for Interactions Between a CF Bond and Aromatic π Systems
Authors: Wu Li‐Lan , Yang Chung‐Ling , Lo Feng‐Chun , Chiang Chih‐Hsiang , Chang Chun‐Wei , Ng Kok Yaoh , Chou Ho‐Hsuan , Hung Huei‐Ying , Chan Sunney I. , Yu Steve S.‐F.
Published: March 2011

We employed the water‐ soluble cytochrome P450 BM‐3 to study the activity and regiospecificity of oxidation of fluorinated n‐octanes. Three mutations, A74G, F87V, and L188Q, were introduced into P450 BM‐3 to allow the system to undergo n‐octane oxidation. In addition, the alanine at residue 328 was replaced with a phenylalanine to introduce an aromatic residue into the hydrophobic pocket to examine whether or not van der Waals interactions between a CF substituent in the substrate and the polarizable π system of the phenylalanine may be used to steer the positioning of the substrate within the active‐site pocket of the enzyme and control the regioselectivity and stereoselectivity of hydroxylation. Interestingly, not only was the regioselectivity controlled when the fluorine substituent was judiciously positioned in the substrate, but the electron input into the iron–heme group became tightly coupled to the formation of product, essentially without abortive side reactions. Remarkable enhancement of the coupling efficiency between electron input and product formation was observed for a range of fluorinated octanes in the enzyme even without the A328F mutation, presumably because of interactions of the CF substituent with the π system of the porphyrin macrocycle within the active‐site pocket. Evidently, tightening the protein domain containing the heme pocket tunes the distribution of accessible enzyme conformations and the associated protein dynamics that activate the iron porphyrin for substrate hydroxylation to allow the reactions mediated by the high‐valent FeIVO to become kinetically more commensurate with electron transfer from the flavin adenine dinucleotide (FAD)/flavin mononucleotide (FMN) reductase. These observations lend compelling evidence to support significant van der Waals interactions between the CF2 group and aromatic π systems within the heme pocket when the fluorinated octane substrate is bound.
Micellar Extraction of Zinc with Di(2‐ethylhexyl)phosphoric Acid and the Addition of the Cationic Surfactant Cetyltrimethylammonium Bromide
Authors: Raatz Simone , Klapper Peter , Repke Jens‐Uwe
Published: March 2011

Durch den Zusatz von Tensiden kann die Extraktion deutlich beeinflusst werden. Für Tensidkonzentration geringfügig oberhalb der kritischen Mizellbildungskonzentration steigt die Stofftransportrate durch die Bildung inverser Mizellen und eines dadurch verursachten mizellaren Zinkextraktionsmechanismus. Anhand von Extraktionsgleichgewichten und Stoffaustauschuntersuchungen wird die Beeinflussung der Zinkextraktion mit dem Kationenaustauscher Di(2‐ethylhexyl)phosphorsäure (D2EHPA) unter Zugabe des Tensids Cetyltrimethylamoniumbromid (CTAB) aufgezeigt und phänomenologisch erläutert.
Evaluation of Readily Accessible Azoles as Mimics of the Aromatic Ring of D‐Phenylalanine in the Turn Region of Gramicidin S
Authors: van der Knaap Matthijs , Lageveen Lianne T. , Busscher Henk J. , Mars‐Groenendijk Roos , Noort Daan , Otero José M. , Llamas‐Saiz Antonio L. , van Raaij Mark J. , van der Marel Gijsbert A. , Overkleeft Herman S. , Overhand Mark
Published: March 2011

