Home About us Contact
|
Home About us Contact | ||
|
|
||
Shedding
Kinds of Shedding Terms modified by Shedding Selected AbstractsProteolytic processing of the receptor-type protein tyrosine phosphatase PTPBR7FEBS JOURNAL, Issue 1 2007Gönül Dilaver The single-copy mouse gene Ptprr gives rise to different protein tyrosine phosphatase (PTP) isoforms in neuronal cells through the use of distinct promoters, alternative splicing, and multiple translation initiation sites. Here, we examined the array of post-translational modifications imposed on the PTPRR protein isoforms PTPBR7, PTP-SL, PTPPBS,42 and PTPPBS,37, which have distinct N-terminal segments and localize to different parts of the cell. All isoforms were found to be short-lived, constitutively phosphorylated proteins. In addition, the transmembrane isoform, PTPBR7, was subject to N-terminal proteolytic processing, in between amino acid position 136 and 137, resulting in an additional, 65-kDa transmembrane PTPRR isoform. Unlike for some other receptor-type PTPs, the proteolytically produced N-terminal ectodomain does not remain associated with this PTPRR-65. Shedding of PTPBR7-derived polypeptides at the cell surface further adds to the molecular complexity of PTPRR biology. [source] Human T-cell leukemia virus type-I Tax induces expression of interleukin-6 receptor (IL-6R): Shedding of soluble IL-6R and activation of STAT3 signalingINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Sankichi Horiuchi Abstract Human T-cell leukemia virus type-I (HTLV-I) encodes for the viral protein Tax, which is known to significantly disrupt transcriptional control of cytokines, cytokine receptors and other immuno-modulatory proteins in T cells. Specific dysregulation of these factors can alter the course and pathogenesis of infection. Soluble interleukin-6 receptor (sIL-6R) was shown to circulate at elevated levels in HTLV-I-infected patients, and high expressions of IL-6R and sIL-6R by HTLV-I-infected T cells were clinically and experimentally associated with Tax activity. To examine roles of Tax in expression of the IL-6R gene, the JPX-9 cell line was used, which is derived from Jurkat cell line expressing Tax cDNA. Over-expression of Tax enhanced IL-6R expression but not in Tax mutant JPX-9/M cell line. The clinical relevance of these observations was further demonstrated by ELISA using sera obtained from HTLV-I-infected patients. Our results revealed that sIL-6R levels were apparently elevated in HAM/TSP patients who were expressing Tax in their cells, while ATL patients' cells barely expressed Tax. HTLV-I-infected T-cell lines stimulated by IL-6/sIL-6R showed gp130-mediated STAT3 activity. IL-6/sIL-6R enhanced proliferation of HTLV-I-infected T cells in association with activation of STAT3. Consequently, Tax-mediated regulations of IL-6R and sIL-6R observed in HTLV-I-associated disorders may contribute to proliferation of HTLV-I-infected T cells through activation of inducible STAT3, and ultimately affect malignant growth and transformation of T cells by HTLV-I. © 2006 Wiley-Liss, Inc. [source] Shedding of microparticles by myofibroblasts as mediator of cellular cross-talk during normal wound healingJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Véronique J. Moulin Interactions between cells are a crucial mechanism to correctly heal a wounded tissue. Myofibroblasts have a central role during healing but their means to communicate with other cells is unknown. Microparticles (MP) have demonstrated a potential role as mediators of cellular interactions during various diseases. We have analyzed the production of MP by normal (Wmyo) and pathological (hypertrophic scar, Hmyo) myofibroblasts and human dermal fibroblasts (Fb) when treated with serum or plasma as examples of body fluids. We have shown that the presence of these body fluids induced a very significant increase in MP production by Wmyo while no MP production was denoted for Hmyo and Fb. These effects were at least due to thermally sensitive protein(s) with a molecular mass >30,kDa. Furthermore, the increase in MP production was not linked to an increase in apoptotic Wmyo. MP characterization showed that VEGF and FGF2 were present in MP and that endothelial and (myo)fibroblast cell growth can be stimulated by MP treatment. We postulated that MP production by myofibroblasts could modulate mesenchymal cell growth and angiogenesis during normal healing. J. Cell. Physiol. 225: 734,740, 2010. © 2010 Wiley-Liss, Inc. [source] Mycobacterium avium ssp. paratuberculosis High Shedding in an Adult Female Alpaca, and its Implications for the Rest of the HerdJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2009M.