inefficient complement system: Topics by Science.gov

Sample records for inefficient complement system

Complement and the control of HIV infection: an evolving story.

PubMed

Frank, Michael M; Hester, Christopher; Jiang, Haixiang

2014-05-01

Thirty years ago, investigators isolated and later determined the structure of HIV-1 and its envelope proteins. Using techniques that were effective with other viruses, they prepared vaccines designed to generate antibody or T-cell responses, but they were ineffective in clinical trials. In this article, we consider the role of complement in host defense against enveloped viruses, the role it might play in the antibody response and why complement has not controlled HIV-1 infection. Complement consists of a large group of cell-bound and plasma proteins that are an integral part of the innate immune system. They provide a first line of defense against microbes and also play a role in the immune response. Here we review the studies of complement-mediated HIV destruction and the role of complement in the HIV antibody response. HIV-1 has evolved a complex defense to prevent complement-mediated killing reviewed here. As part of these studies, we have discovered that HIV-1 envelope, on administration into animals, is rapidly broken down into small peptides that may prove to be very inefficient at provident the type of antigenic stimulation that leads to an effective immune response. Improving complement binding and stabilizing envelope may improve the vaccine response.
Novel Scabies Mite Serpins Inhibit the Three Pathways of the Human Complement System

PubMed Central

Mika, Angela; Reynolds, Simone L.; Mohlin, Frida C.; Willis, Charlene; Swe, Pearl M.; Pickering, Darren A.; Halilovic, Vanja; Wijeyewickrema, Lakshmi C.; Pike, Robert N.; Blom, Anna M.; Kemp, David J.; Fischer, Katja

2012-01-01

Scabies is a parasitic infestation of the skin by the mite Sarcoptes scabiei that causes significant morbidity worldwide, in particular within socially disadvantaged populations. In order to identify mechanisms that enable the scabies mite to evade human immune defenses, we have studied molecules associated with proteolytic systems in the mite, including two novel scabies mite serine protease inhibitors (SMSs) of the serpin superfamily. Immunohistochemical studies revealed that within mite-infected human skin SMSB4 (54 kDa) and SMSB3 (47 kDa) were both localized in the mite gut and feces. Recombinant purified SMSB3 and SMSB4 did not inhibit mite serine and cysteine proteases, but did inhibit mammalian serine proteases, such as chymotrypsin, albeit inefficiently. Detailed functional analysis revealed that both serpins interfered with all three pathways of the human complement system at different stages of their activation. SMSB4 inhibited mostly the initial and progressing steps of the cascades, while SMSB3 showed the strongest effects at the C9 level in the terminal pathway. Additive effects of both serpins were shown at the C9 level in the lectin pathway. Both SMSs were able to interfere with complement factors without protease function. A range of binding assays showed direct binding between SMSB4 and seven complement proteins (C1, properdin, MBL, C4, C3, C6 and C8), while significant binding of SMSB3 occurred exclusively to complement factors without protease function (C4, C3, C8). Direct binding was observed between SMSB4 and the complement proteases C1s and C1r. However no complex formation was observed between either mite serpin and the complement serine proteases C1r, C1s, MASP-1, MASP-2 and MASP-3. No catalytic inhibition by either serpin was observed for any of these enzymes. In summary, the SMSs were acting at several levels mediating overall inhibition of the complement system and thus we propose that they may protect scabies mites from complement-mediated gut damage. PMID:22792350
Implementation of efficient trajectories for an ultrasonic scanner using chaotic maps

NASA Astrophysics Data System (ADS)

Almeda, A.; Baltazar, A.; Treesatayapun, C.; Mijarez, R.

2012-05-01

Typical ultrasonic methodology for nondestructive scanning evaluation uses systematic scanning paths. In many cases, this approach is time inefficient and also energy and computational power consuming. Here, a methodology for the scanning of defects using an ultrasonic echo-pulse scanning technique combined with chaotic trajectory generation is proposed. This is implemented in a Cartesian coordinate robotic system developed in our lab. To cover the entire search area, a chaotic function and a proposed mirror mapping were incorporated. To improve detection probability, our proposed scanning methodology is complemented with a probabilistic approach of discontinuity detection. The developed methodology was found to be more efficient than traditional ones used to localize and characterize hidden flaws.
Extended producer responsibility for consumer waste: the gap between economic theory and implementation.

PubMed

Dubois, Maarten

2012-09-01

Although economic theory supports the use of extended producer responsibility (EPR) to stimulate prevention and recycling of waste, EPR systems implemented in Europe are often criticized as a result of weak incentives for prevention and green product design. Using a stylized economic model, this article evaluates the efficiency of European EPR systems. The model reveals that the introduction of static collection targets creates a gap between theory and implementation. Static targets lead to inefficient market outcomes and weak incentives for prevention and green product design. The minimum collection targets should be complemented with a tax on producers for the non-collected waste fraction. Because such a tax internalizes the cost of waste disposal, more efficient price signals will lead to better incentives for waste management in a complex and dynamic market.
Measuring and explaining multi-directional inefficiency in the Malaysian dairy industry.

PubMed

Mohd Suhaimi, Nurul Aisyah Binti; de Mey, Yann; Oude Lansink, Alfons

2017-01-01

The purpose of this paper is to measure the technical inefficiency of dairy farms and subsequently investigate the factors affecting technical inefficiency in the Malaysian dairy industry. This study uses multi-directional efficiency analysis to measure the technical inefficiency scores on a sample of 200 farm observations and single-bootstrap truncated regression model to define factors affecting technical inefficiency. Managerial and program inefficiency scores are presented for intensive and semi-intensive production systems. The results reveal marked differences in the inefficiency scores across inputs and between production systems. Intensive systems generally have lowest managerial and program inefficiency scores in the Malaysian dairy farming sector. Policy makers could use this information to advise dairy farmers to convert their farming system to the intensive system. The results suggest that the Malaysian Government should redefine its policy for providing farm finance and should target young farmers when designing training and extension programs in order to improve the performance of the dairy sector. The existing literature on Southeast Asian dairy farming has neither focused on investigating input-specific efficiency nor on comparing managerial and program efficiency. This paper aims to fill this gap.
Does autonomization of public hospitals and exposure to market pressure complement or debilitate social health insurance systems? Evidence from a low-income country.

PubMed

Sepehri, Ardeshir

2014-01-01

Granting public hospitals greater autonomy and creating organizational arrangements that mimic the private sector and encourage competition is often promoted as a way to increase efficiency and public accountability and to improve quality of care at these facilities. The existence of good-quality health infrastructure, in turn, encourages the population to join and support the social health insurance system and achieve universal coverage. This article provides a critical review of hospital autonomization, using Vietnam's experience to assess the influence of hospital autonomy on the sustainability of Vietnam's social health insurance. The evidence suggests that a reform process based on greater autonomy of resource mobilization and on the retention and use of own-source revenues can create perverse incentives among managers and health care providers, leading to the development of a two-tiered provision of clinical care, provider-induced supply of an inefficient service mix, a high degree of duplication, wasteful investment, and cost escalation. Rather than complementing social health insurance and helping the country to achieve universal coverage, granting public hospitals greater autonomy that mimics the private sector may indeed undermine the legitimacy and sustainability of social health insurance as health care costs escalate and higher quality of care remains elusive.
How to prevent burnout in cardiologists? A review of the current evidence, gaps, and future directions.

PubMed

Panagioti, Maria; Geraghty, Keith; Johnson, Judith

2018-01-01

Burnout is rising in all physicians, and cardiologists are not an exemption. Cardiology is a very popular specialty among medical students as it is associated with outstanding training standards and high prestige and income. In this review, we critically summarize the evidence on consequences, causes, and evidence-based interventions for burnout with a view toward recommending the best strategies for promoting wellness in cardiologists. Only a handful of studies have examined burnout specifically in cardiologists. Evidence therefore was mainly extrapolated by larger studies in all physicians and other physician specialties. Burnout in cardiologists has serious negative personal and professional consequences and is associated with suboptimal healthcare outcomes for patients. Burnout in cardiologists is primarily driven by professional and healthcare system demands and inefficiencies such as excessive workload and role complexity, training and certification demands, inefficient compensation models and lack of resources, computerization, and loss of autonomy. Moreover, loss of connectedness with patients, difficulties in balancing work and personal life and overvaluing compulsiveness and perfectionism in medical practice further increase the risk for burnout. Burnout among cardiologists may be best mitigated by organizational strategies complemented by individual stress reduction and reflection techniques under the resilience-based approach. Large-scale strategies are needed to mitigate burnout and promote physician wellness as a shared responsibility of healthcare systems and individuals and be committed in creating a new culture in medicine. Copyright © 2018 Elsevier Inc. All rights reserved.
Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus

PubMed Central

Park, Joo Youn; Moon, Bo Youn; Park, Juw Won; Thornton, Justin A.; Park, Yong Ho; Seo, Keun Seok

2017-01-01

Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of virulence genes by generalized transduction. In this study, we demonstrate genetic engineering strategies to overcome these shortcomings by integrating CRISPR/Cas9 system into a temperate phage genome, removing major virulence genes from the host chromosome, and expanding host specificity of the phage by complementing tail fiber protein. This significantly improved the efficacy and safety of CRISPR/Cas9 antimicrobials to therapeutic levels in both in vitro and in vivo assays. The genetic engineering tools and resources established in this study are expected to provide an efficacious and safe CRISPR/Cas9 antimicrobial, broadly applicable to Staphylococcus aureus. PMID:28322317
Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus.

PubMed

Park, Joo Youn; Moon, Bo Youn; Park, Juw Won; Thornton, Justin A; Park, Yong Ho; Seo, Keun Seok

2017-03-21

Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of virulence genes by generalized transduction. In this study, we demonstrate genetic engineering strategies to overcome these shortcomings by integrating CRISPR/Cas9 system into a temperate phage genome, removing major virulence genes from the host chromosome, and expanding host specificity of the phage by complementing tail fiber protein. This significantly improved the efficacy and safety of CRISPR/Cas9 antimicrobials to therapeutic levels in both in vitro and in vivo assays. The genetic engineering tools and resources established in this study are expected to provide an efficacious and safe CRISPR/Cas9 antimicrobial, broadly applicable to Staphylococcus aureus.
Interpreting MAD within multiple accretion regimes

NASA Astrophysics Data System (ADS)

Mocz, Philip; Guo, Xinyi

2015-02-01

General relativistic magnetohydrodynamic (GRMHD) simulations of accreting black holes in the radiatively inefficient regime show that systems with sufficient magnetic poloidal flux become magnetically arrested disc (MAD) systems, with a well-defined relationship between the magnetic flux and the mass accretion rate. Recently, Zamaninasab et al. report that the jet magnetic flux and accretion disc luminosity are tightly correlated over 7 orders of magnitude for a sample of 76 radio-loud active galaxies, concluding that the data are explained by the MAD mode of accretion. Their analysis assumes radiatively efficient accretion, and their sample consists primarily of radiatively efficient sources, while GRMHD simulations of MAD thus far have been carried out in the radiatively inefficient regime. We propose a model to interpret MAD systems in the context of multiple accretion regimes, and apply it to the sample in Zamaninasab et al., along with additional radiatively inefficient sources from archival data. We show that most of the radiatively inefficient radio-loud galaxies are consistent with being MAD systems. Assuming the MAD relationship found in radiatively inefficient simulations holds at other accretion regimes, a significant fraction of our sample can be candidates for MAD systems. Future GRMHD simulations have yet to verify the validity of this assumption.
Impact of HMO penetration and other environmental factors on hospital X-inefficiency.

PubMed

Rosko, M D

2001-12-01

This study examined the impact of health maintenance organization (HMO) market penetration and other internal and external environmental factors on hospital X-inefficiency in a national sample (N = 1,966) of urban U.S. hospitals in 1997. Stochastic frontier analysis, a frontier regression technique, was used to measure X-inefficiency and estimate parameters of the correlates of X-inefficiency. Log-likelihood restriction tests were used to test a variety of assumptions about the empirical model that guided its selection. Average estimated X-inefficiency in study hospitals was 12.96 percent. Increases in managed care penetration, dependence on Medicare and Medicaid, membership in a multihospital system, and location in areas where competitive pressures and the pool of uncompensated care are greater were associated with less X-inefficiency. Not-for-profit ownership was associated with increased X-inefficiency.
Performance analysis of distributed applications using automatic classification of communication inefficiencies

DOEpatents

Vetter, Jeffrey S.

2005-02-01

The method and system described herein presents a technique for performance analysis that helps users understand the communication behavior of their message passing applications. The method and system described herein may automatically classifies individual communication operations and reveal the cause of communication inefficiencies in the application. This classification allows the developer to quickly focus on the culprits of truly inefficient behavior, rather than manually foraging through massive amounts of performance data. Specifically, the method and system described herein trace the message operations of Message Passing Interface (MPI) applications and then classify each individual communication event using a supervised learning technique: decision tree classification. The decision tree may be trained using microbenchmarks that demonstrate both efficient and inefficient communication. Since the method and system described herein adapt to the target system's configuration through these microbenchmarks, they simultaneously automate the performance analysis process and improve classification accuracy. The method and system described herein may improve the accuracy of performance analysis and dramatically reduce the amount of data that users must encounter.
Session 1: Feeding and infant development breast-feeding and immune function.

PubMed

Hanson, Lars A

2007-08-01

The newborn receives, via the placenta, maternal IgG antibodies against the microbes present in its surroundings, but such antibodies have a pro-inflammatory action, initiating the complement system and phagocytes. Although the host defence mechanisms of the neonate that involve inflammatory reactivity are somewhat inefficient, this defence system can still have catabolic effects. Breast-feeding compensates for this relative inefficiency of host defence in the neonate by providing considerable amounts of secretory IgA antibodies directed particularly against the microbial flora of the mother and her environment. These antibodies bind the microbes that are appearing on the infant's mucosal membranes, preventing activation of the pro-inflammatory defence. The major milk protein lactoferrin can destroy microbes and reduce inflammatory responses. The non-absorbed milk oligosaccharides block attachment of microbes to the infant's mucosae, preventing infections. The milk may contain anti-secretory factor, which is anti-inflammatory, preventing mastitis in mothers and diarrhoea in infants. Numerous additional factors in the milk are of unknown function, although IL-7 is linked to the larger size of the thymus and the enhanced development of intestinal Tgammadelta lymphocytes in breast-fed compared with non-breast-fed infants. Several additional components in the milk may help to explain why breast-feeding can reduce infant mortality, protecting against neonatal septicaemia and meningitis. It is therefore important to start breast-feeding immediately. Protection is also apparent against diarrhoea, respiratory infections and otitis media. There may be protection against urinary tract infections and necrotizing enterocolitis, and possibly also against allergy and certain other immunological diseases, and tumours. In conclusion, breast-feeding provides a very broad multifactorial anti-inflammatory defence for the infant.
Validation of Mission Plans Through Simulation

NASA Astrophysics Data System (ADS)

St-Pierre, J.; Melanson, P.; Brunet, C.; Crabtree, D.

