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Novel Strategy (novel + strategy)
Selected AbstractsMetallotherapeutics: Novel Strategies in Drug DesignCHEMISTRY - A EUROPEAN JOURNAL, Issue 35 2009Lalintip Hocharoen Abstract A new paradigm for drug activity is presented, which includes both recognition and subsequent irreversible inactivation of therapeutic targets. Application to both RNA and protein biomolecules has been demonstrated. In contrast to RNA targets that are subject to strand scission chemistry mediated by ribose H-atom abstraction, proteins appear to be inactivated either through oxidative damage to amino acid side chains around the enzyme active site, or by backbone hydrolysis. [source] RGB Emission through Controlled Donor Self-Assembly and Modulation of Excitation Energy Transfer: A Novel Strategy to White-Light-Emitting OrganogelsADVANCED MATERIALS, Issue 20 2009Chakkooth Vijayakumar A white-light-emitting organogel is designed by the controlled self-assembly of a bischolesterol-functionalized OPV donor that allows slow energy migration and partial energy transfer in the gel state to an encapsulated acceptor. The white-light emission occurs because of the combination of blue-light emission from the OPV monomers, green-light emission from the OPV self-assembly, and red-light emission from the acceptor. [source] A Novel Strategy for the Construction of Functionalized 1,5- Benzodiazepines via a Tandem Conjugated Addition/Cyclization ProcessADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 2-3 2010Jian Li Abstract A novel approach for the synthesis of functionalized 1,5-benzodiazepine is described. The protocol is triggered by a tandem conjugated addition/cyclization process from the readily available starting materials 1,2-phenylenediamine and ethyl propiolate. The products have secondary amino and ester groups, and a ,-enamino ester, which can serve in further functionalizations to produce molecular diversity. [source] A Novel Strategy to Synthesize Double Comb-Shaped Water Soluble Copolymer by RAFT PolymerizationMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 9 2006De-Hui Han Abstract Summary: A double comb-shaped water soluble copolymer, poly[poly(ethylene oxide) methyl ether methacrylate]- block -poly(N -isopropylacrylamide)- block -poly[poly (ethylene oxide) methyl ether methacrylate], abbreviated as [P(MA-MPEO)- block -PNIPAM- block -P(MA-MPEO)], with a controlled molecular weight and narrow polydispersity was successively synthesized using a macromonomer technique. The 60Co , irradiation polymerization of MA-MPEO in the presence of dibenzyl trithiocarbonate (DBTTC) at room temperature afforded a polymer, P(MA-MPEO)-SC(S)S-P(MA-MPEO), which was subsequently used as a macro RAFT agent in the RAFT polymerization of N -isopropylacrylamide, and water soluble double comb-shaped copolymers, P(MA-MPEO)- block -PNIPAM- block -P(MA-MPEO), were successfully obtained. Structure of the double comb-shaped copolymer. [source] Therapy with Nonglycosaminoglycan-Binding Mutant CCL7: A Novel Strategy to Limit Allograft InflammationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010S. Ali Chemokines are immobilized by binding to glycosaminoglycans (GAGs). A non-GAG-binding mutant CCL7 (mtCCL7) was developed that retained its affinity for chemokine receptors. This mtCCL7 induced leukocyte chemotaxis in diffusion gradients but did not stimulate trans-endothelial migration (p < 0.01). Unlike wild-type CCL7, mtCCL7 persisted in the circulation of BALB/c mice for more than 6 h and prevented leukocyte infiltration of skin isografts (p < 0.05). Treatment with mtCCL7 marginally increased the survival of C57BL/6 to BALB/c skin allografts and reduced graft infiltration by CD3+ cells (p < 0.05). Importantly, mtCCL7 promoted long-term (>40 day) graft survival following minor histocompatibility (HY) antigen mismatched C57BL/6 skin transplantation; control grafts were rejected by day 24. Treatment with mtCCL7 produced a significant decrease in the frequency of IFN-, producing donor-reactive splenic T cells, reduced CCR2 expression by circulating leukocytes for 6 h (p < 0.01) and blocked the normal increase in affinity of ,4,1 integrins for VCAM-1 following transient chemokine stimulation. These data suggest that mtCCL7 persists in the circulation and reduces both specific T-cell priming and the capacity of circulating immune cells to respond to GAG-bound chemokine at sites of developing inflammation. [source] Novel Strategy to Engineer Trachea Cartilage Graft With Marrow Mesenchymal Stem Cell Macroaggregate and Hydrolyzable ScaffoldARTIFICIAL ORGANS, Issue 5 2010Liangqi Liu Abstract Limited donor sites of cartilage and dedifferentiation of chondrocytes during expansion, low tissue