-E. Fecteau First page of article [source] Molecular and Cellular Mechanisms of Ectodomain SheddingTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 6 2010Kazutaka Hayashida Abstract The extracellular domain of several membrane-anchored proteins is released from the cell surface as soluble proteins through a regulated proteolytic mechanism called ectodomain shedding. Cells use ectodomain shedding to actively regulate the expression and function of surface molecules, and modulate a wide variety of cellular and physiological processes. Ectodomain shedding rapidly converts membrane-associated proteins into soluble effectors and, at the same time, rapidly reduces the level of cell surface expression. For some proteins, ectodomain shedding is also a prerequisite for intramembrane proteolysis, which liberates the cytoplasmic domain of the affected molecule and associated signaling factors to regulate transcription. Ectodomain shedding is a process that is highly regulated by specific agonists, antagonists, and intracellular signaling pathways. Moreover, only about 2% of cell surface proteins are released from the surface by ectodomain shedding, indicating that cells selectively shed their protein ectodomains. This review will describe the molecular and cellular mechanisms of ectodomain shedding, and discuss its major functions in lung development and disease. Anat Rec, 293:925,937, 2010. © 2010 Wiley,Liss, Inc. [source] Poly(ethylene glycol) with Observable Shedding,ANGEWANDTE CHEMIE, Issue 37 2010Weiwei Gao Dr. Die Spaltung eines Polyethylenglycol(PEG)-Nanopartikel(NP)-Konjugats mit FRET resultiert in einer Fluoreszenz bei 520,nm (siehe Bild). Wurden die Nanopartikel auf Krebszelllinien als Ziel gerichtet, bewirkte die reduzierende Umgebung des Endosoms die Spaltung der Disulfidbindung und das Auflösen der PEG-Schicht. [source] Impaired lactation in mice expressing dominant-negative FADD in mammary epitheliumDEVELOPMENTAL DYNAMICS, Issue 4 2009Mark Shackleton Abstract The Fas-associated death domain (FADD/Mort1) adaptor protein was originally identified as a key mediator of apoptosis, although pleiotropic functions for FADD have also been reported. FADD-mediated tumoricidal effects have been described in breast cancer cells; however, its physiological role in normal mammary gland epithelium is not well understood. To determine the role of FADD signaling during mammary gland development, we generated transgenic mice overexpressing dominant-negative FADD (DN-FADD) in mammary epithelium, using the steroid responsive mouse mammary tumor virus promoter. Transgenic mice exhibited a perturbation in lactation resulting in impaired milk production and pup growth retardation. Reduced expansion of alveoli was evident during early lactation with extensive shedding of luminal alveolar cells. Significantly more TUNEL (terminal deoxynucleotidyl transferase,mediated deoxyuridinetriphosphate nick end-labeling)-positive cells were present at this time point and a subsequent increase in bromodeoxyuridine-positive cells was observed. These findings suggest a role for FADD in maintaining the survival of mammary secretory alveolar cells after the establishment of lactation. Developmental Dynamics 238:1010,1016, 2009. © 2009 Wiley-Liss, Inc. [source] Regionalized expression of ADAM13 during chicken embryonic developmentDEVELOPMENTAL DYNAMICS, Issue 3 2007Juntang Lin Abstract ADAMs are a family of membrane proteins possessing a disintegrin domain and a metalloprotease domain, which have functions in cell,cell adhesion, cell,matrix adhesion, and protein shedding, respectively. ADAMs are involved in morphogenesis and tissue formation during embryonic development. In the present study, chicken ADAM13 was cloned and identified, and its expression was investigated by semiquantitative reverse transcriptase-polymerase chain reaction and in situ hybridization during chicken embryonic development. Our results show that ADAM13 expression is temporally and spatially regulated in chicken embryos. At early developmental stages, ADAM13 is expressed in the head mesenchyme, which later develops into the craniofacial skeleton, in the branchial arches, and in the meninges surrounding the brain. Furthermore, ADAM13 mRNA was also detected in several tissues and organs, such as the somites and their derived muscles, the meninges surrounding the spinal cord, the dorsal aorta, the developing kidney, and several digestive organs. Developmental Dynamics 236:862,870, 2007. © 2007 Wiley-Liss, Inc. [source] Novel metalloprotease,disintegrin, meltrin , (ADAM35), expressed in epithelial tissues during chick embryogenesisDEVELOPMENTAL DYNAMICS, Issue 3 2004Mitsuko Watabe-Uchida Abstract Members of the ADAM (adisintegrin and metalloprotease) family are involved in fertilization, morphogenesis, and pathogenesis. Their metalloprotease domains mediate limited proteolysis, including ectodomain shedding of membrane-anchored growth factors and intercellular-signaling proteins, and their disintegrin domains play regulatory roles in cell adhesion and migration. In screening for cDNAs encoding chicken ADAM proteins expressed during muscle development, we identified Meltrin , as a novel member of this family. To elucidate its functions, we investigated its expression during development by using antibodies raised against its protease domain. In the somites, Meltrin , protein was specifically expressed in the myotomal cells, which delaminate from the dermomyotome to form epithelial sheets. It was also found in the surface ectoderm, lens placodes, otic vesicles, and the gut epithelia. Basolateral localization of Meltrin , in these epithelial cells suggests its unique roles in the organization of the epithelial tissues and development of the sensory organs and the gut. Developmental Dynamics 230:557,568, 2004. © 2004 Wiley-Liss, Inc. [source] The influence of pool length on local turbulence production and energy slope: a flume experimentEARTH SURFACE PROCESSES AND LANDFORMS, Issue 11 2004Douglas M. Thompson Abstract The in,uence of pool length on the strength of turbulence generated by vortex shedding was investigated in a 6 m long recirculating ,ume. The experiment utilized a 38% constriction of ,ow and an average channel-bed slope of 