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Minimal Number (minimal + number)
Selected AbstractsUsing Phylogenetic Diversity Measures to Set Priorities in Conservation: an Example from Southern South AmericaCONSERVATION BIOLOGY, Issue 5 2001Paula Posadas The goal of these ranks for conservation is to consider as many factors as possible that provide additional taxic information, such as taxa richness, taxa distributional patterns, area endemicity, and complementarity between areas. At present there are many measures that consider phylogenetic information, including node-based, genetic-distance, and feature-based measures. We devised a modified phylogenetic node-based index that we call "taxonomic endemicity standardized weight," which considers not only the taxonomic distinctness of the taxa that inhabit a given area but their endemicity as well. Once the standardized weight of the taxonomic endemicity identifies the area of highest priority, complementarity can be used to identify the second area and so on. We used this node-based index to rank priority areas for conservation in southern South America, and we compared the results of our rankings to results based on other node-based indexes. Our index identified Santiago district, in Central Chile province, as the highest priority area for conservation, followed by Maule, Malvinas, and districts of Subantarctic province. Malvinas exhibits greater complementarity relative to Santiago than Maule does, however, so Malvinas is ranked second in priority. Indexes based on phylogenetic information measure the evolutionary component of biodiversity and allow one to identify areas that will ensure the preservation of evolutionary potential and phylogenetically rare taxa. The modified index we propose is sensitive to taxic distinctness and endemicity as well and allows information from diverse taxa to be combined (i.e., different cladograms). The use of complementarity allows for preservation of the maximum quantity of taxa in a minimal number of protected areas. Resumen: Las medidas de diversidad filogenética jerarquiza a las áreas para prioridades de conservación de biodiversidad con base en información codificada en filogenias (cladogramas), La meta de estas categorías de conservación requiere tomar en consideración tantos factores que proporcionan información adicional (riqueza de taxones, patrones de distribución de los taxones, endemicidad del área y complementariedad entre áreas) como sea posible. Actualmente hay muchas medidas que consideran información filogenética (basadas en nodos, distancia genética y basadas en características). Diseñamos un índice filogenético modificado basado en nodos que denominamos "peso estandarizado de endemicidad taxonómica", el cual considera no solo la peculiaridad genética de los taxa que habitan una región determinada sino también su endemicidad. Una vez que el peso estandarizado de endemicidad identifica el área de mayor prioridad, la complementariedad se puede usar para identificar la segunda área y así sucesivamente. Utilizamos este índice basado en nodos para jerarquizar áreas prioritarias para conservación en el sur de América del Sur, y comparamos los resultados de nuestras jerarquizaciones con resultados obtenidos con otros índices basados en nodos. Nuestro índice identificó al distrito de Santiago, en la provincia de Chile Central, como el área de mayor prioridad para conservación, seguido por Maule, Malvinas y distritos de la provincia Subantártica. Sin embargo, Malvinas presenta mayor complementariedad en relación con Santiago que el Maule y, por tanto, Malvinas ocupa la segunda prioridad. Los índices basados en información filogenética miden el componente evolutivo de la biodiversidad y permiten la identificación de áreas que aseguran la preservación de taxones con potencial evolutivo y filogenéticamente peculiares. El índice modificado que proponemos es sensible tanto a la peculiaridad de los taxones como a la endemicidad y permite combinar información de diversos taxones (i.e. cladogramas diferentes). El uso de la complementariedad permite la preservación de la mayor cantidad de taxones en un número mínimo de áreas protegidas. [source] A minimalist approach to the effects of density-dependent competition on insect life-history traitsECOLOGICAL ENTOMOLOGY, Issue 4 2002Philip Agnew Abstract ,1. Due to its effects on the phenotypic and genotypic expression of life-history traits, density-dependent competition is an important factor regulating the growth of populations. Specifically for insects, density-dependent competition among juveniles is often associated with increased juvenile mortality, delayed maturity, and reduced adult size. 2. The aim of the work reported here was to test whether the established phenotypic effects of density-dependent competition on life-history traits could be reproduced in an experimental design requiring a minimal number of individuals. Larvae of the mosquito Aedes aegypti were reared at densities of one, two, or three individuals per standard Drosophila vial and in six different conditions of larval food availability. This design required relatively few individuals per independent replicate and included a control treatment where individuals reared at a density of one larva per vial experienced no density-dependent interactions with other larvae. 