reconstruction efficiency, and uncontrollable immune reactions to foreign materials are the main obstacles to overcome before cartilage tissue engineering can be widely used in the clinic. In the current study, we developed a novel strategy to fabricate tissue-engineered trachea cartilage grafts using marrow mesenchymal stem cell (MSC) macroaggregates and hydrolyzable scaffold of polylactic acid,polyglycolic acid copolymer (PLGA). Rabbit MSCs were continuously cultured to prepare macroaggregates in sheet form. The macroaggregates were studied for their potential for chondrogenesis. The macroaggregates were wrapped against the PLGA scaffold to make a tubular composite. The composites were incubated in spinner flasks for 4 weeks to fabricate trachea cartilage grafts. Histological observation and polymerase chain reaction array showed that MSC macroaggregates could obtain the optimal chondrogenic capacity under the induction of transforming growth factor-,. Engineered trachea cartilage consisted of evenly spaced lacunae embedded in a matrix rich in proteoglycans. PLGA scaffold degraded totally during in vitro incubation and the engineered cartilage graft was composed of autologous tissue. Based on this novel, MSC macroaggregate and hydrolyzable scaffold composite strategy, ready-to-implant autologous trachea cartilage grafts could be successfully fabricated. The strategy also had the advantages of high efficiency in cell seeding and tissue regeneration, and could possibly be used in future in vivo experiments. [source] ChemInform Abstract: Nitrone Cycloaddition to Quinones: A Novel Strategy for the Synthesis of Benzisoxazolidenes.CHEMINFORM, Issue 35 2010Rony Rajan Paul Abstract The presented quinone,nitrone reactions are considered as a special case among quinone-1,3-dipole cycloaddition reactions. [source] ChemInform Abstract: Reactions of Morita,Baylis,Hillman Acetates with Huisgen Zwitterions: A Novel Strategy for the Synthesis of ,-Amino Acid Derivatives.CHEMINFORM, Issue 42 2009Anu Jose Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] A Novel Strategy for the Key Fully Substituted Cyclopentenedione Moiety of Madindolines via AlEt3 -promoted Tandem Reductive Rearrangement of ,-Hydroxy EpoxidesCHINESE JOURNAL OF CHEMISTRY, Issue 5 2006Shuan-Hu Gao Abstract The fully substituted cyclopentenedione core of madindoline A (1) and B (2) as potent and selective inhibitor of IL-6 has been synthesized efficiently. The quaternary carbon center C-2, was constructed on the basis of a newly developed AlEt3 -promoted tandem reductive rearrangement of , -hydroxy epoxides. [source] Signal denoising and baseline correction by discrete wavelet transform for microchip capillary electrophoresisELECTROPHORESIS, Issue 18 2003Bi-Feng Liu Abstract Signal denoising and baseline correction using discrete wavelet transform (DWT) are described for microchip capillary electrophoresis (MCE). DWT was performed on an electropherogram describing a separation of nine tetramethylrohodamine-5-isothiocyanate labeled amino acids, following MCE with laser-induced fluorescence detection, using Daubechies 5 wavelet at a decomposition level of 6. The denoising efficiency was compared with, and proved to be superior to, other commonly used denoising techniques such as Fourier transform, Savitzky-Golay smoothing and moving average, in terms of noise removal and peak preservation by directly visual inspection. Novel strategies for baseline correction were proposed, with a special interest in baseline drift that frequently occurred in chromatographic and electrophoretic separations. [source] Novel strategies targeting pathogen transmission reduction in insect vectors: Tsetse-transmitted trypanosomiasis controlENTOMOLOGICAL RESEARCH, Issue 4 2007Brian L. WEISS Abstract Insect vectors are essential for the transmission of important human diseases such as malaria, leishmaniasis, Chagas and sleeping sickness. Insects are also responsible for the transmission of agricultural diseases that affect livestock and crops. Traditionally, control of the vector populations has been an effective disease management strategy. Recently, vector control strategies have been fortified by research in insect biology and in insect,pathogen interactions as well as by the development of transgenic technologies. In addition to insect population reduction methods, disease control via selective elimination of pathogens in insects can now be explored. Here we explore the tsetse vectors of African trypanosomes and describe the application of recent knowledge gained in their symbiotic, reproductive and vectorial biology to develop novel disease control strategies. [source] Therapeutic targets in chronic myeloid leukaemiaHEMATOLOGICAL ONCOLOGY, Issue 2 2007Nicholas B. Heaney