2002-01-01

The purpose of a spacecraft mission planning system is to automatically generate safe and optimized mission plans for a single spacecraft, or more functioning in unison. The system verifies user input syntax, conformance to commanding constraints, absence of duty cycle violations, timing conflicts, state conflicts, etc. Present day constraint-based systems with state-based predictive models use verification rules derived from expert knowledge. A familiar solution found in Mission Operations Centers, is to complement the planning system with a high fidelity spacecraft simulator. Often a dedicated workstation, the simulator is frequently used for operator training and procedure validation, and may be interfaced to actual control stations with command and telemetry links. While there are distinct advantages to having a planning system offer realistic operator training using the actual flight control console, physical verification of data transfer across layers and procedure validation, experience has revealed some drawbacks and inefficiencies in ground segment operations: With these considerations, two simulation-based mission plan validation projects are under way at the Canadian Space Agency (CSA): RVMP and ViSION. The tools proposed in these projects will automatically run scenarios and provide execution reports to operations planning personnel, prior to actual command upload. This can provide an important safeguard for system or human errors that can only be detected with high fidelity, interdependent spacecraft models running concurrently. The core element common to these projects is a spacecraft simulator, built with off-the- shelf components such as CAE's Real-Time Object-Based Simulation Environment (ROSE) technology, MathWork's MATLAB/Simulink, and Analytical Graphics' Satellite Tool Kit (STK). To complement these tools, additional components were developed, such as an emulated Spacecraft Test and Operations Language (STOL) interpreter and CCSDS TM/TC encoders and decoders. This paper discusses the use of simulation in the context of space mission planning, describes the projects under way and proposes additional venues of investigation and development.
Natural IgM mediates complement-dependent uptake of Francisella tularensis by human neutrophils via CR1 and CR3 in nonimmune serum

PubMed Central

Schwartz, Justin T.; Barker, Jason H.; Long, Matthew E.; Kaufman, Justin; McCracken, Jenna; Allen, Lee-Ann H.

2012-01-01

A fundamental step in the life cycle of F. tularensis is bacterial entry into host cells. F. tularensis activates complement, and recent data suggest that the classical pathway is required for complement factor C3 deposition on the bacterial surface. Nevertheless, C3 deposition is inefficient and neither the specific serum components necessary for classical pathway activation by F. tularensis in nonimmune human serum, nor the receptors that mediate infection of neutrophils has been defined. Herein human neutrophil uptake of GFP-expressing F. tularensis strains LVS and Schu S4 was quantified with high efficiency by flow cytometry. Using depleted sera and purified complement components we demonstrated first that C1q and C3 were essential for F. tularensis phagocytosis whereas C5 was not. Second, we used purification and immuno-depletion approaches to identify a critical role for natural IgM in this process, and then used a wbtA2 mutant to identify LPS O-antigen and capsule as prominent targets of these antibodies on the bacterial surface. Finally, we demonstrate using receptor-blocking antibodies that CR1 (CD35) and CR3 (CD11b/CD18) acted in concert for phagocytosis of opsonized F. tularensis by human neutrophils, whereas CR3 and CR4 (CD11c/CD18) mediated infection of human monocyte-derived macrophages. Altogether, our data provide fundamental insight into mechanisms of F. tularensis phagocytosis and support a model whereby natural IgM binds to surface capsular and O-antigen polysaccharides of F. tularensis and initiates the classical complement cascade via C1q to promote C3-opsonization of the bacterium and phagocytosis via CR3 and either CR1 or CR4 in a phagocyte-specific manner. PMID:22888138
Long-range transport and universality classes in in vitro viral infection spread

NASA Astrophysics Data System (ADS)

Manrubia, S. C.; García-Arriaza, J.; Domingo, E.; Escarmís, C.

2006-05-01

Dispersal mechanisms play a main role in the dynamics of infection spread. Recent experimental results with in vitro infections of foot-and-mouth disease virus reveal that the time needed for the virus to kill a cellular monolayer depends qualitatively on the number of viral particles required to initiate infection in a susceptible cell. A two-dimensional susceptible-infected-removed (SIR) model based on the experimental setting agrees with the observations only when viral particles are subject to long-range transport. Numerical and analytical results show that this long-range transport plays a role when a single particle causes infection, while it is inefficient when complementation between two or more particles is necessary.
The Defense Acquisitions System Through the Eyes of a Marine Corps Project Officer: Observations, Inefficiencies, and Proposed Solutions

DTIC Science & Technology

2013-04-03

adequate return on investments . As part of a results-oriented culture, acquisitions leaders must identify and hold accountable those employees who are...accountability and leadership is at the heart of acquisitions inefficiency. Employees that lack a sense of urgency and that are not fully invested in...inefficiency. Employees that lack a sense of urgency and that are not fully invested in delivering a quality product to the user, in a timely manner, are
Biomimetic Design of an Under-Actuated Leg Exoskeleton for Load-Carrying Augmentation

DTIC Science & Technology

2006-02-01

exoskeleton design has not considered the passive dynamics of walking and has focused on fully actuated systems that are inefficient and heavy. In this...passive dynamics of walking and has focused on fully actuated systems that are inefficient and heavy. In this thesis, an under-actuated exoskeleton...40 Figure 3.22 Braking torque of the magnetorheological damper vs. current .................... 41 Figure
Innovations in Science Education in Europe

NASA Astrophysics Data System (ADS)

Schuepbach, E.

2001-12-01

At many European Universities, the retention of skilled science graduates is hindered mainly by organisational structures. In particular, women students are often under-represented in sciences, and career progression is in general difficult. The linear system of knowhow transfer is inefficient from the pedagogical point of view and unsatisfactory for many students. Owing to fast changes in society and the working environment, a re-building of curricula in tertiary education (including University Education) has begun. Conceptual visions aim at influencing the investment in the largely untapped human capital and preparing the students for quick adaptation and enhanced flexiblity. Traditional methods of classroom teaching and knowhow transfer are increasingly complemented by New Learning Technologies and Mentoring. The EU Project INDECS (Potentials of Interdisciplinary Degree Courses in Engineering, Information Technology, Natural and Socio-Economic Sciences in a Changing Society) examines such pedagogical aspects in European degree courses combining engineering, IT, physical sciences and socio-economic sciences. Inclusion of specific IT and social science topics in modular form is examined. How innovation in University Teaching will meet the attractiveness to both students and employers in Europe is major focus of the study.
Sequence and expression of the genes for HPr (ptsH) and enzyme I (ptsI) of the phosphoenolpyruvate-dependent phosphotransferase transport system from Streptococcus mutans.

PubMed Central

Boyd, D A; Cvitkovitch, D G; Hamilton, I R

1994-01-01

We report the sequencing of a 2,242-bp region of the Streptococcus mutants NG5 genome containing the genes for ptsH and ptsI, which encode HPr and enzyme I (EI), respectively, of the phosphoenolpyruvate-dependent phosphotransferase transport system. The sequence was obtained from two cloned overlapping genomic fragments; one expresses HPr and a truncated EI, while the other expresses a full-length EI in Escherichia coli, as determined by Western immunoblotting. The ptsI gene appeared to be expressed from a region located in the ptsH gene. The S. mutans NG5 pts operon does not appear to be linked to other phosphotransferase transport system proteins as has been found in other bacteria. A positive fermentation pattern on MacConkey-glucose plates by an E. coli ptsI mutant harboring the S. mutans NG5 ptsI gene on a plasmid indicated that the S. mutans NG5 EI can complement a defect in the E. coli gene. This was confirmed by protein phosphorylation experiments with 32P-labeled phosphoenolpyruvate indicating phosphotransfer from the S. mutans NG5 EI to the E. coli HPr. Two forms of the cloned EI, both truncated to varying degrees in the C-terminal region, were inefficiently phosphorylated and unable to complement fully the ptsI defect in the E. coli mutant. The deduced amino acid sequence of HPr shows a high degree of homology, particularly around the active site, to the same protein from other gram-positive bacteria, notably, S. salivarius, and to a lesser extent with those of gram-negative bacteria. The deduced amino acid sequence of S. mutans NG5 EI also shares several regions of homology with other sequenced EIs, notably, with the region around the active site, a region that contains the only conserved cystidyl residue among the various proteins and which may be involved in substrate binding. Images PMID:8132321

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 ...
Inefficiency, heterogeneity and spillover effects in maternal care in India: a spatial stochastic frontier analysis.

PubMed

Kinfu, Yohannes; Sawhney, Monika

2015-03-25

Institutional delivery is one of the key and proven strategies to reduce maternal deaths. Since the 1990s, the government of India has made substantial investment on maternal care to reduce the huge burden of maternal deaths in the country. However, despite the effort access to institutional delivery in India remains below the global average. In addition, even in places where health investments have been comparable, inter- and intra-state difference in access to maternal care services remain wide and substantial. This raises a fundamental question on whether the sub-national units themselves differ in terms of the efficiency with which they use available resources, and if so, why? Data obtained from round 3 of the country's District Level Health and Facility Survey was analyzed to measure the level and determinants of inefficiency of institutional delivery in the country. Analysis was conducted using spatial stochastic frontier models that correct for heterogeneity and spatial interactions between sub-national units. Inefficiency differences in maternal care services between and within states are substantial. The top one third of districts in the country has a mean efficiency score of 90 per cent or more, while the bottom 10 per cent of districts exhibit mean inefficiency score of as high as over 75 per cent or more. Overall mean inefficiency is about 30 per cent. The result also reveals the existence of both heterogeneity and spatial correlation in institutional delivery in the country. Given the high level of inefficiency in the system, further progress in improving coverage of institutional delivery in the country should focus both on improving the efficiency of resource utilization--especially where inefficiency levels are extremely high--and on bringing new resources in to the system. The additional investment should specifically focus on those parts of the country where coverage rates are still low but efficiency levels are already at a high level. In addition, given that inefficiency was also associated inversely with literacy and urbanization and positively related with proportion of households belonging to poor households, investment in these areas can also improve coverage of institutional delivery in the country.
Probing Radiatively Inefficient Accretion Flow in the Neutron Star X-ray Binary System Aquila X-1

NASA Astrophysics Data System (ADS)

Maitra, Dipankar

2016-09-01

The nature of radiatively inefficient accretion flows (RIAF) near neutron stars and black holes remains largely enshrouded in mystery, primarily due to their low luminosity. Long term monitoring of Aql X-1 has revealed that during certain outbursts, the system goes into a relatively bright RIAF state for periods lasting several weeks. These low-intensity states offer a unique opportunity to probe radiatively inefficient flows. We request a 75 ksec Chandra/HETG ToO observation of Aql X-1 during a low-intensity state. Emission line diagnostics of the observed spectrum will be used to test different RIAF models and constrain flow properties such as the radial temperature and density profile, existence of an outflowing wind, spatial extent of the RIAF, and gas dynamics within the flow.
Probing Radiatively Inefficient Accretion Flow in the Neutron Star X-ray Binary System Aquila X-1

NASA Astrophysics Data System (ADS)

Maitra, Dipankar

2017-09-01

The nature of radiatively inefficient accretion flows (RIAF) near neutron stars and black holes remains largely enshrouded in mystery, primarily due to their low luminosity. Long term monitoring of Aql X-1 has revealed that during certain outbursts, the system goes into a relatively bright RIAF state for periods lasting several weeks. These low-intensity states offer a unique opportunity to probe radiatively inefficient flows. We request a 75 ksec Chandra/HETG ToO observation of Aql X-1 during a low-intensity state. Emission line diagnostics of the observed spectrum will be used to test different RIAF models and constrain flow properties such as the radial temperature and density profile, existence of an outflowing wind, spatial extent of the RIAF, and gas dynamics within the flow.
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 ...
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
21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5240 Complement components immunological test system. (a) Identification. A complement components... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement components immunological test system...
Parkinson's Law quantified: three investigations on bureaucratic inefficiency

NASA Astrophysics Data System (ADS)

Klimek, Peter; Hanel, Rudolf; Thurner, Stefan

2009-03-01

We formulate three famous, descriptive essays of Parkinson on bureaucratic inefficiency in a quantifiable and dynamical socio-physical framework. In the first model we show how the use of recent opinion formation models for small groups can be used to understand Parkinson's observation that decision-making bodies such as cabinets or boards become highly inefficient once their size exceeds a critical 'Coefficient of Inefficiency', typically around 20. A second observation of Parkinson—which is sometimes referred to as Parkinson's Law—is that the growth of bureaucratic or administrative bodies usually goes hand in hand with a drastic decrease of its overall efficiency. In our second model we view a bureaucratic body as a system of a flow of workers, who enter, become promoted to various internal levels within the system over time, and leave the system after having served for a certain time. Promotion usually is associated with an increase of subordinates. Within the proposed model it becomes possible to work out the phase diagram under which conditions of bureaucratic growth can be confined. In our last model we assign individual efficiency curves to workers throughout their life in administration, and compute the optimum time to give them the old age pension, in order to ensure a maximum of efficiency within the body—in Parkinson's words we compute the 'Pension Point'.
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
Design Tools for Evaluating Multiprocessor Programs

DTIC Science & Technology

1976-07-01

than large uniprocessing machines, and 2. economies of scale in manufacturing. Perhaps the most compelling reason (possibly a consequence of the...speed, redundancy, (inefficiency, resource utilization, and economies of the components. [Browne 73, Lehman 66] 6. How can the system be scheduled...mejsures are interesting about the computation? Somn may be: speed, redundancy, (inefficiency, resource utilization, and economies of the components
Parsing interindividual drug variability: an emerging role for systems pharmacology

PubMed Central

Turner, Richard M; Park, B Kevin; Pirmohamed, Munir

2015-01-01

There is notable interindividual heterogeneity in drug response, affecting both drug efficacy and toxicity, resulting in patient harm and the inefficient utilization of limited healthcare resources. Pharmacogenomics is at the forefront of research to understand interindividual drug response variability, but although many genotype-drug response associations have been identified, translation of pharmacogenomic associations into clinical practice has been hampered by inconsistent findings and inadequate predictive values. These limitations are in part due to the complex interplay between drug-specific, human body and environmental factors influencing drug response and therefore pharmacogenomics, whilst intrinsically necessary, is by itself unlikely to adequately parse drug variability. The emergent, interdisciplinary and rapidly developing field of systems pharmacology, which incorporates but goes beyond pharmacogenomics, holds significant potential to further parse interindividual drug variability. Systems pharmacology broadly encompasses two distinct research efforts, pharmacologically-orientated systems biology and pharmacometrics. Pharmacologically-orientated systems biology utilizes high throughput omics technologies, including next-generation sequencing, transcriptomics and proteomics, to identify factors associated with differential drug response within the different levels of biological organization in the hierarchical human body. Increasingly complex pharmacometric models are being developed that quantitatively integrate factors associated with drug response. Although distinct, these research areas complement one another and continual development can be facilitated by iterating between dynamic experimental and computational findings. Ultimately, quantitative data-derived models of sufficient detail will be required to help realize the goal of precision medicine. WIREs Syst Biol Med 2015, 7:221–241. doi: 10.1002/wsbm.1302 PMID:25950758
Technology Solutions Case Study: Balancing Hydronic Systems in Multifamily Buildings, Chicago, Illinois

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

None

2014-09-01

In multifamily building hydronic systems, temperature imbalance may be caused by undersized piping, improperly adjusted balancing valves, inefficient water temperature and flow levels, and owner/occupant interaction with the boilers, distribution and controls. The effects of imbalance include tenant discomfort, higher energy use intensity and inefficient building operation. In this case study , Partnership for Advanced Residential Retrofit and Elevate Energy. explores cost-effective distribution upgrades and balancing measures in multifamily hydronic systems, providing a resource to contractors, auditors, and building owners on best practices to improve tenant comfort and lower operating costs.
Association studies of excision repair cross-complementation group 1 (ERCC1) haplotypes with lung and head and neck cancer risk in a Caucasian population.