3. Increased larval densities or reduced food availability led to increased larval mortality, delayed pupation, and the emergence of smaller adults that starved to death in a shorter time (indicating emergence with fewer nutritional reserves). 4. Female mosquitoes were relatively larger than males (as measured by wing length) but males tended to survive for longer. These differences increased as larval food availability increased, indicating the relative importance of these two traits for the fitness of each sex. The role of nutritional reserves for the reproductive success of males was highlighted in particular. 5. This minimalist approach may provide a useful model for investigating the effects of density-dependent competition on insect life-history traits. [source] Analysis of single-locus tests to detect gene/disease associations,GENETIC EPIDEMIOLOGY, Issue 3 2005Kathryn Roeder Abstract A goal of association analysis is to determine whether variation in a particular candidate region or gene is associated with liability to complex disease. To evaluate such candidates, ubiquitous Single Nucleotide Polymorphisms (SNPs) are useful. It is critical, however, to select a set of SNPs that are in substantial linkage disequilibrium (LD) with all other polymorphisms in the region. Whether there is an ideal statistical framework to test such a set of ,tag SNPs' for association is unknown. Compared to tests for association based on frequencies of haplotypes, recent evidence suggests tests for association based on linear combinations of the tag SNPs (Hotelling T2 test) are more powerful. Following this logical progression, we wondered if single-locus tests would prove generally more powerful than the regression-based tests? We answer this question by investigating four inferential procedures: the maximum of a series of test statistics corrected for multiple testing by the Bonferroni procedure, TB, or by permutation of case-control status, TP; a procedure that tests the maximum of a smoothed curve fitted to the series of of test statistics, TS; and the Hotelling T2 procedure, which we call TR. These procedures are evaluated by simulating data like that from human populations, including realistic levels of LD and realistic effects of alleles conferring liability to disease. We find that power depends on the correlation structure of SNPs within a gene, the density of tag SNPs, and the placement of the liability allele. The clearest pattern emerges between power and the number of SNPs selected. When a large fraction of the SNPs within a gene are tested, and multiple SNPs are highly correlated with the liability allele, TS has better power. Using a SNP selection scheme that optimizes power but also requires a substantial number of SNPs to be genotyped (roughly 10,20 SNPs per gene), power of TP is generally superior to that for the other procedures, including TR. Finally, when a SNP selection procedure that targets a minimal number of SNPs per gene is applied, the average performances of TP and TR are indistinguishable. Genet. Epidemiol. © 2005 Wiley-Liss, Inc. [source] c-Type method of unified CAMG and FEA.INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 9 20032D non-linear, 3D linear, Part 1: Beam, arch mega-elements Abstract Computer-aided mesh generation (CAMG) dictated solely by the minimal key set of requirements of geometry, material, loading and support condition can produce ,mega-sized', arbitrary-shaped distorted elements. However, this may result in substantial cost saving and reduced bookkeeping for the subsequent finite element analysis (FEA) and reduced engineering manpower requirement for final quality assurance. A method, denoted as c-type, has been proposed by constructively defining a finite element space whereby the above hurdles may be overcome with a minimal number of hyper-sized elements. Bezier (and de Boor) control vectors are used as the generalized displacements and the Bernstein polynomials (and B-splines) as the elemental basis functions. A concomitant idea of coerced parametry