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Excellent Candidates (excellent + candidate)
Selected AbstractsProduction of Taxol fromPhyllosticta spinarum, an endophytic fungus ofCupressus sp.ENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 4 2008R. Senthil Kumaran Abstract Taxol production during the cultivation on a modified liquid and potato dextrose broth medium was indicated for the first time to occur in Phyllosticta spinarum, an endophytic fungus isolated from the needles of Cupressus sp. The presence of taxol in the fungal culture filtrate was confirmed by chromatographic and spectroscopic methods of analysis. The amount of taxol produced by this fungus was quantified by high performance liquid chromatography. The maximum amount of taxol production was obtained in this fungus when grown on M1D medium (235,,g/L) followed by PDB medium (125,,g/L). The results indicate that P.,spinarum is an excellent candidate for taxol production. The production rate was 4.7,×,103 -fold higher than that found in the culture broth of an earlier reported fungus, Taxomyces andreanae. The fungal taxol extracted also showed a strong cytotoxic activity in the in vitro culture of human cancer cells tested in an apoptotic assay. [source] Genomic organization and amplification of the human plakoglobin gene (JUP)EXPERIMENTAL DERMATOLOGY, Issue 5 2000N. V. Whittock Abstract: Plakoglobin is a globular protein common to the intracellular plaques of adhesive junctions, predominantly desmosomes and adherens junctions. Recently, a number of pathogenic mutations have been described in other components of desmosomes, specifically in plakophilin 1, desmoplakin and desmoglein 1. The phenotype of affected patients mainly involves thickening of palm and sole skin (keratoderma). Although no human mutations in plakoglobin have been described thus far, this protein represents an excellent candidate for other human genetic disorders, possibly involving skin and heart, sites of high plakoglobin expression. To facilitate future mutation detection analyses in such conditions, we have characterized the intron,exon organization of the human plakoglobin gene, which comprises 13 distinct exons spanning approximately 17 kb on 17q21. We have also developed a PCR-based mutation detection strategy using primers placed on flanking introns followed by direct sequencing of the PCR products. [source] Use of quantitative real-time polymerase chain reaction to estimate the size of the house-fly Musca domestica genomeINSECT MOLECULAR BIOLOGY, Issue 6 2006J. Gao Abstract House-flies, Musca domestica, are carriers of more than 100 devastating diseases that have severe consequences for human and animal health. A key bottleneck to progress in controlling the devastating human diseases transmitted by house-flies is lack of knowledge of the basic molecular biology of this species. However, before sequencing of the house-fly genome can be seriously considered it is important to know the size of the genome. In this paper, we used quantitative real-time polymerase chain reaction to calculate genome size of the house-fly in side-by-side experiments with Drosophila melanogaster (known genome size of 180 Mb). Our results indicate the size of the house-fly genome is 295 ± 10 Mb and that of D. melanogaster is 184 Mb. Thus, the house-fly genome is only about 1.6-fold larger than the genome of D. melanogaster. This indicates that the size of the house-fly genome makes it an excellent candidate for whole genome sequencing and that quantitative real-time polymerase chain reaction is an accurate method for the estimation of the size of insect genomes. [source] Quality of service for satellite IP networks: a surveyINTERNATIONAL JOURNAL OF SATELLITE COMMUNICATIONS AND NETWORKING, Issue 4-5 2003Sastri Kota Abstract The future media rich applications such as media streaming, content delivery distribution and broadband access require a network infrastructure that offers greater bandwidth and service level guarantees. As the demand for new applications increases, ,best effort' service is inadequate and results in lack of user satisfaction. End-to-end quality of service (QoS) requires the functional co-operation of all network layers. To meet future application requirements, satellite is an excellent candidate due to features such as global coverage, bandwidth flexibility, broadcast, multicast and reliability. At each layer, the user performance requirements should be achieved by implementation of efficient bandwidth allocation algorithms and satellite link impairment mitigation techniques. In this paper, a QoS framework for satellite IP networks including requirements, objectives and mechanisms are described. To fully understand end-to-end QoS at each layer, QoS parameters and the current research are surveyed. For example at physical layer (modulation, adaptive coding), link layer (bandwidth allocation), network layer (IntServ/DiffServ, MPLS traffic engineering), transport layer (TCP enhancements, and alternative transport protocols) and security issues are discussed. Some planned system examples, QoS simulations and experimental results are provided. The paper also includes the current status of the standardization