EVALUATING THE IMPACTS OF COINFECTION ON IMMUNE SYSTEM FUNCTION OF THE DEER MOUSE ( PEROMYSCUS MANICULATUS) USING SIN NOMBRE VIRUS AND BARTONELLA AS MODEL PATHOGEN SYSTEMS.

PubMed

Lehmer, Erin M; Lavengood, Kathryn; Miller, Mason; Rodgers, Jacob; Fenster, Steven D

2018-01-01

:  Simultaneous infections with multiple pathogens can alter the function of the host's immune system, often resulting in additive or synergistic morbidity. We examined how coinfection with the common pathogens Sin Nombre virus (SNV) and Bartonella sp. affected aspects of the adaptive and innate immune responses of wild deer mice ( Peromyscus maniculatus). Adaptive immunity was assessed by measuring SNV antibody production; innate immunity was determined by measuring levels of C-reactive protein (CRP) in blood and the complement activity of plasma. Coinfected mice had reduced plasma complement activity and higher levels of CRP compared to mice infected with either SNV or Bartonella. However, antibody titers of deer mice infected with SNV were more than double those of coinfected mice. Plasma complement activity and CRP levels did not differ between uninfected deer mice and those infected with only Bartonella, suggesting that comorbid SNV and Bartonella infections act synergistically, altering the innate immune response. Collectively, our results indicated that the immune response of deer mice coinfected with both SNV and Bartonella differed substantially from individuals infected with only one of these pathogens. Results of our study provided unique, albeit preliminary, insight into the impacts of coinfection on immune system function in wild animal hosts and underscore the complexity of the immune pathways that exist in coinfected hosts.

A complementation assay for in vivo protein structure/function analysis in Physcomitrella patens (Funariaceae)

DOE PAGES

Scavuzzo-Duggan, Tess R.; Chaves, Arielle M.; Roberts, Alison W.

2015-07-14

Here, a method for rapid in vivo functional analysis of engineered proteins was developed using Physcomitrella patens. A complementation assay was designed for testing structure/function relationships in cellulose synthase (CESA) proteins. The components of the assay include (1) construction of test vectors that drive expression of epitope-tagged PpCESA5 carrying engineered mutations, (2) transformation of a ppcesa5 knockout line that fails to produce gametophores with test and control vectors, (3) scoring the stable transformants for gametophore production, (4) statistical analysis comparing complementation rates for test vectors to positive and negative control vectors, and (5) analysis of transgenic protein expression by Westernmore » blotting. The assay distinguished mutations that generate fully functional, nonfunctional, and partially functional proteins. In conclusion, compared with existing methods for in vivo testing of protein function, this complementation assay provides a rapid method for investigating protein structure/function relationships in plants.« less

A criterion for the existence of zero modes for the Pauli operator with fastly decaying fields

NASA Astrophysics Data System (ADS)

Benguria, R. D.; Van Den Bosch, H.

2015-05-01

We consider the Pauli operator in ℝ3 for magnetic fields in L3/2 that decay at infinity as |x|-2-β with β > 0. In this case, we are able to prove that the existence of a zero mode for this operator is equivalent to a quantity δ(B), defined below, being equal to zero. Complementing a result from Balinsky et al. [J. Phys. A: Math. Gen. 34, L19-L23 (2001)], this implies that for the class of magnetic fields considered, Sobolev, Hardy, and Cwikel, Lieb, Rosenblum (CLR) inequalities hold whenever the magnetic field has no zero mode.

Toward Dietary Assessment via Mobile Phone Video Cameras.

PubMed

Chen, Nicholas; Lee, Yun Young; Rabb, Maurice; Schatz, Bruce

2010-11-13

Reliable dietary assessment is a challenging yet essential task for determining general health. Existing efforts are manual, require considerable effort, and are prone to underestimation and misrepresentation of food intake. We propose leveraging mobile phones to make this process faster, easier and automatic. Using mobile phones with built-in video cameras, individuals capture short videos of their meals; our software then automatically analyzes the videos to recognize dishes and estimate calories. Preliminary experiments on 20 typical dishes from a local cafeteria show promising results. Our approach complements existing dietary assessment methods to help individuals better manage their diet to prevent obesity and other diet-related diseases.

Localizing Ground Penetrating RADAR: A Step Towards Robust Autonomous Ground Vehicle Localization

DTIC Science & Technology

2016-07-14

localization designed to complement existing approaches with a low sensitivity to failure modes of LIDAR, camera, and GPS/INS sensors due to its low...the detailed design and results from highway testing, which uses a simple heuristic for fusing LGPR estimates with a GPS/INS system. Cross-track... designed to enable a priori map-based local- ization. LGPR offers complementary capabilities to tradi- tional optics-based approaches to map-based

Admission Chest CT Complements Fiberoptic Bronchoscopy in Prediction of Adverse Outcomes in Thermally Injured Patients

DTIC Science & Technology

2012-08-01

other CT scoring systems exist for conditions including cystic fibrosis and ARDS, these are not in widespread clinical use and have not been... diagnosis of inhalation injury.10,11 However, degree and depth of damage to main airway mucosa cannot at present be accurately distinguished by eye...injury can result in progressive pulmonary dysfunction, infection, and death. Although bronchoscopy is the standard for diagnosis , it only assesses

Exploring a Multiphysics Resolution Approach for Additive Manufacturing

NASA Astrophysics Data System (ADS)

Estupinan Donoso, Alvaro Antonio; Peters, Bernhard

2018-06-01

Metal additive manufacturing (AM) is a fast-evolving technology aiming to efficiently produce complex parts while saving resources. Worldwide, active research is being performed to solve the existing challenges of this growing technique. Constant computational advances have enabled multiscale and multiphysics numerical tools that complement the traditional physical experimentation. In this contribution, an advanced discrete-continuous concept is proposed to address the physical phenomena involved during laser powder bed fusion. The concept treats powder as discrete by the extended discrete element method, which predicts the thermodynamic state and phase change for each particle. The fluid surrounding is solved with multiphase computational fluid dynamics techniques to determine momentum, heat, gas and liquid transfer. Thus, results track the positions and thermochemical history of individual particles in conjunction with the prevailing fluid phases' temperature and composition. It is believed that this methodology can be employed to complement experimental research by analysis of the comprehensive results, which can be extracted from it to enable AM processes optimization for parts qualification.

Hypocomplementemia is associated with worse renal survival in ANCA-positive granulomatosis with polyangiitis and microscopic polyangiitis

PubMed Central

Aouba, Achille; Khoy, Kathy; Mariotte, Delphine; Lobbedez, Thierry; Martin Silva, Nicolas

2018-01-01

Recent data suggest the existence of a complement alternative pathway activation in the pathogenesis of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a condition that remains poorly understood. This study aims to assess the clinical characteristics and outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with regard to their plasma complement levels at diagnosis. A retrospective monocentric study carried out at Caen University Hospital led to the identification of proteinase-3- or myeloperoxidase-ANCA-positive GPA and MPA patients from January 2000 to June 2016 and from September 2011 to June 2016, respectively. All patients with available C3 and C4 levels at diagnosis were included. Patients were categorized in the hypocomplementemia group if their C3 and/or C4 levels at diagnosis were below the lower limit of the normal range. Among the 76 AAV patients (43 GPA, 33 MPA), 4 (5%) had hypocomplementemia, and the 72 remaining patients exhibited normal plasma complement levels. All 4 hypocomplementemia patients had renal involvement. Hypocomplementemia was followed in 1 patient whose post-treatment complement level normalized within 1 month. Among all clinical and ANCA specificity, including relapse-free survival (p = 0.093), only overall and renal survival rates were significantly lower in the hypocomplementemia group (p = 0.0011 and p<0.001, respectively). Hypocomplementemia with low C3 and/or C4 levels at GPA or MPA diagnosis may be responsible for worse survival and renal prognosis. These results argue for larger and prospective studies to better determine the epidemiology of the disease and to assess complement-targeting therapy in these patients. PMID:29621352

Arbitrary amplitude ion-acoustic solitary waves in electronegative plasmas with electrons featuring Tsallis distribution

NASA Astrophysics Data System (ADS)

Ghebache, Siham; Tribeche, Mouloud

2017-10-01

The problem of arbitrary amplitude ion-acoustic solitary waves (IASWs), which accompany electronegative plasmas having positive ions, negative ions, and nonextensive electrons is addressed. The energy integral equation with a new Sagdeev potential is analyzed to examine the existence regions of the IASWs. Different types of electronegative plasmas inspired from the experimental studies of Ichiki et al. (2001) are discussed. Our results show that in such plasmas IASWs, the amplitude and nature of which depend sensitively on the mass and density ratio of the positive and negative ions as well as the q-nonextensive parameter, can exist. Interestingly, one finds that our plasma model supports the coexistence of smooth rarefactive and spiky compressive IASWs. Our results complement and provide new insights on previously published findings on this problem.

The Semantics of Complementation in English: A Cognitive Semantic Account of Two English Complement Constructions

ERIC Educational Resources Information Center

Smith, Michael B.

2009-01-01

Studies on complementation in English and other languages have traditionally focused on syntactic issues, most notably on the constituent structures of different complement types. As a result, they have neglected the role of meaning in the choice of different complements. This paper investigates the semantics of complementation within the…

A Program of Ground-Based Astronomy to Complement Einstein Observations.

DTIC Science & Technology

1982-11-30

Astronomy D T I C i CO-,,, Uv I,. WA TOPE: -. Gary A. Cbanan Assistant Professor of Phy.3[cs i t0V.l.., 1982 %30𔃼 0 ii CONTENTS Page A. REPORT DOCUMENTATION...block number) A total of eight ground-based astronomical observing programs were carried out in pursuit of a multiwavelength approach to a number of...astro- physical problems. Synthesis of these results with existing X-ray data led to considerable progress on problems of the emission mechanisms and

Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation*

PubMed Central

Kunchithapautham, Kannan; Atkinson, Carl; Rohrer, Bärbel

2014-01-01

Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD. PMID:24711457

Fair Package Assignment

NASA Astrophysics Data System (ADS)

Lahaie, Sébastien; Parkes, David C.

We consider the problem of fair allocation in the package assignment model, where a set of indivisible items, held by single seller, must be efficiently allocated to agents with quasi-linear utilities. A fair assignment is one that is efficient and envy-free. We consider a model where bidders have superadditive valuations, meaning that items are pure complements. Our central result is that core outcomes are fair and even coalition-fair over this domain, while fair distributions may not even exist for general valuations. Of relevance to auction design, we also establish that the core is equivalent to the set of anonymous-price competitive equilibria, and that superadditive valuations are a maximal domain that guarantees the existence of anonymous-price competitive equilibrium. Our results are analogs of core equivalence results for linear prices in the standard assignment model, and for nonlinear, non-anonymous prices in the package assignment model with general valuations.

Wyoming Department of Transportation geographic information system implementation project

DOT National Transportation Integrated Search

2000-01-01

A geographic information system (GIS) was needed by the Wyoming Department of Transportation (WYDOT) to complement existing information management procedures and leverage the spatial components of its data. WYDOT contracted with Environmental Systems...

Variola virus immune evasion design: expression of a highly efficient inhibitor of human complement.

PubMed

Rosengard, Ariella M; Liu, Yu; Nie, Zhiping; Jimenez, Robert

2002-06-25

Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and has no other animal reservoir. Variola causes the contagious disease smallpox, which has a 30-40% mortality rate. Conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. However, the threat of smallpox persists because clandestine stockpiles of variola still exist. Although variola and vaccinia share remarkable DNA homology, the strict human tropism of variola suggests that its proteins are better suited than those of vaccinia to overcome the human immune response. Here, we demonstrate the functional advantage of a variola complement regulatory protein over that of its vaccinia homologue. Because authentic variola proteins are not available for study, we molecularly engineered and characterized the smallpox inhibitor of complement enzymes (SPICE), a homologue of a vaccinia virulence factor, vaccinia virus complement control protein (VCP). SPICE is nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE is also more human complement-specific than is VCP. By inactivating complement components, SPICE serves to inhibit the formation of the C3/C5 convertases necessary for complement-mediated viral clearance. SPICE provides the first evidence that variola proteins are particularly adept at overcoming human immunity, and the decreased function of VCP suggests one reason why the vaccinia virus vaccine was associated with relatively low mortality. Disabling SPICE may be therapeutically useful if smallpox reemerges.

Variola virus immune evasion design: Expression of a highly efficient inhibitor of human complement

PubMed Central

Rosengard, Ariella M.; Liu, Yu; Nie, Zhiping; Jimenez, Robert

2002-01-01

Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and has no other animal reservoir. Variola causes the contagious disease smallpox, which has a 30–40% mortality rate. Conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. However, the threat of smallpox persists because clandestine stockpiles of variola still exist. Although variola and vaccinia share remarkable DNA homology, the strict human tropism of variola suggests that its proteins are better suited than those of vaccinia to overcome the human immune response. Here, we demonstrate the functional advantage of a variola complement regulatory protein over that of its vaccinia homologue. Because authentic variola proteins are not available for study, we molecularly engineered and characterized the smallpox inhibitor of complement enzymes (SPICE), a homologue of a vaccinia virulence factor, vaccinia virus complement control protein (VCP). SPICE is nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE is also more human complement-specific than is VCP. By inactivating complement components, SPICE serves to inhibit the formation of the C3/C5 convertases necessary for complement-mediated viral clearance. SPICE provides the first evidence that variola proteins are particularly adept at overcoming human immunity, and the decreased function of VCP suggests one reason why the vaccinia virus vaccine was associated with relatively low mortality. Disabling SPICE may be therapeutically useful if smallpox reemerges. PMID:12034872

Juvenile obesity and its association with utilisation and costs of pharmaceuticals - results from the KiGGS study

PubMed Central

2011-01-01

Background According to a national reference, 15% of German children and adolescents are overweight (including obese) and 6.3% are obese. An earlier study analysed the impact of childhood overweight and obesity on different components of direct medical costs (physician, hospital and therapists). To complement the existing literature for Germany, this study aims to explore the association of body mass index (BMI) with utilisation of pharmaceuticals and related costs in German children and adolescents. Methods Based on data from 14, 836 respondents aged 3-17 years in the German Interview and Examination Survey for Children and Adolescents (KiGGS), drug intake and associated costs were estimated using a bottom-up approach. To investigate the association of BMI with utilisation and costs, univariate analyses and multivariate generalised mixed models were conducted. Results There was no significant difference between BMI groups regarding the probability of drug utilisation. However, the number of pharmaceuticals used was significantly higher (14%) for obese children than for normal weight children. Furthermore, there was a trend for more physician-prescribed medication in obese children and adolescents. Among children with pharmaceutical intake, estimated costs were 24% higher for obese children compared with the normal weight group. Conclusions This is the first study to estimate excess drug costs for obesity based on a representative cross-sectional sample of the child and adolescent population in Germany. The results suggest that obese children should be classified as a priority group for prevention. This study complements the existing literature and provides important information concerning the relevance of childhood obesity as a health problem. PMID:22176689

Actual consumption amount of personal care products reflecting Japanese cosmetic habits.

PubMed

Yamaguchi, Masahiko; Araki, Daisuke; Kanamori, Takeshi; Okiyama, Yasuko; Seto, Hirokazu; Uda, Masaki; Usami, Masahito; Yamamoto, Yutaka; Masunaga, Takuji; Sasa, Hitoshi

2017-01-01

Safety assessments of cosmetics are carried out by identifying possible harmful effects of substances in cosmetic products and assessing the exposure to products containing these substances. The present study provided data on the amounts of cosmetic products consumed in Japan to enhance and complement the existing data from Europe and the United States, i.e., the West. The outcomes of this study increase the accuracy of exposure assessments and enable more sophisticated risk assessment as a part of the safety assessment of cosmetic products. Actual amounts of products applied were calculated by determining the difference in the weight of products before and after use by approximately 300 subjects. The results of the study of skincare products revealed that in comparison with the West, large amounts of lotions and emulsions were applied, whereas lower amounts of cream and essence were applied in Japan. In the study of sunscreen products, actual measured values during outdoor leisure use were obtained, and these were lower than the values from the West. The study of the use of facial mask packs yielded data on typical Japanese sheet-type impregnated masks and revealed that high amounts were applied. Furthermore, data were obtained on cleansing foams, makeup removers and makeup products. The data from the present study enhance and complement existing information and will facilitate more sophisticated risk assessments. The present results should be extremely useful in safety assessments of newly developed cosmetic products and to regulatory authorities in Japan and around the world.

[The complement system as a main actor in the pathogenesis of obstetric antiphospholipid syndrome].

PubMed

Alijotas-Reig, Jaume

2010-01-23

Pregnancy losses are the main obstetrical complications of the obstetric antiphospholipid syndrome (obstetric-APS). Classically, they have been strongly attributed to thrombosis and further placental infarcts. But in some cases is not possible to show evidence of decidual thrombosis or placental vasculopathy, and sometimes inflammatory signs are present. Besides, the prevalence of systemic thrombosis is low in obstetric APS patients. Some cases have low plasma C4/C3 levels. Animal models show a local inflammatory mechanism. The beta2-glycoprotein-I/anti-beta2-glycoprotein-I complexes activate both, classical and alternative complement pathways. Complement proteins may injure trophoblast cells, recruiting and activating monocytes and neutrophils. Free radicals and proteolytic enzymes could also attack trophoblastic cells. In addition, an amplifier loop between the tissue factor, inflammatory cells and complement proteins could exist. Overall, these diverse mechanisms may explain both, inflammatory and thrombophilic placental alterations. In the end, the role played in this binomial by certain pro-inflammatory cytokines, mainly TNF-alpha, remains to clarify. Copyright 2009 Elsevier España, S.L. All rights reserved.

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion.

PubMed

Hovingh, Elise S; van den Broek, Bryan; Jongerius, Ilse

2016-01-01

The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion

PubMed Central

Hovingh, Elise S.; van den Broek, Bryan; Jongerius, Ilse

2016-01-01

The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed. PMID:28066340

The feasibility of equilibria in large ecosystems: A primary but neglected concept in the complexity-stability debate

PubMed Central

Dougoud, Michaël; Rohr, Rudolf P.

2018-01-01

The consensus that complexity begets stability in ecosystems was challenged in the seventies, a result recently extended to ecologically-inspired networks. The approaches assume the existence of a feasible equilibrium, i.e. with positive abundances. However, this key assumption has not been tested. We provide analytical results complemented by simulations which show that equilibrium feasibility vanishes in species rich systems. This result leaves us in the uncomfortable situation in which the existence of a feasible equilibrium assumed in local stability criteria is far from granted. We extend our analyses by changing interaction structure and intensity, and find that feasibility and stability is warranted irrespective of species richness with weak interactions. Interestingly, we find that the dynamical behaviour of ecologically inspired architectures is very different and richer than that of unstructured systems. Our results suggest that a general understanding of ecosystem dynamics requires focusing on the interplay between interaction strength and network architecture. PMID:29420532

Discriminating the hemolytic risk of blood type A plasmas using the complement hemolysis using human erythrocytes (CHUHE) assay.

PubMed

Cunnion, Kenji M; Hair, Pamela S; Krishna, Neel K; Sass, Megan A; Enos, Clinton W; Whitley, Pamela H; Maes, Lanne Y; Goldberg, Corinne L

2017-03-01

The agglutination-based cross-matching method is sensitive for antibody binding to red blood cells but is only partially predictive of complement-mediated hemolysis, which is important in many acute hemolytic transfusion reactions. Here, we describe complement hemolysis using human erythrocytes (CHUHE) assays that directly evaluate complement-mediated hemolysis between individual serum-plasma and red blood cell combinations. The CHUHE assay is used to evaluate correlations between agglutination titers and complement-mediated hemolysis as well as the hemolytic potential of plasma from type A blood donors. Plasma or serum from each type A blood donor was incubated with AB or B red blood cells in the CHUHE assay and measured for free hemoglobin release. CHUHE assays for serum or plasma demonstrate a wide, dynamic range and high sensitivity for complement-mediated hemolysis for individual serum/plasma and red blood cell combinations. CHUHE results suggest that agglutination assays alone are only moderately predictive of complement-mediated hemolysis. CHUHE results also suggest that plasma from particular type A blood donors produce minimal complement-mediated hemolysis, whereas plasma from other type A blood donors produce moderate to high-level complement-mediated hemolysis, depending on the red blood cell donor. The current results indicate that the CHUHE assay can be used to assess complement-mediated hemolysis for plasma or serum from a type A blood donor, providing additional risk discrimination over agglutination titers alone. © 2016 AABB.

Current status of matrix-assisted laser desorption ionisation-time of flight mass spectrometry in the clinical microbiology laboratory.

PubMed

Kok, Jen; Chen, Sharon C A; Dwyer, Dominic E; Iredell, Jonathan R

2013-01-01

The integration of matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) into many clinical microbiology laboratories has revolutionised routine pathogen identification. MALDI-TOF MS complements and has good potential to replace existing phenotypic identification methods. Results are available in a more clinically relevant timeframe, particularly in bacteraemic septic shock. Novel applications include strain typing and the detection of antimicrobial resistance, but these are not widely used. This review discusses the technical aspects, current applications, and limitations of MALDI-TOF MS.

Moral Enhancement Should Target Self-Interest and Cognitive Capacity.

PubMed

Ahlskog, Rafael

2017-01-01

Current suggestions for capacities that should be targeted for moral enhancement has centered on traits like empathy, fairness or aggression. The literature, however, lacks a proper model for understanding the interplay and complexity of moral capacities, which limits the practicability of proposed interventions. In this paper, I integrate some existing knowledge on the nature of human moral behavior and present a formal model of prosocial motivation. The model provides two important results regarding the most friction-free route to moral enhancement. First, we should consider decreasing self-interested motivation rather than increasing prosociality directly. Second, this should be complemented with cognitive enhancement. These suggestions are tested against existing and emerging evidence on cognitive capacity, mindfulness meditation and the effects of psychedelic drugs and are found to have sufficient grounding for further theoretical and empirical exploration. Furthermore, moral effects of the latter two are hypothesized to result from a diminished sense of self with subsequent reductions in self-interest.

Existence and global exponential stability of periodic solution of memristor-based BAM neural networks with time-varying delays.

PubMed

Li, Hongfei; Jiang, Haijun; Hu, Cheng

2016-03-01

In this paper, we investigate a class of memristor-based BAM neural networks with time-varying delays. Under the framework of Filippov solutions, boundedness and ultimate boundedness of solutions of memristor-based BAM neural networks are guaranteed by Chain rule and inequalities technique. Moreover, a new method involving Yoshizawa-like theorem is favorably employed to acquire the existence of periodic solution. By applying the theory of set-valued maps and functional differential inclusions, an available Lyapunov functional and some new testable algebraic criteria are derived for ensuring the uniqueness and global exponential stability of periodic solution of memristor-based BAM neural networks. The obtained results expand and complement some previous work on memristor-based BAM neural networks. Finally, a numerical example is provided to show the applicability and effectiveness of our theoretical results. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of Zea mays endosperm C-24 sterol methyltransferase: one of two types of sterol methyltransferase in higher plants.

PubMed

Grebenok, R J; Galbraith, D W; Penna, D D

1997-08-01

We report the characterization of a higher-plant C-24 sterol methyltransferase by yeast complementation. A Zea mays endosperm expressed sequence tag (EST) was identified which, upon complete sequencing, showed 46% identity to the yeast C-24 methyltransferase gene (ERG6) and 75% and 37% amino acid identity to recently isolated higher-plant sterol methyltransferases from soybean and Arabidopsis, respectively. When placed under GALA regulation, the Z. mays cDNA functionally complemented the erg6 mutation, restoring ergosterol production and conferring resistance to cycloheximide. Complementation was both plasmid-dependent and galactose-inducible. The Z. mays cDNA clone contains an open reading frame encoding a 40 kDa protein containing motifs common to a large number of S-adenosyl-L-methionine methyltransferases (SMTs). Sequence comparisons and functional studies of the maize, soybean and Arabidopsis cDNAs indicates two types of C-24 SMTs exist in higher plants.

Motivational Design in Information Literacy Instruction

ERIC Educational Resources Information Center

Hess, Amanda Nichols

2015-01-01

Motivational design theory complements instructional design theory and, when used together, both principles can affect learning, knowledge acquisition, and knowledge retention. In information literacy instruction, motivational design exists throughout the appropriate standards documents. However, there is limited current research on the best…

Aerobic Biodegradation of Oily Wastes: A Field Guide For Federal On-scene Coordinators

EPA Pesticide Factsheets

Intentionally limited in scope to best serve the requirements of the Region 6 Oil Program, this field guide consists of three parts complemented by appendices. Helps evaluate environment and consider factors, existing regulations/policies, operation issues

Evasion of Complement-Mediated Lysis and Complement C3 Deposition Are Regulated by Francisella tularensis Lipopolysaccharide O Antigen1

PubMed Central

Clay, Corey D.; Soni, Shilpa; Gunn, John S.; Schlesinger, Larry S.

2009-01-01

The bacterium Francisella tularensis (Ft) is a potential weapon of bioterrorism when aerosolized. Macrophage infection is necessary for disease progression and efficient phagocytosis by human macrophages requires serum opsonization by complement. Microbial complement activation leads to surface deposition of a highly regulated protein complex resulting in opsonization or membrane lysis. The nature of complement component C3 deposition, i.e., C3b (opsonization and lysis) or C3bi (opsonization only) fragment deposition, is central to the outcome of activation. In this study, we examine the mechanisms of Ft resistance to complement-mediated lysis, C3 component deposition on the Ft surface, and complement activation. Upon incubation in fresh nonimmune human serum, Schu S4 (Ft subsp. tularensis), Fn (Ft subsp. novicida), and LVS (Ft subsp. holarctica live vaccine strain) were resistant to complement-mediated lysis, but LVSG and LVSR (LVS strains altered in surface carbohydrate structures) were susceptible. C3 deposition, however, occurred on all strains. Complement-susceptible strains had markedly increased C3 fragment deposition, including the persistent presence of C3b compared with C3bi, which indicates that C3b inactivation results in survival of complement-resistant strains. C1q, an essential component of the classical activation pathway, was necessary for lysis of complement-susceptible strains and optimal C3 deposition on all strains. Finally, use of Francisella LPS mutants confirmed O Ag as a major regulator of complement resistance. These data provide evidence that pathogenic Francisella activate complement, but are resistant to complement-mediated lysis in part due to limited C3 deposition, rapid conversion of surface-bound C3b to C3bi, and the presence of LPS O Ag. PMID:18832715

Tuning complement activation and pathway through controlled molecular architecture of dextran chains in nanoparticle corona.

PubMed

Coty, Jean-Baptiste; Eleamen Oliveira, Elquio; Vauthier, Christine

2017-11-05

The understanding of complement activation by nanomaterials is a key to a rational design of safe and efficient nanomedicines. This work proposed a systematic study investigating how molecular design of nanoparticle coronas made of dextran impacts on mechanisms that trigger complement activation. The nanoparticles used for this work consisted of dextran-coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly characterized. Their different capacity to trigger complement activation established on the cleavage of the protein C3 was also already described making these nanoparticles good models to investigate the relation between the molecular feature of their corona and the mechanism by which they triggered complement activation. Results of this new study show that complement activation pathways can be selected by distinct architectures formed by dextran chains composing the nanoparticle corona. Assumptions that explain the relation between complement activation mechanisms triggered by the nanoparticles and the nanoparticle corona molecular feature were proposed. These results are of interest to better understand how the design of dextran-coated nanomaterials will impact interactions with the complement system. It can open perspectives with regard to the selection of a preferential complement activation pathway or prevent the nanoparticles to activate the complement system, based on a rational choice of the corona configuration. Copyright © 2017 Elsevier B.V. All rights reserved.

Local Voltage Control in Distribution Networks: A Game-Theoretic Perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Xinyang; Tian, Jie; Chen, Lijun

Inverter-based voltage regulation is gaining importance to alleviate emerging reliability and power-quality concerns related to distribution systems with high penetration of photovoltaic (PV) systems. This paper seeks contribution in the domain of reactive power compensation by establishing stability of local Volt/VAr controllers. In lieu of the approximate linear surrogate used in the existing work, the paper establishes existence and uniqueness of an equilibrium point using nonlinear AC power flow model. Key to this end is to consider a nonlinear dynamical system with non-incremental local Volt/VAr control, cast the Volt/VAr dynamics as a game, and leverage the fixed-point theorem as wellmore » as pertinent contraction mapping argument. Numerical examples are provided to complement the analytical results.« less

Local Voltage Control in Distribution Networks: A Game-Theoretic Perspective: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Xinyang; Tian, Jie; Chen, Lijun

Inverter-based voltage regulation is gaining importance to alleviate emerging reliability and power-quality concerns related to distribution systems with high penetration of photovoltaic (PV) systems. This paper seeks contribution in the domain of reactive power compensation by establishing stability of local Volt/VAr controllers. In lieu of the approximate linear surrogate used in the existing work, the paper establishes existence and uniqueness of an equilibrium point using nonlinear AC power flow model. Key to this end is to consider a nonlinear dynamical system with non-incremental local Volt/VAr control, cast the Volt/VAr dynamics as a game, and leverage the fixed-point theorem as wellmore » as pertinent contraction mapping argument. Numerical examples are provided to complement the analytical results.« less

Role of Shellfish Aquaculture in the Reduction of Eutrophication in an Urban Estuary

EPA Science Inventory

Land-based management has reduced nutrient discharges; however, many coastal waterbodies remain impaired. Oyster “bioextraction” of nutrients and how oyster aquaculture might complement existing management measures in urban estuaries was examined in Long Island Sound, Connecticut...

INDOOR AIR QUALITY AND INHALATION EXPOSURE - SIMULATION TOOL KIT

EPA Science Inventory

A Microsoft Windows-based indoor air quality (IAQ) simulation software package is presented. Named Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short, this package complements and supplements existing IAQ simulation programs and is desi...

Complement Activation in Inflammatory Skin Diseases

PubMed Central

Giang, Jenny; Seelen, Marc A. J.; van Doorn, Martijn B. A.; Rissmann, Robert; Prens, Errol P.; Damman, Jeffrey

2018-01-01

The complement system is a fundamental part of the innate immune system, playing a crucial role in host defense against various pathogens, such as bacteria, viruses, and fungi. Activation of complement results in production of several molecules mediating chemotaxis, opsonization, and mast cell degranulation, which can contribute to the elimination of pathogenic organisms and inflammation. Furthermore, the complement system also has regulating properties in inflammatory and immune responses. Complement activity in diseases is rather complex and may involve both aberrant expression of complement and genetic deficiencies of complement components or regulators. The skin represents an active immune organ with complex interactions between cellular components and various mediators. Complement involvement has been associated with several skin diseases, such as psoriasis, lupus erythematosus, cutaneous vasculitis, urticaria, and bullous dermatoses. Several triggers including auto-antibodies and micro-organisms can activate complement, while on the other hand complement deficiencies can contribute to impaired immune complex clearance, leading to disease. This review provides an overview of the role of complement in inflammatory skin diseases and discusses complement factors as potential new targets for therapeutic intervention. PMID:29713318

Complementing Gender Analysis Methods.

PubMed

Kumar, Anant

2016-01-01

The existing gender analysis frameworks start with a premise that men and women are equal and should be treated equally. These frameworks give emphasis on equal distribution of resources between men and women and believe that this will bring equality which is not always true. Despite equal distribution of resources, women tend to suffer and experience discrimination in many areas of their lives such as the power to control resources within social relationships, and the need for emotional security and reproductive rights within interpersonal relationships. These frameworks believe that patriarchy as an institution plays an important role in women's oppression, exploitation, and it is a barrier in their empowerment and rights. Thus, some think that by ensuring equal distribution of resources and empowering women economically, institutions like patriarchy can be challenged. These frameworks are based on proposed equality principle which puts men and women in competing roles. Thus, the real equality will never be achieved. Contrary to the existing gender analysis frameworks, the Complementing Gender Analysis framework proposed by the author provides a new approach toward gender analysis which not only recognizes the role of economic empowerment and equal distribution of resources but suggests to incorporate the concept and role of social capital, equity, and doing gender in gender analysis which is based on perceived equity principle, putting men and women in complementing roles that may lead to equality. In this article the author reviews the mainstream gender theories in development from the viewpoint of the complementary roles of gender. This alternative view is argued based on existing literature and an anecdote of observations made by the author. While criticizing the equality theory, the author offers equity theory in resolving the gender conflict by using the concept of social and psychological capital.

The Complement System in Dialysis: A Forgotten Story?

PubMed Central

Poppelaars, Felix; Faria, Bernardo; Gaya da Costa, Mariana; Franssen, Casper F. M.; van Son, Willem J.; Berger, Stefan P.; Daha, Mohamed R.; Seelen, Marc A.

2018-01-01

Significant advances have lead to a greater understanding of the role of the complement system within nephrology. The success of the first clinically approved complement inhibitor has created renewed appreciation of complement-targeting therapeutics. Several clinical trials are currently underway to evaluate the therapeutic potential of complement inhibition in renal diseases and kidney transplantation. Although, complement has been known to be activated during dialysis for over four decades, this area of research has been neglected in recent years. Despite significant progress in biocompatibility of hemodialysis (HD) membranes and peritoneal dialysis (PD) fluids, complement activation remains an undesired effect and relevant issue. Short-term effects of complement activation include promoting inflammation and coagulation. In addition, long-term complications of dialysis, such as infection, fibrosis and cardiovascular events, are linked to the complement system. These results suggest that interventions targeting the complement system in dialysis could improve biocompatibility, dialysis efficacy, and long-term outcome. Combined with the clinical availability to safely target complement in patients, the question is not if we should inhibit complement in dialysis, but when and how. The purpose of this review is to summarize previous findings and provide a comprehensive overview of the role of the complement system in both HD and PD. PMID:29422906

A mutational approach for the detection of genetic factors affecting seed size in maize.

PubMed

Sangiorgio, Stefano; Carabelli, Laura; Gabotti, Damiano; Manzotti, Priscilla Sofia; Persico, Martina; Consonni, Gabriella; Gavazzi, Giuseppe

2016-12-01

Genes influencing seed size. The designation emp (empty pericarp) refers to a group of defective kernel mutants that exhibit a drastic reduction in endosperm tissue production. They allow the isolation of genes controlling seed development and affecting seed size. Nine independently isolated emp mutants have been analyzed in this study and in all cases longitudinal sections of mature seeds revealed the absence of morphogenesis in the embryo proper, an observation that correlates with their failure to germinate. Complementation tests with the nine emp mutants, crossed inter se in all pairwise combinations, identified complementing and non-complementing pairs in the F 1 progenies. Data were then validated in the F 2 /F 3 generations. Mutant chromosomal location was also established. Overall our study has identified two novel emp genes and a novel allele at the previously identified emp4 gene. The introgression of single emp mutants in a different genetic background revealed the existence of a cryptic genetic variation (CGV) recognizable as a variable increase in the endosperm tissue. The unmasking of CGV by introducing single mutants in different genetic backgrounds is the result of the interaction of the emp mutants with a suppressor that has no obvious phenotype of its own and is present in the genetic background of the inbred lines into which the emp mutants were transferred. On the basis of these results, emp mutants could be used as tools for the detection of genetic factors that enhance the amount of endosperm tissue in the maize kernel and which could thus become valuable targets to exploit in future breeding programs.

Into the 80s: Our Schools and Their Purposes.

ERIC Educational Resources Information Center

South Australia Education Dept., Adelaide.

Complementing existing regulations, this policy statement for South Australian schools presents educational goals and priorities for the decade and general implications for classroom, curriculum, and resource allocation. Background discussion covers factors influencing recent developments in South Australian education, a summary of the role of…

Many Thousand Words . . . Work Pictures.

ERIC Educational Resources Information Center

Office of Career Education (DHEW/OE), Washington, DC.

This collection of photographs and discussion questions for elementary students is designed to complement and supplement already existing instructional materials by showing females and males engaged in nonstereotyped jobs and activities. The guide provides definitions of terms such as work, career, duty, sexism, and stereotype; fourteen facts on…

Feasibility of correlation mapping optical coherence tomography (cmOCT) for anti-spoof sub-surface fingerprinting.

PubMed

Zam, Azhar; Dsouza, Roshan; Subhash, Hrebesh M; O'Connell, Marie-Louise; Enfield, Joey; Larin, Kirill; Leahy, Martin J

2013-09-01

We propose the use of correlation mapping optical coherence tomography (cmOCT) to deliver additional biometrics associated with the finger that could complement existing fingerprint technology for law enforcement applications. The current study extends the existing fingerprint paradigm by measuring additional biometrics associated with sub-surface finger tissue such as sub-surface fingerprints, sweat glands, and the pattern of the capillary bed to yield a user-friendly cost effective and anti-spoof multi-mode biometric solution associated with the finger. To our knowledge no other method has been able to capture sub-surface fingerprint, papillary pattern and horizontal vessel pattern in a single scan or to show the correspondence between these patterns in live adult human fingertip. Unlike many current technologies this approach incorporates 'liveness' testing by default. The ultimate output is a biometric module which is difficult to defeat and complements fingerprint scanners that currently are used in border control and law enforcement applications. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

"Sniffing" Jupiter's moon Europa through ground-based IR observations

NASA Astrophysics Data System (ADS)

Paganini, Lucas; Mumma, Michael J.; Hurford, Terry; Roth, Lorenz; Villanueva, Geronimo Luis

2016-10-01

The ability to sample possible plumes from the subsurface ocean in Europa represents a major step in our search for extraterrestrial life. If plumes exist, sampling the effluent material would provide insights into their chemistry and relevant information about the prospect that life could exist, or now exists, within the ocean. Most of the difficulties in detecting plumes come from the less frequent observational coverage of Europa, which contrasts strongly with the frequent Cassini flybys of Enceladus (Spencer & Nimmo 2013). Recent observations have been taken with HST/STIS in 2014/2015, but results have shown no evident confirmation of the 2012 plume detection (Roth et al. 2014, 2015). Future in situ observations (Europa Mission) will provide definitive insights, but not before the spacecraft's arrival in ~2025, thus an interim approach is needed to inform such space mission planning and to complement existing observations at other wavelengths.In 2015, we initiated a strong campaign to build a comprehensive survey of possible plumes on Europa through high-resolution IR spectroscopy with Keck/NIRSPEC. We were awarded 10 nights out of 15 total nights available for Key Strategic Mission Support projects for the 2016A, 2016B, 2017A, and 2017B semesters under NASA time with the Keck Observatory. In 2016A, we observed Europa during 10 half-nights and will continue to do so for another 10 half-nights in 2017A. We target a serendipitous search of gaseous activity from Europa to confirm and constrain the chemical composition of possible Europan plumes that can aid the investigation of physical processes underlying (or on) its surface. Ultimately, we seek to: (1) provide information that can inform planning for NASA's Europa mission, (2) further our current understanding of Europa's gas environment, and (3) complement studies that are currently underway with other facilities (like the Hubble Space Telescope). In this presentation, we will discuss preliminary results, challenges, and future plans of our observing campaign.* This work was supported by a NASA Keck PI Data Award (PI LP), administered by the NASA Exoplanet Science Institute, and by the NASA Astrobiology Institute under proposal 13-13NAI7-0032 (PI MJM).

Complement Evasion Strategies of Viruses: An Overview

PubMed Central

Agrawal, Palak; Nawadkar, Renuka; Ojha, Hina; Kumar, Jitendra; Sahu, Arvind

2017-01-01

Being a major first line of immune defense, the complement system keeps a constant vigil against viruses. Its ability to recognize large panoply of viruses and virus-infected cells, and trigger the effector pathways, results in neutralization of viruses and killing of the infected cells. This selection pressure exerted by complement on viruses has made them evolve a multitude of countermeasures. These include targeting the recognition molecules for the avoidance of detection, targeting key enzymes and complexes of the complement pathways like C3 convertases and C5b-9 formation – either by encoding complement regulators or by recruiting membrane-bound and soluble host complement regulators, cleaving complement proteins by encoding protease, and inhibiting the synthesis of complement proteins. Additionally, viruses also exploit the complement system for their own benefit. For example, they use complement receptors as well as membrane regulators for cellular entry as well as their spread. Here, we provide an overview on the complement subversion mechanisms adopted by the members of various viral families including Poxviridae, Herpesviridae, Adenoviridae, Flaviviridae, Retroviridae, Picornaviridae, Astroviridae, Togaviridae, Orthomyxoviridae and Paramyxoviridae. PMID:28670306

Activation of the complement system in patients with porphyrias after irradiation in vivo.

PubMed Central

Lim, H W; Poh-Fitzpatrick, M B; Gigli, I

1984-01-01

Irradiation of the forearms of two patients with erythropoietic protoporphyria and one patient with porphyria cutanea tarda resulted in an in vivo activation of the complement system, as assessed by diminution of the hemolytic titers of the third component of complement by 23-57%, and of the fifth component of complement (C5) by 19-47%. Such treatment also generated chemotactic activity for human polymorphonuclear cells; the chemotactic activity was stable at 56 degrees C and antigenically related to human C5. On Sephadex G-75 chromatography the chemotactic activity eluted with an apparent molecular weight of 15,000. These in vivo results extend our previous in vitro observation of photoactivation of complement in sera from patients with erythropoietic protoporphyria and porphyria cutanea tarda, and suggest that the complement system may participate in the pathogenesis of cutaneous phototoxicity in these patients. PMID:6392339

Guinea pig complement potently measures vibriocidal activity of human antibodies in response to cholera vaccines.

PubMed

Kim, Kyoung Whun; Jeong, Soyoung; Ahn, Ki Bum; Yang, Jae Seung; Yun, Cheol-Heui; Han, Seung Hyun

2017-12-01

The vibriocidal assay using guinea pig complement is widely used for the evaluation of immune responses to cholera vaccines in human clinical trials. However, it is unclear why guinea pig complement has been used over human complement in the measurement of vibriocidal activity of human sera and there have not been comparison studies for the use of guinea pig complement over those from other species. Therefore, we comparatively investigated the effects of complements derived from human, guinea pig, rabbit, and sheep on vibriocidal activity. Complements from guinea pig, rabbit, and human showed concentration-dependent vibriocidal activity in the presence of quality control serum antibodies. Of these complements, guinea pig complement was the most sensitive and effective over a wide concentration range. When the vibriocidal activity of complements was measured in the absence of serum antibodies, human, sheep, and guinea pig complements showed vibriocidal activity up to 40-fold, 20-fold, and 1-fold dilution, respectively. For human pre- and post-vaccination sera, the most potent vibriocidal activity was observed when guinea pig complement was used. In addition, the highest fold-increases between pre- and post- vaccinated sera were obtained with guinea pig complement. Furthermore, human complement contained a higher amount of V. cholerae- and its lipopolysaccharide-specific antibodies than guinea pig complement. Collectively, these results suggest that guinea pig complements are suitable for vibriocidal assays due to their high sensitivity and effectiveness to human sera.

Sex matters: Systemic complement activity of female C57BL/6J and BALB/cJ mice is limited by serum terminal pathway components.

PubMed

Kotimaa, Juha; Klar-Mohammad, Ngaisah; Gueler, Faikah; Schilders, Geurt; Jansen, Aswin; Rutjes, Helma; Daha, Mohamed R; van Kooten, Cees

2016-08-01

Experimental mouse models have been extensively used to elucidate the role of the complement system in different diseases and injuries. Contribution of gender has revealed an intriguing gender specific difference; female mice often show protection against most complement driven injuries such as ischemia/reperfusion injury, graft rejection and sepsis. Interestingly, early studies to the mouse complement system revealed that female mice have very low total complement activity (CH50), which is related to androgen regulation of hepatic complement synthesis. Here, our aim was to understand at which level the female specific differences in mouse complement resides. We have used recently developed complement assays to study the functional activities of female and male mice at the level of C3 and C9 activation, and furthermore assayed key complement factor levels in serum of age-matched female and male C57BL/6 mice. Our results show that the female mice have normal complement cascade functionality at the level of C3 activation, which was supported by determinations of early complement factors. However, all pathways are strongly reduced at the level of C9 activation, suggesting a terminal pathway specific difference. This was in line with C6 and C9 measurements, showing strongly decreased levels in females. Furthermore, similar gender differences were also found in BALB/cJ mice, but not in CD-1 mice. Our results clearly demonstrate that the complement system in females of frequently used mouse strains is restricted by the terminal pathway components and that the perceived female specific protection against experimental disease and injury might be in part explained by the inability promote inflammation through C5b-9. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Load Model Verification, Validation and Calibration Framework by Statistical Analysis on Field Data

NASA Astrophysics Data System (ADS)

Jiao, Xiangqing; Liao, Yuan; Nguyen, Thai

2017-11-01

Accurate load models are critical for power system analysis and operation. A large amount of research work has been done on load modeling. Most of the existing research focuses on developing load models, while little has been done on developing formal load model verification and validation (V&V) methodologies or procedures. Most of the existing load model validation is based on qualitative rather than quantitative analysis. In addition, not all aspects of model V&V problem have been addressed by the existing approaches. To complement the existing methods, this paper proposes a novel load model verification and validation framework that can systematically and more comprehensively examine load model's effectiveness and accuracy. Statistical analysis, instead of visual check, quantifies the load model's accuracy, and provides a confidence level of the developed load model for model users. The analysis results can also be used to calibrate load models. The proposed framework can be used as a guidance to systematically examine load models for utility engineers and researchers. The proposed method is demonstrated through analysis of field measurements collected from a utility system.

CatReg Software for Categorical Regression Analysis (May 2016)

EPA Science Inventory

CatReg 3.0 is a Microsoft Windows enhanced version of the Agency’s categorical regression analysis (CatReg) program. CatReg complements EPA’s existing Benchmark Dose Software (BMDS) by greatly enhancing a risk assessor’s ability to determine whether data from separate toxicologic...

Project WET: Facilitator Handbook for Implementation of Activities in Virginia.

ERIC Educational Resources Information Center

Sevebeck, Kathryn P.

This handbook features ideas for implementing Project WET activities in Virginia. Project WET activities are designed for a variety of educational programs and can be used to complement existing curricula while addressing curricular objectives and educational standards nationwide. Activities include: (1) "Life Systems"; (2)…

Development of Guidelines for Identification of SCC Sites and Estimation of Re-Inspection Intervals for SCC Direct Assessment

DOT National Transportation Integrated Search

2010-05-31

This report describes the development of a series of guidelines for the identification of SCC sites and the estimation of re-inspection intervals. These SCC Guidelines are designed to complement and supplement existing SCC Direct Assessment protocols...

An observation of nanotwin lamellae in Cd 0.6Mn 0.4Te crystal by atomic force microscopy

NASA Astrophysics Data System (ADS)

George, M. A.; Azoulay, M.; Collins, W. E.; Burger, A.; Silberman, E.

1993-05-01

Atomic force microscopy (AFM) is used to examine the structure of freshly cleaved Cd 0.6Mn 0.4Te surfaces. The present report complements previous results obtained with X-ray diffraction and optical microscopy which showed the existence of microtwins. The AFM analysis was performed under ambient conditions and yielded nanometer scale resolution images of single twin lamellae that ranged between 20 and 100 nm in width. This is a first observation using AFM of such a substructure, which we interpret as evidence for the presence of nonotwins.

Zebra Crossing Spotter: Automatic Population of Spatial Databases for Increased Safety of Blind Travelers

PubMed Central

Ahmetovic, Dragan; Manduchi, Roberto; Coughlan, James M.; Mascetti, Sergio

2016-01-01

In this paper we propose a computer vision-based technique that mines existing spatial image databases for discovery of zebra crosswalks in urban settings. Knowing the location of crosswalks is critical for a blind person planning a trip that includes street crossing. By augmenting existing spatial databases (such as Google Maps or OpenStreetMap) with this information, a blind traveler may make more informed routing decisions, resulting in greater safety during independent travel. Our algorithm first searches for zebra crosswalks in satellite images; all candidates thus found are validated against spatially registered Google Street View images. This cascaded approach enables fast and reliable discovery and localization of zebra crosswalks in large image datasets. While fully automatic, our algorithm could also be complemented by a final crowdsourcing validation stage for increased accuracy. PMID:26824080

From linear to nonlinear control means: a practical progression.

PubMed

Gao, Zhiqiang

2002-04-01

With the rapid advance of digital control hardware, it is time to take the simple but effective proportional-integral-derivative (PID) control technology to the next level of performance and robustness. For this purpose, a nonlinear PID and active disturbance rejection framework are introduced in this paper. It complements the existing theory in that (1) it actively and systematically explores the use of nonlinear control mechanisms for better performance, even for linear plants; (2) it represents a control strategy that is rather independent of mathematical models of the plants, thus achieving inherent robustness and reducing design complexity. Stability analysis, as well as software/hardware test results, are presented. It is evident that the proposed framework lends itself well in seeking innovative solutions to practical problems while maintaining the simplicity and the intuitiveness of the existing technology.

Electric currents in F-like planetary ionospheres

NASA Technical Reports Server (NTRS)

Cole, K. D.

1990-01-01

In this paper, electrical transport coefficients are found for charged particles in such lightly ionized gases as exist in planetary and stellar atmospheres, like the F-region of the earth's ionosphere. Electric fields and gradients of pressure in the ions and the electrons are taken as the drivers of electric current. Collisions of electrons with ions, and of ions and electrons with neutral particles, are taken into account, and new expressions are generated for electrical conductivity, heating rates, and diffusion of magnetic field. The paper extends and complements the results of an earlier paper by Cole (1990) which dealt with 'E-like' ionospheric regions. A comparison of the results with those of kinetic theory is made.

Parent-Collected Behavioral Observations: An Empirical Comparison of Methods

ERIC Educational Resources Information Center

Nadler, Cy B.; Roberts, Mark W.

2013-01-01

Treatments for disruptive behaviors are often guided by parent reports on questionnaires, rather than by multiple methods of assessment. Professional observations and clinic analogs exist to complement questionnaires, but parents can also collect useful behavioral observations to inform and guide treatment. Two parent observation methods of child…

Creative Retirement: Survey of Older Adults' Educational Interests and Motivations

ERIC Educational Resources Information Center

Sloane-Seale, Atlanta; Kops, Bill

2004-01-01

The University of Manitoba's Continuing Education Division (CED) and Creative Retirement Manitoba (CRM) formed a partnership to promote applied research on lifelong learning and older adults, to develop new and to complement existing educational activities, and to explore new program models and instructional methods to meet the educational needs…

On Systems Thinking and Ways of Building It in Learning

ERIC Educational Resources Information Center

Abdyrova, Aitzhan; Galiyev, Temir; Yessekeshova, Maral; Aldabergenova, Saule; Alshynbayeva, Zhuldyz

2016-01-01

The article focuses on the issue of shaping learners' systems thinking skills in the context of traditional education using specially elaborated system methods that are implemented based on the standard textbook. Applying these methods naturally complements the existing learning process and contributes to an efficient development of learners'…

Accelerated Reader. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2009

2009-01-01

"Accelerated Reader" is a computer-based reading management system designed to complement an existing classroom literacy program for grades pre-K-12. It is designed to increase the amount of time students spend reading independently. Students choose reading-level appropriate books or short stories for which Accelerated Reader tests are…

A Grammar of Inupiaq Morphosyntax

ERIC Educational Resources Information Center

Lanz, Linda A.

2010-01-01

This dissertation is a reference grammar of the Malimiut Coastal dialect of Inupiaq (ISO: ESI, ESK, IPK), an Eskimo-Aleut language of northwestern Alaska spoken by the Inupiat people. It complements existing descriptions of Inupiaq by filling gaps in documentation. With approximately 2000 speakers, mainly above 50 years of age, Inupiaq is…

Teaching Guide on Preventing Violent International Conflict.

ERIC Educational Resources Information Center

United States Inst. of Peace, Washington, DC.

In the belief that questions about peace, justice, freedom, and security are vital to civic education, the United States Institute of Peace established the National Peace Essay Contest, which is designed to promote discussion of international peace and conflict resolution, complement existing curricula, and strengthen students' research, writing,…

Development of the Exercise Motives and Gains Inventory

ERIC Educational Resources Information Center

Strömmer, Sofia T.; Ingledew, David K.; Markland, David

2015-01-01

There are existing measures of exercise motives (what people want from exercise), but corresponding measures of gains (what people get) are needed, because motives and gains could influence each other and together influence other variables. An exercise motives and gains inventory (EMGI) was developed by creating gains scales to complement existing…

SIMULATION TOOL KIT FOR INDOOR AIR QUALITY AND INHALATION EXPOSURE (IAQX) VERSION 1.0 USER'S GUIDE

EPA Science Inventory

The User's Guide describes a Microsoft Windows-based indoor air quality (IAQ) simulation software package designed Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short. This software complements and supplements existing IAQ simulation programs and...

Rationale for classical biological control of cattle fever ticks and proposed methods for field collection of natural enemies

USDA-ARS?s Scientific Manuscript database

Classical biological control using specialist parasitoids, predators and/or nematodes from the native ranges of cattle fever ticks Rhipicephalus microplus and Rhipicephalus annulatus could complement existing control strategies for this livestock pest in the transboundary region between Mexico and T...

The Power of Movement: Body-Engaging Activities for Teaching Economics

ERIC Educational Resources Information Center

Roncolato, Leanne; Koh, Cairynne

2017-01-01

Existing research points to the critical connection between student engagement and deep learning. This paper explores body engagement as one type of student centered learning. While other disciplines are making progress in developing body-engaging pedagogical methods as a complement to traditional lectures, the use of such innovations in…

MODELING THE DYNAMICS OF THREE FUNCTIONAL GROUPS OF MACROALGAE IN TROPICAL SEAGRASS HABITATS. (R828677C004)

EPA Science Inventory

A model of three functional groups of macroalgae, drift algae, rhizophytic calcareous algae, and seagrass epiphytes, was developed to complement an existing seagrass production model for tropical habitats dominated by Thalassia testudinum (Turtle-grass). The current modeling e...

The Educational and Economic Value of Online Learning for Museums

ERIC Educational Resources Information Center

Crow, William B.; Din, Herminia

2010-01-01

Given the increasingly interactive, dynamic, and cost-effective online learning platforms that are available, as well as studies that demonstrate the efficacy of online and blended learning, museums should consider how these new formats may complement their existing educational programs. Besides offering new possibilities for education, online…

The Use of User-Centered Participatory Design in Serious Games for Anxiety and Depression.

PubMed

Dekker, Maria R; Williams, Alishia D

2017-12-01

There is increasing interest in using serious games to deliver or complement healthcare interventions for mental health, particularly for the most common mental health conditions such as anxiety and depression. Initial results seem promising, yet variations exist in the effectiveness of serious games, highlighting the importance of understanding optimal design features. It has been suggested that the involvement of end-users in the design and decision-making process could influence game effectiveness. In user-centered design (UCD) or participatory design (PD), users are involved in stages of the process, including planning, designing, implementing, and testing the serious game. To the authors' knowledge, no literature review to date has assessed the use of UCD/PD in games that are designed for mental health, specifically for anxiety or depression. The aim of this review is, therefore, to document the extent to which published studies of serious games that are designed to prevent or treat anxiety and depression have adopted a PD framework. A search of keywords in PubMed and PsychINFO databases through to December 2016 was conducted. We identified 20 serious games developed to prevent, treat or complement existing therapies for anxiety and/or depression. Half (N = 10; 50%) of these games were developed with input from the intended end-users, in either informant (N = 7; 70%) or full participatory co-design roles (N = 3; 30%). Less than half of games (45%) included users only in the testing phase.

Theory of mind in SLI revisited: links with syntax, comparisons with ASD.

PubMed

Durrleman, Stephanie; Burnel, Morgane; Reboul, Anne

2017-11-01

According to the linguistic determinism approach, knowledge of sentential complements such as: John says that the earth is flat plays a crucial role in theory of mind (ToM) development by providing a means to represent explicitly people's mental attitudes and beliefs. This approach predicts that mastery of complements determines successful belief reasoning across explicit ToM tasks, even low-verbal ones, and across populations. (1) To investigate the link between a low-verbal ToM-task and complements in Specific Language Impairment (SLI), (2) To determine whether this population shows similar ToM performance to that of children with Autism Spectrum Disorder (ASD) or those with Typical Development (TD) once these groups are matched on competency for complements, (3) To explore whether complements conveying a falsehood without jeopardizing the veracity of the entire sentence, such as complements of verbs of communication, are more crucial for belief attribution than complements which do not have this property, namely complements of verbs of perception, (?John sees that the earth is flat). Children with SLI (n = 20), with ASD (n = 34) and TD (n = 30) completed sentence-picture-matching tasks assessing complementation with communication and perception verbs, as well as a picture-sequencing task assessing ToM. Children were furthermore evaluated for general grammatical and lexical abilities and non-verbal IQ. Results reveal that competency on complements relates to ToM performance with a low-verbal task in SLI, and that SLI, ASD and TD groups of equivalent performance on complements also perform similarly for ToM. Results further suggest that complements with an independent truth-value are the only ones to show a significant relation to ToM performance after teasing out the impact of non-verbal reasoning. This study suggests that clinical groups of different aetiologies as well as TD children perform comparably for ToM once they have similar complementation skills. Findings further highlight that specific types of complements, namely those with an independent truth value, relate in a special way to mentalizing. Future work should determine whether these specific structures could be effective in ToM remediation programmes. © 2017 Royal College of Speech and Language Therapists.

Percutaneous drainage and/or nephrectomy in the treatment of emphysematous pyelonephritis.

PubMed

Mydlo, Jack H; Maybee, Gabrielle J; Ali-Khan, Mustafa M

2003-01-01

To assess the current and past literature relating to the differential treatment of emphysematous pyelonephritis (EPN). Some of the newer literature suggests percutaneous drainage (PCD), as compared to the standard nephrectomy, as a better modality. Since these two may complement each other, we sought to seek indications when to perform each treatment. Medline and MD Consult were used for our journal review. Ten articles, ranging from 1980 to 2000, were chosen, which covered 162 patients. The criteria for selecting these articles were study size (n < 3 were excluded) and non-overlapping of patient information. Patient data was then used to certain risks of the various treatment modalities. Due to the lack of randomization of the studies, it is difficult to say whether PCD is superior to nephrectomy or not. It appears to be that each treatment may complement each other, and that treatment should be individualized based on the severity of the EPN and the medical condition of the patient. PCD though appears to be acceptable for use in the initial phases of the disease. However, long-term data is lacking to corroborate the overall benefit of PCD compared to nephrectomy. PCD could be utilized initially in some cases of EPN if certain conditions exist. This treatment may complement nephrectomy if the need exists, and therefore, treatment may be staged. Truly randomized studies need to be done to determine if one treatment is better than the other, and provide documented long-term follow-up of these patients.

Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy (DR) by Activating Classical Complement Pathway.

PubMed

Huang, Chao; Fisher, Kiera P; Hammer, Sandra S; Navitskaya, Svetlana; Blanchard, Gary J; Busik, Julia V

2018-06-04

Diabetic Retinopathy (DR) is a micro-vascular complication of diabetes and is the leading cause of vision loss in working-age adults. Recent studies have implicated the complement system as an emerging player in development of vascular damage and progression of DR. However, the role and activation of the complement system in DR is not well understood. Exosomes, small vesicles that are secreted into the extracellular environment, have a cargo of complement proteins in plasma suggesting that they can participate in causing vascular damage associated with DR. We demonstrate that IgG-laden exosomes in plasma activate the classical complement pathway, and that the quantity of these exosomes is increased in diabetes. Moreover, we show that lack of IgG in exosomes results in a reduction of retinal vascular damage in diabetic mice. Together, the results of this study demonstrate that complement activation by IgG-laden plasma exosomes could contribute to the development of DR. © 2018 by the American Diabetes Association.

[Legal aspects of the REACH regulation. The control system of the REACH regulation--new approaches in the EU chemical legislation].

PubMed

Pache, Eckhard

2008-12-01

The REACH regulation from 2006 shall overcome the deficiencies of the previously existing inconsistent legal system of chemicals and build an efficient and innovative regulation for industrial chemicals in the EU. For this purpose, the REACH regulation is not inventing a completely new legislation for chemical substances, but refers to the existing rules, regulates and structures them in a new manner and complements them. With REACH a consistent control system for chemicals in Europe has been created, which basically is managed and coordinated by the newly established European Chemicals Agency (ECHA). In the first phases of the REACH system, information about chemicals is generated and afterwards evaluated. Then this information is used in a process of authorization and restriction, to ensure adequate proliferation and safe exposure to chemical substances. Numerous duties to furnish information complement the readjustment's procedural steps, particularly with regard to the supply chain and down to the consumer. It is mainly affected by the abrogation of the determination between new and existing substances, the principle of substitution and is based on the idea that industry itself is best suited to ensure that the substances it manufactures and places on the market in the EU do not adversely affect human health or the environment.

Interallelic complementation of mutations in propionic acidemia by microinjection of mutant cDNAs into fibroblasts of affected patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loyer, M.; Leclerc, D.; Gravel, R.A.

1994-09-01

Propionic acidemia is a rare autosomal recessive disorder resulting from defects of the {alpha} or {beta} subunit of biotin-dependent propionyl-CoA carboxylase (PCC). Mutations are assigned to defects of the PCCA ({alpha} subunit) or PCCB ({beta} subunit) gene through complementation studies after somatic fusion of patient cell lines. About two-thirds of patients with {beta} subunit defects (complementation group pccBC) show interallelic complementation in cell fusion experiments (subgroups pccB and pccC), monitored by the PCC-dependent metabolisms of {sup 14}C-propionate. Most patient cell lines are heteroallelic for two different mutations, leaving ambiguous the identity of the mutation participating in interallelic complementation. To identifymore » the complementing mutations, we have expressed {beta}-subunit cDNAs containing individual mutations by microinjection of the cDNAs in recipient cells from patients with {beta} subunit defects. Correction of the PCC defect was monitored by autoradiography of {sup 14}C-propionate incorporation. In some experiments, cDNAs were co-injected with a plasmid expressing the E. coli lacZ gene as a positive control for successful injection. Two mutations from the pccB subgroup showed complementation when injected into pccC cells; dupKICK140-143 and Pro228Leu. Similarly, two mutations from the pccC subgroup complemented after injection into pccB cells; {Delta}Ile408 and Arg410Trp. No mutation complemented with mutation of the pccBC group which are classified as non-complementing in cell fusion experiments. The results show that the complementing pccB mutations are found in the N-terminal half of the {beta} subunit, while the complementing pccC mutations cluxter at a site in the C-terminal half. The latter site is a candidate for the propionyl-CoA binding site based on sequence identity with a region of transcarboxylase from Propionibacterium shermanii.« less

Protective immune responses against West Nile virus are primed by distinct complement activation pathways.

PubMed

Mehlhop, Erin; Diamond, Michael S

2006-05-15

West Nile virus (WNV) causes a severe infection of the central nervous system in several vertebrate animals including humans. Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3(-/-) and complement receptor 1/2(-/-) mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8+ T cell responses yet near normal anti-WNV antibody profiles. Animals lacking the classical and lectin pathways had deficits in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q was required for productive infection in the spleen but not for development of adaptive immune responses after WNV infection. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.

Non-specific adsorption of complement proteins affects complement activation pathways of gold nanomaterials.

PubMed

Quach, Quang Huy; Kah, James Chen Yong

2017-04-01

The complement system is a key humoral component of innate immunity, serving as the first line of defense against intruders, including foreign synthetic nanomaterials. Although gold nanomaterials (AuNMs) are widely used in nanomedicine, their immunological response is not well understood. Using AuNMs of three shapes commonly used in biomedical applications: spherical gold nanoparticles, gold nanostars and gold nanorods, we demonstrated that AuNMs activated whole complement system, leading to the formation of SC5b-9 complex. All three complement pathways were simultaneously activated by all the AuNMs. Recognition molecules of the complement system interacted with all AuNMs in vitro, except for l-ficolin, but the correlation between these interactions and corresponding complement pathway activation was only observed in the classical and alternative pathways. We also observed the mediating role of complement activation in cellular uptake of all AuNMs by human U937 promonocytic cells, which expresses complement receptors. Taken together, our results highlighted the potential immunological challenges for clinical applications of AuNMs that were often overlooked.