The influence of replacing the d‐phenylalanine residue with substituted and unsubstituted azoles on the structure and biological activity of the antibiotic gramicidin S was investigated against a representative panel of Gram‐positive and Gram‐negative bacteria strains. Substituted triazole derivatives, obtained using a convergent synthetic strategy, are as active as gramicidin S, provided that any substituent on the triazole moiety is not too large. The unsubstituted triazole derivative was biologically less active than the parent natural product, gramicidin S. In general for the triazole series, the hemolytic activity could be correlated with the antibacterial activity, that is, the higher the antibacterial activity, the higher the toxicity towards blood cells. Interestingly, its imidazole counterpart showed high antibacterial activity, combined with significantly diminished hemolytic activity.
Sulfonylthiadiazoles with an Unusual Binding Mode as Partial Dual Peroxisome Proliferator‐Activated Receptor (PPAR) γ/δ Agonists with High Potency and in vivo Efficacy
Authors: Keil Stefanie , Matter Hans , Schönafinger Karl , Glien Maike , Mathieu Magali , Marquette Jean‐Pierre , Michot Nadine , Haag‐Diergarten Silke , Urmann Matthias , Wendler Wolfgang
Published: March 2011

Compounds that simultaneously activate the peroxisome proliferator‐activated receptor (PPAR) subtypes PPARγ and PPARδ have the potential to effectively target dyslipidemia and type II diabetes in a single pharmaceutically active molecule. The frequently observed side effects of selective PPARγ agonists, such as edema and weight gain, are expected to be overcome by using partial instead of full agonists for this nuclear receptor family. Herein we report the discovery, synthesis, and optimization of a novel series of sulfonylthiadiazoles that are active as partial agonists. The initial compound 6 was discovered by high‐throughput screening as a moderate partial PPARδ agonist; its optimization was based on the X‐ray crystal structure in complex with PPARδ. In contrast to other PPARδ agonists, this ligand does not interact directly with residues from the activation helix AF‐2, which might be linked to its partial agonistic effect. Interestingly, the thiadiazole moiety fills a novel subpocket, which becomes accessible after moderate conformational rearrangement. The optimization was focused on introducing conformational constraints and replacing intramolecular hydrogen bonding interactions. Highly potent molecules with activity as dual partial PPARγ/δ agonists in the low nanomolar range were then identified. One of the most active members, compound 20 a, displayed EC50 values of 1.6 and 336 nM for PPARδ and γ, respectively. The X‐ray crystal structure of its complex with PPARδ confirms our design hypothesis. Compound 20 a clearly displayed in vivo activity in two chronic mice studies. Lipids were modified in a beneficial way in normolipidemic mice, and the development of overt diabetes could be prevented in pre‐diabetic db/db mice. However, body weight gain was similar to that observed with the PPARγ agonist rosiglitazone. Hence, active compounds from this series can be considered as valuable tools to elucidate the complex roles of dual PPARγ/δ agonists for potential treatment of metabolic syndrome.
Keynote address: The past, the present, the future
Authors: Ho Reginald C. S.
Published: March 2011

Lung cancer in women has replaced uterine cancer among the cancers causing the highest mortality in women. However, breast cancer remains a leading cause of death because of increasing incidence. Potential causes for the increase in both these diseases in women will be explored.

An exciting development in recent years has been the clarification of the role of oncogenes in carcinogenesis. It appears that some cancers require multiple sequential mutations for malignant transformation to occur. This may be the model for the study of carcinogenesis. These developments in molecular genetics have important implications in screening, diagnosis, prevention, and in treatment strategies.

We may be witnessing the beginning of the era of cell differentiation therapy. Retinoids have a potential for impacting on the treatment of neoplasms such as promyelocytic leukemia and oropharyngeal cancers. Understanding of the mechanism of cell differentiation may be forthcoming although molecular genetic studies.
An overview of screening and early detection of gynecologic malignancies
Authors: White Linda N.
Published: March 2011