PubMed

Jones, Nathan R; Spratt, Thomas E; Berg, Arthur S; Muscat, Joshua E; Lazarus, Philip; Gallagher, Carla J

2011-04-01

The formation of bulky DNA adducts caused by diol epoxide derivatives of polycyclic aromatic hydrocarbons has been associated with tobacco-induced cancers, and inefficient repair of such adducts by the nucleotide excision repair (NER) system has been linked to increased risk of tobacco-induced lung and head and neck (H&N) cancers. The human excision repair cross-complementation group 1 (ERCC1) protein is essential for a functional NER system and genetic variation in ERCC1 may contribute to impaired DNA repair capacity and increased lung and H&N cancer risk. In order to comprehensively capture common genetic variation in the ERCC1 gene, Caucasian data from the International HapMap project was used to assess linkage disequilibrium and choose four tagSNPs (rs1319052, rs3212955, rs3212948, and rs735482) in the ERCC1 gene to genotype 452 lung cancer cases, 175 H&N cancer cases, and 790 healthy controls. Haplotypes were estimated using expectation maximization (EM) algorithm, and haplotype association with cancer was investigated using Haplo.stats software adjusting for known covariates. The genotype and haplotype frequencies matched previous estimates from Caucasians. There was no significant difference in the prevalence of rs1319052, rs3212955, rs3212948, and rs735482 when comparing lung or H&N cancer cases with controls (p-values>0.05). Similarly, there was no association between ERCC1 haplotypes and lung or H&N cancer susceptibility in this Caucasian population (p-values>0.05). No associations were found when stratifying lung cancer cases by histology, sex, smoking status, or smoking intensity. This study suggests that ERCC1 polymorphisms and haplotypes do not play a role in lung and H&N cancer susceptibility in Caucasians. Copyright © 2010 Elsevier Ltd. 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.
Compressed Air System Optimization: Case Study Food Industry in Indonesia

NASA Astrophysics Data System (ADS)

Widayati, Endang; Nuzahar, Hasril

2016-01-01

Compressors and compressed air systems was one of the most important utilities in industries or factories. Approximately 10% of the cost of electricity in the industry was used to produce compressed air. Therefore the potential for energy savings in the compressors and compressed air systems had a big challenge. This field was conducted especially in Indonesia food industry or factory. Compressed air system optimization was a technique approach to determine the optimal conditions for the operation of compressors and compressed air systems that included evaluation of the energy needs, supply adjustment, eliminating or reconfiguring the use and operation of inefficient, changing and complementing some equipment and improving operating efficiencies. This technique gave the significant impact for energy saving and costs. The potential savings based on this study through measurement and optimization e.g. system that lowers the pressure of 7.5 barg to 6.8 barg would reduce energy consumption and running costs approximately 4.2%, switch off the compressor GA110 and GA75 was obtained annual savings of USD 52,947 ≈ 455 714 kWh, running GA75 light load or unloaded then obtained annual savings of USD 31,841≈ 270,685 kWh, install new compressor 2x132 kW and 1x 132 kW VSD obtained annual savings of USD 108,325≈ 928,500 kWh. Furthermore it was needed to conduct study of technical aspect of energy saving potential (Investment Grade Audit) and performed Cost Benefit Analysis. This study was one of best practice solutions how to save energy and improve energy performance in compressors and compressed air system.
Integrating Public Health and Personal Care in a Reformed US Health Care System

PubMed Central

Chernichovsky, Dov

2010-01-01

Compared with other developed countries, the United States has an inefficient and expensive health care system with poor outcomes and many citizens who are denied access. Inefficiency is increased by the lack of an integrated system that could promote an optimal mix of personal medical care and population health measures. We advocate a health trust system to provide core medical benefits to every American, while improving efficiency and reducing redundancy. The major innovation of this plan would be to incorporate existing private health insurance plans in a national system that rebalances health care spending between personal and population health services and directs spending to investments with the greatest long-run returns. PMID:20019310
Decomposing Cost Efficiency in Regional Long-term Care Provision in Japan.

PubMed

Yamauchi, Yasuhiro

2015-07-12

Many developed countries face a growing need for long-term care provision because of population ageing. Japan is one such example, given its population's longevity and low birth rate. In this study, we examine the efficiency of Japan's regional long-term care system in FY2010 by performing a data envelopment analysis, a non-parametric frontier approach, on prefectural data and separating cost efficiency into technical, allocative, and price efficiencies under different average unit costs across regions. In doing so, we elucidate the structure of cost inefficiency by incorporating a method for restricting weight flexibility to avoid unrealistic concerns arising from zero optimal weight. The results indicate that technical inefficiency accounts for the highest share of losses, followed by price inefficiency and allocation inefficiency. Moreover, the majority of technical inefficiency losses stem from labor costs, particularly those for professional caregivers providing institutional services. We show that the largest share of allocative inefficiency losses can also be traced to labor costs for professional caregivers providing institutional services, while the labor provision of in-home care services shows an efficiency gain. However, although none of the prefectures gains efficiency by increasing the number of professional caregivers for institutional services, quite a few prefectures would gain allocative efficiency by increasing capital inputs for institutional services. These results indicate that preferred policies for promoting efficiency might vary from region to region, and thus, policy implications should be drawn with care.
21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5260 Complement C3b inactivator immunological test system. (a) Identification. A complement... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement C3b inactivator immunological test...
Complement System in Dermatological Diseases – Fire Under the Skin

PubMed Central

Panelius, Jaana; Meri, Seppo

2015-01-01

The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex on epidermal or vascular cells can cause direct tissue damage and inflammation, e.g., in systemic lupus erythematosus (SLE), phospholipid antibody syndrome, and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like Borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review, we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g., hydralazine, procainamide) could interact with C4A, C4B, or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1-inhibitor and anti-C5 antibody, eculizumab) that could alleviate symptoms in diseases associated with excessive complement activation. The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders. PMID:25688346
A fully distributed implementation of mean annual streamflow regional regression equations

USGS Publications Warehouse

Verdin, K.L.; Worstell, B.

2008-01-01

Estimates of mean annual streamflow are needed for a variety of hydrologic assessments. Away from gage locations, regional regression equations that are a function of upstream area, precipitation, and temperature are commonly used. Geographic information systems technology has facilitated their use for projects, but traditional approaches using the polygon overlay operator have been too inefficient for national scale applications. As an alternative, the Elevation Derivatives for National Applications (EDNA) database was used as a framework for a fully distributed implementation of mean annual streamflow regional regression equations. The raster “flow accumulation” operator was used to efficiently achieve spatially continuous parameterization of the equations for every 30 m grid cell of the conterminous United States (U.S.). Results were confirmed by comparing with measured flows at stations of the Hydro-Climatic Data Network, and their applications value demonstrated in the development of a national geospatial hydropower assessment. Interactive tools at the EDNA website make possible the fast and efficient query of mean annual streamflow for any location in the conterminous U.S., providing a valuable complement to other national initiatives (StreamStats and the National Hydrography Dataset Plus).

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
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
How to design a targeted agricultural subsidy system: efficiency or equity?

PubMed

Cong, Rong-Gang; Brady, Mark

2012-01-01

In this paper we appraise current agricultural subsidy policy in the EU. Several sources of its inefficiency are identified: it is inefficient for supporting farmers' incomes or guaranteeing food security, and irrational transfer payments decoupled from actual performance that may be negative for environmental protection, social cohesion, etc. Based on a simplified economic model, we prove that there is "reverse redistribution" in the current tax-subsidy system, which cannot be avoided. To find a possible way to distribute subsidies more efficiently and equitably, several alternative subsidy systems (the pure loan, the harvest tax and the income contingent loan) are presented and examined.
How to Design a Targeted Agricultural Subsidy System: Efficiency or Equity?

PubMed Central

Cong, Rong-Gang; Brady, Mark

2012-01-01

In this paper we appraise current agricultural subsidy policy in the EU. Several sources of its inefficiency are identified: it is inefficient for supporting farmers’ incomes or guaranteeing food security, and irrational transfer payments decoupled from actual performance that may be negative for environmental protection, social cohesion, etc. Based on a simplified economic model, we prove that there is “reverse redistribution” in the current tax-subsidy system, which cannot be avoided. To find a possible way to distribute subsidies more efficiently and equitably, several alternative subsidy systems (the pure loan, the harvest tax and the income contingent loan) are presented and examined. PMID:22876283
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.
An architecture model for multiple disease management information systems.

PubMed

Chen, Lichin; Yu, Hui-Chu; Li, Hao-Chun; Wang, Yi-Van; Chen, Huang-Jen; Wang, I-Ching; Wang, Chiou-Shiang; Peng, Hui-Yu; Hsu, Yu-Ling; Chen, Chi-Huang; Chuang, Lee-Ming; Lee, Hung-Chang; Chung, Yufang; Lai, Feipei

2013-04-01

Disease management is a program which attempts to overcome the fragmentation of healthcare system and improve the quality of care. Many studies have proven the effectiveness of disease management. However, the case managers were spending the majority of time in documentation, coordinating the members of the care team. They need a tool to support them with daily practice and optimizing the inefficient workflow. Several discussions have indicated that information technology plays an important role in the era of disease management. Whereas applications have been developed, it is inefficient to develop information system for each disease management program individually. The aim of this research is to support the work of disease management, reform the inefficient workflow, and propose an architecture model that enhance on the reusability and time saving of information system development. The proposed architecture model had been successfully implemented into two disease management information system, and the result was evaluated through reusability analysis, time consumed analysis, pre- and post-implement workflow analysis, and user questionnaire survey. The reusability of the proposed model was high, less than half of the time was consumed, and the workflow had been improved. The overall user aspect is positive. The supportiveness during daily workflow is high. The system empowers the case managers with better information and leads to better decision making.
Budgeting in health care systems.

PubMed

Maynard, A

1984-01-01

During the last decade there has been a recognition that all health care systems, public and private, are characterised by perverse incentives (especially moral hazard and third party pays) which generate inefficiency in the use of scarce economic resources. Inefficiency is unethical: doctors who use resources inefficiently deprive potential patients of care from which they could benefit. To eradicate unethical and inefficient practices two economic rules have to be followed: (i) no service should be provided if its total costs exceed its total benefits; (ii) if total benefits exceed total costs, the level of provision should be at that level at which the additional input cost (marginal cost) is equal to the additional benefits (marginal benefit). This efficiency test can be applied to health care systems, their component parts and the individuals (especially doctors) who control resource allocation within them. Unfortunately, all health care systems neither generate this relevant decision making data nor are they flexible enough to use it to affect health care decisions. There are two basic varieties of budgeting system: resource based and production targeted. The former generates obsession with cash limits and too little regard of the benefits, particularly at the margins, of alternative patterns of resource allocation. The latter generates undue attention to the production of processes of care and scant regard for costs, especially at the margins. Consequently, one set of budget rules may lead to cost containment regardless of benefits and the other set of budget rules may lead to output maximization regardless of costs. To close this circle of inefficiency it is necessary to evolve market-like structures. To do this a system of client group (defined broadly across all existing activities public and private) budgets is advocated with an identification of the budget holder who has the capacity to shift resources and seek out cost effective policies. Negotiated output targets with defined budgets and incentives for decision makers to economise in their use of resources are being incorporated into experiments in the health care systems of Western Europe and the United States. Undue optimism about the success of these experiments must be avoided because these problems have existed in the West and in the Soviet bloc for decades and efficient solutions are noticeable by their absence.
Decomposing Cost Efficiency in Regional Long-term Care Provision in Japan

PubMed Central

Yamauchi, Yasuhiro

2016-01-01

Many developed countries face a growing need for long-term care provision because of population ageing. Japan is one such example, given its population's longevity and low birth rate. In this study, we examine the efficiency of Japan's regional long-term care system in FY2010 by performing a data envelopment analysis, a non-parametric frontier approach, on prefectural data and separating cost efficiency into technical, allocative, and price efficiencies under different average unit costs across regions. In doing so, we elucidate the structure of cost inefficiency by incorporating a method for restricting weight flexibility to avoid unrealistic concerns arising from zero optimal weight. The results indicate that technical inefficiency accounts for the highest share of losses, followed by price inefficiency and allocation inefficiency. Moreover, the majority of technical inefficiency losses stem from labor costs, particularly those for professional caregivers providing institutional services. We show that the largest share of allocative inefficiency losses can also be traced to labor costs for professional caregivers providing institutional services, while the labor provision of in-home care services shows an efficiency gain. However, although none of the prefectures gains efficiency by increasing the number of professional caregivers for institutional services, quite a few prefectures would gain allocative efficiency by increasing capital inputs for institutional services. These results indicate that preferred policies for promoting efficiency might vary from region to region, and thus, policy implications should be drawn with care. PMID:26493427
Is complement good, bad, or both? New functions of the complement factors associated with inflammation mechanisms in the central nervous system.

PubMed

Tahtouh, Muriel; Croq, Françoise; Lefebvre, Christophe; Pestel, Joël

2009-09-01

The complement system is well known as an enzyme cascade that helps to defend against infections. Indeed, this ancestral system bridges innate and adaptive immunity. Its implication in diseases of the central nervous system (CNS), has led to an increased number of studies. Complement activation in the CNS has been generally considered to contribute to tissue damage. However, recent studies suggest that complement may be neuroprotective, and can participate in maintenance and repair of the adult brain. Here, we will review this dual role of complement proteins and some of their functional interactions with part of the chemokine and cytokine network associated with the protection of CNS integrity.
Inter-Regional Performance of the Public Health System in a High-Inequality Country

PubMed Central

Gramani, Maria Cristina

2014-01-01

Previous cross-country studies have revealed a relationship between health and socio-economic factors. However, multinational studies that use aggregate figures could obfuscate the actual situation in each individual region, or even in each individual federal unit, mainly in a developing country that spans a continent and has large socioeconomic inequalities. We conducted a within-country study, in Brazil, of health system performance that examined data in the four perspectives that most strongly affect the performance of public health systems: financial, customer, internal processes and learning&growth. After estimating the interregional health system performance from each perspective, we identified the determinants of inefficiency (i.e., the factors that have the greatest potential for improvement in each region). The results showed that the major determinants of inefficiency in the less efficient regions (N and NE) are concentrated in the perspective of learning&growth (the number of health professionals and the number of graduates with a health-related undergraduate degree) and, in the regions with the best performance (S and SE) the major determinants of inefficiency are concentrated in the financial perspective (spending on health care and the amount paid for hospitalization). PMID:24466201
Complement System Part II: Role in Immunity

PubMed Central

Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

2015-01-01

The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. PMID:26074922
Evolution of complement as an effector system in innate and adaptive immunity.

PubMed

Sunyer, J Oriol; Boshra, Hani; Lorenzo, Gema; Parra, David; Freedman, Bruce; Bosch, Nina

2003-01-01

For a long time, the complement system in mammals has been regarded as a biological system that plays an essential role in innate immunity. More recently, it has been recognized that the complement system contributes heavily to the generation and development of an acquired immune response. In fact, this ancient mechanism of defense has evolved from a primitive mechanism of innate immune recognition in invertebrate species to that of an effector system that bridges the innate with the adaptive immune response in vertebrate species. When and how did complement evolve into a shared effector system between innate and adaptive immunity? To answer this question, our group is interested in understanding the role of complement in innate and adaptive immune responses in an evolutionary relevant species: the teleost fish. The attractiveness of this species as an animal model is based on two important facts. First, teleost fish are one of the oldest animal species to have developed an adaptive immune response. Second, the complement system of teleost fish offers a unique feature, which is the structural and functional diversity of its main effector protein, C3, the third component of the complement system.
Potential nanotechnology applications for reducing freshwater consumption at coal fired power plants : an early view.

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

Elcock, D.