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

PubMed Central

Brocklebank, Vicky

2017-01-01

Abstract Thrombotic microangiopathy (TMA), characterized by organ injury occurring consequent to severe endothelial damage, can manifest in a diverse range of diseases. In complement-mediated atypical haemolytic uraemic syndrome (aHUS) a primary defect in complement, such as a mutation or autoantibody leading to over activation of the alternative pathway, predisposes to the development of disease, usually following exposure to an environmental trigger. The elucidation of the pathogenesis of aHUS resulted in the successful introduction of the complement inhibitor eculizumab into clinical practice. In other TMAs, although complement activation may be seen, its role in the pathogenesis remains to be confirmed by an interventional trial. Although many case reports in TMAs other than complement-mediated aHUS hint at efficacy, publication bias, concurrent therapies and in some cases the self-limiting nature of disease make broader interpretation difficult. In this article, we will review the evidence for the role of complement inhibition in complement-mediated aHUS and other TMAs. PMID:28980670

Streptococcus pyogenes Endopeptidase O Contributes to Evasion from Complement-mediated Bacteriolysis via Binding to Human Complement Factor C1q*

PubMed Central

Honda-Ogawa, Mariko; Sumitomo, Tomoko; Mori, Yasushi; Hamd, Dalia Talat; Ogawa, Taiji; Yamaguchi, Masaya; Nakata, Masanobu; Kawabata, Shigetada

2017-01-01

Streptococcus pyogenes secretes various virulence factors for evasion from complement-mediated bacteriolysis. However, full understanding of the molecules possessed by this organism that interact with complement C1q, an initiator of the classical complement pathway, remains elusive. In this study, we identified an endopeptidase of S. pyogenes, PepO, as an interacting molecule, and investigated its effects on complement immunity and pathogenesis. Enzyme-linked immunosorbent assay and surface plasmon resonance analysis findings revealed that S. pyogenes recombinant PepO bound to human C1q in a concentration-dependent manner under physiological conditions. Sites of inflammation are known to have decreased pH levels, thus the effects of PepO on bacterial evasion from complement immunity was analyzed in a low pH condition. Notably, under low pH conditions, PepO exhibited a higher affinity for C1q as compared with IgG, and PepO inhibited the binding of IgG to C1q. In addition, pepO deletion rendered S. pyogenes more susceptible to the bacteriocidal activity of human serum. Also, observations of the morphological features of the pepO mutant strain (ΔpepO) showed damaged irregular surfaces as compared with the wild-type strain (WT). WT-infected tissues exhibited greater severity and lower complement activity as compared with those infected by ΔpepO in a mouse skin infection model. Furthermore, WT infection resulted in a larger accumulation of C1q than that with ΔpepO. Our results suggest that interaction of S. pyogenes PepO with C1q interferes with the complement pathway, which enables S. pyogenes to evade complement-mediated bacteriolysis under acidic conditions, such as seen in inflammatory sites. PMID:28154192

Complement activation promotes muscle inflammation during modified muscle use

NASA Technical Reports Server (NTRS)

Frenette, J.; Cai, B.; Tidball, J. G.

2000-01-01

Modified muscle use can result in muscle inflammation that is triggered by unidentified events. In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. Modified rat hindlimb muscle loading was achieved by removing weight-bearing from the hindlimbs for 10 days followed by reloading through normal ambulation. Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. Analysis of complement C4 concentration in serum in untreated animals showed that the classical pathway was activated during the first 2 hours of reloading. Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. Administration of sCR1 significantly attenuated the invasion of neutrophils (-49%) and ED1(+) macrophages (-52%) that occurred in nontreated animals after 6 hours of reloading. The presence of sCR1 also reduced significantly the degree of edema by 22% as compared to untreated animals. Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading.

Elementary Science Supplement to the Syllabus. Level I (Ages 4 through 7).

ERIC Educational Resources Information Center

New York State Education Dept., Albany.

Developed to complement existing elementary science programs, the materials in this first volume of New York's Elementary Science Supplement to the Syllabus emphasize a direct experience, hands-on approach for children of ages 4 through 7. Major sections include: (1) guidelines for program activities (explaining the organizational format of the…

Increasing Physical Activity during the School Day through Physical Activity Classes: Implications for Physical Educators

ERIC Educational Resources Information Center

Adkins, Megan; Bice, Matt; Bartee, Todd; Heelan, Kate

2015-01-01

Across the nation schools are adopting health and wellness policies, specifically physical activity (PA) initiatives that aid healthy long-term lifestyles. Interest has been generated about the inclusion of physical activity classes to complement existing physical education classes. Furthermore, discussion has evolved as to if additional…

Older Adult Learners: A Comparison of Active and Non-Active Learners

ERIC Educational Resources Information Center

Sloane-Seale, Atlanta; Kops, Bill

2007-01-01

This paper reports on a 2004 follow-up study conducted in partnership with the University of Manitoba Continuing Education Division and local senior's organizations. The partnership was formed in 2002-03 to promote applied research on lifelong learning and older adults, develop new and complement existing educational activities, and explore new…

Correlates of Quality Sleep and Academic Performance

ERIC Educational Resources Information Center

Becker, Craig M.; Adams, Troy; Orr, Caroline; Quilter, Lyndsay

2008-01-01

Sleep problems have become epidemic and traditional research has discovered many causes of poor sleep. The purpose of this study was to complement existing research by using a salutogenic or health origins framework to investigate the correlates of good sleep. The analysis for this study used the National College Health Assessment data that…

Solving the problems we face: the United States Environmental Protection Agency, sustainability, and the challenges of the twenty-first century

EPA Science Inventory

Addressing the problems of the twenty-first century will require new initiatives that complement traditional regulatory activities. Existing regulations, such as the Clean Air Act and Clean Water Act are important safety nets in the United States for protecting human health and t...

A Model Formative Assessment Strategy to Promote Student-Centered Self-Regulated Learning in Higher Education

ERIC Educational Resources Information Center

Bose, Jayakumar; Rengel, Zed

2009-01-01

Adult learners are already involved in the process of self-regulation; hence, higher education institutions should focus on strengthening students' self-regulatory skills. Self-regulation can be facilitated through formative assessment. This paper proposes a model formative assessment strategy that would complement existing university teaching,…

The role of simulation in neurosurgery.

PubMed

Rehder, Roberta; Abd-El-Barr, Muhammad; Hooten, Kristopher; Weinstock, Peter; Madsen, Joseph R; Cohen, Alan R

2016-01-01

In an era of residency duty-hour restrictions, there has been a recent effort to implement simulation-based training methods in neurosurgery teaching institutions. Several surgical simulators have been developed, ranging from physical models to sophisticated virtual reality systems. To date, there is a paucity of information describing the clinical benefits of existing simulators and the assessment strategies to help implement them into neurosurgical curricula. Here, we present a systematic review of the current models of simulation and discuss the state-of-the-art and future directions for simulation in neurosurgery. Retrospective literature review. Multiple simulators have been developed for neurosurgical training, including those for minimally invasive procedures, vascular, skull base, pediatric, tumor resection, functional neurosurgery, and spine surgery. The pros and cons of existing systems are reviewed. Advances in imaging and computer technology have led to the development of different simulation models to complement traditional surgical training. Sophisticated virtual reality (VR) simulators with haptic feedback and impressive imaging technology have provided novel options for training in neurosurgery. Breakthrough training simulation using 3D printing technology holds promise for future simulation practice, proving high-fidelity patient-specific models to complement residency surgical learning.

Theory of gearing

NASA Technical Reports Server (NTRS)

Litvin, Faydor L.

1989-01-01

Basic mathematical problems on the theory of gearing are covered in this book, such as the necessary and sufficient conditions of envelope existence, relations between principal curvatures and directions for surfaces of mating gears. Also included are singularities of surfaces accompanied by undercutting the process of generation, the phenomena of envelope of lines of contact, and the principles for generation of conjugate surfaces. Special attention is given to the algorithms for computer aided simulation of meshing and tooth contact. This edition was complemented with the results of research recently performed by the author and his doctoral students. The book contains sample problems and also problems for the reader to solve.

Probing magnetic order in CuFeO2 through nuclear forward scattering in high magnetic fields

NASA Astrophysics Data System (ADS)

Strohm, C.; Lummen, T. T. A.; Handayani, I. P.; Roth, T.; Detlefs, C.; van der Linden, P. J. E. M.; van Loosdrecht, P. H. M.

2013-08-01

Determining the magnetic order of solids in high magnetic fields is technologically challenging. Here we probe the cascade of magnetic phase transitions in frustrated multiferroic CuFeO2 using nuclear forward scattering (NFS) in pulsed magnetic fields up to 30 T. Our results are in excellent agreement with detailed neutron diffraction experiments, currently limited to 15 T, while providing experimental confirmation of the proposed higher field phases for both H∥c and H⊥c. We thus establish NFS as a valuable tool for spin structure studies in very high fields, both complementing and expanding on the applicability of existing techniques.

Application of a forest-simulation model to assess the energy yield and ecological impact of forest utilization for energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doyle, T W; Shugart, H H; West, D C

1981-01-01

This study examines the utilization and management of natural forest lands to meet growing wood-energy demands. An application of a forest simulation model is described for assessing energy returns and long-term ecological impacts of wood-energy harvesting under four general silvicultural practices. Results indicate that moderate energy yields could be expected from mild cutting operations which would significantly effect neither the commercial timber market nor the composition, structure, or diversity of these forests. Forest models can provide an effective tool for determining optimal management strategies that maximize energy returns, minimize environmental detriment, and complement existing land-use plans.

Peer Effects in the Workplace: Evidence from Random Groupings in Professional Golf Tournaments

PubMed Central

Guryan, Jonathan; Kroft, Kory; Notowidigdo, Matthew J.

2010-01-01

This paper uses random assignment in professional golf tournaments to test for peer effects in the workplace. We find no evidence that playing partners’ ability affects performance, contrary to recent evidence on peer effects in the workplace from laboratory experiments, grocery scanners, and soft-fruit pickers. In our preferred specification we can rule out peer effects larger than 0.043 strokes for a one stroke increase in playing partners’ ability. Our results complement existing studies on workplace peer effects and are useful in explaining how social effects vary across labor markets, across individuals, and with the form of incentives faced. PMID:20454555

Analysis of Streamline Separation at Infinity Using Time-Discrete Markov Chains.

PubMed

Reich, W; Scheuermann, G

2012-12-01

Existing methods for analyzing separation of streamlines are often restricted to a finite time or a local area. In our paper we introduce a new method that complements them by allowing an infinite-time-evaluation of steady planar vector fields. Our algorithm unifies combinatorial and probabilistic methods and introduces the concept of separation in time-discrete Markov-Chains. We compute particle distributions instead of the streamlines of single particles. We encode the flow into a map and then into a transition matrix for each time direction. Finally, we compare the results of our grid-independent algorithm to the popular Finite-Time-Lyapunov-Exponents and discuss the discrepancies.

Complement-Mediated Enhancement of Monocyte Adhesion to Endothelial Cells by HLA Antibodies, and Blockade by a Specific Inhibitor of the Classical Complement Cascade, TNT003

PubMed Central

Valenzuela, Nicole M.; Thomas, Kimberly A.; Mulder, Arend; Parry, Graham C.; Panicker, Sandip; Reed, Elaine F.

2017-01-01

Background Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling. Methods Primary human aortic endothelial cells (HAEC) were stimulated with HLA class I antibodies in the presence of intact human serum complement. C3a and C5a generation, endothelial P-selectin expression, and adhesion of human primary and immortalized monocytes (Mono Mac 6) were measured. Alternatively, HAEC or monocytes were directly stimulated with purified C3a or C5a. Classical complement activation was inhibited by pretreatment of complement with an anti-C1s antibody (TNT003). Results Treatment of HAEC with HLA antibody and human complement increased the formation of C3a and C5a. Monocyte recruitment by human HLA antibodies was enhanced in the presence of intact human serum complement or purified C3a or C5a. Specific inhibition of the classical complement pathway using TNT003 or C1q-depleted serum significantly reduced adhesion of monocytes in the presence of human complement. Conclusions Despite persistent endothelial viability in the presence of HLA antibodies and complement, upstream complement anaphylatoxin production exacerbates endothelial exocytosis and leukocyte recruitment. Upstream inhibition of classical complement may be therapeutic to dampen mononuclear cell recruitment and endothelial activation characteristic of microvascular inflammation during AMR. PMID:28640789

THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET

PubMed Central

Schmidt-Erfurth, Ursula; van Lookeren Campagne, Menno; Henry, Erin C.; Brittain, Christopher

2017-01-01

Purpose: Geographic atrophy (GA) is an advanced, vision-threatening form of age-related macular degeneration (AMD) affecting approximately five million individuals worldwide. To date, there are no approved therapeutics for GA treatment; however, several are in clinical trials. This review focuses on the pathophysiology of GA, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade. Methods: Primary literature search on PubMed for GA, complement cascade in age-related macular degeneration. ClinicalTrials.gov was searched for natural history studies in GA and clinical trials of drugs targeting the complement cascade for GA. Results: Cumulative damage to the retina by aging, environmental stress, and other factors triggers inflammation via multiple pathways, including the complement cascade. When regulatory components in these pathways are compromised, as with several GA-linked genetic risk factors in the complement cascade, chronic inflammation can ultimately lead to the retinal cell death characteristic of GA. Complement inhibition has been identified as a key candidate for therapeutic intervention, and drugs targeting the complement pathway are currently in clinical trials. Conclusion: The complement cascade is a strategic target for GA therapy. Further research, including on natural history and genetics, is crucial to expand the understanding of GA pathophysiology and identify effective therapeutic targets. PMID:27902638

Using the EXIST Active Shields for Earth Occultation Observations of X-Ray Sources

NASA Technical Reports Server (NTRS)

Wilson, Colleen A.; Fishman, Gerald; Hong, Jae-Sub; Gridlay, Jonathan; Krawczynski, Henric

2005-01-01

The EXIST active shields, now being planned for the main detectors of the coded aperture telescope, will have approximately 15 times the area of the BATSE detectors; and they will have a good geometry on the spacecraft for viewing both the leading and training Earth's limb for occultation observations. These occultation observations will complement the imaging observations of EXIST and can extend them to higher energies. Earth occultatio observations of the hard X-ray sky with BATSE on the Compton Gamma Ray Observatory developed and demonstrated the capabilities of large, flat, uncollimated detectors for this method. With BATSE, a catalog of 179 X-ray sources was monitored twice every spacecraft orbit for 9 years at energies above about 25 keV, resulting in 83 definite detections and 36 possible detections with 5-sigma detection sensitivities of 3.5-20 mcrab (20-430 keV) depending on the sky location. This catalog included four transients discovered with this technique and many variable objects (galactic and extragalactic). This poster will describe the Earth occultation technique, summarize the BATSE occultation observations, and compare the basic observational parameters of the occultation detector elements of BATSE and EXIST.

Assessment of Complement Activation by Nanoparticles: Development of a SPR Based Method and Comparison with Current High Throughput Methods.

PubMed

Coty, Jean-Baptiste; Noiray, Magali; Vauthier, Christine

2018-04-26

A Surface Plasmon Resonance chip (SPR) was developed to study the activation of complement system triggered by nanomaterials in contact with human serum, which is an important concern today to warrant safety of nanomedicines. The developed chip was tested for its specificity in complex medium and its longevity of use. It was then employed to assess the release of complement fragments upon incubation of nanoparticles in serum. A comparison was made with other current methods assessing complement activation (μC-IE, ELISA). The SPR chip was found to give a consistent response for C3a release upon activation by nanoparticles. Results were similar to those obtained by μC-IE. However, ELISA detection of iC3b fragments showed an explained high non-specific background. The impact of sample preparation preceding the analysis was assessed with the newly develop SPR method. The removal of nanoparticles before analysis showed an important modification in the obtained response, possibly leading to false negative results. The SPR chip developed in this work allows for an automated assessment of complement activation triggered by nanoparticles with possibility of multiplexed analysis. The design of the chip proved to give consistent results of complement activation by nanoparticles.

Identification of a central role for complement in osteoarthritis

PubMed Central

Wang, Qian; Rozelle, Andrew L.; Lepus, Christin M.; Scanzello, Carla R.; Song, Jason J.; Larsen, D. Meegan; Crish, James F.; Bebek, Gurkan; Ritter, Susan Y.; Lindstrom, Tamsin M.; Hwang, Inyong; Wong, Heidi H.; Punzi, Leonardo; Encarnacion, Angelo; Shamloo, Mehrdad; Goodman, Stuart B.; Wyss-Coray, Tony; Goldring, Steven R.; Banda, Nirmal K.; Thurman, Joshua M.; Gobezie, Reuben; Crow, Mary K.; Holers, V. Michael; Lee, David M.; Robinson, William H.

2011-01-01

Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of “wear and tear”1. Although low-grade inflammation is detected in osteoarthritis, its role is unclear2–4. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in C5, C6, or CD59a, we show that complement, and specifically the membrane attack complex (MAC)-mediated arm of complement, is critical to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints of C5-deficient mice than C5-sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Furthermore, MAC co-localized with matrix metalloprotease (MMP)-13 and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints plays a critical role in the pathogenesis of osteoarthritis. PMID:22057346

Regulation of macrophage migration by products of the complement system.

PubMed Central

Bianco, C; Götze, O; Cohn, Z A

1979-01-01

Agents formerly shown to induce rapid macrophage spreading were examined for their ability to modify the migration of macrophages in the capillary tube assay. Products of the activation of the contact phase of blood coagulation as well as the purified component Bb, the large cleavage fragment of factor B of the alternative complement pathway produced a dose-dependent inhibition of migration. In addition, inflammatory macrophages elicited with either a lipopolysaccharide endotoxin or thioglycollate medium exhibited rapid spreading and inhibited migration, whereas resident cells did not. A close correlation existed, therefore, between enhanced spreading and inhibited migration under both in vitro induced and in vivo situations. Cleavage products of component C5 of the classical complement pathway enhanced macrophage migration and did not alter spreading. In mixtures of C5 cleavage products and Bb, the predominant peptide determined the outcome of the reaction. Factor B, a normal secretory product of macrophages, may represent a common substrate for several of the proteases that induce spreading, inhibit migration, and lead to the generation of the enzymatically active fragment Bb. PMID:284412

Trials, tricks and transparency: how disclosure rules affect clinical knowledge.

PubMed

Dahm, Matthias; González, Paula; Porteiro, Nicolás

2009-12-01

Scandals of selective reporting of clinical trial results by pharmaceutical firms have underlined the need for more transparency in clinical trials. We provide a theoretical framework which reproduces incentives for selective reporting and yields three key implications concerning regulation. First, a compulsory clinical trial registry complemented through a voluntary clinical trial results database can implement full transparency (the existence of all trials as well as their results is known). Second, full transparency comes at a price. It has a deterrence effect on the incentives to conduct clinical trials, as it reduces the firms' gains from trials. Third, in principle, a voluntary clinical trial results database without a compulsory registry is a superior regulatory tool; but we provide some qualified support for additional compulsory registries when medical decision-makers cannot anticipate correctly the drug companies' decisions whether to conduct trials.

Studies of Dynamic Protein-Protein Interactions in Bacteria Using Renilla Luciferase Complementation Are Undermined by Nonspecific Enzyme Inhibition

PubMed Central

Hatzios, Stavroula K.; Ringgaard, Simon; Davis, Brigid M.; Waldor, Matthew K.

2012-01-01

The luciferase protein fragment complementation assay is a powerful tool for studying protein-protein interactions. Two inactive fragments of luciferase are genetically fused to interacting proteins, and when these two proteins interact, the luciferase fragments can reversibly associate and reconstitute enzyme activity. Though this technology has been used extensively in live eukaryotic cells, split luciferase complementation has not yet been applied to studies of dynamic protein-protein interactions in live bacteria. As proof of concept and to develop a new tool for studies of bacterial chemotaxis, fragments of Renilla luciferase (Rluc) were fused to the chemotaxis-associated response regulator CheY3 and its phosphatase CheZ in the enteric pathogen Vibrio cholerae. Luciferase activity was dependent on the presence of both CheY3 and CheZ fusion proteins, demonstrating the specificity of the assay. Furthermore, enzyme activity was markedly reduced in V. cholerae chemotaxis mutants, suggesting that this approach can measure defects in chemotactic signaling. However, attempts to measure changes in dynamic CheY3-CheZ interactions in response to various chemoeffectors were undermined by nonspecific inhibition of the full-length luciferase. These observations reveal an unexpected limitation of split Rluc complementation that may have implications for existing data and highlight the need for great caution when evaluating small molecule effects on dynamic protein-protein interactions using the split luciferase technology. PMID:22905225

Studies of dynamic protein-protein interactions in bacteria using Renilla luciferase complementation are undermined by nonspecific enzyme inhibition.

PubMed

Hatzios, Stavroula K; Ringgaard, Simon; Davis, Brigid M; Waldor, Matthew K

2012-01-01

The luciferase protein fragment complementation assay is a powerful tool for studying protein-protein interactions. Two inactive fragments of luciferase are genetically fused to interacting proteins, and when these two proteins interact, the luciferase fragments can reversibly associate and reconstitute enzyme activity. Though this technology has been used extensively in live eukaryotic cells, split luciferase complementation has not yet been applied to studies of dynamic protein-protein interactions in live bacteria. As proof of concept and to develop a new tool for studies of bacterial chemotaxis, fragments of Renilla luciferase (Rluc) were fused to the chemotaxis-associated response regulator CheY3 and its phosphatase CheZ in the enteric pathogen Vibrio cholerae. Luciferase activity was dependent on the presence of both CheY3 and CheZ fusion proteins, demonstrating the specificity of the assay. Furthermore, enzyme activity was markedly reduced in V. cholerae chemotaxis mutants, suggesting that this approach can measure defects in chemotactic signaling. However, attempts to measure changes in dynamic CheY3-CheZ interactions in response to various chemoeffectors were undermined by nonspecific inhibition of the full-length luciferase. These observations reveal an unexpected limitation of split Rluc complementation that may have implications for existing data and highlight the need for great caution when evaluating small molecule effects on dynamic protein-protein interactions using the split luciferase technology.

Unstructured Adaptive (UA) NAS Parallel Benchmark. Version 1.0

NASA Technical Reports Server (NTRS)

Feng, Huiyu; VanderWijngaart, Rob; Biswas, Rupak; Mavriplis, Catherine

2004-01-01

We present a complete specification of a new benchmark for measuring the performance of modern computer systems when solving scientific problems featuring irregular, dynamic memory accesses. It complements the existing NAS Parallel Benchmark suite. The benchmark involves the solution of a stylized heat transfer problem in a cubic domain, discretized on an adaptively refined, unstructured mesh.

Mediating HIV/AIDS Strategies in Children's Literature in Zimbabwe

ERIC Educational Resources Information Center

Ngoshi, Hazel Tafadzwa; Pasi, Juliet Sylvia

2007-01-01

The Ministry of Education and Culture in Zimbabwe has introduced an intervention into the school curricula to complement the already existing mechanisms in the fight against HIV/AIDS. The literature in this programme is said to be designed to develop children's knowledge of HIV/AIDS and to maximise both individual and community commitment to the…

Data Mining: A Hybrid Methodology for Complex and Dynamic Research

ERIC Educational Resources Information Center

Lang, Susan; Baehr, Craig

2012-01-01

This article provides an overview of the ways in which data and text mining have potential as research methodologies in composition studies. It introduces data mining in the context of the field of composition studies and discusses ways in which this methodology can complement and extend our existing research practices by blending the best of what…

Molecular comparison of cattle fever ticks from native and introduced ranges with insights into optimal search areas for classical biological control agents

USDA-ARS?s Scientific Manuscript database

Classical biological control using specialist parasitoids, predators and/or nematodes from the native ranges of cattle fever ticks could complement existing control strategies for this livestock pest in the transboundary region between Mexico and Texas. DNA fingerprinting tools were used to compare ...

Identifying Knowledge Sharing Barriers in the Collaboration of Traditional and Western Medicine Professionals in Chinese Hospitals: A Case Study

ERIC Educational Resources Information Center

Zhou, Lihong; Nunes, Miguel Baptista

2012-01-01

This paper reports on a research project that aims at identifying knowledge sharing (KS) barriers between traditional and western medicine practitioners co-existing and complementing each other in Chinese healthcare organisations. The study focuses on the tacit aspects of patient knowledge, rather than the traditional technical information shared…

Quantifying Pilot Contribution to Flight Safety During Dual Generator Failure

NASA Technical Reports Server (NTRS)

Etherington, Timothy J.; Kramer, Lynda J.; Kennedy, Kellie D.; Bailey, Randall E.; Last, Mary Carolyn

2017-01-01

Accident statistics cite flight crew error in over 60% of accidents involving transport category aircraft. Yet, a well-trained and well-qualified pilot is acknowledged as the critical center point of aircraft systems safety and an integral safety component of the entire commercial aviation system. No data currently exists that quantifies the contribution of the flight crew in this role. Neither does data exist for how often the flight crew handles non-normal procedures or system failures on a daily basis in the National Airspace System. A pilot-in-the-loop high fidelity motion simulation study was conducted by the NASA Langley Research Center in partnership with the Federal Aviation Administration (FAA) to evaluate the pilot's contribution to flight safety during normal flight and in response to aircraft system failures. Eighteen crews flew various normal and non-normal procedures over a two-day period and their actions were recorded in response to failures. To quantify the human's contribution, crew complement was used as the experiment independent variable in a between-subjects design. Pilot actions and performance when one of the flight crew was unavailable were also recorded for comparison against the nominal two-crew operations. This paper details diversion decisions, perceived safety of flight, workload, time to complete pertinent checklists, and approach and landing results while dealing with a complete loss of electrical generators. Loss of electrical power requires pilots to complete the flight without automation support of autopilots, flight directors, or auto throttles. For reduced crew complements, the additional workload and perceived safety of flight was considered unacceptable.

Characterization of shark complement factor I gene(s): genomic analysis of a novel shark-specific sequence.

PubMed

Shin, Dong-Ho; Webb, Barbara M; Nakao, Miki; Smith, Sylvia L

2009-07-01

Complement factor I is a crucial regulator of mammalian complement activity. Very little is known of complement regulators in non-mammalian species. We isolated and sequenced four highly similar complement factor I cDNAs from the liver of the nurse shark (Ginglymostoma cirratum), designated as GcIf-1, GcIf-2, GcIf-3 and GcIf-4 (previously referred to as nsFI-a, -b, -c and -d) which encode 689, 673, 673 and 657 amino acid residues, respectively. They share 95% (

Characterization of shark complement factor I gene(s): genomic analysis of a novel shark-specific sequence

PubMed Central

Shin, Dong-Ho; Webb, Barbara M.; Nakao, Miki; Smith, Sylvia L.

2009-01-01

Complement factor I is a crucial regulator of mammalian complement activity. Very little is known of complement regulators in non-mammalian species. We isolated and sequenced four highly similar complement factor I cDNAs from the liver of the nurse shark (Ginglymostoma cirratum), designated as GcIf-1, GcIf-2, GcIf-3 and GcIf-4 (previously referred to as nsFI-a, -b, -c and –d) which encode 689, 673, 673 and 657 amino acid residues, respectively. They share 95% (≤) amino acid identities with each other, 35.4 ~ 39.6% and 62.8 ~ 65.9% with factor I of mammals and banded houndshark (Triakis scyllium), respectively. The modular structure of the GcIf is similar to that of mammals with one notable exception, the presence of a novel shark-specific sequence between the leader peptide (LP) and the factor I membrane attack complex (FIMAC) domain. The cDNA sequences differ only in the size and composition of the shark-specific region (SSR). Sequence analysis of each SSR has identified within the region two novel short sequences (SS1 and SS2) and three repeat sequences (RS1, 2 and 3). Genomic analysis has revealed the existence of three introns between the leader peptide and the FIMAC domain, tentatively designated intron 1, intron 2, and intron 3 which span 4067, 2293 and 2082 bp, respectively. Southern blot analysis suggests the presence of a single gene copy for each cDNA type. Phylogenetic analysis suggests that complement factor I of cartilaginous fish diverged prior to the emergence of mammals. All four GcIf cDNA species are expressed in four different tissues and the liver is the main tissue in which expression level of all four is high. This suggests that the expression of GcIf isotypes is tissue-dependent. PMID:19423168

Jane: a new tool for the cophylogeny reconstruction problem.

PubMed

Conow, Chris; Fielder, Daniel; Ovadia, Yaniv; Libeskind-Hadas, Ran

2010-02-03

This paper describes the theory and implementation of a new software tool, called Jane, for the study of historical associations. This problem arises in parasitology (associations of hosts and parasites), molecular systematics (associations of orderings and genes), and biogeography (associations of regions and orderings). The underlying problem is that of reconciling pairs of trees subject to biologically plausible events and costs associated with these events. Existing software tools for this problem have strengths and limitations, and the new Jane tool described here provides functionality that complements existing tools. The Jane software tool uses a polynomial time dynamic programming algorithm in conjunction with a genetic algorithm to find very good, and often optimal, solutions even for relatively large pairs of trees. The tool allows the user to provide rich timing information on both the host and parasite trees. In addition the user can limit host switch distance and specify multiple host switch costs by specifying regions in the host tree and costs for host switches between pairs of regions. Jane also provides a graphical user interface that allows the user to interactively experiment with modifications to the solutions found by the program. Jane is shown to be a useful tool for cophylogenetic reconstruction. Its functionality complements existing tools and it is therefore likely to be of use to researchers in the areas of parasitology, molecular systematics, and biogeography.

Human L-ficolin, a recognition molecule of the lectin activation pathway of complement, activates complement by binding to pneumolysin, the major toxin of Streptococcus pneumoniae.

PubMed

Ali, Youssif M; Kenawy, Hany I; Muhammad, Adnan; Sim, Robert B; Andrew, Peter W; Schwaeble, Wilhelm J

2013-01-01

The complement system is an essential component of the immune response, providing a critical line of defense against different pathogens including S. pneumoniae. Complement is activated via three distinct pathways: the classical (CP), the alternative (AP) and the lectin pathway (LP). The role of Pneumolysin (PLY), a bacterial toxin released by S. pneumoniae, in triggering complement activation has been studied in vitro. Our results demonstrate that in both human and mouse sera complement was activated via the CP, initiated by direct binding of even non-specific IgM and IgG3 to PLY. Absence of CP activity in C1q(-/-) mouse serum completely abolished any C3 deposition. However, C1q depleted human serum strongly opsonized PLY through abundant deposition of C3 activation products, indicating that the LP may have a vital role in activating the human complement system on PLY. We identified that human L-ficolin is the critical LP recognition molecule that drives LP activation on PLY, while all of the murine LP recognition components fail to bind and activate complement on PLY. This work elucidates the detailed interactions between PLY and complement and shows for the first time a specific role of the LP in PLY-mediated complement activation in human serum.

Human L-ficolin, a Recognition Molecule of the Lectin Activation Pathway of Complement, Activates Complement by Binding to Pneumolysin, the Major Toxin of Streptococcus pneumoniae

PubMed Central

Ali, Youssif M.; Kenawy, Hany I.; Muhammad, Adnan; Sim, Robert B.

2013-01-01

The complement system is an essential component of the immune response, providing a critical line of defense against different pathogens including S. pneumoniae. Complement is activated via three distinct pathways: the classical (CP), the alternative (AP) and the lectin pathway (LP). The role of Pneumolysin (PLY), a bacterial toxin released by S. pneumoniae, in triggering complement activation has been studied in vitro. Our results demonstrate that in both human and mouse sera complement was activated via the CP, initiated by direct binding of even non-specific IgM and IgG3 to PLY. Absence of CP activity in C1q−/− mouse serum completely abolished any C3 deposition. However, C1q depleted human serum strongly opsonized PLY through abundant deposition of C3 activation products, indicating that the LP may have a vital role in activating the human complement system on PLY. We identified that human L-ficolin is the critical LP recognition molecule that drives LP activation on PLY, while all of the murine LP recognition components fail to bind and activate complement on PLY. This work elucidates the detailed interactions between PLY and complement and shows for the first time a specific role of the LP in PLY-mediated complement activation in human serum. PMID:24349316

Dynamics of the mental health workforce: investigating the composition of physicians and other health providers.

PubMed

Stefos, Theodore; Burgess, James F; Cohen, Jeffrey P; Lehner, Laura; Moran, Eileen

2012-12-01

We evaluate how changes to mental health workforce levels, composition, and degree of labor substitution, may impact typical practice output. Using a generalized Leontief production function and data from 134 U.S. Department of Veterans Affairs (VA) mental health practices, we estimate the q-complementarity/q-substitutability of mental health workers. We look at the entire spectrum of mental health services rather than just outpatient or physician office services. We also examine more labor types, including residents, than previous studies. The marginal patient care output contribution is estimated for each labor type as well as the degree to which physicians and other mental health workers may be substitutes or complements. Results indicate that numerous channels exist through which input substitution can improve productivity. Seven of eight labor and capital inputs have positive estimated marginal products. Most factor inputs exhibit diminishing marginal productivity. Of 28 unique labor-capital pairs, 17 are q-complements and 11 are q-substitutes. Complementarity among several labor types provides evidence of a team approach to mental health service provision. Our approach may serve to better inform healthcare providers regarding more productive mental health workforce composition both in and outside of VA.

Streptococcus pyogenes Endopeptidase O Contributes to Evasion from Complement-mediated Bacteriolysis via Binding to Human Complement Factor C1q.

PubMed

Honda-Ogawa, Mariko; Sumitomo, Tomoko; Mori, Yasushi; Hamd, Dalia Talat; Ogawa, Taiji; Yamaguchi, Masaya; Nakata, Masanobu; Kawabata, Shigetada

2017-03-10

Streptococcus pyogenes secretes various virulence factors for evasion from complement-mediated bacteriolysis. However, full understanding of the molecules possessed by this organism that interact with complement C1q, an initiator of the classical complement pathway, remains elusive. In this study, we identified an endopeptidase of S. pyogenes , PepO, as an interacting molecule, and investigated its effects on complement immunity and pathogenesis. Enzyme-linked immunosorbent assay and surface plasmon resonance analysis findings revealed that S. pyogenes recombinant PepO bound to human C1q in a concentration-dependent manner under physiological conditions. Sites of inflammation are known to have decreased pH levels, thus the effects of PepO on bacterial evasion from complement immunity was analyzed in a low pH condition. Notably, under low pH conditions, PepO exhibited a higher affinity for C1q as compared with IgG, and PepO inhibited the binding of IgG to C1q. In addition, pepO deletion rendered S. pyogenes more susceptible to the bacteriocidal activity of human serum. Also, observations of the morphological features of the pepO mutant strain (Δ pepO ) showed damaged irregular surfaces as compared with the wild-type strain (WT). WT-infected tissues exhibited greater severity and lower complement activity as compared with those infected by Δ pepO in a mouse skin infection model. Furthermore, WT infection resulted in a larger accumulation of C1q than that with Δ pepO. Our results suggest that interaction of S. pyogenes PepO with C1q interferes with the complement pathway, which enables S. pyogenes to evade complement-mediated bacteriolysis under acidic conditions, such as seen in inflammatory sites. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A comparative analysis of the encapsulated end-organs of mammalian skeletal muscles and of their sensory nerve endings.

PubMed

Banks, R W; Hulliger, M; Saed, H H; Stacey, M J

2009-06-01

The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend to be located closer to the main divisions of the nerve. Next, based on a sample of tendon organs from several hind-foot muscles of the cat, we demonstrate the existence in at least a large proportion of tendon organs of a structural substrate to account for multiple spike-initiation sites and pacemaker switching, namely the distribution of sensory terminals supplied by the different first-order branches of the Ib afferent to separate, parallel, tendinous compartments of individual tendon organs. We then show that the numbers of spindles, tendon organs and paciniform corpuscles vary independently in a sample of (mainly) hind-foot muscles of the cat. Grouping muscles by anatomical region in the cat indicated the existence of a gradual proximo-distal decline in the overall average size of the afferent complement of muscle spindles from axial through hind limb to intrinsic foot muscles, but with considerable muscle-specific variability. Finally, we present some comparative data on muscle-spindle afferent complements of rat, rabbit and guinea pig, one particularly notable feature being the high incidence of multiple primary endings in the rat.

Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN.

PubMed

Iatropoulos, Paraskevas; Daina, Erica; Curreri, Manuela; Piras, Rossella; Valoti, Elisabetta; Mele, Caterina; Bresin, Elena; Gamba, Sara; Alberti, Marta; Breno, Matteo; Perna, Annalisa; Bettoni, Serena; Sabadini, Ettore; Murer, Luisa; Vivarelli, Marina; Noris, Marina; Remuzzi, Giuseppe

2018-01-01

Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment. Copyright © 2018 by the American Society of Nephrology.

Relative roles of general and complementation language in theory-of-mind development: evidence from Cantonese and English.

PubMed

Cheung, Him; Hsuan-Chih, Chen; Creed, Nikki; Ng, Lisa; Ping Wang, Sui; Mo, Lei

2004-01-01

Complex complements are clausal objects containing tensed verbs (e.g., that she cried) or infinitives (e.g., to cry), following main verbs of communication or mental activities (e.g., say, want). This research examined whether English- and Cantonese-speaking 4-year-olds' complement understanding uniquely predicts their representation of other minds (i.e., theory of mind). Results showed that neither meaning of main verbs (communication vs. desire) nor complement structure (tensed vs. infinitival) affected the correlation between complement understanding and theory of mind. More important, the correlation became insignificant after controlling for general language comprehension. These findings led to the conclusion that the syntax of complement per se does not contribute uniquely to theory-of-mind development; general language comprehension is a more important factor to consider. Copyright 2004 Society for Research in Child Development, Inc.

Early Complementopathy after Multiple Injuries in Humans

PubMed Central

Burk, Anne-Maud; Martin, Myriam; Flierl, Michael A.; Rittirsch, Daniel; Helm, Matthias; Lampl, Lorenz; Bruckner, Uwe; Stahl, Gregory L.; Blom, Anna M.; Perl, Mario; Gebhard, Florian; Huber-Lang, Markus

2012-01-01

After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study we hypothesized that multiple trauma results in immediate activation, consumption and dysfunction of the complement cascade and that the resulting severe “complementopathy” may be associated with morbidity and mortality. Therefore a prospective multicenter study with 25 healthy volunteers and 40 polytrauma patients (mean injury severity score [ISS] = 30.3 ± 2.9) was performed. After polytrauma serum was collected as early as possible at the scene, upon admission to the emergency room and 4, 12, 24, 120 and 240 hours post trauma and analysed for the complement profile. Complement hemolytic activity (CH-50) was massively reduced within the first 24 h after injury, recovered only 5 days after trauma and discriminated between lethal and non-lethal 28-day outcome. Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlated with the severity of traumatic brain injury and survival. The soluble terminal complement complex SC5b-9 and mannose-binding lectin (MBL) showed a biphasic response after trauma. Key fluid phase inhibitors of complement, such as C4b-binding protein (C4BP) and factor I, were significantly diminished early after trauma. The present data indicate an almost synchronically rapid activation and dysfunction of complement suggesting a trauma-induced “complementopathy” early after injury. These events may participate to the impairment of the innate immune response observed after severe trauma. PMID:22258234

Binding of Free and Immune Complex-Associated Hepatitis C Virus to Erythrocytes Is Mediated by the Complement System.

PubMed

Salam, Kazi Abdus; Wang, Richard Y; Grandinetti, Teresa; De Giorgi, Valeria; Alter, Harvey J; Allison, Robert D

2018-05-09

Erythrocytes bind circulating immune complexes (IC) and facilitate IC clearance from the circulation. Chronic hepatitis C virus (HCV) infection is associated with IC-related disorders. In this study we investigated the kinetics and mechanism of HCV and HCV-IC binding to and dissociation from erythrocytes. Cell culture-produced HCV was mixed with erythrocytes from healthy blood donors and erythrocyte-associated virus particles were quantified. Purified complement proteins, complement-depleted serum, and complement receptor antibodies were used to investigate complement-mediated HCV-erythrocyte binding. Purified HCV-specific immunoglobulin G from a chronic HCV-infected patient was used to study complement-mediated HCV-IC-erythrocyte binding. Binding of HCV to erythrocytes increased 200 to 1,000 fold after adding complement active human serum in the absence of antibody. Opsonization of free HCV occurred within 10 minutes and peak binding to erythrocytes was observed at 20-30 minutes. Complement protein C1 was required for binding, while C2, C3 and C4 significantly enhanced binding. Complement receptor 1 (CR1, CD35) antibodies blocked the binding of HCV to erythrocytes isolated from chronically infected HCV patients and healthy blood donors. HCV-ICs significantly enhanced complement-mediated binding to erythrocytes compared to unbound HCV. Dissociation of complement-opsonized HCV from erythrocytes depended on the presence of Factor I. HCV released by Factor I bound preferentially to CD19+ B cells compared to other leukocytes. These results demonstrate that complement mediates the binding of free and IC-associated HCV to CR1 on erythrocytes, and provide a mechanistic rationale for investigating the differential phenotypic expression of HCV-IC-related disease. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Language and theory of mind in autism spectrum disorder: the relationship between complement syntax and false belief task performance.

PubMed

Lind, Sophie E; Bowler, Dermot M

2009-06-01

This study aimed to test the hypothesis that children with autism spectrum disorder (ASD) use their knowledge of complement syntax as a means of "hacking out" solutions to false belief tasks, despite lacking a representational theory of mind (ToM). Participants completed a "memory for complements" task, a measure of receptive vocabulary, and traditional location change and unexpected contents false belief tasks. Consistent with predictions, the correlation between complement syntax score and location change task performance was significantly stronger within the ASD group than within the comparison group. However, contrary to predictions, complement syntax score was not significantly correlated with unexpected contents task performance within either group. Possible explanations for this pattern of results are considered.

Ectromelia virus inhibitor of complement enzymes protects intracellular mature virus and infected cells from mouse complement.

PubMed

Moulton, Elizabeth A; Bertram, Paula; Chen, Nanhai; Buller, R Mark L; Atkinson, John P

2010-09-01

Poxviruses produce complement regulatory proteins to subvert the host's immune response. Similar to the human pathogen variola virus, ectromelia virus has a limited host range and provides a mouse model where the virus and the host's immune response have coevolved. We previously demonstrated that multiple components (C3, C4, and factor B) of the classical and alternative pathways are required to survive ectromelia virus infection. Complement's role in the innate and adaptive immune responses likely drove the evolution of a virus-encoded virulence factor that regulates complement activation. In this study, we characterized the ectromelia virus inhibitor of complement enzymes (EMICE). Recombinant EMICE regulated complement activation on the surface of CHO cells, and it protected complement-sensitive intracellular mature virions (IMV) from neutralization in vitro. It accomplished this by serving as a cofactor for the inactivation of C3b and C4b and by dissociating the catalytic domain of the classical pathway C3 convertase. Infected murine cells initiated synthesis of EMICE within 4 to 6 h postinoculation. The levels were sufficient in the supernatant to protect the IMV, upon release, from complement-mediated neutralization. EMICE on the surface of infected murine cells also reduced complement activation by the alternative pathway. In contrast, classical pathway activation by high-titer antibody overwhelmed EMICE's regulatory capacity. These results suggest that EMICE's role is early during infection when it counteracts the innate immune response. In summary, ectromelia virus produced EMICE within a few hours of an infection, and EMICE in turn decreased complement activation on IMV and infected cells.

Human-centred design in global health: A scoping review of applications and contexts.

PubMed

Bazzano, Alessandra N; Martin, Jane; Hicks, Elaine; Faughnan, Maille; Murphy, Laura

2017-01-01

Health and wellbeing are determined by a number of complex, interrelated factors. The application of design thinking to questions around health may prove valuable and complement existing approaches. A number of public health projects utilizing human centered design (HCD), or design thinking, have recently emerged, but no synthesis of the literature around these exists. The results of a scoping review of current research on human centered design for health outcomes are presented. The review aimed to understand why and how HCD can be valuable in the contexts of health related research. Results identified pertinent literature as well as gaps in information on the use of HCD for public health research, design, implementation and evaluation. A variety of contexts were identified in which design has been used for health. Global health and design thinking have different underlying conceptual models and terminology, creating some inherent tensions, which could be overcome through clear communication and documentation in collaborative projects. The review concludes with lessons learned from the review on how future projects can better integrate design thinking with global health research.

Regional reconstruction of flash flood history in the Guadarrama range (Central System, Spain).

PubMed

Rodriguez-Morata, C; Ballesteros-Cánovas, J A; Trappmann, D; Beniston, M; Stoffel, M

2016-04-15

Flash floods are a common natural hazard in Mediterranean mountain environments and responsible for serious economic and human disasters. The study of flash flood dynamics and their triggers is a key issue; however, the retrieval of historical data is often limited in mountain regions as a result of short time series and the systematic lack of historical data. In this study, we attempt to overcome data deficiency by supplementing existing records with dendrogeomorphic techniques which were employed in seven mountain streams along the northern slopes of the Guadarrama Mountain range. Here we present results derived from the tree-ring analysis of 117 samples from 63 Pinus sylvestris L. trees injured by flash floods, to complement existing flash flood records covering the last ~200years and comment on their hydro-meteorological triggers. To understand the varying number of reconstructed flash flood events in each of the catchments, we also performed a comparative analysis of geomorphic catchment characteristics, land use evolution and forest management. Furthermore, we discuss the limitations of dendrogeomorphic techniques applied in managed forests. Copyright © 2016 Elsevier B.V. All rights reserved.

Crowding by Invisible Flankers

PubMed Central

Ho, Cristy; Cheung, Sing-Hang

2011-01-01

Background Human object recognition degrades sharply as the target object moves from central vision into peripheral vision. In particular, one's ability to recognize a peripheral target is severely impaired by the presence of flanking objects, a phenomenon known as visual crowding. Recent studies on how visual awareness of flanker existence influences crowding had shown mixed results. More importantly, it is not known whether conscious awareness of the existence of both the target and flankers are necessary for crowding to occur. Methodology/Principal Findings Here we show that crowding persists even when people are completely unaware of the flankers, which are rendered invisible through the continuous flash suppression technique. Contrast threshold for identifying the orientation of a grating pattern was elevated in the flanked condition, even when the subjects reported that they were unaware of the perceptually suppressed flankers. Moreover, we find that orientation-specific adaptation is attenuated by flankers even when both the target and flankers are invisible. Conclusions These findings complement the suggested correlation between crowding and visual awareness. What's more, our results demonstrate that conscious awareness and attention are not prerequisite for crowding. PMID:22194919

Human-centred design in global health: A scoping review of applications and contexts

PubMed Central

Martin, Jane; Hicks, Elaine; Faughnan, Maille; Murphy, Laura

2017-01-01

Health and wellbeing are determined by a number of complex, interrelated factors. The application of design thinking to questions around health may prove valuable and complement existing approaches. A number of public health projects utilizing human centered design (HCD), or design thinking, have recently emerged, but no synthesis of the literature around these exists. The results of a scoping review of current research on human centered design for health outcomes are presented. The review aimed to understand why and how HCD can be valuable in the contexts of health related research. Results identified pertinent literature as well as gaps in information on the use of HCD for public health research, design, implementation and evaluation. A variety of contexts were identified in which design has been used for health. Global health and design thinking have different underlying conceptual models and terminology, creating some inherent tensions, which could be overcome through clear communication and documentation in collaborative projects. The review concludes with lessons learned from the review on how future projects can better integrate design thinking with global health research. PMID:29091935

Casimir-Lifshitz interaction between dielectrics of arbitrary geometry: A dielectric contrast perturbation theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golestanian, Ramin

2009-07-15

The general theory of electromagnetic-fluctuation-induced interactions in dielectric bodies as formulated by Dzyaloshinskii, Lifshitz, and Pitaevskii is rewritten as a perturbation theory in terms of the spatial contrast in (imaginary) frequency dependent dielectric function. The formulation can be used to calculate the Casimir-Lifshitz forces for dielectric objects of arbitrary geometry, as a perturbative expansion in the dielectric contrast, and could thus complement the existing theories that use perturbation in geometrical features. We find that expansion in dielectric contrast recasts the resulting Lifshitz energy into a sum of the different many-body contributions. The limit of validity and convergence properties of themore » perturbation theory is discussed using the example of parallel semi-infinite objects for which the exact result is known.« less

PubMed Central

Montplaisir, S.; Côté, P. P.; Martineau, B.; Roche, A. J.; Mongeau, J. G.; Robitaille, P.

1976-01-01

The demonstration by immuno-fluorescence of antibodies on the surface of urinary bacteria, a new method of determining the site of a urinary tract infection, was found to be as valuable in children as it is in adults. A clear correlation exists between a positive test result and renal parenchymal infection on one hand, and a negative result and lower urinary tract infection on the other. Moreover, immunoglobulins were still detectable in original positive urine samples that had been standing at 4degrees C for 7 weeks. The constant finding of IgA on bacteria suggests a particular synthesis for this class of immunoglobulin. A pathophysiologic role for complement would appear to be excluded by the facts that the serum concentrations of C3 were normal and that C3 was invariably absent from the bacterial surface. Images FIG. 1 PMID:793701

First passage properties of a generalized Pólya urn

NASA Astrophysics Data System (ADS)

Kearney, Michael J.; Martin, Richard J.

2016-12-01

A generalized two-component Pólya urn process, parameterized by a variable α , is studied in terms of the likelihood that due to fluctuations the initially smaller population in a scenario of competing population growth eventually becomes the larger, or is the larger after a certain passage of time. By casting the problem as an inhomogeneous directed random walk we quantify this role-reversal phenomenon through the first passage probability that equality in size is first reached at a given time, and the related exit probability that equality in size is reached no later than a given time. Using an embedding technique, exact results are obtained which complement existing results and provide new insights into behavioural changes (akin to phase transitions) which occur at defined values of α .

The Role of Complement in Cnidarian-Dinoflagellate Symbiosis and Immune Challenge in the Sea Anemone Aiptasia pallida

PubMed Central

Poole, Angela Z.; Kitchen, Sheila A.; Weis, Virginia M.

2016-01-01

The complement system is an innate immune pathway that in vertebrates, is responsible for initial recognition and ultimately phagocytosis and destruction of microbes. Several complement molecules including C3, Factor B, and mannose binding lectin associated serine proteases (MASP) have been characterized in invertebrates and while most studies have focused on their conserved role in defense against pathogens, little is known about their role in managing beneficial microbes. The purpose of this study was to (1) characterize complement pathway genes in the symbiotic sea anemone Aiptasia pallida, (2) investigate the evolution of complement genes in invertebrates, and (3) examine the potential dual role of complement genes Factor B and MASP in the onset and maintenance of cnidarian-dinoflagellate symbiosis and immune challenge using qPCR based studies. The results demonstrate that A. pallida has multiple Factor B genes (Ap_Bf-1, Ap_Bf-2a, and Ap_Bf-2b) and one MASP gene (Ap_MASP). Phylogenetic analysis indicates that the evolutionary history of complement genes is complex, and there have been many gene duplications or gene loss events, even within members of the same phylum. Gene expression analyses revealed a potential role for complement in both onset and maintenance of cnidarian-dinoflagellate symbiosis and immune challenge. Specifically, Ap_Bf-1 and Ap_MASP are significantly upregulated in the light at the onset of symbiosis and in response to challenge with the pathogen Serratia marcescens suggesting that they play a role in the initial recognition of both beneficial and harmful microbes. Ap_Bf-2b in contrast, was generally downregulated during the onset and maintenance of symbiosis and in response to challenge with S. marcescens. Therefore, the exact role of Ap_Bf-2b in response to microbes remains unclear, but the results suggest that the presence of microbes leads to repressed expression. Together, these results indicate functional divergence between Ap_Bf-1 and Ap_Bf-2b, and that Ap_Bf-1 and Ap_MASP may be functioning together in an ancestral hybrid of the lectin and alternative complement pathways. Overall, this study provides information on the role of the complement system in a basal metazoan and its role in host-microbe interactions. PMID:27148208

The Role of Complement in Cnidarian-Dinoflagellate Symbiosis and Immune Challenge in the Sea Anemone Aiptasia pallida.

PubMed

Poole, Angela Z; Kitchen, Sheila A; Weis, Virginia M

2016-01-01

The complement system is an innate immune pathway that in vertebrates, is responsible for initial recognition and ultimately phagocytosis and destruction of microbes. Several complement molecules including C3, Factor B, and mannose binding lectin associated serine proteases (MASP) have been characterized in invertebrates and while most studies have focused on their conserved role in defense against pathogens, little is known about their role in managing beneficial microbes. The purpose of this study was to (1) characterize complement pathway genes in the symbiotic sea anemone Aiptasia pallida, (2) investigate the evolution of complement genes in invertebrates, and (3) examine the potential dual role of complement genes Factor B and MASP in the onset and maintenance of cnidarian-dinoflagellate symbiosis and immune challenge using qPCR based studies. The results demonstrate that A. pallida has multiple Factor B genes (Ap_Bf-1, Ap_Bf-2a, and Ap_Bf-2b) and one MASP gene (Ap_MASP). Phylogenetic analysis indicates that the evolutionary history of complement genes is complex, and there have been many gene duplications or gene loss events, even within members of the same phylum. Gene expression analyses revealed a potential role for complement in both onset and maintenance of cnidarian-dinoflagellate symbiosis and immune challenge. Specifically, Ap_Bf-1 and Ap_MASP are significantly upregulated in the light at the onset of symbiosis and in response to challenge with the pathogen Serratia marcescens suggesting that they play a role in the initial recognition of both beneficial and harmful microbes. Ap_Bf-2b in contrast, was generally downregulated during the onset and maintenance of symbiosis and in response to challenge with S. marcescens. Therefore, the exact role of Ap_Bf-2b in response to microbes remains unclear, but the results suggest that the presence of microbes leads to repressed expression. Together, these results indicate functional divergence between Ap_Bf-1 and Ap_Bf-2b, and that Ap_Bf-1 and Ap_MASP may be functioning together in an ancestral hybrid of the lectin and alternative complement pathways. Overall, this study provides information on the role of the complement system in a basal metazoan and its role in host-microbe interactions.

Kupffer cell complement receptor clearance function and host defense.

PubMed

Loegering, D J

1986-01-01

Kupffer cells are well known to be important for normal host defense function. The development of methods to evaluate the in vivo function of specific receptors on Kupffer cells has made it possible to assess the role of these receptors in host defense. The rationale for studying complement receptors is based on the proposed important role of these receptors in host defense and on the observation that the hereditary deficiency of a complement receptor is associated with recurrent severe bacterial infections. The studies reviewed here demonstrate that forms of injury that are associated with depressed host defense including thermal injury, hemorrhagic shock, trauma, and surgery also cause a decrease in complement receptor clearance function. This decrease in Kupffer cell receptor clearance function was shown not to be the result of depressed hepatic blood flow or depletion of complement components. Complement receptor function was also depressed following the phagocytosis of particulates that are known to depress Kupffer cell host defense function. Endotoxemia and bacteremia also were associated with a depression of complement receptor function. Complement receptor function was experimentally depressed in uninjured animals by the phagocytosis of IgG-coated erythrocytes. There was a close association between the depression of complement receptor clearance function and increased susceptibility to the lethal effects of endotoxin and bacterial infection. These studies support the hypotheses that complement receptors on Kupffer cells are important for normal host defense and that depression of the function of these receptors impairs host defense.

An Anti-C1s Monoclonal, TNT003, Inhibits Complement Activation Induced by Antibodies Against HLA.

PubMed

Thomas, K A; Valenzuela, N M; Gjertson, D; Mulder, A; Fishbein, M C; Parry, G C; Panicker, S; Reed, E F

2015-08-01

Antibody-mediated rejection (AMR) of solid organ transplants (SOT) is characterized by damage triggered by donor-specific antibodies (DSA) binding donor Class I and II HLA (HLA-I and HLA-II) expressed on endothelial cells. While F(ab')2 portions of DSA cause cellular activation and proliferation, Fc regions activate the classical complement cascade, resulting in complement deposition and leukocyte recruitment, both hallmark features of AMR. We characterized the ability of an anti-C1s monoclonal antibody, TNT003, to inhibit HLA antibody (HLA-Ab)-induced complement activation. Complement deposition induced by HLA-Ab was evaluated using novel cell- and bead-based assays. Human aortic endothelial cells (HAEC) were cultured with HLA-Ab and human complement; production of activated complement proteins was measured by flow cytometry. Additionally, C3d deposition was measured on single antigen beads (SAB) mixed with HLA-Ab and human complement. TNT003 inhibited HLA-Ab mediated complement deposition on HAEC in a concentration-dependent manner; C3a, C4a and C5a anaphylatoxin production was also diminished by TNT003. Finally, TNT003 blocked C3d deposition induced by Class I (HLAI-Ab)- and Class II (HLAII-Ab)-specific antibodies on SAB. These data suggest TNT003 may be useful for modulating the effects of DSA, as TNT003 inhibits complement deposition and split product formation generated by HLA-I/II-Ab in vitro. © 2015 The Authors. American Journal of Transplantation Published by Wiley Periodicals, Inc.

An Anti-C1s Monoclonal, TNT003, Inhibits Complement Activation Induced by Antibodies Against HLA

PubMed Central

Thomas, K A; Valenzuela, N M; Gjertson, D; Mulder, A; Fishbein, M C; Parry, G C; Panicker, S; Reed, E F

2015-01-01

Antibody-mediated rejection (AMR) of solid organ transplants (SOT) is characterized by damage triggered by donor-specific antibodies (DSA) binding donor Class I and II HLA (HLA-I and HLA-II) expressed on endothelial cells. While F(ab′)2 portions of DSA cause cellular activation and proliferation, Fc regions activate the classical complement cascade, resulting in complement deposition and leukocyte recruitment, both hallmark features of AMR. We characterized the ability of an anti-C1s monoclonal antibody, TNT003, to inhibit HLA antibody (HLA-Ab)-induced complement activation. Complement deposition induced by HLA-Ab was evaluated using novel cell- and bead-based assays. Human aortic endothelial cells (HAEC) were cultured with HLA-Ab and human complement; production of activated complement proteins was measured by flow cytometry. Additionally, C3d deposition was measured on single antigen beads (SAB) mixed with HLA-Ab and human complement. TNT003 inhibited HLA-Ab mediated complement deposition on HAEC in a concentration-dependent manner; C3a, C4a and C5a anaphylatoxin production was also diminished by TNT003. Finally, TNT003 blocked C3d deposition induced by Class I (HLAI-Ab)- and Class II (HLAII-Ab)-specific antibodies on SAB. These data suggest TNT003 may be useful for modulating the effects of DSA, as TNT003 inhibits complement deposition and split product formation generated by HLA-I/II-Ab in vitro. PMID:25904443

Discovering the Power of Individual-Based Modelling in Teaching and Learning: The Study of a Predator-Prey System

ERIC Educational Resources Information Center

Ginovart, Marta

2014-01-01

The general aim is to promote the use of individual-based models (biological agent-based models) in teaching and learning contexts in life sciences and to make their progressive incorporation into academic curricula easier, complementing other existing modelling strategies more frequently used in the classroom. Modelling activities for the study…

Addressing the Uncertain Future of Preserving the Past: Towards a Robust Strategy for Digital Archiving and Preservation. Technical Report

ERIC Educational Resources Information Center

Hoorens, Stijn; Rothenberg, Jeff; van Orange, Constantijn; van der Mandele, Martijn; Levitt, Ruth

2007-01-01

Storing and curating authentic academic literature and making it accessible for the long term has been a time-honoured task of national libraries. By guarding existing knowledge and facilitating its use to produce new insights, national and university libraries have formed an integral part of the research environment, complementing the roles of…

Sentinel-1 - the radar mission for GMES operational land and sea services

NASA Astrophysics Data System (ADS)

Attema, Evert; Bargellini, Pierre; Edwards, Peter; Levrini, Guido; Lokas, Svein; Moeller, Ludwig; Rosich-Tell, Betlem; Secchi, Patrizia; Torres, Ramon; Davidson, Malcolm; Snoeij, Paul

2007-08-01

The ESA Sentinels will be the first series of operational satellites to meet the Earth observation needs of the European Union - ESA Global Monitoring for Environment and Security (GMES) programme. Existing and planned space assets will be complemented by new developments from ESA. The first is Sentinel-1, a pair of synthetic aperture radar (SAR) imaging satellites.

Year 5 Booster Units. The National Literacy Strategy.

ERIC Educational Resources Information Center

Department for Education and Employment, London (England).

The eight units of work in this document are designed to complement existing literacy booster units. Each unit is based on teaching objectives from the National Literacy Strategy Framework. They have been produced with the help of Year 5 teachers and have been trialled with pupils in a range of schools. The units support teachers' work with Year 5…

The TOPEX satellite option study

NASA Technical Reports Server (NTRS)

1982-01-01

The applicability of an existing spacecraft bus and subsystems to the requirements of ocean circulation measurements are assessed. The operational meteorological satellite family TIROS and DMSP are recommended. These programs utilize a common bus to satisfy their Earth observation missions. Note that although the instrument complements were different, the pointing accuracies were different, and, initially, the boosters were different, a high degree of commonality was achieved.

Understanding Unimer Exchange Processes in Block Copolymer Micelles using NMR Diffusometry, Time-Resolved NMR, and SANS

NASA Astrophysics Data System (ADS)

Madsen, Louis; Kidd, Bryce; Li, Xiuli; Miller, Katherine; Cooksey, Tyler; Robertson, Megan

Our team seeks to understand dynamic behaviors of block copolymer micelles and their interplay with encapsulated cargo molecules. Quantifying unimer and cargo exchange rates micelles can provide critical information for determining mechanisms of unimer exchange as well as designing systems for specific cargo release dynamics. We are exploring the utility of NMR spectroscopy and diffusometry techniques as complements to existing SANS and fluorescence methods. One promising new method involves time-resolved NMR spin relaxation measurements, wherein mixing of fully protonated and 2H-labeled PEO-b-PCL micelles solutions shows an increase in spin-lattice relaxation time (T1) with time after mixing. This is due to a weakening in magnetic environment surrounding 1H spins as 2H-bearing unimers join fully protonated micelles. We are measuring time constants for unimer exchange of minutes to hours, and we expect to resolve times of <1 min. This method can work on any solution NMR spectrometer and with minimal perturbation to chemical structure (as in dye-labelled fluorescence methods). Multimodal NMR can complement existing characterization tools, expanding and accelerating dynamics measurements for polymer micelle, nanogel, and nanoparticle developers.

Interprofessionalism: Educating to meet patient needs.

PubMed

Kirch, Darrell G; Ast, Cori

2015-01-01

Interprofessional teams in health care are showing promise in achieving the triple aim-providing better care for the individual patient, reducing costs, and improving population health. To complement current changes in health care delivery in the United States, there is a growing consensus among health professions educators that students should be trained in interprofessional models prior to entering clinical practice. Current interprofessional education (IPE) efforts in anatomy education are producing positive results in enhancing professional respect, collaboration, and teamwork among health professions students. In spite of existing structural and cultural barriers to IPE, health professions educators must continue to lead and grow IPE efforts as a critical component to improving the health of our nation. © 2014 American Association of Anatomists.

Spatial correlation of auroral zone geomagnetic variations

NASA Astrophysics Data System (ADS)

Jackel, B. J.; Davalos, A.

2016-12-01

Magnetic field perturbations in the auroral zone are produced by a combination of distant ionospheric and local ground induced currents. Spatial and temporal structure of these currents is scientifically interesting and can also have a significant influence on critical infrastructure.Ground-based magnetometer networks are an essential tool for studying these phenomena, with the existing complement of instruments in Canada providing extended local time coverage. In this study we examine the spatial correlation between magnetic field observations over a range of scale lengths. Principal component and canonical correlation analysis are used to quantify relationships between multiple sites. Results could be used to optimize network configurations, validate computational models, and improve methods for empirical interpolation.

Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients.

PubMed

Perazzio, Sandro Félix; Silva, Neusa Pereira da; Carneiro-Sampaio, Magda; Andrade, Luis Eduardo Coelho

2016-01-01

The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500μg/L), moderate (<500 and ≥100μg/L) or severe (<100μg/L). SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Coagulation cascade and complement system in systemic lupus erythematosus

PubMed Central

Liang, Yan; Xie, Shang-Bo; Wu, Chang-Hao; Hu, Yuan; Zhang, Qin; Li, Si; Fan, Yin-Guang; Leng, Rui-Xue; Pan, Hai-Feng; Xiong, Hua-Bao; Ye, Dong-Qing

2018-01-01

This study was conducted to (1) characterize coagulation cascade and complement system in systemic lupus erythematosus (SLE); (2) evaluate the associations between coagulation cascade, complement system, inflammatory response and SLE disease severity; (3) test the diagnostic value of a combination of D-dimer and C4 for lupus activity. Transcriptomics, proteomics and metabolomics were performed in 24 SLE patients and 24 healthy controls. The levels of ten coagulations, seven complements and three cytokines were measured in 112 SLE patients. Clinical data were collected from 2025 SLE patients. The analysis of multi-omics data revealed the common links for the components of coagulation cascade and complement system. The results of ELISA showed coagulation cascade and complement system had an interaction effect on SLE disease severity, this effect was pronounced among patients with excess inflammation. The analysis of clinical data revealed a combination of D-dimer and C4 provided good diagnostic performance for lupus activity. This study suggested that coagulation cascade and complement system become ‘partners in crime’, contributing to SLE disease severity and identified the diagnostic value of D-dimer combined with C4for lupus activity. PMID:29599912

Expanding access and choice for health care consumers through tax reform.

PubMed

Butler, S; Kendall, D B

1999-01-01

A refundable tax credit for the uninsured would complement the existing job-based health insurance system while letting people keep their job-based coverage if they wish. Among the wide variety of design options for a tax credit, policy and political analysis does not reveal an obvious choice, but a tax credit based on a percentage of spending may have a slight advantage. Congress should give states maximum flexibility to use existing funding sources to supplement the value of a federal tax credit and encourage the use of techniques to create stable insurance pools.