0·007. The base geometry for the intermediate-length pool experiment originated from a highly simpli,ed, 0·10 scale model of a forced pool from North Saint Vrain Creek, Colorado. Discharge in the ,ume was 31·6 l/s, which corresponds to a discharge in the prototype channel of 10 m3/s. Three shorter and four longer pool lengths also were created with a ,xed bed to determine changes in turbulence intensities and energy slope with pool elongation. Three-dimensional velocities were measured with an acoustic Doppler velocimeter at 31,40 different 0·6-depth and near-bed locations downstream of the rectangular constriction. The average velocity and root mean square (RMS) of the absolute magnitude of velocity at both depths are signi,cantly related to the distance from the constriction in most pool locations downstream of the constriction. In many locations, pool elongation results in a non-linear change in turbulence intensities and average velocity. Based on the overall ,ow pattern, the strongest turbulence occurs in the center of the pool along the shear zone between the jet and recirculating eddy. The lateral location of this shear zone is sensitive to changes in pool length. Energy slope also was sensitive to pool length due to a combination of greater length of the pool and greater head loss with shorter pools. The results indicate some form of hydraulic optimization is possible with pools adjusting their length to adjust the location and strength of turbulent intensities in the center of pools, and lower their rate of energy dissipation. Copyright © 2004 John Wiley & Sons, Ltd. [source] Dynamics of Campylobacter colonization of a natural host, Sturnus vulgaris (European Starling)ENVIRONMENTAL MICROBIOLOGY, Issue 1 2009F. M. Colles Summary Wild European Starlings (Sturnus vulgaris) shed Campylobacter at high rates, suggesting that they may be a source of human and farm animal infection. A survey of Campylobacter shedding of 957 wild starlings was undertaken by culture of faecal specimens and genetic analysis of the campylobacters isolated: shedding rates were 30.6% for Campylobacter jejuni, 0.6% for C. coli and 6.3% for C. lari. Genotyping by multilocus sequence typing (MLST) and antigen sequence typing established that these bacteria were distinct from poultry or human disease isolates with the ST-177 and ST-682 clonal complexes possibly representing starling-adapted genotypes. There was seasonal variation in both shedding rate and genotypic diversity, both exhibiting a maximum during the late spring/early summer. Host age also affected Campylobacter shedding, which was higher in younger birds, and turnover was rapid with no evidence of cross-immunity among Campylobacter species or genotypes. In nestlings, C. jejuni shedding was evident from 9 days of age but siblings were not readily co-infected. The dynamics of Campylobacter infection of starlings differed from that observed in commercial poultry and consequently there was no evidence that wild starlings represent a major source of Campylobacter infections of food animals or humans. [source] Faecal shedding and serological cross-sectional study of Lawsonia intracellularis in horses in the state of Minas Gerais, BrazilEQUINE VETERINARY JOURNAL, Issue 6 2009C. V. Guimarães-Ladeira Summary Reason for performing the study: Proliferative enteropathy, caused by the intracellular bacterium Lawsonia intracellularis, has been described in horses in Australia, the USA, Canada and European countries but has not been reported in Latin America. The prevalence of the disease in horses worldwide is unknown. Objective: To evaluate the presence of subclinical L. intracellularis infection in horses in the state of Minas Gerais, Brazil. Methods: A longitudinal study using serology and PCR for detecting antibodies (IgG) and shedding of L. intracellularis in faecal samples, respectively, was conducted using a total of 223 horses from 14 different horse farms in Minas Gerais, and from the Veterinary School of UFMG equine herds in Minas Gerais. The immunoperoxidase technique in glass slides was used as the serological test. Results: Twenty-one horse sera had immunoglobulin G titres of 1:60 and were considered positive. The PCR technique in faeces for L. intracellularis DNA identified 7 horses as faecal shedders. Horses shedding the organism appeared healthy, indicating that subclinical infection of L. intracellularis occurred in the horses. Conclusion: Seropositivity and detection of faecal shedding of L. intracellularis indicates the presence of the agent in the equine population in Minas Gerais. Potential relevance: Results of this study should alert clinicians in countries where proliferative enteropthy in horses has not been reported to consider this disease as a possible cause of enteric disease. [source] Influenza A viruses with truncated NS1 as modified live virus vaccines: Pilot studies of safety and efficacy in horsesEQUINE VETERINARY JOURNAL, Issue 1 2009T. M. Chambers Summary Reasons for performing study: Three previously described NS1 mutant equine influenza viruses encoding carboxyterminally truncated NS1 proteins are impaired in their ability to inhibit type I IFN production in vitro and are replication attenuated, and thus are candidates for use as a modified live influenza virus vaccine in the horse. Hypothesis: One or more of these mutant viruses is safe when administered to horses, and recipient horses when challenged with wild-type influenza