2010-09-17

This report was funded by the U.S. Department of Energy's (DOE's) National Energy Technology Laboratory (NETL) Existing Plants Research Program, which has an energy-water research effort that focuses on water use at power plants. This study complements the overall research effort of the Existing Plants Research Program by evaluating water issues that could impact power plants. A growing challenge to the economic production of electricity from coal-fired power plants is the demand for freshwater, particularly in light of the projected trends for increasing demands and decreasing supplies of freshwater. Nanotechnology uses the unique chemical, physical, and biological properties that aremore » associated with materials at the nanoscale to create and use materials, devices, and systems with new functions and properties. It is possible that nanotechnology may open the door to a variety of potentially interesting ways to reduce freshwater consumption at power plants. This report provides an overview of how applications of nanotechnology could potentially help reduce freshwater use at coal-fired power plants. It was developed by (1) identifying areas within a coal-fired power plant's operations where freshwater use occurs and could possibly be reduced, (2) conducting a literature review to identify potential applications of nanotechnology for facilitating such reductions, and (3) collecting additional information on potential applications from researchers and companies to clarify or expand on information obtained from the literature. Opportunities, areas, and processes for reducing freshwater use in coal-fired power plants considered in this report include the use of nontraditional waters in process and cooling water systems, carbon capture alternatives, more efficient processes for removing sulfur dioxide and nitrogen oxides, coolants that have higher thermal conductivities than water alone, energy storage options, and a variety of plant inefficiencies, which, if improved, would reduce energy use and concomitant water consumption. These inefficiencies include air heater inefficiencies, boiler corrosion, low operating temperatures, fuel inefficiencies, and older components that are subject to strain and failure. A variety of nanotechnology applications that could potentially be used to reduce the amount of freshwater consumed - either directly or indirectly - by these areas and activities was identified. These applications include membranes that use nanotechnology or contain nanomaterials for improved water purification and carbon capture; nano-based coatings and lubricants to insulate and reduce heat loss, inhibit corrosion, and improve fuel efficiency; nano-based catalysts and enzymes that improve fuel efficiency and improve sulfur removal efficiency; nanomaterials that can withstand high temperatures; nanofluids that have better heat transfer characteristics than water; nanosensors that can help identify strain and impact damage, detect and monitor water quality parameters, and measure mercury in flue gas; and batteries and capacitors that use nanotechnology to enable utility-scale storage. Most of these potential applications are in the research stage, and few have been deployed at coal-fired power plants. Moving from research to deployment in today's economic environment will be facilitated with federal support. Additional support for research development and deployment (RD&D) for some subset of these applications could lead to reductions in water consumption and could provide lessons learned that could be applied to future efforts. To take advantage of this situation, it is recommended that NETL pursue funding for further research, development, or deployment for one or more of the potential applications identified in this report.« less
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.
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.
Evolution and diversity of the complement system of poikilothermic vertebrates.

PubMed

Sunyer, J O; Lambris, J D

1998-12-01

In mammals the complement system plays an important role in innate and acquired host defense mechanisms against infection and in various immunoregulatory processes. The complement system is an ancient defense mechanism that is already present in the invertebrate deuterostomes. In these species as well as in agnathans (the most primitive vertebrate species), both the alternative and lectin pathway of complement activation are already present, and the complement system appears to be involved mainly in opsonization of foreign material. With the emergence of immunoglobulins in cartilaginous fish, the classical and lytic pathways first appear. The rest of the poikilothermic species, from teleosts to reptilians, appear to contain a well-developed complement system resembling that of homeothermic vertebrates. However, important differences remain. Unlike homeotherms, several species of poikilotherms have recently been shown to possess multiple forms of complement components (C3 and factor B) that are structurally and functionally more diverse than those of higher vertebrates. It is noteworthy that the multiple forms of C3 that have been characterized in several teleost fish are able to bind with varying efficiencies to various complement-activating surfaces. We hypothesize that this diversity has allowed these animals to expand their innate capacity for immune recognition.
Complement, a target for therapy in inflammatory and degenerative diseases.

PubMed

Morgan, B Paul; Harris, Claire L

2015-12-01

The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.
Exopolysaccharides Isolated from Hydrothermal Vent Bacteria Can Modulate the Complement System

PubMed Central

Courtois, Anthony; Berthou, Christian; Guézennec, Jean

2014-01-01

The complement system is involved in the defence against bacterial infection, or in the elimination of tumour cells. However, disturbances in this system contributes to the pathogenesis of various inflammatory diseases. The efficiency of therapeutic anti-tumour antibodies is enhanced when the complement system is stimulated. In contrast, cancer cells are able to inhibit the complement system and thus proliferate. Some marine molecules are currently being developed as new drugs for use in humans. Among them, known exopolyssacharides (EPSs) generally originate from fungi, but few studies have been performed on bacterial EPSs and even fewer on EPSs extracted from deep-sea hydrothermal vent microbes. For use in humans, these high molecular weight EPSs must be depolymerised. Furthermore, the over-sulphation of EPSs can modify their biological activity. The aim of this study was to investigate the immunodulation of the complement system by either native or over-sulphated low molecular weight EPSs isolated from vent bacteria in order to find pro or anti-activators of complement. PMID:24736648
Physicochemical characterization and study of in vitro interactions of pH-sensitive liposomes with the complement system.

PubMed

Carmo, Vildete A S; De Oliveira, Mônica C; Reis, Eduardo C O; Guimarães, Tânia M P D; Vilela, José M C; Andrade, Margareth S; Michalick, Marilene S M; Cardoso, Valbert N

2008-01-01

Complement activation is an important step in the acceleration of liposome clearance. The anaphylatoxins released following complement activation may motivate a wide variety of physiologic changes. We performed physicochemical characterization and in vitro studies of the interaction of complement system with both noncirculating and long-circulating pH-sensitive and nonpH-sensitive liposomes. The liposomes were characterized by diameter, zeta potential, and atomic force microscopy (AFM). The study of liposome interactions with complement system was conducted using hemolytic assay in rat serum. All liposomes presented a similar mean diameter (between 99.8 and 124.3 nm). The zeta potential was negative in all liposome preparations, except in liposomes modified with aminopoly (ethyleneglycol) 2000-distearoylphosphatidylethanolamine (aPEG(2000)-DSPE), which presented positive zeta potential. Atomic force microscopy images showed that non-long-circulating pH-sensitive liposomes are prone to vesicles aggregation. Non-pH-sensitive liposomes complement system activates, while pH-sensitive liposomes showed to be poor complement activators in rat serum.
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.

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
Dynamic Inefficiencies in an Employment-Based Health Insurance System: Theory and Evidence.

PubMed

Fang, Hanming; Gavazza, Alessandro

2011-12-01

We investigate the effects of the institutional settings of the US health care system on individuals' life-cycle medical expenditures. Health is a form of general human capital; labor turnover and labor-market frictions prevent an employer-employee pair from capturing the entire surplus from investment in an employee’s health. Thus, the pair underinvests in health during working years, thereby increasing medical expenditures during retirement. We provide empirical evidence consistent with the comparative statics predictions of our model using the Medical Expenditure Panel Survey (MEPS) and the Health and Retirement Study (HRS). Our estimates suggest significant inefficiencies in health investment in the United States.
Strategies for the quality assessment of the health care service providers in the treatment of Gastric Cancer in Colombia.

PubMed

Villamil, María Del Pilar; Barrera, David; Velasco, Nubia; Bernal, Oscar; Fajardo, Esteban; Urango, Carlos; Buitrago, Sebastian

2017-09-15

While, at its inception in 1993, the health care system in Colombia was publicized as a paradigm to be copied across the developing world, numerous problems in its implementation have led to, what is now, an inefficient and crisis-ridden health system. Furthermore, as a result of inappropriate tools to measure the quality of the health service providers, several corruption scandals have arisen in the country. This study attempts to tackle this situation by proposing a strategy for the quality assessment of the health service providers (Entidades Promotoras de Salud, EPS) in the Colombian health system. In particular, as a case study, the quality of the treatment of stomach cancer is analyzed. The study uses two complementary techniques to address the problem. These techniques are applied based on data of the treatment of gastric cancer collected on a nation-wide scale by the Colombian Ministry of Health and Welfare. First, Data Envelopment Analysis (DEA) and the Malmquist Index (MI) are used to establish the most efficient EPS's within the system, according to indicators such as opportunity indicators. Second, sequential clustering algorithm, related to process mining a field of data mining, is used to determine the medical history of all patients and to construct typical care pathways of the patients belonging to efficient and inefficient EPS's. Lastly, efforts are made to identify traits and differences between efficient and inefficient EPS's. Efficient and inefficient EPS were identified for the years 2010 and 2011. Additionally, a Malmquist Index was used to calculate the relative changes in the efficiency of the health providers. Using these efficiency rates, the typical treatment path of patients with gastric cancer was found for two EPSs: one efficient and another inefficient. Finally, the typical traits of the care pathways were established. Combining DEA and process mining proved to be a powerful approach understanding the problem and gaining valuable insight into the inner workings of the Colombian Health System, especially in terms of the treatment process performed by health care providers in critical illnesses such as cancer. However, no sufficiently compelling results were found to establish the contribution of such a combination to evaluate the quality in the delivery of health services.
Complement

MedlinePlus

... activity (CH50, CH100) looks at the overall activity of the complement system. In most cases, other tests that are more ... Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I - molecular mechanisms of activation and regulation. Front Immunol . 2015;6:262. ...
Bed usage in a Dublin teaching hospital: a prospective audit.

PubMed

John, A; Breen, D P; Ghafar, Aabdul; Olphert, T; Burke, C M

2004-01-01

We prospectively audited inpatient bed use in our hospital for the first three months of this year. While 70% (mean age 54 +/- 20.8 years) of our patients went home on the day they were medically discharged, 30% (mean age 70.3 +/- 18.3 years) remained in the hospital awaiting step-down facilities. The total of 486 bed days occupied by overstaying patients would if available, have allowed treatment of 54% more patients without any increase in the hospital complement of beds, preventing the cancellation of elective procedures and preventing patients remaining on trolleys overnight. These prospective data emphasise (1) a highly inefficient use of acute hospital beds; (2) the need for step-down facilities; (3) efficient use of existing hospital beds is the highest priority both for optimal patient care and optimal use of expensive hospital resources; (4) efficient use of existing facilities should be achieved before the construction of additional facilities.
Multimodal imaging of vascular grafts using time-resolved fluorescence and ultrasound

NASA Astrophysics Data System (ADS)

Fatakdawala, Hussain; Griffiths, Leigh G.; Wong, Maelene L.; Humphrey, Sterling; Marcu, Laura

2015-02-01

The translation of engineered tissues into clinic requires robust monitoring of tissue development, both in vitro and in vivo. Traditional methods for the same are destructive, inefficient in time and cost and do not allow time-lapse measurements from the same sample or animal. This study reports on the ability of time-resolved fluorescence and ultrasound measurements for non-destructive characterization of explanted tissue engineered vascular grafts. Results show that TRFS and FLIm are able to assess alterations in luminal composition namely elastin, collagen and cellular (hyperplasia) content via changes in fluorescence lifetime values between normal and grafted tissue. These observations are complemented by structural changes observed in UBM pertaining to graft integration and intimal thickness over the grafted region. These results encourage the future application of a catheter-based technique that combines these imaging modalities for non-destructive characterization of vascular grafts in vivo.
The role of microcredit in reducing women's vulnerabilities to multiple disasters.

PubMed

Ray-Bennett, Nibedita S

2010-01-01

This article explores the relationship between microcredit and vulnerability reduction for women-headed households in'multiple disasters'. Here multiple disasters are understood as disasters that occur in one specific place and cause severe devastation. The case study covers the super-cyclone in 1999, floods in 2001 and 2003, and drought in 2002 in Orissa, India. The study entailed eight months fieldwork and interviews with several governmental and non-governmental officials and 12 women-headed households from different social castes. The findings suggest that microcredit is a useful tool to replace women's livelihood assets that have been lost in multiple disasters. But inefficient microcredit delivery can cause microdebts and exacerbate caste, class and gender inequalities. It is posited that microcredit delivery cannot achieve vulnerability reduction for women in multiple disasters unless it is complemented by effective financial services, integrated policy planning and disaster management between government, non-governmental organisations and the community.
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.
The role of complement in the success of vaccination with conjugated vs. unconjugated polysaccharide antigen.

PubMed

Salehen, Nur'ain; Stover, Cordula

2008-01-24

The complement system, a well-characterised arm of the innate immune system, significantly influences the adaptive immune response via direct cell-cell interaction and maintenance of lymphoid organ architecture. Development of vaccines is a major advance in modern health care. In this review, we highlight the importance of the marginal zone in response to both, polysaccharide and conjugated vaccines, and discuss the relevance of complement herein, based on findings obtained from animal models with specific deletions of certain complement components and from vaccination reports of complement-deficient individuals. We conclude that both, intactness of the complement system and maturity of expression of its components, are relatively more important to aid in the immune response to polysaccharide vaccine than to conjugated vaccines.
Traffic off-balancing algorithm for energy efficient networks

NASA Astrophysics Data System (ADS)

Kim, Junhyuk; Lee, Chankyun; Rhee, June-Koo Kevin

2011-12-01

Physical layer of high-end network system uses multiple interface arrays. Under the load-balancing perspective, light load can be distributed to multiple interfaces. However, it can cause energy inefficiency in terms of the number of poor utilization interfaces. To tackle this energy inefficiency, traffic off-balancing algorithm for traffic adaptive interface sleep/awake is investigated. As a reference model, 40G/100G Ethernet is investigated. We report that suggested algorithm can achieve energy efficiency while satisfying traffic transmission requirement.
To What Extent Should the Criminal Justice System Be a "System"?

ERIC Educational Resources Information Center

Forst, Martin L.

1977-01-01

This article examines recent criticism of the current criminal justice system which characterizes it as a "nonsystem" because its three main components--law enforcement, courts, and correction--are often poorly managed and inefficient. (Author)
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
Determinants of Regional Variation in Health Expenditures in Germany.

PubMed

Göpffarth, Dirk; Kopetsch, Thomas; Schmitz, Hendrik

2016-07-01

Health care expenditure in Germany shows clear regional differences. Such geographic variations are often seen as an indicator for inefficiency. With its homogeneous health care system, low co-payments and uniform prices, Germany is a particularly suited example to analyse regional variations. We use data for the year 2011 on expenditure, utilization of health services and state of health in Germany's statutory health insurance system. This data, which originate from a variety of administrative sources and cover about 90% of the population, are enriched with a wealth of socio-economic variables, data on pollutants, prices and individual preferences. State of health and demography explains 55% of the differences as measured by the standard deviation while all control variables account for a total of 72% of the differences at county level. With other measures of variation, we can account for an even greater proportion. A higher proportion of variation than usually supposed can thus be explained. Whilst this study cannot quantify inefficiencies, our results contradict the thesis that regional variations reflect inefficiency. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Role of Complement on Broken Surfaces After Trauma.

PubMed

Huber-Lang, Markus; Ignatius, Anita; Brenner, Rolf E

2015-01-01

Activation of both the complement and coagulation cascade after trauma and subsequent local and systemic inflammatory response represent a major scientific and clinical problem. After severe tissue injury and bone fracture, exposure of innate immunity to damaged cells and molecular debris is considered a main trigger of the posttraumatic danger response. However, the effects of cellular fragments (e.g., histones) on complement activation remain enigmatic. Furthermore, direct effects of "broken" bone and cartilage surfaces on the fluid phase response of complement and its interaction with key cells of connective tissues are still unknown. Here, we summarize data suggesting direct and indirect complement activation by extracellular and cellular danger associated molecular patterns. In addition, key complement components and the corresponding receptors (such as C3aR, C5aR) have been detected on "exposed surfaces" of the damaged regions. On a cellular level, multiple effects of complement activation products on osteoblasts, osteoclasts, chondrocytes and mesenchymal stem cells have been found.In conclusion, the complement system may be activated by trauma-altered surfaces and is crucially involved in connective tissue healing and posttraumatic systemic inflammatory response.
The Serum Complement System: A Simplified Laboratory Exercise to Measure the Activity of an Important Component of the Immune System

ERIC Educational Resources Information Center

Inglis, Jordan E.; Radziwon, Kimberly A.; Maniero, Gregory D.

