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Attractive Candidates (attractive + candidate)
Selected AbstractsAnticonvulsant profile and teratogenicity of 3,3-dimethylbutanoylurea: A potential for a second generation drug to valproic acidEPILEPSIA, Issue 7 2008Jakob Avi Shimshoni Summary Purpose: The purpose of this study was to evaluate the anticonvulsant activity and teratogenic potential of branched aliphatic acylureas represented by isovaleroylurea (IVU), pivaloylurea (PVU) and 3,3-dimethylbutanoylurea (DBU), as potential second-generation drugs to valproic acid (VPA). Methods: The anticonvulsant activity of IVU, PVU, and DBU was determined in mice and rats utilizing the maximal electroshock seizure (MES) and the pentylenetetrazole (scMet) tests. The ability of DBU to block electrical-, or chemical-induced seizures was further examined in three acute seizure models: the psychomotor 6 Hz model, the bicuculline and picrotoxin models and one model of chronic epilepsy (i.e., the hippocampal kindled rat model). The induction of neural tube defects (NTDs) by IVU, PVU, and DBU was evaluated after i.p. administration at day 8.5 of gestation to a mouse strain highly susceptible to VPA-induced teratogenicity. The pharmacokinetics of DBU was studied following i.v. administration to rats. Results: DBU emerged as the most potent compound having an MES-ED50of 186 mg/kg (mice) and 64 mg/kg (rats) and an scMet-ED50of 66 mg/kg (mice) and 26 mg/kg (rats). DBU underwent further evaluation in the hippocampal kindled rat (ED50= 35 mg/kg), the psychomotor 6 Hz mouse model (ED50= 80 mg/kg at 32 mA and ED50= 133 mg/kg at 44 mA), the bicuculline- and picrotoxin-induced seizure mouse model (ED50= 205 mg/kg and 167 mg/kg, respectively). In contrast to VPA, DBU, IVU, and PVU did not induce a significant increase in NTDs as compared to control. DBU was eliminated by metabolism with a half-life of 4.5 h. Conclusions: DBU's broad spectrum and potent anticonvulsant activity, along with its high safety margin and favorable pharmacokinetic profile, make it an attractive candidate to become a new, potent, and safe AED. [source] Recombinant glycodelin carrying the same type of glycan structures as contraceptive glycodelin-A can be produced in human kidney 293 cellsbut not in Chinese hamster ovary cellsFEBS JOURNAL, Issue 15 2000Ingrid M. Van den Nieuwenhof We have produced human recombinant glycodelin in human kidney 293 cells and in Chinese hamster ovary (CHO) cells. Structural analyses by lectin immunoassays and fast atom bombardment mass spectrometry showed that recombinant human glycodelin produced in CHO cells contains only typical CHO-type glycans and is devoid of any of the N,N,- diacetyllactosediamine (lacdiNAc)-based chains previously identified in glycodelin-A (GdA). By contrast, human kidney 293 cells produced recombinant glycodelin with the same type of carbohydrate structures as GdA. The presence of a ,1,4- N- acetylgalactosaminyltransferase functioning in the synthesis of lacdiNAc-based glycans in human kidney 293 cells is concluded to be the cause of the occurrence of lacdiNAc-based glycans on glycodelin produced in these cells. Furthermore, human kidney 293 cells were found to be particularly suited for the production of recombinant glycodelin when they were cultured in high glucose media. Lowering the glucose concentration and the addition of glucosamine resulted in higher relative amounts of oligomannosidic-type glycans and complex glycans with truncated antennae. Human glycodelin is an attractive candidate for the development of a contraceptive agent, and this study gives valuable information for selecting the proper expression system and cell culture conditions for the production of a correctly glycosylated recombinant form. [source] Sustained expression of Epstein,Barr virus episomal vector mediated factor VIII in vivo following muscle electroporationHAEMOPHILIA, Issue 3 2006W.-H. MEI Summary., Haemophilia A treatment is an attractive candidate for gene therapy. The aim of haemophilia gene therapy is to obtain long-term therapeutic level of factor VIII (FVIII). We investigated Epstein,Barr virus (EBV)-based episomal vector combined with in vivo electroporation of naked DNA as a safe, efficient and simple method for correcting FVIII deficiency. A combinant FVIII expression EBV-based episomal vector pcDNA3-FVIII-EBVR was constructed and expressed in COS-7 cells. Then the naked plasmid DNA was injected into the quadriceps of mice following the electric pulse stimulation. Our data showed that pcDNA3-FVIII-EBVR expression in transfected COS-7 can maintain stably for at least 60 days and the hFVIII:Ag in plasma in two pcDNA3-FVIII-EBVR groups mice was higher than that in pcDNA-FVIII groups no matter with or without electric pulse stimulation. With the stimulating of electric pulse, the FVIII expression in plasma of recipient mice was increased two- to fourfolds and can be lasted for at least 90 days. No severe muscle damage was detected. So this novel strategy that FVIII expression mediated by EBV episomal vector following muscle electroporation is efficient, safe, simple and economic and may be applicable to clinical usage. [source] The shared tumor associated antigen cyclin-A2 is recognized by high-avidity T-cellsINTERNATIONAL JOURNAL OF CANCER, Issue 10 2009Eisei Kondo Abstract Cyclin-A2, a key cell cycle regulator, has