Complement in autoimmune diseases.

PubMed

Vignesh, Pandiarajan; Rawat, Amit; Sharma, Madhubala; Singh, Surjit

2017-02-01

The complement system is an ancient and evolutionary conserved element of the innate immune mechanism. It comprises of more than 20 serum proteins most of which are synthesized in the liver. These proteins are synthesized as inactive precursor proteins which are activated by appropriate stimuli. The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to exponential generation of final effectors. Three major pathways of complement pathways have been described, namely the classical, alternative and lectin pathways which are activated by different stimuli. However, all the 3 pathways converge on Complement C3. Cleavage of C3 and C5 successively leads to the production of the membrane attack complex which is final common effector. Excessive and uncontrolled activation of the complement has been implicated in the host of autoimmune diseases. But the complement has also been bemusedly described as the proverbial "double edged sword". On one hand, complement is the final effector of tissue injury in autoimmune diseases and on the other, deficiencies of some components of the complement can result in autoimmune diseases. Currently available tools such as enzyme based immunoassays for functional assessment of complement pathways, flow cytometry, next generation sequencing and proteomics-based approaches provide an exciting opportunity to study this ancient yet mysterious element of innate immunity. Copyright © 2017 Elsevier B.V. All rights reserved.

Myasthenia gravis: the role of complement at the neuromuscular junction.

PubMed

Howard, James F

2018-01-01

Generalized myasthenia gravis (gMG) is a rare autoimmune disorder characterized by skeletal muscle weakness caused by disrupted neurotransmission at the neuromuscular junction (NMJ). Approximately 74-88% of patients with gMG have acetylcholine receptor (AChR) autoantibodies. Complement plays an important role in innate and antibody-mediated immunity, and activation and amplification of complement results in the formation of membrane attack complexes (MACs), lipophilic proteins that damage cell membranes. The role of complement in gMG has been demonstrated in animal models and patients. Studies in animals lacking specific complement proteins have confirmed that MAC formation is required to induce experimental autoimmune MG (EAMG) and NMJ damage. Complement inhibition in EAMG models can prevent disease induction and reverse its progression. Patients with anti-AChR + MG have autoantibodies and MACs present at NMJs. Damaged NMJs are associated with more severe disease, fewer AChRs, and MACs in synaptic debris. Current MG therapies do not target complement directly. Eculizumab is a humanized monoclonal antibody that inhibits cleavage of complement protein C5, preventing MAC formation. Eculizumab treatment improved symptoms compared with placebo in a phase II study in patients with refractory gMG. Direct complement inhibition could preserve NMJ physiology and muscle function in patients with anti-AChR + gMG. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Code conversion from signed-digit to complement representation based on look-ahead optical logic operations

NASA Astrophysics Data System (ADS)

Li, Guoqiang; Qian, Feng

2001-11-01

We present, for the first time to our knowledge, a generalized lookahead logic algorithm for number conversion from signed-digit to complement representation. By properly encoding the signed-digits, all the operations are performed by binary logic, and unified logical expressions can be obtained for conversion from modified-signed- digit (MSD) to 2's complement, trinary signed-digit (TSD) to 3's complement, and quarternary signed-digit (QSD) to 4's complement. For optical implementation, a parallel logical array module using an electron-trapping device is employed and experimental results are shown. This optical module is suitable for implementing complex logic functions in the form of the sum of the product. The algorithm and architecture are compatible with a general-purpose optoelectronic computing system.

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

PubMed

Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

2015-01-01

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

On the evaluation of segmentation editing tools

PubMed Central

Heckel, Frank; Moltz, Jan H.; Meine, Hans; Geisler, Benjamin; Kießling, Andreas; D’Anastasi, Melvin; dos Santos, Daniel Pinto; Theruvath, Ashok Joseph; Hahn, Horst K.

2014-01-01

Abstract. Efficient segmentation editing tools are important components in the segmentation process, as no automatic methods exist that always generate sufficient results. Evaluating segmentation editing algorithms is challenging, because their quality depends on the user’s subjective impression. So far, no established methods for an objective, comprehensive evaluation of such tools exist and, particularly, intermediate segmentation results are not taken into account. We discuss the evaluation of editing algorithms in the context of tumor segmentation in computed tomography. We propose a rating scheme to qualitatively measure the accuracy and efficiency of editing tools in user studies. In order to objectively summarize the overall quality, we propose two scores based on the subjective rating and the quantified segmentation quality over time. Finally, a simulation-based evaluation approach is discussed, which allows a more reproducible evaluation without the need for human input. This automated evaluation complements user studies, allowing a more convincing evaluation, particularly during development, where frequent user studies are not possible. The proposed methods have been used to evaluate two dedicated editing algorithms on 131 representative tumor segmentations. We show how the comparison of editing algorithms benefits from the proposed methods. Our results also show the correlation of the suggested quality score with the qualitative ratings. PMID:26158063

Role of Complement Activation in a Model of Adult Respiratory Distress Syndrome

PubMed Central

Hosea, Stephen; Brown, Eric; Hammer, Carl; Frank, Michael

1980-01-01

The adult respiratory distress syndrome is characterized by arterial hypoxemia as a result of increased alveolar capillary permeability to serum proteins in the setting of normal capillary hydrostatic pressures. Because bacterial sepsis is prominent among the various diverse conditions associated with altered alveolar capillary permeability, we studied the effect of bacteremia with attendant complement activation on the sequestration of microorganisms and the leakage of albumin in the lungs of guinea pigs. Pneumococci were injected intravenously into guinea pigs and their localization was studied. Unlike normal guinea pigs, complement-depleted guinea pigs did not localize injected bacteria to the lungs. Preopsonization of organisms did not correct this defect in pulmonary localization of bacteria in complement-depleted animals, suggesting that a fluid-phase component of complement activation was required. Genetically C5-deficient mice showed no pulmonary localization of bacteria. C5-sufficient mice demonstrated the usual pulmonary localization, thus further suggesting that the activation of C5 might be important in this localization. The infusion of activated C5 increased alveolar capillary permeability to serum proteins as assayed by the amount of radioactive albumin sequestered in the lung. Neutropenic animals did not develop altered capillary permeability after challenge with activated C5. Thus, complement activation through C5, in the presence of neutrophils, induces alterations in pulmonary alveolar capillary permeability and causes localization of bacteria to the pulmonary parenchyma. Complement activation in other disease states could potentially result in similar clinical manifestations. PMID:7400321

Preparation of Low Molecular Weight Chondroitin Sulfates, Screening of a High Anti-Complement Capacity of Low Molecular Weight Chondroitin Sulfate and Its Biological Activity Studies in Attenuating Osteoarthritis.

PubMed

Li, Lian; Li, Yan; Feng, Danyang; Xu, Linghua; Yin, Fengxin; Zang, Hengchang; Liu, Chunhui; Wang, Fengshan

2016-10-11

Chondroitin sulfate (CS) plays important roles in the complement system. However, the CS structure is complicated due to different sources and the number and positions of sulfate groups. The objective of this study was to prepare different low molecular weight chondroitin sulfates (LMWCSs) and to investigate the biological activity in anti-complement capacity. A series of LMWCSs was prepared from different sources and characterized by ultraviolet-visible (UV) spectroscopy, high-performance liquid chromatography (HPLC), size exclusion chromatography-multiangle laser light scattering (SEC-MALLS) and nuclear magnetic resonance (NMR) spectroscopy. Hemolytic, anti-complement 3 deposition capacity and cell viability assays were carried out to investigate the biological activities in vitro. The results showed that LMWCS prepared from shark cartilage with the oxidative degradation method (LMWCS-S-O) had the best anti-complement capacity. LMWCS-S-O could inhibit the alternative pathway of the complement system and protect chondrocytes from cell death. The attenuating effect of LMWCS-S-O on Osteoarthritis (OA) was investigated by destabilization of the medial meniscus (DMM) model in vivo. Functional wind-up, histological and C5b-9 analyses were used to evaluate the treatment effect on the OA model. In vivo results showed that LMWCS-S-O could attenuate OA. LMWCS-S-O with a high content of ΔDi-2,6diS and ΔDi-6S could be used for attenuating OA through regulating the complement system.

Language and False-Belief Task Performance in Children With Autism Spectrum Disorder.

PubMed

Jeffrey Farrar, M; Seung, Hye Kyeung; Lee, Hyeonjin

2017-07-12

Language is related to false-belief (FB) understanding in both typically developing children and children with autism spectrum disorder (ASD). The current study examined the role of complementation and general language in FB understanding. Of interest was whether language plays similar or different roles in the groups' FB performance. Participants were 16 typically developing children (mean age = 5.0 years; mental age = 6.7) and 18 with ASD (mean age = 7.3 years; mental age = 8.3). Children were administered FB and language tasks (say- and think-complements), receptive and expressive vocabulary tests, and relative clauses. When mental age and receptive and expressive vocabulary were used as separate covariates, the typical control group outperformed the children with ASD in FB task performance. Chi-square analyses indicated that passing both complementation tasks was linked to the FB understanding of children with ASD. Children with ASD who passed FB tasks all passed say- and think-complement tasks. However, some children in the control group were able to pass the FB tasks, even if they failed the say- and think-complement tasks. The results indicate that children with ASD relied more on complement understanding to pass FB than typically developing children. Results are discussed regarding the developmental pathways for FB understanding.

Oscillatory brain activity differentially reflects false belief understanding and complementation syntax processing.

PubMed

Guan, Yao; Farrar, M Jeffrey; Keil, Andreas

2018-02-01

False belief understanding (FBU) enables people to consider conflicting beliefs about the same situation. While language has been demonstrated to be a correlate of FBU, there is still controversy about the extent to which a specific aspect of language, complementation syntax, is a necessary condition for FBU. The present study tested an important notion from the debate proposing that complementation syntax task is redundant to FBU measures. Specifically, we examined electrophysiological correlates of false belief, false complementation, and their respective true conditions in adults using electroencephalography (EEG), focusing on indices of oscillatory brain activity and large-scale connectivity. The results showed strong modulation of parieto-occipital alpha (8-12 Hz) and beta (13-20 Hz) power by the experimental manipulations, with heightened sustained alpha power reflective of effortful internal processing observed in the false compared to the true conditions and reliable beta power reductions sensitive to mentalizing and/or syntactic demands in the belief versus the complementation conditions. In addition, higher coupling between parieto-occipital regions and widespread frontal sites in the beta band was found for the false-belief condition selectively. The result of divergence in beta oscillatory activity and in connectivity between false belief and false complementation does not support the redundancy hypothesis.

Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface

PubMed Central

Hovingh, Elise S.; Kuipers, Betsy; Pinelli, Elena; Rooijakkers, Suzan H. M.

2017-01-01

Whooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis. PMID:28742139

Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface.

PubMed

Hovingh, Elise S; van den Broek, Bryan; Kuipers, Betsy; Pinelli, Elena; Rooijakkers, Suzan H M; Jongerius, Ilse

2017-07-01

Whooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis.

Molecular characterization of the alpha subunit of complement component C8 (GcC8α) in the nurse shark (Ginglymostoma cirratum)

PubMed Central

Aybar, Lydia; Shin, Dong-Ho; Smith, Sylvia L.

2009-01-01

Target cell lysis by complement is achieved by the assembly and insertion of the membrane attack complex (MAC) composed of glycoproteins C5b through C9. The lytic activity of shark complement involves functional analogues of mammalian C8 and C9. Mammalian C8 is composed of α, β, and γ subunits. The subunit structure of shark C8 is not known. This report describes a 2341 nucleotide sequence that translates into a polypeptide of 589 amino acid residues, orthologue to mammalian C8α and has the same modular architecture with conserved cysteines forming the peptide bond backbone. The C8γ-binding cysteine is conserved in the perforin-like domain. Hydrophobicity profile indicates the presence of hydrophobic residues essential for membrane insertion. It shares 41.1% and 47.4 % identity with human and Xenopus C8α respectively. Southern blot analysis showed GcC8α exists as a single copy gene expressed in most tissues except the spleen with the liver being the main site of synthesis. Phylogenetic analysis places it in a clade with C8α orthologs and as a sister taxa to the Xenopus. PMID:19524681

Existing branches correlatively inhibit further branching in Trifolium repens: possible mechanisms

PubMed Central

Thomas, R. G.; Hay, M. J. M.

2011-01-01

In Trifolium repens removal of any number of existing branches distal to a nodal root stimulates development of axillary buds further along the stem such that the complement of branches distal to a nodal root remains constant. This study aimed to assess possible mechanisms by which existing branches correlatively inhibit the outgrowth of axillary buds distal to them. Treatments were applied to basal branches to evaluate the roles of three postulated inhibitory mechanisms: (I) the transport of a phloem-mobile inhibitory feedback signal from branches into the main stem; (II) the polar flow of auxin from branches into the main stem acting to limit further branch development; or (III) the basal branches functioning as sinks for a net root-derived stimulatory signal (NRS). Results showed that transport of auxin, or of a non-auxin phloem-mobile signal, from basal branches did not influence regulation of correlative inhibition and were consistent with the possibility that the intra-plant distribution of NRS could be involved in the correlative inhibition of distal buds by basal branches. This study supports existing evidence that regulation of branching in T. repens is dominated by a root-derived stimulatory signal, initially distributed via the xylem, the characterization of which will progress the generic understanding of branching regulation. PMID:21071681

Breaking down the complement system: a review and update on novel therapies.

PubMed

Reddy, Yuvaram N V; Siedlecki, Andrew M; Francis, Jean M

2017-03-01

The complement system represents one of the more primitive forms of innate immunity. It has increasingly been found to contribute to pathologies in the native and transplanted kidney. We provide a concise review of the physiology of the complement cascade, and discuss current and upcoming complement-based therapies. Current agents in clinical use either bind to complement components directly or prevent complement from binding to antibodies affixed to the endothelial surface. These include C1 esterase inhibitors, anti-C5 mAbs, anti-CD20 mAbs, and proteasome inhibitors. Treatment continues to show efficacy in the atypical hemolytic uremic syndrome and antibody-mediated rejection. Promising agents not currently available include CCX168, TP10, AMY-101, factor D inhibitors, coversin, and compstatin. Several new trials are targeting complement inhibition to treat antineutrophilic cystoplasmic antibody (ANCA)-associated vasculitis, C3 glomerulopathy, thrombotic microangiopathy, and IgA nephropathy. New agents for the treatment of the atypical hemolytic uremic syndrome are also in development. Complement-based therapies are being considered for targeted therapy in the atypical hemolytic uremic syndrome and antibody-mediated rejection, C3 glomerulopathy, and ANCA-associated vasculitis. A few agents are currently in use as orphan drugs. A number of other drugs are in clinical trials and, overall, are showing promising preliminary results.

Mutations participating in interallelic complementation in propionic acidemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gravel, R.A.; Akerman, B.R.; Lamhonwah, A.M.

1994-07-01

Deficiency of propionyl-CoA carboxylase (PCC; [alpha][sub 4][beta][sub 4]) results in the rare, autosomal recessive disease propionic acidemia. Cell fusion experiments have revealed two complementation groups, pccA and pccB, corresponding to defects of the PCCA ([alpha]-subunit) and PCCB ([beta]-subunit) genes, respectively. The pccBCC group includes subgroups, pccB and pccC, which are thought to reflect interallelic complementation between certain mutations of the PCCB gene. In this study, the authors have identified the mutations in two pccB, one pccC, and two pccBC cell lines and have deduced those alleles participating in interallelic complementation. One pccB line was a compound hetrozygote of Pro228Leu andmore » Asn536Asp. The latter mutation was also detected in a noncomplementing pccBC line. This leaves Pro228Leu responsible for complementation in the pccB cells. The second pccB line contained an insertional duplication, dupKICK140-143, and a splice mutation IVS+1 G[yields]T, located after Lys466. The authors suggest that the dupKICK mutation is the complementing allele, since the second allele is incompatible with normal splicing. The pccC line studied was homozygous for Arg410Trp, which is necessarily the complementing allele in that line. For a second pccC line, they previously had proposed that [Delta]Ile408 was the complementing allele. They now show that its second allele, [open quotes]Ins[center dot]Del[close quotes], a 14-bp deletion replaced by a 12-bp insertion beginning at codon 407, fails to complement in homozygous form. The authors conclude that the interallelic complementation results from mutations in domains that can interact between [beta]-subunits in the PCC heteromer to restore enzymatic function. On the basis of sequence homology with the Propionibacterium shermanii transcarboxylase 12S subunit, they suggest that the pccC domain, defined by Ile408 and Arg410, may involve the propionyl-CoA binding site. 37 refs., 5 figs., 2 tabs.« less

Complement deficiency predisposes for meningitis due to nongroupable meningococci and Neisseria-related bacteria.

PubMed

Fijen, C A; Kuijper, E J; Tjia, H G; Daha, M R; Dankert, J

1994-05-01

Nongroupable meningococci or bacteria related to the genus Neisseria rarely cause meningitis. Complement deficiency has been identified as a major predisposing factor for meningococcal disease. To assess whether patients with meningitis due to such strains have a complement deficiency, we studied 12 persons. Six patients had meningitis due to nongroupable strains of meningococci, and six patients had meningitis due to Moraxella species or Acinetobacter species. Inherited complement component C7 or C8 deficiency was found in two persons who had had meningitis due to nongroupable meningococci, and one C8-deficient person had had meningitis caused by Moraxella osloensis. Hypocomplementemia resulting from CSF drain-associated shunt nephritis was found in one person with meningitis due to Moraxella nonliquefaciens and in one person with meningitis due to Acinetobacter lwoffi. This rather high frequency of inherited or acquired complement deficiencies among patients with meningitis due to nongroupable meningococci, Moraxella species, and Acinetobacter species justifies the recommendation that such patients must be studied for complement deficiency.

A web-based rapid prototyping and clinical conversational system that complements electronic patient record system.

PubMed

Kim, J H; Ferziger, R; Kawaloff, H B; Sands, D Z; Safran, C; Slack, W V

2001-01-01

Even the most extensive hospital information system cannot support all the complex and ever-changing demands associated with a clinical database, such as providing department or personal data forms, and rating scales. Well-designed clinical dialogue programs may facilitate direct interaction of patients with their medical records. Incorporation of extensive and loosely structured clinical data into an existing medical record system is an essential step towards a comprehensive clinical information system, and can best be achieved when the practitioner and the patient directly enter the contents. We have developed a rapid prototyping and clinical conversational system that complements the electronic medical record system, with its generic data structure and standard communication interfaces based on Web technology. We believe our approach can enhance collaboration between consumer-oriented and provider-oriented information systems.

Free iterative-complement-interaction calculations of the hydrogen molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurokawa, Yusaku; Nakashima, Hiroyuki; Nakatsuji, Hiroshi

2005-12-15

The free iterative-complement-interaction (ICI) method based on the scaled Schroedinger equation proposed previously has been applied to the calculations of very accurate wave functions of the hydrogen molecule in an analytical expansion form. All the variables were determined with the variational principle by calculating the necessary integrals analytically. The initial wave function and the scaling function were changes to see the effects on the convergence speed of the ICI calculations. The free ICI wave functions that were generated automatically were different from the existing wave functions, and this difference was shown to be physically important. The best wave function reportedmore » in this paper seems to be the best worldwide in the literature from the variational point of view. The quality of the wave function was examined by calculating the nuclear and electron cusps.« less

Masturbation and Partnered Sex: Substitutes or Complements?

PubMed

Regnerus, Mark; Price, Joseph; Gordon, David

2017-10-01

Drawing upon a large, recent probability sample of American adults ages 18-60 (7648 men and 8090 women), we explored the association between sexual frequency and masturbation, evaluating the evidence for whether masturbation compensates for unavailable sex, complements (or augments) existing paired sexual activity, or bears little association with it. We found evidence supporting a compensatory relationship between masturbation and sexual frequency for men, and a complementary one among women, but each association was both modest and contingent on how content participants were with their self-reported frequency of sex. Among men and women, both partnered status and their sexual contentment were more obvious predictors of masturbation than was recent frequency of sex. We conclude that both hypotheses as commonly evaluated suffer from failing to account for the pivotal role of subjective sexual contentment in predicting masturbation.

Development of a flexible higher education curriculum framework for geographic information science

NASA Astrophysics Data System (ADS)

Veenendaal, B.

2014-04-01

A wide range of geographic information science (GIScience) educational programs currently exist, the oldest now over 25 years. Offerings vary from those specifically focussed on geographic information science, to those that utilise geographic information systems in various applications and disciplines. Over the past two decades, there have been a number of initiatives to design curricula for GIScience, including the NCGIA Core Curriculum, GIS&T Body of Knowledge and the Geospatial Technology Competency Model developments. The rapid developments in geospatial technology, applications and organisations means that curricula need to constantly be updated and developed to maintain currency and relevance. This paper reviews the curriculum initiatives and outlines a new and flexible GIScience higher education curriculum framework which complements and utilises existing curricula. This new framework was applied to the GIScience programs at Curtin University in Perth, Australia which has surpassed 25 years of GIScience education. Some of the results of applying this framework are outlined and discussed.

On α‧ precipitate composition in thermally annealed and neutron-irradiated Fe- 9-18Cr alloys

NASA Astrophysics Data System (ADS)

Reese, Elaina R.; Bachhav, Mukesh; Wells, Peter; Yamamoto, Takuya; Robert Odette, G.; Marquis, Emmanuelle A.

2018-03-01

Ferritic-martensitic steels are leading candidates for many nuclear energy applications. However, formation of nanoscale α‧ precipitates during thermal aging at temperatures above 450 °C, or during neutron irradiation at lower temperatures, makes these Fe-Cr steels susceptible to embrittlement. To complement the existing literature, a series of Fe-9 to 18 Cr alloys were neutron-irradiated at temperatures between 320 and 455 °C up to doses of 20 dpa. In addition, post-irradiation annealing treatments at 500 and 600 °C were performed on a neutron-irradiated Fe-18 Cr alloy to validate the α-α‧ phase boundary. The microstructures were characterized using atom probe tomography and the results were analyzed in light of the existing literature. Under neutron irradiation and thermal annealing, the measured α‧ concentrations ranged from ∼81 to 96 at.% Cr, as influenced by temperature, precipitate size, technique artifacts, and, possibly, cascade ballistic mixing.

Cardiac Rehabilitation Online Pilot: Extending Reach of Cardiac Rehabilitation.

PubMed

Higgins, Rosemary O; Rogerson, Michelle; Murphy, Barbara M; Navaratnam, Hema; Butler, Michael V; Barker, Lauren; Turner, Alyna; Lefkovits, Jeffrey; Jackson, Alun C

While cardiac rehabilitation (CR) is recommended for all patients after an acute cardiac event, limitations exist in reach. The purpose of the current study was to develop and pilot a flexible online CR program based on self-management principles "Help Yourself Online." The program was designed as an alternative to group-based CR as well as to complement traditional CR. The program was based on existing self-management resources developed previously by the Heart Research Centre. Twenty-one patients admitted to Cabrini Health for an acute cardiac event were recruited to test the program. The program was evaluated using qualitative and quantitative methods. Quantitative results demonstrated that patients believed the program would assist them in their self-management. Qualitative evaluation, using focus group and interview methods with 15 patients, showed that patients perceived the online CR approach to be a useful instrument for self-management. Broader implications of the data include the acceptability of the intervention, timing of intervention delivery, and patients' desire for additional online community support.

Generalized Hill-stability criteria for hierarchical three-body systems at arbitrary inclinations

NASA Astrophysics Data System (ADS)

Grishin, Evgeni; Perets, Hagai B.; Zenati, Yossef; Michaely, Erez

2017-04-01

A fundamental aspect of the three-body problem is its stability. Most stability studies have focused on the co-planar three-body problem, deriving analytic criteria for the dynamical stability of such pro/retrograde systems. Numerical studies of inclined systems phenomenologically mapped their stability regions, but neither complement it by theoretical framework, nor provided satisfactory fit for their dependence on mutual inclinations. Here we present a novel approach to study the stability of hierarchical three-body systems at arbitrary inclinations, which accounts not only for the instantaneous stability of such systems, but also for the secular stability and evolution through Lidov-Kozai cycles and evection. We generalize the Hill-stability criteria to arbitrarily inclined triple systems, explain the existence of quasi-stable regimes and characterize the inclination dependence of their stability. We complement the analytic treatment with an extensive numerical study, to test our analytic results. We find excellent correspondence up to high inclinations (˜120°), beyond which the agreement is marginal. At such high inclinations, the stability radius is larger, the ratio between the outer and inner periods becomes comparable and our secular averaging approach is no longer strictly valid. We therefore combine our analytic results with polynomial fits to the numerical results to obtain a generalized stability formula for triple systems at arbitrary inclinations. Besides providing a generalized secular-based physical explanation for the stability of non-co-planar systems, our results have direct implications for any triple systems and, in particular, binary planets and moon/satellite systems; we briefly discuss the latter as a test case for our models.

Optical 1's and 2's complement devices using lithium-niobate-based waveguide

NASA Astrophysics Data System (ADS)

Pal, Amrindra; Kumar, Santosh; Sharma, Sandeep

2016-12-01

Optical 1's and 2's complement devices are proposed with the help of lithium-niobate-based Mach-Zehnder interferometers. It has a powerful capability of switching an optical signal from one port to the other port with the help of an electrical control signal. The paper includes the optical conversion scheme using sets of optical switches. 2's complement is common in computer systems and is used in binary subtraction and logical manipulation. The operation of the circuits is studied theoretically and analyzed through numerical simulations. The truth table of these complement methods is verified with the beam propagation method and MATLAB® simulation results.

Glioma-derived mutations in isocitrate dehydrogenase 2 beneficial to traditional chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Yuejun, E-mail: yjfu@sxu.edu.cn; Huang, Rui; Zheng, Yali

2011-07-01

Highlights: {yields} IDH1 and IDH2 mutations are not detected in the rat C6 glioma cell line model. {yields} IDH2 mutations are not required for the tumorigenesis of glioma. {yields} IDH2{sup R172G} can sensitize glioma sensitivity to chemotherapy through NADPH levels. {yields} IDH2{sup R172G} can give a benefit to traditional chemotherapy of glioma. {yields} This finding serves as an important complement to existing research on this topic. -- Abstract: Heterozygous mutations in either the R132 residue of isocitrate dehydrogenase I (IDH1) or the R172 residue of IDH2 in human gliomas were recently highlighted. In the present study, we report that mutationsmore » of IDH1 and IDH2 are not detected in the rat C6 glioma cell line model, which suggests that these mutations are not required for the development of glioblastoma induced by N,N'-nitroso-methylurea. The effects of IDH2 and IDH2{sup R172G} on C6 cells proliferation and sensitivity to chemotherapy and the possible mechanism are analyzed at the cellular level. IDH1 and IDH2 mutations lead to simultaneous loss and gain of activities in the production of {alpha}-ketoglutarate ({alpha}-KG) and 2-hydroxyglutarate (2HG), respectively, and result in lowering NADPH levels even further. The low NADPH levels can sensitize tumors to chemotherapy, and account for the prolonged survival of patients harboring the mutations. Our data extrapolate potential importance of the in vitro rat C6 glioma cell model, show that the IDH2{sup R172G} mutation in gliomas may give a benefit to traditional chemotherapy of this cancer and serve as an important complement to existing research on this topic.« less

A reversible Renilla luciferase protein complementation assay for rapid identification of protein–protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus

PubMed Central

Lund, Christian H.; Bromley, Jennifer R.; Stenbæk, Anne; Rasmussen, Randi E.; Scheller, Henrik V.; Sakuragi, Yumiko

2015-01-01

A growing body of evidence suggests that protein–protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. We tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. Our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta. PMID:25326916

A novel L-ficolin/mannose-binding lectin chimeric molecule with enhanced activity against Ebola virus.

PubMed

Michelow, Ian C; Dong, Mingdong; Mungall, Bruce A; Yantosca, L Michael; Lear, Calli; Ji, Xin; Karpel, Marshall; Rootes, Christina L; Brudner, Matthew; Houen, Gunnar; Eisen, Damon P; Kinane, T Bernard; Takahashi, Kazue; Stahl, Gregory L; Olinger, Gene G; Spear, Gregory T; Ezekowitz, R Alan B; Schmidt, Emmett V

2010-08-06

Ebola viruses constitute a newly emerging public threat because they cause rapidly fatal hemorrhagic fevers for which no treatment exists, and they can be manipulated as bioweapons. We targeted conserved N-glycosylated carbohydrate ligands on viral envelope surfaces using novel immune therapies. Mannose-binding lectin (MBL) and L-ficolin (L-FCN) were selected because they function as opsonins and activate complement. Given that MBL has a complex quaternary structure unsuitable for large scale cost-effective production, we sought to develop a less complex chimeric fusion protein with similar ligand recognition and enhanced effector functions. We tested recombinant human MBL and three L-FCN/MBL variants that contained the MBL carbohydrate recognition domain and varying lengths of the L-FCN collagenous domain. Non-reduced chimeric proteins formed predominantly nona- and dodecameric oligomers, whereas recombinant human MBL formed octadecameric and larger oligomers. Surface plasmon resonance revealed that L-FCN/MBL76 had the highest binding affinities for N-acetylglucosamine-bovine serum albumin and mannan. The same chimeric protein displayed superior complement C4 cleavage and binding to calreticulin (cC1qR), a putative receptor for MBL. L-FCN/MBL76 reduced infection by wild type Ebola virus Zaire significantly greater than the other molecules. Tapping mode atomic force microscopy revealed that L-FCN/MBL76 was significantly less tall than the other molecules despite similar polypeptide lengths. We propose that alterations in the quaternary structure of L-FCN/MBL76 resulted in greater flexibility in the collagenous or neck region. Similarly, a more pliable molecule might enhance cooperativity between the carbohydrate recognition domains and their cognate ligands, complement activation, and calreticulin binding dynamics. L-FCN/MBL chimeric proteins should be considered as potential novel therapeutics.

The innate immune repertoire in Cnidaria - ancestral complexity and stochastic gene loss

PubMed Central

Miller, David J; Hemmrich, Georg; Ball, Eldon E; Hayward, David C; Khalturin, Konstantin; Funayama, Noriko; Agata, Kiyokazu; Bosch, Thomas CG

2007-01-01

Background Characterization of the innate immune repertoire of extant cnidarians is of both fundamental and applied interest - it not only provides insights into the basic immunological 'tool kit' of the common ancestor of all animals, but is also likely to be important in understanding the global decline of coral reefs that is presently occurring. Recently, whole genome sequences became available for two cnidarians, Hydra magnipapillata and Nematostella vectensis, and large expressed sequence tag (EST) datasets are available for these and for the coral Acropora millepora. Results To better understand the basis of innate immunity in cnidarians, we scanned the available EST and genomic resources for some of the key components of the vertebrate innate immune repertoire, focusing on the Toll/Toll-like receptor (TLR) and complement pathways. A canonical Toll/TLR pathway is present in representatives of the basal cnidarian class Anthozoa, but neither a classic Toll/TLR receptor nor a conventional nuclear factor (NF)-κB could be identified in the anthozoan Hydra. Moreover, the detection of complement C3 and several membrane attack complex/perforin domain (MAC/PF) proteins suggests that a prototypic complement effector pathway may exist in anthozoans, but not in hydrozoans. Together with data for several other gene families, this implies that Hydra may have undergone substantial secondary gene loss during evolution. Such losses are not confined to Hydra, however, and at least one MAC/PF gene appears to have been lost from Nematostella. Conclusion Consideration of these patterns of gene distribution underscores the likely significance of gene loss during animal evolution whilst indicating ancient origins for many components of the vertebrate innate immune system. PMID:17437634

A reversible Renilla luciferase protein complementation assay for rapid identification of protein-protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus

DOE PAGES

Lund, C. H.; Bromley, J. R.; Stenbaek, A.; ...

2014-10-18

A growing body of evidence suggests that protein–protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. Wemore » tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. In conclusion, our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta.« less

An ultra-high-density map as a community resource for discerning the genetic basis of quantitative traits in maize

USDA-ARS?s Scientific Manuscript database

In this study, we generated a linkage map containing 1,151,856 high quality SNPs between Mo17 and B73, which were verified in the maize intermated B73'×'Mo17 (IBM) Syn10 population. This resource is an excellent complement to existing maize genetic maps available in an online database (iPlant, http:...

A History of Women in the Trades for Integration with the Gender Equity in Education and the Workplace Curriculum.

ERIC Educational Resources Information Center

Grey, Morgan, Comp.

This document, which was originally intended to complement a curriculum titled "Gender Equity in Education and the Workplace," is a compilation of the historical contributions made by women in trade and technical careers that may be used as a source of materials suitable for integration into existing trade and industrial education programs.…

Addressing the Uncertain Future of Preserving the Past: Towards a Robust Strategy for Digital Archiving and Preservation. Technical Report. Executive Summary

ERIC Educational Resources Information Center

Hoorens, Stijn; Rothenberg, Jeff; van Oranje-Nassau, Constantijn; van der Mandele, Martin; Levitt, Ruth

2007-01-01

Storing and curating authentic academic literature and making it accessible for the long term has been a time-honoured task of national libraries. By guarding existing knowledge and facilitating its use to produce new insights, national and university libraries have formed an integral part of the research environment, complementing the roles of…

Complementing or Conflicting Human Rights Conventions? Realising an Inclusive Approach to Families with a Young Person with a Disability and Challenging Behaviour

ERIC Educational Resources Information Center

Muir, Kristy; Goldblatt, Beth

2011-01-01

United Nation's conventions exist to help facilitate and protect vulnerable people's human rights: including people with disabilities (Convention on the Rights of Persons with Disabilities, 2006) and children (Convention on the Rights of the Child, 1989). However, for some families where a family member has a disability, there may be inherent…

Flow Chemistry on Multigram Scale: Continuous Synthesis of Boronic Acids within 1 s.

PubMed

Hafner, Andreas; Meisenbach, Mark; Sedelmeier, Joerg

2016-08-05

The benefits and limitations of a simple continuous flow setup for handling and performing of organolithium chemistry on the multigram scale is described. The developed metalation platform embodies a valuable complement to existing methodologies, as it combines the benefits of Flash Chemistry (chemical synthesis on a time scale of <1 s) with remarkable throughput (g/min) while mitigating the risk of blockages.

Complement in Action: An Analysis of Patent Trends from 1976 Through 2011.

PubMed

Yang, Kun; Deangelis, Robert A; Reed, Janet E; Ricklin, Daniel; Lambris, John D

2013-01-01

Complement is an essential part of the innate immune response. It interacts with diverse endogenous pathways and contributes to the maintenance of homeostasis, the modulation of adaptive immune responses, and the development of various pathologies. The potential usefulness, in both research and clinical settings, of compounds that detect or modulate complement activity has resulted in thousands of publications on complement-related innovations in fields such as drug discovery, disease diagnosis and treatment, and immunoassays, among others. This study highlights the distribution and publication trends of patents related to the complement system that were granted by the United States Patent and Trademark Office from 1976 to the present day. A comparison to complement-related documents published by the World Intellectual Property Organization is also included. Statistical analyses revealed increasing diversity in complement-related research interests over time. More than half of the patents were found to focus on the discovery of inhibitors; interest in various inhibitor classes exhibited a remarkable transformation from chemical compounds early on to proteins and antibodies in more recent years. Among clinical applications, complement proteins and their modulators have been extensively patented for the diagnosis and treatment of eye diseases (especially age-related macular degeneration), graft rejection, cancer, sepsis, and a variety of other inflammatory and immune diseases. All of the patents discussed in this chapter, as well as those from other databases, are available from our newly constructed complement patent database: www.innateimmunity.us/patent .

Complement in action: an analysis of patent trends from 1976 through 2011.

PubMed

Yang, Kun; DeAngelis, Robert A; Reed, Janet E; Ricklin, Daniel; Lambris, John D

2013-01-01

Complement is an essential part of the innate immune response. It interacts with diverse endogenous pathways and contributes to the maintenance of homeostasis, the modulation of adaptive immune responses, and the development of various pathologies. The potential usefulness, in both research and clinical settings, of compounds that detect or modulate complement activity has resulted in thousands of publications on complement-related innovations in fields such as drug discovery, disease diagnosis and treatment, and immunoassays, among others. This study highlights the distribution and publication trends of patents related to the complement system that were granted by the United States Patent and Trademark Office from 1976 to the present day. A comparison to complement-related documents published by the World Intellectual Property Organization is also included. Statistical analyses revealed increasing diversity in complement-related research interests over time. More than half of the patents were found to focus on the discovery of inhibitors; interest in various inhibitor classes exhibited a remarkable transformation from chemical compounds early on to proteins and antibodies in more recent years. Among clinical applications, complement proteins and their modulators have been extensively patented for the diagnosis and treatment of eye diseases (especially age-related macular degeneration), graft rejection, cancer, sepsis, and a variety of other inflammatory and immune diseases. All of the patents discussed in this chapter, as well as those from other databases, are available from our newly constructed complement patent database: www.innateimmunity.us/patent.

Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway.

PubMed

Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter

2017-01-01

The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination.

Solvability of some partial functional integrodifferential equations with finite delay and optimal controls in Banach spaces.

PubMed

Ezzinbi, Khalil; Ndambomve, Patrice

2016-01-01

In this work, we consider the control system governed by some partial functional integrodifferential equations with finite delay in Banach spaces. We assume that the undelayed part admits a resolvent operator in the sense of Grimmer. Firstly, some suitable conditions are established to guarantee the existence and uniqueness of mild solutions for a broad class of partial functional integrodifferential infinite dimensional control systems. Secondly, it is proved that, under generally mild conditions of cost functional, the associated Lagrange problem has an optimal solution, and that for each optimal solution there is a minimizing sequence of the problem that converges to the optimal solution with respect to the trajectory, the control, and the functional in appropriate topologies. Our results extend and complement many other important results in the literature. Finally, a concrete example of application is given to illustrate the effectiveness of our main results.

Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox.

PubMed

Johnson, Reed F; Yellayi, Srikanth; Cann, Jennifer A; Johnson, Anthony; Smith, Alvin L; Paragas, Jason; Jahrling, Peter B; Blaney, Joseph E

2011-09-30

Hemorrhagic smallpox was a rare but severe manifestation of variola virus infection that resulted in nearly 100% mortality. Here we describe intravenous (IV) inoculation of cowpox virus Brighton Red strain in cynomolgus macaques (Macaca fascicularis) which resulted in disease similar in presentation to hemorrhagic smallpox in humans. IV inoculation of macaques resulted in a uniformly lethal disease within 12 days post-inoculation in two independent experiments. Clinical observations and hematological and histopathological findings support hemorrhagic disease. Cowpox virus replicated to high levels in blood (8.0-9.0 log(10) gene copies/mL) and tissues including lymph nodes, thymus, spleen, bone marrow, and lungs. This unique model of hemorrhagic orthopoxvirus infection provides an accessible means to further study orthopoxvirus pathogenesis and to identify virus-specific and nonspecific therapies. Such studies will serve to complement the existing nonhuman primate models of more classical poxviral disease. Published by Elsevier Inc.

Preparation of Low Molecular Weight Chondroitin Sulfates, Screening of a High Anti-Complement Capacity of Low Molecular Weight Chondroitin Sulfate and Its Biological Activity Studies in Attenuating Osteoarthritis

PubMed Central

Li, Lian; Li, Yan; Feng, Danyang; Xu, Linghua; Yin, Fengxin; Zang, Hengchang; Liu, Chunhui; Wang, Fengshan

2016-01-01

Chondroitin sulfate (CS) plays important roles in the complement system. However, the CS structure is complicated due to different sources and the number and positions of sulfate groups. The objective of this study was to prepare different low molecular weight chondroitin sulfates (LMWCSs) and to investigate the biological activity in anti-complement capacity. A series of LMWCSs was prepared from different sources and characterized by ultraviolet-visible (UV) spectroscopy, high-performance liquid chromatography (HPLC), size exclusion chromatography-multiangle laser light scattering (SEC-MALLS) and nuclear magnetic resonance (NMR) spectroscopy. Hemolytic, anti-complement 3 deposition capacity and cell viability assays were carried out to investigate the biological activities in vitro. The results showed that LMWCS prepared from shark cartilage with the oxidative degradation method (LMWCS-S-O) had the best anti-complement capacity. LMWCS-S-O could inhibit the alternative pathway of the complement system and protect chondrocytes from cell death. The attenuating effect of LMWCS-S-O on Osteoarthritis (OA) was investigated by destabilization of the medial meniscus (DMM) model in vivo. Functional wind-up, histological and C5b-9 analyses were used to evaluate the treatment effect on the OA model. In vivo results showed that LMWCS-S-O could attenuate OA. LMWCS-S-O with a high content of ΔDi-2,6diS and ΔDi-6S could be used for attenuating OA through regulating the complement system. PMID:27727159

Ultimate dynamics of the Kirschner-Panetta model: Tumor eradication and related problems

NASA Astrophysics Data System (ADS)

Starkov, Konstantin E.; Krishchenko, Alexander P.

2017-10-01

In this paper we consider the ultimate dynamics of the Kirschner-Panetta model which was created for studying the immune response to tumors under special types of immunotherapy. New ultimate upper bounds for compact invariant sets of this model are given, as well as sufficient conditions for the existence of a positively invariant polytope. We establish three types of conditions for the nonexistence of compact invariant sets in the domain of the tumor-cell population. Our main results are two types of conditions for global tumor elimination depending on the ratio between the proliferation rate of the immune cells and their mortality rate. These conditions are described in terms of simple algebraic inequalities imposed on model parameters and treatment parameters. Our theoretical studies of ultimate dynamics are complemented by numerical simulation results.

Identification of C3b-Binding Small-Molecule Complement Inhibitors Using Cheminformatics.

PubMed

Garcia, Brandon L; Skaff, D Andrew; Chatterjee, Arindam; Hanning, Anders; Walker, John K; Wyckoff, Gerald J; Geisbrecht, Brian V

2017-05-01

The complement system is an elegantly regulated biochemical cascade formed by the collective molecular recognition properties and proteolytic activities of more than two dozen membrane-bound or serum proteins. Complement plays diverse roles in human physiology, such as acting as a sentry against invading microorganisms, priming of the adaptive immune response, and removal of immune complexes. However, dysregulation of complement can serve as a trigger for a wide range of human diseases, which include autoimmune, inflammatory, and degenerative conditions. Despite several potential advantages of modulating complement with small-molecule inhibitors, small-molecule drugs are highly underrepresented in the current complement-directed therapeutics pipeline. In this study, we have employed a cheminformatics drug discovery approach based on the extensive structural and functional knowledge available for the central proteolytic fragment of the cascade, C3b. Using parallel in silico screening methodologies, we identified 45 small molecules that putatively bind C3b near ligand-guided functional hot spots. Surface plasmon resonance experiments resulted in the validation of seven dose-dependent C3b-binding compounds. Competition-based biochemical assays demonstrated the ability of several C3b-binding compounds to interfere with binding of the original C3b ligand that guided their discovery. In vitro assays of complement function identified a single complement inhibitory compound, termed cmp-5, and mechanistic studies of the cmp-5 inhibitory mode revealed it acts at the level of C5 activation. This study has led to the identification of a promising new class of C3b-binding small-molecule complement inhibitors and, to our knowledge, provides the first demonstration of cheminformatics-based, complement-directed drug discovery. Copyright © 2017 by The American Association of Immunologists, Inc.

Identification of C3b-binding Small Molecule Complement Inhibitors Using Cheminformatics

PubMed Central

Garcia, Brandon L.; Skaff, D. Andrew; Chatterjee, Arindam; Hanning, Anders; Walker, John K.; Wyckoff, Gerald J.; Geisbrecht, Brian V.

2017-01-01

The complement system is an elegantly regulated biochemical cascade formed by the collective molecular recognition properties and proteolytic activities of over two dozen membrane-bound or serum proteins. Complement plays diverse roles in human physiology which include acting as a sentry against invading microorganisms, priming of the adaptive immune response, and removal of immune complexes. However, dysregulation of complement can serve as a trigger for a wide range of human diseases which include autoimmune, inflammatory, and degenerative conditions. Despite several potential advantages of modulating complement with small molecule inhibitors, small molecule drugs are highly underrepresented in the current complement-directed therapeutics pipeline. In this study we have employed a cheminformatics drug discovery approach based on the extensive structural and functional knowledge available for the central proteolytic fragment of the cascade, C3b. Using parallel in silico screening methodologies we identified 45 small molecules which putatively bind C3b near ligand-guided functional hot-spots. Surface plasmon resonance experiments resulted in the validation of seven dose-dependent C3b-binding compounds. Competition-based biochemical assays demonstrated the ability of several C3b-binding compounds to interfere with binding of the original C3b ligand which guided their discovery. In vitro assays of complement function identified a single complement inhibitory compound, termed cmp-5, and mechanistic studies of the cmp-5 inhibitory mode revealed it acts at the level of C5 activation. This study has led to the identification of a promising new class of C3b-binding small molecule complement inhibitors, and to our knowledge, provides the first demonstration of cheminformatics-based complement-directed drug discovery. PMID:28298523

Dynamics and reproductive effects of complement factors in the spontaneous abortion model of CBA/J×DBA/2 mice.

PubMed

Takeshita, Ai; Kusakabe, Ken Takeshi; Hiyama, Masato; Kuniyoshi, Nobue; Kondo, Tomohiro; Kano, Kiyoshi; Kiso, Yasuo; Okada, Toshiya

2014-05-01

The complement system is one component of innate immunity that could participate in fetal loss. We have already reported that adipsin, a complement activator in the alternative pathway, is stably expressed in the placenta and that an increase in this expression is related to spontaneous abortion. However, complement inhibitor Crry was concurrently expressed in the placenta, and the role of complement factors during pregnancy was not clear. In the present study, we examined the endogenous regulation of complement factors in placenta and serum by using another model mouse for spontaneous abortion and studied the effect of exogenous complement disruption on pregnancy. Compared to control mice, the CBA/J×DBA/2 model mice had higher expression levels of adipsin in the placenta and serum. Adipsin and complement C3 were localized in the metrial gland and labyrinth regions, and both positive reactive ranges were limited in the maternal blood current in normal implantation sites. These results suggest that extrauterine adipsin hematogenously reaches the placenta, activates complement C3, and promotes destruction of the feto-maternal barrier in aborted implantation sites. Crry was consistently expressed in the placenta and serum and reduced in the resorption sites of CBA/J×DBA/2 mice as compared to normal sites. Injection of recombinant adipsin increased the resorption rate and changed the expression of Th-type cytokines toward a Th1 bias. The present study indicates that adipsin could induce the fetal loss that accompanies the Th1 bias and may be a crucial cause of spontaneous abortion. In addition, the local expression of Crry prevents complement activation in placenta in response to a systemic increase of adipsin. Copyright © 2014 Elsevier GmbH. All rights reserved.

Complement Evasion by Pathogenic Leptospira.

PubMed

Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

2016-01-01

Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira . Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira , have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host.

Complement Evasion by Pathogenic Leptospira

PubMed Central

Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

2016-01-01

Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira. Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira, have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host. PMID:28066433

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

PubMed Central

Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

2013-01-01

Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

Milk complement and the opsonophagocytosis and killing of Staphylococcus aureus mastitis isolates by bovine neutrophils.

PubMed

Barrio, Maria Belén; Rainard, Pascal; Poutrel, Bernard

2003-01-01

Phagocytosis of bacteria by bovine polymorphonuclear neutrophils (PMN) has long been regarded as essential for host defense against mastitis infection. Complement-mediated opsonisation by complement component 3 (C3) binding is an important component of the innate immune system. We investigated the role of milk complement as an opsonin and its involvement in the phagocytosis and killing of Staphylococcus aureus isolates from cases of bovine mastitis by bovine blood PMN. We show that deposition of milk C3 component occurred on six different isolates of S. aureus and that the alternative pathway was the sole complement pathway operating in milk of uninflamed mammary gland. This deposition was shown to occur at the same location as the capsule, but not on capsular antigen. Milk complement enhanced the chemiluminescence response of PMN induced by S. aureus. Nevertheless, the association of S. aureus to cells and the overall killing of bacteria by bovine PMN were not affected by the presence of milk complement. Therefore, as all milk samples contained antibodies to capsular polysaccharide type 5 and to other surface antigens, it is likely that milk antibodies were responsible for these two phagocytic events. Results of this study suggest that the deposition of milk complement components on the surface of S. aureus does not contribute to the defence of the mammary gland against S. aureus.

Sensitivity of health sector indicators' response to climate change in Ghana.

PubMed

Dovie, Delali B K; Dzodzomenyo, Mawuli; Ogunseitan, Oladele A

2017-01-01

There is accumulating evidence that the emerging burden of global climate change threatens the fidelity of routine indicators for disease detection and management of risks to public health. The threat partially reflects the conservative character of the health sector and the reluctance to adopt new indicators, despite the growing awareness that existing environmental health indicators were developed to respond to risks that may no longer be relevant, and are too simplistic to also act as indicators for newer global-scale risk factors. This study sought to understand the scope of existing health indicators, while aiming to discover new indicators for building resilience against three climate sensitive diseases (cerebro spinal meningitis, malaria and diarrhea). Therefore, new potential indicators derived from human and biophysical origins were developed to complement existing health indicators, thereby creating climate-sensitive battery of robust composite indices of resilience in health planning. Using Ghana's health sector as a case study systematic international literature review, national expert consultation, and focus group outcomes yielded insights into the relevance, sensitivity and impacts of 45 indicators in 11 categories in responding to climate change. In total, 65% of the indicators were sensitive to health impacts of climate change; 24% acted directly; 31% synergistically; and 45% indirectly, with indicator relevance strongly associated with type of health response. Epidemiological indicators (e.g. morbidity) and health demographic indicators (e.g. population structure) require adjustments with external indicators (e.g. biophysical, policy) to be resilient to climate change. Therefore, selective integration of social and ecological indicators with existing public health indicators improves the fidelity of the health sector to adopt more robust planning of interdependent systems to build resilience. The study highlights growing uncertainties in translating research into protective policies when new indicators associated with non-health sources are needed to complement existing health indicators that are expected to respond to climate change. Copyright © 2016 Elsevier B.V. All rights reserved.

Bioluminescent indicators for Ca2+ based on split Renilla luciferase complementation in living cells.

PubMed

Kaihara, Asami; Umezawa, Yoshio; Furukawa, Tetsushi

2008-01-01

Genetically encoded bioluminescent indicators for intracellular Ca2+ are described here with CaM-M13 interaction-induced complementation of split Renilla luciferase. The Ca2+-induced interaction between CaM and M13 leads to complementation of the N- and C-terminal halves of split Renilla luciferase in living cells. This intramolecular interaction results in the spontaneous and simultaneous emission of bioluminescence split Renilla luciferase. This is how intracellular Ca2+ is illuminated with the intramolecular complementation of split Renilla luciferase. The Ca2+-dependent spontaneous and simultaneous emission of bioluminescence promises to reveal Ca2+ dynamics in living cells, and also in vivo using the present indicators.

A Novel fry1 Allele Reveals the Existence of a Mutant Phenotype Unrelated to 5′->3′ Exoribonuclease (XRN) Activities in Arabidopsis thaliana Roots

PubMed Central

Hirsch, Judith; Estavillo, Gonzalo M.; Javot, Hélène; Chiarenza, Serge; Mallory, Allison C.; Maizel, Alexis; Declerck, Marie; Pogson, Barry J.; Vaucheret, Hervé; Crespi, Martin; Desnos, Thierry; Thibaud, Marie-Christine; Nussaume, Laurent; Marin, Elena

2011-01-01

Background Mutations in the FRY1/SAL1 Arabidopsis locus are highly pleiotropic, affecting drought tolerance, leaf shape and root growth. FRY1 encodes a nucleotide phosphatase that in vitro has inositol polyphosphate 1-phosphatase and 3′,(2′),5′-bisphosphate nucleotide phosphatase activities. It is not clear which activity mediates each of the diverse biological functions of FRY1 in planta. Principal Findings A fry1 mutant was identified in a genetic screen for Arabidopsis mutants deregulated in the expression of Pi High affinity Transporter 1;4 (PHT1;4). Histological analysis revealed that, in roots, FRY1 expression was restricted to the stele and meristems. The fry1 mutant displayed an altered root architecture phenotype and an increased drought tolerance. All of the phenotypes analyzed were complemented with the AHL gene encoding a protein that converts 3′-polyadenosine 5′-phosphate (PAP) into AMP and Pi. PAP is known to inhibit exoribonucleases (XRN) in vitro. Accordingly, an xrn triple mutant with mutations in all three XRNs shared the fry1 drought tolerance and root architecture phenotypes. Interestingly these two traits were also complemented by grafting, revealing that drought tolerance was primarily conferred by the rosette and that the root architecture can be complemented by long-distance regulation derived from leaves. By contrast, PHT1 expression was not altered in xrn mutants or in grafting experiments. Thus, PHT1 up-regulation probably resulted from a local depletion of Pi in the fry1 stele. This hypothesis is supported by the identification of other genes modulated by Pi deficiency in the stele, which are found induced in a fry1 background. Conclusions/Significance Our results indicate that the 3′,(2′),5′-bisphosphate nucleotide phosphatase activity of FRY1 is involved in long-distance as well as local regulatory activities in roots. The local up-regulation of PHT1 genes transcription in roots likely results from local depletion of Pi and is independent of the XRNs. PMID:21304819

Complement dysregulation and disease: from genes and proteins to diagnostics and drugs.

PubMed

de Cordoba, Santiago Rodriguez; Tortajada, Agustin; Harris, Claire L; Morgan, B Paul

2012-11-01

During the last decade, numerous studies have associated genetic variations in complement components and regulators with a number of chronic and infectious diseases. The functional characterization of these complement protein variants, in addition to recent structural advances in understanding of the assembly, activation and regulation of the AP C3 convertase, have provided important insights into the pathogenic mechanisms involved in some of these complement related disorders. This knowledge has identified potential targets for complement inhibitory therapies which are demonstrating efficacy and generating considerable expectation in changing the natural history of these diseases. Comprehensive understanding of the genetic and non-genetic risk factors contributing to these disorders will also result in targeting of the right patient groups in a stratified medicine approach through better diagnostics and individually tailored treatments, thereby improving management of patients. Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease.

PubMed

Granoff, Dan M

2009-06-24

Killing of Neisseria meningitidis can result from complement-mediated serum bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers > or =1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers > or =1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease.

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease

PubMed Central

Granoff, Dan M.

2009-01-01

Killing of Neisseria meningitidis can result from complement-mediated bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers ≥1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers ≥1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease. PMID:19477054

An extended set of yeast-based functional assays accurately identifies human disease mutations

PubMed Central

Sun, Song; Yang, Fan; Tan, Guihong; Costanzo, Michael; Oughtred, Rose; Hirschman, Jodi; Theesfeld, Chandra L.; Bansal, Pritpal; Sahni, Nidhi; Yi, Song; Yu, Analyn; Tyagi, Tanya; Tie, Cathy; Hill, David E.; Vidal, Marc; Andrews, Brenda J.; Boone, Charles; Dolinski, Kara; Roth, Frederick P.

2016-01-01

We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease- and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods. PMID:26975778

New indicators proposed to assess tuberculosis control and elimination in Cuba.

PubMed

González, Edilberto R; Armas, Luisa

2012-10-01

Following 48 years of successful operation of the National Tuberculosis Control Program, Cuban health authorities have placed tuberculosis elimination on the agenda. To this end some tuberculosis control processes and their indicators need redesigned and new ones introduced, related to: number and proportion of suspected tuberculosis cases among vulnerable population groups; tuberculosis suspects with sputum microscopy and culture results useful for diagnosis (interpretable); and number of identified contacts of reported tuberculosis cases who were fully investigated. Such new indicators have been validated and successfully implemented in all provinces (2011-12) and are in the approval pipeline for generalized use in the National Tuberculosis Control Program. These indicators complement existing criteria for quality of case detection and support more comprehensive program performance assessment.

An Extended Damage Plasticity Model for Shotcrete: Formulation and Comparison with Other Shotcrete Models

PubMed Central

Neuner, Matthias; Gamnitzer, Peter; Hofstetter, Günter

2017-01-01

The aims of the present paper are (i) to briefly review single-field and multi-field shotcrete models proposed in the literature; (ii) to propose the extension of a damage-plasticity model for concrete to shotcrete; and (iii) to evaluate the capabilities of the proposed extended damage-plasticity model for shotcrete by comparing the predicted response with experimental data for shotcrete and with the response predicted by shotcrete models, available in the literature. The results of the evaluation will be used for recommendations concerning the application and further improvements of the investigated shotcrete models and they will serve as a basis for the design of a new lab test program, complementing the existing ones. PMID:28772445

Cryptohermitian Picture of Scattering Using Quasilocal Metric Operators

NASA Astrophysics Data System (ADS)

Znojil, Miloslav

2009-08-01

One-dimensional unitary scattering controlled by non-Hermitian (typically, PT-symmetric) quantum Hamiltonians H ≠ H† is considered. Treating these operators via Runge-Kutta approximation, our three-Hilbert-space formulation of quantum theory is reviewed as explaining the unitarity of scattering. Our recent paper on bound states [Znojil M., SIGMA 5 (2009), 001, 19 pages, arXiv:0901.0700] is complemented by the text on scattering. An elementary example illustrates the feasibility of the resulting innovative theoretical recipe. A new family of the so called quasilocal inner products in Hilbert space is found to exist. Constructively, these products are all described in terms of certain non-equivalent short-range metric operators Θ ≠ I represented, in Runge-Kutta approximation, by (2R-1)-diagonal matrices.

Modular modelling with Physiome standards

PubMed Central

Nickerson, David P.; Nielsen, Poul M. F.; Hunter, Peter J.

2016-01-01

Key points The complexity of computational models is increasing, supported by research in modelling tools and frameworks. But relatively little thought has gone into design principles for complex models.We propose a set of design principles for complex model construction with the Physiome standard modelling protocol CellML.By following the principles, models are generated that are extensible and are themselves suitable for reuse in larger models of increasing complexity.We illustrate these principles with examples including an architectural prototype linking, for the first time, electrophysiology, thermodynamically compliant metabolism, signal transduction, gene regulation and synthetic biology.The design principles complement other Physiome research projects, facilitating the application of virtual experiment protocols and model analysis techniques to assist the modelling community in creating libraries of composable, characterised and simulatable quantitative descriptions of physiology. Abstract The ability to produce and customise complex computational models has great potential to have a positive impact on human health. As the field develops towards whole‐cell models and linking such models in multi‐scale frameworks to encompass tissue, organ, or organism levels, reuse of previous modelling efforts will become increasingly necessary. Any modelling group wishing to reuse existing computational models as modules for their own work faces many challenges in the context of construction, storage, retrieval, documentation and analysis of such modules. Physiome standards, frameworks and tools seek to address several of these challenges, especially for models expressed in the modular protocol CellML. Aside from providing a general ability to produce modules, there has been relatively little research work on architectural principles of CellML models that will enable reuse at larger scales. To complement and support the existing tools and frameworks, we develop a set of principles to address this consideration. The principles are illustrated with examples that couple electrophysiology, signalling, metabolism, gene regulation and synthetic biology, together forming an architectural prototype for whole‐cell modelling (including human intervention) in CellML. Such models illustrate how testable units of quantitative biophysical simulation can be constructed. Finally, future relationships between modular models so constructed and Physiome frameworks and tools are discussed, with particular reference to how such frameworks and tools can in turn be extended to complement and gain more benefit from the results of applying the principles. PMID:27353233

There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes.

PubMed

Marcinkiewicz, Ashley L; Kraiczy, Peter; Lin, Yi-Pin

2017-01-01

Lyme disease and relapsing fever are caused by various Borrelia species. Lyme disease borreliae , the most common vector-borne pathogens in both the U.S. and Europe, are transmitted by Ixodes ticks and disseminate from the site of tick bites to tissues leading to erythema migrans skin rash, arthritis, carditis, and neuroborreliosis. Relapsing fever borreliae , carried by ticks and lice, trigger reoccurring fever episodes. Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system. The complement system acts as an important innate immune defense mechanism in humans and vertebrates. Upon activation, the cleaved complement components form complexes on the pathogen surface to eventually promote bacteriolysis. The complement system is negatively modulated by a number of functionally diverse regulators to avoid tissue damage. To evade and inhibit the complement system, spirochetes are capable of binding complement components and regulators. Complement inhibition results in bacterial survival in serum (serum resistance) and is thought to promote bloodstream survival, which facilitates spirochete dissemination and disease manifestations. In this review, we discuss current methodologies to elucidate the mechanisms of Borrelia spp. that promote serum resistance and bloodstream survival, as well as novel methods to study factors responsible for bloodstream survival of Lyme disease borreliae that can be applied to relapsing fever borreliae . Understanding the mechanisms these pathogens utilize to evade the complement system will ultimately aid in the development of novel therapeutic strategies and disease prevention to improve human health.

Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

PubMed Central

Khattab, Ayman; Barroso, Marta; Miettinen, Tiera; Meri, Seppo

2015-01-01

Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood. PMID:25679788

Immunity to human cytomegalovirus measured and compared by complement fixation, indirect fluorescent-antibody, indirect hemagglutination, and enzyme-linked immunosorbent assays.

PubMed Central

Brandt, J A; Kettering, J D; Lewis, J E

1984-01-01

The complement fixation test is currently the test employed most frequently to determine the presence of antibody to human cytomegalovirus. Several other techniques have been adapted for this purpose. A comparison of cytomegalovirus antibody titers was made between the complement fixation test, a commercially available enzyme-linked immunosorbent assay, an indirect immunofluorescent technique, and a modified indirect hemagglutination test. Forty-three serum samples were tested for antibodies by each of the above procedures. The enzyme-linked immunosorbent, immunofluorescent, and indirect hemagglutination assays were in close agreement on all samples tested; the titers obtained with these methods were all equal to or greater than the complement fixation titer for 38 of the 41 samples (92.6%). Two samples were anticomplementary in the complement fixation test but gave readable results in the other tests. The complement fixation test was the least sensitive of the procedures examined. The commercial enzyme-linked immunosorbent assay system was the most practical method and offered the highest degree of sensitivity in detecting antibodies to cytomegalovirus. PMID:6321544

Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo

NASA Astrophysics Data System (ADS)

Chen, Fangfang; Wang, Guankui; Griffin, James I.; Brenneman, Barbara; Banda, Nirmal K.; Holers, V. Michael; Backos, Donald S.; Wu, Linping; Moghimi, Seyed Moein; Simberg, Dmitri

2017-05-01

When nanoparticles are intravenously injected into the body, complement proteins deposit on the surface of nanoparticles in a process called opsonization. These proteins prime the particle for removal by immune cells and may contribute toward infusion-related adverse effects such as allergic responses. The ways complement proteins assemble on nanoparticles have remained unclear. Here, we show that dextran-coated superparamagnetic iron oxide core-shell nanoworms incubated in human serum and plasma are rapidly opsonized with the third complement component (C3) via the alternative pathway. Serum and plasma proteins bound to the nanoworms are mostly intercalated into the nanoworm shell. We show that C3 covalently binds to these absorbed proteins rather than the dextran shell and the protein-bound C3 undergoes dynamic exchange in vitro. Surface-bound proteins accelerate the assembly of the complement components of the alternative pathway on the nanoworm surface. When nanoworms pre-coated with human plasma were injected into mice, C3 and other adsorbed proteins undergo rapid loss. Our results provide important insight into dynamics of protein adsorption and complement opsonization of nanomedicines.

"PowerUp"!: A Tool for Calculating Minimum Detectable Effect Sizes and Minimum Required Sample Sizes for Experimental and Quasi-Experimental Design Studies

ERIC Educational Resources Information Center

Dong, Nianbo; Maynard, Rebecca

2013-01-01

This paper and the accompanying tool are intended to complement existing supports for conducting power analysis tools by offering a tool based on the framework of Minimum Detectable Effect Sizes (MDES) formulae that can be used in determining sample size requirements and in estimating minimum detectable effect sizes for a range of individual- and…

SOFIA: A Stratospheric Observatory for Infrared Astronomy

NASA Technical Reports Server (NTRS)

Erickson, E. F.; Davidson, J. A.; Thorley, G.; Caroff, L. J.

1991-01-01

SOFIA is described as it was originally (May 1988) for the Space and Earth Sciences Advisory Committee (SESAC). The format and questions were provided by SESAC as a standard for judging the merit of potential U.S. space science projects. This version deletes Section IIF, which addressed development costs of the SOFIA facility. SOFIA's unique astronomical potential is described and it is shown how it complements and supports existing and planned facilities.

Predicting the Ability of Marine Mammal Populations to Compensate for Behavioral Disturbances

DTIC Science & Technology

2013-09-30

can impact vital rates. Influence of life history strategies Recent work on PCOD has developed some first insights in the differences that exist...IMPACT/APPLICATIONS We will address needs to assess population consequences of acoustic disturbance (PCAD using PCOD framework) and provide a...particularly in data poor conditions. In addition, this work will provide new metrics to complement efforts to implement PCOD in situations where data

The Vanishing Mexicana/o: (Dis)Locating the Native in Ruiz de Burton's "Who Would Have thought It?" and "The Squatter and the Don"

ERIC Educational Resources Information Center

Szeghi, Tereza M.

