bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiolabeled Small Molecule Protein Kinase Inhibitors for Imaging with PET or SPECT
Authors: Hicks Justin W. , VanBrocklin Henry F. , Wilson Alan A. , Houle Sylvain , Vasdev Neil
Published: November 2010

Imaging protein kinase expression with radiolabeled small molecule inhibitors has been actively pursued to monitor the clinical potential of targeted therapeutics and treatments as well as to determine kinase receptor density changes related to disease progression. The goal of the present review is to provide an overview of the breadth of radiolabeled small molecules that have been synthesized to target intracellular protein kinases, not only for imaging in oncology, but also for other areas of interest, particularly the central nervous system. Considerable radiotracer development has focused on imaging receptor tyrosine kinases of growth factors, protein kinases A, B and C, and glycogen synthase kinase–3β. Design considerations, structural attributes and relevant biological results are summarized.
MimoDB: a New Repository for Mimotope Data Derived from Phage Display Technology
Authors: Ru Beibei , Huang Jian , Dai Ping , Li Shiyong , Xia Zhongkui , Ding Hui , Lin Hao , Guo Feng-Biao , Wang Xianlong
Published: November 2010

Peptides selected from phage-displayed random peptide libraries are valuable in two aspects. On one hand, these peptides are candidates for new diagnostics, therapeutics and vaccines. On the other hand, they can be used to predict the networks or sites of protein-protein interactions. MimoDB, a new repository for these peptides, was developed, in which 10,716 peptides collected from 571 publications were grouped into 1,229 sets. Besides peptide sequences, other important information, such as the target, template, library and complex structure, was also included. MimoDB can be browsed and searched through a user-friendly web interface. For computational biologists, MimoDB can be used to derive customized data sets and benchmarks, which are useful for new algorithm development and tool evaluation. For experimental biologists, their results can be searched against the MimoDB database to exclude possible target-unrelated peptides. The MimoDB database is freely accessible at http://immunet.cn/mimodb/.
Towards the Development of Synthetic Routes Using Theoretical Calculations: An Application of In Silico Screening to 2,6-Dimethylchroman-4-one
Authors: Hori Kenji , Sadatomi Hirotaka , Miyamoto Atsuo , Kuroda Takaaki , Sumimoto Michinori , Yamamoto Hidetoshi
Published: November 2010

This study describes an attempt to develop a synthetic route using theoretical calculations, i.e., in silico synthesis route development. The KOSP program created four potential synthetic routes for generating 2,6-dimethylchroman-4-one. In silico screening of these four synthetic routes was then performed. In silico screening involves theoretical analysis of synthetic routes prior to actual experimental work. A synthetic route using the Mitsunobu reaction had already been reported by Hoddgets et al. Theoretical investigations were also conducted on two SNAr reactions as well as a Michael reaction before they were examined experimentally. In silico screening using DFT calculations indicated that only the Michael reaction was likely to produce the target. Experimental work confirmed that the target was obtained in a yield of 76.4% using the Michael reaction. The other two routes, except for the Mitsunobu reaction, failed to generate the target. Our results demonstrate that theoretical calculations can be used to narrow down the number of experiments that need to be conducted when developing novel synthetic routes.
Synthesis, Structures and Properties of Cu(II) and Mn(II) Complexes with 1,10-Phenanthroline-2-carboxylic acid and 2,2’-Bipyridine Ligands
Authors: Sun Jingya , Xu Huanzhi
Published: November 2010

Four new 2,2’-bipyridine and 1,10-phenanthroline complexes, namely [Mn(phenca)2]·(H2O)2 (1), [Cu4(phen)4(OH-)4(H2O)2](DMF)4(ClO4-)4(H2O) (2), [Cu2(2,2-bipy)2(C2O42-)(H2O)2(NO3)2] (3) and [Cu(2,2-bipy)2(ClO4-)](ClO4-) (4) (2,2’-bpy = 2,2’-bipyridine, Hphenca = 1,10-phenanthroline-2-carboxylic acid) have been synthesized by a hydrothermal reaction. The products were characterized by elemental analysis, infrared spectroscopy and X-ray crystal diffraction. While strong hydrogen bonds play central roles in the formation of the 3D structure, the combined influence of the weak interactions such as π···π interactions is also evident in the structures. A preliminary investigation on the ion exchange properties of the complexes is presented.
Functionalization, Compatibilization and Properties of Polyolefin Composites with Natural Fibers
Authors: Pracella Mariano , Haque Md. Minhaz-Ul , Alvarez Vera
Published: November 2010