2008-01-01

The immune system is a vital physiological component that affords animals protection from disease and is composed of innate and adaptive mechanisms that rely on cellular and dissolved components. The serum complement system is a series of dissolved proteins that protect against a variety of pathogens. The activity of complement in serum can be…
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.
Targeting the complement system for the management of retinal inflammatory and degenerative diseases.

PubMed

Xu, Heping; Chen, Mei

2016-09-15

The retina, an immune privileged tissue, has specialized immune defense mechanisms against noxious insults that may exist in diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), uveoretinitis and glaucoma. The defense system consists of retinal innate immune cells (including microglia, perivascular macrophages, and a small population of dendritic cells) and the complement system. Under normal aging conditions, retinal innate immune cells and the complement system undergo a low-grade activation (parainflammation) which is important for retinal homeostasis. In disease states such as AMD and DR, the parainflammatory response is dysregulated and develops into detrimental chronic inflammation. Complement activation in the retina is an important part of chronic inflammation and may contribute to retinal pathology in these disease states. Here, we review the evidence that supports the role of uncontrolled or dysregulated complement activation in various retinal degenerative and angiogenic conditions. We also discuss current strategies that are used to develop complement-based therapies for retinal diseases such as AMD. The potential benefits of complement inhibition in DR, uveoretinitis and glaucoma are also discussed, as well as the need for further research to better understand the mechanisms of complement-mediated retinal damage in these disease states. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Sprinkler Body Fact Sheet

EPA Pesticide Factsheets

Landscape irrigation sprinklers are often installed at sites where the system pressure is higher than what is recommended for the sprinkler body, thus resulting in system inefficiencies. WaterSense labeled sprinkler bodies can address this problem.
Quality improvement utilizing in-situ simulation for a dual-hospital pediatric code response team.

PubMed

Yager, Phoebe; Collins, Corey; Blais, Carlene; O'Connor, Kathy; Donovan, Patricia; Martinez, Maureen; Cummings, Brian; Hartnick, Christopher; Noviski, Natan

2016-09-01

Given the rarity of in-hospital pediatric emergency events, identification of gaps and inefficiencies in the code response can be difficult. In-situ, simulation-based medical education programs can identify unrecognized systems-based challenges. We hypothesized that developing an in-situ, simulation-based pediatric emergency response program would identify latent inefficiencies in a complex, dual-hospital pediatric code response system and allow rapid intervention testing to improve performance before implementation at an institutional level. Pediatric leadership from two hospitals with a shared pediatric code response team employed the Institute for Healthcare Improvement's (IHI) Breakthrough Model for Collaborative Improvement to design a program consisting of Plan-Do-Study-Act cycles occurring in a simulated environment. The objectives of the program were to 1) identify inefficiencies in our pediatric code response; 2) correlate to current workflow; 3) employ an iterative process to test quality improvement interventions in a safe environment; and 4) measure performance before actual implementation at the institutional level. Twelve dual-hospital, in-situ, simulated, pediatric emergencies occurred over one year. The initial simulated event allowed identification of inefficiencies including delayed provider response, delayed initiation of cardiopulmonary resuscitation (CPR), and delayed vascular access. These gaps were linked to process issues including unreliable code pager activation, slow elevator response, and lack of responder familiarity with layout and contents of code cart. From first to last simulation with multiple simulated process improvements, code response time for secondary providers coming from the second hospital decreased from 29 to 7 min, time to CPR initiation decreased from 90 to 15 s, and vascular access obtainment decreased from 15 to 3 min. Some of these simulated process improvements were adopted into the institutional response while others continue to be trended over time for evidence that observed changes represent a true new state of control. Utilizing the IHI's Breakthrough Model, we developed a simulation-based program to 1) successfully identify gaps and inefficiencies in a complex, dual-hospital, pediatric code response system and 2) provide an environment in which to safely test quality improvement interventions before institutional dissemination. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Black holes in short period X-ray binaries and the transition to radiatively inefficient accretion

NASA Astrophysics Data System (ADS)

Knevitt, G.; Wynn, G. A.; Vaughan, S.; Watson, M. G.

2014-02-01

By comparing the orbital period distributions of black hole and neutron star low-mass X-ray binaries (LMXBs) in the Ritter-Kolb catalogue we show that there is statistical evidence for a dearth of black hole systems at short orbital periods (Porb < 4 h). This could either be due to a true divergence in orbital period distributions of these two types of system, or to black hole LMXBs being preferentially hidden from view at short orbital periods. We explore the latter possibility, by investigating whether black hole LMXBs could be concealed by a switch to radiatively inefficient accretion at low luminosities. The peak luminosity and the duration of X-ray binary outbursts are related to the disc radius and, hence, the orbital period. At short periods, where the peak outburst luminosity drops close to the threshold for radiatively inefficient accretion, black hole LMXBs have lower outburst luminosities, shorter outburst durations and lower X-ray duty cycles than comparable neutron star systems. These factors can combine to severely reduce the detection probability of short period black hole LMXBs relative to those containing neutron stars. We estimate the outburst properties and orbital period distribution of black hole LMXBs using two models of the transition to radiatively inefficient accretion: an instantaneous drop in accretion efficiency (η) to zero, at a fraction (f) of the Eddington luminosity (LEdd) and a power-law efficiency decrease, η ∝ dot{M}^n, for L < f LEdd. We show that a population of black hole LMXBs at short orbital periods can only be hidden by a sharp drop in efficiency, either instantaneous or for n ≳ 3. This could be achieved by a genuine drop in luminosity or through abrupt spectral changes that shift the accretion power out of a given X-ray band.
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.
Transportation and Greenhouse Gas Emissions Trading. Final Technical Report

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

Steve Winkelman; Tim Hargrave; Christine Vanderlan

1999-10-01

The authors conclude in this report that an upstream system would ensure complete regulatory coverage of transportation sector emissions in an efficient and feasible manner, and as such represents a key component of a national least-cost GHG emissions abatement strategy. The broad coverage provided by an upstream system recommends this approach over vehicle-maker based approaches, which would not cover emissions from heavy-duty vehicles and the aviation, marine and off-road sub-sectors. The on-road fleet approach unfairly and inefficiently burdens vehicle manufacturers with responsibility for emissions that they cannot control. A new vehicles approach would exclude emissions from vehicles on the roadmore » prior to program inception. The hybrid approach faces significant technical and political complications, and it is not clear that the approach would actually change behavior among vehicle makers and users, which is its main purpose. They also note that a trading system would fail to encourage many land use and infrastructure measures that affect VMT growth and GHG emissions. They recommend that this market failure be addressed by complementing the trading system with a program specifically targeting land use- and infrastructure-related activities. A key issue that must be addressed in designing a national GHG control strategy is whether or not it is necessary to guarantee GHG reductions from the transport sector. Neither an upstream system nor a downstream approach would do so, since both would direct capital to the least-cost abatement opportunities wherever they were found. They review two reasons why it may be desirable to force transportation sector reductions: first, that the long-term response to climate change will require reductions in all sectors; and second, the many ancillary benefits associated with transportation-related, and especially VMT-related, emissions reduction activities. If policy makers find it desirable to establish transportation-specific policies, they recommend (in addition to the land use policies mentioned above), that they combine an upstream trading system with a carbon efficiency standard similar to the current CAFE standard. Under this approach a fuel price signal would be complemented by incentives for manufacturers to produce more carbon efficient vehicles. To prevent vehicle manufacturers from being forced to pay more than other sectors for reducing GHG emissions, they recommend that the vehicle makers be allowed to pay a cash penalty equal to the market price of allowances in lieu of meeting carbon efficiency requirements.« less
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...
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...
The intestinal complement system in inflammatory bowel disease: Shaping intestinal barrier function.

PubMed

Sina, Christian; Kemper, Claudia; Derer, Stefanie

2018-06-01

The complement system is part of innate sensor and effector systems such as the Toll-like receptors (TLRs). It recognizes and quickly systemically and/or locally respond to microbial-associated molecular patterns (MAMPs) with a tailored defense reaction. MAMP recognition by intestinal epithelial cells (IECs) and appropriate immune responses are of major importance for the maintenance of intestinal barrier function. Enterocytes highly express various complement components that are suggested to be pivotal for proper IEC function. Appropriate activation of the intestinal complement system seems to play an important role in the resolution of chronic intestinal inflammation, while over-activation and/or dysregulation may worsen intestinal inflammation. Mice deficient for single complement components suffer from enhanced intestinal inflammation mimicking the phenotype of patients with chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD) or ulcerative colitis (UC). However, the mechanisms leading to complement expression in IECs seem to differ markedly between UC and CD patients. Hence, how IECs, intestinal bacteria and epithelial cell expressed complement components interact in the course of IBD still remains to be mostly elucidated to define potential unique patterns contributing to the distinct subtypes of intestinal inflammation observed in CD and UC. Copyright © 2018 Elsevier Ltd. All rights reserved.
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
Transportation engineering project management : survey of practice.

DOT National Transportation Integrated Search

2017-01-01

Utah Department of Transportation (UDOT) project managers (PMs) have identified inefficiencies in the legacy : system electronic Program Management (ePM) used to manage consultant contracts and invoices. To help UDOT : prepare for potential system im...
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.
Phylogenetic aspects of the complement system.

PubMed

Zarkadis, I K; Mastellos, D; Lambris, J D

2001-01-01

During evolution two general systems of immunity have emerged: innate or, natural immunity and adaptive (acquired), or specific immunity. The innate system is phylogenetically older and is found in some form in all multicellular organisms, whereas the adaptive system appeared about 450 million years ago and is found in all vertebrates except jawless fish. The complement system in higher vertebrates plays an important role as an effector of both the innate and the acquired immune response, and also participates in various immunoregulatory processes. In lower vertebrates complement is activated by the alternative and lectin pathways and is primarily involved in the opsonization of foreign material. The Agnatha (the most primitive vertebrate species) possess the alternative and lectin pathways while cartilaginous fish are the first species in which the classical pathway appears following the emergence of immunoglobulins. The rest of the poikilothermic species, ranging from teleosts to reptilians, appear to contain a well-developed complement system resembling that of the homeothermic vertebrates. It seems that most of the complement components have appeared after the duplication of primordial genes encoding C3/C4/C5, fB/C2, C1s/C1r/MASP-1/MASP-2, and C6/C7/C8/C9 molecules, in a process that led to the formation of distinct activation pathways. However, unlike homeotherms, several species of poikilotherms (e.g. trout) have recently been shown to possess multiple forms of complement components (C3, factor B) that are structurally and functionally more diverse than those of higher vertebrates. We hypothesize that this remarkable diversity has allowed these animals to expand their innate capacity for immune recognition and response. Recent studies have also indicated the possible presence of complement receptors in protochordates and lower vertebrates. In conclusion, there is considerable evidence suggesting that the complement system is present in the entire lineage of deuterostomes, and regulatory complement components have been identified in all species beyond the protochordates, indicating that the mechanisms of complement activation and regulation have developed in parallel.
Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages.

PubMed

Pondman, Kirsten M; Sobik, Martin; Nayak, Annapurna; Tsolaki, Anthony G; Jäkel, Anne; Flahaut, Emmanuel; Hampel, Silke; Ten Haken, Bennie; Sim, Robert B; Kishore, Uday

2014-08-01

Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. Copyright © 2014 Elsevier Inc. All rights reserved.
Cost efficiency of US hospitals: a stochastic frontier approach.

PubMed

Rosko, M D

2001-09-01

This study examined the impact of managed care and other environmental factors on hospital inefficiency in 1631 US hospitals during the period 1990-1996. A panel, stochastic frontier regression model was used to estimate inefficiency parameters and inefficiency scores. The results suggest that mean estimated inefficiency decreased by about 28% during the study period. Inefficiency was negatively associated with health maintenance organization (HMO) penetration and industry concentration. It was positively related with Medicare share and for-profit ownership status. Copyright 2001 John Wiley & Sons, Ltd.
Autoantibodies against complement components in systemic lupus erythematosus - role in the pathogenesis and clinical manifestations.

PubMed

Hristova, M H; Stoyanova, V S

2017-12-01

Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Genetic defects in the complement as well as functional deficiency due to antibodies against its components lead to different pathological conditions, usually clinically presented. Among them hypocomplementemic urticarial vasculitis, different types of glomerulonephritis as dense deposit disease, IgA nephropathy, atypical haemolytic uremic syndrome and lupus nephritis are very common. These antibodies cause conformational changes leading to pathological activation or inhibition of complement with organ damage and/or limited capacity of the immune system to clear immune complexes and apoptotic debris. Finally, we summarize the role of complement antibodies in the pathogenesis of systemic lupus erythematosus and discuss the mechanism of some related clinical conditions such as infections, thyroiditis, thrombosis, acquired von Willebrand disease, etc.
Research on the identification of inefficient and invalid circulation in ultra-high water cut stage

NASA Astrophysics Data System (ADS)

Han, Shaoxin

2018-06-01

After oil field entered into ultra-high water cut stage, big channels are formed in some oil and water wells and lead to the inefficient and ineffective circulation of injected water, which not only inhibit the increase of recovery ratio of oil and gas, but also cause the waste of resources. This article selects three static parameters and four dynamic parameters which can perform inefficient and ineffective circulation characteristics between oil and water wells, integrates the fuzzy mathematics theory, establishes fuzzy comprehensive evaluation model to identify the inefficient and ineffective circulation wells in the research area, on this basis, inefficient and ineffective circulation position is further determined through the logging curve characteristics and logging ratio method, the identification of inefficient and ineffective circulation "determine well and layer" is achieved, and provide powerful basis for governance work of inefficient and ineffective circulation.
Increased activity of the complement system in the liver of patients with alcoholic hepatitis.

PubMed

Shen, Hong; French, Barbara A; Liu, Hui; Tillman, Brittany C; French, Samuel W

2014-12-01

Inflammation has been suggested as a mechanism underlying the development of alcoholic hepatitis (AH). The activation of the complement system plays an important role in inflammation. Although it has been shown that ethanol-induced activation of the complement system contributes to the pathophysiology of ethanol-induced liver injury in mice, whether ethanol consumption activates the complement system in the human liver has not been investigated. Using antibodies against C1q, C3, and C5, the immunoreactivity of the complement system in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of C1q, C3, and C5 in patients with AH was significantly higher than that seen in normal controls. Further, the gene expression of C1q, C3, and C5 was examined using real-time PCR. There were increases in the levels of C1q and C5, but not C3 mRNA in AH. Moreover, the immunoreactivity of C5a receptor (C5aR) also increased in AH. To explore the functional implication of the activation of the complement system in AH, we examined the colocalization of C5aR in Mallory-Denk bodies (MDBs) forming balloon hepatocytes. C5aR was focally overexpressed in the MDB forming cells. Collectively, our study suggests that alcohol consumption increases the activity of the complement system in the liver cells, which contributes to the inflammation-associated pathogenesis of AH. Copyright © 2014 Elsevier Inc. All rights reserved.
A real-time online decision support system for intermodal passenger travel.

DOT National Transportation Integrated Search

2015-09-01

The transportation system in the United States is disjointed and inefficient as a result of the : different transportation modes in use and their respective industries which have developed : independently. In addition, public transportation is not we...
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

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.
Complement system studies in systemic lupus erythematosus (SLE)

PubMed

Teisberg, P

1975-01-01

Complement system involvement has been studied in 16 patients with systemic lupus erythematosus (SLE). Circulating conversion products of C3 were observed in 4 cases. Low mean values of C4 and C3 were found, while C3 proactivator (properdin factor B) levels were low in only a few of the patients. The levels of C4, C3 and C3 proactivator were not lower in the 4 patients in whom C3 conversion products could be demonstrated than in the others. It is concluded that the low complement values found in SLE may be caused mainly by deficient synthesis. Signs of complement activation are in this patient material demonstrated early in the disease, and chiefly in patients not receiving immunosuppressive therapy.
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.
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.
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.
Targeting complement-mediated immunoregulation for cancer immunotherapy.