2011-01-01

This article complements the existing body of Ruiz de Burton scholarship by providing the first sustained examination of her literary representations of American Indians in both "Who Would Have Thought It?" (1872) and "The Squatter and the Don" (1885), and by exploring how these representations serve her broader aims of social and political…

Telemedicine and the sharing economy: the "Uber" for healthcare.

PubMed

Miller, Brian J; Moore, Derek W; Schmidt, Chester W

2016-12-01

Telehealth platforms, which include both competitors and complements to traditional care delivery, will offer many benefits for both consumers and clinicians, and may promote increased specialization and competition in service delivery. Traditional medical services providers face a challenge similar to that faced by traditional taxicabs after Uber entered the marketplace: how to compete with a connection services platform that threatens to disrupt existing, regulated, and licensed service providers.

Federal Plan for Cyber Security and Information Assurance Research and Development

DTIC Science & Technology

2006-04-01

Security Systems 103 varieties of the BB84 scheme have been developed, and other forms of quantum key distribution have been proposed. Rapid progress has led... key . Capability Gaps Existing quantum cryptographic protocols may also have weaknesses. Although BB84 is generally regarded as secure , researchers...complement agency-specific prioritization and R&D planning efforts in cyber security and information assurance. The Plan also describes the key Federal

Identification of C1q as a Binding Protein for Advanced Glycation End Products.

PubMed

Chikazawa, Miho; Shibata, Takahiro; Hatasa, Yukinori; Hirose, Sayumi; Otaki, Natsuki; Nakashima, Fumie; Ito, Mika; Machida, Sachiko; Maruyama, Shoichi; Uchida, Koji

2016-01-26

Advanced glycation end products (AGEs) make up a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with the free amino groups of proteins. The abundance of AGEs in a variety of age-related diseases, including diabetic complications and atherosclerosis, and their pathophysiological effects suggest the existence of innate defense mechanisms. Here we examined the presence of serum proteins that are capable of binding glycated bovine serum albumin (AGEs-BSA), prepared upon incubation of BSA with dehydroascorbate, and identified complement component C1q subcomponent subunit A as a novel AGE-binding protein in human serum. A molecular interaction analysis showed the specific binding of C1q to the AGEs-BSA. In addition, we identified DNA-binding regions of C1q, including a collagen-like domain, as the AGE-binding site and established that the amount of positive charge on the binding site was the determining factor. C1q indeed recognized several other modified proteins, including acylated proteins, suggesting that the binding specificity of C1q might be ascribed, at least in part, to the electronegative potential of the ligand proteins. We also observed that C1q was involved in the AGEs-BSA-activated deposition of complement proteins, C3b and C4b. In addition, the AGEs-BSA mediated the proteolytic cleavage of complement protein 5 to release C5a. These findings provide the first evidence of AGEs as a new ligand recognized by C1q, stimulating the C1q-dependent classical complement pathway.

Dynamic labelling of neural connections in multiple colours by trans-synaptic fluorescence complementation

PubMed Central

Macpherson, Lindsey J.; Zaharieva, Emanuela E.; Kearney, Patrick J.; Alpert, Michael H.; Lin, Tzu-Yang; Turan, Zeynep; Lee, Chi-Hon; Gallio, Marco

2015-01-01

Determining the pattern of activity of individual connections within a neural circuit could provide insights into the computational processes that underlie brain function. Here, we develop new strategies to label active synapses by trans-synaptic fluorescence complementation in Drosophila. First, we demonstrate that a synaptobrevin-GRASP chimera functions as a powerful activity-dependent marker for synapses in vivo. Next, we create cyan and yellow variants, achieving activity-dependent, multi-colour fluorescence reconstitution across synapses (X-RASP). Our system allows for the first time retrospective labelling of synapses (rather than whole neurons) based on their activity, in multiple colours, in the same animal. As individual synapses often act as computational units in the brain, our method will promote the design of experiments that are not possible using existing techniques. Moreover, our strategies are easily adaptable to circuit mapping in any genetic system. PMID:26635273

Human NKCC2 cation–Cl– co-transporter complements lack of Vhc1 transporter in yeast vacuolar membranes.

PubMed

Petrezselyova, Silvia; Dominguez, Angel; Herynkova, Pavla; Macias, Juan F; Sychrova, Hana

2013-10-01

Cation–chloride co-transporters serve to transport Cl– and alkali metal cations. Whereas a large family of these exists in higher eukaryotes, yeasts only possess one cation–chloride co-transporter, Vhc1, localized to the vacuolar membrane. In this study, the human cation–chloride co-transporter NKCC2 complemented the phenotype of VHC1 deletion in Saccharomyces cerevisiae and its activity controlled the growth of salt-sensitive yeast cells in the presence of high KCl, NaCl and LiCl. A S. cerevisiae mutant lacking plasma-membrane alkali–metal cation exporters Nha1 and Ena1-5 and the vacuolar cation–chloride co-transporter Vhc1 is highly sensitive to increased concentrations of alkali–metal cations, and it proved to be a suitable model for characterizing the substrate specificity and transport activity of human wild-type and mutated cation–chloride co-transporters. Copyright © 2013 John Wiley & Sons, Ltd.

Test plan for 32-bit microcomputers for the Water Resources Division; Chapter A, Test plan for acquisition of prototype 32-bit microcomputers

USGS Publications Warehouse

Hutchison, N.E.; Harbaugh, A.W.; Holloway, R.A.; Merk, C.F.

1987-01-01

The Water Resources Division (WRD) of the U.S. Geological Survey is evaluating 32-bit microcomputers to determine how they can complement, and perhaps later replace, the existing network of minicomputers. The WRD is also designing a National Water Information System (NWIS) that will combine and integrate the existing National Water Data Storage and Retrieval System (WATSTORE), National Water Data Exchange (NAWDEX), and components of several other existing systems. The procedures and testing done in a market evaluation of 32-bit microcomputers are documented. The results of the testing are documented in the NWIS Project Office. The market evaluation was done to identify commercially available hardware and software that could be used for implementing early NWIS prototypes to determine the applicability of 32-bit microcomputers for data base and general computing applications. Three microcomputers will be used for these prototype studies. The results of the prototype studies will be used to compile requirements for a Request for Procurement (RFP) for hardware and software to meet the WRD 's needs in the early 1990's. The identification of qualified vendors to provide the prototype hardware and software included reviewing industry literature, and making telephone calls and personal visits to prospective vendors. Those vendors that appeared to meet general requirements were required to run benchmark tests. (Author 's abstract)

Plasma complement and vascular complement deposition in patients with coronary artery disease with and without inflammatory rheumatic diseases

PubMed Central

2017-01-01

Purpose Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. Methods We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. Results IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA). Conclusion The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD biomarker, and represent a target for new therapies. PMID:28362874

Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

PubMed Central

Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter

2017-01-01

The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination. PMID:28553281

Transcriptome profile of a bovine respiratory disease pathogen: Mannheimia haemolytica PHL213

PubMed Central

2012-01-01

Background Computational methods for structural gene annotation have propelled gene discovery but face certain drawbacks with regards to prokaryotic genome annotation. Identification of transcriptional start sites, demarcating overlapping gene boundaries, and identifying regulatory elements such as small RNA are not accurate using these approaches. In this study, we re-visit the structural annotation of Mannheimia haemolytica PHL213, a bovine respiratory disease pathogen. M. haemolytica is one of the causative agents of bovine respiratory disease that results in about $3 billion annual losses to the cattle industry. We used RNA-Seq and analyzed the data using freely-available computational methods and resources. The aim was to identify previously unannotated regions of the genome using RNA-Seq based expression profile to complement the existing annotation of this pathogen. Results Using the Illumina Genome Analyzer, we generated 9,055,826 reads (average length ~76 bp) and aligned them to the reference genome using Bowtie. The transcribed regions were analyzed using SAMTOOLS and custom Perl scripts in conjunction with BLAST searches and available gene annotation information. The single nucleotide resolution map enabled the identification of 14 novel protein coding regions as well as 44 potential novel sRNA. The basal transcription profile revealed that 2,506 of the 2,837 annotated regions were expressed in vitro, at 95.25% coverage, representing all broad functional gene categories in the genome. The expression profile also helped identify 518 potential operon structures involving 1,086 co-expressed pairs. We also identified 11 proteins with mutated/alternate start codons. Conclusions The application of RNA-Seq based transcriptome profiling to structural gene annotation helped correct existing annotation errors and identify potential novel protein coding regions and sRNA. We used computational tools to predict regulatory elements such as promoters and terminators associated with the novel expressed regions for further characterization of these novel functional elements. Our study complements the existing structural annotation of Mannheimia haemolytica PHL213 based on experimental evidence. Given the role of sRNA in virulence gene regulation and stress response, potential novel sRNA described in this study can form the framework for future studies to determine the role of sRNA, if any, in M. haemolytica pathogenesis. PMID:23046475

Eye-Tracking and Corpus-Based Analyses of Syntax-Semantics Interactions in Complement Coercion

PubMed Central

Lowder, Matthew W.; Gordon, Peter C.

2016-01-01

Previous work has shown that the difficulty associated with processing complex semantic expressions is reduced when the critical constituents appear in separate clauses as opposed to when they appear together in the same clause. We investigated this effect further, focusing in particular on complement coercion, in which an event-selecting verb (e.g., began) combines with a complement that represents an entity (e.g., began the memo). Experiment 1 compared reading times for coercion versus control expressions when the critical verb and complement appeared together in a subject-extracted relative clause (SRC) (e.g., The secretary that began/wrote the memo) compared to when they appeared together in a simple sentence. Readers spent more time processing coercion expressions than control expressions, replicating the typical coercion cost. In addition, readers spent less time processing the verb and complement in SRCs than in simple sentences; however, the magnitude of the coercion cost did not depend on sentence structure. In contrast, Experiment 2 showed that the coercion cost was reduced when the complement appeared as the head of an object-extracted relative clause (ORC) (e.g., The memo that the secretary began/wrote) compared to when the constituents appeared together in an SRC. Consistent with the eye-tracking results of Experiment 2, a corpus analysis showed that expressions requiring complement coercion are more frequent when the constituents are separated by the clause boundary of an ORC compared to when they are embedded together within an SRC. The results provide important information about the types of structural configurations that contribute to reduced difficulty with complex semantic expressions, as well as how these processing patterns are reflected in naturally occurring language. PMID:28529960

Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase

PubMed Central

Reglinski, Mark; Calay, Damien; Siggins, Matthew K.; Mason, Justin C.; Botto, Marina; Sriskandan, Shiranee

2017-01-01

The complement cascade is crucial for clearance and control of invading pathogens, and as such is a key target for pathogen mediated host modulation. C3 is the central molecule of the complement cascade, and plays a vital role in opsonization of bacteria and recruitment of neutrophils to the site of infection. Streptococcal species have evolved multiple mechanisms to disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), a C5a inactivating enzyme, is widely conserved. Here we demonstrate for the first time that pyogenic streptococcal species are capable of cleaving C3, and identify C3 and C3a as novel substrates for the streptococcal ScpA, which are functionally inactivated as a result of cleavage 7 amino acids upstream of the natural C3 convertase. Cleavage of C3a by ScpA resulted in disruption of human neutrophil activation, phagocytosis and chemotaxis, while cleavage of C3 generated abnormally-sized C3a and C3b moieties with impaired function, in particular reducing C3 deposition on the bacterial surface. Despite clear effects on human complement, expression of ScpA reduced clearance of group A streptococci in vivo in wildtype and C5 deficient mice, and promoted systemic bacterial dissemination in mice that lacked both C3 and C5, suggesting an additional complement-independent role for ScpA in streptococcal pathogenesis. ScpA was shown to mediate streptococcal adhesion to both human epithelial and endothelial cells, consistent with a role in promoting bacterial invasion within the host. Taken together, these data show that ScpA is a multi-functional virulence factor with both complement-dependent and independent roles in streptococcal pathogenesis. PMID:28806402

Modification of the Microtiter Reading Mirror for Use in the Standardized Micro Complement Fixation Test

PubMed Central

Hui, Gabriel W. K.

1971-01-01

Modification of the Microtiter reading mirror used in the standardized diagnostic complement fixation method permits convenient estimation of the results in per cent hemolysis by direct visual comparison with the hemolytic standards. Images PMID:5564678

Bottom-Up Gazetteers: Learning from the Implicit Semantics of Geotags

NASA Astrophysics Data System (ADS)

Keßler, Carsten; Maué, Patrick; Heuer, Jan Torben; Bartoschek, Thomas

As directories of named places, gazetteers link the names to geographic footprints and place types. Most existing gazetteers are managed strictly top-down: entries can only be added or changed by the responsible toponymic authority. The covered vocabulary is therefore often limited to an administrative view on places, using only official place names. In this paper, we propose a bottom-up approach for gazetteer building based on geotagged photos harvested from the web. We discuss the building blocks of a geotag and how they relate to each other to formally define the notion of a geotag. Based on this formalization, we introduce an extraction process for gazetteer entries that captures the emergent semantics of collections of geotagged photos and provides a group-cognitive perspective on named places. Using an experimental setup based on clustering and filtering algorithms, we demonstrate how to identify place names and assign adequate geographic footprints. The results for three different place names (Soho, Camino de Santiago and Kilimanjaro), representing different geographic feature types, are evaluated and compared to the results obtained from traditional gazetteers. Finally, we sketch how our approach can be combined with other (for example, linguistic) approaches and discuss how such a bottom-up gazetteer can complement existing gazetteers.

Giant cross polarization in a nanoimprinted metamaterial combining a fishnet with its Babinet complement.

PubMed

Dong, Lin; Haslinger, Michael J; Danzberger, Jürgen; Bergmair, Iris; Hingerl, Kurt; Hrelescu, Calin; Klar, Thomas A

2015-07-27

We present a large area (1 cm2) nanoimprinted metamaterial comprising a fishnet structure and its Babinet complement, which shows giant cross polarization. When illuminated with s-polarized light, the reflected beam can be p-polarized up to 96%, depending on the azimuthal orientation of the sample. This experimental result is close to the result of numerical simulations, which predict 98.7% of cross-polarization. It is further shown, that 95-100% cross polarization is only achieved in the case when the fishnet is combined with its Babinet complement. Each structure alone (either an ordinary fishnet or a plane with metallic rectangles only) shows substantially less polarization conversion.

C4B gene influences intestinal microbiota through complement activation in patients with paediatric-onset inflammatory bowel disease.

PubMed

Nissilä, E; Korpela, K; Lokki, A I; Paakkanen, R; Jokiranta, S; de Vos, W M; Lokki, M-L; Kolho, K-L; Meri, S

2017-12-01

Complement C4 genes are linked to paediatric inflammatory bowel disease (PIBD), but the mechanisms have remained unclear. We examined the influence of C4B gene number on intestinal microbiota and in-vitro serum complement activation by intestinal microbes in PIBD patients. Complement C4A and C4B gene numbers were determined by genomic reverse transcription-polymerase chain reaction (RT-PCR) from 64 patients with PIBD (Crohn's disease or ulcerative colitis). The severity of the disease course was determined from faecal calprotectin levels. Intestinal microbiota was assessed using the HITChip microarray. Complement reactivity in patients was analysed by incubating their sera with Yersinia pseudotuberculosis and Akkermansia muciniphila and determining the levels of C3a and soluble terminal complement complex (SC5b-9) using enzyme immunoassays. The microbiota diversity was wider in patients with no C4B genes than in those with one or two C4B genes, irrespective of intestinal inflammation. C4B and total C4 gene numbers correlated positively with soluble terminal complement complex (TCC, SC5b-9) levels when patient serum samples were stimulated with bacteria. Our results suggest that the C4B gene number associates positively with inflammation in patients with PIBD. Multiple copies of the C4B gene may thus aggravate the IBD-associated dysbiosis through escalated complement reactivity towards the microbiota. © 2017 British Society for Immunology.

Complement factor B expression profile in a spontaneous uveitis model.

PubMed

Zipplies, Johanna K; Kirschfink, Michael; Amann, Barbara; Hauck, Stefanie M; Stangassinger, Manfred; Deeg, Cornelia A

2010-12-01

Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status of the complement system, sera were subsequently examined for complement split products. We could demonstrate a significant higher concentration of the activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic condition compared to healthy controls, whereas for C5b-9 no differences were detected. Additionally, we investigated complement activation directly in the retina by immunohistochemistry, since it is the main target organ of this autoimmune disease. Interestingly, infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d as well as CD68, a macrophage marker. In this study, we could demonstrate activation of the complement system both systemically as well as in the eye, the target organ of spontaneous recurrent uveitis. Based on these novel findings, we postulate a novel role for macrophages in connection with complement synthesis at the site of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM.

PubMed

Goetz, Lindsey; Laskowski, Jennifer; Renner, Brandon; Pickering, Matthew C; Kulik, Liudmila; Klawitter, Jelena; Stites, Erik; Christians, Uwe; van der Vlag, Johan; Ravichandran, Kameswaran; Holers, V Michael; Thurman, Joshua M

2018-05-01

Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM-mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild-type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular characterization of the alpha subunit of complement component C8 (GcC8alpha) in the nurse shark (Ginglymostoma cirratum).

PubMed

Aybar, Lydia; Shin, Dong-Ho; Smith, Sylvia L

2009-09-01

Target cell lysis by complement is achieved by the assembly and insertion of the membrane attack complex (MAC) composed of glycoproteins C5b through C9. The lytic activity of shark complement involves functional analogues of mammalian C8 and C9. Mammalian C8 is composed of alpha, beta, and gamma subunits. The subunit structure of shark C8 is not known. This report describes a 2341 nucleotide sequence that translates into a polypeptide of 589 amino acid residues, orthologue to mammalian C8alpha and has the same modular architecture with conserved cysteines forming the peptide bond backbone. The C8gamma-binding cysteine is conserved in the perforin-like domain. Hydrophobicity profile indicates the presence of hydrophobic residues essential for membrane insertion. It shares 41.1% and 47.4% identity with human and Xenopus C8alpha respectively. Southern blot analysis showed GcC8alpha exists as a single copy gene expressed in most tissues except the spleen with the liver being the main site of synthesis. Phylogenetic analysis places it in a clade with C8alpha orthologs and as a sister taxa to the Xenopus. 2009 Elsevier Ltd.

Acute and prolonged complement activation in the central nervous system during herpes simplex encephalitis.

PubMed

Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas

2016-06-15

Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

Micrurus snake venoms activate human complement system and generate anaphylatoxins

PubMed Central

2012-01-01

Background The genus Micrurus, coral snakes (Serpentes, Elapidae), comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s) present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process. PMID:22248157

Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo.

PubMed

Buscema, Marzia; Matviykiv, Sofiya; Mészáros, Tamás; Gerganova, Gabriela; Weinberger, Andreas; Mettal, Ute; Mueller, Dennis; Neuhaus, Frederik; Stalder, Etienne; Ishikawa, Takashi; Urbanics, Rudolf; Saxer, Till; Pfohl, Thomas; Szebeni, János; Zumbuehl, Andreas; Müller, Bert

2017-10-28

Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear-responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC-Pad formulations in human and porcine sera, along with the nanopharmaceutical-mediated cardiopulmonary responses in pigs. The evaluated formulations comprised of Pad-PC-Pad liposomes, with and without polyethylene glycol on the surface of the liposomes, and nitroglycerin as a model vasodilator. The nitroglycerin incorporation efficiency ranged from 25% to 50%. In human sera, liposome formulations with 20mg/mL phospholipid gave rise to complement activation, mainly via the alternative pathway, as reflected by the rises in SC5b-9 and Bb protein complex concentrations. Formulations having a factor of ten lower phospholipid content did not result in measurable complement activation. The weak complement activation induced by Pad-PC-Pad liposomal formulations was confirmed by the results obtained by performing an in vivo study in a porcine model, where hemodynamic parameters were monitored continuously. Our study suggests that, compared to FDA-approved liposomal drugs, Pad-PC-Pad exhibits less or similar risks of CARPA. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization.

PubMed

Ji, Xin; Olinger, Gene G; Aris, Sheena; Chen, Ying; Gewurz, Henry; Spear, Gregory T

2005-09-01

Mannose-binding lectin (MBL), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. In this study, the ability of MBL to bind to virus particles pseudotyped with Ebola and Marburg envelope glycoproteins was evaluated. Virus particles bearing either Ebola (Zaire strain) or Marburg (Musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized MBL compared with virus particles pseudotyped with vesicular stomatitis virus glycoprotein or with no virus glycoprotein. As observed in previous studies, Ebola-pseudotyped virus bound to cells expressing the lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin). However, pre-incubation of virus with MBL blocked DC-SIGN-mediated binding to cells, suggesting that the two lectins bind at the same or overlapping sites on the Ebola glycoprotein. Neutralization experiments showed that virus pseudotyped with Ebola or Marburg (Musoke) glycoprotein was neutralized by complement, while the Marburg (Ravn strain) glycoprotein-pseudotyped virus was less sensitive to neutralization. Neutralization was partially mediated through the lectin complement pathway, since a complement source deficient in MBL was significantly less effective at neutralizing viruses pseudotyped with filovirus glycoproteins and addition of purified MBL to the MBL-deficient complement increased neutralization. These experiments demonstrated that MBL binds to filovirus envelope glycoproteins resulting in important biological effects and suggest that MBL can interact with filoviruses during infection in humans.

Role of Two Types of Syntactic Embedding in Belief Attribution in Adults with or without Asperger Syndrome

PubMed Central

Burnel, Morgane Clémentine; Perrone-Bertolotti, Marcela; Durrleman, Stephanie; Reboul, Anne C.; Baciu, Monica

2017-01-01

The role of syntax in belief attribution (BA) is not completely understood in healthy adults and understudied in adults with autism spectrum disorder. Embedded syntax could be useful either for the development of Theory of Mind (ToM) (Emergence account) or more generally over the lifespan (Reasoning account). Two hypotheses have been explored, one suggesting that embedding itself (Relatives and Complement sentences and Metarepresentation account) is important for ToM and another one considering that the embedding of a false proposition into a true one (Complement sentences and Misrepresentation account) is important. The goals of this study were to evaluate (1) the role of syntax in ToM (Emergence vs. Reasoning account), (2) the type of syntax implied in ToM (Metarepresentation vs. Misrepresentation account), and (3) the verbally mediated strategies which compensate for ToM deficits in adults with Asperger Syndrome (AS). Fifty NeuroTypical (NT) adults and 22 adults with AS were involved in a forced-choice task including ±ToM tasks (BA and a control task, physical causation, PC) under four Interference conditions (silence, syllable repetition, relative sentences repetition, and complement sentences repetition). The non-significant ±ToM × Interference interaction effect in the NT group did not support the Reasoning account and thus suggests that syntax is useful only for ToM development (i.e., Emergence account). Results also indicated that repeating complement clauses put NT participants in a dual task whereas repeating relative clauses did not, suggesting that repeating relatives is easier for NT than repeating complements. This could be an argument in favor of the Misrepresentation account. However, this result should be interpreted with caution because our results did not support the Reasoning account. Moreover, AS participants (but not NT participants) were more disrupted by ±ToM tasks when asked to repeat complement sentences compared to relative clause sentences. This result is in favor of the Misrepresentation account and indirectly suggests verbally mediated strategies for ToM in AS. To summarize, our results are in favor of the Emergence account in NT and of Reasoning and Misrepresentation accounts in adults with AS. Overall, this suggests that adults with AS use complement syntax to compensate for ToM deficits. PMID:28553246

Role of Two Types of Syntactic Embedding in Belief Attribution in Adults with or without Asperger Syndrome.

PubMed

Burnel, Morgane Clémentine; Perrone-Bertolotti, Marcela; Durrleman, Stephanie; Reboul, Anne C; Baciu, Monica

2017-01-01

The role of syntax in belief attribution (BA) is not completely understood in healthy adults and understudied in adults with autism spectrum disorder. Embedded syntax could be useful either for the development of Theory of Mind (ToM) ( Emergence account) or more generally over the lifespan ( Reasoning account). Two hypotheses have been explored, one suggesting that embedding itself (Relatives and Complement sentences and Metarepresentation account) is important for ToM and another one considering that the embedding of a false proposition into a true one (Complement sentences and Misrepresentation account) is important. The goals of this study were to evaluate (1) the role of syntax in ToM ( Emergence vs. Reasoning account), (2) the type of syntax implied in ToM ( Metarepresentation vs. Misrepresentation account), and (3) the verbally mediated strategies which compensate for ToM deficits in adults with Asperger Syndrome (AS). Fifty NeuroTypical (NT) adults and 22 adults with AS were involved in a forced-choice task including ±ToM tasks (BA and a control task, physical causation, PC) under four Interference conditions (silence, syllable repetition, relative sentences repetition, and complement sentences repetition). The non-significant ±ToM × Interference interaction effect in the NT group did not support the Reasoning account and thus suggests that syntax is useful only for ToM development (i.e., Emergence account). Results also indicated that repeating complement clauses put NT participants in a dual task whereas repeating relative clauses did not, suggesting that repeating relatives is easier for NT than repeating complements. This could be an argument in favor of the Misrepresentation account. However, this result should be interpreted with caution because our results did not support the Reasoning account. Moreover, AS participants (but not NT participants) were more disrupted by ±ToM tasks when asked to repeat complement sentences compared to relative clause sentences. This result is in favor of the Misrepresentation account and indirectly suggests verbally mediated strategies for ToM in AS. To summarize, our results are in favor of the Emergence account in NT and of Reasoning and Misrepresentation accounts in adults with AS. Overall, this suggests that adults with AS use complement syntax to compensate for ToM deficits.

Electrical Prospecting Methods Employed by Junta de Energia Nuclear. Report No. 28; METODOS DE PROSPECCAO ELECTRICA ADOPTADOS NA JUNTA DE ENERGIA NUCLEAR. MEMORIA NO. 28

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferrao, C.A.N.

1960-01-01

The electrical prospecting methods are described which bave been incorporated in the routine operations of the Prospecting and Mining Services. The methods are concerned with structure and are useful in prospecting for uranium, other minerals, and water. The methods were developed to complement other existing prospecting methods and to provide geological and structural information. (J.R.D.)

Comparison of U.S. Forest Land AreaEstimates From Forest Inventory and Analysis, National Resources Inventory, and Four Satellite Image-Derived Land Cover Data Sets

Treesearch

Mark D. Nelson; Ronald E. McRoberts; Veronica C. Lessard

2005-01-01

Our objective was to test one application of remote sensing technology for complementing forest resource assessments by comparing a variety of existing satellite image-derived land cover maps with national inventory-derived estimates of United States forest land area. National Resources Inventory (NRI) 1997 estimates of non-Federal forest land area differed by 7.5...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilgrim, Corey D.; Zavarin, Mavrik; Casey, William H.

Here, the rates of ligand exchange into the geochemically important [NpO 2(CO 3) 3] 4– aqueous complex are measured as a function of pressure in order to complement existing data on the isostructural [UO 2(CO 3) 3] 4– complex. Experiments are conducted at pH conditions where the rate of exchange is independent of the proton concentration. Unexpectedly, the experiments show a distinct difference in the pressure dependencies of rates of exchange for the uranyl and neptunyl complexes.

Field trial of the enhanced data authentication system (EDAS)

DOE PAGES

Thomas, Maikael A.; Hymel, Ross W.; Baldwin, George; ...

2016-11-01

The Enhanced Data Authentication System (EDAS) is means to securely branch information from an existing measurement system or data stream to a secondary observer. In an international nuclear safeguards context, the EDAS connects to operator instrumentation, and provides a cryptographically secure copy of the information for a safeguards inspectorate. However, this novel capability could be a valuable complement to inspector-owned safeguards instrumentation, offering context that is valuable for anomaly resolution and contingency.

Security of the food supply chain.

PubMed

Setola, Roberto; De Maggio, Maria Carla

2009-01-01

The food supply chain could became a dangerous weapon in the hands of enemies, for this reason the strategies developed to fight food adulteration (food safety) should be complemented with specific actions devoted to improve food "security" in the sense of food defence. This paper illustrate the methodological approach used in the EU project SecuFood to analyze threats, vulnerabilities and countermeasures existing in major European countries about what concerns deliberate attacks and manipulations of food.

Searching for Sterile Neutrinos with MINOS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timmons, Ashley

2016-01-01

This document presents the latest results for a 3+1 sterile neutrino search using themore » $$10.56 \\times 10^{20}$$ protons-on-target data set taken from 2005 - 2012. By searching for oscillations driven by a large mass splitting, MINOS is sensitive to the existence of sterile neutrinos through any energy dependent deviations using a charged current sample, as well as looking at any relative deficit between neutral current events between the far and near detectors. This document will discuss the novel analysis that enabled a search for sterile neutrinos setting a limit in the previously unexplored regions in the parameter space $$\\{\\Delta m^{2}_{41}, \\sin^2\\theta_{24}\\}$$. The results presented can be compared to the parameter space suggested by LSND and MiniBooNE and complements other previous experimental searches for sterile neutrinos in the electron neutrino appearance channel.« less

Comparison of NASTRAN analysis with ground vibration results of UH-60A NASA/AEFA test configuration

NASA Technical Reports Server (NTRS)

Idosor, Florentino; Seible, Frieder

1990-01-01

Preceding program flight tests, a ground vibration test and modal test analysis of a UH-60A Black Hawk helicopter was conducted by Sikorsky Aircraft to complement the UH-60A test plan and NASA/ARMY Modern Technology Rotor Airloads Program. The 'NASA/AEFA' shake test configuration was tested for modal frequencies and shapes and compared with its NASTRAN finite element model counterpart to give correlative results. Based upon previous findings, significant differences in modal data existed and were attributed to assumptions regarding the influence of secondary structure contributions in the preliminary NASTRAN modeling. An analysis of an updated finite element model including several secondary structural additions has confirmed that the inclusion of specific secondary components produces a significant effect on modal frequency and free-response shapes and improves correlations at lower frequencies with shake test data.

The high-temperature heat capacity of the (Th,U)O 2 and (U,Pu)O 2 solid solutions

DOE PAGES

Valu, S. O.; Benes, O.; Manara, D.; ...

2016-11-09

The enthalpy increment data for the (Th,U)O 2 and (U,Pu)O 2 solid solutions are reviewed and complemented with new experimental data (400–1773 K) and many-body potential model simulations. The results of the review show that from room temperature up to about 2000 K the enthalpy data are in agreement with the additivity rule (Neumann-Kopp) in the whole composition range. Above 2000 K the effect of Oxygen Frenkel Pair (OFP) formation leads to an excess enthalpy (heat capacity) that is modeled using the enthalpy and entropy of OFP formation from the end-members. Here, a good agreement with existing experimental work ismore » observed, and a reasonable agreement with the results of the many-body potential model, which indicate the presence of the diffuse Bredig (superionic) transition that is not found in the experimental enthalpy increment data.« less

Anti-complementary constituents of Houttuynia cordata and their targets in complement activation cascade.

PubMed

Jiang, Yun; Lu, Yan; Zhang, Yun-Yi; Chen, Dao-Feng

2014-01-01

Activity-guided fractionation for complement inhibitors led to the isolation of 23 known compounds from Houttuynia cordata Thunb. Seven flavonoids, two alkaloids, one coumarin and two phenols showed anti-complementary activity. Preliminary inhibitory mechanism of four flavonoids, including quercitrin, afzelin, isoquercitrin and quercetin in the complement activation cascade were examined for the first time. The results indicated that the target components of flavonols are different from those of flavonosides, and the glycoside moieties may be necessary to block C3 and C4 components.

Mutations in new cell cycle genes that fail to complement a multiply mutant third chromosome of Drosophila.

PubMed

White-Cooper, H; Carmena, M; Gonzalez, C; Glover, D M

1996-11-01

We have simultaneously screened for new alleles and second site mutations that fail to complement five cell cycle mutations of Drosphila carried on a single third chromosome (gnu, polo, mgr, asp, stg). Females that are either transheterozygous for scott of the antartic (scant) and polo, or homozygous for scant produce embryos that show mitotic defects. A maternal effect upon embryonic mitoses is also seen in embryos derived from females transheterozygous with helter skelter (hsk) and either mgr or asp. cleopatra (cleo), fails to complement asp but is not uncovered by a deficiency for asp. The mitotic phenotype of larvae heterozygous for cleo and the multiple mutant chromosome is similar to weak alleles of asp, but there are no defects in male meiosis. Mutations that failed to complement stg fell into two complementation groups corresponding to stg and a new gene noose. Three of the new stg alleles are early zygotic lethals, whereas the fourth is a pharate adult lethal allele that affects both mitosis and meiosis. Mutations in noose fully complement a small deficiency that removes stg, but when placed in trans to certain stg alleles, result in late lethality and mitotic abnormalities in larval brains.

Evaluation of Pasteurella multocida serotype B:2 resistance to immune serum and complement system

PubMed Central

Ataei Kachooei, Saeed; Ranjbar, Mohammad Mehdi; Ataei Kachooei, Saba

2017-01-01

Members of gram-negative bacteria family Pasteurellaceae, include a large number of important economically human and veterinary pathogens. Organisms belonging to the family can colonize in mucosal surfaces of the respiratory, alimentary, genital tracts and cause diseases in various mammals, birds, and reptiles. Hemorrhagic septicemia is an acute disease of cattle and buffaloes in tropical countries caused by Pasteurella multocida serotype B:2. In the present study, the possible bactericidal activity of immune calf sera in the presence and absence of complement system was investigated. The results showed that P. multocida B:2 is highly resistant to positive serum, containing high levels of IgG and IgM obtained from calves after vaccination, and complement activity in normal fresh calf serum. This organism also grew rapidly in the normal fresh calf serum and the mixture of positive serum as well as normal fresh calf serum. As a control test an E. coli strain was subjected to the same experiment and found completely sensitive to the bactericidal activity of complement in calf and guinea pig fresh sera. Results were indicative of the presence of inhibitory mechanism(s) in P. multocida B:2 against bactericidal activity of immune calf serum and complement system. PMID:29085604

Characterization of phagocytic hemocytes in Ornithodoros moubata (Acari: Ixodidae).

PubMed

Inoue, N; Hanada, K; Tsuji, N; Igarashi, I; Nagasawa, H; Mikami, T; Fujisaki, K

2001-07-01

Effects of fetal bovine serum (FBS) and complement on phagocytic activity in Ornithodaros moubata (Murray 1877) hemocytes and protease activity in the hemocytes were examined. At least three morphologically different cell types, granulocytes, plasmatocytes, and prohemocytes, were detected in hemolymph of O. moubata, and granulocytes and plasmatocytes showed phagocytic activity. FBS altered phagocytic activity of granulocytes, and complement affected phagocytic activity of plasmatocytes. Ticks were inoculated with fluorescent polystyrene beads in combination with FBS or complement. The average number of beads in granulocytes was significantly higher in the FBS injected group than the control (P < 0.01). The percentage of bead-ingesting plasmatocytes in complement inoculated ticks was significantly lower than that in heat-inactivated complement inoculated and control ticks (P < 0.05). Proteases of tick hemocytes localized in small granules in the cytoplasm not only in phagocytic hemocytes but also in prohemocytes. Results suggested modulation of tick hemocyte function through serum components, and digestion of phagocytosed foreign bodies in the hemocytes.

A kinase-focused compound collection: compilation and screening strategy.

PubMed

Sun, Dongyu; Chuaqui, Claudio; Deng, Zhan; Bowes, Scott; Chin, Donovan; Singh, Juswinder; Cullen, Patrick; Hankins, Gretchen; Lee, Wen-Cherng; Donnelly, Jason; Friedman, Jessica; Josiah, Serene

2006-06-01

Lead identification by high-throughput screening of large compound libraries has been supplemented with virtual screening and focused compound libraries. To complement existing approaches for lead identification at Biogen Idec, a kinase-focused compound collection was designed, developed and validated. Two strategies were adopted to populate the compound collection: a ligand shape-based virtual screening and a receptor-based approach (structural interaction fingerprint). Compounds selected with the two approaches were cherry-picked from an existing high-throughput screening compound library, ordered from suppliers and supplemented with specific medicinal compounds from internal programs. Promising hits and leads have been generated from the kinase-focused compound collection against multiple kinase targets. The principle of the collection design and screening strategy was validated and the use of the kinase-focused compound collection for lead identification has been added to existing strategies.

Susceptibility of pathogenic and nonpathogenic Naegleria ssp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whiteman, L.Y.

1988-01-01

The susceptibility of four species of Naegleria amoebae to complement-mediated lysis was determined. The amoebicidal activity of normal human serum (NHS) and normal guinea pig serum (NGPS) for Naegleria amoebae was measured by an in vitro cytotoxicity assay. Release of radioactivity from amoebae labeled with {sup 3}H-uridine and visual observation with a compound microscope were used as indices of lysis. Susceptibility or resistance to complement-mediated lysis in vitro correlated with the in vivo pathogenic potential. Nonpathogenic Naegleria amoebae were lysed at a faster rate and at higher cell concentrations than were pathogenic amoebae. Electrophoretic analysis of NHS incubated with pathogenicmore » or nonpathogenic Naegleria spp. demonstrated that amoebae activate the complement cascade resulting in the production of C3 and C5 complement cleavage products. Treatment with papain or trypsin for 1 h, but not with sialidase, increase the susceptibility of highly pathogenic, mouse-passaged N. fowleri to lysis. Treatment with actinomycin D, cycloheximide or various protease inhibitors for 4 h did not increase susceptibility to lysis. Neither a repair process involving de novo protein synthesis nor a complement-inactivating protease appear to account for the increase resistance of N. fowleri amoebae to complement-mediated lysis. A binding study with {sup 125}I radiolabeled C9 indicated that the terminal complement component does not remain stably bound to the membrane of pathogenic amoebae.« less

Sublytic complement protects prostate cancer cells from tumour necrosis factor-α-induced cell death.

PubMed

Liu, L; Li, W; Li, Z; Kirschfink, M

2012-08-01

Inflammation is a critical component of tumour progression. Although complement and tumour necrosis factor (TNF)-α potentially exert significant anti-tumour effects, both mediators may also promote tumour progression. It has been demonstrated that sublytic complement confers resistance on tumour cells not only against lytic complement, but also other danger molecules such as perforin. In low concentrations, TNF promotes survival of malignant cells rather than exerting cytotoxic activity. In this study, we tested if sublytic complement is able to interfere with TNF-mediated tumour cell killing. Our results demonstrate that either subcytotoxic concentrations of TNF or sublytic complement rescue prostate carcinoma cells (DU145) from TNF-α-mediated cell death. Upon pretreatment with low-dose TNF-α, but not upon pre-exposure to sublytic complement, TNF resistance was associated with the down-regulation of TNF receptor 1 (TNF-R1) expression. Complement-induced protection against TNF-mediated apoptosis accompanied the induction of anti-apoptotic proteins [B cell leukaemia/lymphoma (Bcl)-2 and Bcl-xL] at an early stage followed by inhibition of the TNF-induced decrease in the amount of Bcl-2 and Bcl-xL. Cell protection also accompanied the inhibition of caspase-8 activation, poly (ADP-ribose) polymerase (PARP)-1 cleavage and the activation of nuclear factor (NF)-κB. Our data extend our current view on the induction of tumour cell resistance against cytotoxic mediators supporting the role of the tumour microenvironment in mediating protection against the anti-cancer immune response. © 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.

Donor Brain Death Exacerbates Complement-Dependent Ischemia Reperfusion Injury in Transplanted Hearts

PubMed Central

Atkinson, Carl; Floerchinger, Bernhard; Qiao, Fei; Casey, Sarah; Williamson, Tucker; Moseley, Ellen; Stoica, Serban; Goddard, Martin; Ge, Xupeng; Tullius, Stefan G.; Tomlinson, Stephen

2013-01-01

Background Brain death (BD) can immunologically prime the donor organ and is thought to lead to exacerbated ischemia reperfusion injury (IRI) post-transplantation. Using a newly developed mouse model of BD, we investigated the effect of donor BD on post transplant cardiac IRI. We further investigated the therapeutic effect of a targeted complement inhibitor in recipients of BD donor hearts, and addressed the clinical relevance of these studies by analysis of human heart biopsies from BD and domino (living) donors. Methods and Results Hearts from living or brain dead donor C57BL/6 mice were transplanted into C57BL/6 or BALB/c recipients. Recipient mice were treated with the complement inhibitor CR2-Crry or vehicle control (n=6). Isografts were analyzed 48 hours post-transplant for injury, inflammation and complement deposition, and allografts monitored for graft survival. Human cardiac biopsies were analyzed for complement deposition and inflammatory cell infiltration. In the murine model, donor BD exacerbated IRI and graft rejection as demonstrated by increased myocardial injury, serum cardiac troponin, cellular infiltration, inflammatory chemokine and cytokine levels, complement deposition, and decreased graft survival. CR2-Crry treatment of recipients significantly reduced all measured outcomes in grafts from both BD and living donors compared to controls. Analysis of human samples documented the relevance of our experimental findings and revealed exacerbated complement deposition and inflammation in grafts from BD donors compared to grafts from living donors. Conclusions BD exacerbates post-transplant cardiac IRI in mice and humans, and decreases survival of mouse allografts. Further, targeted complement inhibition in recipient mice ameliorates BD-exacerbated IRI. PMID:23443736

Defining the Complement Biomarker Profile of C3 Glomerulopathy

PubMed Central

Zhang, Yuzhou; Nester, Carla M.; Martin, Bertha; Skjoedt, Mikkel-Ole; Meyer, Nicole C.; Shao, Dingwu; Borsa, Nicolò; Palarasah, Yaseelan

2014-01-01

Background and objectives C3 glomerulopathy (C3G) applies to a group of renal diseases defined by a specific renal biopsy finding: a dominant pattern of C3 fragment deposition on immunofluorescence. The primary pathogenic mechanism involves abnormal control of the alternative complement pathway, although a full description of the disease spectrum remains to be determined. This study sought to validate and define the association of complement dysregulation with C3G and to determine whether specific complement pathway abnormalities could inform disease definition. Design, setting, participants, & measurements This study included 34 patients with C3G (17 with C3 glomerulonephritis [C3GN] and 17 with dense deposit disease [DDD]) diagnosed between 2008 and 2013 selected from the C3G Registry. Control samples (n=100) were recruited from regional blood drives. Nineteen complement biomarkers were assayed on all samples. Results were compared between C3G disease categories and with normal controls. Results Assessment of the alternative complement pathway showed that compared with controls, patients with C3G had lower levels of serum C3 (P<0.001 for both DDD and C3GN) and factor B (P<0.001 for both DDD and C3GN) as well as higher levels of complement breakdown products including C3d (P<0.001 for both DDD and C3GN) and Bb (P<0.001 for both DDD and C3GN). A comparison of terminal complement pathway proteins showed that although C5 levels were significantly suppressed (P<0.001 for both DDD and C3GN) its breakdown product C5a was significantly higher only in patients with C3GN (P<0.05). Of the other terminal pathway components (C6–C9), the only significant difference was in C7 levels between patients with C3GN and controls (P<0.01). Soluble C5b-9 was elevated in both diseases but only the difference between patients with C3GN and controls reached statistical significance (P<0.001). Levels of C3 nephritic factor activity were qualitatively higher in patients with DDD compared with patients with C3GN. Conclusions Complement biomarkers are significantly abnormal in patients with C3G compared with controls. These data substantiate the link between complement dysregulation and C3G and identify C3G interdisease differences. PMID:25341722

Understanding surgery: multimedia comes to theatre.

PubMed

Dakin, S; Garner, M; Plura, M

1997-01-01

Educational technology is well established within Schools of Nursing, however there are few computer based learning packages within the clinical environment. It was felt within the Operating Services Directorate, Royal Hallamshire Hospital, that the development of a multimedia package would enhance and complement existing teaching methods. This paper describes the theory behind the choice of a multimedia presentation and its development within the operating theatres. The package, concentrating on general surgery, has been developed by two experienced theatre nurses and a graphic designer. This has resulted in a structured but flexible, fun package which is relevant to all learners within the operating theatre environment and allied healthcare fields. The feedback obtained from users within the clinical area has reinforced the project team's original feeling that multimedia is a highly appropriate resource for clinical education.

The life-cycle of Emiliania huxleyi: A brief review and a study of relative ploidy levels analysed by flow cytometry

NASA Astrophysics Data System (ADS)

Green, J. C.; Course, P. A.; Tarran, G. A.

1996-10-01

Emiliania huxleyi exists in several principal forms including the familiar coccolith-bearing C-cell, non-motile naked N-cells, and scale-bearing swarmers (S-cells), but the relationships between these cells are unclear. Flow cytometric analyses have been undertaken on whole cells using fluorochrome staining of the DNA in order to determine the relative DNA content and the relative GC content of the S- and C-cells of selected clones. Results showed that the DNA complement of the S-cells was half that of the C-cells and the two cell types are, therefore, haploid and diploid relative to each other. The S-cells may, therefore, represent a gametic stage, though processes such as sexual fusion and meiosis have not been observed.

Forensic examination of ink by high-performance thin layer chromatography--the United States Secret Service Digital Ink Library.

PubMed

Neumann, Cedric; Ramotowski, Robert; Genessay, Thibault

2011-05-13

Forensic examinations of ink have been performed since the beginning of the 20th century. Since the 1960s, the International Ink Library, maintained by the United States Secret Service, has supported those analyses. Until 2009, the search and identification of inks were essentially performed manually. This paper describes the results of a project designed to improve ink samples' analytical and search processes. The project focused on the development of improved standardization procedures to ensure the best possible reproducibility between analyses run on different HPTLC plates. The successful implementation of this new calibration method enabled the development of mathematical algorithms and of a software package to complement the existing ink library. Copyright © 2010 Elsevier B.V. All rights reserved.

Distinct cortical areas for names of numbers and body parts independent of language and input modality.

PubMed

Le Clec'H, G; Dehaene, S; Cohen, L; Mehler, J; Dupoux, E; Poline, J B; Lehéricy, S; van de Moortele, P F; Le Bihan, D

2000-10-01

Some models of word comprehension postulate that the processing of words presented in different modalities and languages ultimately converges toward common cerebral systems associated with semantic-level processing and that the localization of these systems may vary with the category of semantic knowledge being accessed. We used functional magnetic resonance imaging to investigate this hypothesis with two categories of words, numerals, and body parts, for which the existence of distinct category-specific areas is debated in neuropsychology. Across two experiments, one with a blocked design and the other with an event-related design, a reproducible set of left-hemispheric parietal and prefrontal areas showed greater activation during the manipulation of topographical knowledge about body parts and a right-hemispheric parietal network during the manipulation of numerical quantities. These results complement the existing neuropsychological and brain-imaging literature by suggesting that within the extensive network of bilateral parietal regions active during both number and body-part processing, a subset shows category-specific responses independent of the language and modality of presentation. Copyright 2000 Academic Press.

Adjoint-Based Mesh Adaptation for the Sonic Boom Signature Loudness

NASA Technical Reports Server (NTRS)

Rallabhandi, Sriram K.; Park, Michael A.

2017-01-01

The mesh adaptation functionality of FUN3D is utilized to obtain a mesh optimized to calculate sonic boom ground signature loudness. During this process, the coupling between the discrete-adjoints of the computational fluid dynamics tool FUN3D and the atmospheric propagation tool sBOOM is exploited to form the error estimate. This new mesh adaptation methodology will allow generation of suitable meshes adapted to reduce the estimated errors in the ground loudness, which is an optimization metric employed in supersonic aircraft design. This new output-based adaptation could allow new insights into meshing for sonic boom analysis and design, and complements existing output-based adaptation techniques such as adaptation to reduce estimated errors in off-body pressure functional. This effort could also have implications for other coupled multidisciplinary adjoint capabilities (e.g., aeroelasticity) as well as inclusion of propagation specific parameters such as prevailing winds or non-standard atmospheric conditions. Results are discussed in the context of existing methods and appropriate conclusions are drawn as to the efficacy and efficiency of the developed capability.

Activation of the classical pathway of complement by binding of bovine lactoferrin to unencapsulated Streptococcus agalactiae.

PubMed Central

Rainard, P

1993-01-01

The ability of lactoferrin (Lf) bound to Streptococcus agalactiae to interfere with the deposition of complement components on the bacterial surface was investigated by enzyme-linked immunosorbent assay (ELISA). By using a strain of S. agalactiae which activates the alternative pathway of complement in the absence of antibodies, it was found that pretreatment of bacteria with Lf shortened the lag phase preceding the deposition of C3 on bacteria. The kinetics of C3 deposition was comparable to that obtained by adding antibodies against S. agalactiae to agammaglobulinaemic precolostral calf serum (PCS) heated at 56 degrees for 3 min to inactivate the alternative pathway. Accelerated C3 deposition did not occur in the absence of Ca2+ ions. Deposition of C4 on bacteria occurred only when either antibodies or Lf were added to PCS. These results demonstrate that the interaction of lactoferrin with bacteria activated the classical pathway of complement in the absence of antibodies. The binding of purified C1q to bacteria was promoted in a dose-dependent manner by Lf, suggesting that recruitment of classical pathway of complement resulted from the interaction of C1q with Lf adsorbed to the bacterial surface. Phagocytosis of bacteria opsonized with heated PCS (at 56 degrees for 3 min) and Lf was comparable to that occurring in the presence of heated PCS and antibodies. In conclusion, Lf was able to substitute for antibodies in order to activate the classical pathway of complement and to opsonize unencapsulated S. agalactiae efficiently. PMID:8406591

Complement Protein C1q Modulates Neurite Outgrowth In Vitro and Spinal Cord Axon Regeneration In Vivo

PubMed Central

Peterson, Sheri L.; Nguyen, Hal X.; Mendez, Oscar A.

2015-01-01

Traumatic injury to CNS fiber tracts is accompanied by failure of severed axons to regenerate and results in lifelong functional deficits. The inflammatory response to CNS trauma is mediated by a diverse set of cells and proteins with varied, overlapping, and opposing effects on histological and behavioral recovery. Importantly, the contribution of individual inflammatory complement proteins to spinal cord injury (SCI) pathology is not well understood. Although the presence of complement components increases after SCI in association with axons and myelin, it is unknown whether complement proteins affect axon growth or regeneration. We report a novel role for complement C1q in neurite outgrowth in vitro and axon regrowth after SCI. In culture, C1q increased neurite length on myelin. Protein and molecular assays revealed that C1q interacts directly with myelin associated glycoprotein (MAG) in myelin, resulting in reduced activation of growth inhibitory signaling in neurons. In agreement with a C1q-outgrowth-enhancing mechanism in which C1q binding to MAG reduces MAG signaling to neurons, complement C1q blocked both the growth inhibitory and repulsive turning effects of MAG in vitro. Furthermore, C1q KO mice demonstrated increased sensory axon turning within the spinal cord lesion after SCI with peripheral conditioning injury, consistent with C1q-mediated neutralization of MAG. Finally, we present data that extend the role for C1q in axon growth and guidance to include the sprouting patterns of descending corticospinal tract axons into spinal gray matter after dorsal column transection SCI. PMID:25762679

Activation of the lectin pathway of complement in experimental human keratitis with Pseudomonas aeruginosa

PubMed Central

Osthoff, Michael; Brown, Karl D.; Kong, David C.M.; Daniell, Mark

2014-01-01

Purpose Pseudomonas aeruginosa (P. aeruginosa) microbial keratitis (MK) is a sight-threatening disease. Previous animal studies have identified an important contribution of the complement system to the clearance of P. aeruginosa infection of the cornea. Mannose-binding lectin (MBL), a pattern recognition receptor of the lectin pathway of complement, has been implicated in the host defense against P. aeruginosa. However, studies addressing the role of the lectin pathway in P. aeruginosa MK are lacking. Hence, we sought to determine the activity of the lectin pathway in human MK caused by P. aeruginosa. Methods Primary human corneal epithelial cells (HCECs) from cadaveric donors were exposed to two different P. aeruginosa strains. Gene expression of interleukin (IL)-6, IL-8, MBL, and other complement proteins was determined by reverse transcription-polymerase chain reaction (RT–PCR) and MBL synthesis by enzyme-linked immunosorbent assay and intracellular flow cytometry. Results MBL gene expression was not detected in unchallenged HCECs. Exposure of HCECs to P. aeruginosa resulted in rapid induction of the transcriptional expression of MBL, IL-6, and IL-8. In addition, expression of several complement proteins of the classical and lectin pathways, but not the alternative pathway, were upregulated after 5 h of challenge, including MBL-associated serine protease 1. However, MBL protein secretion was not detectable 18 h after challenge with P. aeruginosa. Conclusions MK due to P. aeruginosa triggers activation of MBL and the lectin pathway of complement. However, the physiologic relevance of this finding is unclear, as corresponding MBL oligomer production was not observed. PMID:24426774

Cre/lox-Recombinase-Mediated Cassette Exchange for Reversible Site-Specific Genomic Targeting of the Disease Vector, Aedes aegypti.

PubMed

Häcker, Irina; Harrell Ii, Robert A; Eichner, Gerrit; Pilitt, Kristina L; O'Brochta, David A; Handler, Alfred M; Schetelig, Marc F

2017-03-07

Site-specific genome modification (SSM) is an important tool for mosquito functional genomics and comparative gene expression studies, which contribute to a better understanding of mosquito biology and are thus a key to finding new strategies to eliminate vector-borne diseases. Moreover, it allows for the creation of advanced transgenic strains for vector control programs. SSM circumvents the drawbacks of transposon-mediated transgenesis, where random transgene integration into the host genome results in insertional mutagenesis and variable position effects. We applied the Cre/lox recombinase-mediated cassette exchange (RMCE) system to Aedes aegypti, the vector of dengue, chikungunya, and Zika viruses. In this context we created four target site lines for RMCE and evaluated their fitness costs. Cre-RMCE is functional in a two-step mechanism and with good efficiency in Ae. aegypti. The advantages of Cre-RMCE over existing site-specific modification systems for Ae. aegypti, phiC31-RMCE and CRISPR, originate in the preservation of the recombination sites, which 1) allows successive modifications and rapid expansion or adaptation of existing systems by repeated targeting of the same site; and 2) provides reversibility, thus allowing the excision of undesired sequences. Thereby, Cre-RMCE complements existing genomic modification tools, adding flexibility and versatility to vector genome targeting.

DESM: portal for microbial knowledge exploration systems.

PubMed

Salhi, Adil; Essack, Magbubah; Radovanovic, Aleksandar; Marchand, Benoit; Bougouffa, Salim; Antunes, Andre; Simoes, Marta Filipa; Lafi, Feras F; Motwalli, Olaa A; Bokhari, Ameerah; Malas, Tariq; Amoudi, Soha Al; Othum, Ghofran; Allam, Intikhab; Mineta, Katsuhiko; Gao, Xin; Hoehndorf, Robert; C Archer, John A; Gojobori, Takashi; Bajic, Vladimir B

2016-01-04

Microorganisms produce an enormous variety of chemical compounds. It is of general interest for microbiology and biotechnology researchers to have means to explore information about molecular and genetic basis of functioning of different microorganisms and their ability for bioproduction. To enable such exploration, we compiled 45 topic-specific knowledgebases (KBs) accessible through DESM portal (www.cbrc.kaust.edu.sa/desm). The KBs contain information derived through text-mining of PubMed information and complemented by information data-mined from various other resources (e.g. ChEBI, Entrez Gene, GO, KOBAS, KEGG, UniPathways, BioGrid). All PubMed records were indexed using 4,538,278 concepts from 29 dictionaries, with 1 638 986 records utilized in KBs. Concepts used are normalized whenever possible. Most of the KBs focus on a particular type of microbial activity, such as production of biocatalysts or nutraceuticals. Others are focused on specific categories of microorganisms, e.g. streptomyces or cyanobacteria. KBs are all structured in a uniform manner and have a standardized user interface. Information exploration is enabled through various searches. Users can explore statistically most significant concepts or pairs of concepts, generate hypotheses, create interactive networks of associated concepts and export results. We believe DESM will be a useful complement to the existing resources to benefit microbiology and biotechnology research. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Future of Space Astronomy: A Global Road Map for the Next Decades

NASA Technical Reports Server (NTRS)

Ubertini, Pietro; Gehrels, Neil; Corbett, Ian; DeBernardis, Paolo; Machado, Marcos; Griffin, Matt; Hauser, Michael; Manchanda, Ravinder K.; Kawai, Nobuyuki; Zhang, Shuang-Nan;

Asymmetric interactions in the adenosine-binding pockets of the MS2 coat protein dimer

PubMed Central

Powell, Amy J; Peabody, David S

2001-01-01

Background The X-ray structure of the MS2 coat protein-operator RNA complex reveals the existence of quasi-synmetric interactions of adenosines -4 and -10 in pockets formed on different subunits of the coat protein dimer. Both pockets utilize the same five amino acid residues, namely Val29, Thr45, Ser47, Thr59, and Lys61. We call these sites the adenosine-binding pockets. Results We present here a heterodimer complementation analysis of the contributions of individual A-pocket amino acids to the binding of A-4 and A-10 in different halves of the dimer. Various substitutions of A-pocket residues were introduced into one half of single-chain coat protein heterodimers where they were tested for their abilities to complement Y85H or T91I substitutions (defects in the A-4 and A-10 half-sites, respectively) present in the other dimer half. Conclusions These experiments provide functional tests of interactions predicted from structural analyses, demonstrating the importance of certain amino acid-nucleotide contacts observed in the crystal structure, and showing that others make little or no contribution to the stability of the complex. In summary, Val29 and Lys61 form important stabilizing interactions with both A-4 and A-10. Meanwhile, Ser47 and Thr59 interact primarily with A-10. The important interactions with Thr45 are restricted to A-4. PMID:11504563

Worldwide Distribution of Four SNPs in X‐Ray and Repair and Cross‐Complementing Group 1 (XRCC1)

PubMed Central

Takeshita, Haruo; Yasuda, Toshihiro; Kimura‐Kataoka, Kaori

2014-01-01

Abstract Purpose X‐ray repair cross‐complementing group 1 (XRCC1) repairs single‐strand breaks in DNA. Several reports have shown the association of single nucleotide polymorphisms (SNPs) (Arg194Trp, Pro206Pro, Arg280His, Arg399Gln) in XRCC1 to diseases. Limited population data are available regarding SNPs in XRCC1, especially in African populations. In this study, genotype distributions of four SNPs in worldwide populations were examined and compared with those reported previously. Materials and Methods Four SNPs (Arg194Trp, Pro206Pro, Arg280His, Arg399Gln) in XRCC1 from genomic DNA samples of 10 populations were evaluated by using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results The frequency of the minor allele corresponding to the Trp allele of XRCC1Arg194Trp was higher in Asian populations than in African and Caucasian populations. As for XRCC1Pro206Pro, Africans showed higher minor allele frequencies than did Asian populations, except for Tamils and Sinhalese. XRCC1 Arg280His frequencies were similar among Africans and Caucasians but differed among Asian populations. Similarly, lower mutant XRCC1 Arg399Gln frequencies were observed in Africans. Conclusions This study is the first to show the existence of a certain genetic heterogeneity in the worldwide distribution of four SNPs in XRCC1. PMID:25387884

Expression analysis and identification of antimicrobial peptide transcripts from six North American frog species

USGS Publications Warehouse

Robertson, Laura S.; Fellers, Gary M.; Marranca, Jamie Marie; Kleeman, Patrick M.

2013-01-01

Frogs secrete antimicrobial peptides onto their skin. We describe an assay to preserve and analyze antimicrobial peptide transcripts from field-collected skin secretions that will complement existing methods for peptide analysis. We collected skin secretions from 4 North American species in the field in California and 2 species in the laboratory. Most frogs appeared healthy after release; however, Rana boylii in the Sierra Nevada foothills, but not the Coast Range, showed signs of morbidity and 2 died after handling. The amount of total RNA extracted from skin secretions was higher in R. boylii and R. sierrae compared to R. draytonii, and much higher compared to Pseudacris regilla. Interspecies variation in amount of RNA extracted was not explained by size, but for P. regilla it depended upon collection site and date. RNA extracted from skin secretions from frogs handled with bare hands had poor quality compared to frogs handled with gloves or plastic bags. Thirty-four putative antimicrobial peptide precursor transcripts were identified. This study demonstrates that RNA extracted from skin secretions collected in the field is of high quality suitable for use in sequencing or quantitative PCR (qPCR). However, some species do not secrete profusely, resulting in very little extracted RNA. The ability to measure transcript abundance of antimicrobial peptides in field-collected skin secretions complements proteomic analyses and may provide insight into transcriptional mechanisms that could affect peptide abundance.

Developing a Bacteroides System for Function-Based Screening of DNA from the Human Gut Microbiome.

PubMed

Lam, Kathy N; Martens, Eric C; Charles, Trevor C

2018-01-01

Functional metagenomics is a powerful method that allows the isolation of genes whose role may not have been predicted from DNA sequence. In this approach, first, environmental DNA is cloned to generate metagenomic libraries that are maintained in Escherichia coli, and second, the cloned DNA is screened for activities of interest. Typically, functional screens are carried out using E. coli as a surrogate host, although there likely exist barriers to gene expression, such as lack of recognition of native promoters. Here, we describe efforts to develop Bacteroides thetaiotaomicron as a surrogate host for screening metagenomic DNA from the human gut. We construct a B. thetaiotaomicron-compatible fosmid cloning vector, generate a fosmid clone library using DNA from the human gut, and show successful functional complementation of a B. thetaiotaomicron glycan utilization mutant. Though we were unable to retrieve the physical fosmid after complementation, we used genome sequencing to identify the complementing genes derived from the human gut microbiome. Our results demonstrate that the use of B. thetaiotaomicron to express metagenomic DNA is promising, but they also exemplify the challenges that can be encountered in the development of new surrogate hosts for functional screening. IMPORTANCE Human gut microbiome research has been supported by advances in DNA sequencing that make it possible to obtain gigabases of sequence data from metagenomes but is limited by a lack of knowledge of gene function that leads to incomplete annotation of these data sets. There is a need for the development of methods that can provide experimental data regarding microbial gene function. Functional metagenomics is one such method, but functional screens are often carried out using hosts that may not be able to express the bulk of the environmental DNA being screened. We expand the range of current screening hosts and demonstrate that human gut-derived metagenomic libraries can be introduced into the gut microbe Bacteroides thetaiotaomicron to identify genes based on activity screening. Our results support the continuing development of genetically tractable systems to obtain information about gene function.

A discussion of the merits of random man not excluded and likelihood ratios.

PubMed

Buckleton, John; Curran, James

2008-09-01

DNA mixture interpretation is undertaken either by calculating a LR or an exclusion probability (RMNE or its complement CPI). Debate exists as to which has the greater claim. The merits and drawbacks of the two approaches are discussed. We conclude that the two matters that appear to have real force are: (1) LRs are more difficult to present in court and (2) the RMNE statistic wastes information that should be utilised.

Johann Christoph Sturm's universal mathematics and metaphysics (German Title: Universalmathematik und Metaphysik bei Johann Christoph Sturm)

NASA Astrophysics Data System (ADS)

Leinsle, Ulrich G.

In order to understand Sturm's concept of a universal mathematics as a replacement or complement of metaphysics, one first has to examine the evolution of the idea of a mathesis universalis up to Sturm, and his concept of metaphysics. According to the understanding of those times, natural theology belongs to metaphysics. The last section is concerned with Sturm's statements on the existence of God and his assessments for a physico-theology.

How Do Theories of Cognition and Consciousness in Ancient Indian Thought Systems Relate to Current Western Theorizing and Research?

PubMed Central

Sedlmeier, Peter; Srinivas, Kunchapudi

2016-01-01

Unknown to most Western psychologists, ancient Indian scriptures contain very rich, empirically derived psychological theories that are, however, intertwined with religious and philosophical content. This article represents our attempt to extract the psychological theory of cognition and consciousness from a prominent ancient Indian thought system: Samkhya-Yoga. We derive rather broad hypotheses from this approach that may complement and extend Western mainstream theorizing. These hypotheses address an ancient personality theory, the effects of practicing the applied part of Samkhya-Yoga on normal and extraordinary cognition, as well as different ways of perceiving reality. We summarize empirical evidence collected (mostly without reference to the Indian thought system) in diverse fields of research that allows for making judgments about the hypotheses, and suggest more specific hypotheses to be examined in future research. We conclude that the existing evidence for the (broad) hypotheses is substantial but that there are still considerable gaps in theory and research to be filled. Theories of cognition contained in the ancient Indian systems have the potential to modify and complement existing Western mainstream accounts of cognition. In particular, they might serve as a basis for arriving at more comprehensive theories for several research areas that, so far, lack strong theoretical grounding, such as meditation research or research on aspects of consciousness. PMID:27014150

DeltaPhage—a novel helper phage for high-valence pIX phagemid display

PubMed Central

Nilssen, Nicolay R.; Frigstad, Terje; Pollmann, Sylvie; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger; Løset, Geir Å.