and inter-element continuity on demand unifies modelling and finite element method. The c-type method may introduce additional control, namely, an inter-element continuity condition to the existing h-type and p-type methods. Adaptation of the c-type method to existing commercial and general-purpose computer programs based on a conventional displacement-based finite element method is straightforward. The c-type method with associated subdivision technique can be easily made into a hierarchic adaptive computer method with a suitable a posteriori error analysis. In this context, a summary of a geometrically exact non-linear formulation for the two-dimensional curved beams/arches is presented. Several beam problems ranging from truly three-dimensional tortuous linear curved beams to geometrically extremely non-linear two-dimensional arches are solved to establish numerical efficiency of the method. Incremental Lagrangian curvilinear formulation may be extended to overcome rotational singularity in 3D geometric non-linearity and to treat general material non-linearity. Copyright © 2003 John Wiley & Sons, Ltd. [source] Dynamic power management in new architecture of wireless sensor networksINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 6 2009Chuan Lin Abstract Dynamic power management (DPM) technology has been widely used in sensor networks. Though many specific technical challenges remain and deserve much further study, the primary factor currently limiting progress in sensor networks is not these challenges but is instead the lack of an overall sensor network architecture. In this paper, we first develop a new architecture of sensor networks. Then we modify the sleep state policy developed by Sinha and Chandrakasan in (IEEE Design Test Comput. 2001; 18(2):62,74) and deduce that a new threshold satisfies the sleep-state transition policy. Under this new architecture, nodes in deeper sleep states consume lower energy while asleep, but require longer delays and higher latency costs to awaken. Implementing DPM with considering the battery status and probability of event generation will reduce the energy consumption and prolong the whole lifetime of the sensor networks. We also propose a new energy-efficient DPM, which is a modified sleep state policy and combined with optimal geographical density control (OGDC) (Wireless Ad Hoc Sensor Networks 2005; 1(1,2):89,123) to keep a minimal number of sensor nodes in the active mode in wireless sensor networks. Implementing dynamic power management with considering the battery status, probability of event generation and OGDC will reduce the energy consumption and prolong the whole lifetime of the sensor networks. Copyright © 2008 John Wiley & Sons, Ltd. [source] GPSPA: a new adaptive algorithm for maintaining shortest path routing trees in stochastic networksINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 10 2004Sudip Misra Abstract This paper presents a new efficient solution to the Dynamic Shortest Path Routing Problem, using the principles of Generalized Pursuit Learning. It proposes an efficient algorithm for maintaining shortest path routing trees in networks that undergo stochastic updates in their structure. It involves finding the shortest path in a stochastic network, where there are continuous probabilistically based updates in link-costs. In vast, rapidly changing telecommunications (wired or wireless) networks, where links go up and down continuously and rapidly, and where there are simultaneous random updates in link costs, the existing algorithms are inefficient. In such cases, shortest paths need to be computed within a very short time (often in the order of microseconds) by scanning and processing the minimal number of nodes and links. The proposed algorithm, referred to as the Generalized Pursuit Shortest Path Algorithm (GPSPA), will be very useful in this regard, because after convergence, it seems to be the best algorithm to-date for this purpose. Indeed, it has the advantage that it can be used to find the shortest path within the ,statistical' average network, which converges irrespective of whether there are new changes in link-costs or not. Existing algorithms are not characterized by such a behaviour inasmuch as they would recalculate the affected shortest paths after each link-cost update. The algorithm has been rigorously evaluated experimentally, and it has been found to be a few orders of magnitude superior to the algorithms available in the literature. Copyright © 2004 John Wiley & Sons, Ltd. [source] The pure parsimony haplotyping problem: overview and computational advancesINTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 5 2009Daniele Catanzaro