The article is focused on analyzing the effect of functionalization and reactive processing on the morphological, thermal, rheological and mechanical properties of composites of isotactic polypropylene (PP), polystyrene (PS), poly(ethylene-vinyl acetate) (EVA), with cellulose fibers, hemp or oat as natural fillers. Both polymers and fibers were modified with bi-functional monomers (glycidyl methacrylate, GMA; maleic anhydride, MA) capable of facilitating chemical reactions between the components during melt mixing. Polyolefin copolymers containing reactive groups (PP-g-GMA, SEBS-g-MA, PS-co-MA, etc.) were used as compatibilizers. Optical and SEM microscopy, FTIR, RX, DSC, TGA, DMTA, rheological and mechanical tests were employed for the composites characterization. The properties of binary and ternary systems have been analyzed as a function of both fiber and compatibilizer content. All compatibilized systems showed enhanced fiber dispersion and interfacial adhesion. The phase behavior and the thermal stability of the composites were affected by the chemical modification of the fibers. Marked changes in the overall crystallization processes and crystal morphology of PP composites were observed owing to the nucleating effect of the fibers. The tensile mechanical behavior of the compatibilized composites generally resulted in a higher stiffness, depending on the fiber amount and the structure and concentration of compatibilizer.
The Contribution of Wildlife to Sustainable Natural Resource Utilization in Namibia: A Review
Authors: Schalkwyk Diana L. van , McMillin Kenneth W. , Witthuhn R. Corli , Hoffman Louw C.
Published: November 2010

Namibia is the driest country in sub-Saharan Africa, but well known for its richness in species and sustainable natural resource utilization. The Namibian farming sector consists mainly of extensive farming systems. Cattle production contributes 54% of the livestock sector’s production output, followed by sheep and goats (25%), hides and skins (9%), and other forms of agricultural production (12%). Namibia’s freehold farmers have obtained ownership rights over land and livestock since the early 1900s; commercial rights over wildlife and plants were given to freehold farmers in 1967 and to communal farmers in 1996. Natural resource-based production systems then overtook agricultural production systems and exceeded it by a factor of at least two. The shift from practicing conservation to sustainable utilization of natural resources contributed to the rapid growth of wildlife utilization. The wildlife industry in Namibia is currently the only animal production system that is expanding. There are in total at least two million head of different wildlife species. The broader impact of the utilization of wildlife on the economy is estimated to be around N$ 1.3 billion. Tourism, live sales and trophy hunting, cannot sustain further growth. Wildlife farming could offer better opportunities for ensuring long-term sustainability. As the game meat trade in Namibia is not formalized, harvesting wildlife to satisfy the demand for game meat in export markets is still in its infancy. Sustainable harvesting of wildlife for meat production, however, has the potential to increase earnings to the beneficiaries in the wildlife sector.
Building Association Attendance: Differences Between Chapter, Regional, and Annual Meetings from the Perception of the Association Members
Authors: Fjelstul Jill , Severt Kimberly , Breiter Deborah
Published: November 2010

The objective of this study was to identify meeting patterns and trends related to chapter, regional, and/or annual conference attendance. Factors likely to increase attendance, attendance trends over a 5-year period, recommendations by association members, and the preferred mode of
delivery were identified. Results will assist meeting planners in providing maximum benefits to association members and to potentially increase attendance at each conference level.
Effects of Hosting a Mega-Sport Event on Country Image
Authors: Gripsrud Geir , Nes Erik B. , Olsson Ulf H.
Published: November 2010

Nations and cities compete to host international mega-sport events such as the Olympic Games even if very large costs are incurred. Country image may be changed by hosting such events, and country image dimensions are in turn related to product image and behavioral intentions regarding
product purchase and tourism. In this article a model of these relationships is developed, based on several streams of literature. The empirical study reported relates to the Winter Olympics in Turin, Italy in 2006. A quasi-experimental design was employed based upon two samples of undergraduate
students in Norway. Data was gathered both before and after the Olympic Games took place. The study indicates that dimensions of country image for those being very interested in sports may be changed by hosting a mega-sport event. However, there is no guarantee that the image of the host country
will improve. It may actually deteriorate. This finding underscores the importance of managing international sport events properly.
Safety and Hostility at Special Events: Lessons from Australian Gay and Lesbian Festivals
Authors: Markwell Kevin , Tomsen Stephen
Published: November 2010

This article explores aspects of risk, safety, and hostility as perceived and experienced by participants at large-scale gay and lesbian festivals and special events held in Australia. These public celebrations of gay and lesbian identity have considerable economic, social, and cultural
benefits and they contribute significantly to the creation of cosmopolitan imagery for the cities in which they are held. In particular, the Sydney Gay and Lesbian Mardi Gras (SGLMG) is now internationally known as a major gay and lesbian festival and attracts substantial numbers of both domestic
and inbound tourists. The article reports on the results of an Internet-based questionnaire survey that sought information concerning gay, lesbian, and queer participants' perceptions and experiences of hostility, threats, and violence on the basis of their sexual identity before, during,
and after these events. Event organizers and public officials involved in planning and management emphasize the order and goodwill of these occasions. Nevertheless, participants from these sexual minorities feel notably unsafe or threatened in relation to significant aspects of attendance
at large-scale nighttime events with a wide heterosexual participation, and this may prove to be an important factor in the long term viability of these events.
Aditivos para el hormigón. Calidad y Normativa
Authors: Gaspar-Tebar Demetrio
Published: November 2010