been shown to be overexpressed in various types of malignancies with little expression in normal tissue. Such tumor-associated genes potentially are useful targets for cancer immunotherapy. However, high-avidity cyclin-specific T cells are considered to be thymically deleted. We identified at least one nonameric HLA-A*0201 binding cyclin-A2 epitope by a reverse immunology approach. Using a highly efficient T-cell expansion system that is based on CD40-activated B (CD40-B) cells as sole antigen-presenting cells we successfully generated cyclin-A2 specific CTL from HLA-A*0201+ donors. Interestingly, high-avidity cyclin-A2 specific CTL lines, which recognized peptide-pulsed and antigen expressing target cells, were indeed generated by stimulation with CD40-B cells when pulsed with low concentrations of peptide, whereas CD40-B cells pulsed at saturating concentrations could only induce low-avidity CTL, which recognized peptide-pulsed target cells only. One high-avidity CTL line was subcloned and CTL clones, whose peptide concentration required for half-maximal lysis were less than 1 nM, could lyse cyclin-A2 expressing tumor cells. Taken together, cyclin A2 is an attractive candidate for immune intervention in a significant number of cancer patients and high-avidity T cells can be readily generated using CD40-B cells as antigen-presenting cells. © 2009 UICC [source] Valproic acid blocks adhesion of renal cell carcinoma cells to endothelium and extracellular matrixJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Jon Jones Abstract Treatment strategies for metastatic renal cell carcinoma (RCC) have been limited due to chemotherapy and radiotherapy resistance. The development of targeted drugs has now opened novel therapeutic options. In the present study, anti-tumoral properties of the histone deacetylase inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical RCC models. RCC cell lines Caki-1, KTC-26 or A498 were treated with various concentrations of VPA to evaluate tumour cell adhesion to vascular endothelial cells or to immobilized extracellular matrix proteins. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. VPA was also combined with low dosed interferon-, (IFN-,) and the efficacy of the combination therapy, as opposed to VPA monotherapy, was compared. VPA significantly and dose-dependently prevented tumour cell attachment to endothelium or matrix proteins, accompanied by elevated histones H3 and H4 acetylation. VPA altered integrin-, and -, subtype expression, in particular ,3, ,5 and ,3, and blocked integrin-dependent signalling. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts with the 200 mg/kg being superior to the 400 mg/kg dosing schedule. VPA-IFN-, combination markedly enhanced the effects of VPA on RCC adhesion, and in vivo tumour growth was further reduced by the 400 mg/kg but not by the 200 mg/kg VPA dosing schedule. VPA profoundly blocked the interaction of RCC cells with endothelium and extracellular matrix and reduced tumour growth in vivo. Therefore, VPA should be considered an attractive candidate for clinical trials. [source] Tissue-specific dysregulation of DNA methylation in agingAGING CELL, Issue 4 2010Reid F. Thompson Summary The normal aging process is a complex phenomenon associated with physiological alterations in the function of cells and organs over time. Although an attractive candidate for mediating transcriptional dysregulation, the contribution of epigenetic dysregulation to these progressive changes in cellular physiology remains unclear. In this study, we employed the genome-wide HpaII tiny fragment enrichment by ligation-mediated PCR assay to define patterns of cytosine methylation throughout the rat genome and the luminometric methylation analysis assay to measure global levels of DNA methylation in the same samples. We studied both liver and visceral adipose tissues and demonstrated significant differences in DNA methylation with age at > 5% of sites analyzed. Furthermore, we showed that epigenetic dysregulation with age is a highly tissue-dependent phenomenon. The most distinctive loci were located at intergenic sequences and conserved noncoding elements, and not at promoters nor at CG-dinucleotide-dense loci. Despite this, we found that there was a subset of genes at which cytosine methylation and gene expression changes were concordant. Finally, we demonstrated that changes in methylation occur consistently near genes that are involved in metabolism and metabolic regulation, implicating their potential role in the pathogenesis of age-related diseases. We conclude that different patterns of epigenetic dysregulation occur in each tissue over time and may cause some of the physiological changes associated with normal aging. [source] Identification of small peptides mimicking the R2 C -terminus of Mycobacterium tuberculosis ribonucleotide reductaseJOURNAL OF PEPTIDE SCIENCE, Issue 3 2010Daniel J. Ericsson Abstract Ribonucleotide reductase (RNR) is a viable target for new drugs against the causative agent of tuberculosis, Mycobacterium tuberculosis. Previous work has shown that an N -acetylated heptapeptide based on the C -terminal sequence of the smaller RNR subunit can disrupt the formation of the holoenzyme sufficiently to inhibit its function. Here the synthesis and binding affinity, evaluated by competitive fluorescence polarization, of several truncated and N -protected peptides are described. The protected single-amino acid Fmoc-Trp shows binding affinity comparable to the N -acetylated heptapeptide, making it an attractive candidate for further development of non-peptidic RNR inhibitors. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] High-Energy Density Capacitors Utilizing 0.7 BaTiO3,0.3 BiScO3 CeramicsJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 8 2009Hideki Ogihara A high, temperature-stable dielectric constant (,1000 from 0° to 300°C) coupled with a high electrical resistivity (,1012,·cm at 250°C) make 0.7 BaTiO3,0.3 BiScO3 ceramics an attractive candidate for high-energy density capacitors operating at elevated temperatures. Single dielectric layer capacitors were prepared to confirm the feasibility of BaTiO3,BiScO3 for this application. It was found that an energy density of about 6.1 J/cm3 at a field of 73 kV/mm could be achieved at room temperature, which is superior to typical commercial X7R capacitors. Moreover, the high-energy density values were retained to 300°C. This suggests that BaTiO3,BiScO3 ceramics have some advantages compared with conventional capacitor materials for high-temperature energy storage, and with further improvements in microstructure and composition, could provide realistic solutions for power electronic capacitors. [source] Non-essential dietary factors: from test tube to lifespanJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 10 2007S Luke Hillyard Abstract The agriculture and food industries have an opportunity to change the future of food production by providing foods containing non-essential dietary factors (NEDFs) that improve health beyond a freedom from disease. In order to accomplish this in a safe and time-effective manner, however, each NEDF needs to be tested on a number of levels before it is incorporated into foods. In vitro assays are useful for discovering potential beneficial NEDFS, but in vivo studies are needed to both confirm positive effects and to detect negative effects. The genetic and metabolic similarities between humans and Caenorhabditis elegans, combined with the ease with which this nematode can be manipulated in the laboratory make it an attractive candidate to fulfill the role of an early stage in vivo model. Measuring the lifespan of C. elegans cultured in the presence of a range of concentrations of a NEDF would be of both mechanistic and strategic value in identifying those NEDFs that warrant further testing. Copyright © 2007 Society of Chemical Industry [source] Toward a cell-based cure for diabetes: advances in production and transplant of beta cellsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2008Kathryn C. Claiborn Abstract Type 1 diabetes results from autoimmune destruction of the insulin-producing beta cells of the pancreatic islets of Langerhans. Although developments in exogenous insulin therapy have greatly improved clinical outcomes in patients with diabetes, the ability of the pancreatic beta cell to exquisitely regulate the delivery of insulin and maintain normal levels of blood glucose is still far superior to what can be achieved by external delivery of insulin. As a result, the majority of patients with type 1 diabetes still experience the complications of chronic hyperglycemia or serious and potentially life-threatening hypoglycemia. The shortcomings of medical therapy have driven research toward more direct approaches of beta cell replacement. Indeed, the specificity of beta cell loss in type 1 diabetes makes this disease a particularly attractive candidate for cell-based therapies. In order for significant progress to be made, however, a thorough understanding of beta cell biology and more broadly islet biology is necessary. This review addresses recent advances in developmental biology that have expanded our understanding of islet cell differentiation, assesses the promise and limitations of islet transplantation, and discusses the future of alternative sources of beta cells, including directed differentiation of stem cells, replication of adult beta cells, and transdifferentiation of nonislet cells to a beta cell fate. Mt Sinai J Med 75:362,371, 2008. © 2008 Mount Sinai School of Medicine [source] Fast and faster: A designed variant of the B-domain of protein A folds in 3 ,secPROTEIN SCIENCE, Issue 4 2004Pooja Arora Abstract We have introduced the mutation glycine 29 to alanine, designed to increase the rate of protein folding, into the B-domain of protein A (BdpA). From NMR lineshape analysis, we find the G29A mutation increases the folding rate constant by threefold; the folding time is 3 ,sec. Although wild-type BdpA folds extremely fast, simple-point mutations can still speed up the folding; thus, the folding rate is not evolutionarily maximized. The short folding time of G29A BdpA (the shortest time yet reported) makes it an attractive candidate for an all-atom molecular dynamics simulation that could potentially show a complete folding reaction starting from an extended chain. We also constructed a fluorescent variant of BdpA by mutating phenylalanine 13 to tryptophan, allowing fluorescence-based time-resolved temperature-jump measurements. Temperature jumps and NMR complement each other, and give a very complete picture of the folding kinetics. [source] Structural-based mutational analysis of d -aminoacylase from Alcaligenes faecalis