Abstract Haplotyping estimation from aligned single-nucleotide polymorphism fragments has attracted more and more attention in recent years due to its importance in analysis of many fine-scale genetic data. Its application fields range from mapping of complex disease genes to inferring population histories, passing through designing drugs, functional genomics, and pharmacogenetics. The literature proposes a number of estimation criteria to select a set of haplotypes among possible alternatives. Usually, such criteria can be expressed under the form of objective functions, and the sets of haplotypes that optimize them are referred to as optimal. One of the most important estimation criteria is the pure parsimony, which states that the optimal set of haplotypes for a given set of genotypes is that having minimal cardinality. Finding the minimal number of haplotypes necessary to explain a given set of genotypes involves solving an optimization problem, called the pure parsimony haplotyping (PPH) estimation problem, which is notoriously -hard. This article provides an overview of PPH, and discusses the different approaches to solution that occur in the literature. [source] Protein folding simulations: From coarse-grained model to all-atom modelIUBMB LIFE, Issue 6 2009Jian Zhang Abstract Protein folding is an important and challenging problem in molecular biology. During the last two decades, molecular dynamics (MD) simulation has proved to be a paramount tool and was widely used to study protein structures, folding kinetics and thermodynamics, and structure,stability,function relationship. It was also used to help engineering and designing new proteins, and to answer even more general questions such as the minimal number of amino acid or the evolution principle of protein families. Nowadays, the MD simulation is still undergoing rapid developments. The first trend is to toward developing new coarse-grained models and studying larger and more complex molecular systems such as protein,protein complex and their assembling process, amyloid related aggregations, and structure and motion of chaperons, motors, channels and virus capsides; the second trend is toward building high resolution models and explore more detailed and accurate pictures of protein folding and the associated processes, such as the coordination bond or disulfide bond involved folding, the polarization, charge transfer and protonate/deprotonate process involved in metal coupled folding, and the ion permeation and its coupling with the kinetics of channels. On these new territories, MD simulations have given many promising results and will continue to offer exciting views. Here, we review several new subjects investigated by using MD simulations as well as the corresponding developments of appropriate protein models. These include but are not limited to the attempt to go beyond the topology based G,-like model and characterize the energetic factors in protein structures and dynamics, the study of the thermodynamics and kinetics of disulfide bond involved protein folding, the modeling of the interactions between chaperonin and the encapsulated protein and the protein folding under this circumstance, the effort to clarify the important yet still elusive folding mechanism of protein BBL, the development of discrete MD and its application in studying the ,,, conformational conversion and oligomer assembling process, and the modeling of metal ion involved protein folding. © 2009 IUBMB IUBMB Life, 61(6): 627,643, 2009 [source] Gastrointestinal foreign bodies in dogs and cats: a retrospective study of 208 casesJOURNAL OF SMALL ANIMAL PRACTICE, Issue 11 2009G. Hayes Objectives:To establish predilection sites of obstruction and to investigate clinical factors associated with a poor outcome. Methods:A retrospective study of 208 consecutive cases over a 48-month period from first-opinion practice. Results:Overall, 91 per cent of cases recovered with higher survival rates from discrete foreign bodies (94 per cent in dogs and 100 per cent in cats) as opposed to linear foreign bodies (80 per cent in dogs and 63 per cent in cats). English bull terriers, springer spaniels, Staffordshire bull terriers, Border collies and Jack Russell terriers were over-represented. In dogs, 63 per cent of obstructions occurred in the jejunum but foreign objects were encountered at all points along the gastrointestinal tract. A longer duration of clinical signs, the presence of a linear foreign body and multiple intestinal procedures were associated with significantly increased mortality. Neither the degree of obstruction (partial or complete) nor the location of the foreign body was shown to have a significant