The admixtures have lost a large part of their character of mysterious products with which spectacular transformations of concretes are achieved. On the other hand, they fave effectively contributed (when used properly) to the development of concretes and have become another one of their components to such an extent that, in many cases, their use is necessary.
This paper deals with the current situation of the Spanish Standard and, specially, of the European Standard elaborated by the SC-3 (Admixtures for concrete)/TC 104 (Concrete) of the CEN, where it analysis the testing methods and the characteristics required, specifications and conformity criteria to the principal families of admixtures most used in the concrete manufacturing, taking into account the fact that the admixtures must used once their effects on the concrete are know and that the maintaining of their characteristics must be guaranteed by an adequate quality control.
The sulphate resistance of the portland cements and their grinding fineness degree: analysis of their relation
Authors: Talero R. , Palacios J. , Morales J. E.
Published: November 2010

This work has demonstrated the great influence that the specific surface of a Portland cement has on its qualification as a high or low resistance to sulfate ion attack - SIA, by means of the accelerated method ASTM C 452.
For that purpose two Portland cements have been tested by means of that method. A Portland cement PY (3,83% C3A) (Type V(2)) with 3 different specific surfaces.
The experimental results obtained have demonstrated that, according to the ASTM C452-68 method, a Portland Cement Type III(2) can be qualified as from Type V(2), and vice verse, according to its specific surface being adequated, or not, for each objective.
Stuccos and roman concretes of the Baelo Claudia city (Cádiz): Characterization and causes of decay
Authors: Puertas Francisca , Blanco-Varela María Teresa , Palomo Ángel
Published: November 2010

This paper presents the study of the nature and conservation state of different stuccos and Roman concretes from the Roman city of Baelo Claudia (Cádiz). The chemical, mineralogical and microstructural compositions of the said materials have been established. Different causes of their decay have been found, among which we should emphasize the loss of the binding material (lime), basically due to the processes of partial solubilization; the lack of bond between the stuccos and the support stone, due to the different characteristics and properties of these two materials; and finally, the biological-type attack with the proliferation and colonization of different organisms in the said materials.
Waterproofing of porous carbonate rocks: Efficiency-controlling its properties
Authors: Esbert R. M. , Alonso Sánchez José
Published: November 2010

The aim of this study is to establish which physical properties may be used, in a routine way, in order to know the efficacy rate of a treatment applied on a specific rocky substrate.
Whit this purpose, two types of carbonated rocks, the limestone of Hontoria (Burgos) and the dolomite of Laspra (Asturias) have been chosen, with a very different configuration of their porosity systems. Three protection products, with silico-organic nature and widely used have been used, to wit: two siloxenes and a copolymer.
Tue properties chosen (contact angle and water vapour permeability) have been the proper ones in order to determine the efficacy level of the different treatments. This level was demonstrated to be conditioned by the chemical characteristics of this product, and the influence of the characteristics is practically null.
Other investigations are being carried out with the same rocks and treatment products in order to establish the corelationships between the efficacy rate of these treatments and the durability of the rock-treatment systems.
Carbonation of mortars of aluminous cement under various alkaline conditions
Authors: Yagüe Viana Andrés , Vázquez Ramonich Enric
Published: November 2010

The aim was to reproduce, in an accelerated way in the laboratory, the transformations of what is known as alkaline hydrolysis and observe the results on the properties of the system. To do this, mortars of aluminous cement were made up, a part of which underwent thermic treatment. They were then carbonated under various alkaline conditions. The different carbonation conditions produce different crystalline forms. Significant losses in resistance are also detected as well as increases in porosity, especially high in the mortars which undergo thermic treatment and are in contact with a strong alkaline medium.
Porosidad libre en granitos alterados: Comentarios a las normas
Authors: Íñigo Íñigo A. C. , Vicente Tavera S. , Rives Arnau V. , Vicente Hernández M. A.
Published: November 2010

In the present paper, the possible relation among some petrophysical properties of five types of granitic materials, whether artificially aged or not, subject to different consolidation and/or water repellent treatments, has been studied.
The study indicates a good correlation among imibition values and porosity (free and total). Likewise, correlation exists between apparent density and total porosity.
Differences in relative variation of imbibition values and free porosity when treating samples, advise about modification or enlargment of standards for materials with high microporosity index.
Characterization and conservation of the stone used in the Cathedral of Granada, Spain
Authors: Villegas R. , Martín L. , Valea J. F. , Bello M. A.
Published: November 2010

This paper summarizes a study carried out on the Granada Cathedral which includes studies of indicators, factors and mechanisms of deterioration. A complete chemical and physical characterization of altered and unaltered material from the quarries and the building has been made. Eight commercial treatment products have been tested on the main stone-type used in the monument, including two accelerated weathering tests (salt crystallization and SO2 chemical attack). Some conservation proposals have been made.
La adherencia en los morteros de albañilería
Authors: Cabrera Jorge Luis
Published: November 2010