Reducing the toll of gynecologic cancer not only requires improving treatment, but also incorporating cancer prevention and detection strategies into clinical practice. Reviewing vulvar, cervical, endometrial, and ovarian cancer—their associated risk factors, means of prevention and early detection, and signs and symptoms—alerts patients to the potential risks and the detection methods available. Discussing what behaviors, personal characteristics, family history, and exposures increase their risk; what behaviors reduce their risk; and what self‐examinations and professional examinations may improve early detection permits health care professionals to write prescriptions for health. Neither major expenditure nor reorganization is required to incorporate cancer prevention and detection into existing clinical practice. Health care professionals who follow screening and detection recommendations appropriate in their own lives issue a consistent message and help bring patients into an active and responsibility‐sharing partnership for better health.
Controversies in the management of low‐grade cervical intraepithelial neoplasia
Authors: Richart Ralph M. , Wright Thomas C.
Published: March 2011

During the last 30 years, there have been major changes in the methods used to diagnose and manage cervical cancer precursors. Early detection of precursors through mass cytologic screening programs and the eradication of these precursors when detected are currently the cornerstone of policies aimed at reducing cervical cancer. These policies have been successful, resulting in a marked reduction in both the number of cases and deaths from cervical cancer in North America and Western Europe. Recently, however, significant controversy has arisen over several aspects of the diagnosis and management of cervical intraepithelial neoplasia (CIN). Two of the most important of these controversies are whether all patients with low‐grade CIN lesions require therapy and what is the appropriate role for the newly introduced loop electrosurgical excision procedure in managing patients with CIN. In this article, these controversies are reviewed with emphasis placed on how these controversies affect the practicing gynecologist.
Radical hysterectomy for invasive cervical cancer: A 25‐year prospective experience with the Miami technique
Authors: Averette Hervy E. , Nguyen Hoa N. , Donato Daniel M. , Penalver Manuel A. , Sevin Bernd‐Uwe , Estape Ricardo , Little William A.
Published: March 2011

Background. The Miami modification of the traditional Wertheim–Meigs radical hysterectomy was used to treat Stage IB–IIA cervical cancer in a 25‐year prospective study involving 978 patients.

Methods. The modifications included: vaginal reconstruction and closure using bladder and rectosigmoid serosa, retroperitoneal drainage through abdominal suction catheters, and suspension of the denuded ureters with the ipsilateral obliterated hypogastric artery.

Results. The overall corrected 5‐year survival rate was 90.1%, with a surgical mortality rate of 1.4% and an overall urinary fistula rate of 1.4%. This fistula rate was significantly better than a 4.4% incidence rate in a literature survey. Although not measured, the Miami modification appeared to lengthen the vagina.

Conclusions. Therefore, it was concluded that radical hysterectomy with the Miami modifications can be done safely in most patients with Stage IB–IIA cervical cancer.
International federation of gynecology and obstetrics staging of endometrial cancer 1988
Authors: Mikuta John J.
Published: March 2011

In 1988, the International Federation of Gynecology and Obstetrics (FIGO) Cancer Committee changed the staging of endometrial carcinoma from a clinical one to a surgicopathologic one. The emphasis in the new FIGO system was changed to the pathologic findings in the uterus, cervix, adnexa, and pelvic and/or periaortic nodes, and peritoneal cytologic findings. The major changes in this staging system were (1) the use of the depth of myometrial invasion and (2) the identification of tumor cells in peritoneal cytologic examination and of invasion in the retroperitoneal lymph nodes. Preoperative endocervical curettage was no longer necessary. Currently, the high level of operability of patients with endometrial carcinoma makes this staging system a viable one, which will provide information about the need for additional treatment. The use of the grading system for the tumor also was refined to upgrade nuclear changes that were inappropriate for the architectural grade. In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading took precedence. Adenocarcinomas with squamous differentiation were graded according to the nuclear grade of the glandular component.
Virulence factors in endometrial cancer
Authors: Gusberg S. B.
Published: March 2011

The majority of endometrial cancers are relatively benign and curable; there is a subset of virulent tumors that demands recognition. Factors that must be evaluated include: tumor grade, ploidy, steroid receptors, myometrial invasion, lymph node status, extrauterine disease or positive peritoneal fluid, and certain special tumors. These tumors of special virulence include: papillary adenocarcinoma, papillary serous adenocarcinoma, adenosquamous carcinoma, and clear cell carcinoma. Virulent tumors (approximately 20%) require special consideration and special treatment.
Prognostic significance of hormone receptors in endometrial cancer
Authors: Creasman William T.
Published: March 2011