of satellite IP by ETSI, ITU and IETF organizations. Copyright © 2003 John Wiley & Sons, Ltd. [source] Use of the modified Robbins device to study the in vitro biofilm removal efficacy of NitrAdineŌ, a novel disinfecting formula for the maintenance of oral medical devicesJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2008T. Coenye Abstract Aims:, To evaluate the use of the modified Robbins device (MRD) to test disinfection strategies against biofilms that form on oral medical devices and to test the biofilm removal efficacy of NitrAdineTM, a disinfectant for the maintenance of oral medical devices. Methods and Results:, Biofilms were grown on discs using the MRD and biofilms formed in this system were used to evaluate the efficacy of NitrAdineTM and to determine the optimal disinfection conditions. Our data indicate that the use of the MRD allows for the rapid and reproducible formation of high-density biofilms. Determination of the efficacy of NitrAdineTM revealed high activity against biofilms tested (e.g. >3 log reduction for Candida albicans and Staphylococcus aureus) and allowed the determination of the optimal conditions for its use. Conclusion:, The high reproducibility and flexibility of the MRD make it an excellent candidate for standardized testing of disinfectants aimed at reducing biofilms on oral medical devices. Using this system, we were able to demonstrate that NitrAdineTM exhibits high activity against biofilms formed by the micro-organisms tested. Significance and Impact of the Study:, Our data suggest that our procedure is appropriate for standardized testing of disinfectants aimed at reducing biofilms on oral medical devices. [source] BCCIP associates with the receptor protein tyrosine phosphatase PTPµJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2008Polly J. Phillips-Mason Abstract The receptor protein tyrosine phosphatase PTPµ belongs to a family of adhesion molecules that contain cell,cell adhesion motifs in their extracellular segments and catalytic domains within their intracellular segments. The ability of PTPµ both to mediate adhesion and exhibit enzymatic activity makes PTPµ an excellent candidate to transduce signals in response to cell,cell adhesion. In an effort to identify downstream signaling partners of PTPµ, we performed a modified yeast two-hybrid screen using the first tyrosine phosphatase domain of PTPµ as bait. We isolated an interacting clone encoding BRCA2 and CDKN1A interacting protein (BCCIP) from a HeLa cell library. BCCIP is a p21 and BRCA2 interacting protein that has been shown to play roles in both cell cycle arrest and DNA repair. In this manuscript, we confirm the interaction between BCCIP and PTPµ identified in yeast using in vitro biochemical studies and characterize BCCIP as a PTPµ binding protein. We demonstrate that BCCIP is phosphorylated by the Src tyrosine kinase and dephosphorylated by the PTPµ tyrosine phosphatase in vitro. Furthermore, we show that BCCIP is required for both the permissive and repulsive functions of PTPµ in neurite outgrowth assays, suggesting BCCIP and PTPµ are in a common signal transduction pathway. J. Cell. Biochem. 105: 1059,1072, 2008. © 2008 Wiley-Liss, Inc. [source] Bandwidth enhancement of a coplanar waveguide-fed asymmetrical slot antenna with a rectangular patchMICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 10 2010Shou-Tao Fan Abstract A coplanar waveguide-fed asymmetrical slot antenna with a rectangular patch for bandwidth enhancement is demonstrated. By attaching a rectangular patch to the monopole radiating element, a good performance of bandwidth enhancement for the antenna is achieved. From simulational and experimental results, the enhanced impedance bandwidth of the proposed antenna, defined by ,10 dB return loss, can reach 13.1 GHz, from 2.4 to 15.5 GHz, or about 146% with the center frequency 8.95 GHz, which makes it an excellent candidate for the ultra wideband (UWB, 3.1,10.6 GHz) applications. © 2010 Wiley Periodicals, Inc. Microwave Opt Technol Lett 52:2259,2261, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.25476 [source] Comprehensive evaluation of the role of EZH2 in the growth, invasion, and aggression of a panel of prostate cancer cell linesTHE PROSTATE, Issue 6 2010Breanne D.W. Karanikolas Abstract BACKGROUND Although most prostate cancers respond well to initial treatments, a fraction of prostate cancers are more aggressive and will recur and metastasize. At that point, there are few treatment options available. Significant efforts have been made to identify biomarkers that will identify these more aggressive cancers to tailor a more vigorous treatment in order to improve outcome. Polycomb Group protein enhancer of zeste 2 (EZH2) was found to be overexpressed in metastatic prostate tumors, and is considered an excellent candidate for such a biomarker. Scattered studies have found that EZH2 overexpression causes neoplastic transformation, invasion, and growth of prostate cells. However, these studies utilized different systems and cell lines, and so are difficult to correlate with one another. METHODS In this study, a comprehensive evaluation of the phenotypic effects of EZH2 in a panel of five prostate