DA1PROTEIN SCIENCE, Issue 11 2002Cheng-Sheng Hsu Abstract d -Aminoacylase is an attractive candidate for commercial production of d -amino acids through its catalysis in the zinc-assistant hydrolysis of N -acyl- d -amino acids. We report here the cloning, expression, and structural-based mutation of the d -aminoacylase from Alcaligenes faecalis DA1. A 1,007-bp PCR product amplified with degenerate primers, was used to isolate a 4-kb genomic fragment, encoding a 484-residue d -aminoacylase. The enzyme amino-terminal segment shared significant homology within a variety of enzymes including urease. The structural fold was predicted by 3D-PSSM to be similar to urease and dihydroorotase, which have grouped into a novel ,/,-barrel amidohydrolase superfamily with a virtually indistinguishable binuclear metal centers containing six ligands, four histidines, one aspartate, and one carboxylated lysine. Three histidines, His-67, His-69, and His-250, putative metal ligands in d -aminoacylase, have been mutated previously, the remaining histidine (His-220) and aspartate (Asp-366) Asp-65, and four cysteines were then characterized. Substitution of Asp-65, Cys-96, His-220, and Asp-366 with alanine abolished the enzyme activity. The H220A mutant bound approximately half the normal complement of zinc ion as did H250N. However, the C96A mutant showed little zinc-binding ability, revealing that Cys-96 may replace the carboxylated lysine to serve as a bridging ligand. According to the urease structure, the conserved amino-terminal segment including Asp-65 may be responsible for structural stabilization. [source] Development and characterization of a triple combination gene therapy vector inhibiting HIV-1 multiplicationTHE JOURNAL OF GENE MEDICINE, Issue 10 2008Maria B. Asparuhova Abstract Background RNA-based approaches are promising for long-term gene therapy against HIV-1. They can target virtually any step of the viral replication cycle. It is also possible to combine anti-HIV-1 transgenes targeting different facets of HIV replication to compensate for limitations of any individual construct, maximizing efficacy and decreasing chances of escape mutations. We have previously developed two strategies to inhibit HIV-1 multiplication. One was a short hairpin RNA targeting the host factor cyclophilin A implicated in HIV-1 replication. Additionally, an antisense derivative of U7 small nuclear RNA was designed to induce the skipping of the HIV-1 Tat and Rev internal exons. Results In the present study, we have established an additional tRNAval promoter-driven shRNA against the coding sequence of viral infectivity factor. When human T-cell lines or primary CD4+ T cells are transduced with a triple lentiviral vector encoding these three therapeutic RNAs, HIV-1 multiplication is very efficiently suppressed. Moreover, all three therapeutic RNAs exhibit antiviral effects at early stages of the viral replication cycle (i.e. prior to viral cDNA integration or gene expression). Conclusions These findings make this triple lentiviral vector an attractive candidate for a gene therapy against HIV/AIDS. Copyright © 2008 John Wiley & Sons, Ltd. [source] Treatment with rapamycin prevents fibrosis in tight-skin and bleomycin-induced mouse models of systemic sclerosisARTHRITIS & RHEUMATISM, Issue 8 2010Ayumi Yoshizaki Objective Rapamycin, a novel macrolide immunosuppressive drug, is increasingly used as an agent for posttransplant immunosuppression and treatment of autoimmune disease. The molecular mechanism related to rapamycin-mediated immunosuppression is that rapamycin binds to FK-506 binding protein 12, and the formed complex inhibits the function of the mammalian target of rapamycin (mTOR), which in turn reduces protein phosphorylation, cell cycle progression, and cytokine production. The aim of this study was to examine the effect of rapamycin against the development of fibrosis and autoimmunity in 2 different types of systemic sclerosis (SSc) model mice. Methods Tight skin (TSK/+) mice and bleomycin- induced SSc model mice were used to evaluate the effect of rapamycin on fibrosis and immunologic abnormalities. Furthermore, the antifibrotic effect of rapamycin was assessed using TSK/+ mouse fibroblasts. Results Treatment with rapamycin reduced skin fibrosis of TSK/+ mice and skin and lung fibrosis of bleomycin-induced SSc model mice. The production of fibrogenic cytokines, such as interleukin-4 (IL-4), IL-6, IL-17, and transforming growth factor ,1, was attenuated by rapamycin. Hypergammaglobulinemia and anti,topoisomerase I antibody production were also reduced by rapamycin treatment in TSK/+ mice. In addition, mTOR expression levels were increased in TSK/+ mouse fibroblasts compared with those in wild-type mouse fibroblasts. Rapamycin treatment inhibited proliferation and collagen production of TSK/+ mouse fibroblasts in a dose-dependent manner. Conclusion This study is the first to show that rapamycin has a significant inhibitory effect on fibrosis in both TSK/+ and bleomycin-induced SSc model mice. These results suggest that rapamycin might be an attractive candidate for clinical trials in SSc patients. [source] X-ray structure and characterization of carbamate kinase from the human parasite Giardia lambliaACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2010Andrey Galkin Carbamate kinase catalyzes the reversible conversion of carbamoyl