The work presents a study carried out to determine the bond strength reached by bricklaying mortars at 28 days. 23 different dosages were prepared using 4 cement types, 2 sand types and 4 aggregate types.
The results prove the feasibility of using the mentioned method to determine bond strength. The values at 28 days reached up to 0.7 MPa.
Another look at the deterioration of calcium aluminate cement concrete
Authors: Jambor Jaromir , Skalny Jan
Published: November 2010

Potential degradation of concrete structures made of calcium aluminate cement (CAC) is well known and is caused by transformation (conversion) of the thermodynamically metastable into stable calcium aluminate hydrate phases. This recrystallization is influenced by temperature and humidity; the structural degradation of the concrete itself thus its loss of strength, is strongly related to the pore structure of the hydrated cement paste, the critical parameters being the total volume of pores below 15-20 nm and the median micropore radius. This constitutes a novel procedure for evaluation of existing CAC concrete structure.
New "sandwich" structures conformed from three dimensional
Authors: Alba Juan J. , Jiménez Miguel A. , Miravete A.
Published: November 2010

Poor interlaminar properties as well as poor-skin-to-core adhesion properties are very often the common existing problems we find when designing with "sandwich" structures. A new type of 3D-fabric "sandwich" structure is being developed in order to avoid these problems. Although the manufacturing process is very simple, a very complex "sandwich" structure is obtained as a result of the complexity of the 3D-fabric used. This 3D-fabric is a 3D woven glass fabric produced on velvet weaving machines with glass yarns. It is an integrally woven "sandwich" laminate for all kinds of composite products. The strength of the vertical fibers makes, that also after impregnation with a resin matrix, the "sandwich" structure is maintained. The result is a laminate with high strength and stiffness and low weight. On each side of this "sandwich" laminate additional reinforcement materials can be laminated and a synthetic foam can be injected in the hollow structure. This will allow to establish the mechanical properties of a finished product.
Alteration processes of medieval stained glass windows. Study and protection treatments
Authors: Fernández Navarro J. María
Published: November 2010

The anxiety caused by the fast growing decay of historical stained glass windows as a consequence of increasing environmental pollution, encouraged institutions of several countries to sponsor a series of scientific works aimed both to slow down this fast forwarding deterioration and to develop repair and preservation methods.
After an initial review of the chemical composition of the stained glass windows and of the differences depending on historical epochs and origins, a discussion about chemical attack mechanisms, degradation processes and formation of superficial crusts opens up.
Finally, the methodology used in their cleaning and restoration is briefly exposed and some criteria on the still polemic quest.
The effect of corrosion on stained glass windows
Authors: Laissner Johanna
Published: November 2010

Stained glass windows belong to the most important cultural heritage of Europe. Within the last decades a disastrous deterioration took place. The wonderful stained glass windows and their glass paintings as pieces of art are acutely menaced by environmental corrosive influences. This corrosion process is a very complex reaction which is not only influenced by temperature and humidity changes but also by gaseous pollutants like sulfur dioxide, nitrogen oxides or ozone, by dust and air, microorganisms as well as synergetic interactions.
Strongly affected by these environmental attacks are medieval stained glasses due to their chemical composition. They have a low content in silica and high contents of modifier ions (e.g. potassium and calcium). The corrosion phenomena can range from predominantly pitting on the surface to the formation of thick corrosion crusts which are turning the panel opaque and thus reducing strongly the transparency of the windows.
In order to set up a conservation and restoration concept, it is necessary to know about the environmental conditions to which the stained glass windows are exposed. For this purpose very corrosion sensitive model glasses (so called glass sensors) were developed which have a similar chemical composition as historic stained glasses. They exhibit the same corrosion reactions but react much faster, and are now widely used to estimate corrosive stresses on stained glass windows to give basic information about the corrosive impacts which work on the historic glasses.
In this paper principle corrosion mechanisms of stained glass windows and their enhancing factors are discussed. For the evaluation of the environmental impact, the application of glass sensors is demonstrated.
DEF: As a form of sulfate attack
Authors: Skalny J. , Johansen V. , Thaulow N. , Palomo A.
Published: November 2010

Delayed ettringite formation (DEF) is the term used to describe expansion of some heat cured portland cement concretes. Although meaningful progress has been made, the exact mechanism of the expansion itself is not entirely understood. The ettringite reformation is enabled, primarily, by thermal decomposition of ettringite formed prior to or during the cement paste setting as a result of excessive/improper heat curing. Observance in mature concrete of crystalline ettringite in air voids, cracks, and gaps around the aggregate is not in itself an evidence for DEF, but is the consequence of natural recrystallization of ettringite into available larger spaces. Occurance of DEF is dependent on materials, curing, and environmental conditions, and can easily be distinguished from ASR and other deterioration mechanisms by optical and electron-optical methods.
Interaction of dispersed polyvynil acetate with silicate in finishing materials
Authors: Runova R. F. , Maistrenko A. A.
Published: November 2010