Abstract Chronic myeloid leukaemia (CML) is a clonal disorder of the haemopoietic stem cell arising as a consequence of the formation of the bcr-abl oncogene. The particular molecular basis of this condition has enabled the development of therapies that selectively target diseased cells. The success of the rationally designed first-line therapy imatinib mesylate (IM) is tempered by the problems of disease persistence and resistance. Novel strategies have been identified to take forward therapy in CML and these will be discussed in this review. This work is generated from a review of published literature and contains particular insight into the work performed by our group in this field. Copyright © 2007 John Wiley & Sons, Ltd. [source] Germ line transformation of the yellow fever mosquito, Aedes aegypti, mediated by transpositional insertion of a piggyBac vectorINSECT MOLECULAR BIOLOGY, Issue 2 2002N. F. Lobo Mosquito-vectored diseases such as yellow fever and dengue fever continue to have a substantial impact on human populations world-wide. Novel strategies for control of these mosquito vectored diseases can arise through the development of reliable systems for genetic manipulation of the insect vector. A piggyBac vector marked with the Drosophila melanogaster cinnabar (cn) gene was used to transform the white-eyed khw strain of Aedes aegypti. Microinjection of preblastoderm embryos resulted in four families of cinnabar transformed insects. An overall transformation frequency of 4%, with a range of 0% to as high as 13% for individual experiments, was achieved when using a heat-shock induced transposase providing helper plasmid. Southern hybridizations indicated multiple insertion events in three of four transgenic lines, while the presence of duplicated target TTAA sites at either ends of individual insertions confirmed characteristic piggyBac transposition events in these three transgenic lines. The transgenic phenotype has remained stable for more than twenty generations. The transformations effected using the piggyBac element establish the potential of this element as a germ-line transformation vector for Aedine mosquitoes. [source] Novel strategies to approximate probability trees in penniless propagationINTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS, Issue 2 2003Andrés Cano In this article we introduce some modifications over the Penniless propagation algorithm. When a message through the join tree is approximated, the corresponding error is quantified in terms of an improved information measure, which leads to a new way of pruning several values in a probability tree (representing a message) by a single one, computed from the value stored in the tree being pruned but taking into account the message stored in the opposite direction. Also, we have considered the possibility of replacing small probability values by zero. Locally, this is not an optimal approximation strategy, but in Penniless propagation many different local approximations are carried out in order to estimate the posterior probabilities and, as we show in some experiments, replacing by zeros can improve the quality of the final approximations. © 2003 Wiley Periodicals, Inc. [source] Novel strategies to enhance oxygen transport to cultured mammalian cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2009Article first published online: 20 FEB 200 No abstract is available for this article. [source] ROLE OF MACROPHAGES IN COMPLICATIONS OF TYPE 2 DIABETESCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2007GH TeschArticle first published online: 15 AUG 200 SUMMARY 1Macrophage accumulation is a feature of Type 2 diabetes and is associated with the development of diabetic complications (nephropathy, atherosclerosis, neuropathy and retinopathy). The present article reviews the current evidence that macrophages contribute to the complications of Type 2 diabetes. 2Macrophage-depletion studies in rodent models have demonstrated a causal role for macrophages in the development of diabetic complications. 3Components of the diabetic milieu (high glucose, advanced glycation end-products and oxidized low-density lipoprotein) promote macrophage accumulation (via induction of chemokines and adhesion molecules) and macrophage activation within diabetic tissues. 4Macrophages mediate diabetic injury through a variety of mechanisms, including production of reactive oxygen species, cytokines and proteases, which result in tissue damage leading to sclerosis. 5A number of existing and experimental therapies can indirectly reduce macrophage-mediated injury in diabetic complications. The present article discusses the use of these therapies, given alone and in combination, in suppressing macrophage accumulation and activity. 