phosphate and ADP to ATP and ammonium carbamate, which is hydrolyzed to ammonia and carbonate. The three-dimensional structure of carbamate kinase from the human parasite Giardia lamblia (glCK) has been determined at 3,Å resolution. The crystals belonged to the monoclinic space group P21, with unit-cell parameters a = 69.77, b = 85.41, c = 102.1,Å, , = 106.8°. The structure was refined to a final R factor of 0.227. The essentiality of glCK together with its absence in humans makes the enzyme an attractive candidate for anti- Giardia drug development. Steady-state kinetic rate constants have been determined. The kcat for ATP formation is 319 ± 9,s,1. The Km values for carbamoyl phosphate and ADP are 85 ± 6 and 70 ± 5,µM, respectively. The structure suggests that three invariant lysine residues (Lys131, Lys216 and Lys278) may be involved in the binding of substrates and phosphoryl transfer. The structure of glCK reveals that a glycerol molecule binds in the likely carbamoyl phosphate-binding site. [source] Dendrimers: A Mimic Natural Light-Harvesting SystemCHEMISTRY - AN ASIAN JOURNAL, Issue 5 2010Yi Zeng Dr. Abstract In natural photosynthetic systems, a large array of chlorophyll molecules surrounds a single reaction center and channels the absorbed solar energy to the reaction center, ultimately resulting in ATP production. Dendrimers are well-defined tree-like macromolecules having numerous chain ends all emanating from a single core, which makes them an attractive candidate for light-harvesting applications. More importantly, their synthesis is controllable and the accurate positioning of chromophores can be achieved. Photoinduced electron transfer and energy transfer are main processes involved in photosynthesis. Studies on these processes in dendritic systems are important for the future application of dendrimers in optoelectronic devices. In this Focus Review we will discuss recent advances of light-harvesting dendrimers and emphasize the energy transfer and electron transfer characteristics in these systems. [source] Investigation Of AM-36: A Novel Neuroprotective AgentCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001Jk Callaway SUMMARY 1. The neurochemical sequelae following cerebral ischaemia are complex, involving excess release of excitatory amino acids, particularly glutamate, disruption of ionic homeostasis due to Na+ and Ca2+ influx and generation of toxic free radicals, ultimately leading to cell death by both necrosis and apoptosis. 2. Drugs that block components of this biochemical cascade, such as glutamate receptor antagonists, sodium channel blockers and free radical scavengers, have been investigated as putative neuroprotective agents. The knowledge that multiple mechanisms contribute to neuronal injury in ischaemia have led to the general recognition that a single drug treatment is unlikely to be beneficial in the treatment of cerebral ischaemia. 3. AM-36 [1-(2-(4-chlorophenyl)-2-hydroxy)ethyl-4-(3,5-bis(1,1-dimethyl)-4-hydroxyphenyl)methylpiperazine] is one of a series of hybrid molecules designed to incorporate multiple neuroprotective mechanisms within the one structure. Primary screening tests demonstrated that AM-36 inhibited binding to the polyamine site of glutamate receptors, blocked neuronal sodium channels and had potent anti-oxidant activity. In neuronal cell cultures, AM-36 inhibited toxicity induced by N -methyl- D -aspartate (NMDA) and the sodium channel opener veratridine and, in addition, inhibited veratridine-induced apoptosis. 4. In a middle cerebral artery occlusion model of stroke in conscious rats, systemic administration of AM-36 markedly reduced both cortical and striatal infarct volume and significantly improved functional outcome in motor performance, neurological deficit and sensorimotor neglect tests. AM-36 was neuroprotective even when administration was delayed until 3 h systemically, or 5 h intravenously, after induction of stroke. 5. These studies indicate that AM-36 is a unique neuroprotective agent with multiple modes of action, making it an attractive candidate for the treatment of acute stroke in humans. [source] Heterologous gene expression in Lactococcus lactis; expression of the Azotobacter vinelandii algE6 gene product displaying mannuronan C-5 epimerase activityFEMS MICROBIOLOGY LETTERS, Issue 2 2003Janet M. Blatny Abstract The Azotobacter vinelandii mannuronan C-5 epimerases AlgE1,7 can be used to improve the properties of the commercially important polysaccharide alginate that is widely used in a variety of products, such as food and pharmaceuticals. Since lactic acid bacteria are generally regarded as safe, they are attractive candidates for production of the epimerases. A. vinelandii genes are GC-rich, in contrast to those of lactic acid bacteria, but we show here that significant expression levels of the epimerase AlgE6 can be obtained in Lactococcus lactis using the nisin-controlled expression system. A 1200-fold induction ratio was obtained resulting in an epimerase activity of 23,900 dpm mg,1 h,1, using a tritiated alginate substrate. The epimerase was detected by Western blotting and nuclear magnetic resonance spectroscopy analysis of its reaction product showed that the enzyme displayed catalytic properties similar to those produced in Escherichia coli. [source] From Ag Nanoprisms to Triangular AuAg NanoboxesADVANCED FUNCTIONAL