cancer cell lines was performed. By using multiple cell lines, and examining overexpression and knockdown of EZH2 concurrently, a broad view of EZH2's role in prostate cancer was achieved. RESULTS Overexpression of EZH2 led to more aggressive behaviors in all prostate cell lines tested. In contrast, downregulation of EZH2 reduced invasion and tumorigenicity of androgen-independent (AI) cell lines CWR22Rv1, PC3, and DU145, but not of androgen-dependent (AD) cell lines LAPC4 and LNCaP. CONCLUSIONS Findings from this study suggest that AI prostate tumors are more dependent on EZH2 expression than AD tumors. Our observations provide an explanation for the strong correlation between EZH2 overexpression and advanced stage, aggressive prostate cancers. Prostate 70: 675,688, 2010. © 2010 Wiley-Liss, Inc. [source] A new generation of monoclonal and recombinant antibodies against cell-adherent prostate specific membrane antigen for diagnostic and therapeutic targeting of prostate cancerTHE PROSTATE, Issue 13 2006Ursula Elsässer-Beile Abstract BACKGROUND Prostate-specific membrane antigen (PSMA) is an excellent candidate for targeting prostate cancer by virtue of its restricted expression on prostatic epithelial cells and its upregulation on prostatic carcinoma cells. PSMA is expressed on the cell surface displaying a specific three-dimensional structure. Therefore, only antibodies with a high cell binding activity will have an important impact on antibody-based imaging and therapy. METHODS Monoclonal antibodies (mAbs) and single chain antibody fragments (scFvs) were prepared from spleen cells of mice that had been immunized either with purified PSMA or a cell lysate of prostate cancer LNCaP cells containing native PSMA. mAbs and scFvs were screened for reactivity with purified PSMA and binding to PSMA-expressing LNCaP cells. RESULTS From mice immunized with purified PSMA, we obtained three mAbs (K7, K12, D20) and four scFvs (G0, G1, G2, G4), which were highly reactive with the isolated antigen, but showed weak or no reaction with viable LNCaP cells. From mice immunized with unpurified LNCaP lysate, we obtained three mAbs (3/E7, 3/F11, 3/A12), and one scFv (A5), which were reactive with purified PSMA, also showing a strong and specific binding to viable LNCaP cells and PSMA-transfected cells. CONCLUSIONS Our results suggest that only the mAbs and scFvs, that were elicited with unpurified LNCaP lysate and not with purified PSMA will be useful agents for diagnostic imaging and therapeutic applications of prostate cancer. Prostate 66: 1359,1370, 2006. © 2006 Wiley-Liss, Inc. [source] The Causal Element for the Lactase Persistence/ non-persistence Polymorphism is Located in a 1 Mb Region of Linkage Disequilibrium in EuropeansANNALS OF HUMAN GENETICS, Issue 4 2003M. Poulter Summary Expression of lactase in the intestine persists into adult life in some people and not others, and this is due to a cis -acting regulatory polymorphism. Previous data indicated that a mutation leading to lactase persistence had occurred on the background of a 60 kb 11-site LCT haplotype known as A (Hollox et al. 2001). Recent studies reported a 100% correlation of lactase persistence with the presence of the T allele at a CT SNP at ,14 kb from LCT, in individuals of Finnish origin, suggesting that this SNP may be causal of the lactase persistence polymorphism, and also reported a very tight association with a second SNP (GA ,22 kb) (Enattah et al. 2002). Here we report the existence of a one megabase stretch of linkage disequilibrium in the region of LCT and show that the ,14 kb T allele and the ,22 kb A allele both occur on the background of a very extended A haplotype. In a series of Finnish individuals we found a strong correlation (40/41 people) with lactose digestion and the presence of the T allele. The T allele was present in all 36 lactase persistent individuals from the UK (phenotyped by enzyme assay) studied, 31/36 of whom were of Northern European ancestry, but not in 11 non-persistent individuals who were mainly of non-UK ancestry. However, the CT heterozygotes did not show intermediate lactase enzyme activity, unlike those previously phenotyped by determining allelic transcript expression. Furthermore the one lactase persistent homozygote identified by having equally high expression of A and B haplotype transcripts, was heterozygous for CT at the ,14 kb site. SNP analysis across the 1 megabase region in this person showed no evidence of recombination on either chromosome between the ,14 kb SNP and LCT. The combined data shows that although the ,14 kb CT SNP is an excellent candidate for the cause of the lactase persistence polymorphism, linkage disequilibrium extends far beyond the region searched so far. In addition, the CT SNP does not, on its own, explain all the variation in expression of LCT, suggesting the possibility of genetic heterogeneity. [source] Breeding Influenza: The Political Virology of Offshore FarmingANTIPODE, Issue 5 2009Robert G. Wallace Abstract:, The geographic extent, xenospecificity, and clinical course of influenza A (H5N1), the bird flu strain, suggest the virus is an excellent candidate for a pandemic infection. Much attention has been paid to the