PubMed

Kolev, Martin; Markiewski, Maciej M

2018-06-01

Complement was initially discovered as an assembly of plasma proteins "complementing" the cytolytic activity of antibodies. However, our current knowledge places this complex system of several plasma proteins, receptors, and regulators in the center of innate immunity as a bridge between the initial innate responses and adaptive immune reactions. Consequently, complement appears to be pivotal for elimination of pathogens, not only as an early response defense, but by directing the subsequent adaptive immune response. The discovery of functional intracellular complement and its roles in cellular metabolism opened novel avenues for research and potential therapeutic implications. The recent studies demonstrating immunoregulatory functions of complement in the tumor microenvironment and the premetastatic niche shifted the paradigm on our understanding of functions of the complement system in regulating immunity. Several complement proteins, through their interaction with cells in the tumor microenvironment and in metastasis-targeted organs, contribute to modulating tumor growth, antitumor immunity, angiogenesis, and therefore, the overall progression of malignancy and, perhaps, responsiveness of cancer to different therapies. Here, we focus on recent progress in our understanding of immunostimulatory vs. immunoregulatory functions of complement and potential applications of these findings to the design of novel therapies for cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.
White papers on freight efficiency.

DOT National Transportation Integrated Search

2016-05-31

A number of stakeholders met with the ultimate goal of identifying inefficiencies faced by the freight system and putting forward a set of : strategies to achieve a more efficient freight system. In doing so, a key first step was to provide insight a...
Complement in Non-Antibody-Mediated Kidney Diseases

PubMed Central

Angeletti, Andrea; Reyes-Bahamonde, Joselyn; Cravedi, Paolo; Campbell, Kirk N.

2017-01-01

The complement system is part of the innate immune response that plays important roles in protecting the host from foreign pathogens. The complement components and relative fragment deposition have long been recognized to be strongly involved also in the pathogenesis of autoantibody-related kidney glomerulopathies, leading to direct glomerular injury and recruitment of infiltrating inflammation pathways. More recently, unregulated complement activation has been shown to be associated with progression of non-antibody-mediated kidney diseases, including focal segmental glomerulosclerosis, C3 glomerular disease, thrombotic microangiopathies, or general fibrosis generation in progressive chronic kidney diseases. Some of the specific mechanisms associated with complement activation in these diseases were recently clarified, showing a dominant role of alternative activation pathway. Over the last decade, a growing number of anticomplement agents have been developed, and some of them are being approved for clinical use or already in use. Therefore, anticomplement therapies represent a realistic choice of therapeutic approaches for complement-related diseases. Herein, we review the complement system activation, regulatory mechanisms, their involvement in non-antibody-mediated glomerular diseases, and the recent advances in complement-targeting agents as potential therapeutic strategies. PMID:28748184
Systemic Lupus Erythematosus and Deficiencies of Early Components of the Complement Classical Pathway

PubMed Central

Macedo, Ana Catarina Lunz; Isaac, Lourdes

2016-01-01

The complement system plays an important role in the innate and acquired immune response against pathogens. It consists of more than 30 proteins found in soluble form or attached to cell membranes. Most complement proteins circulate in inactive forms and can be sequentially activated by the classical, alternative, or lectin pathways. Biological functions, such as opsonization, removal of apoptotic cells, adjuvant function, activation of B lymphocytes, degranulation of mast cells and basophils, and solubilization and clearance of immune complex and cell lysis, are dependent on complement activation. Although the activation of the complement system is important to avoid infections, it also can contribute to the inflammatory response triggered by immune complex deposition in tissues in autoimmune diseases. Paradoxically, the deficiency of early complement proteins from the classical pathway (CP) is strongly associated with development of systemic lupus erythematous (SLE) – mainly C1q deficiency (93%) and C4 deficiency (75%). The aim of this review is to focus on the deficiencies of early components of the CP (C1q, C1r, C1s, C4, and C2) proteins in SLE patients. PMID:26941740
Detection and characterisation of Complement protein activity in bovine milk by bactericidal sequestration assay.

PubMed

Maye, Susan; Stanton, Catherine; Fitzgerald, Gerald F; Kelly, Philip M

2015-08-01

While the Complement protein system in human milk is well characterised, there is little information on its presence and activity in bovine milk. Complement forms part of the innate immune system, hence the importance of its contribution during milk ingestion to the overall defences of the neonate. A bactericidal sequestration assay, featuring a Complement sensitive strain, Escherichia coli 0111, originally used to characterise Complement activity in human milk was successfully applied to freshly drawn bovine milk samples, thus, providing an opportunity to compare Complement activities in both human and bovine milks. Although not identical in response, the levels of Complement activity in bovine milk were found to be closely comparable with that of human milk. Differential counts of Esch. coli 0111 after 2 h incubation were 6.20 and 6.06 log CFU/ml, for raw bovine and human milks, respectively - the lower value representing a stronger Complement response. Exposing bovine milk to a range of thermal treatments e.g. 42, 45, 65, 72, 85 or 95 °C for 10 min, progressively inhibited Complement activity by increasing temperature, thus confirming the heat labile nature of this immune protein system. Low level Complement activity was found, however, in 65 and 72 °C heat treated samples and in retailed pasteurised milk which highlights the outer limit to which high temperature, short time (HTST) industrial thermal processes should be applied if retention of activity is a priority. Concentration of Complement in the fat phase was evident following cream separation, and this was also reflected in the further loss of activity recorded in low fat variants of retailed pasteurised milk. Laboratory-based churning of the cream during simulated buttermaking generated an aqueous (buttermilk) phase with higher levels of Complement activity than the fat phase, thus pointing to a likely association with the milk fat globule membrane (MFGM) layer.
48 CFR 752.211-70 - Language and measurement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... recorded in metric system units of measurement, unless otherwise authorized by USAID in writing when it has... inefficiencies or the loss of markets. Where the metric system is not the predominant standard for a particular... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Language and measurement...
48 CFR 752.211-70 - Language and measurement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... recorded in metric system units of measurement, unless otherwise authorized by USAID in writing when it has... inefficiencies or the loss of markets. Where the metric system is not the predominant standard for a particular... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Language and measurement...
48 CFR 752.211-70 - Language and measurement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... recorded in metric system units of measurement, unless otherwise authorized by USAID in writing when it has... inefficiencies or the loss of markets. Where the metric system is not the predominant standard for a particular... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Language and measurement...
48 CFR 752.211-70 - Language and measurement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... recorded in metric system units of measurement, unless otherwise authorized by USAID in writing when it has... inefficiencies or the loss of markets. Where the metric system is not the predominant standard for a particular... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Language and measurement...
Improving the delivery of care and reducing healthcare costs with the digitization of information.

PubMed

Noffsinger, R; Chin, S

2000-01-01

In the coming years, the digitization of information and the Internet will be extremely powerful in reducing healthcare costs while assisting providers in the delivery of care. One example of healthcare inefficiency that can be managed through information digitization is the process of prescription writing. Due to the handwritten and verbal communication surrounding prescription writing, as well as the multiple tiers of authorizations, the prescription drug process causes extensive financial waste as well as medical errors, lost time, and even fatal accidents. Electronic prescription management systems are being designed to address these inefficiencies. By utilizing new electronic prescription systems, physicians not only prescribe more accurately, but also improve formulary compliance thereby reducing pharmacy utilization. These systems expand patient care by presenting proactive alternatives at the point of prescription while reducing costs and providing additional benefits for consumers and healthcare providers.
Delivering pediatric HIV care in resource-limited settings: cost considerations in an expanded response.

PubMed

Tolle, Michael A; Phelps, B Ryan; Desmond, Chris; Sugandhi, Nandita; Omeogu, Chinyere; Jamieson, David; Ahmed, Saeed; Reuben, Elan; Muhe, Lulu; Kellerman, Scott E

2013-11-01

If children are to be protected from HIV, the expansion of PMTCT programs must be complemented by increased provision of paediatric treatment. This is expensive, yet there are humanitarian, equity and children's rights arguments to justify the prioritization of treating HIV-infected children. In the context of limited budgets, inefficiencies cost lives, either through lower coverage or less effective services. With the goal of informing the design and expansion of efficient paediatric treatment programs able to utilize to greatest effect the available resources allocated to the treatment of HIV-infected children, this article reviews what is known about cost drivers in paediatric HIV interventions, and makes suggestions for improving efficiency in paediatric HIV programming. High-impact interventions known to deliver disproportional returns on investment are highlighted and targeted for immediate scale-up. Progress will carry a cost - increased funding, as well as additional data on intervention costs and outcomes, will be required if universal access of HIV-infected children to treatment is to be achieved and sustained.
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.
Locating inefficient links in a large-scale transportation network

NASA Astrophysics Data System (ADS)

Sun, Li; Liu, Like; Xu, Zhongzhi; Jie, Yang; Wei, Dong; Wang, Pu

2015-02-01

Based on data from geographical information system (GIS) and daily commuting origin destination (OD) matrices, we estimated the distribution of traffic flow in the San Francisco road network and studied Braess's paradox in a large-scale transportation network with realistic travel demand. We measured the variation of total travel time Δ T when a road segment is closed, and found that | Δ T | follows a power-law distribution if Δ T < 0 or Δ T > 0. This implies that most roads have a negligible effect on the efficiency of the road network, while the failure of a few crucial links would result in severe travel delays, and closure of a few inefficient links would counter-intuitively reduce travel costs considerably. Generating three theoretical networks, we discovered that the heterogeneously distributed travel demand may be the origin of the observed power-law distributions of | Δ T | . Finally, a genetic algorithm was used to pinpoint inefficient link clusters in the road network. We found that closing specific road clusters would further improve the transportation efficiency.
Advanced scoring method of eco-efficiency in European cities.

PubMed

Moutinho, Victor; Madaleno, Mara; Robaina, Margarita; Villar, José

2018-01-01

This paper analyzes a set of selected German and French cities' performance in terms of the relative behavior of their eco-efficiencies, computed as the ratio of their gross domestic product (GDP) over their CO 2 emissions. For this analysis, eco-efficiency scores of the selected cities are computed using the data envelopment analysis (DEA) technique, taking the eco-efficiencies as outputs, and the inputs being the energy consumption, the population density, the labor productivity, the resource productivity, and the patents per inhabitant. Once DEA results are analyzed, the Malmquist productivity indexes (MPI) are used to assess the time evolution of the technical efficiency, technological efficiency, and productivity of the cities over the window periods 2000 to 2005 and 2005 to 2008. Some of the main conclusions are that (1) most of the analyzed cities seem to have suboptimal scales, being one of the causes of their inefficiency; (2) there is evidence that high GDP over CO 2 emissions does not imply high eco-efficiency scores, meaning that DEA like approaches are useful to complement more simplistic ranking procedures, pointing out potential inefficiencies at the input levels; (3) efficiencies performed worse during the period 2000-2005 than during the period 2005-2008, suggesting the possibility of corrective actions taken during or at the end of the first period but impacting only on the second period, probably due to an increasing environmental awareness of policymakers and governors; and (4) MPI analysis shows a positive technological evolution of all cities, according to the general technological evolution of the reference cities, reflecting a generalized convergence of most cities to their technological frontier and therefore an evolution in the right direction.
Probable systemic lupus erythematosus with cell-bound complement activation products (CB-CAPS).

PubMed

Lamichhane, D; Weinstein, A

2016-08-01

Complement activation is a key feature of systemic lupus erythematosus (SLE). Detection of cell-bound complement activation products (CB-CAPS) occurs more frequently than serum hypocomplementemia in definite lupus. We describe a patient with normocomplementemic probable SLE who did not fulfill ACR classification criteria for lupus, but the diagnosis was supported by the presence of CB-CAPS. © The Author(s) 2016.

Bothrops asper snake venom and its metalloproteinase BaP-1 activate the complement system. Role in leucocyte recruitment.

PubMed Central

Farsky, S H; Gonçalves, L R; Gutiérrez, J M; Correa, A P; Rucavado, A; Gasque, P; Tambourgi, D V

2000-01-01

The venom of the snake Bothrops asper, the most important poisonous snake in Central America, evokes an inflammatory response, the mechanisms of which are not well characterized. The objectives of this study were to investigate whether B. asper venom and its purified toxins--phospholipases and metalloproteinase--activate the complement system and the contribution of the effect on leucocyte recruitment. In vitro chemotaxis assays were performed using Boyden's chamber model to investigate the ability of serum incubated with venom and its purified toxins to induce neutrophil migration. The complement consumption by the venom was evaluated using an in vitro haemolytic assay. The importance of complement activation by the venom on neutrophil migration was investigated in vivo by injecting the venom into the peritoneal cavity of C5-deficient mice. Data obtained demonstrated that serum incubated with crude venom and its purified metalloproteinase BaP-1 are able to induce rat neutrophil chemotaxis, probably mediated by agent(s) derived from the complement system. This hypothesis was corroborated by the capacity of the venom to activate this system in vitro. The involvement of C5a in neutrophil chemotaxis induced by venom-activated serum was demonstrated by abolishing migration when neutrophils were pre-incubated with antirat C5a receptor antibody. The relevance of the complement system in in vivo leucocyte mobilization was further demonstrated by the drastic decrease of this response in C5-deficient mice. Pre-incubation of serum with the soluble human recombinant complement receptor type 1 (sCR 1) did not prevent the response induced by the venom, but abolished the migration evoked by metalloproteinase-activated serum. These data show the role of the complement system in bothropic envenomation and the participation of metalloproteinase in the effect. Also, they suggest that the venom may contain other component(s) which can cause direct activation of C5a. PMID:11200361
Relative Contribution of Cellular Complement Inhibitors CD59, CD46, and CD55 to Parainfluenza Virus 5 Inhibition of Complement-Mediated Neutralization

PubMed Central

Li, Yujia; Parks, Griffith D.

2018-01-01

The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA) to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5) incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways. Using a cell line engineered to express CD59, we show that small levels of functional CD59 are associated with progeny PIV5, which is capable of blocking assembly of the C5b-C9 membrane attack complex (MAC). PIV5 containing CD59 (PIV5-CD59) showed increased resistance to complement-mediated neutralization in vitro comparing to PIV5 lacking regulators. Infection of A549 cells with PIV5 and RSV upregulated CD59 expression. TGF-beta treatment of PIV5-infected cells also increased cell surface CD59 expression and progeny virions were more resistant to complement-mediated neutralization. A comparison of individual viruses containing only CD55, CD46, or CD59 showed a potency of inhibiting complement-mediated neutralization, which followed a pattern of CD55 > CD46 > CD59. PMID:29693588
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
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
Complement Activation: An Emerging Player in the Pathogenesis of Cardiovascular Disease

PubMed Central

Carter, Angela M.