6In conclusion, current evidence supports a critical role for macrophages in the evolution of diabetic complications. Present therapies are limited in slowing the progression of macrophage-mediated injury. Novel strategies that are more specific at targeting macrophages may provide better protection against the development of Type 2 diabetic complications. [source] From segment to somite: Segmentation to epithelialization analyzed within quantitative frameworksDEVELOPMENTAL DYNAMICS, Issue 6 2007Paul M. Kulesa Abstract One of the most visually striking patterns in the early developing embryo is somite segmentation. Somites form as repeated, periodic structures in pairs along nearly the entire caudal vertebrate axis. The morphological process involves short- and long-range signals that drive cell rearrangements and cell shaping to create discrete, epithelialized segments. Key to developing novel strategies to prevent somite birth defects that involve axial bone and skeletal muscle development is understanding how the molecular choreography is coordinated across multiple spatial scales and in a repeating temporal manner. Mathematical models have emerged as useful tools to integrate spatiotemporal data and simulate model mechanisms to provide unique insights into somite pattern formation. In this short review, we present two quantitative frameworks that address the morphogenesis from segment to somite and discuss recent data of segmentation and epithelialization. Developmental Dynamics 236:1392,1402, 2007. © 2007 Wiley-Liss, Inc. [source] The unfolded protein response is required to maintain the integrity of the endoplasmic reticulum, prevent oxidative stress and preserve differentiation in , -cellsDIABETES OBESITY & METABOLISM, Issue 2010R. J. Kaufman Diabetes is an epidemic of worldwide proportions caused by , -cell failure. Nutrient fluctuations and insulin resistance drive , -cells to synthesize insulin beyond their capacity for protein folding and secretion and thereby activate the unfolded protein response (UPR), an adaptive signalling pathway to promote cell survival upon accumulation of unfolded protein in the endoplasmic reticulum (ER). Protein kinase-like endoplasmic reticulum kinase (PERK) signals one component of the UPR through phosphorylation of eukaryotic initiation factor 2 on the , -subunit (eIF2,) to attenuate protein synthesis, thereby reducing the biosynthetic burden. , -Cells uniquely require PERK-mediated phosphorylation of eIF2, to preserve cell function. Unabated protein synthesis in , -cells is sufficient to initiate a cascade of events, including oxidative stress, that are characteristic of , -cell failure observed in type 2 diabetes. In contrast to acute adaptive UPR activation, chronic activation increases expression of the proapoptotic transcription factor CAAT/enhancer-binding protein homologous protein (CHOP). Chop deletion in insulin-resistant mice profoundly increases , -cell mass and prevents , -cell failure to forestall the progression of diabetes. The findings suggest an unprecedented link by which protein synthesis and/or misfolding in the ER causes oxidative stress and should encourage the development of novel strategies to treat diabetes. [source] Amphiphilic block copolymer micelles for nanoscale drug deliveryDRUG DEVELOPMENT RESEARCH, Issue 1 2006Glen S. Kwon Abstract Amphiphilic block copolymers can assemble into supramolecular core-shell structures, termed ABC micelles, that have proven utility in drug delivery, particularly for drug solubilization. Several examples have entered clinical trials, attesting to the biocompatibility of ABCs and the potential advantages for drug delivery, e.g., low toxicity relative to Cremophor® EL, a surfactant commonly used for drug solubilization. Several examples of ABC micelles demonstrate potential for prolonged circulation in blood. Coupled with novel strategies toward controlled release of drug, nanoscale ABC micelles have tremendous potential for the targeting of antitumor agents, many of which are poorly water soluble and possess dose-limiting toxicity. Drug Dev. Res. 67:15,22, 2006. © 2006 Wiley-Liss, Inc. [source] Novel Bonding Modes between Tetrathiafulvalenes (TTFs) and Transition Metal Centers: ,-Bonding and Covalent TTFSiMe2,MLn Coordination to PlatinumEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 13 2004Mathuresh N. Jayaswal Abstract Two novel strategies for coordinating TTF to transition metal centers have been developed. The reaction of tetrathiafulvalene (TTF) or 3,4-dimethyltetrathiafulvalene (o -Me2TTF) with [Pt(,2 -C2H4)(PPh3)2] leads to the , complexes [Pt(,2 -TTF)(PPh3)2] (1) and [Pt(,2 - o -Me2TTF)(PPh3)2] (2), respectively. An X-ray crystallographic study performed on 2 confirmed, that TTFs act as a , acidic ligand. NMR studies revealed the existence, in solution, of an equilibrium between free and complexed TTF. Dilithiation of o -Me2TTF and subsequent silylation with ClSiMe2H afforded 3,4-dimethyl-3,,4,-(dimethylsilyl)tetrathiafulvalene (3), which has been structurally characterized. 