have reduced physiological and virological correlates of disease. Methods: Vaccination and challenge studies were done in horses, with measurement of pyrexia, clinical signs, virus shedding and systemic proinflammatory cytokines. Results: Aerosol or intranasal inoculation of horses with the viruses produced no adverse effects. Seronegative horses inoculated with the NS1-73 and NS1-126 viruses, but not the NS1-99 virus, shed detectable virus and generated significant levels of antibodies. Following challenge with wild-type influenza, horses vaccinated with NS1-126 virus did not develop fever (>38.5°C), had significantly fewer clinical signs of illness and significantly reduced quantities of virus excreted for a shorter duration post challenge compared to unvaccinated controls. Mean levels of proinflammatory cytokines IL-1, and IL-6 were significantly higher in control animals, and were positively correlated with peak viral shedding and pyrexia on Day +2 post challenge. Conclusion and clinical relevance: These data suggest that the recombinant NS1 viruses are safe and effective as modified live virus vaccines against equine influenza. This type of reverse genetics-based vaccine can be easily updated by exchanging viral surface antigens to combat the problem of antigenic drift in influenza viruses. [source] Evaluation of a nested PCR test and bacterial culture of swabs from the nasal passages and from abscesses in relation to diagnosis of Streptococcus equi infection (strangles)EQUINE VETERINARY JOURNAL, Issue 1 2006L. MØLLER GRØNBÆK Summary Reasons for performing study: Streptococcus equi is the cause of strangles in horses. To improve diagnostic sensitivity, development and evaluation of DNA-based methods are necessary. Objectives: To evaluate diagnostic methods and observe the pattern of bacterial shedding during natural outbreaks. Methods: Two herds with natural outbreaks of strangles were visited over a period of 15 weeks and 323 samples originating from 35 horses investigated. The diagnostic use of a nested PCR test was evaluated using a collection of 165 isolates of Lancefield group C streptococci (species specificity) and swabs from nasal passages or from abscesses from horses infected with S. equi (diagnostic sensitivity). Results: All 45 S. equi isolates tested positive in the nested PCR, whereas no amplicon was formed when testing the other 120 Lancefield group C isolates. A total of 43 samples were collected from 11 horses showing clinical signs of strangles during the study period. The diagnostic sensitivity for PCR test was 45% and 80% for samples from the nasal passages and abscesses, respectively; the corresponding diagnostic sensitivity for cultivation was 18% and 20%. The diagnostic sensitivity was significantly higher for PCR than for bacterial cultivation. Furthermore, the shedding of S. equi in 2 infected horse populations was evaluated. An intermittent shedding period of S. equi of up to 15 weeks was recorded in this part of the study. It was also shown that shedding of S. equi occurred both from horses with and without clinical signs. Conclusions and potential relevance: The nested PCR test represents a species-specific and -sensitive method for diagnosis of S. equi from clinical samples. It may, however, be desirable in future to develop detection methods with high diagnostic sensitivity and specificity without the potential problems inherent in nested PCR. [source] Efficacy of a live equine herpesvirus-1 (EHV-1) strain C147 vaccine in foals with maternally-derived antibody: protection against EHV-1 infectionEQUINE VETERINARY JOURNAL, Issue 5 2004J. R. PATEL Summary Reasons for performing study: Currently, there is no recommended immunoprophylaxis against febrile respiratory diseases due to equine herpesvirus-1 (EHV-1) and -4 (EHV-4) in horses below age 5,6 months. This is because of interference by maternally-derived antibody (MDA) of vaccines. Objective: Unweaned equine foals are an important reservoir of EHV-1 transmission; therefore, we experimentally assessed the efficacy of a live EHV-1 vaccine in foals age 1.4-3.5 months with MDA. Methods: Following vaccination and challenge, parameters assessed were virus shedding in nasal mucus, leucocyte-associated viraemia, circulating virus neutralising antibody activity and clinical reactions. Results: Controlled challenge showed that a single intranasal dose of the vaccine afforded partial but significant protection against febrile respiratory disease, virus shedding and viraemia due to EHV-1 infection, despite virus-neutralising MDA. Conclusions and potential relevance: The prospective vaccine would be a significant step forward in reducing the incidence of the disease caused by EHV-1 infection. [source] Study of faecal shedding of Clostridium difficile in horses treated with penicillinEQUINE VETERINARY JOURNAL, Issue 2 2004A. Gustafsson No abstract is available for this article. [source] Sex, Reproductive Status, and Cost of Tail Autotomy via Decreased Running Speed in LizardsETHOLOGY, Issue 1 2009William E. Cooper Jr Autotomy, voluntary shedding of body parts to permit escape, is a theoretically interesting defense because escape benefit is offset by numerous costs, including impaired future escape ability. Reduced sprint speed is a major escape cost in some lizards. We predicted that tail loss causes decreased speed in males and previtellogenic females, but not vitellogenic females already slowed by mass gain. In the