2012-01-01

A wealth of evidence indicates a fundamental role for inflammation in the pathogenesis of cardiovascular disease (CVD), contributing to the development and progression of atherosclerotic lesion formation, plaque rupture, and thrombosis. An increasing body of evidence supports a functional role for complement activation in the pathogenesis of CVD through pleiotropic effects on endothelial and haematopoietic cell function and haemostasis. Prospective and case control studies have reported strong relationships between several complement components and cardiovascular outcomes, and in vitro studies and animal models support a functional effect. Complement activation, in particular, generation of C5a and C5b-9, influences many processes involved in the development and progression of atherosclerosis, including promotion of endothelial cell activation, leukocyte infiltration into the extracellular matrix, stimulation of cytokine release from vascular smooth muscle cells, and promotion of plaque rupture. Complement activation also influences thrombosis, involving components of the mannose-binding lectin pathway, and C5b-9 in particular, through activation of platelets, promotion of fibrin formation, and impairment of fibrinolysis. The participation of the complement system in inflammation and thrombosis is consistent with the physiological role of the complement system as a rapid effector system conferring protection following vessel injury. However, in the context of CVD, these same processes contribute to development of atherosclerosis, plaque rupture, and thrombosis. PMID:24278688
21 CFR 866.5250 - Complement C2 inhibitor (inactivator) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the reagents used to measure by immunochemical techniques the complement C1 inhibitor (a plasma protein) in serum. Complement C1 inhibitor occurs normally in plasma and blocks the action of the C1...
21 CFR 866.5250 - Complement C2 inhibitor (inactivator) immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the reagents used to measure by immunochemical techniques the complement C1 inhibitor (a plasma protein) in serum. Complement C1 inhibitor occurs normally in plasma and blocks the action of the C1...
21 CFR 866.5250 - Complement C2 inhibitor (inactivator) immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the reagents used to measure by immunochemical techniques the complement C1 inhibitor (a plasma protein) in serum. Complement C1 inhibitor occurs normally in plasma and blocks the action of the C1...
21 CFR 866.5250 - Complement C 2 inhibitor (inactivator) immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the reagents used to measure by immunochemical techniques the complement C1 inhibitor (a plasma protein) in serum. Complement C1 inhibitor occurs normally in plasma and blocks the action of the C1...
21 CFR 866.5250 - Complement C 2 inhibitor (inactivator) immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the reagents used to measure by immunochemical techniques the complement C1 inhibitor (a plasma protein) in serum. Complement C1 inhibitor occurs normally in plasma and blocks the action of the C1...
Design of a Competency Administration Toolset (CAT)

DTIC Science & Technology

2017-03-01

Distribution is unlimited. DESIGN OF A COMPETENCY ADMINISTRATION TOOLSET (CAT) by David Cudd, Justin Letwinsky, Allison Moon, David Rodriguez, Blake......processing, which is perceived to be inefficient in both time and cost. The purpose of this systems engineering project was to design a web-based system
48 CFR 711.002-70 - Metric system waivers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... is impractical or is likely to cause U.S. firms to experience significant inefficiencies or the loss... USAID Metric Transition Plan.) Repetitive purchases of commercially produced and marketed items and...
Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention.

PubMed

Mastellos, D C; Ricklin, D; Hajishengallis, E; Hajishengallis, G; Lambris, J D

2016-02-01

There is increasing appreciation that complement dysregulation lies at the heart of numerous immune-mediated and inflammatory disorders. Complement inhibitors are therefore being evaluated as new therapeutic options in various clinical translation programs and the first clinically approved complement-targeted drugs have profoundly impacted the management of certain complement-mediated diseases. Among the many members of the intricate protein network of complement, the central component C3 represents a 'hot-spot' for complement-targeted therapeutic intervention. C3 modulates both innate and adaptive immune responses and is linked to diverse immunomodulatory systems and biological processes that affect human pathophysiology. Compelling evidence from preclinical disease models has shown that C3 interception may offer multiple benefits over existing therapies or even reveal novel therapeutic avenues in disorders that are not commonly regarded as complement-driven, such as periodontal disease. Using the clinically developed compstatin family of C3 inhibitors and periodontitis as illustrative examples, this review highlights emerging therapeutic concepts and developments in the design of C3-targeted drug candidates as novel immunotherapeutics for oral and systemic inflammatory diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Performance of US teaching hospitals: a panel analysis of cost inefficiency.

PubMed

Rosko, Michael D

2004-02-01

This research summarizes an analysis of the impact of environment pressures on hospital inefficiency during the period 1990-1999. The panel design included 616 hospitals. Of these, 211 were academic medical centers and 415 were hospitals with smaller teaching programs. The primary sources of data were the American Hospital Association's Annual Survey of Hospitals and Medicare Cost Reports. Hospital inefficiency was estimated by a regression technique called stochastic frontier analysis. This technique estimates a "best practice cost frontier" for each hospital that is based on the hospital's outputs and input prices. The cost efficiency of each hospital was defined as the ratio of the stochastic frontier total costs to observed total costs. Average inefficiency declined from 14.35% in 1990 to 11.42% in 1998. It increased to 11.78% in 1999. Decreases in inefficiency were associated with the HMO penetration rate and time. Increases in inefficiency were associated with for-profit ownership status and Medicare share of admissions. The implementation of the provisions of the Balanced Budget Act of 1997 was followed by a small decrease in average hospital inefficiency. Analysis found that the SFA results were moderately sensitive to the specification of the teaching output variable. Thus, although the SFA technique can be useful for detecting differences in inefficiency between groups of hospitals (i.e., those with high versus those with low Medicare shares or for-profit versus not-for-profit hospitals), its relatively low precision indicates it should not be used for exact estimates of the magnitude of differences associated with inefficiency-effects variables.
Calcineurin inhibitor-induced complement system activation via ERK1/2 signalling is inhibited by SOCS-3 in human renal tubule cells.

PubMed

Loeschenberger, Beatrix; Niess, Lea; Würzner, Reinhard; Schwelberger, Hubert; Eder, Iris E; Puhr, Martin; Guenther, Julia; Troppmair, Jakob; Rudnicki, Michael; Neuwirt, Hannes

2018-02-01

One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations. Following knock-down and overexpression of SOCS-3, we found that SOCS-3 inhibits ERK1/-2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component-depleted conditions. In vivo, increased ERK1/-2 phosphorylation and SOCS-3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow-up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS-3 inhibits CNI-induced ERK1/-2 signalling, thereby blunting the negative control of C-system activation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Private Agricultural Extension System in Kenya: Practice and Policy Lessons

ERIC Educational Resources Information Center

Muyanga, Milu; Jayne, T. S.

2008-01-01

Private extension system has been at the centre of a debate triggered by inefficient public agricultural extension. The debate is anchored on the premise that the private sector is more efficient in extension service delivery. This study evaluates the private extension system in Kenya. It employs qualitative and quantitative methods. The results…
Doppler Lidar System Design via Interdisciplinary Design Concept at NASA Langley Research Center - Part III

NASA Technical Reports Server (NTRS)

Barnes, Bruce W.; Sessions, Alaric M.; Beyon, Jeffrey; Petway, Larry B.

2014-01-01

Optimized designs of the Navigation Doppler Lidar (NDL) instrument for Autonomous Landing Hazard Avoidance Technology (ALHAT) were accomplished via Interdisciplinary Design Concept (IDEC) at NASA Langley Research Center during the summer of 2013. Three branches in the Engineering Directorate and three students were involved in this joint task through the NASA Langley Aerospace Research Summer Scholars (LARSS) Program. The Laser Remote Sensing Branch (LRSB), Mechanical Systems Branch (MSB), and Structural and Thermal Systems Branch (STSB) were engaged to achieve optimal designs through iterative and interactive collaborative design processes. A preliminary design iteration was able to reduce the power consumption, mass, and footprint by removing redundant components and replacing inefficient components with more efficient ones. A second design iteration reduced volume and mass by replacing bulky components with excessive performance with smaller components custom-designed for the power system. The existing power system was analyzed to rank components in terms of inefficiency, power dissipation, footprint and mass. Design considerations and priorities are compared along with the results of each design iteration. Overall power system improvements are summarized for design implementations.
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes.

PubMed

Tavano, Regina; Gabrielli, Luca; Lubian, Elisa; Fedeli, Chiara; Visentin, Silvia; Polverino De Laureto, Patrizia; Arrigoni, Giorgio; Geffner-Smith, Alessandra; Chen, Fangfang; Simberg, Dmitri; Morgese, Giulia; Benetti, Edmondo M; Wu, Linping; Moghimi, Seyed Moein; Mancin, Fabrizio; Papini, Emanuele

2018-05-23

Poly(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and in vivo performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts. Through detailed immunological and proteomic profiling, we show that PMOXA-coated NPs extensively trigger complement activation in human sera exclusively through the classical pathway. Complement activation is initiated by the sensing molecule C1q, where C1q binds with high affinity ( K d = 11 ± 1 nM) to NP surfaces independent of immunoglobulin binding. C1q-mediated complement activation accelerates PMOXA opsonization with the third complement protein (C3) through the amplification loop of the alternative pathway. This promoted NP recognition by human blood leukocytes and monocyte-derived macrophages. The macrophage capture of PMOXA-coated NPs correlates with sera donor variability in complement activation and opsonization but not with other major corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps.
Fractal stock markets: International evidence of dynamical (in)efficiency.

PubMed

Bianchi, Sergio; Frezza, Massimiliano

2017-07-01

The last systemic financial crisis has reawakened the debate on the efficient nature of financial markets, traditionally described as semimartingales. The standard approaches to endow the general notion of efficiency of an empirical content turned out to be somewhat inconclusive and misleading. We propose a topological-based approach to quantify the informational efficiency of a financial time series. The idea is to measure the efficiency by means of the pointwise regularity of a (stochastic) function, given that the signature of a martingale is that its pointwise regularity equals 12. We provide estimates for real financial time series and investigate their (in)efficient behavior by comparing three main stock indexes.

Fractal stock markets: International evidence of dynamical (in)efficiency

NASA Astrophysics Data System (ADS)

Bianchi, Sergio; Frezza, Massimiliano

2017-07-01

The last systemic financial crisis has reawakened the debate on the efficient nature of financial markets, traditionally described as semimartingales. The standard approaches to endow the general notion of efficiency of an empirical content turned out to be somewhat inconclusive and misleading. We propose a topological-based approach to quantify the informational efficiency of a financial time series. The idea is to measure the efficiency by means of the pointwise regularity of a (stochastic) function, given that the signature of a martingale is that its pointwise regularity equals 1/2 . We provide estimates for real financial time series and investigate their (in)efficient behavior by comparing three main stock indexes.
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.
Integrated arterial and freeway operation control strategies for IVHS advanced traffic management systems : research report

DOT National Transportation Integrated Search

1998-09-01

The main focus of this study is congestion, primarily that occurring on freeway corridors in metropolitan areas. Lack of coordination in the operation of various components of the system is often a major source of inefficiency, : resulting in greater...
Effect of virtual memory on efficient solution of two model problems

NASA Technical Reports Server (NTRS)

Lambiotte, J. J., Jr.

1977-01-01

Computers with virtual memory architecture allow programs to be written as if they were small enough to be contained in memory. Two types of problems are investigated to show that this luxury can lead to quite an inefficient performance if the programmer does not interact strongly with the characteristics of the operating system when developing the program. The two problems considered are the simultaneous solutions of a large linear system of equations by Gaussian elimination and a model three-dimensional finite-difference problem. The Control Data STAR-100 computer runs are made to demonstrate the inefficiencies of programming the problems in the manner one would naturally do if the problems were indeed, small enough to be contained in memory. Program redesigns are presented which achieve large improvements in performance through changes in the computational procedure and the data base arrangement.
A Mutation in PGM2 Causing Inefficient Galactose Metabolism in the Probiotic Yeast Saccharomyces boulardii.

PubMed

Liu, Jing-Jing; Zhang, Guo-Chang; Kong, In Iok; Yun, Eun Ju; Zheng, Jia-Qi; Kweon, Dae-Hyuk; Jin, Yong-Su

2018-05-15

The probiotic yeast Saccharomyces boulardii has been extensively studied for the prevention and treatment of diarrheal diseases, and it is now commercially available in some countries. S. boulardii displays notable phenotypic characteristics, such as a high optimal growth temperature, high tolerance against acidic conditions, and the inability to form ascospores, which differentiate S. boulardii from Saccharomyces cerevisiae The majority of prior studies stated that S. boulardii exhibits sluggish or halted galactose utilization. Nonetheless, the molecular mechanisms underlying inefficient galactose uptake have yet to be elucidated. When the galactose utilization of a widely used S. boulardii strain, ATCC MYA-796, was examined under various culture conditions, the S. boulardii strain could consume galactose, but at a much lower rate than that of S. cerevisiae While all GAL genes were present in the S. boulardii genome, according to analysis of genomic sequencing data in a previous study, a point mutation (G1278A) in PGM2 , which codes for phosphoglucomutase, was identified in the genome of the S. boulardii strain. As the point mutation resulted in the truncation of the Pgm2 protein, which is known to play a pivotal role in galactose utilization, we hypothesized that the truncated Pgm2 might be associated with inefficient galactose metabolism. Indeed, complementation of S. cerevisiae PGM2 in S. boulardii restored galactose utilization. After reverting the point mutation to a full-length PGM2 in S. boulardii by Cas9-based genome editing, the growth rates of wild-type (with a truncated PGM2 gene) and mutant (with a full-length PGM2 ) strains with glucose or galactose as the carbon source were examined. As expected, the mutant (with a full-length PGM2 ) was able to ferment galactose faster than the wild-type strain. Interestingly, the mutant showed a lower growth rate than that of the wild-type strain on glucose at 37°C. Also, the wild-type strain was enriched in the mixed culture of wild-type and mutant strains on glucose at 37°C, suggesting that the truncated PGM2 might offer better growth on glucose at a higher temperature in return for inefficient galactose utilization. Our results suggest that the point mutation in PGM2 might be involved in multiple phenotypes with different effects. IMPORTANCE Saccharomyces boulardii is a probiotic yeast strain capable of preventing and treating diarrheal diseases. However, the genetics and metabolism of this yeast are largely unexplored. In particular, molecular mechanisms underlying the inefficient galactose metabolism of S. boulardii remain unknown. Our study reports that a point mutation in PGM2 , which codes for phosphoglucomutase, is responsible for inferior galactose utilization by S. boulardii After correction of the mutated PGM2 via genome editing, the resulting strain was able to use galactose faster than a parental strain. While the PGM2 mutation made the yeast use galactose slowly, investigation of the genomic sequencing data of other S. boulardii strains revealed that the PGM2 mutation is evolutionarily conserved. Interestingly, the PGM2 mutation was beneficial for growth at a higher temperature on glucose. We speculate that the PGM2 mutation was enriched due to selection of S. boulardii in the natural habitat (sugar-rich fruits in tropical areas). Copyright © 2018 American Society for Microbiology.
The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis.

PubMed

Hovland, Anders; Jonasson, Lena; Garred, Peter; Yndestad, Arne; Aukrust, Pål; Lappegård, Knut T; Espevik, Terje; Mollnes, Tom E

2015-08-01

Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. However, based on recent research showing an intimate interplay between complement and TLRs we propose a model in which combined inhibition of both complement and TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Complement in the Initiation and Evolution of Rheumatoid Arthritis

PubMed Central

Holers, V. Michael; Banda, Nirmal K.

2018-01-01

The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA. PMID:29892280
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.
Some Instructional Implications from a Mathematical Model of Cognitive Development.

ERIC Educational Resources Information Center

Mierkiewicz, Diane B.

Cognitive development and various educational implications are discussed in terms of Donald Saari's model of the interaction of a learner and the enviroment and the constraints imposed by the inefficiency of the learner's cognitive system. Saari proposed a hierarchical system of cognitive structures such that the relationships between structures…
Improving Advising Using Technology and Data Analytics

ERIC Educational Resources Information Center

Phillips, Elizabeth D.

2013-01-01

Traditionally, the collegiate advising system provides each student with a personal academic advisor who designs a pathway to the degree for that student in face-to-face meetings. Ideally, this is a supportive mentoring relationship. In truth, however, this system is highly inefficient, error prone, expensive, and a source of ubiquitous student…
Freight efficiency strategies : a white paper series to inform the California Sustainable Freight Action Plan.