This article focuses on the processes of interaction between calcium silicate hydrates and dispersed polyvinyl acetate in tight films with the aim of developing compounds meant for restoration and finishing works. The basis of this development relies on the concept concerning the determining role of the crystal-chemical factor of the silicate phase in the formation of organic-mineral compounds of increased durability.
The characteristics of dispersed calcium silicate hydrates are portrayed. The preparation conditions, accounting for the synthesis of the product of submicrocrystalline structure, conforming with the stoichiometry CaO∙SiO2 =0.8-2.0 have been determined.
The interaction has been studied for compounds achieved by mixing ingredients in a rapid whirling mixer, and subjected to hardening at T=20+2 T. With the aid of XRD, DTA and Infra-Red Spectrometry methods the formation process of the sophisticated polymer silicate phase in the material was observed for a period of 90 days.
The properties of the film were investigated and its high resistance against the influence of external factors was established. On this basis a conclusion concerning the quite high effectiveness of substituting portland cement with dispersed calcium silicate hydrate in polymer cement compounds has been made. White colour and other various special properties determine the suitability for repair and finishing works on facades of buildings.
La realcalinización y la extracción electroquímica de los cloruros en las construcciones de hormigón armado
Authors: Bertolini Luca , Bolzoni Fabio , Elsener Bernhard , Pedeferri Pietro , Andrade Carmen
Published: November 2010

Realkalisation and electrochemical chloride removal techniques, developed for rehabiliting carbonated and chloride-containing structures, are presented. Electrolysis and electromigration mechanisms and consequences as well as electrochemical conditions at the reinforcement surface are discussed and compared with cathodic protection ones. Furthermore, possible side effects are commented.
Growth of Octopus vulgaris (Cuvier, 1797) in tanks in the Ebro Delta (NE Spain): effects of temperature, salinity and culture density
Authors: Delgado Marina , Gairín Joan Ignasi , Carbó Ricard , Aguilera Cristóbal
Published: November 2010

To assess the possibility of O. vulgaris ongrowing using tanks or cages in the bays of the Ebro Delta, we performed several growth trials of common octopus held in tanks. Effects of environmental factors (temperature and salinity) and zootechnical aspects (culture density) were studied. The thermal ranges that defined positive growth periods in the bays of the Ebro Delta were 19.5ºC to 23ºC (spring-summer) and 23.5ºC to 12.3ºC (autumn-winter), the latter being the most suitable period for ongrowing. Salinity did not affect survival (100%) or growth within the range tested (34-29 psu), though feeding rates (AFR, SFR) were directly related to salinity. On the other hand, after 60 days, final culture density increased three-fold (D1: 12.36 → 44.37 kg m–3; D2: 24.13 → 67.76 kg m–3), with optimal survival results ( > 90%) for the two densities tested. Growth and feeding rates showed a slight inverse relationship with density. Finally, growth and feeding rates showed a clear dependence on temperature in the two experiments (density and salinity). Our results conclude that industrial production of O. vulgaris in tanks is promising: this system offers an alternative to cages and allows for a more exhaustive control of culture.
Contrasting alteration mineral assemblages associated with the Westwood deposit ore zones, Doyon-Bousquet-LaRonde mining camp, Abitibi, Quebec
Authors: Wright-Holfeld A , Mercier-Langevin P , Dubé B
Published: November 2010

The Westwood deposit is located in the prolific Doyon-Bousquet-LaRonde mining camp of the Abitibi greenstone belt. The gold-rich polymetallic ore zones of the Westwood deposit are located in three stacked corridors from north to south: zone 2 extension, north
corridor, and Westwood-Warrenmac corridor. The mineralized zones at the Westwood deposit are associated with contrasting alteration assemblages and ore styles described in this report. The study presented here is focused on a selection of closely spaced drill-holes that are aligned on a vertical
cross-section cutting through the three mineralized corridors in the central part of the deposit. Widespread quartz-chlorite-sericite alteration and proximal Mn-garnet alteration suggest a volcanogenic massive-sulphide-style alteration halo for the Westwood-Warrenmac and north corridors. Intense
deformation and stacking or telescoping of alteration halos hinders a definitive interpretation for the origin of the zone 2 extension veins and dissemination-style mineralization and sericite-quartz alteration assemblage, but a synvolcanic origin cannot be ruled out. Observations made at Westwood
suggest that primary permeability of volcanic rocks played a major role in controlling the ore and alteration distribution. Based on these observa-tions, the north and Westwood-Warrenmac corridors are thought to be Au-rich volcanogenic massive-sulphide lenses. The north corridor polymetallic veins
may also represent feeders to the ore lenses found higher in the stratigraphy. The zone 2 extension shares characteristics with Au-rich sulphide veins and disseminations typical of the neighbouring Doyon intrusion-related deposit, yet has some alteration traits similar to those of the north corridor
and Westwood-Warrenmac ore zones.
Lipases and Related Molecules in Cancer
Authors: Staege Martin S. , Hesse Manuela , Max Daniela
Published: November 2010