Background. Endometrial carcinoma is the most common femalé pelvic genital malignancy. Many studies suggest that approximately 75% of all endometrial cancers are clinical Stage I. More than 50% of cancer deaths are in patients with clinical Stage I disease. As a result, prognostic factors have been evaluated in an attempt to identify those patients with presumed early stage disease who will be at high risk for recurrence. Recently, hormone receptor status (estrogen [ER], progesterone [PR]) in endometrial cancer has been suggested to be a prognostic factor.

Methods. Two hundred seventeen patients with Stage I and II endometrial cancers were evaluated for cytoplasmic steroid‐receptor status. These results were compared with other prognostic factors in both univariant and multivariant analysis.

Results. When ER and PR and combined ER/PR status were analyzed separately, patients with receptor‐positive lesions had significantly better disease‐free survival than those with receptor‐negative lesions. The receptor status was also a significant independent prognostic factor when evaluated by stepwise proportional hazards regression analysis.

Conclusions. Hormone receptor status in endometrial cancer appears to be an important prognostic factor.
Hormone‐replacement therapy in patients with breast cancer: A reappraisal
Authors: Disaia Philip J.
Published: March 2011

Background. It has been common practice to prohibit hormone‐replacement therapy (HRT) in patients with breast cancer. A reappraisal of this practice is necessary because hundreds of reports have established the benefits of HRT in coronary artery disease, osteoporosis, the serum lipid profile, and quality of life.

Methods. An argument is presented to support the safety of HRT use in such patients in the absence of a prospective randomized study addressing these issues. This argument relies primarily on historical data.

Results. There is no direct evidence that the use of HRT adversely affects patients who have previously been afflicted with breast cancer.

Conclusions. A prospective randomized study is essential to resolve this issue. In the meantime, patients should be counseled regarding the theoretical adverse effects of HRT versus the proven beneficial effects and the final decision for its use rests with the patient.
The estrogenic activity of synthetic progestins used in oral contraceptives
Authors: Jordan V. Craig , Jeng M. H. , Catherino W. H. , Parker C. J.
Published: March 2011

Background. Oral contraceptives (OC) contain an orally active estrogen in combination with an orally active synthetic progestin derived from 19‐nortestosterone. OC have had an enormous positive impact on public health for the past three decades, and in the main, there has been a remarkably low incidence of troublesome side effects. Although estrogens are implicated in an increased incidence of breast and endometrial cancer, epidemiologic studies have not provided convincing evidence to support a direct correlation between OC use and an increase in breast cancer incidence. By contrast, OC do cause a decrease in the incidence of endometrial and ovarian carcinoma. During the past decade, several isolated reports have linked an increased incidence of breast cancer with the use of synthetic progestins. No mechanism for the proliferative potential of progestins has been offered. Therefore, the authors investigated this problem to formulate a hypothesis, based on laboratory data, that might be evaluated in populations at risk.

Methods. The synthetic progestins (19‐nortestosterone derivatives) chosen for the study were norethynodrel, norethindrone, norgestrel (levonorgestrel), and gestodene. These were compared with the actions of medroxyprogesterone acetate (MPA). To determine whether the progestins produced their effects via the ER, the cells were transfected with a chloramphenicol acetyl transferase (CAT) reporter gene containing an estrogen response element only activated by ER.

Results. The 19‐nortestosterone derivatives all stimulated the growth of estrogen receptor (ER)‐positive but not ER‐negative breast cancer cells in culture. Antiestrogens, but not the antiprogestin mifepristone (also known as RU 486), inhibited progestin‐stimulated cell proliferation. MPA did not stimulate cell proliferation. All the synthetic progestins that increased replication also activated CAT. Activation was blocked by antiestrogens but not by mifepristone; the synthetic progestin MPA was inactive.