MATERIALS, Issue 8 2010Damian Aherne Abstract In recent years, galvanic replacement reactions have been successfully employed to produce hollow bimetallic nanostructures of a range of shapes, yet to date there has been no example of the formation of hollow triangular AuAg nanostructures from a Ag nanoprism template. In this manuscript the first example of the synthesis of enclosed triangular AuAg nanostructures (triangular nanoboxes) via galvanic replacement reactions from Ag nanoprisms is reported. These triangular nanoboxes are studied by TEM and HAADF-STEM imaging to elucidate their structure. These studies show that the nanostructures are hollow and do not consist of a Ag core surrounded by a Au shell. Discrete dipole approximation calculations for the extinction spectra are carried out and provide additional evidence that the nanostructures are hollow. These new triangular nanoboxes are very attractive candidates for encapsulation and transport of materials of interest such as drugs, radioisotopes, or magnetic materials. [source] Quantitative microsatellite analysis to delineate the commonly deleted region 1p22.3 in mantle cell lymphomasGENES, CHROMOSOMES AND CANCER, Issue 10 2006Asha Balakrishnan The molecular pathogenesis of mantle cell lymphomas (MCL), a subset of B-cell non-Hodgkin's lymphomas with a poor prognosis, is still poorly understood. In addition to the characteristic primary genetic alteration t(11;14)(q13;q32), several further genetic changes are present in most cases. One of the most frequent genomic imbalances is the deletion of 1p22.1,p31.1 observed in nearly one-third of MCL cases. This might indicate the presence of tumor suppressor gene(s) in this critical region of deletion. Quantitative microsatellite analysis (QuMA) is a real-time PCR-based method to detect DNA copy number changes. Since QuMA has the resolving power to detect subtle genomic alterations, including homozygous deletions, this may help to identify candidate tumor suppressor genes from deleted regions. To gain more insight into the molecular pathogenesis of MCL, QuMA was performed on genomic DNA from 57 MCL cases. Eight microsatellite loci mapping to the chromosomal region 1p22.3 were analyzed. Losses were observed in 51 of the 57 (,89.5%) samples. Two cases showed a homozygous deletion at the locus containing the gene SH3GLB1, which plays a key role in Bax-mediated apoptosis. Two hotspots with copy number losses were detected at chromosomal localizations 85.4 and 86.6 Mb encompassing BCL10 and CLCA2. Both the genes seem to be attractive candidates to study tumor suppressor function in MCL. This article contains Supplementary material available at http://www.interscience.wiley.com/jpages/1045,2257/suppmat. © 2006 Wiley-Liss, Inc. [source] Polyfluorene Light-Emitting Diodes: Understanding the Nature of the States Responsible for the Green Emission in Oxidized Poly(9,9-dialkylfluorene)s: Photophysics and Structural Studies of Linear Dialkylfluorene/Fluorenone Model Compounds (Adv. Funct.ADVANCED FUNCTIONAL MATERIALS, Issue 13 2009Mater. Polyfluorenes, whilst attractive candidates for polymer light-emitting diodes, are susceptible to oxidative degradation. This degradation results in significant green emission. Although it has been linked to the formation of fluorenones, the precise relationship between fluorenones and the observed color shift remains widely debated. On page 2147, Chan et al. report a study on this relationship with the use of a series of model compounds. Inter-molecular fluorenone,fluorenone interaction is reported to be an essential requirement for the color shift. [source] 2,7-Carbazolenevinylene-Based Oligomer Thin-Film Transistors: High Mobility Through Structural Ordering,ADVANCED FUNCTIONAL MATERIALS, Issue 10 2005N. Drolet Abstract We have fabricated organic field-effect transistors based on thin films of 2,7-carbazole oligomeric semiconductors 1,4-bis(vinylene-(N -hexyl-2-carbazole))phenylene (CPC), 1,4-bis(vinylene-(N,-methyl-7,-hexyl-2,-carbazole))benzene (RCPCR), N -hexyl-2,7-bis(vinylene-(N -hexyl-2-carbazole))carbazole (CCC), and N -methyl-2,7-bis(vinylene-(7-hexyl- N -methyl-2-carbazole))carbazole (RCCCR). The organic semiconductors are deposited by thermal evaporation on bare and chemically modified silicon dioxide surfaces (SiO2/Si) held at different temperatures varying from 25 to 200,°C during deposition. The resulting thin films have been characterized using UV-vis and Fourier-transform infrared spectroscopies, scanning electron microscopy, and X-ray diffraction, and the observed top-contact transistor performances have been correlated with thin-film properties. We found that these new ,-conjugated oligomers can form highly ordered structures and reach high hole mobilities. Devices using CPC as the active semiconductor have exhibited mobilities as high as 0.3,cm2,V,1,s,1 with on/off current ratios of up to 107. These features make CPC and 2,7-carbazolenevinylene-based oligomers attractive candidates for device applications. [source] Engineering Homochiral Metal-Organic Frameworks for Heterogeneous Asymmetric Catalysis and Enantioselective SeparationADVANCED MATERIALS, Issue 37 2010Yan Liu Abstract Owing to the potential applications in technological areas such as gas storage, catalysis, separation, sensing and nonlinear optics, tremendous efforts have been devoted to the development of porous