Lipases are enzymes that catalyze the hydrolysis of lipids. Based on protein structures and sequences, lipases can be classified into different protein families. The majority of conventional mammalian lipases are members of the protein super-families of serine esterases and alpha-beta hydrolases. Differential expression of lipases and related alpha-beta hydrolases in tumor cells has been observed. The physiological or patho-physiological functions of these tumor related enzymes are largely unknown. However, lipases are not only involved in energy metabolism but also in the metabolism of bioactive molecules, e.g. phosphatidic acid or arachidonic acid, suggesting that tumor-specifically expressed lipases might be interesting targets for the development of future treatment strategies. Moreover, independent of the patho-physiological function, tumor associated lipases can serve as targets for immunological treatment strategies. In addition, lipases with exclusive expression in single tumor entities can serve as potential diagnostic targets.
Inhibition of MLK3 Decreases Proliferation and Increases Antiproliferative Activity of Epidermal Growth Factor Receptor (EGFR) Inhibitor in pancreatic cancer cell Lines
Authors: Chandana Sreenivasa R. , Leece Cheryl M. , Gallo Kathleen A. , Madhukar Burra V. , Conley Barbara A.
Published: November 2010

Pancreatic adenocarcinoma is associated with advanced presentation and poor survival. Currently approved therapies have minimal effect on patient survival. Pancreatic adenocarcinomas have a high incidence of activated K-RAS, which may confer resistance to epidermal growth factor receptor (EGFR) inhibitors. Mixed lineage kinase-3 (MLK3) is a MAP3K that activates multiple MAPK pathways. The role of MLK3 in the pathophysiology and resistance to therapy of pancreatic adenocarcinoma has not been investigated. MLK3 is over expressed in pancreatic cancer cell lines compared to an immortalized pancreatic epithelial cell line. The requirement of MLK3 for cell proliferation and survival of pancreatic cancer cell lines, PANC-1 and MiaPaCa-2, was investigated using RNA interference (siRNA) and MLK inhibitor, K252a, alone or in conjunction with the EGFR inhibitor, Compound 56. Ablation of expression of MLK3 via siRNA-mediated gene silencing and pharmacological inhibition of MLK3 by K252a each decreased cell viability in both pancreatic cancer cell lines, with a concurrent decrease in the activation of ERK, JNK and AKT. Concomitant inhibition of EGFR and MLK3 induced apoptosis, as evidenced by increased cleavage of PARP and caspase-3. These results suggest that MLK3 plays an important role in survival and proliferation of pancreatic cancer cell lines and that inhibition of MLK3 may enhance the therapeutic efficacy of EGFR inhibitors in the treatment of pancreatic cancer.
The Effect of a Mediterranean Meal on Sprague Dawley Rats DMBA-Induced Mammary Tumors
Authors: Pereira Paula C. , Vicente A. Filipa , Mesquita Maria F. , Cabrita Antonio S.
Published: November 2010

The present study intents to find a possible protective role of a Mediterranean type meal on mammary carcinogenesis. Several factors have been associated with breast cancer risk, genetics and environment are the most pointed out in epidemiologic and experimental studies. Diet is an environmental factor that can promote or prevent disease, being responsible for almost 35% of total cancer cases. A total of 72 female rats 50 days old were randomly divided in three groups of 24 rats and housed 4 in each plastic cage in a holding room under constant conditions of 22 ± 2 °C, 55 ± 10% humidity and a 12 h light/dark cycle. All the animals were submitted to the administration of 20 mg of 7, 12 dimethylbenzanthracene (DMBA) in olive oil, by gavages, except group A. The same defined standard food was provided for all the animals in group A and B, supplemented with a Mediterranean meal in group C. All the animals were sacrificed by the end of 150 days. Total carcinoma number did not differ significantly between Groups B and C and there were not found any neoplastic lesions in Group A. Most tumors showed a mixed architectural pattern, with cribriform and papillary areas, comedocarcinoma and necrosis was only seen in Group B. Histopathologic analysis showed that Group C tumors had lower mitotic activity and Pattern Grades, but higher Nuclear Grades. Mediterranean diet type meal showed lower Pattern Grades and lower Mitotic count in spite of that a higher nuclear pleomorphism was also found. Even so, tumors from Group C were better differentiated which can indicate lower malignancy.
Dual KS: Defining Gene Sets with Tissue Set Enrichment Analysis
Authors: Yang Yarong , Kort Eric J. , Ebrahimi Nader , Zhang Zhongfa , Teh Bin T.
Published: November 2010

Background

Gene set enrichment analysis (GSEA) is an analytic approach which simultaneously reduces the dimensionality of microarray data and enables ready inference of the biological meaning of observed gene expression patterns. Here we invert the GSEA process to identify class-specific gene signatures. Because our approach uses the Kolmogorov-Smirnov approach both to define class specific signatures and to classify samples using those signatures, we have termed this methodology “Dual-KS” (DKS).

Results

The optimum gene signature identified by the DKS algorithm was smaller than other methods to which it was compared in 5 out of 10 datasets. The estimated error rate of DKS using the optimum gene signature was smaller than the estimated error rate of the random forest method in 4 out of the 10 datasets, and was equivalent in two additional datasets. DKS performance relative to other benchmarked algorithms was similar to its performance relative to random forests.