Conclusions. These studies provided direct evidence that some synthetic progestins exert estrogenic effects through the ER. The results demonstrated that progestins can have a dual effect on estrogen target tissues either to stimulate or differentiate cells. The results suggest that some beneficial estrogen‐like effects could be produced by synthetic progestins (e.g., bone preservation), but epidemiologic studies of OC use should focus of the “total estrogen” content to establish whether some formulations place some groups of women at greater risk of having breast cancer.
Age‐specific differences in the relationship between oral contraceptive use and breast cancer
Authors: Wingo Phyllis A. , Lee Nancy C. , Ory Howard W. , Beral Valerie , Peterson Herbert B. , Rhodes Philip
Published: March 2011

Background. Nearly all studies have suggested that the use of oral contraceptives (OC) is not associated with the aggregate risk of breast cancer diagnosed in women aged 20–54 years. Because of age‐specific differences in the breast cancer–parity relationship and because of age‐specific differences in other breast cancer risk factors, the Centers for Disease Control reexamined data from the Cancer and Steroid Hormone Study (CASH) to assess whether OC use has different effects on the risk of breast cancer at different ages of diagnosis.

Methods. This population‐based case–control study was designed to examine the relationship between the use of OC and the risk of breast, ovarian, and endometrial cancer. CASH was conducted in eight geographic areas in the United States during 1980–1982. All participants were interviewed at home with a pretested standardized questionnaire including a calendar of life events and a photograph book of all pills marketed in the United States.

Results. We found that the relationship between the risk of breast cancer and OC use appeared to vary by the age at diagnosis. Among women aged 20–34 years at diagnosis or interview, those who had ever used OC had a slightly increased risk of breast cancer (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0–2.1) compared with women of the same ages who had never used OC. Among these women, there were no trends of increasing or decreasing risk with any measure of OC use. Among women aged 35–44 years, there was no association between OC use and breast cancer. Among women aged 45–54 years, those who used OC had a slightly decreased risk of breast cancer (OR, 0.9; 95% CI, 0.8–1.0). Among these women, risk estimates decreased significantly with increasing time since first and last use.

Conclusions. Although the slightly increased risk estimates for the youngest women were compatible with findings by other investigators, the decreased risk estimates for the oldest women have not been described in as many studies. Available data provide no reasons to change prescribing practices or the use of OC that are related to the breast cancer risk.
Ovarian cancer screening
Authors: van Nagell John R. , Depriest Paul D. , Gallion Holly H. , Pavlik Edward J.
Published: March 2011

Background. Despite advances in evaluation and treatment, ovarian cancer mortality has decreased minimally during the past two decades. Most patients have advanced‐stage disease at diagnosis, and the prognosis is poor. As a result, there has been increasing interest in the development of methods for the early detection of ovarian cancer. To benefit from screening, a disease should (1) be a significant cause of mortality, (2) have a high prevalence in the screened population, (3) have a preclinical phase that can be detected by screening, and (4) be amenable to therapy, such that the survival rate of patients with early‐stage disease is significantly higher than that of patients with advanced‐stage disease. Ovarian cancer fulfills all of these criteria.

Methods. An optimal screening method should be safe, easy to do, time efficient, and acceptable to the patients being screened. Most importantly, it should have a high sensitivity and specificity.

Results. Currently, the most effective screening methods for ovarian cancer are serum CA 125 levels and transvaginal sonography (TVS). In screening studies, the serum CA 125 level has had a reasonably high specificity but a low sensitivity. Currently, approximately 8000 asymptomatic women have been screened with TVS. Ten primary ovarian cancers were detected, and all were Stage I lesions. Patients whose tumors were detected by TVS all have been cured by conventional treatment. TVS screening has resulted in a significant reduction in stage at detection and in the case‐specific death rate from ovarian cancer. In these studies, TVS has had a high sensitivity but only a moderate specificity. CA 125 level, Doppler flow sonography, and the use of a morphology index are being evaluated as methods to increase the specificity of TVS.