2012-01-01

Phage display has been instrumental in discovery of novel binding peptides and folded domains for the past two decades. We recently reported a novel pIX phagemid display system that is characterized by a strong preference for phagemid packaging combined with low display levels, two key features that support highly efficient affinity selection. However, high diversity in selected repertoires are intimately coupled to high display levels during initial selection rounds. To incorporate this additional feature into the pIX display system, we have developed a novel helper phage termed DeltaPhage that allows for high-valence display on pIX. This was obtained by inserting two amber mutations close to the pIX start codon, but after the pVII translational stop, conditionally inactivating the helper phage encoded pIX. Until now, the general notion has been that display on pIX is dependent on wild-type complementation, making high-valence display unachievable. However, we found that DeltaPhage does facilitate high-valence pIX display when used with a non-suppressor host. Here, we report a side-by-side comparison with pIII display, and we find that this novel helper phage complements existing pIX phagemid display systems to allow both low and high-valence display, making pIX display a complete and efficient alternative to existing pIII phagemid display systems. PMID:22539265

DeltaPhage--a novel helper phage for high-valence pIX phagemid display.

PubMed

Nilssen, Nicolay R; Frigstad, Terje; Pollmann, Sylvie; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger; Løset, Geir Å

2012-09-01

Phage display has been instrumental in discovery of novel binding peptides and folded domains for the past two decades. We recently reported a novel pIX phagemid display system that is characterized by a strong preference for phagemid packaging combined with low display levels, two key features that support highly efficient affinity selection. However, high diversity in selected repertoires are intimately coupled to high display levels during initial selection rounds. To incorporate this additional feature into the pIX display system, we have developed a novel helper phage termed DeltaPhage that allows for high-valence display on pIX. This was obtained by inserting two amber mutations close to the pIX start codon, but after the pVII translational stop, conditionally inactivating the helper phage encoded pIX. Until now, the general notion has been that display on pIX is dependent on wild-type complementation, making high-valence display unachievable. However, we found that DeltaPhage does facilitate high-valence pIX display when used with a non-suppressor host. Here, we report a side-by-side comparison with pIII display, and we find that this novel helper phage complements existing pIX phagemid display systems to allow both low and high-valence display, making pIX display a complete and efficient alternative to existing pIII phagemid display systems.

Complement factor H-related proteins in IgA nephropathy-sometimes a gentle nudge does the trick.

PubMed

Thurman, Joshua M; Laskowski, Jennifer

2017-10-01

Complement activation probably contributes to glomerular inflammation and damage in IgA nephropathy. In this issue, 2 groups report that levels of factor H-related protein 1 are elevated in patients with IgA nephropathy and correlate with disease progression. These studies provide new evidence that the complement cascade is important to the pathogenesis of this disease. These results also suggest that factor H-related protein 1 levels may be useful for identifying those patients at high risk of disease progression. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Genetics Home Reference: Fanconi anemia

MedlinePlus

... D1 Genetic Testing Registry: Fanconi anemia, complementation group D2 Genetic Testing Registry: Fanconi anemia, complementation group E ... ANEMIA, COMPLEMENTATION GROUP D1 FANCONI ANEMIA, COMPLEMENTATION GROUP D2 FANCONI ANEMIA, COMPLEMENTATION GROUP E FANCONI ANEMIA, COMPLEMENTATION ...

The Effect of Ionic Strength on the Haemolytic Activity of Complement

PubMed Central

Wardlaw, A. C.; Walker, H. G.

1963-01-01

The haemolytic activity of guinea-pig complement has been measured in isotonic solutions of various ionic strengths in the range 0.034–0.28 and shown to be maximum at an ionic strength close to 0.08. Haemolytic activity was virtually abolished at ionic strength 0.034, while at 0.28, the complement titre was only about 20 per cent of the value found at the physiological ionic strength 0.155. NaCl, KCl, LiBr and K2SO4 were the electrolytes used to provide ionic strength, and sucrose, mannitol and inositol the non-electrolytes used to maintain isotonicity. Nine permutations of the four electrolytes with the three non-electrolytes were tested and gave similar results. Human and rabbit complements also showed optimum haemolytic activity at ionic strength 0.08–0.10. PMID:13998876

Results from the APOGEE IN-SYNC Orion: parameters and radial velocities for thousands of young stars in the Orion Complex.

NASA Astrophysics Data System (ADS)

Da Rio, Nicola; SDSS Apogee IN-SYNC ancillary program Team

2015-01-01

I will present the results of our characterization of the dynamical status of the young stellar population in the Orion A star forming region. This is based on radial velocity measurements obtained within the SDSS-III Apogee IN-SYNC Orion Survey, which obtained high-resolution spectroscopy of ~3000 objects in the region, from the dense Orion Nebula Cluster - the prototypical nearby region of active massive star formation - to the low-density environments of the L1641 region. We find evidence for kinematic subclustering along the star forming filament, where the stellar component remains kinematically associated to the gas; in the ONC we find that the stellar population is supervirial and currently expanding. We rule out the existence of a controversial candidate foreground cluster to the south of the ONC. These results, complemented with an analysis of the spatial structure of the population, enables critical tests of theories that describe the formation and early evolution of Orion and young clusters in general.

An X-Ray Analysis Database of Photoionization Cross Sections Including Variable Ionization

NASA Technical Reports Server (NTRS)

Wang, Ping; Cohen, David H.; MacFarlane, Joseph J.; Cassinelli, Joseph P.

1997-01-01

Results of research efforts in the following areas are discussed: review of the major theoretical and experimental data of subshell photoionization cross sections and ionization edges of atomic ions to assess the accuracy of the data, and to compile the most reliable of these data in our own database; detailed atomic physics calculations to complement the database for all ions of 17 cosmically abundant elements; reconciling the data from various sources and our own calculations; and fitting cross sections with functional approximations and incorporating these functions into a compact computer code.Also, efforts included adapting an ionization equilibrium code, tabulating results, and incorporating them into the overall program and testing the code (both ionization equilibrium and opacity codes) with existing observational data. The background and scientific applications of this work are discussed. Atomic physics cross section models and calculations are described. Calculation results are compared with available experimental data and other theoretical data. The functional approximations used for fitting cross sections are outlined and applications of the database are discussed.

Strain improvement of chymosin-producing strains of Aspergillus niger var. awamori using parasexual recombination.

PubMed

Bodie, E A; Armstrong, G L; Dunn-Coleman, N S

1994-05-01

Parasexual recombination was used to obtain improved chymosin-producing strains and to perform genetic analysis on existing strains. Chlorate resistance was used to select for a variety of spontaneous nitrate assimilation pathway mutations in strains previously improved for chymosin production using classical strain improvement methods including mutation and screening, and selection for 2-deoxyglucose resistance (dgr). Diploids of these improved strains were generated via parasexual recombination and were isolated on selective media by complementation of nitrate assimilation mutations. A preliminary genetic analysis of diploid and haploid segregants indicated that the dgr trait, resulting in overexpression of chymosin, was recessive. Also, mutations in two different dgr genes resulted in an increased level of chymosin production. When these mutations were combined via parasexual recombination, the resulting haploid segregants produced about 15% more chymosin than either parental strain. CHEF gel electrophoresis was used to determine the chromosomal location of the integrated chymosin DNA sequences, and to verify diploidy in one case where the chromosome composition of two haploid parents differed.

Pneumococcal polysaccharides complexed with C3d bind to human B lymphocytes via complement receptor type 2.

PubMed Central

Griffioen, A W; Rijkers, G T; Janssens-Korpela, P; Zegers, B J

1991-01-01

The immunoregulatory function of the complement system has been the focus of many investigations. In particular, fragments of complement factor C3 have been shown to play a role in B-lymphocyte activation and proliferation, lymphokine production, and the generation of in vitro antibody production. Purified pneumococcal polysaccharides (PS) can induce direct activation of C3 via the alternative pathway. Using sera of C1q-deficient patients and healthy subjects, we demonstrated that C3d, a split product of C3 that is generated after degradation of iC3b, can be bound to PS antigens. The binding of C3d to PS can occur in the absence of specific antibodies. Subsequently, we showed that PS complexed with C3d can be recognized by complement receptor type 2 that is expressed on B cells. Treatment of B cells with a monoclonal antibody recognizing the C3d-binding site of complement receptor type 2 reduces the binding of PS-C3d to the cells. In addition, we showed that PS4 complexed with C3d exerted an increased immunogenicity compared with free PS4. Our results show that the complement system plays a role in the activation of PS-specific B cells, carrying membrane receptors for C3d. Consequently, the complement system plays a regulatory role in the antibody response to T-cell-independent type 2 antigens such as PS. PMID:1826897

A comprehensive strategy for the subtyping of patients with Fanconi anaemia: conclusions from the Spanish Fanconi Anemia Research Network

PubMed Central

Casado, José Antonio; Callén, Elsa; Jacome, Ariana; Río, Paula; Castella, Maria; Lobitz, Stephan; Ferro, Teresa; Muñoz, Arturo; Sevilla, Julián; Cantalejo, Ángeles; Cela, Elena; Cervera, José; Sánchez‐Calero, Jesús; Badell, Isabel; Estella, Jesús; Dasí, Ángeles; Olivé, Teresa; Ortega, Juan José; Rodriguez‐Villa, Antonia; Tapia, María; Molinés, Antonio; Madero, Luis; Segovia, José C; Neveling, Kornelia; Kalb, Reinhard; Schindler, Detlev; Hanenberg, Helmut; Surrallés, Jordi; Bueren, Juan A

2007-01-01

Background Fanconi anaemia is a heterogeneous genetic disease, where 12 complementation groups have been already described. Identifying the complementation group in patients with Fanconi anaemia constitutes a direct procedure to confirm the diagnosis of the disease and is required for the recruitment of these patients in gene therapy trials. Objective To determine the subtype of Fanconi anaemia patients in Spain, a Mediterranean country with a relatively high population (23%) of Fanconi anaemia patients belonging to the gypsy race. Methods Most patients could be subtyped by retroviral complementation approaches in peripheral blood T cells, although some mosaic patients were subtyped in cultured skin fibroblasts. Other approaches, mainly based on western blot analysis and generation of nuclear RAD51 and FANCJ foci, were required for the subtyping of a minor number of patients. Results and conclusions From a total of 125 patients included in the Registry of Fanconi Anaemia, samples from 102 patients were available for subtyping analyses. In 89 cases the subtype could be determined and in 8 cases exclusions of common complementation groups were made. Compared with other international studies, a skewed distribution of complementation groups was observed in Spain, where 80% of the families belonged to the Fanconi anaemia group A (FA‐A) complementation group. The high proportion of gypsy patients, all of them FA‐A, and the absence of patients with FA‐C account for this characteristic distribution of complementation groups. PMID:17105750

The Surface-Exposed Protein SntA Contributes to Complement Evasion in Zoonotic Streptococcus suis.

PubMed

Deng, Simin; Xu, Tong; Fang, Qiong; Yu, Lei; Zhu, Jiaqi; Chen, Long; Liu, Jiahui; Zhou, Rui

2018-01-01

Streptococcus suis is an emerging zoonotic pathogen causing streptococcal toxic shock like syndrome (STSLS), meningitis, septicemia, and even sudden death in human and pigs. Serious septicemia indicates this bacterium can evade the host complement surveillance. In our previous study, a functionally unknown protein SntA of S. suis has been identified as a heme-binding protein, and contributes to virulence in pigs. SntA can interact with the host antioxidant protein AOP2 and consequently inhibit its antioxidant activity. In the present study, SntA is identified as a cell wall anchored protein that functions as an important player in S. suis complement evasion. The C3 deposition and membrane attack complex (MAC) formation on the surface of sntA -deleted mutant strain Δ sntA are demonstrated to be significantly higher than the parental strain SC-19 and the complementary strain CΔ sntA . The abilities of anti-phagocytosis, survival in blood, and in vivo colonization of Δ sntA are obviously reduced. SntA can interact with C1q and inhibit hemolytic activity via the classical pathway. Complement activation assays reveal that SntA can also directly activate classical and lectin pathways, resulting in complement consumption. These two complement evasion strategies may be crucial for the pathogenesis of this zoonotic pathogen. Concerning that SntA is a bifunctional 2',3'-cyclic nucleotide 2'-phosphodiesterase/3'-nucleotidase in many species of Gram-positive bacteria, these complement evasion strategies may have common biological significance.

Cold activation of complement for monitoring the response to interferon in patients with chronic hepatitis C.

PubMed

Akahane, Y; Miyazaki, Y; Naitoh, S; Takeda, K; Tsuda, F; Okamoto, H; Itoh, K; Miyakawa, Y; Mayumi, M

1996-02-01

Because of its specific association with hepatitis C virus (HCV) infection, the cold activation of complement is an easy and inexpensive indicator of HCV viremia. It was evaluated for eligibility as a marker of response to interferon in patients with hepatitis C. The cold activation of complement was determined by the loss or decrease of hemolytic activity with the microtitration method in sera that had been stored at 4 degrees C overnight. We observed the loss of hemolytic activity by the cold activation of complement in 236 (72%) and a decrease in 56 (17%) of 327 sera from patients with HCV-associated chronic liver disease, which was much more (p < 0.001) that in 1 (1%) and 13 (14%), respectively, of 49 sera from patients with chronic liver disease associated with hepatitis B virus infection. Interferon-alpha (total dose 516 x 10(6) units) or interferon-alpha 2b (774 x 10(6) units) was given to 67 patients with chronic hepatitis C, of whom 56 had the cold activation of complement. The response to interferon was evaluated by the clearance of serum HCV RNA at 6 months after the completion of therapy. The cold activation of complement disappeared in 18 patients, of whom 15 (86%) responded. It persisted or fluctuated in the remaining 38 patients, only six (16%) of whom responded to interferon (p < 0.001). The cold activation of complement once disappeared at the completion of interferon and then reappeared in patients who relapsed after completing interferon therapy. These results indicate that the cold activation of complement may be associated with the presence of HCV in blood and a lower rate of durable response after completion of interferon therapy.

Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration

PubMed Central

Garland, Donita L.; Fernandez-Godino, Rosario; Kaur, Inderjeet; Speicher, Kaye D.; Harnly, James M.; Lambris, John D.; Speicher, David W.; Pierce, Eric A.

2014-01-01

Macular degenerations, inherited and age related, are important causes of vision loss. Human genetic studies have suggested perturbation of the complement system is important in the pathogenesis of age-related macular degeneration. The mechanisms underlying the involvement of the complement system are not understood, although complement and inflammation have been implicated in drusen formation. Drusen are an early clinical hallmark of inherited and age-related forms of macular degeneration. We studied one of the earliest stages of macular degeneration which precedes and leads to the formation of drusen, i.e. the formation of basal deposits. The studies were done using a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by a p.Arg345Trp mutation in EFEMP1. The hallmark of DHRD/ML is the formation of drusen at an early age, and gene targeted Efemp1R345W/R345W mice develop extensive basal deposits. Proteomic analyses of Bruch's membrane/choroid and Bruch's membrane in the Efemp1R345W/R345W mice indicate that the basal deposits comprise normal extracellular matrix (ECM) components present in abnormal amounts. The proteomic analyses also identified significant changes in proteins with immune-related function, including complement components, in the diseased tissue samples. Genetic ablation of the complement response via generation of Efemp1R345W/R345W:C3−/− double-mutant mice inhibited the formation of basal deposits. The results demonstrate a critical role for the complement system in basal deposit formation, and suggest that complement-mediated recognition of abnormal ECM may participate in basal deposit formation in DHRD/ML and perhaps other macular degenerations. PMID:23943789

Chemical studies on damages of Escherichea coli by the immune bactericidal reaction. II. Release of phosphatidylethanolamine from a phospholipase A-deficient mutant of E. coli during the immune bactericidal reaction.

PubMed

Inoue, K; Yano, K; Amano, T

1974-12-01

When an antibody-sensitized, phospholipase A-deficient mutant of Escherichia coli B/SM was treated with complement in the absence of lysozyme, bacterial phosphatidylethanolamine (PE) was liberated into the lipid fraction of the surrounding medium, but only traces of its degradation products were found in this fraction. Therefore, most of the degradation of bacterial PE to FFA and LPE observed in the usual immune bactericidal reaction (Inoue et al., 1974) must be the result of the action of bacterial phospholipase A which is activated or becomes accessible to its substrate on formation of lesions by complement. The mechanism of complement-mediated formation of membrane lesions is discussed on the basis of these results.

Polysaccharides from Sargassum thunbergii: Monthly variations and anti-complement and anti-tumour activities.

PubMed

Jin, Weihua; Liu, Ge; Zhong, Weihong; Sun, Chaomin; Zhang, Quanbin

2017-12-01

Monthly variations of polysaccharides from Sargassum thunbergii and their anti-complement and anti-tumour activities were investigated. It was observed that an increase in fucose and total sugar contents occurred during the growth period (from early April to mid-June), accompanied by a decrease in molar ratios of other monosaccharides to fucose. The highest yields were obtained from early July to early September, which was in accordance with the significant increase in molar ratio of glucose to fucose and decrease in molar ratio of other monosaccharides to fucose. And the above results suggested that S. Thunbergii synthesized large amount of laminaran, the storage substance of brown algae, during the senescence period. However, sulfate contents were relatively stable in the life cycle of S. thunbergii. These results suggested that S. thunbergii synthesized complex sulfated heteropolysacchairdes during inactive period, while during other periods, it synthesized more sulfated galactofucan. All polysaccharides showed anti-complement activity, suggesting that the harvesting time did not influence the anti-complement activities. In the anti-tumour assay in vitro, the polysaccharides taken during the senescence period had much lower anti-tumour activity, suggesting that fucoidan, but not laminaran, determined the anti-tumour activities. Therefore, polysaccharides from S. thunbergii might have great potential in anti-complement and anti-tumour application. Copyright © 2017 Elsevier B.V. All rights reserved.

Reproductive consequences of farmland heterogeneity in little owls (Athene noctua).

PubMed

Michel, Vanja T; Naef-Daenzer, Beat; Keil, Herbert; Grüebler, Martin U

2017-04-01

The amount of high-quality habitat patches, their distribution, and the resource accessibility therein play a key role in regulating habitat effects on reproductive success. Heterogeneous habitats offer non-substitutable resources (e.g. nest sites and food) and substitutable resources (e.g. different types of food) in close proximity, thereby facilitating landscape complementation and supplementation. However, it remains poorly understood how spatial resource separation in homogeneous agricultural landscapes affects reproductive success. To fill this gap, we investigated the relationships between farmland heterogeneity and little owl (Athene noctua) reproductive success, including potential indirect effects of the heterogeneity-dependent home-range size on reproduction. Little owl home-ranges were related to field heterogeneity in summer and to structural heterogeneity in winter. Clutch size was correlated with the amount of food-rich habitat close to the nest irrespective of female home-range size, suggesting importance of landscape complementation. Nestling survival was positively correlated with male home-range size, suggesting importance of landscape supplementation. At the same time, fledgling condition was negatively correlated with male home-range size. We conclude that decreasing farmland heterogeneity constrains population productivity by two processes: increasing separation of food resources from nest or roost sites results in low landscape complementation, and reduction of alternative food resources limits landscape supplementation. Our results suggest that structural heterogeneity affects landscape complementation, whereas the heterogeneity and management of farmland fields affect landscape supplementation. Thus, to what extent a reduction of the heterogeneity within agricultural landscapes results in species-specific habitat degradation depends on the ecological processes (i.e. landscape complementation or supplementation) which are affected.

Deep learning-based subdivision approach for large scale macromolecules structure recovery from electron cryo tomograms

PubMed Central

Xu, Min; Chai, Xiaoqi; Muthakana, Hariank; Liang, Xiaodan; Yang, Ge; Zeev-Ben-Mordehai, Tzviya; Xing, Eric P.

2017-01-01

Abstract Motivation: Cellular Electron CryoTomography (CECT) enables 3D visualization of cellular organization at near-native state and in sub-molecular resolution, making it a powerful tool for analyzing structures of macromolecular complexes and their spatial organizations inside single cells. However, high degree of structural complexity together with practical imaging limitations makes the systematic de novo discovery of structures within cells challenging. It would likely require averaging and classifying millions of subtomograms potentially containing hundreds of highly heterogeneous structural classes. Although it is no longer difficult to acquire CECT data containing such amount of subtomograms due to advances in data acquisition automation, existing computational approaches have very limited scalability or discrimination ability, making them incapable of processing such amount of data. Results: To complement existing approaches, in this article we propose a new approach for subdividing subtomograms into smaller but relatively homogeneous subsets. The structures in these subsets can then be separately recovered using existing computation intensive methods. Our approach is based on supervised structural feature extraction using deep learning, in combination with unsupervised clustering and reference-free classification. Our experiments show that, compared with existing unsupervised rotation invariant feature and pose-normalization based approaches, our new approach achieves significant improvements in both discrimination ability and scalability. More importantly, our new approach is able to discover new structural classes and recover structures that do not exist in training data. Availability and Implementation: Source code freely available at http://www.cs.cmu.edu/∼mxu1/software. Contact: mxu1@cs.cmu.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28881965

Activated complement components and complement activator molecules on the surface of cell‐derived microparticles in patients with rheumatoid arthritis and healthy individuals

PubMed Central

Biró, Éva; Nieuwland, Rienk; Tak, Paul P; Pronk, Loes M; Schaap, Marianne C L; Sturk, Augueste; Hack, C Erik

2007-01-01

Objectives In vitro, microparticles can activate complement via the classical pathway. If demonstrable ex vivo, this mechanism may contribute to the pathogenesis of rheumatoid arthritis (RA). We therefore investigated the presence of activated complement components and complement activator molecules on the surface of cell‐derived microparticles of RA patients and healthy individuals. Methods Microparticles from synovial fluid (n = 8) and plasma (n = 9) of 10 RA patients and plasma of sex‐ and age‐matched healthy individuals (n = 10) were analysed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C‐reactive protein (CRP), serum amyloid P component (SAP), immunoglobulin (Ig) M, IgG). Results Microparticles with bound C1q, C4, and/or C3 were abundant in RA synovial fluid, while in RA and control plasma much lower levels were present. Microparticles with bound C1q correlated with those with bound C3 in synovial fluid (r = 0.961, p = 0.0001), and with those with bound C4 in plasma (RA: r = 0.908, p = 0.0007; control: r = 0.632, p = 0.0498), indicating classical pathway activation. In synovial fluid, microparticles with IgM and IgG correlated with those with C1q (r = 0.728, p = 0.0408; r = 0.952, p = 0.0003, respectively), and in plasma, microparticles with CRP correlated with those with C1q (RA: r = 0.903, p = 0.0021; control: r = 0.683, p = 0.0296), implicating IgG and IgM in the classical pathway activation in RA synovial fluid, and CRP in the low level classical pathway activation in plasma. Conclusions This study demonstrates the presence of bound complement components and activator molecules on microparticles ex vivo, and supports their role in low grade complement activation in plasma and increased complement activation in RA synovial fluid. PMID:17261534

Complement-fixing properties of antinuclear antibodies distinguish drug-induced lupus from systemic lupus erythematosus.

PubMed

Rubin, R L; Teodorescu, M; Beutner, E H; Plunkett, R W

2004-01-01

The immunofluorescence antinuclear antibody (ANA) test has been widely used to monitor autoimmune disease, but its value for diagnostic purposes is compromised by low specificity and high prevalence in disease-free individuals. The capacity of autoantibodies to fix serum complement proteins when bound to antigen is an important effector function because this property is associated with acute and chronic inflammatory processes. The current study evaluates the complement-fixing properties of antinuclear antibodies (CANA) in three well-defined and clinically-related patient groups: systemic lupus erythematosus (SLE), drug-induced lupus (DIL) and drug-induced autoimmunity (DIA). Of 20 patients diagnosed with SLE, 90% displayed complement-fixing ANA while this feature was present in only two of 18 patients with DIL and no patients with DIA without associated disease even though the mean ANA titres were similar among these patient groups. CANA was significantly correlated with anti-Sm activity. Because SLE but not DIL or DIA can be a life-threatening disease associated with complement consumption in vivo, these results demonstrate that measurement of CANA is a diagnostically useful tool and may have immunopathologic implications.

Complement Effectors of Inflammation in Cystic Fibrosis Lung Fluid Correlate with Clinical Measures of Disease.

PubMed

Sass, Laura A; Hair, Pamela S; Perkins, Amy M; Shah, Tushar A; Krishna, Neel K; Cunnion, Kenji M

2015-01-01

In cystic fibrosis (CF), lung damage is mediated by a cycle of obstruction, infection, and inflammation. Here we explored complement inflammatory effectors in CF lung fluid. In this study soluble fractions (sols) from sputum samples of 15 CF patients were assayed for complement effectors and analyzed with clinical measurements. The pro-inflammatory peptide C5a was increased 4.8-fold (P = 0.04) in CF sols compared with controls. Incubation of CF sols with P. aeruginosa or S. aureus increased C5a concentration 2.3-fold (P = 0.02). A peptide inhibitor of complement C1 (PIC1) completely blocked the increase in C5a concentration from P. aeruginosa in CF sol in vitro (P = 0.001). C5a concentration in CF sol correlated inversely with body mass index (BMI) percentile in children (r = -0.77, P = 0.04). C3a, which has anti-inflammatory effects, correlated positively with FEV1% predicted (rs = 0.63, P = 0.02). These results suggest that complement effectors may significantly impact inflammation in CF lung fluid.

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

PubMed Central

Pietrocola, Giampiero; Rindi, Simonetta; Rosini, Roberto; Buccato, Scilla

2016-01-01

The group B Streptococcus (GBS) is a leading cause of neonatal invasive disease. GBS bacteria are surrounded by a thick capsular polysaccharide that is a potent inhibitor of complement deposition via the alternative pathway. Several of its surface molecules can however activate the classical and lectin complement pathways, rendering this species still vulnerable to phagocytic killing. In this study we have identified a novel secreted protein named complement interfering protein (CIP) that downregulates complement activation via the classical and lectin pathways, but not the alternative pathway. The CIP protein showed high affinity toward C4b and inhibited its interaction with C2, presumably preventing the formation of the C4bC2a convertase. Addition of recombinant CIP to GBS cip-negative bacteria resulted in decreased deposition of C3b on their surface and in diminished phagocytic killing in a whole-blood assay. Our data reveal a novel strategy exploited by GBS to counteract innate immunity and could be valuable for the development of anti-infective agents against this important pathogen. PMID:26608922

A reversible Renilla luciferase protein complementation assay for rapid identification of protein-protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus.

PubMed

Lund, Christian H; Bromley, Jennifer R; Stenbæk, Anne; Rasmussen, Randi E; Scheller, Henrik V; Sakuragi, Yumiko

2015-01-01

A growing body of evidence suggests that protein-protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. We tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. Our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Analysis of the interaction between respiratory syncytial virus and lipid-rafts in Hep2 cells during infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Gaie; Jeffree, Chris E.; McDonald, Terence

2004-10-01

The assembly of respiratory syncytial virus (RSV) in lipid-rafts was examined in Hep2 cells. Confocal and electron microscopy showed that during RSV assembly, the cellular distribution of the complement regulatory proteins, decay accelerating factor (CD55) and CD59, changes and high levels of these cellular proteins are incorporated into mature virus filaments. The detergent-solubility properties of CD55, CD59, and the RSV fusion (F) protein were found to be consistent with each protein being located predominantly within lipid-raft structures. The levels of these proteins in cell-released virus were examined by immunoelectronmicroscopy and found to account for between 5% and 15% of themore » virus attachment (G) glycoprotein levels. Collectively, our findings suggest that an intimate association exists between RSV and lipid-raft membranes and that significant levels of these host-derived raft proteins, such as those regulating complement activation, are subsequently incorporated into the envelope of mature virus particles.« less

Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myhre, Marit Renee; Olsen, Gunn-Hege; Gosert, Rainer

High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectiousmore » progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.« less

PUBLIC HEALTH ASPECTS OF LYMPHOGRANULOMA VENEREUM

PubMed Central

Koch, Richard A.; McDonald, Ruth S.; Marshall, Max S.

1949-01-01

The clinical symptoms of lymphogranuloma venereum with the serious pathologic changes often occurring in the late stages of the disease warrant greater attention to the disease. The reported ratio of cases of lymphogranuloma venereum to cases of syphilis and gonorrhea is much higher in San Francisco than in other metropolitan ports of western United States, apparently because of greater use of diagnostic tests for the disease. Tests of persons likely to be exposed and other persons not likely to be exposed to venereal diseases indicate that a positive reaction to a Frei test implies past or present infection with lymphogranuloma venereum. Positive reactions to complement fixation tests are notably more frequent than positive response to Frei tests. The complement fixation test appears to be an unreliable diagnostic aid. The frequency of positive reactions associated with other venereal diseases, and their infrequency otherwise, suggests that lymphogranuloma venereum may exist, unrecognized, in many persons, who may be, potentially at least, carriers of the disease. PMID:18147525

Optimal economic order quantity for buyer-distributor-vendor supply chain with backlogging derived without derivatives

NASA Astrophysics Data System (ADS)

Teng, Jinn-Tsair; Cárdenas-Barrón, Leopoldo Eduardo; Lou, Kuo-Ren; Wee, Hui Ming

2013-05-01

In this article, we first complement an inappropriate mathematical error on the total cost in the previously published paper by Chung and Wee [2007, 'Optimal the Economic Lot Size of a Three-stage Supply Chain With Backlogging Derived Without Derivatives', European Journal of Operational Research, 183, 933-943] related to buyer-distributor-vendor three-stage supply chain with backlogging derived without derivatives. Then, an arithmetic-geometric inequality method is proposed not only to simplify the algebraic method of completing prefect squares, but also to complement their shortcomings. In addition, we provide a closed-form solution to integral number of deliveries for the distributor and the vendor without using complex derivatives. Furthermore, our method can solve many cases in which their method cannot, because they did not consider that a squared root of a negative number does not exist. Finally, we use some numerical examples to show that our proposed optimal solution is cheaper to operate than theirs.

A large hadron electron collider at CERN

DOE PAGES

Abelleira Fernandez, J. L.

2015-04-06

This document provides a brief overview of the recently published report on the design of the Large Hadron Electron Collider (LHeC), which comprises its physics programme, accelerator physics, technology and main detector concepts. The LHeC exploits and develops challenging, though principally existing, accelerator and detector technologies. This summary is complemented by brief illustrations of some of the highlights of the physics programme, which relies on a vastly extended kinematic range, luminosity and unprecedented precision in deep inelastic scattering. Illustrations are provided regarding high precision QCD, new physics (Higgs, SUSY) and eletron-ion physics. The LHeC is designed to run synchronously withmore » the LHC in the twenties and to achieve an integrated luminosity of O(100)fb –1. It will become the cleanest high resolution microscope of mankind and will substantially extend as well as complement the investigation of the physics of the TeV energy scale, which has been enabled by the LHC.« less

Parental determinants of offspring head circumference using a sample of patients attending a government hospital in Lagos, Nigeria.

PubMed

Taiwo, I A; Adeleye, A

2013-01-01

Head circumference at birth is an important neonatal parameter in view of its association with perinatal and postnatal morbidity and mortality. It is an indicator of brain volume and a tool for assessing the development of the central nervous system. Being a complex hereditary trait, predicting baby's head circumference from parental anthropometrics could complement the already existing ultrasonographic method of prediction. To identify the parental anthropometric determinants of baby's head circumference in Lagos, Nigeria, using a sample of patients attending a government hospital. Parental anthropometric parameters were obtained from 250 couples. The baby's head circumference was measured immediately after birth. The data were subjected to multivariate analysis. The parental variables that were most predictive of babies' head circumference were mid-parental weight, maternal height, maternal weight gain during pregnancy and maternal age. Assessment of these parental attributes can complement ultrasonographic data in predicting baby's head circumference for better perinatal outcome.

Expression of complement membrane regulators membrane cofactor protein (CD46), decay accelerating factor (CD55), and protectin (CD59) in human malignant gliomas.

PubMed Central

Mäenpää, A.; Junnikkala, S.; Hakulinen, J.; Timonen, T.; Meri, S.

1996-01-01

Gliomas are malignant brain tumors, which, despite recent progress in surgical and radiological treatment, still have a poor prognosis. Since gliomas apparently resist immunological clearance mechanisms, we became interested in examining bow gliomas resist killing by the human complement system. The resistance of human cells to complement-mediated damage is, in large part, mediated by specific inhibitors of complement:membrane cofactor protein (CD46), decay-accelerating factor (CD55), and protectin (CD59). In the present study we examined the expression of complement regulators in 14 human glioma tumors and in 7 glioma cell lines (U251, U87, HS683, U373, U138, U118, and H2). Protectin was found to be strongly expressed by all glioma tumors and cell lines. Northern blotting analysis demonstrated the typical pattern of four to five protectin mRNAs in the glioma cells. Except for blood vessels, the expression of decay-accelerating factor was weak or absent in the tumors in situ, whereas in the cell lines its expression varied, ranging from negative to intermediate. Membrane cofactor protein was moderately expressed by all the cell lines but only weakly in the tumors. Cell-killing experiments demonstrated that the glioma cell lines were exceptionally resistant to C-mediated lysis. Five of the seven cell lines (U373, HS683, U118, U138, and H2) resisted complement lysis under conditions where most other cell lines were sensitive to killing. Neutralization experiments using specific monoclonal antibodies indicated that protectin was functionally the most important complement regulator in the glioma cells. The killing of the U87 and U251 cells could be significantly increased by a blocking anti-protectin monoclonal antibody, whereas for the other cell lines only moderate or no response was observed. The H2 cell line resisted killing by all antibodies and by complement. These results show that protectin is the most important complement regulator on human glioma cells. The exceptional complement resistance of some glioma cell lines suggests that they may utilize other, hitherto less well characterized, mechanisms to resist complement killing. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 PMID:8644856

Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies

PubMed Central

Meulenbroek, Elisabeth M.; de Haas, Masja; Brouwer, Conny; Folman, Claudia; Zeerleder, Sacha S.; Wouters, Diana

2015-01-01

In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the isotype of the anti-erythrocyte autoantibodies is, therefore, crucial. However, detection of IgM autoantibodies can be challenging. We, therefore, set out to improve the detection of anti-erythrocyte IgM. Direct detection using a flow cytometry-based approach did not yield satisfactory improvements. Next, we analyzed whether the presence of complement C3 on a patient’s erythrocytes could be used for indirect detection of anti-erythrocyte IgM. To this end, we fractionated patients’ sera by size exclusion chromatography and tested which fractions yielded complement deposition on erythrocytes. Strikingly, we found that all patients with C3 on their erythrocytes according to standard diagnostic tests had an IgM anti-erythrocyte component that could activate complement, even if no such autoantibody had been detected with any other test. This also included all tested patients with only IgG and C3 on their erythrocytes, who would previously have been classified as having an IgG-only mediated autoimmune hemolytic anemia. Depleting patients’ sera of either IgG or IgM and testing the remaining complement activation confirmed this result. In conclusion, complement activation in autoimmune hemolytic anemia is mostly IgM-mediated and the presence of covalent C3 on patients’ erythrocytes can be taken as a footprint of the presence of anti-erythrocyte IgM. Based on this finding, we propose a diagnostic workflow that will aid in choosing the optimal treatment strategy. PMID:26354757

Trichinella spiralis Calreticulin Binds Human Complement C1q As an Immune Evasion Strategy.

PubMed

Zhao, Limei; Shao, Shuai; Chen, Yi; Sun, Ximeng; Sun, Ran; Huang, Jingjing; Zhan, Bin; Zhu, Xinping

2017-01-01

As a multicellular parasitic nematode, Trichinella spiralis regulates host immune responses by producing a variety of immunomodulatory molecules to escape from host immune attack, but the mechanisms underlying the immune evasion are not well understood. Here, we identified that T. spiralis calreticulin ( Ts -CRT), a Ca 2+ -binding protein, facilitated T. spiralis immune evasion by interacting with the first component of human classical complement pathway, C1q. In the present study, Ts -CRT was found to be expressed on the surface of different developmental stages of T. spiralis as well as in the secreted products of adult and muscle larval worms. Functional analysis identified that Ts -CRT was able to bind to human C1q, resulting in the inhibition of C1q-initiated complement classical activation pathway reflected by reduced C4/C3 generation and C1q-dependent lysis of antibody-sensitized sheep erythrocytes. Moreover, recombinant Ts -CRT (r Ts -CRT) binding to C1q suppressed C1q-induced THP-1-derived macrophages chemotaxis and reduced monocyte-macrophages release of reactive oxygen intermediates (ROIs). Blocking Ts -CRT on the surface of newborn larvae (NBL) of T. spiralis with anti- Ts -CRT antibody increased the C1q-mediated adherence of monocyte-macrophages to larvae and impaired larval infectivity. All of these results suggest that T. spiralis -expressed Ts -CRT plays crucial roles in T. spiralis immune evasion and survival in host mostly by directly binding to host complement C1q, which not only reduces C1q-mediated activation of classical complement pathway but also inhibits the C1q-induced non-complement activation of macrophages.

Trichinella spiralis Calreticulin Binds Human Complement C1q As an Immune Evasion Strategy

PubMed Central

Zhao, Limei; Shao, Shuai; Chen, Yi; Sun, Ximeng; Sun, Ran; Huang, Jingjing; Zhan, Bin; Zhu, Xinping

2017-01-01

As a multicellular parasitic nematode, Trichinella spiralis regulates host immune responses by producing a variety of immunomodulatory molecules to escape from host immune attack, but the mechanisms underlying the immune evasion are not well understood. Here, we identified that T. spiralis calreticulin (Ts-CRT), a Ca2+-binding protein, facilitated T. spiralis immune evasion by interacting with the first component of human classical complement pathway, C1q. In the present study, Ts-CRT was found to be expressed on the surface of different developmental stages of T. spiralis as well as in the secreted products of adult and muscle larval worms. Functional analysis identified that Ts-CRT was able to bind to human C1q, resulting in the inhibition of C1q-initiated complement classical activation pathway reflected by reduced C4/C3 generation and C1q-dependent lysis of antibody-sensitized sheep erythrocytes. Moreover, recombinant Ts-CRT (rTs-CRT) binding to C1q suppressed C1q-induced THP-1-derived macrophages chemotaxis and reduced monocyte–macrophages release of reactive oxygen intermediates (ROIs). Blocking Ts-CRT on the surface of newborn larvae (NBL) of T. spiralis with anti-Ts-CRT antibody increased the C1q-mediated adherence of monocyte–macrophages to larvae and impaired larval infectivity. All of these results suggest that T. spiralis-expressed Ts-CRT plays crucial roles in T. spiralis immune evasion and survival in host mostly by directly binding to host complement C1q, which not only reduces C1q-mediated activation of classical complement pathway but also inhibits the C1q-induced non-complement activation of macrophages. PMID:28620388

Coating of human decay accelerating factor (hDAF) onto medical devices to improve biocompatibility.

PubMed

Watkins, N J; Braidley, P; Bray, C J; Savill, C M; White, D J

1997-12-01

In passing blood through an artificial circulatory system, the blood is exposed to surfaces that result in activation of the complement system. The consequences of the activation of complement can be extremely serious for the patient ranging from mild discomfort to respiratory distress and even anaphylaxis. An entirely novel approach was to express recombinant GPI anchored human decay accelerating factor (hDAF) using the baculovirus system and then coat the recombinant protein onto the surfaces of these materials to reduce complement activation. Expression of hDAF in Sf9 cells was shown by ELISA, FACS analysis, and Western blot. Functional activity was tested by CH50 assay. For the coating experiments a small scale model of a cardiovascular bypass circuit constructed from COBE tubing was used. hDAF was either coated onto the circuit using adsorption or covalently linked via the photoreactive crosslinker, p-azidobenzoyl hydrazide. After coating, heparinised human blood was pumped around the circuit and samples were collected into EDTA collection tubes at different time points. Complement activation was measured using a Quidel C3a-des-arg EIA. The photolinked circuits gave a reduction in C3a production of 20-50%, compared to 10-20% seen with an absorbed hDAF circuit. Furthermore, the inhibition of complement was seen over the whole time scale of the photolinked circuit, 60-90 min, whilst in the adsorbed circuit inhibition was not seen to a significant degree after 60 min. The time scale of a standard cardiac bypass is 45-90 min, therefore, the photolinked circuit results are encouraging, as significant inhibition of complement activation is seen within this time frame.

Strategic Planning for Chronic Disease Prevention in Rural America: Looking Through a PRISM Lens.

PubMed

Honeycutt, Amanda A; Wile, Kristina; Dove, Cassandra; Hawkins, Jackie; Orenstein, Diane

2015-01-01

Community-level strategic planning for chronic disease prevention. To share the outcomes of the strategic planning process used by Mississippi Delta stakeholders to prevent and reduce the negative impacts of chronic disease in their communities. A key component of strategic planning was participants' use of the Prevention Impacts Simulation Model (PRISM) to project the reduction, compared with the status quo, in deaths and costs from implementing interventions in Mississippi Delta communities. Participants in Mississippi Delta strategic planning meetings used PRISM, a user-friendly, evidence-based simulation tool that includes 22 categories of policy, systems, and environmental change interventions, to pose what-if questions that explore the likely short- and long-term effects of an intervention or any desired combination of the 22 categories of chronic disease intervention programs and policies captured in PRISM. These categories address smoking, air pollution, poor nutrition, and lack of physical activity. Strategic planning participants used PRISM outputs to inform their decisions and actions to implement interventions. Rural communities in the Mississippi Delta. A diverse group of 29 to 34 local chronic disease prevention stakeholders, known as the Mississippi Delta Strategic Alliance. Community plans and actions that were developed and implemented as a result of local strategic planning. Existing strategic planning efforts were complemented by the use of PRISM. The Mississippi Delta Strategic Alliance decided to implement new interventions to improve air quality and transportation and to expand existing interventions to reduce tobacco use and increase access to healthy foods. They also collaborated with the Department of Transportation to raise awareness and use of the current transportation network. The Mississippi Delta Strategic Alliance strategic planning process was complemented by the use of PRISM as a tool for strategic planning, which led to the implementation of new and strengthened chronic disease prevention interventions and policies in the Mississippi Delta.

The spectrum of renal thrombotic microangiopathy in lupus nephritis

PubMed Central

2013-01-01

Introduction Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Methods Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. Results In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group. Renal TMA (hazard ratio (HR): 2.772, 95% confidence interval: 1.009 to 7.617, P = 0.048) was an independent risk factor for renal outcome in patients with lupus nephritis. The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P = 0.007). Conclusions There were various causes of renal TMA in lupus nephritis. Complement over-activation via both classical and alternative pathways might play an important role in the pathogenesis of renal TMA in lupus nephritis. PMID:23320601

Synergy between the classical and alternative pathways of complement is essential for conferring effective protection against the pandemic influenza A(H1N1) 2009 virus infection

PubMed Central

Rattan, Ajitanuj; Pawar, Shailesh D.; Nawadkar, Renuka; Kulkarni, Neeraja

2017-01-01

The pandemic influenza A(H1N1) 2009 virus caused significant morbidity and mortality worldwide thus necessitating the need to understand the host factors that influence its control. Previously, the complement system has been shown to provide protection during the seasonal influenza virus infection, however, the role of individual complement pathways is not yet clear. Here, we have dissected the role of intact complement as well as of its individual activation pathways during the pandemic influenza virus infection using mouse strains deficient in various complement components. We show that the virus infection in C3-/- mice results in increased viral load and 100% mortality, which can be reversed by adoptive transfer of naïve wild-type (WT) splenocytes, purified splenic B cells, or passive transfer of immune sera from WT, but not C3-/- mice. Blocking of C3a and/or C5a receptor signaling in WT mice using receptor antagonists and use of C3aR-/- and C5aR-/- mice showed significant mortality after blocking/ablation of C3aR, with little or no effect after blocking/ablation of C5aR. Intriguingly, deficiency of C4 and FB in mice resulted in only partial mortality (24%-32%) suggesting a necessary cross-talk between the classical/lectin and alternative pathways for providing effective protection. In vitro virus neutralization experiments performed to probe the cross-talk between the various pathways indicated that activation of the classical and alternative pathways in concert, owing to coating of viral surface by antibodies, is needed for its efficient neutralization. Examination of the virus-specific complement-binding antibodies in virus positive subjects showed that their levels vary among individuals. Together these results indicate that cooperation between the classical and alternative pathways not only result in efficient direct neutralization of the pandemic influenza virus, but also lead to the optimum generation of C3a, which when sensed by the immune cells along with the antigen culminates in generation of effective protective immune responses. PMID:28301559

DNA Sequence Variants in PPARGC1A, a Gene Encoding a Coactivator of the ω-3 LCPUFA Sensing PPAR-RXR Transcription Complex, Are Associated with NV AMD and AMD-Associated Loci in Genes of Complement and VEGF Signaling Pathways

PubMed Central

SanGiovanni, John Paul; Chen, Jing; Sapieha, Przemyslaw; Aderman, Christopher M.; Stahl, Andreas; Clemons, Traci E.; Chew, Emily Y.; Smith, Lois E. H.

2013-01-01

Background Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and use of peroxisome proliferator activator receptor (PPAR)-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG) co-activator 1 alpha (PPARGC1A), a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR) transcription complex, may influence neovascularization (NV) in age-related macular degeneration (AMD). Methods We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A. Results A DNA coding variant (rs3736265) and a 3'UTR-resident regulatory variant (rs3774923) in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs). SNP-SNP interactions existed for NV AMD (P<0.005) with rs3736265 and a AMD-associated variant in complement factor B (CFB, rs512559). PPARGC1A influences activation of the AMD-associated complement component 3 (C3) promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P≤0.003) of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033), a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678) showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P≤0.003). C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice – these animals also showed 70% reduction in retinal NV (P≤0.001). Conclusion Ligands and co-activators of the ω-3 LCPUFA sensing PPAR-RXR axis may influence retinal angiogenesis in NV AMD via the complement and VEGF signaling systems. We have linked the co-activator of a lipid-sensing transcription factor (PPARG co-activator 1 alpha, PPARGC1A) to age-related macular degeneration (AMD) and AMD-associated genes. PMID:23335958

The post-genomic era of biological network alignment.

PubMed

Faisal, Fazle E; Meng, Lei; Crawford, Joseph; Milenković, Tijana

2015-12-01

Biological network alignment aims to find regions of topological and functional (dis)similarities between molecular networks of different species. Then, network alignment can guide the transfer of biological knowledge from well-studied model species to less well-studied species between conserved (aligned) network regions, thus complementing valuable insights that have already been provided by genomic sequence alignment. Here, we review computational challenges behind the network alignment problem, existing approaches for solving the problem, ways of evaluating their alignment quality, and the approaches' biomedical applications. We discuss recent innovative efforts of improving the existing view of network alignment. We conclude with open research questions in comparative biological network research that could further our understanding of principles of life, evolution, disease, and therapeutics.

A Shuttle Derived Vehicle launch system

NASA Technical Reports Server (NTRS)

Tewell, J. R.; Buell, D. N.; Ewing, E. S.

1982-01-01

This paper describes a Shuttle Derived Vehicle (SDV) launch system presently being studied for the NASA by Martin Marietta Aerospace which capitalizes on existing Shuttle hardware elements to provide increased accommodations for payload weight, payload volume, or both. The SDV configuration utilizes the existing solid rocket boosters, external tank and the Space Shuttle main engines but replaces the manned orbiter with an unmanned, remotely controlled cargo carrier. This cargo carrier substitution more than doubles the performance capability of the orbiter system and is realistically achievable for minimal cost. The advantages of the SDV are presented in terms of performance and economics. Based on these considerations, it is concluded that an unmanned SDV offers a most attractive complement to the present Space Transportation System.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delahaye, J-P.; Ankenbrandt, C.; Bogacz, A.

A Neutrino Factory where neutrinos of all species are produced in equal quantities by muon decay is described as a facility at the intensity frontier for exquisite precision providing ideal conditions for ultimate neutrino studies and the ideal complement to Long Baseline Facilities like LBNF at Fermilab. It is foreseen to be built in stages with progressively increasing complexity and performance, taking advantage of existing or proposed facilities at an existing laboratory like Fermilab. A tentative layout based on a recirculating linac providing opportunities for considerable saving is discussed as well as its possible evolution toward a muon collider ifmore » and when requested by Physics. Tentative parameters of the various stages are presented as well as the necessary R&D to address the technological issues and demonstrate their feasibility.« less

Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients

PubMed Central

McCormack, Mark; Gui, Hongsheng; Ingason, Andrés; Speed, Doug; Wright, Galen E.B.; Zhang, Eunice J.; Secolin, Rodrigo; Yasuda, Clarissa; Kwok, Maxwell; Wolking, Stefan; Becker, Felicitas; Rau, Sarah; Avbersek, Andreja; Heggeli, Kristin; Leu, Costin; Depondt, Chantal; Sills, Graeme J.; Marson, Anthony G.; Auce, Pauls; Brodie, Martin J.; Francis, Ben; Johnson, Michael R.; Koeleman, Bobby P.C.; Striano, Pasquale; Coppola, Antonietta; Zara, Federico; Kunz, Wolfram S.; Sander, Josemir W.; Lerche, Holger; Klein, Karl Martin; Weckhuysen, Sarah; Krenn, Martin; Gudmundsson, Lárus J.; Stefánsson, Kári; Krause, Roland; Shear, Neil; Ross, Colin J.D.; Delanty, Norman; Pirmohamed, Munir; Carleton, Bruce C.; Cendes, Fernando; Lopes-Cendes, Iscia; Liao, Wei-ping; O'Brien, Terence J.; Sisodiya, Sanjay M.; Cherny, Stacey; Kwan, Patrick; Baum, Larry

2018-01-01

Objective To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. Methods We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. Results We report an association between a rare variant in the complement factor H–related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 × 10–11; odds ratio [95% confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. Conclusions The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H–related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients. PMID:29288229

A New Integrated Threshold Selection Methodology for Spatial Forecast Verification of Extreme Events

NASA Astrophysics Data System (ADS)

Kholodovsky, V.

2017-12-01

Extreme weather and climate events such as heavy precipitation, heat waves and strong winds can cause extensive damage to the society in terms of human lives and financial losses. As climate changes, it is important to understand how extreme weather events may change as a result. Climate and statistical models are often independently used to model those phenomena. To better assess performance of the climate models, a variety of spatial forecast verification methods have been developed. However, spatial verification metrics that are widely used in comparing mean states, in most cases, do not have an adequate theoretical justification to benchmark extreme weather events. We proposed a new integrated threshold selection methodology for spatial forecast verification of extreme events that couples existing pattern recognition indices with high threshold choices. This integrated approach has three main steps: 1) dimension reduction; 2) geometric domain mapping; and 3) thresholds clustering. We apply this approach to an observed precipitation dataset over CONUS. The results are evaluated by displaying threshold distribution seasonally, monthly and annually. The method offers user the flexibility of selecting a high threshold that is linked to desired geometrical properties. The proposed high threshold methodology could either complement existing spatial verification methods, where threshold selection is arbitrary, or be directly applicable in extreme value theory.

Simulation of Healing Threshold in Strain-Induced Inflammation Through a Discrete Informatics Model.

PubMed

Ibrahim, Israr Bin M; Sarma O V, Sanjay; Pidaparti, Ramana M

2018-05-01

Respiratory diseases such as asthma and acute respiratory distress syndrome as well as acute lung injury involve inflammation at the cellular level. The inflammation process is very complex and is characterized by the emergence of cytokines along with other changes in cellular processes. Due to the complexity of the various constituents that makes up the inflammation dynamics, it is necessary to develop models that can complement experiments to fully understand inflammatory diseases. In this study, we developed a discrete informatics model based on cellular automata (CA) approach to investigate the influence of elastic field (stretch/strain) on the dynamics of inflammation and account for probabilistic adaptation based on statistical interpretation of existing experimental data. Our simulation model investigated the effects of low, medium, and high strain conditions on inflammation dynamics. Results suggest that the model is able to indicate the threshold of innate healing of tissue as a response to strain experienced by the tissue. When strain is under the threshold, the tissue is still capable of adapting its structure to heal the damaged part. However, there exists a strain threshold where healing capability breaks down. The results obtained demonstrate that the developed discrete informatics based CA model is capable of modeling and giving insights into inflammation dynamics parameters under various mechanical strain/stretch environments.

Non-local rheology for dense granular flows in avalanches

NASA Astrophysics Data System (ADS)

Izzet, Adrien; Clement, Eric; Andreotti, Bruno

A local constitutive relation was proposed to describe dense granular flows (GDR MiDi, EPJE 2004). It provides a rather good prediction of the flowing regime but does not foresee the existence of a ``creep regime'' as observed by Komatsu et al. (PRL 2001). In the context of a 2D shear cell, a relaxation length for the velocity profile was measured (Bouzid et al., PRL 2013) which confirmed the existence of a flow below the standard Coulomb yield threshold. A correction for the local rheology was proposed. To test further this non-local constitutive relation, we built an inclined narrow channel within which we monitor the flow from the side. We managed to observe the ``creep regime'' over five orders of magnitude in velocity and fit the velocity profiles in the depth with an asymptotic solution of the non-local equation. However, the boundary condition at the free surface needs to be selected in order to calibrate the non-local rheology over the whole range of stresses in the system. In this perspective, we complement the experimental results with 2D simulations of hard and frictional discs on an inclined plane in which we introduce a surface friction force proportional to the effective pressure in the granular. We analyze these results in the light of the non-local rheology.

Inverse problem of central configurations in the collinear 5-body problem

NASA Astrophysics Data System (ADS)

Davis, Candice; Geyer, Scott; Johnson, William; Xie, Zhifu

2018-05-01

In this paper, we study the inverse problem of collinear central configurations of a 5-body problem: given a collinear configuration q = (-s - 1, -1, r, 1, t + 1) of 5 bodies, does there exist positive masses to make the configuration central? Here we proved the following results: If r = 0 and s = t > 0, there always exist positive masses to make the configuration central and the masses are symmetrical such that m1 = m5, m2 = m4, and m3 is an arbitrary parameter. Specially if r = 0 and s =t =s ¯ , the configuration q =(-s ¯ -1 ,-1,0,1 ,s ¯ +1 ) is always a central configuration for any positive masses 0 < m2 = m4 < ∞ when m1 = m5 are fixed at particular values, which only depend on s ¯ and m3. s ¯ is the unique real root of a fifth order polynomial and numerically s ¯ ≈1.396 812 289 . If r = 0 and s ≠ t > 0, there also always exist positive masses to make the configuration central. For any r ∈ (0, 1) [or r ∈ (-1, 0)], there exist a set E14 (or E25) in the first quadrant of st-plane where every configuration is a central configuration for some positive masses. However, no configuration in the complement of E14 (or E25) is a central configuration for any positive masses.

Aspects of the Acquisition of Object Control and ECM-Type Verbs in European Portuguese

ERIC Educational Resources Information Center

Santos, Ana Lúcia; Gonçalves, Anabela; Hyams, Nina

2016-01-01

We investigate the acquisition of sentential complementation under causative, perception, and object control verbs in European Portuguese, a language rich in complement types, including the typologically marked inflected infinitives. We tested 58 children between 3 and 5 years of age and 24 adults on a sentence completion task. The results support…

Propagation-based x-ray phase contrast imaging using an iterative phase diversity technique

NASA Astrophysics Data System (ADS)

Carroll, Aidan J.; van Riessen, Grant A.; Balaur, Eugeniu; Dolbnya, Igor P.; Tran, Giang N.; Peele, Andrew G.

2018-03-01

Through the use of a phase diversity technique, we demonstrate a near-field in-line x-ray phase contrast algorithm that provides improved object reconstruction when compared to our previous iterative methods for a homogeneous sample. Like our previous methods, the new technique uses the sample refractive index distribution during the reconstruction process. The technique complements existing monochromatic and polychromatic methods and is useful in situations where experimental phase contrast data is affected by noise.

Human Resources Test and Evaluation System (HRTES). Volume 1. Comprehensive Handbook

DTIC Science & Technology

1984-08-01

INTRODUCTION I. Overview. 7 -"This handbook is designed to assist you in evaluating the performance of the operators and maintainers in a system. The Human...field data have been collected and to diagnose probable causes of inadequate human performance. HI-I HRTES has been designed to complement the existing...71-3). HRTES was designed to meet the reporting requirements that, according to AR 71-3, are a part of the OT&E cycle. These reports are: (1) the

Deforestation and Secondary Growth in Rondonia, Brazil from SIR-C SAR and Landsat.SPOT data

NASA Technical Reports Server (NTRS)

Rignot, Eric; Salas, William A.; Skole, David L.

1996-01-01

Covers problems with existing data collected with high-resolution optical sensors. They say active microwave sensors could complement other sensors in getting through things like cloud cover. They analyzed SIR-C data in combination with Landsat TM data, a 9-year time series of SPOT XS data, and a preliminary field survey. They report findings and draw conclusions, including that SARs operating at long radar wavelengths, with both like and cross-polarizations, are needed for tropical deforestation studies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kravtsov, A.I.

To determine the effect of geologic factors on the composition of abyssal derivates (complementing existing information on the geochemistry of volcanic gases) isotopic analysis of carbon was used to obtain physicochemical criteria of the origin of gases, independent of geologic-petrographic data. The investigations include component analysis of all the gases, particularly hydrocarbon compounds, repeatedly found in the fumarole emanations of pyroclastic streams. Volcanic carbon dioxide which is the principal component of gases of active volcanoes and hot springs in the Kuril-Kamchatka volcanic arc and of other volcanoes was investigated.

Metagenomes from two microbial consortia associated with Santa Barbara seep oil.

PubMed

Hawley, Erik R; Malfatti, Stephanie A; Pagani, Ioanna; Huntemann, Marcel; Chen, Amy; Foster, Brian; Copeland, Alexander; del Rio, Tijana Glavina; Pati, Amrita; Jansson, Janet R; Gilbert, Jack A; Tringe, Susannah Green; Lorenson, Thomas D; Hess, Matthias

2014-12-01

The metagenomes from two microbial consortia associated with natural oils seeping into the Pacific Ocean offshore the coast of Santa Barbara (California, USA) were determined to complement already existing metagenomes generated from microbial communities associated with hydrocarbons that pollute the marine ecosystem. This genomics resource article is the first of two publications reporting a total of four new metagenomes from oils that seep into the Santa Barbara Channel. Copyright © 2014 Elsevier B.V. All rights reserved.

Biological Research in Canisters (BRIC) - Light Emitting Diode (LED)

NASA Technical Reports Server (NTRS)

Levine, Howard G.; Caron, Allison

2016-01-01

The Biological Research in Canisters - LED (BRIC-LED) is a biological research system that is being designed to complement the capabilities of the existing BRIC-Petri Dish Fixation Unit (PDFU) for the Space Life and Physical Sciences (SLPS) Program. A diverse range of organisms can be supported, including plant seedlings, callus cultures, Caenorhabditis elegans, microbes, and others. In the event of a launch scrub, the entire assembly can be replaced with an identical back-up unit containing freshly loaded specimens.

Ly6G-mediated depletion of neutrophils is dependent on macrophages.

PubMed

Bruhn, Kevin W; Dekitani, Ken; Nielsen, Travis B; Pantapalangkoor, Paul; Spellberg, Brad

2016-01-01

Antibody-mediated depletion of neutrophils is commonly used to study neutropenia. However, the mechanisms by which antibodies deplete neutrophils have not been well defined. We noticed that mice deficient in complement and macrophages had blunted neutrophil depletion in response to anti-Ly6G monoclonal antibody (MAb) treatment. In vitro, exposure of murine neutrophils to anti-Ly6G MAb in the presence of plasma did not result in significant depletion of cells, either in the presence or absence of complement. In vivo, anti-Ly6G-mediated neutrophil depletion was abrogated following macrophage depletion, but not complement depletion, indicating a requirement for macrophages to induce neutropenia by this method. These results inform the use and limitations of anti-Ly6G antibody as an experimental tool for depleting neutrophils in various immunological settings.

Study on recognition technology of complementary image

NASA Astrophysics Data System (ADS)

Liu, Chengxiang; Hu, Xuejuan; Jian, Yaobo; Zhang, Li

2006-11-01

Complementation image is often used as a guard technology in the trademark and paper currency. The key point of recognizing this kind of images is judging the complementary effect of complementation printing. The perspective images are usually not clear and legible, so it is difficult to recognize them. In this paper, a new method is proposed. Firstly, capture the image by reflex. Secondly, find the same norm to man-made pair printing. Lastly, judge the true and false of paper currency by the complementary effect of complementation printing. This is the purpose of inspecting the false. Theoretic analysis and simulation results reveal that the effect of man-made pair printing is good, the method has advantages such as simplicity, high calculating speed, and good robust to different RMB. The experiment results reveal that the conclusion is reasonable, and demonstrates that this approach is effective.

European Union funded project on the development of a whole complement deficiency screening ELISA-A story of success and an exceptional manager: Mohamed R. Daha.

PubMed

Würzner, Reinhard; Tedesco, Francesco; Garred, Peter; Mollnes, Tom Eirik; Truedsson, Lennart; Turner, Malcolm W; Sommarin, Yngve; Wieslander, Jörgen; Sim, Robert B

2015-11-01

A whole complement ELISA-based assay kit, primarily designed to screen for deficiencies in components of the complement system was developed during a European Union grant involving more than a dozen European scientists and a small-medium enterprise company (Wieslab, which later merged into Eurodiagnostica). The consortium was led by Prof. Mohamed R. Daha who had already guided a preceding European grant which prepared the ground for this endeavor to create a novel and sophisticated complement measurement tool. The final result of the grant was a scientific publication (Seelen et al., 2005, J. Immunol. Methods 296, 187-198) and a commercially available complement deficiency screening kit, WIESLAB(®) Complement system Screen. Thereafter, the group decided to carry on with a grant, located at Innsbruck Medical University, and supported by royalties and unrestricted educational grants from Eurodiagnostica, Malmö, entitled "Search for Applications for WIESLAB(®) Complement system Screen (SAW)" with the aim to look for further applications of this assay. During the latter project the group organized several scientific meetings aimed at evaluating the use of the assay as well as developing further branches of its platform. A look back over almost two decades reveals a great story of excellent research which was also commercially successful, fulfilling the aims of European Union grants. It is also a story of ageless friendship, only possible due to the vision and guidance of an exceptional manager: Moh Daha. Copyright © 2015 Elsevier Ltd. All rights reserved.

The in vivo mechanism of action of CD20 monoclonal antibodies depends on local tumor burden

PubMed Central

Boross, Peter; Jansen, J.H. Marco; de Haij, Simone; Beurskens, Frank J.; van der Poel, Cees E.; Bevaart, Lisette; Nederend, Maaike; Golay, Josée; van de Winkel, Jan G.J.; Parren, Paul W.H.I.; Leusen, Jeanette H.W.

2011-01-01

Background CD20 monoclonal antibodies are widely used in clinical practice. Antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and direct cell death have been suggested to be important effector functions for CD20 antibodies. However, their specific contributions to the in vivo mechanism of action of CD20 immunotherapy have not been well defined. Design and Methods Here we studied the in vivo mechanism of action of type I (rituximab and ofatumumab) and type II (HuMab-11B8) CD20 antibodies in a peritoneal, syngeneic, mouse model with EL4-CD20 cells using low and high tumor burden. Results Interestingly, we observed striking differences in the in vivo mechanism of action of CD20 antibodies dependent on tumor load. In conditions of low tumor burden, complement was sufficient for tumor killing both for type I and type II CD20 antibodies. In contrast, in conditions of high tumor burden, activating FcγR (specifically FcγRIII), active complement and complement receptor 3 were all essential for tumor killing. Our data suggest that complement-enhanced antibody-dependent cellular cytotoxicity may critically affect tumor killing by CD20 antibodies in vivo. The type II CD20 antibody 11B8, which is a poor inducer of complement activation, was ineffective against high tumor burden. Conclusions Tumor burden affects the in vivo mechanism of action of CD20 antibodies. Low tumor load can be eliminated by complement alone, whereas elimination of high tumor load requires multiple effector mechanisms. PMID:21880632

Children's understanding of the addition/subtraction complement principle.

PubMed

Torbeyns, Joke; Peters, Greet; De Smedt, Bert; Ghesquière, Pol; Verschaffel, Lieven

2016-09-01

In the last decades, children's understanding of mathematical principles has become an important research topic. Different from the commutativity and inversion principles, only few studies have focused on children's understanding of the addition/subtraction complement principle (if a - b = c, then c + b = a), mainly relying on verbal techniques. This contribution aimed at deepening our understanding of children's knowledge of the addition/subtraction complement principle, combining verbal and non-verbal techniques. Participants were 67 third and fourth graders (9- to 10-year-olds). Children solved two tasks in which verbal reports as well as accuracy and speed data were collected. These two tasks differed only in the order of the problems and the instructions. In the looking-back task, children were told that sometimes the preceding problem might help to answer the next problem. In the baseline task, no helpful preceding items were offered. The looking-back task included 10 trigger-target problem pairs on the complement relation. Children verbally reported looking back on about 40% of all target problems in the looking-back task; the target problems were also solved faster and more accurately than in the baseline task. These results suggest that children used their understanding of the complement principle. The verbal and non-verbal data were highly correlated. This study complements previous work on children's understanding of mathematical principles by highlighting interindividual differences in 9- to 10-year-olds' understanding of the complement principle and indicating the potential of combining verbal and non-verbal techniques to investigate (the acquisition of) this understanding. © 2016 The British Psychological Society.