Conclusions

DKS is an efficient analytic methodology that can identify highly parsimonious gene signatures useful for classification in the context of microarray studies. The algorithm is available as the dualKS package for R as part of the bioconductor project.
Article Commentary: The Power of the Web in Cancer Drug Discovery and Clinical Trial Design: Research without a Laboratory?
Authors: Galustian Christine , Dalgleish Angus G.
Published: November 2010

The discovery of effective cancer treatments is a key goal for pharmaceutical companies. However, the current costs of bringing a cancer drug to the market in the USA is now estimated at $1 billion per FDA approved drug, with many months of research at the bench and costly clinical trials. A growing number of papers highlight the use of data mining tools to determine associations between drugs, genes or protein targets, and possible mechanism of actions or therapeutic efficacy which could be harnessed to provide information that can refine or direct new clinical cancer studies and lower costs. This report reviews the paper by R.J. Epstein, which illustrates the potential of text mining using Boolean parameters in cancer drug discovery, and other studies which use alternative data mining approaches to aid cancer research.
Article Commentary: Bimodal Gene expression and Biomarker Discovery
Authors: Ertel Adam
Published: November 2010

With insights gained through molecular profiling, cancer is recognized as a heterogeneous disease with distinct subtypes and outcomes that can be predicted by a limited number of biomarkers. Statistical methods such as supervised classification and machine learning identify distinguishing features associated with disease subtype but are not necessarily clear or interpretable on a biological level. Genes with bimodal transcript expression, however, may serve as excellent candidates for disease biomarkers with each mode of expression readily interpretable as a biological state. The recent article by Wang et al, entitled “The Bimodality Index: A Criterion for Discovering and Ranking Bimodal Signatures from Cancer Gene Expression Profiling Data,” provides a bimodality index for identifying and scoring transcript expression profiles as biomarker candidates with the benefit of having a direct relation to power and sample size. This represents an important step in candidate biomarker discovery that may help streamline the pipeline through validation and clinical application.
A Robust Gene selection Method for Microarray-based Cancer Classification
Authors: Wang Xiaosheng , Gotoh Osamu
Published: November 2010

Gene selection is of vital importance in molecular classification of cancer using high-dimensional gene expression data. Because of the distinct characteristics inherent to specific cancerous gene expression profiles, developing flexible and robust feature selection methods is extremely crucial. We investigated the properties of one feature selection approach proposed in our previous work, which was the generalization of the feature selection method based on the depended degree of attribute in rough sets. We compared the feature selection method with the established methods: the depended degree, chi-square, information gain, Relief-F and symmetric uncertainty, and analyzed its properties through a series of classification experiments. The results revealed that our method was superior to the canonical depended degree of attribute based method in robustness and applicability. Moreover, the method was comparable to the other four commonly used methods. More importantly, the method can exhibit the inherent classification difficulty with respect to different gene expression datasets, indicating the inherent biology of specific cancers.
Development and Validation of Predictive Indices for a Continuous Outcome Using Gene Expression Profiles
Authors: Zhao Yingdong , Simon Richard
Published: November 2010

There have been relatively few publications using linear regression models to predict a continuous response based on microarray expression profiles. Standard linear regression methods are problematic when the number of predictor variables exceeds the number of cases. We have evaluated three linear regression algorithms that can be used for the prediction of a continuous response based on high dimensional gene expression data. The three algorithms are the least angle regression (LAR), the least absolute shrinkage and selection operator (LASSO), and the averaged linear regression method (ALM). All methods are tested using simulations based on a real gene expression dataset and analyses of two sets of real gene expression data and using an unbiased complete cross validation approach. Our results show that the LASSO algorithm often provides a model with somewhat lower prediction error than the LAR method, but both of them perform more efficiently than the ALM predictor. We have developed a plug-in for BRB-ArrayTools that implements the LAR and the LASSO algorithms with complete cross-validation.
Comparison of Two Output-Coding Strategies for Multi-Class Tumor Classification Using Gene Expression Data and Latent Variable Model as Binary Classifier
Authors: Joseph Sandeep J. , Robbins Kelly R. , Zhang Wensheng , Rekaya Romdhane
Published: November 2010

Multi-class cancer classification based on microarray data is described. A generalized output-coding scheme based on One Versus One (OVO) combined with Latent Variable Model (LVM) is used. Results from the proposed One Versus One (OVO) output-coding strategy is compared with the results obtained from the generalized One Versus All (OVA) method and their efficiencies of using them for multi-class tumor classification have been studied. This comparative study was done using two microarray gene expression data: Global Cancer Map (GCM) dataset and brain cancer (BC) dataset. Primary feature selection was based on fold change and penalized t-statistics. Evaluation was conducted with varying feature numbers. The OVO coding strategy worked quite well with the BC data, while both OVO and O VA results seemed to be similar for the GCM data. The selection of output coding methods for combining binary classifiers for multi-class tumor classification depends on the number of tumor types considered, the discrepancies between the tumor samples used for training as well as the heterogeneity of expression within the cancer subtypes used as training data.
Protein-Protein Interaction Reveals Synergistic Discrimination of Cancer Phenotype
Authors: Xiong Jianghui , Liu Juan , Rayner Simon , Li Yinghui , Chen Shanguang
Published: November 2010