3 reacts by oxidative addition across [Pt(,2 -C2H4)(PPh3)2] to give [Pt{,2 - o -(SiMe2)2TTFMe2}(PPh3)2] (4), in which the TTF ligand is covalently ligated to platinum via SiMe2 bridges. The redox properties of 3 and 4 have been investigated by cyclic voltammetry. Strong cathodic shifts of the two redox processes were observed for 4, implying the TTF core. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Intrinsic Surface Dipoles Control the Energy Levels of Conjugated PolymersADVANCED FUNCTIONAL MATERIALS, Issue 24 2009Georg Heimel Abstract Conjugated polymers are an important class of materials for organic electronics applications. There, the relative alignment of the electronic energy levels at ubiquitous organic/(in)organic interfaces is known to crucially impact device performance. On the prototypical example of poly(3-hexylthiophene) and a fluorinated derivative, the energies of the ionization and affinity levels of , -conjugated polymers are revealed to critically depend on the orientation of the polymer backbones with respect to such interfaces. Based on extensive first-principles calculations, an intuitive electrostatic model is developed that quantitatively traces these observations back to intrinsic intramolecular surface dipoles arising from the , -electron system and intramolecular polar bonds. The results shed new light on the working principles of organic electronic devices and suggest novel strategies for materials design. [source] The screening of the second-site suppressor mutations of the common p53 mutantsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Kazunori Otsuka Abstract Second-site suppressor (SSS) mutations in p53 found by random mutagenesis have shown to restore the inactivated function of some tumor-derived p53. To screen novel SSS mutations against common mutant p53s, intragenic second-site (SS) mutations were introduced into mutant p53 cDNA in a comprehensive manner by using a p53 missense mutation library. The resulting mutant p53s with background and SS mutations were assayed for their ability to restore the p53 transactivation function in both yeast and human cell systems. We identified 12 novel SSS mutations including H178Y against a common mutation G245S. Surprisingly, the G245S phenotype is rescued when coexpressed with p53 bearing the H178Y mutation. This result indicated that there is a possibility that intragenic suppressor mutations might restore the protein function in an intermolecular manner. The intermolecular mechanism may lead to novel strategies for restoring inactivated p53 function and tumor suppression in cancer treatment. © 2007 Wiley-Liss, Inc. [source] Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian populationINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Francesco Graziano Abstract We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) and gastric cancer susceptibility in at-risk populations in central Italy. To explore genomic DNA hypomethylation as a potential etiologic mechanism, this phenomenon was evaluated in carriers of the MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T genotyping. Unconditional regression analysis with ORs and 95% CIs was used to investigate the association of the polymorphism with disease. Genomic DNA methylation status by an established enzymatic assay that measures the DNA accepting capacity of methyl groups (inversely related to endogenous methylation) was assessed in a random sample of 40 carriers of the wild-type MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48,4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52,5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention. © 2005 Wiley-Liss, Inc. [source] Identification of therapeutically relevant mHags and strategies for mHag-based immunotherapy after allogeneic HSCT: where do we stand?ISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue n1 2010B. Eiz-Vesper Minor histocompatibility antigens (mHags) play a major role in graft-versus-host disease (GvHD) and graft-versus-leukaemia (GvL) effect following human leucocyte antigen (HLA)-matched hematopoietic stem cell transplantation (HSCT). These antigens are defined as immunogenic peptides derived from polymorphic proteins and can be recognized by allogeneic cytotoxic T cells (CTLs) in the context of HLA molecules. The tissue distribution of mHags and HLA molecules influences the clinical outcome of T-cell responses to these antigens. Differential T-cell recognition of mHags specifically