Occupational health surveillance: a means to identify work-related risks.

PubMed

Froines, J R; Dellenbaugh, C A; Wegman, D H

1986-09-01

The lack of successful disease surveillance methods has resulted in few reliable estimates of workplace-related disease. Hazard surveillance--the ongoing assessment of chemical use and worker exposure to the chemicals--is presented as a way to supplement occupational disease surveillance. Existing OSHA (Occupational Safety and Health Administration) and NIOSH (National Institute for Occupational Health) data systems are adapted to this function to characterize the distribution and type of hazardous industry in Los Angeles County. A new method is developed for ranking potentially hazardous industries in the county using actual exposure measurements from federal OSHA compliance inspections. The strengths of the different systems are presented along with considerations of industrial employment and types of specific chemical exposures. Applications for information from hazard surveillance are discussed in terms of intervention, monitoring exposure control, planning, research, and as a complement to disease surveillance.

Transient Invariant and Quasi-Invariant Structures in an Example of an Aperiodically Time Dependent Fluid Flow

NASA Astrophysics Data System (ADS)

Fortunati, Alessandro; Wiggins, Stephen

Starting from the concept of invariant KAM tori for nearly-integrable Hamiltonian systems with periodic or quasi-periodic nonautonomous perturbation, the paper analyzes the “analogue” of this class of invariant objects when the dependence on time is aperiodic. The investigation is carried out in a model motivated by the problem of a traveling wave in a channel over a smooth, quasi- and asymptotically flat (from which the “transient” feature) bathymetry, representing a case in which the described structures play the role of barriers to fluid transport in phase space. The paper provides computational evidence for the existence of transient structures also for “large” values of the perturbation size, as a complement to the rigorous results already proven by the first author for real-analytic bathymetry functions.

Rotating non-Boussinesq convection: oscillating hexagons

NASA Astrophysics Data System (ADS)

Moroz, Vadim; Riecke, Hermann; Pesch, Werner

2000-11-01

Within weakly nonlinear theory hexagon patterns are expected to undergo a Hopf bifurcation to oscillating hexagons when the chiral symmetry of the system is broken. Quite generally, the oscillating hexagons are expected to exhibit bistability of spatio-temporal defect chaos and periodic dynamics. This regime is described by the complex Ginzburg-Landau equation, which has been investigated theoretically in great detail. Its complex dynamics have, however, not been observed in experiments. Starting from the Navier-Stokes equations with realistic boundary conditions, we derive the three coupled real Ginzburg-Landau equations describing hexagons in rotating non-Boussinesq convection. We use them to provide quantitative results for the wavenumber range of stability of the stationary hexagons as well as the range of existence and stability of the oscillating hexagons. Our investigation is complemented by direct numerical simulations of the Navier-Stokes equations.

Complement inhibitors for age-related macular degeneration.

PubMed

Williams, Michael A; McKay, Gareth J; Chakravarthy, Usha

2014-01-15

Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD. To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations. We planned to include randomised controlled trials (RCTs) with parallel treatment groups which investigated either the prevention or treatment of advanced AMD by inhibition of the complement cascade. Two authors (MW and GMcK) independently evaluated all the titles and abstracts resulting from the searches. We contacted companies running clinical trials which had not yet reported results to request information. Since no trials met our inclusion criteria, we undertook no assessment of quality or meta-analysis. We identified and screened 317 references but there were no published RCTs that met the inclusion criteria. We identified two ongoing studies: one phase I study and one phase II study. There is insufficient information at present to generate evidence-based recommendations on the potential safety and efficacy of complement inhibitors for prevention or treatment of AMD. However we anticipate the results of ongoing trials.

Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development

PubMed Central

Jäckel, Sven; Saffarzadeh, Mona; Langer, Florian

2017-01-01

Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity, and the coagulation and complement cascades. Here we show in a tissue factor (TF)–dependent model of flow restriction-induced venous thrombosis that complement factors make distinct contributions to platelet activation and fibrin deposition. Complement factor 3 (C3) deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro. Initial fibrin deposition at the vessel wall over 6 hours in this model was dependent on protein disulfide isomerase (PDI) and TF expression by myeloid cells, but did not require neutrophil extracellular trap formation involving peptidyl arginine deiminase 4. In contrast to C3−/− mice, C5-deficient mice had no apparent defect in platelet activation in vitro, and vessel wall platelet deposition and initial hemostasis in vivo. However, fibrin formation, the exposure of negatively charged phosphatidylserine (PS) on adherent leukocytes, and clot burden after 48 hours were significantly reduced in C5−/− mice compared with wild-type controls. These results delineate that C3 plays specific roles in platelet activation independent of formation of the terminal complement complex and provide in vivo evidence for contributions of complement-dependent membrane perturbations to prothrombotic TF activation on myeloid cells. PMID:28223279

Complement opsonization of HIV-1 results in a different intracellular processing pattern and enhanced MHC class I presentation by dendritic cells

PubMed Central

Tjomsland, Veronica; Ellegård, Rada; Burgener, Adam; Mogk, Kenzie; Che, Karlhans F; Westmacott, Garrett; Hinkula, Jorma; Lifson, Jeffrey D; Larsson, Marie

2013-01-01

Induction of optimal HIV-1-specific T-cell responses, which can contribute to controlling viral infection in vivo, depends on antigen processing and presentation processes occurring in DCs. Opsonization can influence the routing of antigen processing and pathways used for presentation. We studied antigen proteolysis and the role of endocytic receptors in MHC class I (MHCI) and II (MHCII) presentation of antigens derived from HIV-1 in human monocyte-derived immature DCs (IDCs) and mature DCs, comparing free and complement opsonized HIV-1 particles. Opsonization of virions promoted MHCI presentation by DCs, indicating that complement opsonization routes more virions toward the MHCI presentation pathway. Blockade of macrophage mannose receptor (MMR) and β7-integrin enhanced MHCI and MHCII presentation by IDCs and mature DCs, whereas the block of complement receptor 3 decreased MHCI and MHCII presentation. In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure; complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and β7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery. PMID:23526630

Defining the genetics of thrombotic microangiopathies.

PubMed

Vieira-Martins, Paula; El Sissy, Carine; Bordereau, Pauline; Gruber, Aurelia; Rosain, Jeremie; Fremeaux-Bacchi, Veronique

2016-04-01

The spectrum of the thrombotic microangiopathies (TMA) encompasses a heterogeneous group of disorders with hereditary and acquired forms. Endothelial cell injury in the microvasculature is common to all TMAs, whatever the pathophysiological process. In this review we describe genetic mutations characteristic of certain TMAs and review their contributions to disease. Recent identification of novel pathologic mutations has been enabled by exome studies. The monogenic forms of TMA are more frequently caused by recessive alterations in von Willebrand factor cleaving protease ADAMST13, leading to congenital thrombotic thrombocytopenic purpura, or cobalamine C and DGKE genes, leading to an atypical hemolytic-uremic syndrome (aHUS)-like TMA. aHUS, whether idiopathic or linked to a known complement amplifying condition, is a TMA that primarily affects kidney function. It often results from a combination of an underlying genetic susceptibility with environmental factors activating the alternative complement pathway. Pathogenic variants in at least five complement genes coding for complement factor H (CFH) complement factor I (CFI), MCP (CD46), C3 and complement factor B (CFB) have been demonstrated to increase the risk of developing aHUS, but several more genes have been implicated. A new challenge is to separate disease-associated genetic variants from the broader background of variants or polymorphisms present in all human genomes that are rare, potentially functional, but may or may not be pathogenic. Copyright © 2016 Elsevier Ltd. All rights reserved.

The profile of adsorbed plasma and serum proteins on methacrylic acid copolymer beads: Effect on complement activation.

PubMed

Wells, Laura A; Guo, Hongbo; Emili, Andrew; Sefton, Michael V

2017-02-01

Polymer beads made of 45% methacrylic acid co methyl methacrylate (MAA beads) promote vascular regenerative responses in contrast to control materials without methacrylic acid (here polymethyl methacrylate beads, PMMA). In vitro and in vivo studies suggest that MAA copolymers induce differences in macrophage phenotype and polarization and inflammatory responses, presumably due to protein adsorption differences between the beads. To explore differences in protein adsorption in an unbiased manner, we used high resolution shotgun mass spectrometry to identify and compare proteins that adsorb from human plasma or serum onto MAA and PMMA beads. From plasma, MAA beads adsorbed many complement proteins, such as C1q, C4-related proteins and the complement inhibitor factor H, while PMMA adsorbed proteins, such as albumin, C3 and apolipoproteins. Because of the differences in complement protein adsorption, follow-up studies focused on using ELISA to assess complement activation. When incubated in serum, MAA beads generated significantly lower levels of soluble C5b9 and C3a/C3a desarg in comparison to PMMA beads, indicating a decrease in complement activation with MAA beads. The differences in adsorbed protein on the two materials likely alter subsequent cell-material interactions that ultimately result in different host responses and local vascularization. Copyright © 2016 Elsevier Ltd. All rights reserved.

A teleost CD46 is involved in the regulation of complement activation and pathogen infection.

PubMed

Li, Mo-Fei; Sui, Zhi-Hai; Sun, Li

2017-11-03

In mammals, CD46 is involved in the inactivation of complement by factor I (FI). In teleost, study on the function of CD46 is very limited. In this study, we examined the immunological property of a CD46 molecule (CsCD46) from tongue sole, a teleost species with important economic value. We found that recombinant CsCD46 (rCsCD46) interacted with FI and inhibited complement activation in an FI-dependent manner. rCsCD46 also interacted with bacterial pathogens via a different mechanism to that responsible for the FI interaction, involving different rCsCD46 sites. Cellular study showed that CsCD46 was expressed on peripheral blood leukocytes (PBL) and protected the cells against the killing effect of complement. When the CsCD46 on PBL was blocked by antibody before incubation of the cells with bacterial pathogens, cellular infection was significantly reduced. Consistently, when tongue sole were infected with bacterial pathogens in the presence of rCsCD46, tissue dissemination and survival of the pathogens were significantly inhibited. These results provide the first evidence to indicate that CD46 in teleosts negatively regulates complement activation via FI and protects host cells from complement-induced damage, and that CD46 is required for optimal bacterial infection probably by serving as a receptor for the bacteria.

Preservation of renal function in atypical hemolytic uremic syndrome by eculizumab: a case report.

PubMed

Giordano, Mario; Castellano, Giuseppe; Messina, Giovanni; Divella, Claretta; Bellantuono, Rosa; Puteo, Flora; Colella, Vincenzo; Depalo, Tommaso; Gesualdo, Loreto

2012-11-01

Genetic mutations in complement components are associated with the development of atypical hemolytic uremic syndrome (aHUS), a rare disease with high morbidity rate triggered by infections or unidentified factors. The uncontrolled activation of the alternative pathway of complement results in systemic endothelial damage leading to progressive development of renal failure. A previously healthy 8-month-old boy was referred to our hospital because of onset of fever, vomiting, and a single episode of nonbloody diarrhea. Acute kidney injury with preserved diuresis, hemolytic anemia, and thrombocytopenia were detected, and common protocols for management of HUS were followed without considerable improvement. The persistent low levels of complement component C3 led us to hypothesize the occurrence of aHUS. In fact, the child carried a specific mutation in complement factor H (Cfh; nonsense mutation in 3514G>T, serum levels of Cfh 138 mg/L, normal range 350-750). Given the lack of response to therapy and the occurrence of kidney failure requiring dialysis, we used eculizumab as rescue therapy, a monoclonal humanized antibody against the complement component C5. One week from the first administration, we observed a significant improvement of all clinical and laboratory parameters with complete recovery from hemodialysis, even in the presence of systemic infections. Our case report shows that complement inhibiting treatment allows the preservation of renal function and avoids disease relapses during systemic infections.

Complement factor h is critical in the maintenance of retinal perfusion.

PubMed

Lundh von Leithner, Peter; Kam, Jaimie Hoh; Bainbridge, James; Catchpole, Ian; Gough, Gerald; Coffey, Peter; Jeffery, Glen

2009-07-01

Vascular pathologies are known to be associated with age-related macular degeneration. Recently, age-related macular degeneration was associated with a single-nucleotide substitution of the complement factor H (CFH) gene, part of the alternative pathway of the complement system, a critical element in the innate immune response. Such polymorphisms are found in more than 50% of cases of age-related macular degeneration. Here we show that the absence of CFH causes an autoimmune response that targets the vascular endothelium of both the inner and outer retinal vascular networks. In CFH-knockout (cfh(-/-)) mice, C3 and C3b, key components of the complement system, are progressively deposited on retinal vessels, which subsequently become restricted and wither, resulting in a reduction of retinal blood supply. This result leads to increased oxygen stress. While such effects are not systemic, these structural changes are mirrored in functional changes with a substantial decline in retinal blood flow dynamics. When the system is challenged functionally by laser-induced choroidal neovascularization, fluorescein leakage was significantly smaller in cfh(-/-) mice compared with controls, likely due to reduced retinal perfusion. These data reveal that in both the presence and absence of exogenous challenge to the innate immune system, CFH is required to maintain normal levels of retinal perfusion. It is likely that C3 and C3b accumulation in the aged CFH-deficient retina is associated with complement-mediated retinal endothelium destruction.

CsMAP34, a teleost MAP with dual role: A promoter of MASP-assisted complement activation and a regulator of immune cell activity.

PubMed

Li, Mo-Fei; Li, Jun; Sun, Li

2016-12-23

In teleost fish, the immune functions of mannan-binding lectin (MBL) associated protein (MAP) and MBL associated serine protease (MASP) are scarcely investigated. In the present study, we examined the biological properties both MAP (CsMAP34) and MASP (CsMASP1) molecules from tongue sole (Cynoglossus semilaevis). We found that CsMAP34 and CsMASP1 expressions occurred in nine different tissues and were upregulated by bacterial challenge. CsMAP34 protein was detected in blood, especially during bacterial infection. Recombinant CsMAP34 (rCsMAP34) bound C. semilaevis MBL (rCsBML) when the latter was activated by bacteria, while recombinant CsMASP1 (rCsMASP1) bound activated rCsBML only in the presence of rCsMAP34. rCsMAP34 stimulated the hemolytic and bactericidal activities of serum complement, whereas anti-CsMAP34 antibody blocked complement activities. Knockdown of CsMASP1 in C. semilaevis resulted in significant inhibition of complement activities. Furthermore, rCsMAP34 interacted directly with peripheral blood leukocytes (PBL) and enhanced the respiratory burst, acid phosphatase activity, chemotactic activity, and gene expression of PBL. These results indicate for the first time that a teleost MAP acts one hand as a regulator that promotes the lectin pathway of complement activation via its ability to recruit MBL to MASP, and other hand as a modulator of immune cell activity.

Defining a Rule for the Use of Infinitive and Gerund Complements

ERIC Educational Resources Information Center

Conti, Gregory

2011-01-01

This essay formulates a rule for the use of the to+verb and verb+ing finite complements designed to help students and teachers of English as a foreign language. The rule results from an analysis of the distinction between the directional function and inceptive aspect of the to+verb form, rooted in the prepositional origins of to, and the…

The Group B Streptococcus-Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways.

PubMed

Pietrocola, Giampiero; Rindi, Simonetta; Rosini, Roberto; Buccato, Scilla; Speziale, Pietro; Margarit, Immaculada

2016-01-01

The group B Streptococcus (GBS) is a leading cause of neonatal invasive disease. GBS bacteria are surrounded by a thick capsular polysaccharide that is a potent inhibitor of complement deposition via the alternative pathway. Several of its surface molecules can however activate the classical and lectin complement pathways, rendering this species still vulnerable to phagocytic killing. In this study we have identified a novel secreted protein named complement interfering protein (CIP) that downregulates complement activation via the classical and lectin pathways, but not the alternative pathway. The CIP protein showed high affinity toward C4b and inhibited its interaction with C2, presumably preventing the formation of the C4bC2a convertase. Addition of recombinant CIP to GBS cip-negative bacteria resulted in decreased deposition of C3b on their surface and in diminished phagocytic killing in a whole-blood assay. Our data reveal a novel strategy exploited by GBS to counteract innate immunity and could be valuable for the development of anti-infective agents against this important pathogen. Copyright © 2015 by The American Association of Immunologists, Inc.

Comparative analysis of salivary zinc level in recurrent herpes labialis

PubMed Central

Khozeimeh, Faezeh; Jafari, Nasim; Attar, Ahmad Movahedian; Jafari, Shahram; Ataie, Masoud

2012-01-01

Background: Recurrent Herpes Labialis (RHL) is one of most common infective vesiculoulcerative lesions. According to some studies administration of topical and/or systemic zinc compositions has been effective in treatment and prevention. This article aims to comparison of zinc level in healthy subjects and RHL patients in acute and convalescent phases. Materials and Methods: This was a retrospective case – control study, carried on 80 individuals (40 normal and 40 RHL patients) mean age=34.5 and 34.4, respectively. Saliva samples were taken in patients in acute phase once and after healing of lesions in convalescent phase (averagely 21 days later) and in normal individuals. Salivary zinc level concentration was measured by flame atomic absorption spectrophotometer by dry digestion method. The results were statistically analyzed with SPSS software by t-test (α=0.05). Results: Results showed that salivary zinc level in case group in acute and convalescent phases were 160.8 ngr/mland 205.7 ngr/ml respectivly and significant differences between them were existed (P <0.05). Also significant differences were existed between zinc concentration in healthy subjects and patient groups (in both phases) (P=.001 and .002 for acute and convalescent phases respectively). Conclusion: According to the results, zinc level is significantly lower in acute phase than in convalescent phase and significantly lower in both phases compared to healthy individuals,so determination of serum zinc level and prescribing zinc complement in low serum status has both treatmental and preventive effects in RHL patients. PMID:22363358

Plasma-based proteomics reveals immune response, complement and coagulation cascades pathway shifts in heat-stressed lactating dairy cows.

PubMed

Min, Li; Cheng, Jianbo; Zhao, Shengguo; Tian, He; Zhang, Yangdong; Li, Songli; Yang, Hongjian; Zheng, Nan; Wang, Jiaqi

2016-09-02

Heat stress (HS) has an enormous economic impact on the dairy industry. In recent years, many researchers have investigated changes in the gene expression and metabolomics profiles in dairy cows caused by HS. However, the proteomics profiles of heat-stressed dairy cows have not yet been completely elucidated. We compared plasma proteomics from HS-free and heat-stressed dairy cows using an iTRAQ labeling approach. After the depletion of high abundant proteins in the plasma, 1472 proteins were identified. Of these, 85 proteins were differentially abundant in cows exposed to HS relative to HS-free. Database searches combined with GO and KEGG pathway enrichment analyses revealed that many components of the complement and coagulation cascades were altered in heat-stressed cows compared with HS-free cows. Of these, many factors in the complement system (including complement components C1, C3, C5, C6, C7, C8, and C9, complement factor B, and factor H) were down-regulated by HS, while components of the coagulation system (including coagulation factors, vitamin K-dependent proteins, and fibrinogens) were up-regulated by HS. In conclusion, our results indicate that HS decreases plasma levels of complement system proteins, suggesting that immune function is impaired in dairy cows exposed to HS. Though many aspects of heat stress (HS) have been extensively researched, relatively little is known about the proteomics profile changes that occur during heat exposure. In this work, we employed a proteomics approach to investigate differential abundance of plasma proteins in HS-free and heat-stressed dairy cows. Database searches combined with GO and KEGG pathway enrichment analyses revealed that HS resulted in a decrease in complement components, suggesting that heat-stressed dairy cows have impaired immune function. In addition, through integrative analyses of proteomics and previous metabolomics, we showed enhanced glycolysis, lipid metabolic pathway shifts, and nitrogen repartitioning in dairy cows exposed to HS. Our findings expand our current knowledge on the effects of HS on plasma proteomics in dairy cows and offer a new perspective for future research. Copyright © 2016 Elsevier B.V. All rights reserved.

Monoclonal antibodies to meningococcal factor H binding protein with overlapping epitopes and discordant functional activity.

PubMed

Giuntini, Serena; Beernink, Peter T; Reason, Donald C; Granoff, Dan M

2012-01-01

Meningococcal factor H binding protein (fHbp) is a promising vaccine candidate. Anti-fHbp antibodies can bind to meningococci and elicit complement-mediated bactericidal activity directly. The antibodies also can block binding of the human complement down-regulator, factor H (fH). Without bound fH, the organism would be expected to have increased susceptibility to bacteriolysis. Here we describe bactericidal activity of two anti-fHbp mAbs with overlapping epitopes in relation to their different effects on fH binding and bactericidal activity. Both mAbs recognized prevalent fHbp sequence variants in variant group 1. Using yeast display and site-specific mutagenesis, binding of one of the mAbs (JAR 1, IgG3) to fHbp was eliminated by a single amino acid substitution, R204A, and was decreased by K143A but not by R204H or D142A. The JAR 1 epitope overlapped that of previously described mAb (mAb502, IgG2a) whose binding to fHbp was eliminated by R204A or R204H substitutions, and was decreased by D142A but not by K143A. Although JAR 1 and mAb502 appeared to have overlapping epitopes, only JAR 1 inhibited binding of fH to fHbp and had human complement-mediated bactericidal activity. mAb502 enhanced fH binding and lacked human complement-mediated bactericidal activity. To control for confounding effects of different mouse IgG subclasses on complement activation, we created chimeric mAbs in which the mouse mAb502 or JAR 1 paratopes were paired with human IgG1 constant regions. While both chimeric mAbs showed similar binding to fHbp, only JAR 1, which inhibited fH binding, had human complement-mediated bactericidal activity. The lack of human complement-mediated bactericidal activity by anti-fHbp mAb502 appeared to result from an inability to inhibit binding of fH. These results underscore the importance of inhibition of fH binding for anti-fHbp mAb bactericidal activity.

C1q-targeted inhibition of the classical complement pathway prevents injury in a novel mouse model of acute motor axonal neuropathy.

PubMed

McGonigal, Rhona; Cunningham, Madeleine E; Yao, Denggao; Barrie, Jennifer A; Sankaranarayanan, Sethu; Fewou, Simon N; Furukawa, Koichi; Yednock, Ted A; Willison, Hugh J

2016-03-02

Guillain-Barré syndrome (GBS) is an autoimmune disease that results in acute paralysis through inflammatory attack on peripheral nerves, and currently has limited, non-specific treatment options. The pathogenesis of the acute motor axonal neuropathy (AMAN) variant is mediated by complement-fixing anti-ganglioside antibodies that directly bind and injure the axon at sites of vulnerability such as nodes of Ranvier and nerve terminals. Consequently, the complement cascade is an attractive target to reduce disease severity. Recently, C5 complement component inhibitors that block the formation of the membrane attack complex and subsequent downstream injury have been shown to be efficacious in an in vivo anti-GQ1b antibody-mediated mouse model of the GBS variant Miller Fisher syndrome (MFS). However, since gangliosides are widely expressed in neurons and glial cells, injury in this model was not targeted exclusively to the axon and there are currently no pure mouse models for AMAN. Additionally, C5 inhibition does not prevent the production of early complement fragments such as C3a and C3b that can be deleterious via their known role in immune cell and macrophage recruitment to sites of neuronal damage. In this study, we first developed a new in vivo transgenic mouse model of AMAN using mice that express complex gangliosides exclusively in neurons, thereby enabling specific targeting of axons with anti-ganglioside antibodies. Secondly, we have evaluated the efficacy of a novel anti-C1q antibody (M1) that blocks initiation of the classical complement cascade, in both the newly developed anti-GM1 antibody-mediated AMAN model and our established MFS model in vivo. Anti-C1q monoclonal antibody treatment attenuated complement cascade activation and deposition, reduced immune cell recruitment and axonal injury, in both mouse models of GBS, along with improvement in respiratory function. These results demonstrate that neutralising C1q function attenuates injury with a consequent neuroprotective effect in acute GBS models and promises to be a useful new target for human therapy.

Inhibition of the Membrane Attack Complex by Dengue Virus NS1 through Interaction with Vitronectin and Terminal Complement Proteins

PubMed Central

Conde, Jonas Nascimento; da Silva, Emiliana Mandarano; Allonso, Diego; Coelho, Diego Rodrigues; Andrade, Iamara da Silva; de Medeiros, Luciano Neves; Menezes, Joice Lima; Barbosa, Angela Silva

2016-01-01

ABSTRACT Dengue virus (DENV) infects millions of people worldwide and is a major public health problem. DENV nonstructural protein 1 (NS1) is a conserved glycoprotein that associates with membranes and is also secreted into the plasma in DENV-infected patients. The present study describes a novel mechanism by which NS1 inhibits the terminal complement pathway. We first identified the terminal complement regulator vitronectin (VN) as a novel DENV2 NS1 binding partner by using a yeast two-hybrid system. This interaction was further assessed by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assay. The NS1-VN complex was also detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the DENV2 NS1 protein, either by itself or by interacting with VN, hinders the formation of the membrane attack complex (MAC) and C9 polymerization. Finally, we showed that DENV2, West Nile virus (WNV), and Zika virus (ZIKV) NS1 proteins produced in mammalian cells inhibited C9 polymerization. Taken together, our results points to a role for NS1 as a terminal pathway inhibitor of the complement system. IMPORTANCE Dengue is the most important arthropod-borne viral disease nowadays and is caused by dengue virus (DENV). The flavivirus NS1 glycoprotein has been characterized functionally as a complement evasion protein that can attenuate the activation of the classical, lectin, and alternative pathways. The present study describes a novel mechanism by which DENV NS1 inhibits the terminal complement pathway. We identified the terminal complement regulator vitronectin (VN) as a novel DENV NS1 binding partner, and the NS1-VN complex was detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the NS1-VN complex inhibited membrane attack complex (MAC) formation, thus interfering with the complement terminal pathway. Interestingly, NS1 itself also inhibited MAC activity, suggesting a direct role of this protein in the inhibition process. Our findings imply a role for NS1 as a terminal pathway inhibitor of the complement system. PMID:27512066

Complement Mutations in Diacylglycerol Kinase-ε–Associated Atypical Hemolytic Uremic Syndrome

PubMed Central

Sánchez Chinchilla, Daniel; Pinto, Sheila; Hoppe, Bernd; Adragna, Marta; Lopez, Laura; Justa Roldan, Maria Luisa; Peña, Antonia; Lopez Trascasa, Margarita; Sánchez-Corral, Pilar; Rodríguez de Córdoba, Santiago

2014-01-01

Background and objectives Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-ε, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-ε gene in a cohort with atypical hemolytic uremic syndrome was analyzed. Design, setting, participants, & measurements Eighty-three patients with early-onset atypical hemolytic uremic syndrome (<2 years) enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999 and 2013 were screened for mutations in diacylglycerol kinase-ε. These patients were also fully characterized for mutations in the genes encoding factor H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs copy number variations and rearrangements, and antifactor H antibodies. Results Four patients carried mutations in diacylglycerol kinase-ε, one p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions controlled atypical hemolytic uremic syndrome recurrences and prevented renal failure in the two patients with diacylglycerol kinase-ε and thrombomodulin mutations. A positive response to plasma infusions and complement inhibition treatment was also observed in the patient with concurrent diacylglycerol kinase-ε and C3 mutations. Conclusions Data suggest that complement dysregulation influences the onset and disease severity in carriers of diacylglycerol kinase-ε mutations and that treatments on the basis of plasma infusions and complement inhibition are potentially useful in patients with combined diacylglycerol kinase-ε and complement mutations. A comprehensive understanding of the genetic component predisposing to atypical hemolytic uremic syndrome is, therefore, critical to guide an effective treatment. PMID:25135762

The Complement System and Adverse Pregnancy Outcomes

PubMed Central

Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

2015-01-01

Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

O1.6. INCREASED COMPLEMENT FACTORS C3 AND C4 IN SCHIZOPHRENIA AND THE EARLY STAGES OF PSYCHOSIS: IMPLICATIONS FOR CLINICAL SYMPTOMATOLOGY AND CORTICAL THICKNESS

PubMed Central

Cropley, Vanessa; Laskaris, Liliana; Zalesky, Andrew; Weickert, Cynthia Shannon; Biase, Maria Di; Chana, Gursharan; Baune, Bernhard; Bousman, Chad; Nelson, Barnaby; McGorry, Patrick D; Everall, Ian; Pantelis, Christos

2018-01-01

Abstract Background The complement system - a key component of the innate immune system, has been proposed to contribute to the pathogenesis of schizophrenia. Recently, complement C4 was associated with increased risk of schizophrenia, and in a mouse model, developmentally-timed synaptic pruning. These observations have led to proposals that abnormal activation of the complement system might contribute to the development of schizophrenia by disrupting synaptic pruning during key developmental periods. However, despite renewed interest in the complement system in schizophrenia it remains unclear whether peripheral complement levels differ in cases compared to controls, change over the course of illness and whether they are associated with current symptomatology and brain cortical thickness. This study aimed to: i) investigate whether peripheral complement protein levels are altered at different stages of illness, and ii) identify patterns among complement protein levels that predict clinical symptoms and grey matter thickness across the cortex. Methods Complement factors C1q, C3 and C4 were quantified in 183 participants [n=83 Healthy Controls (HC), n=10 Ultra-High Risk (UHR) for psychosis, n=40 First Episode Psychosis (FEP), n=50 Chronic schizophrenia] using Multiplex ELISA. Permutation-based t-tests were used to assess between-group differences in complement protein levels at each of the three illness stages, relative to age- and gender-matched healthy controls. Canonical correlation analysis was used to identify patterns of complement protein levels that correlated with clinical symptoms and regional thickness across the cortex. Results C3 and C4 were significantly increased in FEP and UHR patients, whereas only C4 was significantly increased in chronic patients. A molecular pattern of increased C4 and decreased C3 was associated with positive and negative symptom severity in the pooled patient sample. Increased C4 levels alone, or decreased C3 levels alone, did not correlate with symptom severity as strongly as the pattern of increased C4 in combination with decreased C3. Preliminary canonical correlation analyses revealed that, in healthy controls, a molecular pattern characterised by increased C3 and decreased C4 was associated with relatively thinner paracentral, inferior parietal and inferior temporal cortices, but relatively thicker insular, in the left hemisphere. In the pooled patient group, a trend for increased C3 in combination with decreased C1q was associated with relatively thinner left lateral occipital cortex and pars orbitalis but relatively thicker pars opercularis and precuneus. Discussion Our findings indicate that peripheral complement concentration is particularly increased early and preceding psychosis and its imbalance may be associated with symptom severity and variation in regional grey matter thickness across the cortex.

Sundanese Complementation

ERIC Educational Resources Information Center

Kurniawan, Eri

2013-01-01

The focus of this thesis is the description and analysis of clausal complementation in Sundanese, an Austronesian language spoken in Indonesia. The thesis examined a range of clausal complement types in Sundanese, which consists of (i) "yen/(wi)rehna" "that" complements, (ii) "pikeun" "for" complements,…

Development of the geoCamera, a System for Mapping Ice from a Ship

NASA Astrophysics Data System (ADS)

Arsenault, R.; Clemente-Colon, P.

2012-12-01

The geoCamera produces maps of the ice surrounding an ice-capable ship by combining images from one or more digital cameras with the ship's position and attitude data. Maps are produced along the ship's path with the achievable width and resolution depending on camera mounting height as well as camera resolution and lens parameters. Our system has produced maps up to 2000m wide at 1m resolution. Once installed and calibrated, the system is designed to operate automatically producing maps in near real-time and making them available to on-board users via existing information systems. The resulting small-scale maps complement existing satellite based products as well as on-board observations. Development versions have temporarily been deployed in Antarctica on the RV Nathaniel B. Palmer in 2010 and in the Arctic on the USCGC Healy in 2011. A permanent system has been deployed during the summer of 2012 on the USCGC Healy. To make the system attractive to other ships of opportunity, design goals include using existing ship systems when practical, using low costs commercial-off-the-shelf components if additional hardware is necessary, automating the process to virtually eliminate adding to the workload of ships technicians and making the software components modular and flexible enough to allow more seamless integration with a ships particular IT system.

Complement Inhibitors from Scabies Mites Promote Streptococcal Growth – A Novel Mechanism in Infected Epidermis?

PubMed Central

Mika, Angela; Reynolds, Simone L.; Pickering, Darren; McMillan, David; Sriprakash, Kadaba S.; Kemp, David J.; Fischer, Katja

2012-01-01

Background Scabies is highly prevalent in socially disadvantaged communities such as indigenous populations and in developing countries. Generalized itching causes discomfort to the patient; however, serious complications can occur as a result of secondary bacterial pyoderma, commonly caused by Streptococcus pyogenes (GAS) or Staphylococcus aureus. In the tropics, skin damage due to scabies mite infestations has been postulated to be an important link in the pathogenesis of disease associated with acute rheumatic fever and heart disease, poststreptococcal glomerulonephritis and systemic sepsis. Treatment of scabies decreases the prevalence of infections by bacteria. This study aims to identify the molecular mechanisms underlying the link between scabies and GAS infections. Methodology/Principal Findings GAS bacteria were pre-incubated with blood containing active complement, phagocytes and antibodies against the bacteria, and subsequently tested for viability by plate counts. Initial experiments were done with serum from an individual previously exposed to GAS with naturally acquired anti-GAS antibodies. The protocol was optimized for large-scale testing of low-opsonic whole blood from non-exposed human donors by supplementing with a standard dose of heat inactivated human sera previously exposed to GAS. This allowed an extension of the dataset to two additional donors and four proteins tested at a range of concentrations. Shown first is the effect of scabies mite complement inhibitors on human complement using ELISA-based complement activation assays. Six purified recombinant mite proteins tested at a concentration of 50 µg/ml blocked all three complement activation pathways. Further we demonstrate in human whole blood assays that each of four scabies mite complement inhibitors tested increased GAS survival rates by 2–15 fold. Conclusions/Significance We propose that local complement inhibition plays an important role in the development of pyoderma in scabies infested skin. This molecular link between scabies and bacterial infections may provide new avenues to develop alternative treatment options against this neglected disease. PMID:22815998

High effective inverse dynamics modelling for dual-arm robot

NASA Astrophysics Data System (ADS)

Shen, Haoyu; Liu, Yanli; Wu, Hongtao

2018-05-01

To deal with the problem of inverse dynamics modelling for dual arm robot, a recursive inverse dynamics modelling method based on decoupled natural orthogonal complement is presented. In this model, the concepts and methods of Decoupled Natural Orthogonal Complement matrices are used to eliminate the constraint forces in the Newton-Euler kinematic equations, and the screws is used to express the kinematic and dynamics variables. On this basis, the paper has developed a special simulation program with symbol software of Mathematica and conducted a simulation research on the a dual-arm robot. Simulation results show that the proposed method based on decoupled natural orthogonal complement can save an enormous amount of CPU time that was spent in computing compared with the recursive Newton-Euler kinematic equations and the results is correct and reasonable, which can verify the reliability and efficiency of the method.

Analysis of trehalose-6-phosphate synthase (TPS) gene family suggests the formation of TPS complexes in rice.

PubMed

Zang, Baisheng; Li, Haowen; Li, Wenjun; Deng, Xing Wang; Wang, Xiping

2011-08-01

Trehalose-6-phosphate (T6P), an intermediate in the trehalose biosynthesis pathway, is emerging as an important regulator of plant metabolism and development. T6P levels are potentially modulated by a group of trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP) homologues. In this study, we have isolated 11 TPS genes encoding proteins with both TPS and TPP domains, from rice. Functional complement assays performed in yeast tps1 and tps2 mutants, revealed that only OsTPS1 encodes an active TPS enzyme and no OsTPS protein possesses TPP activity. By using a yeast two-hybrid analysis, a complicated interaction network occurred among OsTPS proteins, and the TPS domain might be essential for this interaction to occur. The interaction between OsTPS1 and OsTPS8 in vivo was confirmed by bimolecular fluorescence complementation and coimmunoprecipitation assays. Furthermore, our gel filtration assay showed that there may exist two forms of OsTPS1 (OsTPS1a and OsTPS1b) with different elution profiles in rice. OsTPS1b was particularly cofractionated with OsTPS5 and OsTPS8 in the 360 kDa complex, while OsTPS1a was predominantly incorporated into the complexes larger than 360 kDa. Collectively, these results suggest that OsTPS family members may form trehalose-6-phosphate synthase complexes and therefore potentially modify T6P levels to regulate plant development.

Cloned Erwinia chrysanthemi out genes enable Escherichia coli to selectively secrete a diverse family of heterologous proteins to its milieu.

PubMed

He, S Y; Lindeberg, M; Chatterjee, A K; Collmer, A

1991-02-01

The out genes of the enterobacterial plant pathogen Erwinia chrysanthemi are responsible for the efficient extracellular secretion of multiple plant cell wall-degrading enzymes, including four isozymes of pectate lyase, exo-poly-alpha-D-galacturonosidase, pectin methylesterase, and cellulase. Out- mutants of Er. chrysanthemi are unable to export any of these proteins beyond the periplasm and are severely reduced in virulence. We have cloned out genes from Er. chrysanthemi in the stable, low-copy-number cosmid pCPP19 by complementing several transposon-induced mutations. The cloned out genes were clustered in a 12-kilobase chromosomal DNA region, complemented all existing out mutations in Er. chrysanthemi EC16, and enabled Escherichia coli strains to efficiently secrete the extracellular pectic enzymes produced from cloned Er. chrysanthemi genes, while retaining the periplasmic marker protein beta-lactamase. DNA sequencing of a 2.4-kilobase EcoRI fragment within the out cluster revealed four genes arranged colinearly and sharing substantial similarity with the Klebsiella pneumoniae genes pulH, pulI, pulJ, and pulK, which are necessary for pullulanase secretion. However, K. pneumoniae cells harboring the cloned Er. chrysanthemi pelE gene were unable to secrete the Erwinia pectate lyase. Furthermore, the Er. chrysanthemi Out system was unable to secrete an extracellular pectate lyase encoded by a gene from a closely related plant pathogen. Erwinia carotovora ssp. carotovora. The results suggest that these enterobacteria secrete polysaccharidases by a conserved mechanism whose protein-recognition capacities have diverged.

Effective implementation of the weak Galerkin finite element methods for the biharmonic equation

DOE PAGES

Mu, Lin; Wang, Junping; Ye, Xiu

2017-07-06

The weak Galerkin (WG) methods have been introduced in [11, 12, 17] for solving the biharmonic equation. The purpose of this paper is to develop an algorithm to implement the WG methods effectively. This can be achieved by eliminating local unknowns to obtain a global system with significant reduction of size. In fact this reduced global system is equivalent to the Schur complements of the WG methods. The unknowns of the Schur complement of the WG method are those defined on the element boundaries. The equivalence of theWG method and its Schur complement is established. The numerical results demonstrate themore » effectiveness of this new implementation technique.« less

Effective implementation of the weak Galerkin finite element methods for the biharmonic equation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mu, Lin; Wang, Junping; Ye, Xiu

The weak Galerkin (WG) methods have been introduced in [11, 12, 17] for solving the biharmonic equation. The purpose of this paper is to develop an algorithm to implement the WG methods effectively. This can be achieved by eliminating local unknowns to obtain a global system with significant reduction of size. In fact this reduced global system is equivalent to the Schur complements of the WG methods. The unknowns of the Schur complement of the WG method are those defined on the element boundaries. The equivalence of theWG method and its Schur complement is established. The numerical results demonstrate themore » effectiveness of this new implementation technique.« less

Intentionally flawed manuscripts as means for teaching students to critically evaluate scientific papers.

PubMed

Ferenc, Jaroslav; Červenák, Filip; Birčák, Erik; Juríková, Katarína; Goffová, Ivana; Gorilák, Peter; Huraiová, Barbora; Plavá, Jana; Demecsová, Loriana; Ďuríková, Nikola; Galisová, Veronika; Gazdarica, Matej; Puškár, Marek; Nagy, Tibor; Nagyová, Soňa; Mentelová, Lucia; Slaninová, Miroslava; Ševčovicová, Andrea; Tomáška, Ľubomír

2018-01-01

As future scientists, university students need to learn how to avoid making errors in their own manuscripts, as well as how to identify flaws in papers published by their peers. Here we describe a novel approach on how to promote students' ability to critically evaluate scientific articles. The exercise is based on instructing teams of students to write intentionally flawed manuscripts describing the results of simple experiments. The teams are supervised by instructors advising the students during manuscript writing, choosing the 'appropriate' errors, monitoring the identification of errors made by the other team and evaluating the strength of their arguments in support of the identified errors. We have compared the effectiveness of the method with a journal club-type seminar. Based on the results of our assessment we propose that the described seminar may effectively complement the existing approaches to teach critical scientific thinking. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(1):22-30, 2018. © 2017 The International Union of Biochemistry and Molecular Biology.

HERAFitter: Open source QCD fit project

DOE PAGES

Alekhin, S.; Behnke, O.; Belov, P.; ...

2015-07-01

HERAFitter is an open-source package that provides a framework for the determination of the parton distribution functions (PDFs) of the proton and for many different kinds of analyses in Quantum Chromodynamics (QCD). It encodes results from a wide range of experimental measurements in lepton-proton deep inelastic scattering and proton-proton (proton-antiproton) collisions at hadron colliders. These are complemented with a variety of theoretical options for calculating PDF-dependent cross section predictions corresponding to the measurements. The framework covers a large number of the existing methods and schemes used for PDF determination. The data and theoretical predictions are brought together through numerous methodologicalmore » options for carrying out PDF fits and plotting tools to help visualise the results. While primarily based on the approach of collinear factorisation, HERAFitter also provides facilities for fits of dipole models and transverse-momentum dependent PDFs. The package can be used to study the impact of new precise measurements from hadron colliders. This paper describes the general structure of HERAFitter and its wide choice of options.« less

The potential inclusion of value management subject for postgraduate programmes in Malaysia

NASA Astrophysics Data System (ADS)

Che Mat, M.; Karim, S. B. Abd; Amran, N. A. E.

2018-02-01

The development of construction industry is increasing tremendously. To complement with this scenario, Value Management (VM) is needed to achieve the optimum function by reducing or eliminating the unnecessary cost that does not contribute to the product, system or service. As VM has been increasingly applied to enhance and improve value in construction projects, the purpose of this study is to implement VM as a subject for master’s students at selected public universities in Malaysia. The research is conducted to investigate the potential inclusion of VM as a subject at master degree programmes in Malaysia. Questionnaire survey was designed and delivered to existing master students to explore the current understanding of VM as well as the possibility of introducing VM as a subject. The results showed that the level of awareness on VM is high, yet the understanding of VM is low. This research presents the result of implementing VM as a subject learning for master’s level programme at selected public universities in Malaysia.

The Complexities of Family Caregiving at Work: A Mixed-Methods Study.

PubMed

Gaugler, Joseph E; Pestka, Deborah L; Davila, Heather; Sales, Rebecca; Owen, Greg; Baumgartner, Sarah A; Shook, Rocky; Cunningham, Jane; Kenney, Maureen

2018-01-01

The current project examined the impact of caregiving and caregiving-work conflict on employees' well-being. A sequential explanatory mixed-methods design (QUAN→qual) was utilized, and a total of 880 employees from a large health-care plan employer completed an online survey. Forty-five caregivers who completed the survey also participated in one of the five focus groups held 1 to 2 months later. Employed caregivers were significantly ( p < .05) more likely to indicate poorer physical and mental health than noncaregivers; among caregivers ( n = 370), caregiving-work conflict emerged as the most significant predictor of well-being and fully mediated the empirical relationship between burden and well-being. The focus group findings complemented the quantitative results; many of the challenges employed caregivers experience stem from their ability or inability to effectively balance their employment and caregiving roles. The results suggest the need to focus on caregiving-work conflict when constructing new or translating existing evidence-based caregiver interventions.

Systemic human CR2-targeted complement alternative pathway inhibitor ameliorates mouse laser-induced choroidal neovascularization.

PubMed

Rohrer, Bärbel; Coughlin, Beth; Bandyopadhyay, Mausumi; Holers, V Michael

2012-08-01

Genetic associations and the presence of complement components within pathological structures of age-related macular degeneration (AMD) have generated the hypothesis that AMD is caused by chronic local complement activation. Since the majority of activity in the common terminal pathway results from engagement of the amplification loop, the alternative pathway has been proposed as a logical therapeutic target. We recently generated a factor H (fH)-based complement inhibitor (CR2-fH) with the capacity to be "targeted" to sites of complement C3 activation. We asked whether the human therapeutic (TT30) is effective in a mouse model of AMD. Choroidal neovascularization (CNV) was induced by argon laser photocoagulation of Bruch's membrane. Every other day, mice received intravenous injections of TT30 or vehicles, and after 6 days, the presence or absence of CNV and CNV-related changes were evaluated. Area of CNV, photoreceptor cell function, gene expression for complement components and cytokines, vascular endothelial growth factor (VEGF) protein levels, and TT30 bioavailability were determined. CNV development, which has previously been shown to require local complement activation, could be reduced by intravenous TT30 delivery. Specific inhibition of the alternative pathway not only reduced angiogenesis in CNV, but also ameliorated changes in several associated disease-related biomarkers, including diminished retinal function and molecular events known to be involved in AMD such as VEGF production. After intravenous injection, TT30 localized to CNV lesion sites in the retinal pigmented epithelium-choroid. Systemic administration of TT30 was found to reduce CNV pathology. These data may open new avenues for novel systemic AMD treatment strategies.

A local complement response by RPE causes early-stage macular degeneration

PubMed Central

Fernandez-Godino, Rosario; Garland, Donita L.; Pierce, Eric A.

2015-01-01

Inherited and age-related macular degenerations (AMDs) are important causes of vision loss. An early hallmark of these disorders is the formation of sub-retinal pigment epithelium (RPE) basal deposits. A role for the complement system in MDs was suggested by genetic association studies, but direct functional connections between alterations in the complement system and the pathogenesis of MD remain to be defined. We used primary RPE cells from a mouse model of inherited MD due to a p.R345W mutation in EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) to investigate the role of the RPE in early MD pathogenesis. Efemp1R345W RPE cells recapitulate the basal deposit formation observed in vivo by producing sub-RPE deposits in vitro. The deposits share features with basal deposits, and their formation was mediated by EFEMP1R345W or complement component 3a (C3a), but not by complement component 5a (C5a). Increased activation of complement appears to occur in response to an abnormal extracellular matrix (ECM), generated by the mutant EFEMP1R345W protein and reduced ECM turnover due to inhibition of matrix metalloproteinase 2 by EFEMP1R345W and C3a. Increased production of C3a also stimulated the release of cytokines such as interleukin (IL)-6 and IL-1B, which appear to have a role in deposit formation, albeit downstream of C3a. These studies provide the first direct indication that complement components produced locally by the RPE are involved in the formation of basal deposits. Furthermore, these results suggest that C3a generated by RPE is a potential therapeutic target for the treatment of EFEMP1-associated MD as well as AMD. PMID:26199322

Microinjection of cytoplasm as a test of complementation in Paramecium

PubMed Central

1982-01-01

Mutants in Paramecium tetraurelia, unable to generate action potentials, have been isolated as cells which show no backward swimming in response to ionic stimulation. These "pawn" mutants belong to at least three complementation groups designated pwA, pwB, and pwC. We have found that microinjection of cytoplasm from a wild-type donor into a pawn recipient of any of the three complementation groups restores the ability of the pawn to generate action potentials and hence swim backward. In addition, the cytoplasm from a pawn cannot restore a recipient of the same complementation group, but that from a pawn of a different group can. Electrophysiological analysis had demonstrated that the restoration of backward swimming is not due to a simple addition of ions but represents a profound change in the excitable membrane of the recipient pawn cells. Using known pawn mutants and those which had previously been unclassified, we have been able to establish a perfect concordance of genetic complementation and complementation by cytoplasmic transfer through microinjection. This method has been used to classify pawn mutants that are sterile or hard- to-mate and to examine the ability of cytoplasms from different species of ciliated protozoa to restore the ability to swim backward in the pawn mutants of P. tetraurelia. A cell homogenate has also been fractionated by centrifugation to further purify the active components. These results demonstrate that transfer of cytoplasm between cells by microinjection can be a valid and systematic method to classify mutants. This test is simpler to perform than the genetic complementation test and can be used under favorable conditions in mutants that are sterile and in cells of different species. PMID:7061597

Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury

PubMed Central

Hou, Yunfang; Wong, Karen A.; Lee, Daniel; Rushbrook, Julie I.; Gulaya, Karan; Hines, Roberta; Hollis, Tamika; Nistal Nuno, Beatriz; Mangi, Abeel A.; Hashim, Sabet; Pekna, Marcela; Catalfamo, Amy; Chin, Hsiao-ying; Patel, Foramben; Rayala, Sravani; Shevde, Ketan; Heeger, Peter S.

2017-01-01

The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05) and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05). Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb) in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL), during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01). Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury. PMID:28662037

Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury.

PubMed

Chun, Nicholas; Haddadin, Ala S; Liu, Junying; Hou, Yunfang; Wong, Karen A; Lee, Daniel; Rushbrook, Julie I; Gulaya, Karan; Hines, Roberta; Hollis, Tamika; Nistal Nuno, Beatriz; Mangi, Abeel A; Hashim, Sabet; Pekna, Marcela; Catalfamo, Amy; Chin, Hsiao-Ying; Patel, Foramben; Rayala, Sravani; Shevde, Ketan; Heeger, Peter S; Zhang, Ming

2017-01-01

The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05) and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05). Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb) in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL), during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01). Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury.

Transformation of Schwanniomyces occidentalis with an ADE2 gene cloned from S. occidentalis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, R.D.; Favreau, M.A.

1988-12-01

We have developed an efficient transformation system for the industrial yeast Schwanniomyces occidentalis (formerly Schwanniomyces castellii). The transformation system is based on ade2 mutants of S. occidentalis deficient for phosphoribosylaminoimidazole carboxylase that were generated by mutagenesis. As a selectable marker, we isolated and characterized the S. occidentalis ADE2 gene by complementation in an ade2 strain of Saccharomyces cerevisiae. S. occidentalis was transformed with the recombinant plasmid pADE, consisting of a 4.5-kilobase-pair (kbp) DNA fragment from S. occidentalis containing the ADE2 gene inserted into the S. cerevisiae expression vector pYcDE8 by a modification of the spheroplasting procedure of Beggs. Intact plasmidsmore » were recovered in Escherichia coli from whole-cell lysates of ADE+ transformants, indicating that plasmids were replicating autonomously. High-molecular-mass species of pADE2 were found by Southern hybridization analysis of intact genomic DNA preparations. The shift to higher molecular mass of these plasmids during electrophoresis in the presence ethidium bromide after exposure to shortwave UV suggests that they exist in a supercoiled form in the transformed host. Subclones of the 4.5-kbp insert indicated that ADE2-complementing activity and sequences conferring autonomous replication in S. occidentalis were located within a 2.7-kbp EcoRI-SphI fragment. Plasmids containing this region cloned into the bacterial vector pUC19 complemented ade2 mutants of S. occidentalis with efficiencies identical to those of the original plasmid pADE.« less

Refining the Relationships among Historical Figures by Implementing Inference Rules in SWRL

NASA Astrophysics Data System (ADS)

Fajrin Ariyani, Nurul; Saralita, Madis; Sarwosri; Sarno, Riyanarto

2018-03-01

The biography of historical figures is often fascinating to be known. Everything about their character, work, invention, and personal life sometimes are presented in their biography. The social and family relationships among historical figures also put into concern, especially for political figures, heroes, kings or persons who have ever been ruled a monarchy in their past. Some biographies can be found in Wikipedia as articles. Most of the social and family relationship contents of these figures are not completely depicted due to a various article’s contributors and sources. Fortunately, the missing relatives of a person might reside in the other figures’ biography in different pages. Each Wikipedia article has metadata which represents its essential information of content. By processing the metadata obtained from DBpedia and composing the inferencing rules (in the form of ontology) to identify the relationships content, it can generate several new inferred facts that complement the existing relationships. This work proposes a methodology for finding missing relationships among historical figures using inference rules in an ontology. As a result, our method can present new facts about the relationships that absent in the existing Wikipedia articles.

Urban drainage control applying rational method and geographic information technologies

NASA Astrophysics Data System (ADS)

Aldalur, Beatriz; Campo, Alicia; Fernández, Sandra

2013-09-01

The objective of this study is to develop a method of controlling urban drainages in the town of Ingeniero White motivated by the problems arising as a result of floods, water logging and the combination of southeasterly and high tides. A Rational Method was applied to control urban watersheds and used tools of Geographic Information Technology (GIT). A Geographic Information System was developed on the basis of 28 panchromatic aerial photographs of 2005. They were georeferenced with control points measured with Global Positioning Systems (basin: 6 km2). Flow rates of basins and sub-basins were calculated and it was verified that the existing open channels have a low slope with the presence of permanent water and generate stagnation of water favored by the presence of trash. It is proposed for the output of storm drains, the use of an existing channel to evacuate the flow. The solution proposed in this work is complemented by the placement of three pumping stations: one on a channel to drain rain water which will allow the drain of the excess water from the lower area where is located the Ingeniero White city and the two others that will drain the excess liquid from the port area.

Measurement of motion detection of wireless capsule endoscope inside large intestine.

PubMed

Zhou, Mingda; Bao, Guanqun; Pahlavan, Kaveh

2014-01-01

Wireless Capsule Endoscope (WCE) provides a noninvasive way to inspect the entire Gastrointestinal (GI) tract, including large intestine, where intestinal diseases most likely occur. As a critical component of capsule endoscopic examination, physicians need to know the precise position of the endoscopic capsule in order to identify the position of detected intestinal diseases. Knowing how the capsule moves inside the large intestine would greatly complement the existing wireless localization systems by providing the motion information. Since the most recently released WCE can take up to 6 frames per second, it's possible to estimate the movement of the capsule by processing the successive image sequence. In this paper, a computer vision based approach without utilizing any external device is proposed to estimate the motion of WCE inside the large intestine. The proposed approach estimate the displacement and rotation of the capsule by calculating entropy and mutual information between frames using Fibonacci method. The obtained results of this approach show its stability and better performance over other existing approaches of motion measurements. Meanwhile, findings of this paper lay a foundation for motion pattern of WCEs inside the large intestine, which will benefit other medical applications.

The NuMAX Long Baseline Neutrino Factory Concept

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delahaye, J-P.; Ankenbrandt, C.; Bogacz, A.

A Neutrino Factory where neutrinos of all species are produced in equal quantities by muon decay is described as a facility at the intensity frontier for exquisite precision providing ideal conditions for ultimate neutrino studies and the ideal complement to Long Baseline Facilities like LBNF at Fermilab. It is foreseen to be built in stages with progressively increasing complexity and performance, taking advantage of existing or proposed facilities at an existing laboratory like Fermilab. A tentative layout based on a recirculating linac providing opportunities for considerable saving is discussed as well as its possible evolution toward a muon collider ifmore » and when requested by Physics. Tentative parameters of the various stages are presented as well as the necessary R&D to address the technological issues and demonstrate their feasibility.« less

Reconstructing gravitational wave source parameters via direct comparisons to numerical relativity I: Method

NASA Astrophysics Data System (ADS)

Lange, Jacob; O'Shaughnessy, Richard; Healy, James; Lousto, Carlos; Shoemaker, Deirdre; Lovelace, Geoffrey; Scheel, Mark; Ossokine, Serguei

2016-03-01

In this talk, we describe a procedure to reconstruct the parameters of sufficiently massive coalescing compact binaries via direct comparison with numerical relativity simulations. For sufficiently massive sources, existing numerical relativity simulations are long enough to cover the observationally accessible part of the signal. Due to the signal's brevity, the posterior parameter distribution it implies is broad, simple, and easily reconstructed from information gained by comparing to only the sparse sample of existing numerical relativity simulations. We describe how followup simulations can corroborate and improve our understanding of a detected source. Since our method can include all physics provided by full numerical relativity simulations of coalescing binaries, it provides a valuable complement to alternative techniques which employ approximations to reconstruct source parameters. Supported by NSF Grant PHY-1505629.

The NuMAX Long Baseline Neutrino Factory concept

DOE PAGES

Delahaye, J-P.; Ankenbrandt, C. M.; Bogacz, S. A.; ...

2018-06-01

A Neutrino Factory where neutrinos of all species are produced in equal quantities by muon decay is described as a facility at the intensity frontier for exquisite precision providing ideal conditions for ultimate neutrino studies and the ideal complement to Long Baseline Facilities like LBNF at Fermilab. It is foreseen to be built in stages with progressively increasing complexity and performance, taking advantage of existing or proposed facilities at an existing laboratory like Fermilab. A tentative layout based on a recirculating linac providing opportunities for considerable saving is discussed as well as its possible evolution toward a muon collider ifmore » and when requested by Physics. Tentative parameters of the various stages are presented as well as the necessary R&D to address the technological issues and demonstrate their feasibility.« less

The NuMAX Long Baseline Neutrino Factory concept

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delahaye, J-P.; Ankenbrandt, C. M.; Bogacz, S. A.

A Neutrino Factory where neutrinos of all species are produced in equal quantities by muon decay is described as a facility at the intensity frontier for exquisite precision providing ideal conditions for ultimate neutrino studies and the ideal complement to Long Baseline Facilities like LBNF at Fermilab. It is foreseen to be built in stages with progressively increasing complexity and performance, taking advantage of existing or proposed facilities at an existing laboratory like Fermilab. A tentative layout based on a recirculating linac providing opportunities for considerable saving is discussed as well as its possible evolution toward a muon collider ifmore » and when requested by Physics. Tentative parameters of the various stages are presented as well as the necessary R&D to address the technological issues and demonstrate their feasibility.« less

The NuMAX Long Baseline Neutrino Factory Concept

DOE PAGES

Delahaye, J-P.; Ankenbrandt, C.; Bogacz, A.; ...

2018-06-12

A Neutrino Factory where neutrinos of all species are produced in equal quantities by muon decay is described as a facility at the intensity frontier for exquisite precision providing ideal conditions for ultimate neutrino studies and the ideal complement to Long Baseline Facilities like LBNF at Fermilab. It is foreseen to be built in stages with progressively increasing complexity and performance, taking advantage of existing or proposed facilities at an existing laboratory like Fermilab. A tentative layout based on a recirculating linac providing opportunities for considerable saving is discussed as well as its possible evolution toward a muon collider ifmore » and when requested by Physics. Tentative parameters of the various stages are presented as well as the necessary R&D to address the technological issues and demonstrate their feasibility.« less

Let’s Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse

PubMed Central

Bennett, Kaila M.; Rooijakkers, Suzan H. M.; Gorham, Ronald D.

2017-01-01

The complement system is typically regarded as an effector arm of innate immunity, leading to recognition and killing of microbial invaders in body fluids. Consequently, pathogens have engaged in an arms race, evolving molecules that can interfere with proper complement responses. However, complement is no longer viewed as an isolated system, and links with other immune mechanisms are continually being discovered. Complement forms an important bridge between innate and adaptive immunity. While its roles in innate immunity are well-documented, its function in adaptive immunity is less characterized. Therefore, it is no surprise that the field of pathogenic complement evasion has focused on blockade of innate effector functions, while potential inhibition of adaptive immune responses (via complement) has been overlooked to a certain extent. In this review, we highlight past and recent developments on the involvement of complement in the adaptive immune response. We discuss the mechanisms by which complement aids in lymphocyte stimulation and regulation, as well as in antigen presentation. In addition, we discuss microbial complement evasion strategies, and highlight specific examples in the context of adaptive immune responses. These emerging ties between complement and adaptive immunity provide a catalyst for future discovery in not only the field of adaptive immune evasion but in elucidating new roles of complement. PMID:28197139

Let's Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse.

PubMed

Bennett, Kaila M; Rooijakkers, Suzan H M; Gorham, Ronald D

2017-01-01

The complement system is typically regarded as an effector arm of innate immunity, leading to recognition and killing of microbial invaders in body fluids. Consequently, pathogens have engaged in an arms race, evolving molecules that can interfere with proper complement responses. However, complement is no longer viewed as an isolated system, and links with other immune mechanisms are continually being discovered. Complement forms an important bridge between innate and adaptive immunity. While its roles in innate immunity are well-documented, its function in adaptive immunity is less characterized. Therefore, it is no surprise that the field of pathogenic complement evasion has focused on blockade of innate effector functions, while potential inhibition of adaptive immune responses (via complement) has been overlooked to a certain extent. In this review, we highlight past and recent developments on the involvement of complement in the adaptive immune response. We discuss the mechanisms by which complement aids in lymphocyte stimulation and regulation, as well as in antigen presentation. In addition, we discuss microbial complement evasion strategies, and highlight specific examples in the context of adaptive immune responses. These emerging ties between complement and adaptive immunity provide a catalyst for future discovery in not only the field of adaptive immune evasion but in elucidating new roles of complement.

Genetic control of the alternative pathway of complement in humans and age-related macular degeneration

PubMed Central

Hecker, Laura A.; Edwards, Albert O.; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H.; Brown, William L.; Issa, Peter Charbel; Scholl, Hendrik P.; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E.; Bailey, Kent R.; Oppermann, Martin

2010-01-01

Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues. PMID:19825847

Keeping It All Going-Complement Meets Metabolism.

PubMed

Kolev, Martin; Kemper, Claudia

2017-01-01

The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity-indicating that complement's function is likely broader than initially anticipated-the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond "classic" immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature-mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement's emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions. We will also discuss how taking a closer look into the evolution of key complement components not only made the functional connection between complement and metabolism rather "predictable" but how it may also give clues for the discovery of additional roles for complement in basic cellular processes.

Complement in Lupus Nephritis: New Perspectives.

PubMed

Bao, Lihua; Cunningham, Patrick N; Quigg, Richard J

2015-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical trials support the use of complement-targeted therapy in the treatment of SLE.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samarzija, Ivana; Beard, Peter, E-mail: peter.beard@epfl.ch

Highlights: Black-Right-Pointing-Pointer Unknown cellular mutations complement papillomavirus-induced carcinogenesis. Black-Right-Pointing-Pointer Hedgehog pathway components are expressed by cervical cancer cells. Black-Right-Pointing-Pointer Hedgehog pathway activators and inhibitors regulate cervical cancer cell biology. Black-Right-Pointing-Pointer Cell immortalization by papillomavirus and activation of Hedgehog are independent. -- Abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of themore » Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer.« less

Complement component C5a mediates hemorrhage-induced intestinal damage

PubMed Central

Fleming, Sherry D.; Phillips, Lauren M.; Lambris, John D.; Tsokos, George C.

2008-01-01

Background Complement has been implicated in the pathogenesis of intestinal damage and inflammation in multiple animal models. Although the exact mechanism is unknown, inhibition of complement prevents hemodynamic alterations in hemorrhage. Materials/Methods C57Bl/6, complement 5 deficient (C5−/−) and sufficient (C5+/+) mice were subjected to 25% blood loss. In some cases, C57Bl/6 mice were treated with C5a receptor antagonist (C5aRa) post-hemorrhage. Intestinal injury, leukotriene B4, and myeloperoxidase production were assessed for each treatment group of mice. Results Mice subjected to significant blood loss without major trauma develop intestinal inflammation and tissue damage within two hours. We report here that complement 5 (C5) deficient mice are protected from intestinal tissue damage when subjected to hemorrhage (Injury score = 0.36 compared to wildtype hemorrhaged animal injury score = 2.89; p<0.05). We present evidence that C5a represents the effector molecule because C57Bl/6 mice treated with a C5a receptor antagonist displayed limited intestinal injury (Injury score = 0.88), leukotriene B4 (13.16 pg/mg tissue) and myeloperoxidase (115.6 pg/mg tissue) production compared to hemorrhaged C57Bl/6 mice (p<0.05). Conclusion Complement activation is important in the development of hemorrhage-induced tissue injury and C5a generation is critical for tissue inflammation and damage. Thus, therapeutics targeting C5a may be useful therapeutics for hemorrhage-associated injury. PMID:18639891

Micrurus snake venoms activate human complement system and generate anaphylatoxins.

PubMed

Tanaka, Gabriela D; Pidde-Queiroz, Giselle; de Fátima D Furtado, Maria; van den Berg, Carmen; Tambourgi, Denise V

2012-01-16

The genus Micrurus, coral snakes (Serpentes, Elapidae), comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s) present in the venoms, which disrupts complement activation control. Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

Complement system and immunological mediators: Their involvements in the induced inflammatory process by Androctonus australis hector venom and its toxic components.