striped plateau lizard, Sceloporus virgatus, adults of both sexes are subject to autotomy, and females undergo large increases in body condition (mass/length) during vitellogenesis. Time required for running 1 m was similar in intact autotomized males and previtellogenic females, but increased by nearly half after autotomy. Vitellogenic females were slower than other lizards when intact, but their speed was unaffected by autotomy. Following autotomy, speeds of all groups were similar. Thus, speed costs of autotomy vary with sex and reproductive condition: decreased running speed is not a cost of autotomy in vitellogenic females or presumably gravid females. Costs of autotomy are more complex than previously known. Speed and other costs might interact in unforseen ways, making it difficult to predict whether strategies to compensate for diminished escape ability differ with reproductive condition in females. [source] ADAM17 activity during human neutrophil activation and apoptosisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2006Bruce Walcheck Dr. Abstract Substrates of the metalloprotease ADAM17 (also known as TNF-, converting enzyme or TACE) undergo ectodomain shedding and include various inflammatory modulators. Though polymorphonuclear leukocytes contribute significantly to inflammation, direct analyses of ADAM17 on human neutrophils are very limited. In addition, the current understanding of the processes regulating ADAM17 activity primarily relate to its rapid activation. Therefore, to extend insights into the mechanisms of ADAM17 activity, we examined its surface expression and the shedding of its substrates during extended periods of neutrophil activation and apoptosis. Contrary to studies with immortalized hematopoietic cell lines, we report that surface expression of ADAM17 is maintained by human neutrophils activated with formyl peptides or by FcR/complement receptor-mediated phagocytosis. Interestingly, bacterial phagocytosis resulted in a significant increase in ADAM17 expression several hours after pathogen engulfment. We provide novel evidence that ADAM17 surface expression is also maintained during spontaneous and anti-Fas-induced neutrophil apoptosis. The well-validated ADAM17 substrates L-selectin and proTNF-, were shed efficiently by neutrophils under each of the conditions tested. Our data thus indicate prolonged ADAM17 expression during neutrophil effector functions. The implications of this may be a role by ADAM17 in both the induction and down-regulation of neutrophil activity. [source] On-line dynamic security assessment to mitigate the risk of blackout in the Italian power systemEUROPEAN TRANSACTIONS ON ELECTRICAL POWER, Issue 8 2008Diego Cirio Abstract This paper provides a comprehensive survey of the major initiatives and research projects recently carried out by the Italian system operator, Cesi Ricerca, and Universities on power system monitoring, defense, and security assessment. The technological and methodological features of an advanced wide area measurement system (WAMS) are described and the main aspects of an adaptive system for event-based automatic load shedding are presented. Then preventive and corrective security assessment, with particular emphasis to dynamic security assessment,DSA, is introduced. Results from an EU project, where the Italian power system served as a test site for on-line experimentation, are reported. Considering the need for very fast assessment by stability indices, a complementary approach to the above "conventional" DSA, currently under way, is described in further detail. The methodology relies on a correlation model relating significant power system measurements with local loadability margins. Results of some tests on the Italian power system are presented and discussed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Unit commitment at frequency security conditionEUROPEAN TRANSACTIONS ON ELECTRICAL POWER, Issue 2 2001X. Lei In island grids and weakly interconnected power systems, the loss of a large proportion of generation will cause the system frequency to fall dramatically. In order to ensure a stable operation with the lowest impact to the system, the disturbed power balance must be equalized within a short specified time by activating the second-reserve of on-line units or by load shedding or both. Unit commitment procedures shall consider these factors to ensure a reliable power supply while minimizing the fuel costs. This paper presents a unit commitment procedure taking the frequency security condition of systems into account. The procedure commits and optimizes units, calculates necessary second-reserve capability, and allocates them among the available on-line units. Parallel to the minimization of daily fuel costs, a specified frequency minimum following the loss of generation is employed as a criterion for maintaining system security. A case study on typical island systems with a large number of different units is demonstrated using the proposed procedure. Results from the study validated robust performance of the proposed procedure that minimizes fuel costs while maintaining frequency security condition. This paper considers only the frequency security condition to be handled. However, it can also be extended with other criteria such transmission capability during transient conditions of interconnected systems. [source] The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor proteinFEBS JOURNAL, Issue 