expressed in hematopoietic cells, including malignant cells from the recipient, may result in a beneficial GvL effect without detrimental GvHD. Furthermore, T-cell responses against proteins solely expressed in hematopoietic cell lineages from which the malignancy is derived may be appropriate mediators of GvL reactivity without GvHD induction. mHags with hematopoiesis-restricted expression may therefore serve as primary targets of the T-cell-mediated GvL/graft-versus-tumour (GvT) effect following HLA-identical HSCT. This paper reviews the recent findings on methods for identification of mHags specifically functioning as GvL/GvT targets and outlines perspectives for the development of novel strategies for mHag-based immunotherapy. [source] Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's sarcoma: Bidirectional translational scienceJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006Bruce J. Dezube Through the mentorship process, Dr. Arthur Pardee emphasized the critical importance of bidirectional translational research,not only advancing drug development from bench to bedside, but also bringing back precious clinical material to the laboratory to assess the biologic effects of therapeutic agents on their targets. This mini-review focuses on the signal transduction pathways of Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the rational development of molecularly targeted pathogenesis-driven therapies. Acquired immune deficiency syndrome (AIDS) related-KS results from co-infection with human immunodeficiency virus and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8), which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of KS. KS is driven by KSHV/HHV8-specific pathways, which include viral G protein-coupled receptor (vGPCR), viral interleukin-6 (vIL-6), and viral chemokine homologues. In addition, cellular growth/angiogenic pathways, such as vascular endothelial growth factor (VEGF), insulin-like growth factor, platelet-derived growth factor (PDGF), angiopoietin and matrix metalloproteinases (MMPs) are "pirated" by KSHV/HHV8. As a very tangible example of how translational research has led to a marked improvement in patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors were serially biopsied. Not only did the patients' tumors regress, but also the regression was correlated with the inhibition of PDGF receptor (PDGFR) in the biopsy samples. Recent and future clinical trials of molecularly targeted therapy for the treatment of KS are a prelude to a shift in the paradigm of how KS is managed. J. Cell. Physiol. 209: 659,662, 2006. © 2006 Wiley-Liss, Inc. [source] Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damageJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2009Yun Jeong Lim Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide, which attests to their efficacy as analgesic, antipyretic and anti-inflammatory agents as well as anticancer drugs. However, NSAID use also carries a risk of major gastroduodenal events, including symptomatic ulcers and their serious complications that can lead to fatal outcomes. The development of "coxibs" (selective cyclooxygenase-2 [COX-2] inhibitors) offered similar efficacy with reduced toxicity, but this promise of gastroduodenal safety has only partially been fulfilled, and is now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID-induced gastroduodenal damage beyond COX-2 inhibition. The emergence of newer kinds of NSAIDs should alleviate gastroduodenal toxicity without compromising innate drug efficacy. In this review, novel strategies for avoiding NSAID-associated gastroduodenal damage will be described. [source] Efficient optimization strategies with constraint programming,AICHE JOURNAL, Issue 2 2010Prakash R. Kotecha Abstract In this article, we propose novel strategies for the efficient determination of multiple solutions for a single objective, as well as globally optimal pareto fronts for multiobjective, optimization problems using Constraint Programming (CP). In particular, we propose strategies to determine, (i) all the multiple (globally) optimal solutions of a single objective optimization problem, (ii) K -best feasible solutions of a single objective optimization problem, and (iii) globally optimal pareto fronts (including nonconvex pareto fronts) along with their multiple realizations for multiobjective optimization problems. It is shown here that the proposed strategy for determining K -best feasible solutions can be tuned as per the requirement of the user to determine either K -best distinct or nondistinct solutions. Similarly, the strategy for determining globally optimal pareto fronts can also be modified as per the requirement of the user to determine either only the distinct set of pareto points