PubMed

Bekkari, Nadjia; Martin-Eauclaire, Marie-France; Laraba-Djebari, Fatima

2015-01-01

Androctonus australis hector scorpion venom is well known by its high toxicity, it induces massive release of neurotransmitters that lead to pathophysiological disorders in cardiovascular, neuro-hormonal and immune systems. Previous studies have shown the relationship between the severity of scorpion envenoming and immune system activation. This study was assessed to investigate the involvement of complement system and inflammatory mediators after sublethal injection of Aah venom, its toxic fraction (FtoxG50) and its main toxins (AahI and AahII) into NMRI mice. The Activation complement system by the venom is also compared to that induced of lipopolysaccharides (LPS). Obtained results showed that seric complement system (CS) is activated by the venom and by its toxic components; this activation is more pronounced into liver tissue when toxic components (FtoxG50, AahI or AahII) are used. Increase of cytokine levels (IL1β, TNFα and ICAM) into hepatic tissue induced by AahI or AahII neurotoxins is correlated with tissue alterations. Aprotinin, a non specific inhibitor of complement system seems to be able to reduce CS consumption and to restore partially the induced tissue damage by venom. The mechanisms by which toxic fraction or LPS induced the activation of complement system seem to be different. Sensitivity of hepatic tissue is more pronounced after FtoxG50 injection; however lung tissue is more sensible to LPS than FoxG50. Copyright © 2015 Elsevier GmbH. All rights reserved.

Determinism and Contingency Shape Metabolic Complementation in an Endosymbiotic Consortium

PubMed Central

Ponce-de-Leon, Miguel; Tamarit, Daniel; Calle-Espinosa, Jorge; Mori, Matteo; Latorre, Amparo; Montero, Francisco; Pereto, Juli

2017-01-01

Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism—which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca. Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome-scale metabolic network (GEM) for the bacterial consortium from the cedar aphid iBSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with iBSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is significant in the case of tryptophan biosynthesis, whereas vitamin production pathways seem to adopt suboptimal solutions. PMID:29213256

Determinism and Contingency Shape Metabolic Complementation in an Endosymbiotic Consortium.

PubMed

Ponce-de-Leon, Miguel; Tamarit, Daniel; Calle-Espinosa, Jorge; Mori, Matteo; Latorre, Amparo; Montero, Francisco; Pereto, Juli

2017-01-01

Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism-which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca . Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome-scale metabolic network (GEM) for the bacterial consortium from the cedar aphid i BSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with i BSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is significant in the case of tryptophan biosynthesis, whereas vitamin production pathways seem to adopt suboptimal solutions.

A Viral Receptor Complementation Strategy to Overcome CAV-2 Tropism for Efficient Retrograde Targeting of Neurons.

PubMed

Li, Shu-Jing; Vaughan, Alexander; Sturgill, James Fitzhugh; Kepecs, Adam

2018-06-06

Retrogradely transported neurotropic viruses enable genetic access to neurons based on their long-range projections and have become indispensable tools for linking neural connectivity with function. A major limitation of viral techniques is that they rely on cell-type-specific molecules for uptake and transport. Consequently, viruses fail to infect variable subsets of neurons depending on the complement of surface receptors expressed (viral tropism). We report a receptor complementation strategy to overcome this by potentiating neurons for the infection of the virus of interest-in this case, canine adenovirus type-2 (CAV-2). We designed AAV vectors for expressing the coxsackievirus and adenovirus receptor (CAR) throughout candidate projection neurons. CAR expression greatly increased retrograde-labeling rates, which we demonstrate for several long-range projections, including some resistant to other retrograde-labeling techniques. Our results demonstrate a receptor complementation strategy to abrogate endogenous viral tropism and thereby facilitate efficient retrograde targeting for functional analysis of neural circuits. Copyright © 2018 Elsevier Inc. All rights reserved.

Solving the Schroedinger Equation of Atoms and Molecules without Analytical Integration Based on the Free Iterative-Complement-Interaction Wave Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakatsuji, H.; Nakashima, H.; Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510

2007-12-14

A local Schroedinger equation (LSE) method is proposed for solving the Schroedinger equation (SE) of general atoms and molecules without doing analytic integrations over the complement functions of the free ICI (iterative-complement-interaction) wave functions. Since the free ICI wave function is potentially exact, we can assume a flatness of its local energy. The variational principle is not applicable because the analytic integrations over the free ICI complement functions are very difficult for general atoms and molecules. The LSE method is applied to several 2 to 5 electron atoms and molecules, giving an accuracy of 10{sup -5} Hartree in total energy.more » The potential energy curves of H{sub 2} and LiH molecules are calculated precisely with the free ICI LSE method. The results show the high potentiality of the free ICI LSE method for developing accurate predictive quantum chemistry with the solutions of the SE.« less

Metabolic Complementation in Bacterial Communities: Necessary Conditions and Optimality

PubMed Central

Mori, Matteo; Ponce-de-León, Miguel; Peretó, Juli; Montero, Francisco

2016-01-01

Bacterial communities may display metabolic complementation, in which different members of the association partially contribute to the same biosynthetic pathway. In this way, the end product of the pathway is synthesized by the community as a whole. However, the emergence and the benefits of such complementation are poorly understood. Herein, we present a simple model to analyze the metabolic interactions among bacteria, including the host in the case of endosymbiotic bacteria. The model considers two cell populations, with both cell types encoding for the same linear biosynthetic pathway. We have found that, for metabolic complementation to emerge as an optimal strategy, both product inhibition and large permeabilities are needed. In the light of these results, we then consider the patterns found in the case of tryptophan biosynthesis in the endosymbiont consortium hosted by the aphid Cinara cedri. Using in-silico computed physicochemical properties of metabolites of this and other biosynthetic pathways, we verified that the splitting point of the pathway corresponds to the most permeable intermediate. PMID:27774085

Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.

PubMed

Zhang, Jiaxiang; Zha, Wansheng; Wang, Feng; Jiang, Tao; Xu, Shuhai; Yu, Junfeng; Zhou, Chengfan; Shen, Tong; Wu, Changhao; Zhu, Qixing

2013-01-01

Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.

NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways

PubMed Central

Yuen, Joshua; Pluthero, Fred G.; Douda, David N.; Riedl, Magdalena; Cherry, Ahmed; Ulanova, Marina; Kahr, Walter H. A.; Palaniyar, Nades; Licht, Christoph

2016-01-01

Neutrophils deposit antimicrobial proteins, such as myeloperoxidase and proteases on chromatin, which they release as neutrophil extracellular traps (NETs). Neutrophils also carry key components of the complement alternative pathway (AP) such as properdin or complement factor P (CFP), complement factor B (CFB), and C3. However, the contribution of these complement components and complement activation during NET formation in the presence and absence of bacteria is poorly understood. We studied complement activation on NETs and a Gram-negative opportunistic bacterial pathogen Pseudomonas aeruginosa (PA01, PAKwt, and PAKgfp). Here, we show that anaphylatoxin C5a, formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA), which activates NADPH oxidase, induce the release of CFP, CFB, and C3 from neutrophils. In response to PMA or P. aeruginosa, neutrophils secrete CFP, deposit it on NETs and bacteria, and induce the formation of terminal complement complexes (C5b–9). A blocking anti-CFP antibody inhibited AP-mediated but not non-AP-mediated complement activation on NETs and P. aeruginosa. Therefore, NET-mediated complement activation occurs via both AP- and non AP-based mechanisms, and AP-mediated complement activation during NETosis is dependent on CFP. These findings suggest that neutrophils could use their “AP tool kit” to readily activate complement on NETs and Gram-negative bacteria, such as P. aeruginosa, whereas additional components present in the serum help to fix non-AP-mediated complement both on NETs and bacteria. This unique mechanism may play important roles in host defense and help to explain specific roles of complement activation in NET-related diseases. PMID:27148258

Blood SC5b-9 complement levels increase at parturition during term and preterm labor.

PubMed

Segura-Cervantes, Enrique; Mancilla-Ramirez, Javier; Zurita, Luis; Paredes, Yuriria; Arredondo, José Luis; Galindo-Sevilla, Norma

2015-06-01

We explored the hypothesis that complement, an innate and adaptive immune effector, is active in the plasma of parturient women and is deposited on fetal membranes collected after delivery. A cross-sectional study was designed to evaluate complement activity at parturition. Pregnant women (n = 97) between 15 and 41 years of age were enrolled in a hospital protocol during the perinatal period to assess both SC5b-9 complement activity in blood and complement deposition on fetal membranes during parturition. Soluble SC5b-9 complement activity in plasma fractions was measured using a standard enzyme-linked immunosorbent assay (ELISA) that included specific anti-complement antibodies. Complement deposition on membranes was analyzed using immuno-dot blots and immunohistochemistry. Soluble SC5b-9 complement complex levels were increased in the plasma of women during term labor (TL; median 3361; range 1726-5670 ng/mL), preterm labor (PL; median 2958; range 1552-7092 ng/mL), and preterm premature rupture of membranes (PPROM; median 2272; range 167-6540 ng/mL) compared with pregnant women who were not in labor (P; median 1384; range 174-4570 ng/mL; P < 0.001, Kruskal-Wallis test). Active complement, as assessed by the C9 neo-antigen in C5b-9 complexes, was deposited on fetal membranes, with no difference between term and preterm delivery. The deposition of active complement on fetal membranes was confirmed by immunohistochemistry. Women who underwent non-labor-indicated Cesarean sections did not exhibit complement deposition. Soluble SC5b-9 complement complex levels increased in the plasma of women during parturition, and complement C5b-9 complexes were deposited on fetal membranes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Complement Constructions in English: Fairly Difficult for EFL Language Learners

ERIC Educational Resources Information Center

Fazeli, Fatemeh; Shokrpour, Nasrin

2012-01-01

Complement constructions vary significantly in English and Persian. There are more complementation structures in English than in Persian and a complement structure in Persian might have more than one equivalent in English. Producing complement structures (CSs) in English is very difficult for native speakers of Persian, especially in an EFL…

Direct Maximization of Protein Identifications from Tandem Mass Spectra*

PubMed Central

Spivak, Marina; Weston, Jason; Tomazela, Daniela; MacCoss, Michael J.; Noble, William Stafford

2012-01-01

The goal of many shotgun proteomics experiments is to determine the protein complement of a complex biological mixture. For many mixtures, most methodological approaches fall significantly short of this goal. Existing solutions to this problem typically subdivide the task into two stages: first identifying a collection of peptides with a low false discovery rate and then inferring from the peptides a corresponding set of proteins. In contrast, we formulate the protein identification problem as a single optimization problem, which we solve using machine learning methods. This approach is motivated by the observation that the peptide and protein level tasks are cooperative, and the solution to each can be improved by using information about the solution to the other. The resulting algorithm directly controls the relevant error rate, can incorporate a wide variety of evidence and, for complex samples, provides 18–34% more protein identifications than the current state of the art approaches. PMID:22052992

Contributions of a global network of tree diversity experiments to sustainable forest plantations.

PubMed

Verheyen, Kris; Vanhellemont, Margot; Auge, Harald; Baeten, Lander; Baraloto, Christopher; Barsoum, Nadia; Bilodeau-Gauthier, Simon; Bruelheide, Helge; Castagneyrol, Bastien; Godbold, Douglas; Haase, Josephine; Hector, Andy; Jactel, Hervé; Koricheva, Julia; Loreau, Michel; Mereu, Simone; Messier, Christian; Muys, Bart; Nolet, Philippe; Paquette, Alain; Parker, John; Perring, Mike; Ponette, Quentin; Potvin, Catherine; Reich, Peter; Smith, Andy; Weih, Martin; Scherer-Lorenzen, Michael

2016-02-01

The area of forest plantations is increasing worldwide helping to meet timber demand and protect natural forests. However, with global change, monospecific plantations are increasingly vulnerable to abiotic and biotic disturbances. As an adaption measure we need to move to plantations that are more diverse in genotypes, species, and structure, with a design underpinned by science. TreeDivNet, a global network of tree diversity experiments, responds to this need by assessing the advantages and disadvantages of mixed species plantations. The network currently consists of 18 experiments, distributed over 36 sites and five ecoregions. With plantations 1-15 years old, TreeDivNet can already provide relevant data for forest policy and management. In this paper, we highlight some early results on the carbon sequestration and pest resistance potential of more diverse plantations. Finally, suggestions are made for new, innovative experiments in understudied regions to complement the existing network.

High geothermal energy utilization geothermal/fossil hybrid power cycle: a preliminary investigation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grijalva, R. L.; Sanemitsu, S. K.

1978-11-01

Combining geothermal and fossil fuel energy into the so-called hybrid cycle is compared with a state-of-the-art double-flash geothermal power cycle using resources which vary from 429/sup 0/K (312/sup 0/F) to 588/sup 0/K (598/sup 0/F). It is demonstrated that a hybrid plant can compete thermodynamically with the combined output from both a fossil-fired and a geothermal plant operating separately. Economic comparison of the hybrid and double-flash cycles is outlined, and results are presented that indicate the performance of marginal hydrothermal resources may be improved enough to compete with existing power cycles on a cost basis. It is also concluded that onmore » a site-specific basis a hybrid cycle is capable of complementing double-flash cycles at large-capacity resources, and can operate in a cycling load mode at constant geothermal fluid flow rate.« less

Direct laser writing of micro-supercapacitors on hydrated graphite oxide films.

PubMed

Gao, Wei; Singh, Neelam; Song, Li; Liu, Zheng; Reddy, Arava Leela Mohana; Ci, Lijie; Vajtai, Robert; Zhang, Qing; Wei, Bingqing; Ajayan, Pulickel M

2011-07-31

Microscale supercapacitors provide an important complement to batteries in a variety of applications, including portable electronics. Although they can be manufactured using a number of printing and lithography techniques, continued improvements in cost, scalability and form factor are required to realize their full potential. Here, we demonstrate the scalable fabrication of a new type of all-carbon, monolithic supercapacitor by laser reduction and patterning of graphite oxide films. We pattern both in-plane and conventional electrodes consisting of reduced graphite oxide with micrometre resolution, between which graphite oxide serves as a solid electrolyte. The substantial amounts of trapped water in the graphite oxide makes it simultaneously a good ionic conductor and an electrical insulator, allowing it to serve as both an electrolyte and an electrode separator with ion transport characteristics similar to that observed for Nafion membranes. The resulting micro-supercapacitor devices show good cyclic stability, and energy storage capacities comparable to existing thin-film supercapacitors.

Direct laser writing of micro-supercapacitors on hydrated graphite oxide films

NASA Astrophysics Data System (ADS)

Gao, Wei; Singh, Neelam; Song, Li; Liu, Zheng; Reddy, Arava Leela Mohana; Ci, Lijie; Vajtai, Robert; Zhang, Qing; Wei, Bingqing; Ajayan, Pulickel M.

2011-08-01

Microscale supercapacitors provide an important complement to batteries in a variety of applications, including portable electronics. Although they can be manufactured using a number of printing and lithography techniques, continued improvements in cost, scalability and form factor are required to realize their full potential. Here, we demonstrate the scalable fabrication of a new type of all-carbon, monolithic supercapacitor by laser reduction and patterning of graphite oxide films. We pattern both in-plane and conventional electrodes consisting of reduced graphite oxide with micrometre resolution, between which graphite oxide serves as a solid electrolyte. The substantial amounts of trapped water in the graphite oxide makes it simultaneously a good ionic conductor and an electrical insulator, allowing it to serve as both an electrolyte and an electrode separator with ion transport characteristics similar to that observed for Nafion membranes. The resulting micro-supercapacitor devices show good cyclic stability, and energy storage capacities comparable to existing thin-film supercapacitors.

Radio frequency analog electronics based on carbon nanotube transistors

PubMed Central

Kocabas, Coskun; Kim, Hoon-sik; Banks, Tony; Rogers, John A.; Pesetski, Aaron A.; Baumgardner, James E.; Krishnaswamy, S. V.; Zhang, Hong

2008-01-01

The potential to exploit single-walled carbon nanotubes (SWNTs) in advanced electronics represents a continuing, major source of interest in these materials. However, scalable integration of SWNTs into circuits is challenging because of difficulties in controlling the geometries, spatial positions, and electronic properties of individual tubes. We have implemented solutions to some of these challenges to yield radio frequency (RF) SWNT analog electronic devices, such as narrow band amplifiers operating in the VHF frequency band with power gains as high as 14 dB. As a demonstration, we fabricated nanotube transistor radios, in which SWNT devices provide all of the key functions, including resonant antennas, fixed RF amplifiers, RF mixers, and audio amplifiers. These results represent important first steps to practical implementation of SWNTs in high-speed analog circuits. Comparison studies indicate certain performance advantages over silicon and capabilities that complement those in existing compound semiconductor technologies. PMID:18227509

Secret Lives of Cepheids: beta Dor as a Test of Cepheid X-ray Heating Mechanisms

NASA Astrophysics Data System (ADS)

Engle, Scott

2017-09-01

We propose two 40 ksec phase-constrained ACIS-I observations of the 9.8 day Cepheid beta Dor. This will fill its uncharted 0.9-0.2 phase gap to confirm and define (Lx, kT) its pulsation-driven X-ray variations and help identify the mechanism (shocks, magnetic fields, turbulent dynamos) responsible, in complement to our recent confirmation of pulsation-induced X-ray variations from delta Cep (Engle et al. 2017). Beta Dor has different properties than delta Cep (P = 9.8/5.4d; R = 61/44Rsun), and the proposed visits are crucial to combine with existing X-ray and FUV data and test the X-ray heating mechanisms. This program is the culmination of several years of work, and the resulting nearly complete phase coverage of beta Dor makes this Cepheid the timeliest and most promising target.

Fuzzy Logic Approaches to Multi-Objective Decision-Making in Aerospace Applications

NASA Technical Reports Server (NTRS)

Hardy, Terry L.

1994-01-01

Fuzzy logic allows for the quantitative representation of multi-objective decision-making problems which have vague or fuzzy objectives and parameters. As such, fuzzy logic approaches are well-suited to situations where alternatives must be assessed by using criteria that are subjective and of unequal importance. This paper presents an overview of fuzzy logic and provides sample applications from the aerospace industry. Applications include an evaluation of vendor proposals, an analysis of future space vehicle options, and the selection of a future space propulsion system. On the basis of the results provided in this study, fuzzy logic provides a unique perspective on the decision-making process, allowing the evaluator to assess the degree to which each option meets the evaluation criteria. Future decision-making should take full advantage of fuzzy logic methods to complement existing approaches in the selection of alternatives.

Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice

PubMed Central

Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue

2015-01-01

Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281

Constraints on Cosmic Strings from the LIGO-Virgo Gravitational-Wave Detectors

NASA Astrophysics Data System (ADS)

Aasi, J.; Abadie, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Accadia, T.; Acernese, F.; Adams, C.; Adams, T.; Adhikari, R. X.; Affeldt, C.; Agathos, M.; Aggarwal, N.; Aguiar, O. D.; Ajith, P.; Allen, B.; Allocca, A.; Amador Ceron, E.; Amariutei, D.; Anderson, R. A.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C.; Areeda, J.; Ast, S.; Aston, S. M.; Astone, P.; Aufmuth, P.; Aulbert, C.; Austin, L.; Aylott, B. E.; Babak, S.; Baker, P. T.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barker, D.; Barnum, S. H.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J.; Bauchrowitz, J.; Bauer, Th. S.; Bebronne, M.; Behnke, B.; Bejger, M.; Beker, M. G.; Bell, A. S.; Bell, C.; Belopolski, I.; Bergmann, G.; Berliner, J. M.; Bersanetti, D.; Bertolini, A.; Bessis, D.; Betzwieser, J.; Beyersdorf, P. T.; Bhadbhade, T.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Bitossi, M.; Bizouard, M. A.; Black, E.; Blackburn, J. K.; Blackburn, L.; Blair, D.; Blom, M.; Bock, O.; Bodiya, T. P.; Boer, M.; Bogan, C.; Bond, C.; Bondu, F.; Bonelli, L.; Bonnand, R.; Bork, R.; Born, M.; Boschi, V.; Bose, S.; Bosi, L.; Bowers, J.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brannen, C. A.; Brau, J. E.; Breyer, J.; Briant, T.; Bridges, D. O.; Brillet, A.; Brinkmann, M.; Brisson, V.; Britzger, M.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brückner, F.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Calderón Bustillo, J.; Calloni, E.; Camp, J. B.; Campsie, P.; Cannon, K. C.; Canuel, B.; Cao, J.; Capano, C. D.; Carbognani, F.; Carbone, L.; Caride, S.; Castiglia, A.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C.; Cesarini, E.; Chakraborty, R.; Chalermsongsak, T.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Chen, X.; Chen, Y.; Chincarini, A.; Chiummo, A.; Cho, H. S.; Chow, J.; Christensen, N.; Chu, Q.; Chua, S. S. Y.; Chung, S.; Ciani, G.; Clara, F.; Clark, D. E.; Clark, J. A.; Cleva, F.; Coccia, E.; Cohadon, P.-F.; Colla, A.; Colombini, M.; Constancio, M.; Conte, A.; Conte, R.; Cook, D.; Corbitt, T. R.; Cordier, M.; Cornish, N.; Corsi, A.; Costa, C. A.; Coughlin, M. W.; Coulon, J.-P.; Countryman, S.; Couvares, P.; Coward, D. M.; Cowart, M.; Coyne, D. C.; Craig, K.; Creighton, J. D. E.; Creighton, T. D.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dahl, K.; Canton, T. Dal; Damjanic, M.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Dattilo, V.; Daudert, B.; Daveloza, H.; Davier, M.; Davies, G. S.; Daw, E. J.; Day, R.; Dayanga, T.; De Rosa, R.; Debreczeni, G.; Degallaix, J.; Del Pozzo, W.; Deleeuw, E.; Deléglise, S.; Denker, T.; Dent, T.; Dereli, H.; Dergachev, V.; DeRosa, R.; DeSalvo, R.; Dhurandhar, S.; Di Fiore, L.; Di Lieto, A.; Di Palma, I.; Di Virgilio, A.; Díaz, M.; Dietz, A.; Dmitry, K.; Donovan, F.; Dooley, K. L.; Doravari, S.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Dumas, J.-C.; Dwyer, S.; Eberle, T.; Edwards, M.; Effler, A.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Endrőczi, G.; Essick, R.; Etzel, T.; Evans, K.; Evans, M.; Evans, T.; Factourovich, M.; Fafone, V.; Fairhurst, S.; Fang, Q.; Farinon, S.; Farr, B.; Farr, W.; Favata, M.; Fazi, D.; Fehrmann, H.; Feldbaum, D.; Ferrante, I.; Ferrini, F.; Fidecaro, F.; Finn, L. S.; Fiori, I.; Fisher, R.; Flaminio, R.; Foley, E.; Foley, S.; Forsi, E.; Fotopoulos, N.; Fournier, J.-D.; Franco, S.; Frasca, S.; Frasconi, F.; Frede, M.; Frei, M.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fujimoto, M.-K.; Fulda, P.; Fyffe, M.; Gair, J.; Gammaitoni, L.; Garcia, J.; Garufi, F.; Gehrels, N.; Gemme, G.; Genin, E.; Gennai, A.; Gergely, L.; Ghosh, S.; Giaime, J. A.; Giampanis, S.; Giardina, K. D.; Giazotto, A.; Gil-Casanova, S.; Gill, C.; Gleason, J.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gordon, N.; Gorodetsky, M. L.; Gossan, S.; Goßler, S.; Gouaty, R.; Graef, C.; Graff, P. B.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Griffo, C.; Groot, P.; Grote, H.; Grover, K.; Grunewald, S.; Guidi, G. M.; Guido, C.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hall, B.; Hall, E.; Hammer, D.; Hammond, G.; Hanke, M.; Hanks, J.; Hanna, C.; Hanson, J.; Harms, J.; Harry, G. M.; Harry, I. W.; Harstad, E. D.; Hartman, M. T.; Haughian, K.; Hayama, K.; Heefner, J.; Heidmann, A.; Heintze, M.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Holt, K.; Holtrop, M.; Hong, T.; Hooper, S.; Horrom, T.; Hosken, D. J.; Hough, J.; Howell, E. J.; Hu, Y.; Hua, Z.; Huang, V.; Huerta, E. A.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh, M.; Huynh-Dinh, T.; Iafrate, J.; Ingram, D. R.; Inta, R.; Isogai, T.; Ivanov, A.; Iyer, B. R.; Izumi, K.; Jacobson, M.; James, E.; Jang, H.; Jang, Y. J.; Jaranowski, P.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; Haris, K.; Kalmus, P.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kasprzack, M.; Kasturi, R.; Katsavounidis, E.; Katzman, W.; Kaufer, H.; Kaufman, K.; Kawabe, K.; Kawamura, S.; Kawazoe, F.; Kéfélian, F.; Keitel, D.; Kelley, D. B.; Kells, W.; Keppel, D. G.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, B. K.; Kim, C.; Kim, K.; Kim, N.; Kim, W.; Kim, Y.-M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimenko, S.; Kline, J.; Koehlenbeck, S.; Kokeyama, K.; Kondrashov, V.; Koranda, S.; Korth, W. Z.; Kowalska, I.; Kozak, D.; Kremin, A.; Kringel, V.; Królak, A.; Kucharczyk, C.; Kudla, S.; Kuehn, G.; Kumar, A.; Kumar, P.; Kumar, R.; Kurdyumov, R.; Kwee, P.; Landry, M.; Lantz, B.; Larson, S.; Lasky, P. D.; Lawrie, C.; Lazzarini, A.; Le Roux, A.; Leaci, P.; Lebigot, E. O.; Lee, C.-H.; Lee, H. K.; Lee, H. M.; Lee, J.; Lee, J.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levine, B.; Lewis, J. B.; Lhuillier, V.; Li, T. G. F.; Lin, A. C.; Littenberg, T. B.; Litvine, V.; Liu, F.; Liu, H.; Liu, Y.; Liu, Z.; Lloyd, D.; Lockerbie, N. A.; Lockett, V.; Lodhia, D.; Loew, K.; Logue, J.; Lombardi, A. L.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J.; Luan, J.; Lubinski, M. J.; Lück, H.; Lundgren, A. P.; Macarthur, J.; Macdonald, E.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magana-Sandoval, F.; Mageswaran, M.; Mailand, K.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Manca, G. M.; Mandel, I.; Mandic, V.; Mangano, V.; Mantovani, M.; Marchesoni, F.; Marion, F.; Márka, S.; Márka, Z.; Markosyan, A.; Maros, E.; Marque, J.; Martelli, F.; Martin, I. W.; Martin, R. M.; Martinelli, L.; Martynov, D.; Marx, J. N.; Mason, K.; Masserot, A.; Massinger, T. J.; Matichard, F.; Matone, L.; Matzner, R. A.; Mavalvala, N.; May, G.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McGuire, S. C.; McIntyre, G.; McIver, J.; Meacher, D.; Meadors, G. D.; Mehmet, M.; Meidam, J.; Meier, T.; Melatos, A.; Mendell, G.; Mercer, R. A.; Meshkov, S.; Messenger, C.; Meyer, M. S.; Miao, H.; Michel, C.; Mikhailov, E. E.; Milano, L.; Miller, J.; Minenkov, Y.; Mingarelli, C. M. F.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moe, B.; Mohan, M.; Mohapatra, S. R. P.; Mokler, F.; Moraru, D.; Moreno, G.; Morgado, N.; Mori, T.; Morriss, S. R.; Mossavi, K.; Mours, B.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Munch, J.; Murphy, D.; Murray, P. G.; Mytidis, A.; Nagy, M. F.; Nanda Kumar, D.; Nardecchia, I.; Nash, T.; Naticchioni, L.; Nayak, R.; Necula, V.; Nelemans, G.; Neri, I.; Neri, M.; Newton, G.; Nguyen, T.; Nishida, E.; Nishizawa, A.; Nitz, A.; Nocera, F.; Nolting, D.; Normandin, M. E.; Nuttall, L. K.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oppermann, P.; O'Reilly, B.; Ortega Larcher, W.; O'Shaughnessy, R.; Osthelder, C.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Ou, J.; Overmier, H.; Owen, B. J.; Padilla, C.; Pai, A.; Palomba, C.; Pan, Y.; Pankow, C.; Paoletti, F.; Paoletti, R.; Papa, M. A.; Paris, H.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Pedraza, M.; Peiris, P.; Penn, S.; Perreca, A.; Phelps, M.; Pichot, M.; Pickenpack, M.; Piergiovanni, F.; Pierro, V.; Pinard, L.; Pindor, B.; Pinto, I. M.; Pitkin, M.; Poeld, J.; Poggiani, R.; Poole, V.; Poux, C.; Predoi, V.; Prestegard, T.; Price, L. R.; Prijatelj, M.; Principe, M.; Privitera, S.; Prix, R.; Prodi, G. A.; Prokhorov, L.; Puncken, O.; Punturo, M.; Puppo, P.; Quetschke, V.; Quintero, E.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Rácz, I.; Radkins, H.; Raffai, P.; Raja, S.; Rajalakshmi, G.; Rakhmanov, M.; Ramet, C.; Rapagnani, P.; Raymond, V.; Re, V.; Reed, C. M.; Reed, T.; Regimbau, T.; Reid, S.; Reitze, D. H.; Ricci, F.; Riesen, R.; Riles, K.; Robertson, N. A.; Robinet, F.; Rocchi, A.; Roddy, S.; Rodriguez, C.; Rodruck, M.; Roever, C.; Rolland, L.; Rollins, J. G.; Romano, R.; Romanov, G.; Romie, J. H.; Rosińska, D.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Ryan, K.; Salemi, F.; Sammut, L.; Sandberg, V.; Sanders, J.; Sannibale, V.; Santiago-Prieto, I.; Saracco, E.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Savage, R.; Schilling, R.; Schnabel, R.; Schofield, R. M. S.; Schreiber, E.; Schuette, D.; Schulz, B.; Schutz, B. F.; Schwinberg, P.; Scott, J.; Scott, S. M.; Seifert, F.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sergeev, A.; Shaddock, D.; Shah, S.; Shahriar, M. S.; Shaltev, M.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sidery, T. L.; Siellez, K.; Siemens, X.; Sigg, D.; Simakov, D.; Singer, A.; Singer, L.; Sintes, A. M.; Skelton, G. R.; Slagmolen, B. J. J.; Slutsky, J.; Smith, J. R.; Smith, M. R.; Smith, R. J. E.; Smith-Lefebvre, N. D.; Soden, K.; Son, E. J.; Sorazu, B.; Souradeep, T.; Sperandio, L.; Staley, A.; Steinert, E.; Steinlechner, J.; Steinlechner, S.; Steplewski, S.; Stevens, D.; Stochino, A.; Stone, R.; Strain, K. A.; Straniero, N.; Strigin, S.; Stroeer, A. S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Susmithan, S.; Sutton, P. J.; Swinkels, B.; Szeifert, G.; Tacca, M.; Talukder, D.; Tang, L.; Tanner, D. B.; Tarabrin, S. P.; Taylor, R.; ter Braack, A. P. M.; Thirugnanasambandam, M. P.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, V.; Tokmakov, K. V.; Tomlinson, C.; Toncelli, A.; Tonelli, M.; Torre, O.; Torres, C. V.; Torrie, C. I.; Travasso, F.; Traylor, G.; Tse, M.; Ugolini, D.; Unnikrishnan, C. S.; Vahlbruch, H.; Vajente, G.; Vallisneri, M.; van den Brand, J. F. J.; Van Den Broeck, C.; van der Putten, S.; van der Sluys, M. V.; van Heijningen, J.; van Veggel, A. A.; Vass, S.; Vasúth, M.; Vaulin, R.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Verkindt, D.; Verma, S.; Vetrano, F.; Viceré, A.; Vincent-Finley, R.; Vinet, J.-Y.; Vitale, S.; Vlcek, B.; Vo, T.; Vocca, H.; Vorvick, C.; Vousden, W. D.; Vrinceanu, D.; Vyachanin, S. P.; Wade, A.; Wade, L.; Wade, M.; Waldman, S. J.; Walker, M.; Wallace, L.; Wan, Y.; Wang, J.; Wang, M.; Wang, X.; Wanner, A.; Ward, R. L.; Was, M.; Weaver, B.; Wei, L.-W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.; Wessels, P.; West, M.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Wibowo, S.; Wiesner, K.; Wilkinson, C.; Williams, L.; Williams, R.; Williams, T.; Willis, J. L.; Willke, B.; Wimmer, M.; Winkelmann, L.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Yablon, J.; Yakushin, I.; Yamamoto, H.; Yancey, C. C.; Yang, H.; Yeaton-Massey, D.; Yoshida, S.; Yum, H.; Yvert, M.; ZadroŻny, A.; Zanolin, M.; Zendri, J.-P.; Zhang, F.; Zhang, L.; Zhao, C.; Zhu, H.; Zhu, X. J.; Zotov, N.; Zucker, M. E.; Zweizig, J.; LIGO Scientific Collaboration; Virgo Collaboration

2014-04-01

Cosmic strings can give rise to a large variety of interesting astrophysical phenomena. Among them, powerful bursts of gravitational waves (GWs) produced by cusps are a promising observational signature. In this Letter we present a search for GWs from cosmic string cusps in data collected by the LIGO and Virgo gravitational wave detectors between 2005 and 2010, with over 625 days of live time. We find no evidence of GW signals from cosmic strings. From this result, we derive new constraints on cosmic string parameters, which complement and improve existing limits from previous searches for a stochastic background of GWs from cosmic microwave background measurements and pulsar timing data. In particular, if the size of loops is given by the gravitational backreaction scale, we place upper limits on the string tension Gμ below 10-8 in some regions of the cosmic string parameter space.

Laser pulse bidirectional reflectance from CALIPSO mission

NASA Astrophysics Data System (ADS)

Lu, Xiaomei; Hu, Yongxiang; Yang, Yuekui; Vaughan, Mark; Liu, Zhaoyan; Rodier, Sharon; Hunt, William; Powell, Kathy; Lucker, Patricia; Trepte, Charles

2018-06-01

This paper presents an innovative retrieval method that translates the CALIOP land surface laser pulse returns into the surface bidirectional reflectance. To better analyze the surface returns, the CALIOP receiver impulse response and the downlinked samples' distribution at 30 m vertical resolution are discussed. The saturated laser pulse magnitudes from snow and ice surfaces are recovered based on information extracted from the tail end of the surface signal. The retrieved snow surface bidirectional reflectance is compared with reflectance from both CALIOP cloud-covered regions and MODIS BRDF-albedo model parameters. In addition to the surface bidirectional reflectance, the column top-of-atmosphere bidirectional reflectances are calculated from the CALIOP lidar background data and compared with the bidirectional reflectances derived from WFC radiance measurements. The retrieved CALIOP surface bidirectional reflectance and column top-of-atmosphere bidirectional reflectance results provide unique information to complement existing MODIS standard data products and are expected to have valuable applications for modelers.

Constraints on Cosmic Strings from the LIGO-Virgo Gravitational-Wave Detectors

NASA Technical Reports Server (NTRS)

Aasi, J.; Abadie, J.; Abbott, B.P.; Abbott, R.; Abbott, T.; Abernathy, M.R.; Accadia, T.; Adams, C.; Adams, T.; Adhikari, R.X.;

Levonorgestrel-releasing intrauterine system (LNG-IUS 12) for prevention of pregnancy for up to five years.

PubMed

Nelson, Anita L

2017-08-01

A new five-year low dose, smaller-framed, levonorgestrel-releasing intrauterine contraceptive system (LNG-IUS 12) has been introduced to complement the currently available systems. Areas Covered: This article will provide an overview of this new intrauterine system - its composition and its mechanisms of action as well as the results of the Phase II and III clinical trials of its efficacy, safety and tolerability. Expert Commentary: This new LNG-IUS 12 provides five-year contraceptive protection a pregnancy rate (less than 1%) in first year of use, which puts it into the top tier with the existing LNG-IUS 20 products; however, the LNG-IUS 12 does not have the high rates of amenorrhea often seen with the higher dose devices. On the other hand, this new IUD shares the smaller frame and narrower insertion tube with the lower dose LNG-IUS 8, but offers longer effective life.

Carbonate-Promoted Hydrogenation of Carbon Dioxide to Multicarbon Carboxylates

PubMed Central

2018-01-01

CO2 hydrogenation is a potential alternative to conventional petrochemical methods for making commodity chemicals and fuels. Research in this area has focused mostly on transition-metal-based catalysts. Here we show that hydrated alkali carbonates promote CO2 hydrogenation to formate, oxalate, and other C2+ carboxylates at elevated temperature and pressure in the absence of transition-metal catalysts or solvent. The reactions proceed rapidly, reaching up to 56% yield (with respect to CO32–) within minutes. Isotope labeling experiments indicate facile H2 and C–H deprotonations in the alkali cation-rich reaction media and identify probable intermediates for the C–C bond formations leading to the various C2+ products. The carboxylate salts are in equilibrium with volatile carboxylic acids under CO2 hydrogenation conditions, which may enable catalytic carboxylic acid syntheses. Our results provide a foundation for base-promoted and base-catalyzed CO2 hydrogenation processes that could complement existing approaches. PMID:29806007

The design of two stage to orbit vehicles

NASA Astrophysics Data System (ADS)

Gregorek, G. M.; Ramsay, T. N.

1991-09-01

Two designs are presented for a two-stage-to-orbit vehicle to complement an existing heavy lift vehicle. The payload is 10,000 lbs and 27 ft long by 10 ft in diameter for design purposes and must be carried to a low earth orbit by an air-breathing carrier configuration that can take off horizontally within 15,000 ft. Two designs are presented: a delta wing/body carrier in which the fuselage contains the orbiter; and a cranked-delta wing/body carrier in which the orbiter is carried piggy back. The engines for both carriers are turbofanramjets powered with liquid hydrogen, and the orbiters employ either a Space Shuttle Main Engine or a half-scale version with additional scramjet engines. The orbiter based on a full-scale Space Shuttle Main Engine is found to have a significantly higher takeoff weight which results in a higher total takeoff weight.

Automation effects in a multiloop manual control system

NASA Technical Reports Server (NTRS)

Hess, R. A.; Mcnally, B. D.

1986-01-01

An experimental and analytical study was undertaken to investigate human interaction with a simple multiloop manual control system in which the human's activity was systematically varied by changing the level of automation. The system simulated was the longitudinal dynamics of a hovering helicopter. The automation-systems-stabilized vehicle responses from attitude to velocity to position and also provided for display automation in the form of a flight director. The control-loop structure resulting from the task definition can be considered a simple stereotype of a hierarchical control system. The experimental study was complemented by an analytical modeling effort which utilized simple crossover models of the human operator. It was shown that such models can be extended to the description of multiloop tasks involving preview and precognitive human operator behavior. The existence of time optimal manual control behavior was established for these tasks and the role which internal models may play in establishing human-machine performance was discussed.

The relationship between psychiatric symptomatology and motivation of challenging behaviour: a preliminary study.

PubMed

Holden, Børge; Gitlesen, Jens Petter

2008-01-01

In addition to explaining challenging behaviour by way of behaviour analytic, functional analyses, challenging behaviour is increasingly explained by way of psychiatric symptomatology. According to some researchers, the two approaches complement each other, as psychiatric symptomatology may form a motivational basis for the individual's response to more immediate environmental challenges, like deprivation and aversive conditions. The most common example may be that depressive mood may render task demands aversive. Consequently, the person may show escape-motivated challenging behaviour in the presence of demands. The question becomes whether, or to what extent, relationships between psychiatric symptomatologies and particular functions of challenging behaviour exist. In the present, preliminary study, PAS-ADD checklist, a psychiatric screening instrument, and motivation assessment scale (MAS) were employed in order to investigate this issue. The results show that symptomatologies are largely unrelated to particular behavioural functions. Practical implications are discussed.

Spotting the difference in molecular dynamics simulations of biomolecules

NASA Astrophysics Data System (ADS)

Sakuraba, Shun; Kono, Hidetoshi

2016-08-01

Comparing two trajectories from molecular simulations conducted under different conditions is not a trivial task. In this study, we apply a method called Linear Discriminant Analysis with ITERative procedure (LDA-ITER) to compare two molecular simulation results by finding the appropriate projection vectors. Because LDA-ITER attempts to determine a projection such that the projections of the two trajectories do not overlap, the comparison does not suffer from a strong anisotropy, which is an issue in protein dynamics. LDA-ITER is applied to two test cases: the T4 lysozyme protein simulation with or without a point mutation and the allosteric protein PDZ2 domain of hPTP1E with or without a ligand. The projection determined by the method agrees with the experimental data and previous simulations. The proposed procedure, which complements existing methods, is a versatile analytical method that is specialized to find the "difference" between two trajectories.

Benchmark of ReaxFF force field for subcritical and supercritical water.

PubMed

Manzano, Hegoi; Zhang, Weiwei; Raju, Muralikrishna; Dolado, Jorge S; López-Arbeloa, Iñigo; van Duin, Adri C T

2018-06-21

Water in the subcritical and supercritical states has remarkable properties that make it an excellent solvent for oxidation of hazardous chemicals, waste separation, and green synthesis. Molecular simulations are a valuable complement to experiments in order to understand and improve the relevant sub- and super-critical reaction mechanisms. Since water molecules under these conditions can act not only as a solvent but also as a reactant, dissociative force fields are especially interesting to investigate these processes. In this work, we evaluate the capacity of the ReaxFF force field to reproduce the microstructure, hydrogen bonding, dielectric constant, diffusion, and proton transfer of sub- and super-critical water. Our results indicate that ReaxFF is able to simulate water properties in these states in very good quantitative agreement with the existing experimental data, with the exception of the static dielectric constant that is reproduced only qualitatively.

Constraints on cosmic strings from the LIGO-Virgo gravitational-wave detectors.

PubMed

Aasi, J; Abadie, J; Abbott, B P; Abbott, R; Abbott, T; Abernathy, M R; Accadia, T; Acernese, F; Adams, C; Adams, T; Adhikari, R X; Affeldt, C; Agathos, M; Aggarwal, N; Aguiar, O D; Ajith, P; Allen, B; Allocca, A; Amador Ceron, E; Amariutei, D; Anderson, R A; Anderson, S B; Anderson, W G; Arai, K; Araya, M C; Arceneaux, C; Areeda, J; Ast, S; Aston, S M; Astone, P; Aufmuth, P; Aulbert, C; Austin, L; Aylott, B E; Babak, S; Baker, P T; Ballardin, G; Ballmer, S W; Barayoga, J C; Barker, D; Barnum, S H; Barone, F; Barr, B; Barsotti, L; Barsuglia, M; Barton, M A; Bartos, I; Bassiri, R; Basti, A; Batch, J; Bauchrowitz, J; Bauer, Th S; Bebronne, M; Behnke, B; Bejger, M; Beker, M G; Bell, A S; Bell, C; Belopolski, I; Bergmann, G; Berliner, J M; Bersanetti, D; Bertolini, A; Bessis, D; Betzwieser, J; Beyersdorf, P T; Bhadbhade, T; Bilenko, I A; Billingsley, G; Birch, J; Bitossi, M; Bizouard, M A; Black, E; Blackburn, J K; Blackburn, L; Blair, D; Blom, M; Bock, O; Bodiya, T P; Boer, M; Bogan, C; Bond, C; Bondu, F; Bonelli, L; Bonnand, R; Bork, R; Born, M; Boschi, V; Bose, S; Bosi, L; Bowers, J; Bradaschia, C; Brady, P R; Braginsky, V B; Branchesi, M; Brannen, C A; Brau, J E; Breyer, J; Briant, T; Bridges, D O; Brillet, A; Brinkmann, M; Brisson, V; Britzger, M; Brooks, A F; Brown, D A; Brown, D D; Brückner, F; Bulik, T; Bulten, H J; Buonanno, A; Buskulic, D; Buy, C; Byer, R L; Cadonati, L; Cagnoli, G; Calderón Bustillo, J; Calloni, E; Camp, J B; Campsie, P; Cannon, K C; Canuel, B; Cao, J; Capano, C D; Carbognani, F; Carbone, L; Caride, S; Castiglia, A; Caudill, S; Cavaglià, M; Cavalier, F; Cavalieri, R; Cella, G; Cepeda, C; Cesarini, E; Chakraborty, R; Chalermsongsak, T; Chao, S; Charlton, P; Chassande-Mottin, E; Chen, X; Chen, Y; Chincarini, A; Chiummo, A; Cho, H S; Chow, J; Christensen, N; Chu, Q; Chua, S S Y; Chung, S; Ciani, G; Clara, F; Clark, D E; Clark, J A; Cleva, F; Coccia, E; Cohadon, P-F; Colla, A; Colombini, M; Constancio, M; Conte, A; Conte, R; Cook, D; Corbitt, T R; Cordier, M; Cornish, N; Corsi, A; Costa, C A; Coughlin, M W; Coulon, J-P; Countryman, S; Couvares, P; Coward, D M; Cowart, M; Coyne, D C; Craig, K; Creighton, J D E; Creighton, T D; Crowder, S G; Cumming, A; Cunningham, L; Cuoco, E; Dahl, K; Dal Canton, T; Damjanic, M; Danilishin, S L; D'Antonio, S; Danzmann, K; Dattilo, V; Daudert, B; Daveloza, H; Davier, M; Davies, G S; Daw, E J; Day, R; Dayanga, T; De Rosa, R; Debreczeni, G; Degallaix, J; Del Pozzo, W; Deleeuw, E; Deléglise, S; Denker, T; Dent, T; Dereli, H; Dergachev, V; DeRosa, R; DeSalvo, R; Dhurandhar, S; Di Fiore, L; Di Lieto, A; Di Palma, I; Di Virgilio, A; Díaz, M; Dietz, A; Dmitry, K; Donovan, F; Dooley, K L; Doravari, S; Drago, M; Drever, R W P; Driggers, J C; Du, Z; Dumas, J-C; Dwyer, S; Eberle, T; Edwards, M; Effler, A; Ehrens, P; Eichholz, J; Eikenberry, S S; Endrőczi, G; Essick, R; Etzel, T; Evans, K; Evans, M; Evans, T; Factourovich, M; Fafone, V; Fairhurst, S; Fang, Q; Farinon, S; Farr, B; Farr, W; Favata, M; Fazi, D; Fehrmann, H; Feldbaum, D; Ferrante, I; Ferrini, F; Fidecaro, F; Finn, L S; Fiori, I; Fisher, R; Flaminio, R; Foley, E; Foley, S; Forsi, E; Fotopoulos, N; Fournier, J-D; Franco, S; Frasca, S; Frasconi, F; Frede, M; Frei, M; Frei, Z; Freise, A; Frey, R; Fricke, T T; Fritschel, P; Frolov, V V; Fujimoto, M-K; Fulda, P; Fyffe, M; Gair, J; Gammaitoni, L; Garcia, J; Garufi, F; Gehrels, N; Gemme, G; Genin, E; Gennai, A; Gergely, L; Ghosh, S; Giaime, J A; Giampanis, S; Giardina, K D; Giazotto, A; Gil-Casanova, S; Gill, C; Gleason, J; Goetz, E; Goetz, R; Gondan, L; González, G; Gordon, N; Gorodetsky, M L; Gossan, S; Goßler, S; Gouaty, R; Graef, C; Graff, P B; Granata, M; Grant, A; Gras, S; Gray, C; Greenhalgh, R J S; Gretarsson, A M; Griffo, C; Groot, P; Grote, H; Grover, K; Grunewald, S; Guidi, G M; Guido, C; Gushwa, K E; Gustafson, E K; Gustafson, R; Hall, B; Hall, E; Hammer, D; Hammond, G; Hanke, M; Hanks, J; Hanna, C; Hanson, J; Harms, J; Harry, G M; Harry, I W; Harstad, E D; Hartman, M T; Haughian, K; Hayama, K; Heefner, J; Heidmann, A; Heintze, M; Heitmann, H; Hello, P; Hemming, G; Hendry, M; Heng, I S; Heptonstall, A W; Heurs, M; Hild, S; Hoak, D; Hodge, K A; Holt, K; Holtrop, M; Hong, T; Hooper, S; Horrom, T; Hosken, D J; Hough, J; Howell, E J; Hu, Y; Hua, Z; Huang, V; Huerta, E A; Hughey, B; Husa, S; Huttner, S H; Huynh, M; Huynh-Dinh, T; Iafrate, J; Ingram, D R; Inta, R; Isogai, T; Ivanov, A; Iyer, B R; Izumi, K; Jacobson, M; James, E; Jang, H; Jang, Y J; Jaranowski, P; Jiménez-Forteza, F; Johnson, W W; Jones, D; Jones, D I; Jones, R; Jonker, R J G; Ju, L; K, Haris; Kalmus, P; Kalogera, V; Kandhasamy, S; Kang, G; Kanner, J B; Kasprzack, M; Kasturi, R; Katsavounidis, E; Katzman, W; Kaufer, H; Kaufman, K; Kawabe, K; Kawamura, S; Kawazoe, F; Kéfélian, F; Keitel, D; Kelley, D B; Kells, W; Keppel, D G; Khalaidovski, A; Khalili, F Y; Khazanov, E A; Kim, B K; Kim, C; Kim, K; Kim, N; Kim, W; Kim, Y-M; King, E J; King, P J; Kinzel, D L; Kissel, J S; Klimenko, S; Kline, J; Koehlenbeck, S; Kokeyama, K; Kondrashov, V; Koranda, S; Korth, W Z; Kowalska, I; Kozak, D; Kremin, A; Kringel, V; Królak, A; Kucharczyk, C; Kudla, S; Kuehn, G; Kumar, A; Kumar, P; Kumar, R; Kurdyumov, R; Kwee, P; Landry, M; Lantz, B; Larson, S; Lasky, P D; Lawrie, C; Lazzarini, A; Le Roux, A; Leaci, P; Lebigot, E O; Lee, C-H; Lee, H K; Lee, H M; Lee, J; Lee, J; Leonardi, M; Leong, J R; Leroy, N; Letendre, N; Levine, B; Lewis, J B; Lhuillier, V; Li, T G F; Lin, A C; Littenberg, T B; Litvine, V; Liu, F; Liu, H; Liu, Y; Liu, Z; Lloyd, D; Lockerbie, N A; Lockett, V; Lodhia, D; Loew, K; Logue, J; Lombardi, A L; Lorenzini, M; Loriette, V; Lormand, M; Losurdo, G; Lough, J; Luan, J; Lubinski, M J; Lück, H; Lundgren, A P; Macarthur, J; Macdonald, E; Machenschalk, B; MacInnis, M; Macleod, D M; Magana-Sandoval, F; Mageswaran, M; Mailand, K; Majorana, E; Maksimovic, I; Malvezzi, V; Man, N; Manca, G M; Mandel, I; Mandic, V; Mangano, V; Mantovani, M; Marchesoni, F; Marion, F; Márka, S; Márka, Z; Markosyan, A; Maros, E; Marque, J; Martelli, F; Martin, I W; Martin, R M; Martinelli, L; Martynov, D; Marx, J N; Mason, K; Masserot, A; Massinger, T J; Matichard, F; Matone, L; Matzner, R A; Mavalvala, N; May, G; Mazumder, N; Mazzolo, G; McCarthy, R; McClelland, D E; McGuire, S C; McIntyre, G; McIver, J; Meacher, D; Meadors, G D; Mehmet, M; Meidam, J; Meier, T; Melatos, A; Mendell, G; Mercer, R A; Meshkov, S; Messenger, C; Meyer, M S; Miao, H; Michel, C; Mikhailov, E E; Milano, L; Miller, J; Minenkov, Y; Mingarelli, C M F; Mitra, S; Mitrofanov, V P; Mitselmakher, G; Mittleman, R; Moe, B; Mohan, M; Mohapatra, S R P; Mokler, F; Moraru, D; Moreno, G; Morgado, N; Mori, T; Morriss, S R; Mossavi, K; Mours, B; Mow-Lowry, C M; Mueller, C L; Mueller, G; Mukherjee, S; Mullavey, A; Munch, J; Murphy, D; Murray, P G; Mytidis, A; Nagy, M F; Nanda Kumar, D; Nardecchia, I; Nash, T; Naticchioni, L; Nayak, R; Necula, V; Nelemans, G; Neri, I; Neri, M; Newton, G; Nguyen, T; Nishida, E; Nishizawa, A; Nitz, A; Nocera, F; Nolting, D; Normandin, M E; Nuttall, L K; Ochsner, E; O'Dell, J; Oelker, E; Ogin, G H; Oh, J J; Oh, S H; Ohme, F; Oppermann, P; O'Reilly, B; Ortega Larcher, W; O'Shaughnessy, R; Osthelder, C; Ott, C D; Ottaway, D J; Ottens, R S; Ou, J; Overmier, H; Owen, B J; Padilla, C; Pai, A; Palomba, C; Pan, Y; Pankow, C; Paoletti, F; Paoletti, R; Papa, M A; Paris, H; Pasqualetti, A; Passaquieti, R; Passuello, D; Pedraza, M; Peiris, P; Penn, S; Perreca, A; Phelps, M; Pichot, M; Pickenpack, M; Piergiovanni, F; Pierro, V; Pinard, L; Pindor, B; Pinto, I M; Pitkin, M; Poeld, J; Poggiani, R; Poole, V; Poux, C; Predoi, V; Prestegard, T; Price, L R; Prijatelj, M; Principe, M; Privitera, S; Prix, R; Prodi, G A; Prokhorov, L; Puncken, O; Punturo, M; Puppo, P; Quetschke, V; Quintero, E; Quitzow-James, R; Raab, F J; Rabeling, D S; Rácz, I; Radkins, H; Raffai, P; Raja, S; Rajalakshmi, G; Rakhmanov, M; Ramet, C; Rapagnani, P; Raymond, V; Re, V; Reed, C M; Reed, T; Regimbau, T; Reid, S; Reitze, D H; Ricci, F; Riesen, R; Riles, K; Robertson, N A; Robinet, F; Rocchi, A; Roddy, S; Rodriguez, C; Rodruck, M; Roever, C; Rolland, L; Rollins, J G; Romano, R; Romanov, G; Romie, J H; Rosińska, D; Rowan, S; Rüdiger, A; Ruggi, P; Ryan, K; Salemi, F; Sammut, L; Sandberg, V; Sanders, J; Sannibale, V; Santiago-Prieto, I; Saracco, E; Sassolas, B; Sathyaprakash, B S; Saulson, P R; Savage, R; Schilling, R; Schnabel, R; Schofield, R M S; Schreiber, E; Schuette, D; Schulz, B; Schutz, B F; Schwinberg, P; Scott, J; Scott, S M; Seifert, F; Sellers, D; Sengupta, A S; Sentenac, D; Sergeev, A; Shaddock, D; Shah, S; Shahriar, M S; Shaltev, M; Shapiro, B; Shawhan, P; Shoemaker, D H; Sidery, T L; Siellez, K; Siemens, X; Sigg, D; Simakov, D; Singer, A; Singer, L; Sintes, A M; Skelton, G R; Slagmolen, B J J; Slutsky, J; Smith, J R; Smith, M R; Smith, R J E; Smith-Lefebvre, N D; Soden, K; Son, E J; Sorazu, B; Souradeep, T; Sperandio, L; Staley, A; Steinert, E; Steinlechner, J; Steinlechner, S; Steplewski, S; Stevens, D; Stochino, A; Stone, R; Strain, K A; Straniero, N; Strigin, S; Stroeer, A S; Sturani, R; Stuver, A L; Summerscales, T Z; Susmithan, S; Sutton, P J; Swinkels, B; Szeifert, G; Tacca, M; Talukder, D; Tang, L; Tanner, D B; Tarabrin, S P; Taylor, R; ter Braack, A P M; Thirugnanasambandam, M P; Thomas, M; Thomas, P; Thorne, K A; Thorne, K S; Thrane, E; Tiwari, V; Tokmakov, K V; Tomlinson, C; Toncelli, A; Tonelli, M; Torre, O; Torres, C V; Torrie, C I; Travasso, F; Traylor, G; Tse, M; Ugolini, D; Unnikrishnan, C S; Vahlbruch, H; Vajente, G; Vallisneri, M; van den Brand, J F J; Van Den Broeck, C; van der Putten, S; van der Sluys, M V; van Heijningen, J; van Veggel, A A; Vass, S; Vasúth, M; Vaulin, R; Vecchio, A; Vedovato, G; Veitch, J; Veitch, P J; Venkateswara, K; Verkindt, D; Verma, S; Vetrano, F; Viceré, A; Vincent-Finley, R; Vinet, J-Y; Vitale, S; Vlcek, B; Vo, T; Vocca, H; Vorvick, C; Vousden, W D; Vrinceanu, D; Vyachanin, S P; Wade, A; Wade, L; Wade, M; Waldman, S J; Walker, M; Wallace, L; Wan, Y; Wang, J; Wang, M; Wang, X; Wanner, A; Ward, R L; Was, M; Weaver, B; Wei, L-W; Weinert, M; Weinstein, A J; Weiss, R; Welborn, T; Wen, L; Wessels, P; West, M; Westphal, T; Wette, K; Whelan, J T; Whitcomb, S E; White, D J; Whiting, B F; Wibowo, S; Wiesner, K; Wilkinson, C; Williams, L; Williams, R; Williams, T; Willis, J L; Willke, B; Wimmer, M; Winkelmann, L; Winkler, W; Wipf, C C; Wittel, H; Woan, G; Worden, J; Yablon, J; Yakushin, I; Yamamoto, H; Yancey, C C; Yang, H; Yeaton-Massey, D; Yoshida, S; Yum, H; Yvert, M; Zadrożny, A; Zanolin, M; Zendri, J-P; Zhang, F; Zhang, L; Zhao, C; Zhu, H; Zhu, X J; Zotov, N; Zucker, M E; Zweizig, J

2014-04-04

Cosmic strings can give rise to a large variety of interesting astrophysical phenomena. Among them, powerful bursts of gravitational waves (GWs) produced by cusps are a promising observational signature. In this Letter we present a search for GWs from cosmic string cusps in data collected by the LIGO and Virgo gravitational wave detectors between 2005 and 2010, with over 625 days of live time. We find no evidence of GW signals from cosmic strings. From this result, we derive new constraints on cosmic string parameters, which complement and improve existing limits from previous searches for a stochastic background of GWs from cosmic microwave background measurements and pulsar timing data. In particular, if the size of loops is given by the gravitational backreaction scale, we place upper limits on the string tension Gμ below 10(-8) in some regions of the cosmic string parameter space.

[Anxious School Absenteeism: Cognitive-Behavioral Treatment of School Phobia at a Psychological Counseling Center].

PubMed

Diegel, Klaus

2015-01-01

Resulting from a shortage of possibilities in the ambulant treatment of school phobia behavior-therapeutic interventions were established at a psychological counseling center for families twenty years ago, which have been in existence to this day. The criteria of anxiety-based absenteeism as well as problems of terminology and classification will be presented with emphasis on school phobia as a combination of separation anxiety and social anxiety ("Schulphobie"). The multimodal treatment focuses on cognitive interventions, graduated exposition and close cooperation with teachers. The counselor is also in charge of the networking and cooperation of all people concerned. A short case study is used to illustrate the process. Measures such as training and information for teachers and school social workers and a manual for the comprehension and the treatment of school phobia, which was edited in cooperation with a psychological counseling center for schools complement the treatment.

Robust Takagi-Sugeno fuzzy control for fractional order hydro-turbine governing system.

PubMed

Wang, Bin; Xue, Jianyi; Wu, Fengjiao; Zhu, Delan

2016-11-01

A robust fuzzy control method for fractional order hydro-turbine governing system (FOHGS) in the presence of random disturbances is investigated in this paper. Firstly, the mathematical model of FOHGS is introduced, and based on Takagi-Sugeno (T-S) fuzzy rules, the generalized T-S fuzzy model of FOHGS is presented. Secondly, based on fractional order Lyapunov stability theory, a novel T-S fuzzy control method is designed for the stability control of FOHGS. Thirdly, the relatively loose sufficient stability condition is acquired, which could be transformed into a group of linear matrix inequalities (LMIs) via Schur complement as well as the strict mathematical derivation is given. Furthermore, the control method could resist random disturbances, which shows the good robustness. Simulation results indicate the designed fractional order T-S fuzzy control scheme works well compared with the existing method. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Design and Evaluation of a Cross-Cultural Training System

NASA Technical Reports Server (NTRS)

Santarelli, Thomas; Stagl, Kevin C.

2011-01-01

Cross-cultural competency, and the underlying communication and affective skills required to develop such expertise, is becoming increasingly important for a wide variety of domains. To address this need, we developed a blended learning platform which combines virtual role-play with tutorials, assessment and feedback. A Middle-Eastern Curriculum (MEC) exemplar for cross-cultural training U.S. military personnel was developed to guide the refinement of an existing game-based training platform. To complement this curriculum, we developed scenario authoring tools to enable end-users to define training objectives, link performance measures and feedback/remediation to these objectives, and deploy experiential scenarios within a game-based virtual environment (VE). Lessons learned from the design and development of this exemplar cross-cultural competency curriculum, as well as formative evaluation results, are discussed. Initial findings suggest that the underlying training technology promotes deep levels of semantic processing of the key information of relevant cultural and communication skills.

Forgiveness and justice: a research agenda for social and personality psychology.

PubMed

Exline, Julie Juola; Worthington, Everett L; Hill, Peter; McCullough, Michael E

2003-01-01

Forgiveness and related constructs (e.g., repentance, mercy, reconciliation) are ripe for study by social and personality psychologists, including those interested in justice. Current trends in social science, law, management, philosophy, and theology suggest a need to expand existing justice frameworks to incorporate alternatives or complements to retribution, including forgiveness and related processes. In this article, we raise five challenging empirical questions about forgiveness. For each question, we briefly review representative research, raise hypotheses, and suggest specific ways in which social and personality psychologists could make distinctive contributions.

Synchronization of chaotic and nonchaotic oscillators: Application to bipolar disorder

NASA Astrophysics Data System (ADS)

Nono Dueyou Buckjohn, C.; Siewe Siewe, M.; Tchawoua, C.; Kofane, T. C.

2010-08-01

In this Letter, we use a synchronization scheme on two bipolar disorder models consisting of a strong nonlinear system with multiplicative excitation and a nonlinear oscillator without parametric harmonic forcing. The stability condition following our control function is analytically demonstrated using the Lyapunov theory and Routh-Hurwitz criteria, we then have the condition for the existence of a feedback gain matrix. A convenient demonstration of the accuracy of the method is complemented by the numerical simulations from which we illustrate the synchronized dynamics between the two non-identical bipolar disorder patients.

Data that empower: The success and promise of CF patient registries.

PubMed

Fink, Aliza K; Loeffler, Deena R; Marshall, Bruce C; Goss, Christopher H; Morgan, Wayne J

2017-11-01

In this article, we describe existing CF registries with a focus on US registry data collected through the CF Foundation Patient Registry (CFFPR) and the Epidemiologic Study of CF (ESCF); highlight what registries have taught us regarding epidemiology of CF; showcase the impact of registries on research and clinical care; and discuss future directions. This manuscript complements the plenary address given by Dr Wayne Morgan at the 2016 North American CF Conference by summarizing the key points from the presentation and providing additional detail and information. © 2017 Wiley Periodicals, Inc.

Systematic approaches to toxicology in the zebrafish.

PubMed

Peterson, Randall T; Macrae, Calum A

2012-01-01

As the current paradigms of drug discovery evolve, it has become clear that a more comprehensive understanding of the interactions between small molecules and organismal biology will be vital. The zebrafish is emerging as a complement to existing in vitro technologies and established preclinical in vivo models that can be scaled for high-throughput. In this review, we highlight the current status of zebrafish toxicology studies, identify potential future niches for the model in the drug development pipeline, and define the hurdles that must be overcome as zebrafish technologies are refined for systematic toxicology.

Partners in Technology

NASA Technical Reports Server (NTRS)

1984-01-01

Deere and Company scientists are working with various NASA centers in a multifaceted technical exchange program investigating areas of aerospace technology that can be applied to company's products. This is a non-traditional type spinoff in that it does not simply reapply existing technology but development of new technology using Deere's extensive R & D capability to complement NASA's efforts, adapting NASA information to new research paths and providing feedback of importance to NASA's own work. NASA/Deere exchange extends to these areas: Composite materials, ceramics, wear and lubrication, plasma coatings and sensors, and electronics.

Nuclear Resonance Fluorescence of U-235 above 3 MeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Glen A.; Caggiano, Joseph A.; Miller, Erin A.

Pacific Northwest National Laboratory and Passport Systems have collaborated to conduct measurements to search for a nuclear resonance fluorescence response of U-235 from 3 to 5 MeV using an 8 g sample of highly enriched uranium. These new measurements complement previously reported measurements below 3 MeV. Preliminary analysis indicates that no strong resonances exist for U-235 in this energy range. A second set of measurements focused on a signature search in the 5 to 10 MeV range is still under analysis.

Radiation testing of GaAs on CRRES and LIPS experiment

NASA Technical Reports Server (NTRS)

Trumble, T. M.; Masloski, K.

1984-01-01

The radiation damage of solar cells has become a prime concern to the U.S. Air Force due to longer satellite lifetime requirements. Flight experiments were undertaken on the Navy Living Plume Shield (LPS) satellite and the NASA/Air Force Combined Release and Radiation Effects Satellite (CRRES) to complement existing radiation testing. Each experiment, the rationale behind it, and its approach and status are presented. The effect of space radiation on gallium arsenide (GaAs) solar cells was the central parameter investigated. Specifications of the GaAs solar cells are given.