Conclusions. A large multiinstitutional study is indicated to determine if annual TVS screening will cause a significant decrease in site‐specific mortality from ovarian cancer.
Prophylaxis in ovarian cancer
Authors: Barber Hugh R. K.
Published: March 2011

The only prophylaxis for ovarian cancer is oophorectomy, except in the very rare case when an ovarian cancer appears to arise from the mesothelial tissue of the abdominal cavity.

It has been shown that women who have taken the oral contraceptive pill for 4 or 5 years decreases the incidence of ovarian cancer by approximately 40%. It is estimated that the oral contraceptive pill can prevent approximately 1500 ovarian cancers each year.

The postmenopausal palpable ovary syndrome is simply the palpation of what is interpreted as a normal‐sized ovary in the premenopausal woman represents an ovarian tumor in the postmenopausal woman. It addresses the size and consistency and has nothing to do with the small cysts reported by the sonographer.

A patient who has two first‐degree blood relatives or a mother, sister, or daughter who has developed ovarian cancer premenopausally is at high risk to develop ovarian cancer.

Because ovarian cancer is the leading cause of death from gynecologic cancer, it is important to explore all options for prophylaxis in the prevention of ovarian cancer.
Intraperitoneal chemotherapy in the management of ovarian cancer
Authors: Markman Maurie , Reichman Bonnie , Hakes Thomas , Curtin John , Jones Walter , Lewis John L. , Barakat Richard , Rubin Stephen , Mychalczak Borys , Saigo Patricia , Almadrones Lois , Hoskins William
Published: March 2011

During the past decade, intraperitoneal therapy of ovarian cancer has evolved from a pharmacologic model into an established treatment technique for women with this malignancy. Approximately 40% of patients with small‐volume residual ovarian cancer (microscopic disease or macroscopic tumor, ≤ 0.5 cm in maximum tumor diameter), after an objective response to initial organoplatinum‐based systemic chemotherapy, may have a surgically documented complete response to platinum‐based intraperitoneal chemotherapy. Patients who have not responded to systemic platinum administration rarely will respond to the drug given intraperitoneally, despite the presence of only small‐volume residual disease when this regional treatment strategy is used. Other agents with antineoplastic activity after intraperitoneal administration in women with ovarian cancer include mitoxantrone, taxol, alpha‐interferon and gamma‐interferon, and interleukin‐2. Although intraperitoneal therapy currently is being examined as a component of the initial chemotherapeutic program for patients with ovarian cancer, a precise role for regional drug delivery in this clinical setting remains to be defined.
Update on malignant ovarian germ cell tumors
Authors: Gershenson David M.
Published: March 2011

The evolution of therapy for malignant ovarian germ cell tumors has been one of the true success stories in oncology. This article reviews the major advances in this field, with emphasis on more recent developments. During the past two decades, the nomenclature and histologic criteria for the major histologic subtypes have been standardized. Although the role of secondary debulking is uncertain, it probably has merit in selected patients. The use of second‐look laparotomy should be limited as much as possible. Chemotherapeutic regimens have evolved to the current “gold standard” —the combination of bleomycin, etoposide, and cisplatin, with overall disease‐free survival rates of greater than 95%. For patients with metastatic dysgerminoma, chemotherapy has replaced radiation therapy as the treatment of choice. For those few patients who do not respond to first‐line therapy, the combination of vinblastine, ifosfamide, and cisplatin is the most popular regimen for the subset of platinum‐sensitive tumors. For those with platinum‐resistant tumors, dose intensification with autologous bone marrow rescue or Phase II drugs are being investigated. Studies on the late effects of treatment reveal that reproductive potential can be preserved in most young patients. In summary, although the progress in this field has been phenomenal, small incremental advances will continue to occur during the 1990s.