influence on survival. Clinical Significance:Prompt presentation, diagnosis and surgical intervention improve the outcome of gastrointestinal obstruction by foreign bodies. At surgery, the minimal number of intestinal procedures should be performed to restore the integrity of the alimentary tract. [source] Toward mechanistic elucidation of iron acquisition in barley: efficient synthesis of mugineic acids and their transport activitiesTHE CHEMICAL RECORD, Issue 2 2010Kosuke Namba Iron acquisition of graminaceous plants is characterized by the synthesis and secretion of iron-chelating compounds, mugineic acids (MAs), and by a specific uptake system for MAs-iron(III) complexes. We identified a transporter, HvYS1 (Hordeum vulgare L. yellow stripe 1), that is highly specific for MAs-iron(III) in barley roots. In this article we outline the characterization of HvYS1, and our recent work on the practical syntheses of MAs and investigations into the molecular basis of the specific transport of their iron(III) complexes by HvYS1. 2,-Deoxymugineic acid (DMA) was synthesized in a good overall yield from commercially available Boc-l-allylglycine using a minimal number of short simple operations with minimal protecting groups and work-up/purification procedures. The same strategy was also successfully applied to , -hydroxy-l-allylglycine, which was obtained by an allylic oxidation of l-allylglycine derivatives, to give MA and 2,-epi-MA efficiently. HvYS1 transported the iron(III) complexes of all three synthetic specimens with efficiency similar to that of a natural mugineic acid complex. With sufficient quantities of MAs in hand, we analyzed the function of HvYS1 and revealed by preparing chimeric transporters that the sixth outer membrane loop of the transporter plays a vital role in substrate specificity. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 10: 140,150; 2010: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.200900028 [source] Changes of Circulating Antibody Levels Induced by ABO Antibody Adsorption for ABO-Incompatible Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009P. V. Valli ABO-incompatible kidney transplantation using immunoadsorption to remove anti-A/B antibodies has become a successful clinical practice. Since the data on the specificity of the ABO columns are controversial, the present study assessed the efficiency and specificity of the ABO immunoadsorption, the effect on total immunoglobulins and antibodies previously induced by vaccination. Anti-A/B antibodies were measured by agglutination and ABO flow cytometry, total IgG/IgM, carbohydrate- and protein-specific antibodies by nephelometry and ELISA. The first immunoadsorption not only efficiently reduced donor-specific anti-A/B IgM (81%) and IgG (56%) but also reduced compatible anti-A/B IgM (59%) and IgG (34%). The measurements of antidonor A/B antibodies by direct agglutination (IgM) or flow cytometry better represented the effective antibody levels than the indirect agglutination test (IgG). The median reduction of total IgM and total IgG levels after a single immunoadsorption was 34% and 18%, respectively. Antibodies against pneumococcus and haemophilus polysaccharide antigens were significantly reduced, whereas antitetanus and antidiphtheria protein antibodies were not affected. Intravenous immunoglobulin administration restored the protective anticarbohydrate antibody levels. In summary, immunoadsorption efficiently removed antidonor A/B antibodies, but was not specific for A/B antigens. Anti-A/B antibody levels as determined by ABO flow cytometry are useful to establish the minimal number of immunoadsorptions needed for successful ABO-incompatible transplantation. [source] Rigidity and persistence for ensuring shape maintenance of multi-agent meta-formations,ASIAN JOURNAL OF CONTROL, Issue 2 2008Julien M. Hendrickx Abstract This paper treats the problem of merging formations, where the underlying model of a formation is graphical. We first analyze the rigidity and persistence of meta-formations, which are formations obtained by connecting several rigid or persistent formations. Persistence is a generalization to directed graphs of the undirected notion of rigidity. In the context of moving autonomous agent formations, persistence characterizes the efficacy of a directed structure of unilateral distance constraints seeking to preserve a formation shape. We derive then, for agents evolving in a two- or three-dimensional space, the conditions under which a set of persistent formations can be merged into a persistent meta-formation, and give the minimal number of interconnections needed for such a merging. We also give conditions for a meta-formation obtained