virus's virology, pathogenesis and spread. In contrast, little effort has been aimed at identifying influenza's social origins. In this article, I review H5N1's phylogeographic properties, including mechanisms for its evolving virulence. The novel contribution here is the attempt to integrate these with the political economies of agribusiness and global finance. Particular effort is made to explain why H5N1 emerged in southern China in 1997. It appears the region's reservoir of near-human-specific recombinants was subjected to a phase change in opportunity structure brought about by China's newly liberalized economy. Influenza, 200 nm long, seems able to integrate selection pressures imposed by human production across continental distances, an integration any analysis of the virus should assimilate in turn. [source] Female gametophyte development in Aristolochia labiata Willd. (Aristolochiaceae)BOTANICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 1 2008ERIC N. MADRID Piperales are an extremely diverse angiosperm lineage in terms of female gametophyte structure and, as such, an excellent candidate for comparative investigations of developmental evolution. In Piperales, Aristolochiaceae are sister to clades in which several divergent patterns of female gametophyte development are prevalent. Outgroup comparisons and explicit analyses of character evolution demonstrate that Polygonum -type female gametophyte development and structure in Aristolochiaceae appears to represent the plesiomorphic condition from which the divergent ontogenies of Piperales evolved. Here, we present detailed analyses of female gametophyte development in Aristolochia labiata that combine light and confocal microscopy with three-dimensional computer reconstruction. Our reconstructions demonstrate that, at the two-nucleate stage of development, separation of nuclei to opposite poles of the female gametophyte does not appear to be dependent on vacuolar expansion as generally hypothesized. We also found a decrease in antipodal volume following formation of the secondary nucleus. Our data provide a baseline for future efforts to describe developmental modifications responsible for evolutionary transitions in female gametophyte ontogeny throughout Piperales. © 2008 The Linnean Society of London, Botanical Journal of the Linnean Society, 2008, 158, 19,29. [source] Identification of genes expressed preferentially in the developing peripheral margin of the optic cupDEVELOPMENTAL DYNAMICS, Issue 9 2009Jeffrey M. Trimarchi Abstract Specification of the peripheral optic cup by Wnt signaling is critical for formation of the ciliary body/iris. Identification of marker genes for this region during development provides a starting point for functional analyses. During transcriptional profiling of single cells from the developing eye, two cells were identified that expressed genes not found in most other single cell profiles. In situ hybridizations demonstrated that many of these genes were expressed in the peripheral optic cup in both early mouse and chicken development, and in the ciliary body/iris at subsequent developmental stages. These analyses indicate that the two cells probably originated from the developing ciliary body/iris. Changes in expression of these genes were assayed in embryonic chicken retinas when canonical Wnt signaling was ectopically activated by CA-,-catenin. Twelve ciliary body/iris genes were identified as upregulated following induction, suggesting they are excellent candidates for downstream effectors of Wnt signaling in the optic cup. Developmental Dynamics 238:2327,2339, 2009. © 2009 Wiley-Liss, Inc. [source] How Do the Different Defect Structures and Element Substitutions Affect the Nonlinear Optical Properties of Lacunary Keggin Polyoxometalates?EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 20 2006A DFT Study Abstract Systematic DFT calculations have been carried out on the lacunary ,-Keggin polyoxometalate derivatives [PW11O39]7,, [XW9O34]n, (X = AlIII, SiIV, GeIV, PV, AsV, and SbV), [XW9M2O39]n,, and [XW9M3O40]n, (X = PV and SiIV, M = MoVI, VV, NbV, and TaV) to investigate the geometric structure and element substitution effects on the molecular nonlinear optical response. Analysis of the computed static second-order polarizability (,0) predicts that the molecular nonlinear optical activity of lacunary Keggin polyoxometalate derivatives can be modified by replacing the central heteroatom and the addenda metal atom. Substitution of the central Al atom or the addenda V atom causes significant enhancement in the molecular nonlinearity. Moreover, the ,0 values are substantially dependent on the defect structures. This class of inorganic complexes possesses remarkably large molecular optical nonlinearity, especially for the partial substitution complex [SiW9Nb2O39]10, (IIIc), which has a computed ,0 value of 2071.0 a.u. Thus, lacunary Keggin polyoxometalates could become excellent candidates in the field of second-order NLO. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] A Theoretical ab initio Study of the Capacity of Several Binding Units for the Molecular Recognition of AnionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 1 2005Carolina Garau Abstract Noncovalent bonding between anions and the ,-cloud of electron-deficient aromatic rings has recently attracted considerable attention. Complexes of bromide with different electron-deficient aromatic rings and with other binding units based on hydrogen bonding (urea, thiourea and squaramide) have been studied and compared using high level B3LYP/6-31++G** ab initio and Molecular Interaction Potential with polarization (MIPp) calculations. Our findings reveal that electron-deficient aromatic rings are excellent candidates for constructing anion receptors and that the interaction strength can be modulated by the nature of the ring. Supporting experimental evidence has been obtained from X-ray structures retrieved from the Cambridge Structural Database. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Selection and identification of anaerobic lactobacilli producing inhibitory compounds against vaginal pathogensFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2006Jasadee Kaewsrichan Abstract Two strains of Lactobacillus crispatus (15L08 and 21L07) and one strain of Lactobacillus jensenii (5L08) were selected from amongst 100 isolates from the vaginas of healthy premenopausal women for properties relevant to mucosal colonization and the production of H2O2 and/or bacteriocin-like compound. All three strains self-aggregated and adhered to vaginal epithelial cells, displacing well-known vaginal pathogens, such as Gardnerella vaginalis and Candida albicans. Lactobacillus crispatus 15L08 was characterized as a potential H2O2 producer. A high level of bacteriocin-like compound was synthesized by L. jensenii 5L08, with a bactericidal mode of action for G. vaginalis, C. albicans and Escherichia coli. However, H2O2 -dependent activity alone was not sufficient to inhibit the growth of C. albicans. Simultaneous actions of H2O2 and bacteriocin-like compound produced by lactobacilli may be important for antagonizing pathogenic bacteria. These strains of lactobacilli may be excellent candidates for eventual use as probiotics to restore the normal microbial communities in the vaginal ecosystem. [source] Functionalized Self-Assembled InAs/GaAs Quantum-Dot Structures Hybridized with Organic MoleculesADVANCED FUNCTIONAL MATERIALS, Issue 3 2010Miaoxiang Chen Abstract Low-dimensional III,V semiconductors have many advantages over other semiconductors; however, they are not particularly stable under physiological conditions. Hybridizing biocompatible organic molecules with advanced optical and electronic semiconductor devices based on quantum dots (QDs) and quantum wires could provide an efficient solution to realize stress-free and nontoxic interfaces to attach larger functional biomolecules. Monitoring the modifications of the optical properties of the hybrid molecule,QD systems by grafting various types of air-stable diazonium salts onto the QD structures surfaces provides a direct approach to prove the above concepts. The InAs/GaAs QD structures used in this work consist of a layer of surface InAs QDs and a layer of buried InAs QDs embedded in a wider-bandgap GaAs matrix. An enhancement in photoluminescence intensity by a factor of 3.3 from the buried QDs is achieved owing to the efficient elimination of the dangling bonds on the surface of the structures and to the decrease in non-radiative recombination caused by their surface states. Furthermore, a narrow photoluminescence band peaking at 1620,nm with a linewidth of 49 meV corresponding to the eigenstates interband transition of the surface InAs QDs is for the first time clearly observed at room temperature, which is something that has rarely been achieved without the use of such engineered surfaces. The experimental results demonstrate that the hybrid molecule,QD systems possess a high stability, and both the surface and buried QDs are very sensitive to changes in their surficial conditions, indicating that they are excellent candidates as basic sensing elements for novel biosensor applications. [source] Long-Cycle Electrochemical Behavior of Multiwall Carbon Nanotubes Synthesized on Stainless Steel in Li Ion BatteriesADVANCED FUNCTIONAL MATERIALS, Issue 7 2009Charan Masarapu Abstract Carbon nanotubes (CNTs) are considered to be excellent candidates for high performance electrode materials in Li ion batteries. The nanometer-sized pore structures of CNTs can provide the hosting sites for storing large numbers of Li ions. A short diffusion distance for the Li ions may bring about a high discharge rate. The long-cycle performance of aligned multiwalled carbon nanotubes (MWNTs) directly synthesized on stainless-steel foil as an anode material in lithium battery is demonstrated. An increase in the specific capacity with an increase in the cycle number is observed. Starting at a value of 132,mA hg,1 in the first cycle at a current rate of 1,C, the specific capacity increased about 250% to a value of 460,mA hg,1 after 1,200 cycles. This is an unusual but a welcoming behavior for battery applications. It is found that the morphology of the MWNTs with structural and surface defects and the stainless-steel substrate play an important role in enhancing the capacity during the cycling process. [source] Cadmium