12 2004Tobias M. J. Allinson Numerous transmembrane proteins, including the blood pressure regulating angiotensin converting enzyme (ACE) and the Alzheimer's disease amyloid precursor protein (APP), are proteolytically shed from the plasma membrane by metalloproteases. We have used an antisense oligonucleotide (ASO) approach to delineate the role of ADAM10 and tumour necrosis factor-, converting enzyme (TACE; ADAM17) in the ectodomain shedding of ACE and APP from human SH-SY5Y cells. Although the ADAM10 ASO and TACE ASO significantly reduced (> 81%) their respective mRNA levels and reduced the ,-secretase shedding of APP by 60% and 30%, respectively, neither ASO reduced the shedding of ACE. The mercurial compound 4-aminophenylmercuric acetate (APMA) stimulated the shedding of ACE but not of APP. The APMA-stimulated secretase cleaved ACE at the same Arg-Ser bond in the juxtamembrane stalk as the constitutive secretase but was more sensitive to inhibition by a hydroxamate-based compound. The APMA-activated shedding of ACE was not reduced by the ADAM10 or TACE ASOs. These results indicate that neither ADAM10 nor TACE are involved in the shedding of ACE and that APMA, which activates a distinct ACE secretase, is the first pharmacological agent to distinguish between the shedding of ACE and APP. [source] Pathophysiologic importance of E- and L-selectin for neutrophil-induced liver injury during endotoxemia in miceHEPATOLOGY, Issue 5 2000Judy A. Lawson Neutrophils can cause parenchymal cell injury in the liver during ischemia-reperfusion and endotoxemia. Neutrophils relevant for the injury accumulate in sinusoids, transmigrate, and adhere to hepatocytes. To investigate the role of E- and L-selectin in this process, C3Heb/FeJ mice were treated with 700 mg/kg galactosamine and 100 ,g/kg endotoxin (Gal/ET). Immunogold labeling verified the expression of E-selectin on sinusoidal endothelial cells 4 hours after Gal/ET injection. In addition, Gal/ET caused up-regulation of Mac-1 (CD11b/CD18) and shedding of L-selectin from circulating neutrophils. Gal/ET induced hepatic neutrophil accumulation (422 ± 32 polymorphonuclear leukocytes [PMN]/50 high power fields [HPF]) and severe liver injury (plasma alanine transaminase [ALT] activities: 4,120 ± 960 U/L; necrosis: 44 ± 3%) at 7 hours. Treatment with an anti,E-selectin antibody (3 mg/kg, intravenously) at the time of Gal/ET administration did not significantly affect hepatic neutrophil accumulation and localization. However, the anti,E-selectin antibody significantly attenuated liver injury as indicated by reduced ALT levels (,84%) and 43% less necrotic hepatocytes. In contrast, animals treated with an anti,L-selectin antibody or L-selectin gene knock out mice were not protected against Gal/ET-induced liver injury. However, E-, L-, and P-selectin triple knock out mice showed significantly reduced liver injury after Gal/ET treatment as indicated by lower ALT levels (,65%) and reduced necrosis (,68%). Previous studies showed that circulating neutrophils of E-selectin,overexpressing mice are primed and activated similar to neutrophils adhering to E-selectin in vitro. Therefore, we conclude that blocking E-selectin or eliminating this gene may have protected against Gal/ET-induced liver injury in vivoby inhibiting the full activation of neutrophils during the transmigration process. [source] Proper Splitting of Interconnected Power SystemsIEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, Issue 2 2010S. Najafi Non-member Abstract Power system islanding is the last defense line to protect power grids from incidence of wide-area blackout. As a wide-area control action, power system splitting is a comprehensive decision making problem that includes different subproblems. This paper introduces a novel approach for separation of the entire power system into several stable islands in different loading levels. The proposed method combines both the dynamic and the static characteristics of interconnected power network and determines the proper splitting schemes. The presented algorithm searches for proper islanding strategy in the boundary of primary determined coherent machines using Krylov subspace method and finds the proper splitting points by transferring some of the buses in one island to another island such that total load shedding is minimized. A spanning tree-based depth first search algorithm is used to find all possible combination of transferred buses. The presented method reduces the huge initial search space of islanding strategy considering dynamic characteristics of integrated power system and reduction of search space to only boundary network. The speed of the proposed algorithm is remarkably high and can be applied for islanding the power system in real-time. The presented algorithm is applied to IEEE 118 BUS test system. Results show the robustness, effectiveness, and capability of the algorithm to determine fast and accurate proper islanding strategy. Time domain simulation of the islanding strategies confirms that all the islands which are specified by the proposed method are stable. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [source] Application and comparison of metaheuristic techniques to reactive power planning problemIEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, Issue 6 2008Mehdi Eghbal Non-Member Abstract This paper presents the application and comparison of metaheuristic techniques to reactive power planning (RPP) problem which involves optimal allocation and combination of to-be-installed VAr sources to satisfy voltage constraints during normal and contingency states for multiple load levels. The main objective of the proposed RPP problem is to minimize the investment cost through balanced installation of SCs and SVCs while keeping a specified security level and minimizing the amount of load shedding. The problem is formulated as a large scale mixed integer nonlinear programming problem, which is a nonsmooth and nondifferentiable optimization problem using conventional optimization techniques and induces lots of local minima. Among the metaheuristic techniques, genetic algorithm (GA), particle swarm optimization (PSO) and evolutionary particle swarm optimization (EPSO) are applied to solve the RPP problem. To investigate the effectiveness of the metaheuristic techniques, the proposed approaches have been successfully tested on IEEE-14 buses, as well as IEEE-57 buses test system. The results obtained are compared and the effectiveness of each technique has been illustrated. Copyright © 2008 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [source] Interleukin-4 supports interleukin-12-induced proliferation and interferon-, secretion in human activated lymphoblasts and T helper type 1 cellsIMMUNOLOGY, Issue 1 2006Martin A. Kriegel Summary Interleukin-12 (IL-12) and IL-4 are known to differentially promote T helper (Th) cell differentiation. While IL-12 induces interferon-, (IFN-,) production and maturation of Th1 cells, IL-4 is thought to antagonize IL-12 and to favour Th2 development. Here we studied the combined action of various concentrations of common ,-chain (,c -chain) cytokines, including IL-4 and the Th1 cytokine IL-12, in human activated lymphoblasts and Th1 cells. IL-4 and IL-7 potentiated IL-12-induced proliferation at every concentration tested (1,10 ng/ml) without increasing rescue from apoptosis, indicating that proliferation was directly affected by these cytokine combinations. With regards to cytokine secretion, IL-2 together with IL-12 initiated tumour necrosis factor-, synthesis, enhanced IFN-, production, and shedding of soluble IL-2 receptor , as expected. Importantly, combining IL-4 with IL-12 also enhanced IFN-, secretion in lymphoblasts and a Th1 cell line. Investigating signal transduction in lymphoblasts induced by these cytokines, we found that not only IL-2 but also IL-4 enhances signal transducer and activator of transcription 3 (STAT3) tyrosine phosphorylation by IL-12. Tyrosine phosphorylations of janus kinase 2 (JAK-2), tyrosine kinase 2 (TYK2), extracellular signal-regulated kinase (ERK) and STAT4, STAT5 and STAT6 were not potentiated by combinations of these cytokines, suggesting specificity for increased STAT3 phosphorylation. In conclusion, two otherwise antagonizing cytokines co-operate in activated human lymphoblasts and Th1 cells, possibly via STAT3 as a converging signal. These data demonstrate that IL-4 can directly enhance human Th1 cell function independently of its known actions on antigen-presenting cells. These findings should be of importance for the design of cytokine-targeted therapies of human Th-cell-driven diseases. [source] Granulocyte,macrophage colony-stimulating factor regulates cytokine production in cultured macrophages through CD14-dependent and -independent mechanismsIMMUNOLOGY, Issue 2 2000A. Bergamini Summary Granulocyte,macrophage colony-stimulating factor (GM-CSF) has multiple effects on the antigen phenotype and function of macrophages. In this study we investigated the effect of GM-CSF on cytokine production by macrophages. We found that GM-CSF may modify the tumour necrosis factor-, (TNF-,) and interleukin-6 (IL-6) response to lipopolysaccharide (LPS) through two different mechanisms. Relatively early in culture, GM-CSF increases the amount of cytokines synthesized by responding cells; this effect appears to be unrelated to modulation of CD14 expression and LPS-binding capacity. After prolonged incubation, GM-CSF up-regulates both CD14 expression and LPS-binding capacity, and the frequency of cytokine-producing cells. Release of CD14 in the culture supernatant was decreased in the presence of GM-CSF, suggesting that a reduced shedding was responsible for the effect of GM-CSF on CD14 expression. Enhancement of cytokine production was also observed in GM-CSF-treated macrophages after stimulation by phorbol 12-myristate 13-acetate (PMA), thus indicating that GM-CSF affects both CD14-dependent and -independent cytokine production. Finally, GM-CSF did not modulate the LPS- and PMA-induced production of IL-10 and IL-12. We conclude that GM-CSF may play a role in manipulating the activation-induced expression of pro-inflammatory cytokines by macrophages. Enhanced production of these cytokines could play an important role in the pathogenesis of Gram-negative septic shock syndrome and in defence against infectious agents. [source] A monolithic approach for interaction of incompressible viscous fluid and an elastic body based on fluid pressure Poisson equationINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 2 2005Daisuke Ishihara Abstract This paper describes a new monolithic approach based on the fluid pressure Poisson equation (PPE) to solve an interaction problem of incompressible viscous fluid and an elastic body. The PPE is derived so as to be consistent with the coupled equation system for the fluid-structure interaction (FSI). Based