metal-organic frameworks (MOFs) over the past ten years. Homochiral porous MOFs are particularly attractive candidates as heterogeneous asymmetric catalysts and enantioselective adsorbents and separators for production of optically active organic compounds due to the lack of homochiral inorganic porous materials such as zeolites. In this review, we summarize the recent research progress in homochiral MOF materials, including their synthetic strategy, distinctive structural features and latest advances in asymmetric heterogeneous catalysis and enantioselective separation. [source] Transgene expression from the Tribolium castaneum Polyubiquitin promoterINSECT MOLECULAR BIOLOGY, Issue 5 2002M. D. Lorenzen Abstract The highly conserved Ubiquitin proteins are expressed from genes with strong, constitutively active promoters in many species, making these promoters attractive candidates for use in driving transgene expression. Here we report the cloning and characterization of the Tribolium castaneum Polyubiquitin (TcPUb) gene. We placed the TcPUb promoter upstream of the coding region of the T. castaneum eye-colour gene Tc vermilion (Tcv) and injected this construct into embryos from a Tcv -deficient strain. Transient expression of Tcv during embryogenesis resulted in complete rescue of the larval mutant phenotype. We then incorporated the TcPUb-Tcv chimera into a piggyBac donor. Resulting germline transformants were easily recognized by rescue of eye pigmentation, illustrating the potential of the TcPUb promoter for use in driving transgene expression. [source] Fully Transparent Thin-Film Transistors Based on Aligned Carbon Nanotube Arrays and Indium Tin Oxide Electrodes,ADVANCED MATERIALS, Issue 5 2009Sunkook Kim Fully transparent thin-film transistors (TFTs) based on well-aligned single-walled carbon nanotube (SWCNT) arrays with indium tin oxide (ITO) electrodes are achieved. The fully transparent SWCNT-TFTs could be attractive candidates for future flexible or transparent electronics. [source] Leading Sectors and Leading Regions: Economic Restructuring and Regional Inequality in Hungary since 1990INTERNATIONAL JOURNAL OF URBAN AND REGIONAL RESEARCH, Issue 3 2007DAVID L. BROWN Abstract This article examines factors accounting for persisting regional inequality in Hungary during the regime change from socialism to a market economy in 1990. We examine the determinants of regional inequality through the lens of leading sector theory which has been used to explain why some ex-socialist countries have done better than others during the transformation. In other words, we ask whether some regions of Hungary are doing better than others for the same reasons that some ex-socialist countries have outperformed their counterparts. We use county level data from the Hungarian Central Statistical Office to examine whether the quantity and types of foreign direct investment counties have received since 1990 are associated with regional inequality in per capita GDP. We find that foreign capitalists concentrate human-capital-intensive investment in already well performing locations because they have similar supply structures to their home economies. We also contend that no measure of institutional modernization is likely to make lagging regions attractive candidates for human-capital-intensive investments in the near future. Hence, regardless of the national state's efforts to target development to lagging areas, or the effectiveness of local institutions, lagging regions are likely to remain underdeveloped. We recommend that future field-based research be conducted to examine the nexus between FDI, the nation state and localities. Unraveling interrelationships between these three political economy sites will expose the causal forces sustaining regional inequalities during post-socialism. Résumé Cet article analyse les facteurs qui expliquent l'inégalité persistante entre régions hongroises lors du passage du socialisme à une économie de marché en 1990. Nous examinons les déterminants de l'inégalité régionale à travers la théorie du secteur moteur qui a servi à expliquer pourquoi certains ex-pays socialistes ont mieux réussi que d'autres pendant la transition. Plus précisément, nous cherchons à savoir si des régions de Hongrie font mieux que d'autres pour les mêmes raisons que certains ex-pays socialistes ont eu de meilleurs résultats que leurs homologues. Nous utilisons des données départementales provenant du Bureau central hongrois de la statistique afin d'examiner si la quantité et les types d'investissement direct à l'étranger que les départements ont reçu depuis 1990 sont associés à une inégalité régionale en termes de PIB par habitant. Nous établissons ainsi que les capitalistes étrangers concentrent leur investissement à fort capital humain dans des sites qui présentent déjà de bons résultats, les structures d'approvisionnement étant similaires à celles de leur économie nationale. Nous soutenons également que, dans le court terme, aucune mesure de modernisation institutionnelle ne va sans doute transformer les régions en retard en candidates intéressantes pour des investissements à fort capital humain. En conséquence, quels que soient les efforts de l'État national en vue de développer spécifiquement les zones en décalage, ou l'efficacité des institutions locales, les régions en retard resteront sans doute moins développées. Nous