Pressure dependence of carbonate exchange with [NpO 2(CO 3) 3] 4– in aqueous solutions

DOE PAGES

Pilgrim, Corey D.; Zavarin, Mavrik; Casey, William H.

2016-12-13

Here, the rates of ligand exchange into the geochemically important [NpO 2(CO 3) 3] 4– aqueous complex are measured as a function of pressure in order to complement existing data on the isostructural [UO 2(CO 3) 3] 4– complex. Experiments are conducted at pH conditions where the rate of exchange is independent of the proton concentration. Unexpectedly, the experiments show a distinct difference in the pressure dependencies of rates of exchange for the uranyl and neptunyl complexes.

Distal radical migration strategy: an emerging synthetic means.

PubMed

Li, Weipeng; Xu, Wentao; Xie, Jin; Yu, Shouyun; Zhu, Chengjian

2018-02-05

The remote radical migration strategy has gained considerable momentum. During the past three years, we have witnessed the rapid development of sustainable and practical C-C and C-H bond functionalization by means of long-distance 1,n-radical migration (n = 4, 5, 6) events. Its advent brings our chemical community a new platform to deal with the challenging migration transformations and thus complements the existing ionic-type migration protocols. In this review, the recent achievements in distal radical migration triggered C-C and C-H bond functionalization are summarized.

Complement fixation test to C burnetii

MedlinePlus

... complement fixation test; Coxiella burnetii - complement fixation test; C burnetii - complement fixation test ... a specific foreign substance ( antigen ), in this case, C burnetii . Antibodies defend the body against bacteria, viruses, ...

Dengue virus induces increased activity of the complement alternative pathway in infected cells.

PubMed

Cabezas, Sheila; Bracho, Gustavo; L Aloia, Amanda; Adamson, Penelope J; Bonder, Claudine S; Smith, Justine R; Gordon, David L; Carr, Jillian M

2018-05-09

Severe dengue virus (DENV) infection is associated with overactivity of the complement alternative pathway (AP) in patient studies. Here, the molecular changes in components of the AP during DENV infection in vitro are investigated. mRNA for factor H (FH) a major negative regulator of the AP, is significantly increased in DENV-infected endothelial cells (EC) and macrophages but in contrast production of extracellular FH protein is not. This discord is not seen for the AP activator, factor B (FB), with DENV induction of both FB mRNA and protein, nor with Toll-like receptor 3 or 4 stimulation of EC and macrophages, which induces both FH and FB mRNA and protein. Surface bound and intracellular FH protein is however induced by DENV, but only in DENV antigen-positive cells, while in two other DENV-susceptible immortalised cell lines (ARPE-19 and HREC) FH protein is induced both intracellularly and extracellularly by DENV infection. Regardless of the cell type, there is an imbalance in AP components and an increase in markers of complement AP activity associated with DENV-infected cells - with lower FH relative to FB protein, increased ability to promote AP-mediated lytic activity and increased deposition of complement component C3b on the surface of DENV-infected cells. For EC in particular, these changes are predicted to result in higher complement activity in the local cellular microenvironment, with the potential to induce functional changes that may result in increased vascular permeability, a hallmark of dengue disease. IMPORTANCE Dengue virus (DENV) is a significant human viral pathogen with global medical and economic impact. DENV may cause serious and life-threatening disease with increased vascular permeability and plasma leakage. The pathogenic mechanisms underlying these features remain unclear; however overactivity of the complement alternative pathway has been suggested to play a role. In this study we investigate the molecular events that may be responsible for this observed alternative pathway overactivity and provide novel findings of changes in the complement system in response to DENV infection in primary cell types that are a major target for DENV infection (macrophages) and pathogenesis (endothelial cells) in vivo Our results suggest a new dimension of cellular events that may influence endothelial cell barrier function during DENV infection that could expand strategies for developing therapeutics to prevent or control DENV-mediated vascular disease. Copyright © 2018 American Society for Microbiology.

Effect of Nanoparticles on Complement System in Cell Culture Model

DTIC Science & Technology

2006-09-15

case complement activation considerably differs between nanoparticles , being the highest in case of fullerene, ferric oxide and aluminium oxide ... oxide (CdO; 1 µm), manganese oxide (MnO2; 1-2 µm), and tungsten (W; 27 µm) were assessed. Additionally the effects of nanoparticles coated with...using in vitro system. Obtained results indicate that: 1. Nanoparticles toxicity in vitro can’t be measured using methods which were designed

Complement pathway biomarkers and age-related macular degeneration

PubMed Central

Gemenetzi, M; Lotery, A J

2016-01-01

In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

Effects of partial replacement of fish meal by yeast hydrolysate on complement system and stress resistance in juvenile Jian carp (Cyprinus carpio var. Jian).

PubMed

Yuan, Xiang-Yang; Liu, Wen-Bin; Liang, Chao; Sun, Cun-Xin; Xue, Yun-Fei; Wan, Zu-De; Jiang, Guang-Zhen

2017-08-01

A 10-week feeding trial was carried out to investigate the effects of dietary fish meal replacement by yeast hydrolysate (YH) on growth performance, complement system and stress resistance of juvenile Jian carp (Cyprinus carpio var. Jian) (initial average weight 19.44 ± 0.06 g). In the study, there were five groups: one control group was fed with a basal diet (YH0), and four treatment groups were fed with dietary fish meal replaced by 1% YH (YH1), 3% (YH3), 5% (YH5) and 7% (YH7), respectively. Each group had four replicates. At the end of feeding trial, twelve fish from each group (three fish per replicate) were randomly selected for assessing the growth and immunity. Meanwhile, 20 fish per replicate were injected by Aeromonas hydrophila. The results showed that (1) Replacement levels of YH significantly affected the growth of the fish with the highest values of weight gain (WG) occurred in fish fed YH3 diet. However, no significant difference in feed conversion ratios (FCR) was observed among all groups. (2) Pre-stressed plasma lysozyme activity, total protein and albumin contents and complement component 3 (C3) and complement component 4 (C4) levels of fish fed YH3 diet were significantly higher than those of fish fed YH0 diet. However, post-stressed immune parameters of fish in all groups were significantly lower. (3) There was a trend that the expression levels of the complement-related genes (c1r/s-A, c4-1, c3-H1, c5-1, fb/c2-A, mbl-2 and masp) initially increased and then decreased except mbl-2 and masp, with the maximum values observed in fish fed YH3 diet. Before stress, the expression levels of the inflammation-related genes (alp, il-1β and tnf-α) in the hepatopancreas and spleen of fish fed YH1 diet and YH7 diet were significant higher than that of fish fed YH0 diet. After stress, no significant difference in the expression levels of those genes was observed among all groups. These results indicated that FM replacement by YH could improve growth performance, enhance innate immunity, and activate complement via the alternative complement pathway (ACP) and the classical complement pathway (CCP). Copyright © 2017 Elsevier Ltd. All rights reserved.

Compatibility of switchgrass as an energy crop in farming systems of the southeastern USA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bransby, D.I.; Rodriguez-Kabana, R.; Sladden, S.E.

1993-12-31

The objective of this paper is to examine the compatibility of switchgrass as an energy crop in farming systems in the southeastern USA, relative to other regions. In particular, the issues addressed are (1) competition between switchgrass as an energy crop and existing farm enterprises, based primarily on economic returns, (2) complementarity between switchgrass and existing farm enterprises, and (3) environmental benefits. Because projected economic returns for switchgrass as an energy crop are highest in the Southeast, and returns from forestry and beef pastures (the major existing enterprises) are low, there is a very strong economic incentive in this region.more » In contrast, based on current information, economic viability of switchgrass as an energy crop in other regions appears doubtful. In addition, switchgrass in the southeastern USA would complement forage-livestock production, row crop production and wildlife and would provide several additional environmental benefits. It is concluded that the southeastern USA offers the greatest opportunity for developing switchgrass as an economically viable energy crop.« less

A chromosomally encoded virulence factor protects the Lyme disease pathogen against host-adaptive immunity.

PubMed

Yang, Xiuli; Coleman, Adam S; Anguita, Juan; Pal, Utpal

2009-03-01

Borrelia burgdorferi, the bacterial pathogen of Lyme borreliosis, differentially expresses select genes in vivo, likely contributing to microbial persistence and disease. Expression analysis of spirochete genes encoding potential membrane proteins showed that surface-located membrane protein 1 (lmp1) transcripts were expressed at high levels in the infected murine heart, especially during early stages of infection. Mice and humans with diagnosed Lyme borreliosis also developed antibodies against Lmp1. Deletion of lmp1 severely impaired the pathogen's ability to persist in diverse murine tissues including the heart, and to induce disease, which was restored upon chromosomal complementation of the mutant with the lmp1 gene. Lmp1 performs an immune-related rather than a metabolic function, as its deletion did not affect microbial persistence in immunodeficient mice, but significantly decreased spirochete resistance to the borreliacidal effects of anti-B. burgdorferi sera in a complement-independent manner. These data demonstrate the existence of a virulence factor that helps the pathogen evade host-acquired immune defense and establish persistent infection in mammals.

Using animal models to determine the significance of complement activation in Alzheimer's disease

PubMed Central

Loeffler, David A

2004-01-01

Complement inflammation is a major inflammatory mechanism whose function is to promote the removal of microorganisms and the processing of immune complexes. Numerous studies have provided evidence for an increase in this process in areas of pathology in the Alzheimer's disease (AD) brain. Because complement activation proteins have been demonstrated in vitro to exert both neuroprotective and neurotoxic effects, the significance of this process in the development and progression of AD is unclear. Studies in animal models of AD, in which brain complement activation can be experimentally altered, should be of value for clarifying this issue. However, surprisingly little is known about complement activation in the transgenic animal models that are popular for studying this disorder. An optimal animal model for studying the significance of complement activation on Alzheimer's – related neuropathology should have complete complement activation associated with senile plaques, neurofibrillary tangles (if present), and dystrophic neurites. Other desirable features include both classical and alternative pathway activation, increased neuronal synthesis of native complement proteins, and evidence for an increase in complement activation prior to the development of extensive pathology. In order to determine the suitability of different animal models for studying the role of complement activation in AD, the extent of complement activation and its association with neuropathology in these models must be understood. PMID:15479474

PathNER: a tool for systematic identification of biological pathway mentions in the literature

PubMed Central

2013-01-01

Background Biological pathways are central to many biomedical studies and are frequently discussed in the literature. Several curated databases have been established to collate the knowledge of molecular processes constituting pathways. Yet, there has been little focus on enabling systematic detection of pathway mentions in the literature. Results We developed a tool, named PathNER (Pathway Named Entity Recognition), for the systematic identification of pathway mentions in the literature. PathNER is based on soft dictionary matching and rules, with the dictionary generated from public pathway databases. The rules utilise general pathway-specific keywords, syntactic information and gene/protein mentions. Detection results from both components are merged. On a gold-standard corpus, PathNER achieved an F1-score of 84%. To illustrate its potential, we applied PathNER on a collection of articles related to Alzheimer's disease to identify associated pathways, highlighting cases that can complement an existing manually curated knowledgebase. Conclusions In contrast to existing text-mining efforts that target the automatic reconstruction of pathway details from molecular interactions mentioned in the literature, PathNER focuses on identifying specific named pathway mentions. These mentions can be used to support large-scale curation and pathway-related systems biology applications, as demonstrated in the example of Alzheimer's disease. PathNER is implemented in Java and made freely available online at http://sourceforge.net/projects/pathner/. PMID:24555844

3D multimodal MRI brain glioma tumor and edema segmentation: a graph cut distribution matching approach.

PubMed

Njeh, Ines; Sallemi, Lamia; Ayed, Ismail Ben; Chtourou, Khalil; Lehericy, Stephane; Galanaud, Damien; Hamida, Ahmed Ben

2015-03-01

This study investigates a fast distribution-matching, data-driven algorithm for 3D multimodal MRI brain glioma tumor and edema segmentation in different modalities. We learn non-parametric model distributions which characterize the normal regions in the current data. Then, we state our segmentation problems as the optimization of several cost functions of the same form, each containing two terms: (i) a distribution matching prior, which evaluates a global similarity between distributions, and (ii) a smoothness prior to avoid the occurrence of small, isolated regions in the solution. Obtained following recent bound-relaxation results, the optima of the cost functions yield the complement of the tumor region or edema region in nearly real-time. Based on global rather than pixel wise information, the proposed algorithm does not require an external learning from a large, manually-segmented training set, as is the case of the existing methods. Therefore, the ensuing results are independent of the choice of a training set. Quantitative evaluations over the publicly available training and testing data set from the MICCAI multimodal brain tumor segmentation challenge (BraTS 2012) demonstrated that our algorithm yields a highly competitive performance for complete edema and tumor segmentation, among nine existing competing methods, with an interesting computing execution time (less than 0.5s per image). Copyright © 2014 Elsevier Ltd. All rights reserved.

Late-time behaviour of the tilted Bianchi type VIh models

NASA Astrophysics Data System (ADS)

Hervik, S.; van den Hoogen, R. J.; Lim, W. C.; Coley, A. A.

2007-08-01

We study tilted perfect fluid cosmological models with a constant equation of state parameter in spatially homogeneous models of Bianchi type VIh using dynamical systems methods and numerical experimentation, with an emphasis on their future asymptotic evolution. We determine all of the equilibrium points of the type VIh state space (which correspond to exact self-similar solutions of the Einstein equations, some of which are new), and their stability is investigated. We find that there are vacuum plane-wave solutions that act as future attractors. In the parameter space, a 'loophole' is shown to exist in which there are no stable equilibrium points. We then show that a Hopf-bifurcation can occur resulting in a stable closed orbit (which we refer to as the Mussel attractor) corresponding to points both inside the loophole and points just outside the loophole; in the former case the closed curves act as late-time attractors while in the latter case these attracting curves will co-exist with attracting equilibrium points. In the special Bianchi type III case, centre manifold theory is required to determine the future attractors. Comprehensive numerical experiments are carried out to complement and confirm the analytical results presented. We note that the Bianchi type VIh case is of particular interest in that it contains many different subcases which exhibit many of the different possible future asymptotic behaviours of Bianchi cosmological models.

State investments in high-technology job growth.

PubMed

Leicht, Kevin T; Jenkins, J Craig

2017-07-01

Since the early 1970's state and local governments have launched an array of economic development programs designed to promote high-technology development. The question our analysis addresses is whether these programs promote long-term high-technology employment growth net of state location and agglomeration advantages. Proponents talk about an infrastructure strategy that promotes investment in public research and specialized infrastructure to attract and grow new high technology industries in specific locations, and a more decentralized entrepreneurial strategy that reinforces local agglomeration capacities by investing in new enterprises and products, promoting the development of local networks and partnerships. Our results support the entrepreneurial strategy, suggesting that state governments can accelerate high technology development by adopting market-supportive programs that complement private sector initiatives. In addition to positive direct benefits of technology deployment/transfer programs and SBIR programs, entrepreneurial programs affect change in high-technology employment in concert with existing locational and agglomeration advantages. Rural (i.e. low population density) states tend to benefit by technology development programs. Infrastructure strategy programs also facilitate high technology job growth in places where local advantages already exist. Our results suggest that critics of industrial policy are correct that high technology growth is organic and endogenous, yet state governments are able to "pick winners and losers" in ways that grow their local economy. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of platelets with riboflavin and ultraviolet light mediates complement activation and suppresses monocyte interleukin-12 production in whole blood.

PubMed

Loh, Y S; Dean, M M; Johnson, L; Marks, D C

2015-11-01

Pathogen inactivation (PI) and storage may alter the immunomodulatory capacity of platelets (PLTs). The aim of this study was to examine the effect of PI (Riboflavin and ultraviolet light treatment) and storage on the capacity of PLTs to induce cytokine responses in recipient inflammatory cells. A pool and split design was used to prepare untreated and PI-treated buffy coat-derived platelet concentrates (PCs). Samples were taken on days 2 and 7 postcollection and incubated with ABO/RhD-matched fresh whole blood for 6 h with or without lipopolysaccharide (LPS). The intracellular production of IP-10, MCP-1, MIP-1α, IL-8, IL-6, IL-10, IL-12, TNF-α and MIP-1β in monocytes and neutrophils was assessed using flow cytometry. Complement proteins in PLT supernatants were measured using a cytometric bead array. PLTs and PLT supernatant (both untreated and PI-treated) resulted in modulation of intracellular MIP-1β and IL-12 production in monocytes. Compared to untreated PLTs, PI-treated PLTs resulted in significantly lower LPS-induced monocyte IL-12 production (day 7). The concentration of C3a and C5a (and their desArg forms) was significantly increased in PLT supernatants following PI. PI results in decreased LPS-induced monocyte IL-12 production and increased complement activation. The association between platelet-induced complement activation and IL-12 production warrants further investigation. © 2015 International Society of Blood Transfusion.

Substitution and complementarity of alcohol and cannabis: A review of the literature

PubMed Central

2016-01-01

Background Whether alcohol and cannabis are used as substitutes or complements remains debated, and findings across various disciplines have not been synthesized to date. Objective This paper is a first step towards organizing the interdisciplinary literature on alcohol and cannabis substitution and complementarity. Method Electronic searches were performed using PubMed and ISI Web of Knowledge. Behavioral studies of humans with ‘alcohol’ (or ‘ethanol’) and ‘cannabis’ (or ‘marijuana”) and ‘complement*’ (or ‘substitut*’) in the title or as a keyword were considered. Studies were organized according to sample characteristics (youth, general population, clinical and community-based). These groups were not set a priori, but were informed by the literature review process. Results Of the 39 studies reviewed, 16 support substitution, ten support complementarity, 12 support neither and one supports both. Results from studies of youth suggest that youth may reduce alcohol in more liberal cannabis environments (substitute), but reduce cannabis in more stringent alcohol environments (complement). Results from the general population suggest that substitution of cannabis for alcohol may occur under more lenient cannabis policies, though cannabis-related laws may affect alcohol use differently across genders and racial groups. Conclusions Alcohol and cannabis act as both substitutes and complements. Policies aimed at one substance may inadvertently affect consumption of other substances. Future studies should collect fine-grained longitudinal, prospective data from the general population and subgroups of interest, especially in locations likely to legalize cannabis. PMID:27249324

Inhibition of the Membrane Attack Complex by Dengue Virus NS1 through Interaction with Vitronectin and Terminal Complement Proteins.

PubMed

Conde, Jonas Nascimento; da Silva, Emiliana Mandarano; Allonso, Diego; Coelho, Diego Rodrigues; Andrade, Iamara da Silva; de Medeiros, Luciano Neves; Menezes, Joice Lima; Barbosa, Angela Silva; Mohana-Borges, Ronaldo

2016-11-01

Dengue virus (DENV) infects millions of people worldwide and is a major public health problem. DENV nonstructural protein 1 (NS1) is a conserved glycoprotein that associates with membranes and is also secreted into the plasma in DENV-infected patients. The present study describes a novel mechanism by which NS1 inhibits the terminal complement pathway. We first identified the terminal complement regulator vitronectin (VN) as a novel DENV2 NS1 binding partner by using a yeast two-hybrid system. This interaction was further assessed by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assay. The NS1-VN complex was also detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the DENV2 NS1 protein, either by itself or by interacting with VN, hinders the formation of the membrane attack complex (MAC) and C9 polymerization. Finally, we showed that DENV2, West Nile virus (WNV), and Zika virus (ZIKV) NS1 proteins produced in mammalian cells inhibited C9 polymerization. Taken together, our results points to a role for NS1 as a terminal pathway inhibitor of the complement system. Dengue is the most important arthropod-borne viral disease nowadays and is caused by dengue virus (DENV). The flavivirus NS1 glycoprotein has been characterized functionally as a complement evasion protein that can attenuate the activation of the classical, lectin, and alternative pathways. The present study describes a novel mechanism by which DENV NS1 inhibits the terminal complement pathway. We identified the terminal complement regulator vitronectin (VN) as a novel DENV NS1 binding partner, and the NS1-VN complex was detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the NS1-VN complex inhibited membrane attack complex (MAC) formation, thus interfering with the complement terminal pathway. Interestingly, NS1 itself also inhibited MAC activity, suggesting a direct role of this protein in the inhibition process. Our findings imply a role for NS1 as a terminal pathway inhibitor of the complement system. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Complement activation on the surface of cell-derived microparticles during cardiac surgery with cardiopulmonary bypass - is retransfusion of pericardial blood harmful?

PubMed

Biró, E; van den Goor, J M; de Mol, B A; Schaap, M C; Ko, L-Y; Sturk, A; Hack, C E; Nieuwland, R

2011-01-01

To investigate whether cell-derived microparticles play a role in complement activation in pericardial blood of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and whether microparticles in pericardial blood contribute to systemic complement activation upon retransfusion. Pericardial blood of 13 patients was retransfused in 9 and discarded in 4 cases. Microparticles were isolated from systemic blood collected before anesthesia (T1) and at the end of CPB (T2), and from pericardial blood. The microparticles were analyzed by flow cytometry for bound complement components C1q, C4 and C3, and bound complement activator molecules C-reactive protein (CRP), serum amyloid P-component (SAP), immunoglobulin (Ig)M and IgG. Fluid-phase complement activation products (C4b/c, C3b/c) and activator molecules were determined by ELISA. Compared with systemic T1 blood, pericardial blood contained increased C4b/c and C3b/c, and increased levels of microparticles with bound complement components. In systemic T1 samples, microparticle-bound CRP, whereas in pericardial blood, microparticle-bound SAP and IgM were associated with complement activation. At the end of CPB, increased C3b/c (but not C4b/c) was present in systemic T2 blood compared with T1, while concentrations of microparticles binding complement components and of those binding complement activator molecules were similar. Concentrations of fluid-phase complement activation products and microparticles were similar in patients whether or not retransfused with pericardial blood. In pericardial blood of patients undergoing cardiac surgery with CPB, microparticles contribute to activation of the complement system via bound SAP and IgM. Retransfusion of pericardial blood, however, does not contribute to systemic complement activation.

An amphioxus gC1q protein binds human IgG and initiates the classical pathway: Implications for a C1q-mediated complement system in the basal chordate.

PubMed

Gao, Zhan; Li, Mengyang; Ma, Jie; Zhang, Shicui

2014-12-01

The origin of the classical complement pathway remains open during chordate evolution. A C1q-like member, BjC1q, was identified in the basal chordate amphioxus. It is predominantly expressed in the hepatic caecum, hindgut, and notochord, and is significantly upregulated following challenge with bacteria or lipoteichoic acid and LPS. Recombinant BjC1q and its globular head domain specifically interact with lipoteichoic acid and LPS, but BjC1q displays little lectin activity. Moreover, rBjC1q can assemble to form the high molecular weight oligomers necessary for binding to proteases C1r/C1s and for complement activation, and binds human C1r/C1s/mannan-binding lectin-associated serine protease-2 as well as amphioxus serine proteases involved in the cleavage of C4/C2, and C3 activation. Importantly, rBjC1q binds with human IgG as well as an amphioxus Ig domain containing protein, resulting in the activation of the classical complement pathway. This is the first report showing that a C1q-like protein in invertebrates is able to initiate classical pathway, raising the possibility that amphioxus possesses a C1q-mediated complement system. It also suggests a new scenario for the emergence of the classical complement pathway, in contrast to the proposal that the lectin pathway evolved into the classical pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Activation of the lectin pathway of complement in experimental human keratitis with Pseudomonas aeruginosa.

PubMed

Osthoff, Michael; Brown, Karl D; Kong, David C M; Daniell, Mark; Eisen, Damon P

2014-01-01

Pseudomonas aeruginosa (P. aeruginosa) microbial keratitis (MK) is a sight-threatening disease. Previous animal studies have identified an important contribution of the complement system to the clearance of P. aeruginosa infection of the cornea. Mannose-binding lectin (MBL), a pattern recognition receptor of the lectin pathway of complement, has been implicated in the host defense against P. aeruginosa. However, studies addressing the role of the lectin pathway in P. aeruginosa MK are lacking. Hence, we sought to determine the activity of the lectin pathway in human MK caused by P. aeruginosa. Primary human corneal epithelial cells (HCECs) from cadaveric donors were exposed to two different P. aeruginosa strains. Gene expression of interleukin (IL)-6, IL-8, MBL, and other complement proteins was determined by reverse transcription-polymerase chain reaction (RT-PCR) and MBL synthesis by enzyme-linked immunosorbent assay and intracellular flow cytometry. MBL gene expression was not detected in unchallenged HCECs. Exposure of HCECs to P. aeruginosa resulted in rapid induction of the transcriptional expression of MBL, IL-6, and IL-8. In addition, expression of several complement proteins of the classical and lectin pathways, but not the alternative pathway, were upregulated after 5 h of challenge, including MBL-associated serine protease 1. However, MBL protein secretion was not detectable 18 h after challenge with P. aeruginosa. MK due to P. aeruginosa triggers activation of MBL and the lectin pathway of complement. However, the physiologic relevance of this finding is unclear, as corresponding MBL oligomer production was not observed.

On the value of therapeutic interventions targeting the complement system in acute myocardial infarction.

PubMed

Emmens, Reindert W; Wouters, Diana; Zeerleder, Sacha; van Ham, S Marieke; Niessen, Hans W M; Krijnen, Paul A J

2017-04-01

The complement system plays an important role in the inflammatory response subsequent to acute myocardial infarction (AMI). The aim of this study is to create a systematic overview of studies that have investigated therapeutic administration of complement inhibitors in both AMI animal models and human clinical trials. To enable extrapolation of observations from included animal studies toward post-AMI clinical trials, ex vivo studies on isolated hearts and proof-of-principle studies on inhibitor administration before experimental AMI induction were excluded. Positive therapeutic effects in AMI animal models have been described for cobra venom factor, soluble complement receptor 1, C1-esterase inhibitor (C1-inh), FUT-175, C1s-inhibitor, anti-C5, ADC-1004, clusterin, and glycosaminoglycans. Two types of complement inhibitors have been tested in clinical trials, being C1-inh and anti-C5. Pexelizumab (anti-C5) did not result in reproducible beneficial effects for AMI patients. Beneficial effects were reported in AMI patients for C1-inhibitor, albeit in small patient groups. In general, despite the absence of consistent positive effects in clinical trials thus far, the complement system remains a potentially interesting target for therapy in AMI patients. Based on the study designs of previous animal studies and clinical trials, we discuss several issues which require attention in the design of future studies: adjustment of clinical trial design to precise mechanism of action of administered inhibitor, optimizing the duration of therapy, and optimization of time point(s) on which therapeutic effects will be evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

Cobra venom factor immunoconjugates: effects of carbohydrate-directed versus amino group-directed conjugation.

PubMed

Zara, J; Pomato, N; McCabe, R P; Bredehorst, R; Vogel, C W

1995-01-01

Human IgM monoclonal antibody 16-88, derived from patients immunized with autologous colon carcinoma cells, was derivatized with two different cross-linkers, S-(2-thiopyridyl)-L-cysteine hydrazide (TPCH), which is carbohydrate-directed, and N-succinimidyl-3-(2- pyridyldithio)propionate (SPDP), which is amino group-directed. Two antibody functions, antigen binding and complement activation, were assayed upon derivatization with TPCH and SPDP. TPCH allowed for extensive modification (up to 17 TPCH molecules per antibody) without impairment of antigen binding activity, while this function was significantly compromised upon derivatization with SPDP. Antibody molecules derivatized with 16 SPDP residues showed almost complete loss of their antigen binding function. The complement activating ability of antibody 16-88 was significantly decreased after derivatization with TPCH or SPDP. In the case of SPDP derivatization, this decrease of the complement activating ability is predominantly a consequence of the impaired binding function. Upon conjugation of cobra venom factor (CVF), a nontoxic 137-kDa glycoprotein which is capable of activating the alternative pathway of complement, the antigen binding activity of SPDP-derivatized antibody was further compromised, whereas that of TPCH-derivatized antibody remained unaffected even after attachment of three or four CVF molecules per antibody. In both conjugates CVF retained good functional activity. CVF was slightly more active when attached to SPDP-derivatized antibody, suggesting a better accessibility of amino group-coupled CVF for its interaction with other complement proteins. These results indicate that carbohydrate-directed conjugation compromises the antibody function of complement activation, but allows for the generation of immunoconjugates with unimpaired antigen binding capability.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies to PcpA and PhtD protect mice against Streptococcus pneumoniae by a macrophage- and complement-dependent mechanism.

PubMed

Visan, Lucian; Rouleau, Nicolas; Proust, Emilie; Peyrot, Loïc; Donadieu, Arnaud; Ochs, Martina

2018-02-01

Currently marketed Streptococcus pneumoniae (Spn) vaccines, which contain polysaccharide capsular antigens from the most common Spn serotypes, have substantially reduced pneumococcal disease rates but have limited coverage. A trivalent pneumococcal protein vaccine containing pneumococcal choline-binding protein A (PcpA), pneumococcal histidine triad protein D (PhtD), and detoxified pneumolysin is being developed to provide broader, cross-serotype protection. Antibodies against detoxified pneumolysin protect against bacterial pneumonia by neutralizing Spn-produced pneumolysin, but how anti-PhtD and anti-PcpA antibodies protect against Spn has not been established. Here, we used a murine passive protection sepsis model to investigate the mechanism of protection by anti-PhtD and anti-PcpA antibodies. Depleting complement using cobra venom factor eliminated protection by anti-PhtD and anti-PcpA monoclonal antibodies (mAbs). Consistent with a requirement for complement, complement C3 deposition on Spn in vitro was enhanced by anti-PhtD and anti-PcpA mAbs and by sera from PhtD- and PcpA-immunized rabbits and humans. Moreover, in the presence of complement, anti-PhtD and anti-PcpA mAbs increased uptake of Spn by human granulocytes. Depleting neutrophils using anti-Ly6G mAbs, splenectomy, or a combination of both did not affect passive protection against Spn, whereas depleting macrophages using clodronate liposomes eliminated protection. These results suggest anti-PhtD and anti-PcpA antibodies induced by pneumococcal protein vaccines protect against Spn by a complement- and macrophage-dependent opsonophagocytosis.

Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium.

PubMed

Prechl, József; Papp, Krisztián; Hérincs, Zoltán; Péterfy, Hajna; Lóránd, Veronika; Szittner, Zoltán; Estonba, Andone; Rovero, Paolo; Paolini, Ilaria; Del Amo, Jokin; Uribarri, Maria; Alcaro, Maria Claudia; Ruiz-Larrañaga, Otsanda; Migliorini, Paola; Czirják, László

2016-01-01

Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement opsonized immune complexes promotes the development of class-switched autoantibodies targeting nucleic acids.

Complement component 4

MedlinePlus

... of a certain protein. This protein is part of the complement system. The complement system is a group of proteins ... system and play a role in the development of inflammation. The complement system protects the body from infections, dead cells and ...

LONG TERM RESULTS AFTER STAPLED HEMORRHOIDOPEXY ALONE AND COMPLEMENTED BY EXCISIONAL HEMORRHOIDECTOMY: A RETROSPECTIVE COHORT STUDY

PubMed Central

ARAUJO, Sergio Eduardo Alonso; HORCEL, Lucas de Araujo; SEID, Victor Edmond; BERTONCINI, Alexandre Bruno; KLAJNER, Sidney

2016-01-01

ABSTRACT Background: Stapled hemorrhoidopexy is associated with less postoperative pain and faster recovery. However, it may be associated with a greater risk of symptomatic recurrence. We hypothesized that undertaking a limited surgical excision of hemorrhoid disease after stapling may be a valid approach for selected patients. Aim: To compare long-term results after stapled hemorrhoidopexy with and without complementation with closed excisional technique. Method: In a retrospective uni-institutional cohort study, sixty-five (29 men) patients underwent stapled hemorrhoidopexy and 21 (13 men) underwent stapled hemorrhoidopexy with excision. The same surgeons operated on all cases. Patients underwent stapled hemorrhoidectomy associated with excisional surgery if symptoms attributable to external hemorrhoid piles were observed preoperatively, or if residual prolapse or bulky external disease was observed after the firing of the stapler. A closed excisional diathermy hemorrhoidectomy without vascular ligation was utilized in all complemented cases. All clinical variables were obtained from a questionnaire evaluation obtained through e-mail, telephone interview, or office follow-up. Results: The median duration of postoperative follow-up was 48.5 (6-40) months. Patients with grades 3 and 4 hemorrhoid disease were operated on more frequently using stapled hemorrhoidopexy complemented with excisional technique (95.2% vs. 55.4%, p=0.001). Regarding respectively stapled hemorrhoidopexy and stapled hemorrhoidopexy complemented with excision, there was no difference between the techniques in relation to symptom recurrence (43% and 33%, p=0.45) and median interval between surgery and symptom recurrence (30 (8-84) and 38.8 (8-65) months, p=0.80). Eight (12.3%) patients were re-operated after stapled hemorrhoidopexy and 2 (9.6%), after hemorrhoidopexy with excision (p=0.78). Patient distribution in both groups according to the degree of postoperative satisfaction was similar (p=0.97). Conclusion: Stapled hemorrhoidopexy combined with an excisional technique was effective for more advanced hemorrhoid disease. The combination may have prevented symptomatic recurrence associated to stapled hemorrhoidopexy alone. PMID:27759778

Existence of a return direction for plasma escaping from a pinched column in a plasma focus discharge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubes, P.; Cikhardt, J.; Klir, D.

2015-05-15

The use of multi-frame interferometry used on the PF-1000 device with the deuterium filling showed the existence of a return motion of the top of several lobules of the pinched column formed at the pinched plasma column. This phenomenon was observed in the presence of an over-optimal mass in front of the anode, which depressed the intensity of the implosion and the smooth surface of the pinched plasma column. The observed evolution was explored through the use of closed poloidal currents transmitted outside the pinched plasma. This interpretation complements the scenario of the closed currents flowing within the structures insidemore » the pinched column, which has been published recently on the basis of observations from interferometry, neutron, and magnetic probe diagnostics on this device.« less

Herbal medicines for the management of opioid addiction: safe and effective alternatives to conventional pharmacotherapy?

PubMed

Ward, Jeanine; Rosenbaum, Christopher; Hernon, Christina; McCurdy, Christopher R; Boyer, Edward W

2011-12-01

Striking increases in the abuse of opioids have expanded the need for pharmacotherapeutic interventions. The obstacles that confront effective treatment of opioid addiction - shortage of treatment professionals, stigma associated with treatment and the ability to maintain abstinence - have led to increased interest in alternative treatment strategies among both treatment providers and patients alike. Herbal products for opioid addiction and withdrawal, such as kratom and specific Chinese herbal medications such as WeiniCom, can complement existing treatments. Unfortunately, herbal treatments, while offering some advantages over existing evidence-based pharmacotherapies, have poorly described pharmacokinetics, a lack of supportive data derived from well controlled clinical trials, and severe toxicity, the cause for which remains poorly defined. Herbal products, therefore, require greater additional testing in rigorous clinical trials before they can expect widespread acceptance in the management of opioid addiction.

Developing a new syndromic surveillance system for the London 2012 Olympic and Paralympic Games.

PubMed

Harcourt, S E; Fletcher, J; Loveridge, P; Bains, A; Morbey, R; Yeates, A; McCloskey, B; Smyth, B; Ibbotson, S; Smith, G E; Elliot, A J

2012-12-01

Syndromic surveillance is vital for monitoring public health during mass gatherings. The London 2012 Olympic and Paralympic Games represents a major challenge to health protection services and community surveillance. In response to this challenge the Health Protection Agency has developed a new syndromic surveillance system that monitors daily general practitioner out-of-hours and unscheduled care attendances. This new national system will fill a gap identified in the existing general practice-based syndromic surveillance systems by providing surveillance capability of general practice activity during evenings/nights, over weekends and public holidays. The system will complement and supplement the existing tele-health phone line, general practitioner and emergency department syndromic surveillance systems. This new national system will contribute to improving public health reassurance, especially to meet the challenges of the London 2012 Olympic and Paralympic Games.

Incorporating Semantics into Data Driven Workflows for Content Based Analysis

NASA Astrophysics Data System (ADS)

Argüello, M.; Fernandez-Prieto, M. J.

Finding meaningful associations between text elements and knowledge structures within clinical narratives in a highly verbal domain, such as psychiatry, is a challenging goal. The research presented here uses a small corpus of case histories and brings into play pre-existing knowledge, and therefore, complements other approaches that use large corpus (millions of words) and no pre-existing knowledge. The paper describes a variety of experiments for content-based analysis: Linguistic Analysis using NLP-oriented approaches, Sentiment Analysis, and Semantically Meaningful Analysis. Although it is not standard practice, the paper advocates providing automatic support to annotate the functionality as well as the data for each experiment by performing semantic annotation that uses OWL and OWL-S. Lessons learnt can be transmitted to legacy clinical databases facing the conversion of clinical narratives according to prominent Electronic Health Records standards.

Open source Modeling and optimization tools for Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peles, S.

Open source modeling and optimization tools for planning The existing tools and software used for planning and analysis in California are either expensive, difficult to use, or not generally accessible to a large number of participants. These limitations restrict the availability of participants for larger scale energy and grid studies in the state. The proposed initiative would build upon federal and state investments in open source software, and create and improve open source tools for use in the state planning and analysis activities. Computational analysis and simulation frameworks in development at national labs and universities can be brought forward tomore » complement existing tools. An open source platform would provide a path for novel techniques and strategies to be brought into the larger community and reviewed by a broad set of stakeholders.« less

CRISPR/Cas9 mediates efficient conditional mutagenesis in Drosophila.

PubMed

Xue, Zhaoyu; Wu, Menghua; Wen, Kejia; Ren, Menda; Long, Li; Zhang, Xuedi; Gao, Guanjun

2014-09-05

Existing transgenic RNA interference (RNAi) methods greatly facilitate functional genome studies via controlled silencing of targeted mRNA in Drosophila. Although the RNAi approach is extremely powerful, concerns still linger about its low efficiency. Here, we developed a CRISPR/Cas9-mediated conditional mutagenesis system by combining tissue-specific expression of Cas9 driven by the Gal4/upstream activating site system with various ubiquitously expressed guide RNA transgenes to effectively inactivate gene expression in a temporally and spatially controlled manner. Furthermore, by including multiple guide RNAs in a transgenic vector to target a single gene, we achieved a high degree of gene mutagenesis in specific tissues. The CRISPR/Cas9-mediated conditional mutagenesis system provides a simple and effective tool for gene function analysis, and complements the existing RNAi approach. Copyright © 2014 Xue et al.

Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration

PubMed Central

Haynes, Tracy; Luz-Madrigal, Agustin; Reis, Edimara S.; Echeverri Ruiz, Nancy P.; Grajales-Esquivel, Erika; Tzekou, Apostolia; Tsonis, Panagiotis A.; Lambris, John D.; Del Rio-Tsonis, Katia

2013-01-01

Identifying the initiation signals for tissue regeneration in vertebrates is one of the major challenges in regenerative biology. Much of the research thus far has indicated that certain growth factors have key roles. Here we show that complement fragment C3a is sufficient to induce complete regeneration of the embryonic chick retina from stem/progenitor cells present in the eye, independent of fibroblast growth factor receptor signaling. Instead, C3a induces retina regeneration via STAT3 activation, which in turn activates the injury- and inflammation-responsive factors, IL-6, IL-8 and TNF-α. This activation sets forth regulation of Wnt2b, Six3 and Sox2, genes associated with retina stem and progenitor cells. Thus, our results establish a mechanism for retina regeneration based on injury and inflammation signals. Furthermore, our results indicate a unique function for complement anaphylatoxins that implicate these molecules in the induction and complete regeneration of the retina, opening new avenues of experimentation in the field. PMID:23942241

Dispersion of Nanoparticles in Different Media Importantly Determines the Composition of Their Protein Corona.

PubMed

Strojan, Klemen; Leonardi, Adrijana; Bregar, Vladimir B; Križaj, Igor; Svete, Jurij; Pavlin, Mojca

2017-01-01

Protein corona of nanoparticles (NPs), which forms when these particles come in to contact with protein-containing fluids, is considered as an overlooked factor in nanomedicine. Through numerous studies it has been becoming increasingly evident that it importantly dictates the interaction of NPs with their surroundings. Several factors that determine the compositions of NPs protein corona have been identified in recent years, but one has remained largely ignored-the composition of media used for dispersion of NPs. Here, we determined the effect of dispersion media on the composition of protein corona of polyacrylic acid-coated cobalt ferrite NPs (PAA NPs) and silica NPs. Our results confirmed some of the basic premises such as NPs type-dependent specificity of the protein corona. But more importantly, we demonstrated the effect of the dispersion media on the protein corona composition. The differences between constituents of the media used for dispersion of NPs, such as divalent ions and macromolecules were responsible for the differences in protein corona composition formed in the presence of fetal bovine serum (FBS). Our results suggest that the protein corona composition is a complex function of the constituents present in the media used for dispersion of NPs. Regardless of the dispersion media and FBS concentration, majority of proteins from either PAA NPs or silica NPs coronas were involved in the process of transport and hemostasis. Interestingly, corona of silica NPs contained three complement system related proteins: complement factor H, complement C3 and complement C4 while PAA NPs bound only one immune system related protein, α-2-glycoprotein. Importantly, relative abundance of complement C3 protein in corona of silica NPs was increased when NPs were dispersed in NaCl, which further implies the relevance of dispersion media used to prepare NPs.

Dispersion of Nanoparticles in Different Media Importantly Determines the Composition of Their Protein Corona

PubMed Central

Strojan, Klemen; Leonardi, Adrijana; Bregar, Vladimir B.; Križaj, Igor; Svete, Jurij; Pavlin, Mojca

2017-01-01

Protein corona of nanoparticles (NPs), which forms when these particles come in to contact with protein-containing fluids, is considered as an overlooked factor in nanomedicine. Through numerous studies it has been becoming increasingly evident that it importantly dictates the interaction of NPs with their surroundings. Several factors that determine the compositions of NPs protein corona have been identified in recent years, but one has remained largely ignored—the composition of media used for dispersion of NPs. Here, we determined the effect of dispersion media on the composition of protein corona of polyacrylic acid-coated cobalt ferrite NPs (PAA NPs) and silica NPs. Our results confirmed some of the basic premises such as NPs type-dependent specificity of the protein corona. But more importantly, we demonstrated the effect of the dispersion media on the protein corona composition. The differences between constituents of the media used for dispersion of NPs, such as divalent ions and macromolecules were responsible for the differences in protein corona composition formed in the presence of fetal bovine serum (FBS). Our results suggest that the protein corona composition is a complex function of the constituents present in the media used for dispersion of NPs. Regardless of the dispersion media and FBS concentration, majority of proteins from either PAA NPs or silica NPs coronas were involved in the process of transport and hemostasis. Interestingly, corona of silica NPs contained three complement system related proteins: complement factor H, complement C3 and complement C4 while PAA NPs bound only one immune system related protein, α-2-glycoprotein. Importantly, relative abundance of complement C3 protein in corona of silica NPs was increased when NPs were dispersed in NaCl, which further implies the relevance of dispersion media used to prepare NPs. PMID:28052135

Polyanion-Induced Self Association of Complement Factor H1

PubMed Central

Pangburn, Michael K.; Rawal, Nenoo; Cortes, Claudio; Alam, M. Nurul; Ferreira, Viviana P.; Atkinson, Mark A. L.

2008-01-01

Factor H is the primary soluble regulator of activation of the alternative pathway of complement. It prevents activation of complement on host cells and tissues upon association with C3b and surface polyanions such as sialic acids, heparin and other glycosaminoglycans. Here we show that interaction with polyanions causes self-association forming tetramers of the 155,000 Da glycosylated protein. Monomeric human factor H is an extended flexible protein that exhibits an apparent size of 330,000 Da, relative to globular standards, during gel filtration chromatography in the absence of polyanions. In the presence of dextran sulfate (5,000 Da) or heparin an intermediate species of apparent m.w. 700,000 and a limit species of m.w. 1,400,000 were observed by gel filtration. Sedimentation equilibrium analysis by analytical ultracentrifugation indicated a monomer Mr of 163,000 in the absence of polyanions and a Mr of 607,000, corresponding to a tetramer, in the presence of less than a 2-fold molar excess of dextran sulfate. Increasing concentrations of dextran sulfate increased binding of factor H to zymosan-C3b 4.5-fold. This was accompanied by an increase in both the decay accelerating and cofactor activity of factor H on these cells. An expressed fragment encompassing the C-terminal polyanion binding site (complement control protein domains 18–20) also exhibited polyanion-induced self association, suggesting that the C-terminal ends of factor H mediate self-association. The results suggest that recognition of polyanionic markers on host cells and tissues by factor H, and the resulting regulation of complement activation, may involve formation of dimers and tetramers of factor H. PMID:19124749

Antimicrobial Peptides and Complement in Neonatal Hypoxia-Ischemia Induced Brain Damage

PubMed Central

Rocha-Ferreira, Eridan; Hristova, Mariya

2015-01-01

Hypoxic-ischemic encephalopathy (HIE) is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1–5/1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy, and cognitive disabilities. Even though the brain is considered as an immune-privileged site, it has innate and adaptive immune response and can produce complement (C) components and antimicrobial peptides (AMPs). Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain. Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS), including neonatal hypoxia-ischemia (HI), resident microglia, and astroglia are the main cells providing immune defense to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins, which can chemoattract and promote maturation of dendritic cells (DC), and can also limit inflammation by controlling the viability of these same DC. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI injury and the effect of that balance on the subsequent brain damage. PMID:25729383

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in the...

Landscape complementation revealed through bipartite networks: An example with the Florida manatee

USGS Publications Warehouse

Haase, Catherine G.; Fletcher, Robert J.; Slone, Daniel H.; Reid, James P.; Butler, Susan M.

2017-01-01

Landscape complementation is an important predictor of selection and thus classic complementation measures are not sufficient in describing the process. Formalization of complementation with bipartite network can therefor reveal effects potentially missed with conventional measures.

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in the...

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in the...

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in the...

Complement component 3 (C3)

MedlinePlus

... of a certain protein. This protein is part of the complement system. The complement system is a group of proteins ... system and play a role in the development of inflammation. The complement system protects the body from infections, dead cells and ...

Complement evasion by Bordetella pertussis: implications for improving current vaccines.

PubMed

Jongerius, Ilse; Schuijt, Tim J; Mooi, Frits R; Pinelli, Elena

2015-04-01

Bordetella pertussis causes whooping cough or pertussis, a highly contagious disease of the respiratory tract. Despite high vaccination coverage, reported cases of pertussis are rising worldwide and it has become clear that the current vaccines must be improved. In addition to the well-known protective role of antibodies and T cells during B. pertussis infection, innate immune responses such as the complement system play an essential role in B. pertussis killing. In order to evade this complement activation and colonize the human host, B. pertussis expresses several molecules that inhibit complement activation. Interestingly, one of the known complement evasion proteins, autotransporter Vag8, is highly expressed in the recently emerged B. pertussis isolates. Here, we describe the current knowledge on how B. pertussis evades complement-mediated killing. In addition, we compare this to complement evasion strategies used by other bacterial species. Finally, we discuss the consequences of complement evasion by B. pertussis on adaptive immunity and how identification of the bacterial molecules and the mechanisms involved in complement evasion might help improve pertussis vaccines.

Genetic Localization and Molecular Characterization of the nonS Gene Required for Macrotetrolide Biosynthesis in Streptomyces griseus DSM40695

PubMed Central

Smith, Wyatt C.; Xiang, Longkuan; Shen, Ben

2000-01-01

The macrotetrolides are a family of cyclic polyethers derived from tetramerization, in a stereospecific fashion, of the enantiomeric nonactic acid (NA) and its homologs. Isotope labeling experiments established that NA is of polyketide origin, and biochemical investigations demonstrated that 2-methyl-6,8-dihydroxynon-2E-enoic acid can be converted into NA by a cell-free preparation from Streptomyces lividans that expresses nonS. These results lead to the hypothesis that macrotetrolide biosynthesis involves a pair of enantiospecific polyketide pathways. In this work, a 55-kb contiguous DNA region was cloned from Streptomyces griseus DSM40695, a 6.3-kb fragment of which was sequenced to reveal five open reading frames, including the previously reported nonR and nonS genes. Inactivation of nonS in vivo completely abolished macrotetrolide production. Complementation of the nonS mutant by the expression of nonS in trans fully restored its macrotetrolide production ability, with a distribution of individual macrotetrolides similar to that for the wild-type producer. In contrast, fermentation of the nonS mutant in the presence of exogenous (±)-NA resulted in the production of nonactin, monactin, and dinactin but not in the production of trinactin and tetranactin. These results prove the direct involvement of nonS in macrotetrolide biosynthesis. The difference in macrotetrolide production between in vivo complementation of the nonS mutant by the plasmid-borne nonS gene and fermentation of the nonS mutant in the presence of exogenously added (±)-NA suggests that NonS catalyzes the formation of (−)-NA and its homologs, supporting the existence of a pair of enantiospecific polyketide pathways for macrotetrolide biosynthesis in S. griseus. The latter should provide a model that can be used to study the mechanism by which polyketide synthase controls stereochemistry during polyketide biosynthesis. PMID:10858335

Community resilience and decision theory challenges for catastrophic events.

PubMed

Cox, Louis Anthony

2012-11-01

Extreme and catastrophic events pose challenges for normative models of risk management decision making. They invite development of new methods and principles to complement existing normative decision and risk analysis. Because such events are rare, it is difficult to learn about them from experience. They can prompt both too little concern before the fact, and too much after. Emotionally charged and vivid outcomes promote probability neglect and distort risk perceptions. Aversion to acting on uncertain probabilities saps precautionary action; moral hazard distorts incentives to take care; imperfect learning and social adaptation (e.g., herd-following, group-think) complicate forecasting and coordination of individual behaviors and undermine prediction, preparation, and insurance of catastrophic events. Such difficulties raise substantial challenges for normative decision theories prescribing how catastrophe risks should be managed. This article summarizes challenges for catastrophic hazards with uncertain or unpredictable frequencies and severities, hard-to-envision and incompletely described decision alternatives and consequences, and individual responses that influence each other. Conceptual models and examples clarify where and why new methods are needed to complement traditional normative decision theories for individuals and groups. For example, prospective and retrospective preferences for risk management alternatives may conflict; procedures for combining individual beliefs or preferences can produce collective decisions that no one favors; and individual choices or behaviors in preparing for possible disasters may have no equilibrium. Recent ideas for building "disaster-resilient" communities can complement traditional normative decision theories, helping to meet the practical need for better ways to manage risks of extreme and catastrophic events. © 2012 Society for Risk Analysis.

Intratracheally instilled titanium dioxide nanoparticles translocate to heart and liver and activate complement cascade in the heart of C57BL/6 mice

PubMed Central

Husain, Mainul; Wu, Dongmei; Saber, Anne T.; Decan, Nathalie; Jacobsen, Nicklas R.; Williams, Andrew; Yauk, Carole L.; Wallin, Hakan; Vogel, Ulla; Halappanavar, Sabina

2015-01-01

Abstract An estimated 1% or less of nanoparticles (NPs) deposited in the lungs translocate to systemic circulation and enter other organs; however, this estimation may not be accurate given the low sensitivity of existing in vivo NP detection methods. Moreover, the biological effects of such low levels of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following translocation from the lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 µg of industrially relevant titanium dioxide nanoparticles (nano-TiO2) alongside vehicle controls. Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. This study characterizes the subtle systemic effects that occur in liver and heart tissues following pulmonary exposure and low levels of translocation of nano-TiO2 from lungs. PMID:25993494

The innate immune repertoire in cnidaria--ancestral complexity and stochastic gene loss.

PubMed

Miller, David J; Hemmrich, Georg; Ball, Eldon E; Hayward, David C; Khalturin, Konstantin; Funayama, Noriko; Agata, Kiyokazu; Bosch, Thomas C G

2007-01-01

Characterization of the innate immune repertoire of extant cnidarians is of both fundamental and applied interest--it not only provides insights into the basic immunological 'tool kit' of the common ancestor of all animals, but is also likely to be important in understanding the global decline of coral reefs that is presently occurring. Recently, whole genome sequences became available for two cnidarians, Hydra magnipapillata and Nematostella vectensis, and large expressed sequence tag (EST) datasets are available for these and for the coral Acropora millepora. To better understand the basis of innate immunity in cnidarians, we scanned the available EST and genomic resources for some of the key components of the vertebrate innate immune repertoire, focusing on the Toll/Toll-like receptor (TLR) and complement pathways. A canonical Toll/TLR pathway is present in representatives of the basal cnidarian class Anthozoa, but neither a classic Toll/TLR receptor nor a conventional nuclear factor (NF)-kappaB could be identified in the anthozoan Hydra. Moreover, the detection of complement C3 and several membrane attack complex/perforin domain (MAC/PF) proteins suggests that a prototypic complement effector pathway may exist in anthozoans, but not in hydrozoans. Together with data for several other gene families, this implies that Hydra may have undergone substantial secondary gene loss during evolution. Such losses are not confined to Hydra, however, and at least one MAC/PF gene appears to have been lost from Nematostella. Consideration of these patterns of gene distribution underscores the likely significance of gene loss during animal evolution whilst indicating ancient origins for many components of the vertebrate innate immune system.

Novel roles of complement in renal diseases and their therapeutic consequences.

PubMed

Wada, Takehiko; Nangaku, Masaomi

2013-09-01

The complement system functions as a part of the innate immune system. Inappropriate activation of the complement pathways has a deleterious effect on kidneys. Recent advances in complement research have provided new insights into the pathogenesis of glomerular and tubulointerstitial injury associated with complement activation. A new disease entity termed 'C3 glomerulopathy' has recently been proposed and is characterized by isolated C3 deposition in glomeruli without positive staining for immunoglobulins. Genetic and functional studies have demonstrated that several different mutations and disease variants, as well as the generation of autoantibodies, are potentially associated with its pathogenesis. The data from comprehensive analyses suggest that complement dysregulation can also be associated with hemolytic uremic syndrome and more common glomerular diseases, such as IgA nephropathy and diabetic kidney disease. In addition, animal studies utilizing genetically modified mice have begun to elucidate the molecular pathomechanisms associated with the complement system. From a diagnostic point of view, a noninvasive, MRI-based method for detecting C3 has recently been developed to serve as a novel tool for diagnosing complement-mediated kidney diseases. While novel therapeutic tools related to complement regulation are emerging, studies evaluating the precise roles of the complement system in kidney diseases will still be useful for developing new therapeutic approaches.

Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation.

PubMed

Smith, John D; Ibrahim, Mohamed W; Newell, Helen; Danskine, Anna J; Soresi, Simona; Burke, Margaret M; Rose, Marlene L; Carby, Martin

2014-10-01

The impact of Luminex-detected HLA antibodies on outcomes after lung transplantation is unclear. Herein we have undertaken a retrospective study of pre-transplant sera from 425 lung transplants performed between 1991 and 2003. Pre-transplant sera, originally screened by complement-dependent cytotoxicity (CDC) assays, were retrospectively tested for the presence of HLA-specific antibodies using HLA-coated Luminex beads and C4d deposition on Luminex beads. The results were correlated with graft survival at 1 year. Twenty-seven patients were retrospectively identified as having been transplanted against donor-specific HLA antibodies (DSA) and 36 patients against non-donor-specific HLA antibodies (NDSA). DSA-positive patients had 1-year survival of 51.9% compared with 77.8% for NDSA and 71.8% for antibody-negative patients (p = 0.029). One-year survival of patients with complement-fixing DSA was 12.5% compared with 62.5% for non-complement-fixing DSA, 75.8% for non-complement-fixing NDSA and 71.8% for antibody-negative patients (p < 0.0001). DSA-positive patients with mean fluorescence intensity (MFI) >5,000 had 1-year survival of 33.3% compared with 71.4% for MFI 2,000 to 5000 and 62.5% for MFI <2,000 (p = 0.0046). Multivariable analysis revealed DSA to be an independent predictor of poor patient survival within 1 year (p = 0.0010, hazard ratio [HR] = 3.569) as well as complement-fixing DSA (p < 0.0001, HR = 11.083) and DSA with MFI >5,000 (p = 0.0001, HR = 5.512). Pre-formed DSA, particularly complement-fixing DSA, and high MFI are associated with poor survival within the first year after lung transplantation. Risk stratification according to complement fixation or MFI levels may allow for increased transplantation in sensitized patients. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation.

PubMed

Cserhalmi, Marcell; Csincsi, Ádám I; Mezei, Zoltán; Kopp, Anne; Hebecker, Mario; Uzonyi, Barbara; Józsi, Mihály

2017-01-01

Factor H-related (FHR) proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH). While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3), and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM) extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

Scabies Mite Peritrophins Are Potential Targets of Human Host Innate Immunity

PubMed Central

Holt, Deborah C.; Kemp, Dave J.; Fischer, Katja

2011-01-01

Background Pruritic scabies lesions caused by Sarcoptes scabiei burrowing in the stratum corneum of human skin facilitate opportunistic bacterial infections. Emerging resistance to current therapeutics emphasizes the need to identify novel targets for protective intervention. We have characterized several protein families located in the mite gut as crucial factors for host-parasite interactions. Among these multiple proteins inhibit human complement, presumably to avoid complement-mediated damage of gut epithelial cells. Peritrophins are major components of the peritrophic matrix often found in the gut of arthropods. We hypothesized that a peritrophin, if abundant in the scabies mite gut, could be an activator of complement. Methodology/Principal Findings A novel full length scabies mite peritrophin (SsPTP1) was identified in a cDNA library from scabies mites. The amino acid sequence revealed four putative chitin binding domains (CBD). Recombinant expression of one CBD of the highly repetitive SsPTP1 sequence as TSP-hexaHis-fusion protein resulted in soluble protein, which demonstrated chitin binding activity in affinity chromatography assays. Antibodies against a recombinant SsPTP1 fragment were used to immunohistochemically localize native SsPTP1 in the mite gut and in fecal pellets within the upper epidermis, co-localizing with serum components such as host IgG and complement. Enzymatic deglycosylation confirmed strong N- and O-glycosylation of the native peritrophin. Serum incubation followed by immunoblotting with a monoclonal antibody against mannan binding lectin (MBL), the recognition molecule of the lectin pathway of human complement activation, indicated that MBL may specifically bind to glycosylated SsPTP1. Conclusions/Significance This study adds a new aspect to the accumulating evidence that complement plays a major role in scabies mite biology. It identifies a novel peritrophin localized in the mite gut as a potential target of the lectin pathway of the complement cascade. These initial findings indicate a novel role of scabies mite peritrophins in triggering a host innate immune response within the mite gut. PMID:21980545

Alternative complement activity in the egg cytosol of amphioxus Branchiostoma belcheri: evidence for the defense role of maternal complement components.

PubMed

Liang, Yujun; Zhang, Shicui; Wang, Zhiping

2009-01-01

The eggs in most invertebrates are fertilized externally, and therefore their resulting embryos are exposed to an environment full of microbes, many of which are pathogens capable of killing other organisms. How the developing embryos of invertebrates defend themselves against pathogenic attacks is an intriguing question to biologists, and remains largely unknown. Here we clearly demonstrated that the egg cytosol prepared from the newly fertilized eggs of amphioxus Branchiostoma belcheri, an invertebrate chordate, was able to inhibit the growth of both the Gram-negative bacterium Vibrio anguillarum and the Gram-positive bacterium Staphylococcus aureus. All findings point to that it is the complement system operating via the alternative pathway that is attributable to the bacteriostatic activity. This appears to be the first report providing the evidence for the functional role of the maternal complement components in the eggs of invertebrate species, paving the way for the study of maternal immunity in other invertebrate organisms whose eggs are fertilized in vitro. It also supports the notion that the early developing embryos share some defense mechanisms common with the adult species.

Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs

PubMed Central

Matsunari, Hitomi; Nagashima, Hiroshi; Watanabe, Masahito; Umeyama, Kazuhiro; Nakano, Kazuaki; Nagaya, Masaki; Kobayashi, Toshihiro; Yamaguchi, Tomoyuki; Sumazaki, Ryo; Herzenberg, Leonard A.; Nakauchi, Hiromitsu

2013-01-01

In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals. PMID:23431169

Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs.

PubMed

Matsunari, Hitomi; Nagashima, Hiroshi; Watanabe, Masahito; Umeyama, Kazuhiro; Nakano, Kazuaki; Nagaya, Masaki; Kobayashi, Toshihiro; Yamaguchi, Tomoyuki; Sumazaki, Ryo; Herzenberg, Leonard A; Nakauchi, Hiromitsu

2013-03-19

In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals.

Targeting α-synuclein oligomers by protein-fragment complementation for drug discovery in synucleinopathies.

PubMed

Moussaud, Simon; Malany, Siobhan; Mehta, Alka; Vasile, Stefan; Smith, Layton H; McLean, Pamela J

2015-05-01

Reducing the burden of α-synuclein oligomeric species represents a promising approach for disease-modifying therapies against synucleinopathies such as Parkinson's disease and dementia with Lewy bodies. However, the lack of efficient drug discovery strategies that specifically target α-synuclein oligomers has been a limitation to drug discovery programs. Here we describe an innovative strategy that harnesses the power of bimolecular protein-fragment complementation to monitor synuclein-synuclein interactions. We have developed two robust models to monitor α-synuclein oligomerization by generating novel stable cell lines expressing α-synuclein fusion proteins for either fluorescent or bioluminescent protein-fragment complementation under the tetracycline-controlled transcriptional activation system. A pilot screen was performed resulting in the identification of two potential hits, a p38 MAPK inhibitor and a casein kinase 2 inhibitor, thereby demonstrating the suitability of our protein-fragment complementation assay for the measurement of α-synuclein oligomerization in living cells at high throughput. The application of the strategy described herein to monitor α-synuclein oligomer formation in living cells with high throughput will facilitate drug discovery efforts for disease-modifying therapies against synucleinopathies and other proteinopathies.

Interallelic Complementation at the Suppressor of Forked Locus of Drosophila Reveals Complementation between Suppressor of Forked Proteins Mutated in Different Regions

PubMed Central

Simonelig, M.; Elliott, K.; Mitchelson, A.; O'Hare, K.

1996-01-01

The Su(f) protein of Drosophila melanogaster shares extensive homologies with proteins from yeast (RNA14) and man (77 kD subunit of cleavage stimulation factor) that are required for 3' end processing of mRNA. These homologies suggest that su(f) is involved in mRNA 3' end formation and that some aspects of this process are conserved throughout eukaryotes. We have investigated the genetic and molecular complexity of the su(f) locus. The su(f) gene is transcribed to produce three RNAs and could encode two proteins. Using constructs that contain different parts of the locus, we show that only the larger predicted gene product of 84 kD is required for the wild-type function of su(f). Some lethal alleles of su(f) complement to produce viable combinations. The structures of complementing and noncomplementing su(f) alleles indicate that 84-kD Su(f) proteins mutated in different domains can act in combination for partial su(f) function. Our results suggest protein-protein interaction between or within wild-type Su(f) molecules. PMID:8846900

Complement Coercion: The Joint Effects of Type and Typicality.

PubMed

Zarcone, Alessandra; McRae, Ken; Lenci, Alessandro; Padó, Sebastian

2017-01-01

Complement coercion ( begin a book → reading ) involves a type clash between an event-selecting verb and an entity-denoting object, triggering a covert event ( reading ). Two main factors involved in complement coercion have been investigated: the semantic type of the object (event vs. entity), and the typicality of the covert event ( the author began a book → writing ). In previous research, reading times have been measured at the object. However, the influence of the typicality of the subject-object combination on processing an aspectual verb such as begin has not been studied. Using a self-paced reading study, we manipulated semantic type and subject-object typicality, exploiting German word order to measure reading times at the aspectual verb. These variables interacted at the target verb. We conclude that both type and typicality probabilistically guide expectations about upcoming input. These results are compatible with an expectation-based view of complement coercion and language comprehension more generally in which there is rapid interaction between what is typically viewed as linguistic knowledge, and what is typically viewed as domain general knowledge about how the world works.

Complement Coercion: The Joint Effects of Type and Typicality

PubMed Central

Zarcone, Alessandra; McRae, Ken; Lenci, Alessandro; Padó, Sebastian

2017-01-01

Complement coercion (begin a book →reading) involves a type clash between an event-selecting verb and an entity-denoting object, triggering a covert event (reading). Two main factors involved in complement coercion have been investigated: the semantic type of the object (event vs. entity), and the typicality of the covert event (the author began a book →writing). In previous research, reading times have been measured at the object. However, the influence of the typicality of the subject–object combination on processing an aspectual verb such as begin has not been studied. Using a self-paced reading study, we manipulated semantic type and subject–object typicality, exploiting German word order to measure reading times at the aspectual verb. These variables interacted at the target verb. We conclude that both type and typicality probabilistically guide expectations about upcoming input. These results are compatible with an expectation-based view of complement coercion and language comprehension more generally in which there is rapid interaction between what is typically viewed as linguistic knowledge, and what is typically viewed as domain general knowledge about how the world works. PMID:29225585