on this approach, we develop two kinds of efficient monolithic methods. In both methods, the fluid pressure is derived implicitly so as to satisfy the incompressibility constraint, and all other unknown variables are derived fully explicitly or partially explicitly. The coefficient matrix of the PPE for the FSI becomes symmetric and positive definite and its condition is insensitive to inhomogeneity of material properties. The arbitrary Lagrangian,Eulerian (ALE) method is employed for the fluid part in order to take into account the deformable fluid-structure interface. To demonstrate fundamental performances of the proposed approach, the developed two monolithic methods are applied to evaluate the added mass and the added damping of a circular cylinder as well as to simulate the vibration of a rectangular cylinder induced by vortex shedding. Copyright © 2005 John Wiley & Sons, Ltd. [source] Toward accurate hybrid prediction techniques for cavity flow noise applicationsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 12 2009W. De Roeck Abstract A large variety of hybrid computational aeroacoustics (CAA) approaches exist differing from each other in the way the source region is modeled, in the way the equations are used to compute the propagation of acoustic waves in a non-quiescent medium, and in the way the coupling between source and acoustic propagation regions is made. This paper makes a comparison between some commonly used numerical methods for aeroacoustic applications. The aerodynamically generated tonal noise by a flow over a 2D rectangular cavity is investigated. Two different cavities are studied. In the first cavity (L/D=4, M=0.5), the sound field is dominated by the cavity wake mode and its higher harmonics, originating from a periodical vortex shedding at the cavity leading edge. In the second cavity (L/D=2, M=0.6), shear-layer modes, due to flow-acoustic interaction phenomena, generate the major components in the noise spectrum. Source domain modeling is carried out using a second-order finite-volume large eddy simulation. Propagation equations, taking into account convection and refraction effects, are solved using high-order finite-difference schemes for the linearized Euler equations and the acoustic perturbation equations. Both schemes are compared with each other for various coupling methods between source region and acoustic region. Conventional acoustic analogies and Kirchhoff methods are rewritten for the various propagation equations and used to obtain near-field acoustic results. The accuracy of the various coupling methods in identifying the noise-generating mechanisms is evaluated. In this way, this paper provides more insight into the practical use of various hybrid CAA techniques to predict the aerodynamically generated sound field by a flow over rectangular cavities. Copyright © 2009 John Wiley & Sons, Ltd. [source] Reduced-order controllers for control of flow past an airfoilINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 5 2006S. S. Ravindran Abstract Reduced-order controller design by means of reduced-order model for control of a wake flow is presented. Reduced-order model is derived by combining the Galerkin projection with proper orthogonal decomposition (POD) or with other related reduced-order approaches such as singular value decomposition or reduced-basis method. In the present investigation, we discuss the applicability of the reduced-order approaches for fast computation of the optimal control for control of vortex shedding behind a thin airfoil through unsteady blowing on the airfoil surface. Accuracy of the reduced-order model is quantified by comparing flow fields obtained from the reduced-order models with those from the full-order simulations under the same free-stream conditions. A control of vortex shedding is demonstrated for Reynolds number 100. It is found that downstream directed blowing on the upper surface of the airfoil near the leading edge is more efficient in mitigating flow separation and suppressing the vortex shedding. Copyright © 2005 John Wiley & Sons, Ltd. [source] Numerical analysis on the propulsive performance and vortex shedding of fish-like travelling wavy plateINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 12 2005Gen-Jin Dong Abstract Numerical analysis is carried out to investigate viscous flow over a travelling wavy plate undergoing lateral motion in the form of a streamwise travelling wave, which is similar to the backbone undulation of swimming fish. The two-dimensional incompressible Navier,Stokes equations are solved using the finite element technique with the deforming-spatial-domain/stabilized space,time formulation. The objective of this study is to elucidate hydrodynamic features of flow structure and vortex shedding near the travelling wavy plate and to get into physical insights to the understanding of fish-like swimming mechanisms in terms of drag reduction and optimal propulsive performance. The effects of some typical parameters, including the phase speed, amplitude, and relative wavelength of travelling wavy plate, on the flow structures, the forces, and the power consumption required for the propulsive motion of the plate are analysed. These results predicted by the present numerical analysis are well consistent with the available data obtained for the wave-like swimming motion of live fish in nature. Copyright © 2005 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||||||||