or determine the pareto points along with all their multiple realizations. All the proposed techniques involve appropriately modifying the search techniques and are shown to be computationally efficient in terms of not requiring successive re-solving of the problem to obtain the required solutions. This work therefore convincingly addresses the issue of efficiently determining globally optimal pareto fronts; in addition, it also guarantees the determination of all the possible realizations associated with each pareto point. The uncovering of such solutions can greatly aid the designer in making informed decisions. The proposed approaches are demonstrated via two case studies, which are nonlinear, combinatorial optimization problems, taken from the area of sensor network design. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Effect of dynamic loading on solute transport in soft gels implication for drug deliveryAICHE JOURNAL, Issue 3 2008F. Urciuolo Abstract Solute transport through soft gels and tissues is intimately coupled to mechanical stress and deformation of the macromolecular network. The aim of this study was to investigate the effect of periodic mechanical stimuli upon solute transport through agarose gels at different concentrations. For this purpose it was experimentally evaluated the materials parameters that govern the coupling between elasto-dynamic and solute transport: hydraulic conductivity (K), elastic modulus (HA), and macromolecular diffusivity (Dg) along with their strain dependence behavior. Mechanical activated solute transport simulation was carried out in order to elucidate the role of amplitude and frequency of soliciting mechanical stimuli on mass kinetics release. Results show that mechanical loading affects the release of macromolecules from a gel in a frequency and strain dependent manner. These findings pave the way for novel strategies for the design and engineering of smart drug delivery devices with transport mechanisms triggered by mechanical stimuli. © 2008 American Institute of Chemical Engineers AIChE J, 2008 [source] EARLY INITIATION OF PHOSPHATE LOWERING DIETARY THERAPY IN NON-DIALYSIS CHRONIC KIDNEY DISEASE: A CRITICAL REVIEWJOURNAL OF RENAL CARE, Issue 2009M.K. Sigrist SUMMARY Dietary management of hyperphosphatemia and hyperparathyroidism have long been important elements in the clinical management of CKD stage 4 and 5 for the prevention of mineral bone disease. The rationale for phosphate lowering has been further justified, given the accumulating data to support the association of phosphate with vascular damage, in this population who are at high risk of cardiovascular (CV) death. Phosphate is a novel CV risk factor in both CKD and in the general population, and a growing body of literature suggests that high normal serum phosphate may be a risk factor for progression of CKD. Few studies have examined hard outcomes after phosphate lowering. Nonetheless, given the balance of data both in cell, animal and human studies, the use of phosphate lowering strategies at earlier stages of CKD, perhaps even prior to serum phosphate level rising, may well be justified. This review will discuss the complications associated with higher serum phosphate, the potential benefits of early phosphate intervention, practical considerations of low phosphate diets and novel strategies for evaluating these strategies in clinical practice. [source] Developments in Oxide Fiber CompositesJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 11 2006Frank W. Zok Prospects for revolutionary design of future power generation systems are contingent on the development of durable high-performance ceramic composites. With recent discoveries in materials and manufacturing concepts, composites with all-oxide constituents have emerged as leading candidates, especially for components requiring a long service life in oxidizing environments. Their insertion into engineering systems is imminent. The intent of this article is to present a synopsis of the current understanding of oxide composites as well as to identify outstanding issues that require resolution for successful implementation. Emphasis is directed toward material systems and microstructural concepts that lead to high toughness and long-term durability. These include: the emergence of La monazite and related compounds as fiber-coating materials, the introduction of the porous-matrix concept as an alternative to fiber coatings, and novel strategies for enabling damage tolerance while retaining long-term morphological stability. Additionally, materials and mechanics models that provide insights into material design, morphology evolution, and composite properties are reviewed. [source] | ||||||||||||||||||||||||||||||||||||||||||||||