by merging several persistent formations to be persistent. Copyright © 2008 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society [source] Development of a simultaneous liquid,liquid extraction and chiral derivatization method for stereospecific GC-MS analysis of amphetamine-type stimulants in human urine using fractional factorial designBIOMEDICAL CHROMATOGRAPHY, Issue 9 2008W. R. Wan Aasim Abstract A stereospecific gas chromatography,mass spectrometry analysis method for amphetamine-type stimulants in human urine was recently developed. For maximum efficiency, liquid,liquid extraction and chiral derivatization of the analytes using (R)-(,)- , -methoxy- , -(trifluoromethyl)phenylacetyl chloride were performed simultaneously. The effects of (1) use of saturated sodium chloride in 2.0 m sodium hydroxide, (2) extraction solvent volume, (3) percentage of triethylamine, (4) derivatization reagent volume, (5) sample mixing time, (6) incubation temperature and (7) incubation time on method sensitivity and variability were assessed using a two-level, eight-run Plackett,Burman design followed by a fold-over design. The use of saturated sodium chloride solution and the derivatization reagent volume were significant factors (ANOVA, p < 0.01). The saturated sodium chloride solution decreased sensitivity whereas an increased volume of derivatization reagent increased sensitivity. Calibration curves for all analytes were linear between 5 and 500 µg/L, with correlation coefficients of >0.99. Detection limits were ,2.3 µg/L and quantitation limits ,7.7 µg/L. Reproducibility was good, with relative standard deviation values at <20%. Recovery exceeded 100% for most analytes. The experimental design enabled easy and rapid identification of significant factors using a minimal number of samples. This method has good potential for studies requiring rapid and sensitive stereospecific quantification of amphetamine-type stimulants. Copyright © 2008 John Wiley & Sons, Ltd. [source] Microbioreactor array for full-factorial analysis of provision of multiple soluble factors in cellular microenvironmentsBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2009Drew Titmarsh Abstract We report a scalable microbioreactor architecture which uses nested dilution structures to generate a full-factorial array of cell culture conditions. The proof-of-concept microbioreactor array produces all combinations of three concentration levels of two soluble factors (32,=,9 unique conditions in total). The full-factorial design is especially useful in optimizing soluble factor treatments and elucidating interaction effects between factors which are otherwise difficult to deconvolute. By nesting hierarchical levels of dilution structures, and designing the device purely by resistive flow (no valves are required), suitable diffusive mixing of growth factors up to 40,kDa is achieved such that the nine culture conditions can be generated and maintained from a minimal number of stock solutions. Biotechnol. Bioeng. 2009; 104: 1240,1244. © 2009 Wiley Periodicals, Inc. [source] Infertility, infertility treatment and psychomotor development: the Danish National Birth CohortPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 2 2009Jin Liang Zhu Summary Babies born of infertile couples, regardless of treatment, have a higher risk of preterm birth and low birthweight, conditions associated with delayed development. We examined developmental milestones in singletons as a function of parental infertility [time to pregnancy (TTP) > 12 months] and infertility treatment. From the Danish National Birth Cohort (1997,2003), we identified 37 897 singletons born of fertile couples (TTP , 12 months), 4351 born of infertile couples conceiving naturally (TTP > 12 months), and 3309 born after infertility treatment. When the children were about 18 months old, mothers reported 12 developmental milestones by responding to structured questions. We defined a failure to achieve the assessed milestone or the minimal numbers of milestones in a summary (motor, or cognitive/language skills) as delay. Naturally conceived children born of infertile couples had a pattern of psychomotor development similar to that of children born of fertile couples, but increasing TTP correlated with a modest delay. When the analysis was restricted to infertile couples (treated and untreated), children born after treatment showed a slight delay in cognitive/language development (odds ratio 1.24, [95% confidence interval 1.01, 1.53]) for not meeting at least three out of six cognitive/language milestones); children born after intracytoplasmic sperm injection (ICSI) had the highest estimated relative risk of delay for most