conseillons d'entreprendre à l'avenir des études de terrain afin d'analyser le lien entre IDE, État national et régions. Démêler les relations entre ces trois centres de l'économie politique révélera les forces en cause dans la durabilité des inégalités régionales pendant l'après-socialisme. [source] Chitosan scaffolds for in vitro buffalo embryonic stem-like cell culture: An approach to tissue engineeringJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2007Wah W. Thein-Han Abstract Three-dimensional (3D) porous chitosan scaffolds are attractive candidates for tissue engineering applications. Chitosan scaffolds of 70, 88, and 95% degree of deacetylation (% DD) with the same molecular weight were developed and their properties with buffalo embryonic stem-like (ES-like) cells were investigated in vitro. Scaffolds were fabricated by freezing and lyophilization. They showed open pore structure with interconnecting pores under scanning electron microscopy (SEM). Higher % DD chitosan scaffolds had greater mechanical strength, slower degradation rate, lower water uptake ability, but similar water retention ability, when compared to lower % DD chitosan. As a strategy to tissue engineering, buffalo ES-like cells were cultured on scaffolds for 28 days. It appeared that chitosan was cytocompatible and cells proliferated well on 88 and 95% DD scaffolds. In addition, the buffalo ES-like cells maintained their pluripotency during the culture period. Furthermore, the SEM and histological study showed that the polygonal buffalo ES-like cells proliferated well and attached to the pores. This study proved that 3D biodegradable highly deacetylated chitosan scaffolds are promising candidates for ES-like cell based tissue engineering and this chitosan scaffold and ES cell based system can be used as in vitro model for subsequent clinical applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007 [source] Characterization of dilute species within CVD-grown silicon nanowires doped using trimethylboron: protected lift-out specimen preparation for atom probe tomographyJOURNAL OF MICROSCOPY, Issue 2 2010T. J. PROSA Summary Three-dimensional quantitative compositional analysis of nanowires is a challenge for standard techniques such as secondary ion mass spectrometry because of specimen size and geometry considerations; however, it is precisely the size and geometry of nanowires that makes them attractive candidates for analysis via atom probe tomography. The resulting boron composition of various trimethylboron vapour,liquid,solid grown silicon nanowires were measured both with time-of-flight secondary ion mass spectrometry and pulsed-laser atom probe tomography. Both characterization techniques yielded similar results for relative composition. Specialized specimen preparation for pulsed-laser atom probe tomography was utilized and is described in detail whereby individual silicon nanowires are first protected, then lifted out, trimmed, and finally wet etched to remove the protective layer for subsequent three-dimensional analysis. [source] Is there a core national doctrine?NATIONS AND NATIONALISM, Issue 2 2001Erica Benner National doctrines are notoriously diverse, and often embody contradictory political values and criteria for membership. This article asks whether there is a ,core' national doctrine that connects republican, cultural, ethnic and liberal concepts of nationality. It considers two attractive candidates: one locating the ,core' in a doctrine about the political and psychological significance of pre-political cultural identities, the other in the constitutional principle of popular sovereignty. After assessing the limitations of both, I sketch a different core national doctrine. This doctrine is constitutive and geopolitical, not constitutional or cultural. It has deep roots in the security concerns specific to the modern, pluralistic system of sovereign states, and prescribes in general terms the form that any community should take in order to survive or distinguish itself in that system. It says very little about the appropriate basis for such communities; the choice of political, cultural, ethnic or even racial criteria is left wide open. More than other versions, this ,core' is able to identify the common ground between cultural, constitutional, and other national doctrines. It also puts a sharp focus on the reasons why, historically, national and liberal values have been so hard to combine. [source] High-performance nanoparticle-enhanced tunnel junctions for photonic devicesPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 10 2010Adam M. Crook Abstract We describe GaAs-based tunnel junctions that are compatible with photonic devices, including long-wavelength vertical-cavity surface-emitting lasers and multi-junction solar cells. Tunneling was enhanced with semimetallic ErAs nanoparticles, particularly when grown at reduced substrate temperatures. Additionally, we present the first direct measurement of the quality of III-V layers grown above ErAs nanoparticles. Photoluminescence measurements indicate that III-V material quality does not degrade when grown above ErAs nanoparticles, despite the mismatch in crystal structures. These findings validate these tunnel junctions as attractive candidates for GaAs-based photonic devices (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] | ||||||||||||||||||||||