Cancer is a disease associated with the deregulation of multiple gene networks. Microarray data has permitted researchers to identify gene panel markers for diagnosis or prognosis of cancer but these are not sufficient to make specific mechanistic assertions about phenotype switches. We propose a strategy to identify putative mechanisms of cancer phenotypes by protein-protein interactions (PPI). We first extracted the logic status of a PPI via the relative expression of the corresponding gene pair. The joint association of a gene pair on a cancer phenotype was calculated by entropy minimization and assessed using a support vector machine. A typical predictor is “ If Src high-expression, and Cav-1 low-expression, then cancer.“ We achieved 90% accuracy on test data with a majority of predictions associated with the MAPK pathway, focal adhesion, apoptosis and cell cycle. Our results can aid in the development of phenotype discrimination biomarkers and identification of putative therapeutic interference targets for drug development.
Characterization of the Effectiveness of Reporting Lists of Small Feature Sets Relative to the Accuracy of the Prior Biological Knowledge
Authors: Zhao Chen , Bittner Michael L. , Chapkin Robert S. , Dougherty Edward R.
Published: November 2010

When confronted with a small sample, feature-selection algorithms often fail to find good feature sets, a problem exacerbated for high-dimensional data and large feature sets. The problem is compounded by the fact that, if one obtains a feature set with a low error estimate, the estimate is unreliable because training-data-based error estimators typically perform poorly on small samples, exhibiting optimistic bias or high variance. One way around the problem is limit the number of features being considered, restrict features sets to sizes such that all feature sets can be examined by exhaustive search, and report a list of the best performing feature sets. If the list is short, then it greatly restricts the possible feature sets to be considered as candidates; however, one can expect the lowest error estimates obtained to be optimistically biased so that there may not be a close-to-optimal feature set on the list. This paper provides a power analysis of this methodology; in particular, it examines the kind of results one should expect to obtain relative to the length of the list and the number of discriminating features among those considered. Two measures are employed. The first is the probability that there is at least one feature set on the list whose true classification error is within some given tolerance of the best feature set and the second is the expected number of feature sets on the list whose true errors are within the given tolerance of the best feature set. These values are plotted as functions of the list length to generate power curves. The results show that, if the number of discriminating features is not too small—that is, the prior biological knowledge is not too poor—then one should expect, with high probability, to find good feature sets. Availability: companion website at http://gsp.tamu.edu/Publications/supplementary/zhao09a/
Genes with Relevance for Early to Late Progression of Colon Carcinoma Based on Combined Genomic and Transcriptomic Information from the Same Patients
Authors: Lagerstedt Kristina K. , Kristiansson Erik , Lönnroth Christina , Andersson Marianne , IresjÖ Britt-Marie , Gustafsson Annika , Hansson Elisabeth , Kressner Ulf , Nordgren Svante , Enlund Fredrik , Lundholm Kent
Published: November 2010

Background

Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression.

Methods

Tumor and normal colon tissue were obtained at primary operations from 24 patients selected by chance. DNA, RNA and microRNAs were extracted from the same biopsy material in all individuals and analyzed by oligo-nucleotide array-based comparative genomic hybridization (CGH), mRNA- and microRNA oligo-arrays. Statistical analyses were performed to assess statistical interactions (correlations, co-variations) between DNA copy number changes and significant alterations in gene and microRNA expression using appropriate parametric and non-parametric statistics.

Results

Main DNA alterations were located on chromosome 7, 8, 13 and 20. Tumor DNA copy number gain increased with tumor progression, significantly related to increased gene expression. Copy number loss was not observed in Dukes A tumors. There was no significant relationship between expressed genes and tumor progression across Dukes A–D tumors; and no relationship between tumor stage and the number of microRNAs with significantly altered expression. Interaction analyses identified overall 41 genes, which discriminated early Dukes A plus B tumors from late Dukes C plus D tumor; 28 of these genes remained with correlations between genomic and transcriptomic alterations in Dukes C plus D tumors and 17 in Dukes D. One microRNA (microR-663) showed interactions with DNA alterations in all Dukes A-D tumors.

Conclusions

Our modeling confirms that colon cancer progression is related to genomic instability and altered gene expression. However, early invasive tumor growth seemed rather related to transcriptomic alterations, where changes in microRNA may be an early phenomenon, and less to DNA copy number changes.
An Efficient Gatekeeper Algorithm for Detecting GxE
Authors: Efird Jimmy T.
Published: November 2010

The risk for many complex diseases is believed to be a result of the interactive effects of genetic and environmental factors. Developing efficient techniques to identify gene-environment interactions (GxE) is important for unraveling the etiologic basis of many modern day diseases including cancer. The problem of false positives and false negatives continues to pose significant roadblocks to detecting GxE and informing targeted public health screening and intervention. A heuristic gatekeeper method is presented to guide the selection of single nucleotide polymorphisms (SNPs) in the design phase of a GxE study.