phytoextraction capacity in eight C3 herbage grass speciesGRASSLAND SCIENCE, Issue 1 2008Shamima Sabreen Abstract Grasses are excellent candidates for phytoremediation because of their high biomass production, high adaptability and low management cost. This study assesses interspecific variation of cadmium (Cd) phytoextraction capabilities in eight C3 grass species. Populations of 30-day-old C3 grass species , namely, Agrostis alba, Anthoxanthum odoratum, Dactylis glomerata, Festuca arundinacea, Festuca pratensis, Lolium multiflorum, Lolium perenne and Poa pratensis, were grown hydroponically for 15 days with different concentrations of Cd (0, 5, 10 and 50 µM). For each species, shoot biomass, the proportion of growth inhibition (GI, %), shoot Cd concentration and accumulation, shoot nutrient uptake, and the proportion of uptake inhibition (UI, %) of nutrient minerals were evaluated. Effects of Cd application included stunted growth. The GI increased from 5% to 70% with an increase in Cd concentrations. For all Cd treatments, L. multiflorum showed the highest shoot dry biomass. Shoot Cd concentrations negatively affected mineral nutrient uptake. The highest Cd treatment caused UI of various elements of 37,95%. Under 50-µM Cd treatment, Cd accumulation varied by 20 times among species, and L. multiflorum showed the highest Cd accumulation (116.46 µg plant,1). Our results indicate that L. multiflorum exhibited high degrees of both Cd tolerance and Cd phytoextraction capacity among grass species. [source] Surface-Modified High- k Oxide Gate Dielectrics for Low-Voltage High-Performance Pentacene Thin-Film Transistors,ADVANCED FUNCTIONAL MATERIALS, Issue 6 2007S. Kim Abstract In this study, pentacene thin-film transistors (TFTs) operating at low voltages with high mobilities and low leakage currents are successfully fabricated by the surface modification of the CeO2,SiO2 gate dielectrics. The surface of the gate dielectric plays a crucial role in determining the performance and electrical reliability of the pentacene TFTs. Nearly hysteresis-free transistors are obtained by passivating the devices with appropriate polymeric dielectrics. After coating with poly(4-vinylphenol) (PVP), the reduced roughness of the surface induces the formation of uniform and large pentacene grains; moreover, ,OH groups on CeO2,SiO2 are terminated by C6H5, resulting in the formation of a more hydrophobic surface. Enhanced pentacene quality and reduced hysteresis is observed in current,voltage (I,V) measurements of the PVP-coated pentacene TFTs. Since grain boundaries and ,OH groups are believed to act as electron traps, an OH-free and smooth gate dielectric leads to a low trap density at the interface between the pentacene and the gate dielectric. The realization of electrically stable devices that can be operated at low voltages makes the OTFTs excellent candidates for future flexible displays and electronics applications. [source] Immunotargeting of Functional Nanoparticles for MRI detection of Apoptotic Tumor Cells,ADVANCED MATERIALS, Issue 5 2009Benjamin Thierry Hybrid MRI nanoprobes, immunotargeted to the La ribonucleoprotein, which becomes available for binding in the cytoplasm of post-apoptotic permeable cells, are designed for the improved detection of apoptotic tumor cells. The high level of specificity achieved through the use of an optimal polyethyleneglycol interlayer makes them excellent candidates for the in vivo detection of intratumoral apoptosis. [source] Anisotropic Metal Nanoparticles for Use as Surface-Enhanced Raman Substrates,ADVANCED MATERIALS, Issue 13 2007R. Jana Silver platelets and silver-coated gold nanorods 20,100,nm in size (with a 10,20,nm short axis; see figure) have been identified as excellent candidates for surface-enhanced Raman spectroscopy (SERS) substrates. Salt-induced particle aggregation is essential in obtaining high sensitivity. [source] Ion channels in toxicologyJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2010Ivįn Restrepo-Angulo Abstract Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases. Copyright © 2010 John Wiley & Sons, Ltd. [source] Effects of dimerization of the cell-penetrating peptide Tat analog on antimicrobial activity and mechanism of bactericidal actionJOURNAL OF PEPTIDE SCIENCE, Issue 5 2009Wan Long Zhu Abstract The cell-penetrating peptide Tat (48,60) (GRKKRRQRRRPPQ) derived from HIV-1 Tat protein showed potent antibacterial activity (MIC: 2,8 µM). To investigate the effect of dimerization of Tat (48,60) analog, [Tat(W): GRKKRRQRRRPWQ-NH2], on antimicrobial activity and mechanism of bactericidal action, its dimeric peptides, di-Tat(W)-C and di-Tat(W)-K, were synthesized by a disulfide bond linkage and lysine linkage of monomeric Tat(W), respectively. From the viewpoint of a weight basis and the monomer concentration, these dimeric peptides displayed almost similar antimicrobial activity against six bacterial strains tested but acted more rapidly against Staphylococcus aureus on kinetics of bactericidal activity, compared with monomeric Tat(W). Unlike monomeric Tat(W), these dimeric peptides significantly depolarized the cytoplasmic membrane of intact S. aureus cells at MIC and induced dye leakage from bacterial-membrane-mimicking egg yolk L -,-phosphatidylethanolamine/egg yolk L -,-phosphatidyl- DL -glycerol (7:3, w/w) vesicles. Furthermore, these dimeric peptides were less effective to translocate across lipid bilayers than monomeric Tat(W). These results indicated that the dimerization of Tat analog induces a partial change in the mode of its bactericidal action from intracellular target mechanism to membrane-targeting mechanism. Collectively, our designed dimeric Tat peptides with high antimicrobial activity and rapid bactericidal activity appear to be excellent candidates for future development as novel antimicrobial agents. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Facile preparation of core-crosslinked micelles from azide-containing thermoresponsive double hydrophilic diblock copolymer via click chemistryJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 3 2008Xiaoze Jiang Abstract Double hydrophilic diblock copolymer, poly(N,N -dimethylacrylamide)- b -poly(N -isopropylacrylamide- co -3-azidopropylacrylamide) (PDMA- b -P(NIPAM- co -AzPAM), containing azide moieties in one of the blocks was synthesized via consecutive reversible addition-fragmentation chain transfer polymerization. The obtained diblock copolymer molecularly dissolves in aqueous solution at room temperature, and can further supramolecularly self-assemble into core-shell nanoparticles consisting of thermoresponsive P(NIPAM- co -AzPAM) cores and water-soluble PDMA coronas above the lower critical solution temperature of P(NIPAM- co -AzPAM) block. As the micelle cores contain reactive azide residues, core crosslinking can be facilely achieved upon addition of difunctional propargyl ether via click chemistry. In an alternate approach in which the PDMA- b -P(NIPAM- co -AzPAM) diblock copolymer was dissolved in a common organic solvent (DMF), the core-crosslinked (CCL) micelles can be fabricated via "click" crosslinking upon addition of propargyl ether and subsequent dialysis against water. CCL micelles prepared by the latter approach typically possess larger sizes and broader size distributions, compared with that obtained by the former one. In both cases, the obtained (CCL) micelles possess thermoresponsive cores, and the swelling/shrinking of which can be finely tuned with temperature, rendering them as excellent candidates as intelligent drug nanocarriers. Because of the high efficiency and quite mild conditions of click reactions, we expect that this strategy can be generalized for the structural fixation of other self-assembled nanostructures. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 860,871, 2008 [source] Review article: the modern management of autoimmune hepatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010A. D. YEOMAN Aliment Pharmacol Ther,31, 771,787 Summary Background, The management of autoimmune hepatitis (AIH) continues to be refined. However, several issues remain unresolved, primarily as a consequence of the low incidence of the disease. This factor has contributed both to a lack of understanding of and a paucity of large scale clinical trials involving therapeutic agents. Aim, To summarize the latest evidence regarding the pathogenesis, diagnosis, therapy and long-term management of AIH with a focus on clinical aspects of the disease. Method, We searched PUBMED for articles pertaining to AIH, its pathogenesis, treatment and clinical outcomes, combined with the authors' own knowledge of the literature. Results, Standard therapy (corticosteroids and azathioprine) is effective in more than 80% of patients which renders study of novel agents difficult. Budesonide appears to show equivalence to prednisolone. Available, but limited, data suggest that mycophenolate mofetil, tacrolimus and ciclosporin are all variably effective second line agents. Patients with AIH and cirrhosis are at risk of hepatocellular carcinoma (HCC) and require screening. Patients with end stage liver disease represent excellent candidates for liver transplantation. Conclusions, Despite ongoing limitations in the understanding of pathogenesis and difficulties in evaluating novel therapies, the management of AIH continues to evolve slowly. Multi-centre collaboration is necessary to obtain sufficient patient numbers to undertake good quality therapeutic studies. [source] Gold compounds as anticancer agents: chemistry, cellular pharmacology, and preclinical studiesMEDICINAL RESEARCH REVIEWS, Issue 3 2010Stefania Nobili Abstract Gold compounds are a class of metallodrugs with great potential for cancer treatment. During the last two decades, a large variety of gold(I) and gold(III) compounds are reported to possess relevant antiproliferative properties in vitro against selected human tumor cell lines, qualifying themselves as excellent candidates for further pharmacological evaluation. The unique chemical properties of the gold center confer very interesting and innovative pharmacological profiles to gold-based metallodrugs. The primary goal of this review is to define the state of the art of preclinical studies on anticancer gold compounds, carried out either in vitro or in vivo. The available investigations of anticancer gold compounds are analyzed in detail, and particular attention is devoted to underlying molecular mechanisms. Notably, a few biophysical studies reveal that the interactions of cytotoxic gold compounds with DNA are generally far weaker than those of platinum drugs, implying the occurrence of a substantially different mode of action. A variety of alternative mechanisms were thus proposed, of which those involving either direct mitochondrial damage or proteasome inhibition or modulation of specific kinases are now highly credited. The overall perspectives on the development of gold compounds as effective anticancer drugs with an innovative mechanism of action are critically discussed on the basis of the available experimental evidence. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 3, 550,580, 2010 [source] Leukotriene pathway genetics and pharmacogenetics in allergyALLERGY, Issue 6 2009N. P. Duroudier Leukotrienes (LT) are biologically active lipid mediators known to be involved in allergic inflammation. Leukotrienes have been shown to mediate diverse features of allergic conditions including inflammatory cell chemotaxis/activation and smooth muscle contraction. Cysteinyl leukotrienes (LTC4, LTD4 and, LTE4) and the dihydroxy leukotriene LTB4 are generated by a series of enzymes/proteins constituting the LT synthetic pathway or 5-lipoxygenase (5-LO) pathway. Their function is mediated by interacting with multiple receptors. Leukotriene receptor antagonists (LTRA) and LT synthesis inhibitors (LTSI) have shown clinical efficacy in asthma and more recently in allergic rhinitis. Despite growing knowledge of leukotriene biology, the molecular regulation of these inflammatory mediators remains to be fully understood. Genes encoding enzymes of the 5-LO pathway (i.e. ALOX5, LTC4S and LTA4H) and encoding for LT receptors (CYSLTR1/2 and LTB4R1/2) provide excellent candidates for disease susceptibility and severity; however, their role remains unclear. Preliminary data also suggest that 5-LO pathway/receptor gene polymorphism can predict patient responses to LTSI and LTRA; however, the exact mechanisms require elucidation. The aim of this review was to summarize the recent advances in the knowledge of these important mediators, focusing on genetic and pharmacogenetic aspects in the context of allergic phenotypes. [source] Structure and function of the Mur enzymes: development of novel inhibitorsMOLECULAR MICROBIOLOGY, Issue 1 2003Ahmed El Zoeiby Summary One of the biggest challenges for recent medical research is the continuous development of new antibiotics interacting with bacterial essential mechanisms. The machinery for peptidoglycan biosynthesis is a rich source of crucial targets for antibacterial chemotherapy. The cytoplasmic steps of the biosynthesis of peptidoglycan precursor, catalysed by a series of Mur enzymes, are excellent candidates for drug development. There has been growing interest in these bacterial enzymes over the last decade. Many studies attempted to understand the detailed mechanisms and structural features of the key enzymes MurA to MurF. Only MurA is inhibited by a known antibiotic, fosfomycin. Several attempts made to develop novel inhibitors of this pathway are discussed in this review. Three novel inhibitors of MurA were identified recently. 4-Thiazolidinone compounds were designed as MurB inhibitors. Many phosphinic acid derivatives and substrate analogues were identified as inhibitors of the MurC to MurF amino acid ligases. [source] Phenotypic and functional characterization of mature dendritic cells from pediatric cancer patientsPEDIATRIC BLOOD & CANCER, Issue 7 2007Joannes F.M. Jacobs MD Abstract Background Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system. Clinical trials have demonstrated that mature DCs loaded with tumor-associated antigens can induce tumor-specific immune responses. Theoretically, pediatric patients are excellent candidates for immunotherapy since their immune system is more potent compared to adults. We studied whether sufficient amounts of mature monocyte-derived DCs can be cultured from peripheral blood of pediatric cancer patients. Procedure DCs from 15 pediatric patients with an untreated primary tumor were cultured from monocytes and matured with clinical grade cytokines. Phenotype and function were tested with flow cytometry, mixed lymphocyte reaction (MLR), and an in vitro migration assay. DCs of children with a solid tumor were compared with monocyte-derived DCs from age-related non-malignant controls. Results Ex vivo-generated monocyte-derived DCs from pediatric patients can be generated in numbers sufficient for DC vaccination trials. Upon cytokine stimulation the DCs highly upregulate the expression of the maturation markers CD80, CD83, and CD86. The mature DCs are six times more potent in inducing T cell proliferation compared to immature DCs. Furthermore, mature DCs, but not immature DCs, express the chemokine receptor CCR7 and have the capacity to migrate in vitro. Conclusions These data indicate that mature DCs can be generated ex vivo to further optimize DC-vaccination trials in pediatric cancer patients. Pediatr Blood Cancer 2007;49:924,927. © 2007 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||