milestones, especially motor milestones. These results suggest that a long TTP may be associated with a modest developmental delay. Infertility treatment, especially ICSI, may be associated with a slight delay for some of these early milestones. [source] Inflammatory arthritis in caspase 1 gene,deficient mice: Contribution of proteinase 3 to caspase 1,independent production of bioactive interleukin-1,ARTHRITIS & RHEUMATISM, Issue 12 2009Leo A. B. Joosten Objective Caspase 1, a known cysteine protease, is a critical component of the inflammasome. Both caspase 1 and neutrophil serine proteases such as proteinase 3 (PR3) can process pro,interleukin-1, (proIL-1,), a crucial cytokine linked to the pathogenesis of rheumatoid arthritis. This study was undertaken to establish the relative importance of caspase 1 and serine proteases in mouse models of acute and chronic inflammatory arthritis. Methods Acute and chronic arthritis were induced in caspase 1,/, mice, and the lack of caspase 1 was investigated for its effects on joint swelling, cartilage metabolism, and histopathologic features. In addition, caspase 1 activity was inhibited in mice lacking active cysteine proteases, and the effects of dual blockade of caspase 1 and serine proteases on arthritis severity and histopathologic features were evaluated. Results Surprisingly, caspase 1,/, mice, in a model of acute (neutrophil-dominated) arthritis, developed joint swelling to an extent similar to that in wild-type control mice. Joint fluid concentrations of bioactive IL-1, were comparable in caspase 1,/, mice and controls. In contrast, induction of chronic arthritis (characterized by minimal numbers of neutrophils) in caspase 1,/, mice led to reduced joint inflammation and less cartilage damage, implying a caspase 1,dependent role in this process. In mice lacking neutrophil serine PR3, inhibition of caspase 1 activity resulted in decreased bioactive IL-1, concentrations in the synovial tissue and less suppression of chondrocyte anabolic function. In addition, dual blockade of both PR3 and caspase 1 led to protection against cartilage and bone destruction. Conclusion Caspase 1 deficiency does not affect neutrophil-dominated joint inflammation, whereas in chronic arthritis, the lack of caspase 1 results in reduced joint inflammation and cartilage destruction. These findings suggest that inhibitors of caspase 1 are not able to interfere with the whole spectrum of IL-1, production, and therefore such inhibitors may be of therapeutic value only in inflammatory conditions in which limited numbers of neutrophils are present. [source] Neutrophilic-chronic myeloid leukemiaCANCER, Issue 9 2002Low levels of p230 BCR/ABL mRNA, undetectable p230 BCR/ABL protein may predict an indolent course Abstract BACKGROUND Neutrophilic-chronic myeloid leukemia (CML-N) has been described as a CML variant associated both with a distinctive molecular defect of the Philadelphia chromosome and with a more benign clinical course than classic CML. The translocation (9;22) in CML-N results in the transcription of an e19/a2 type BCR/ABL mRNA that codes for a 230-kD BCR/ABL protein (p230). The indolence of the clinical course of patients with CML-N has been disputed. METHODS The objectives of this study were to quantify and correlate with clinical outcome the p230 mRNA and protein in patients with CML-N, to describe six new patients and the follow-up (with molecular analysis) of five previously reported patients with CML-N, and to review characteristics of all patients with CML-N and p230 BCR/ABL reported to date in the literature. RESULTS Quantitative polymerase chain reaction assays on specimens from the great majority of patients with CML-N revealed minimal numbers of molecules of p230 BCR/ABL transcripts per total RNA. This also was associated with a lack of detectable p230 BCR/ABL protein in patient specimens, even in one patient who was followed for 16 years after diagnosis. This may explain the milder leukemic phenotype in most patients with CML-N. A review of all 23 patients who had an e19/a2 type BCR/ABL translocation suggested that the low level of p230 BCR/ABL mRNA and the lack of detectable p230 BCR/ABL protein in patients with no additional cytogenetic abnormalities may predict their indolent clinical course. CONCLUSIONS Patients with p230 positive CML-N have indolent course, probably as a result of low p230 mRNA and protein levels. This supports the need to conduct additional molecular studies, even if cytogenetic studies have revealed t(9;22), because of the prognostic importance of the molecular findings. Cancer 2002;94:2416,25. © 2002 American Cancer Society. DOI 10.1002/cncr.10490 [source] | |||||||||||||||||||