DOT National Transportation Integrated Search

2016-03-01

A number of stakeholders met with the ultimate goal of identifying inefficiencies faced by the freight system and putting forward a set of : strategies to achieve a more efficient freight system. In doing so, a key first step was to provide insight a...
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.
Mobile radiography CQI: an inter-national study.

PubMed

Kamat, M R; Wein, B; Cohan, R

1999-01-01

Mobile or bedside radiography has been and is a staple diagnostic and follow-up tool used readily by the many medical disciplines, such as cardiology, surgery, orthopedics, pediatrics, neonatology, etc. Ironically, in the past a student or the least qualified technologist was sent to perform the bedside exam. Moreover, it was almost expected that poor but acceptable film quality would result or that repeat films were almost always to be taken. Inefficiency with respect to quality of exam, the time the exam takes, or film repeats can be costly. The price of inefficiency is the cost involved in doing things incorrectly or not in the most efficient manner, i.e., incurring inefficiencies instead of operating in an ideal manner. The purpose of this study was to compare the total cost of inefficiently organized, scheduled and performed mobile radiography at three large teaching hospitals in various locations and of diverse patient loads, as a means of determining how best to increase utilization and performance. The study was performed at the 489-bed New England Deaconess Hospital (NEDH), the 644-bed Sentara Norfolk General Hospital (SNGH), and the 1500-bed Rheinische Westfalische Technische Hochschule (RWTH) in Aachen, Germany. Similar standardized study methods were utilized at all three institutions where extended observation of mobile utilization, areas of inefficiency, time wasted per episode and number of episodes per time period were determined. Data were loggedin at three standardized time periods, summated, and then multiplied by technologist hourly pay rate. This sum was extrapolated over 52 weeks to give the total annual cost of inefficiently organized mobile radiography. For NEDH the cost of total inefficiency was $75,453, for SNGH $49,586, while for RWTH it was $9,519. Eighteen areas of inefficiency were identified and grouped, such as lack of spatial cohesiveness and lack of communication leading to film duplication, etc. While inefficiencies in the delivery of hospital based health care are well known, this study attempts to quantify and determine a dollar value for each process found as inefficient. Key inefficiencies were found to be common at large hospitals no matter whether in the United States or Europe. These impairments are responsible for a disproportionate share of overall inefficiency, and their elimination (achievable by simple solutions) would result in drastic cost reductions (ranging from 40-75% at the institutions studied). Thus this study is important in view of spiralling costs, as it is a key component of total quality management (TQM) in radiology and a continuous quality improvement (CQI) tool for mobile radiology specifically.
Pediatric Trauma Transfer Imaging Inefficiencies-Opportunities for Improvement with Cloud Technology.

PubMed

Puckett, Yana; To, Alvin

2016-01-01

This study examines the inefficiencies of radiologic imaging transfers from one hospital to the other during pediatric trauma transfers in an era of cloud based information sharing. Retrospective review of all patients transferred to a pediatric trauma center from 2008-2014 was performed. Imaging was reviewed for whether imaging accompanied the patient, whether imaging was able to be uploaded onto computer for records, whether imaging had to be repeated, and whether imaging obtained at outside hospitals (OSH) was done per universal pediatric trauma guidelines. Of the 1761 patients retrospectively reviewed, 559 met our inclusion criteria. Imaging was sent with the patient 87.7% of the time. Imaging was unable to be uploaded 31.9% of the time. CT imaging had to be repeated 1.8% of the time. CT scan was not done per universal pediatric trauma guidelines 1.2% of the time. Our study demonstrated that current imaging transfer is inefficient, leads to excess ionizing radiation, and increased healthcare costs. Universal implementation of cloud based radiology has the potential to eliminate excess ionizing radiation to children, improve patient care, and save cost to healthcare system.
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.
Health insurance in Croatia: dynamics and politics of balancing revenues and expenditures.

PubMed

Voncina, Luka; Kehler, Jenni; Evetovits, Tamas; Bagat, Mario

2010-04-01

Since 2002, the Croatian social health insurance system has undergone substantial reforms, initiated for the most part with the aim of addressing the perpetual financial deficits of the state health insurance fund. While the reforms focussed heavily on increasing the inflow of private funds into the health care system, underlying inefficiencies contributing significantly to poor financial performance have been largely ignored. Furthermore, contrary to demographic trends and developments in social health insurance schemes in other countries, funding health care became even more dependent on its main collection mechanism-payroll tax-and consequently on the employment ratio and wage level. Little effort has been made to diversify the revenue base or to increase the efficiency of revenue collection. Like other countries, Croatia is facing difficulties in adjusting its 'Bismarck' system to its changing demographic and socioeconomic context. Instead of targetting a comprehensive effort at improving revenue collection and limitating unnecessary expenditure and system inefficiencies, simplified approaches to balance the budget have been implemented at a high price to users and with limited effect. As a result, the Croatian health insurance system now offers a lower level of financial protection, while still facing the problem of spending more than can be collected through the current mix of revenue collection mechanisms. The authors suggest that, in order to meet the sustainability requirement of the health financing system, measures affecting both revenue and expenditure should be considered and implemented. On the revenue collection side, the Croatian government must make further efforts to improve collection from the informally employed to broaden the base of contributing members; equally important is the diversification of revenue sources by increasing transfers from general taxation revenues. On the expenditure side, exploring inefficiencies of the delivery system can be delayed no longer, and the introduction of effective cost-control mechanisms and financial discipline would seem to be unavoidable.
Model of Coastal Transit Oriented Development (TOD) Based on the Potential of Local Port and marine Tourism Port, Case Study: Fort Rotterdam Makassar and the Surrounding Areas

NASA Astrophysics Data System (ADS)

Arief, A. B.; Yudono, A.; Akil, A.; Ramli, I.

2017-08-01

The lack of social and public facilties of seven small islands around Makassar, causing the commuters to experience inefficiency in fulfilling their basic needs in the mainland of Makassar city. The purpose of this study is finding the location of coastal TOD in accordance with the principles of development model of coastal TOD. The result showed that inefficiency of time, cost and distance could be eliminated by applying vertical, united and integrated development model of coastal TOD. Using survey, interview and literature study through expert system analysis based on GIS deliniates coastal TOD.
Factors influencing the work efficiency of district health managers in low-resource settings: a qualitative study in Ghana.

PubMed

Bonenberger, Marc; Aikins, Moses; Akweongo, Patricia; Wyss, Kaspar

2016-01-14

There is increasing evidence that good district management practices can improve health system performance and conversely, that poor and inefficient management practices have detrimental effects. The aim of the present study was to identify factors contributing to inefficient management practices of district health managers and ways to improve their overall efficiency. Nineteen semi-structured interviews were conducted with district health managers in three districts of the Eastern Region in Ghana. The 19 interviews conducted comprised 90% of the managerial workforce in these districts in 2013. A thematic analysis was carried out using the WHO's leadership and management strengthening framework to structure the results. Key factors for inefficient district health management practices were identified to be: human resource shortages, inadequate planning and communication skills, financial constraints, and a narrow decision space that constrains the authority of district health managers and their ability to influence decision-making. Strategies that may improve managerial efficiency at both an individual and organizational level included improvements to planning, communication, and time management skills, and ensuring the timely release of district funds. Filling District Health Management Team vacancies, developing leadership and management skills of district health managers, ensuring a better flow of district funds, and delegating more authority to the districts seems to be a promising intervention package, which may result in better and more efficient management practices and stronger health system performance.
Regulation of humoral immunity by complement.

PubMed

Carroll, Michael C; Isenman, David E

2012-08-24

The complement system of innate immunity is important in regulating humoral immunity largely through the complement receptor CR2, which forms a coreceptor on B cells during antigen-induced activation. However, CR2 also retains antigens on follicular dendritic cells (FDCs). Display of antigen on FDCs is critical for clonal selection and affinity maturation of activated B cells. This review will discuss the role of complement in adaptive immunity in general with a focus on the interplay between CR2-associated antigen on B cells with CR2 expressed on FDCs. This latter interaction provides an opportunity for memory B cells to sample antigen over prolonged periods. The cocrystal structure of CR2 with its ligand C3d provides insight into how the complement system regulates access of antigen by B cells with implications for therapeutic manipulations to modulate aberrant B cell responses in the case of autoimmunity. Copyright © 2012 Elsevier Inc. All rights reserved.
Cryptanalysis and improvement of Yan et al.'s biometric-based authentication scheme for telecare medicine information systems.

PubMed

Mishra, Dheerendra; Mukhopadhyay, Sourav; Chaturvedi, Ankita; Kumari, Saru; Khan, Muhammad Khurram

2014-06-01

Remote user authentication is desirable for a Telecare Medicine Information System (TMIS) for the safety, security and integrity of transmitted data over the public channel. In 2013, Tan presented a biometric based remote user authentication scheme and claimed that his scheme is secure. Recently, Yan et al. demonstrated some drawbacks in Tan's scheme and proposed an improved scheme to erase the drawbacks of Tan's scheme. We analyze Yan et al.'s scheme and identify that their scheme is vulnerable to off-line password guessing attack, and does not protect anonymity. Moreover, in their scheme, login and password change phases are inefficient to identify the correctness of input where inefficiency in password change phase can cause denial of service attack. Further, we design an improved scheme for TMIS with the aim to eliminate the drawbacks of Yan et al.'s scheme.

Effectiveness of Kanban Approaches in Systems Engineering within Rapid Response Environments

DTIC Science & Technology

2012-01-01

Procedia Computer Science Procedia Computer Science 00 (2012) 000–000 www.elsevier.com/locate/ procedia New Challenges in Systems...Author name / Procedia Computer Science 00 (2011) 000–000 inefficient use of resources. The move from ―one step to glory‖ system initiatives to...University of Science and Technology Effectiveness of kanban approaches in systems engineering within rapid response environments Richard Turner
Gaps, inexperience, inconsistencies, and overlaps: crisis in the regulation of genetically modified plants and animals.

PubMed

Mandal, Gregory N

2004-04-01

The regulation of genetically modified products pursuant to statutes enacted decades prior to the advent of biotechnology has created a regulatory system that is passive rather than proactive about risks, has difficulty adapting to biotechnology advances, and is highly fractured and inefficient--transgenic plants and animals are governed by at least twelve different statutes and five different agencies or services. The deficiencies resulting from this piecemeal approach to regulation unnecessarily expose society and the environment to adverse risks of biotechnology and introduce numerous inefficiencies into the regulatory system. These risks and inefficiencies include gaps in regulation, duplicative and inconsistent regulation, unnecessary increases in the cost of and delay in the development and commercialization of new biotechnology products. These deficiencies also increase the risk of further unnecessary biotechnology scares, which may cause public overreaction against biotechnology products, preventing the maximization of social welfare. With science and society poised to soar from first-generation biotechnology (focused on crops modified for agricultural benefit), to next-generation developments (including transgenic fish, insects, and livestock, and pharmaceutical-producing and industrial compound-producing plants and animals), it is necessary to establish a comprehensive, efficient, and scientifically rigorous regulatory system. This Article details how to achieve such a result through fixing the deficiencies in, and risks created by, the current regulatory structure. Ignoring many details, the solutions can be summarized in two categories. First, statutory and regulatory gaps that are identified must be closed with new legislation and regulation. Second, regulation of genetically modified products must be shifted from a haphazard model based on statutes not intended to cover biotechnology to a system based upon agency expertise in handling particular types of risks.
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
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.
Cultural differences in the imitation and transmission of inefficient actions.

PubMed

Corriveau, Kathleen H; DiYanni, Cara J; Clegg, Jennifer M; Min, Grace; Chin, Jason; Nasrini, Jad

2017-09-01

Across two studies, we explored cultural differences in children's imitation and transmission of inefficient actions. Chinese American and Caucasian American preschoolers (N=115) viewed either one or three models using two inefficient tools to perform two different tasks. In the video, when the model(s) performed the task, only the inefficient tool was available; thus, their choice to use that tool could be considered rational. Next, children were invited to complete the task with either the inefficient tool or an efficient alternative. Whereas the two cultural groups imitated a single model at similar rates, Chinese American children imitated significantly more than Caucasian American children after viewing a consensus. Similar results were found when exploring differences in information transmission. The Chinese American children were significantly more likely than their Caucasian American peers to instruct using an inefficient tool when they had initially viewed a consensus demonstrate it. We discuss these findings with respect to differences in children's use of social versus task-specific cues for learning and teaching. Copyright © 2017 Elsevier Inc. All rights reserved.
Exacerbating the Tragedy of the Commons: Private Inefficient Outcomes and Peer Effect in Experimental Games with Fishing Communities

PubMed Central

2016-01-01

Economic Experimental Games have shown that individuals make decisions that deviate down from the suboptimal Nash equilibrium. However, few studies have analyzed the case when deviation is above the Nash equilibrium. Extracting from above the Nash equilibrium is inefficient not only socially but also privately and it would exacerbate the tragedy of the commons. That would be the case of a race to the fish when stocks are becoming depleted or driver behavior on a highly congested road. The objective of this study is to analyze private inefficient extraction behavior in experimental games and to associate the type of player and the type of player group with such inefficient outcomes. To do this, we carried out economic experimental games with local coastal fishermen in Colombia, using a setting where the scarcity of the resource allows for an interior Nash equilibrium and inefficient over-extraction is possible. The state of the resource, the type of player and the composition of the group explain, in part, this inefficient behavior. PMID:26863228
Different host complement systems and their interactions with saliva from Lutzomyia longipalpis (Diptera, Psychodidae) and Leishmania infantum promastigotes.

PubMed

Mendes-Sousa, Antonio Ferreira; Nascimento, Alexandre Alves Sousa; Queiroz, Daniel Costa; Vale, Vladimir Fazito; Fujiwara, Ricardo Toshio; Araújo, Ricardo Nascimento; Pereira, Marcos Horácio; Gontijo, Nelder Figueiredo

2013-01-01

Lutzomyia longipalpis is the vector of Leishmania infantum in the New World, and its saliva inhibits classical and alternative human complement system pathways. This inhibition is important in protecting the insect´s midgut from damage by the complement. L. longipalpis is a promiscuous blood feeder and must be protected against its host's complement. The objective of this study was to investigate the action of salivary complement inhibitors on the sera of different host species, such as dogs, guinea pigs, rats and chickens, at a pH of 7.4 (normal blood pH) and 8.15 (the midgut pH immediately after a blood meal). We also investigated the role of the chicken complement system in Leishmania clearance in the presence and absence of vector saliva. The saliva was capable of inhibiting classical pathways in dogs, guinea pigs and rats at both pHs. The alternative pathway was not inhibited except in dogs at a pH of 8.15. The chicken classical pathway was inhibited only by high concentrations of saliva and it was better inhibited by the midgut contents of sand flies. Neither the saliva nor the midgut contents had any effect on the avian alternative pathway. Fowl sera killed L. infantum promastigotes, even at a low concentration (2%), and the addition of L. longipalpis saliva did not protect the parasites. The high body temperature of chickens (40°C) had no effect on Leishmania viability during our assays. Salivary inhibitors act in a species-specific manner. It is important to determine their effects in the natural hosts of Leishmania infantum because they act on canid and rodent complements but not on chickens (which do not harbour the parasite). Moreover, we concluded that the avian complement system is the probable mechanism through which chickens eliminate Leishmania and that their high body temperature does not influence this parasite.
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
Systems Engineering Knowledge Asset (SEKA) Management for Higher Performing Engineering Teams: People, Process and Technology toward Effective Knowledge-Workers

ERIC Educational Resources Information Center

Shelby, Kenneth R., Jr.

2013-01-01

Systems engineering teams' value-creation for enterprises is slower than possible due to inefficiencies in communication, learning, common knowledge collaboration and leadership conduct. This dissertation outlines the surrounding people, process and technology dimensions for higher performing engineering teams. It describes a true experiment…
Rebalancing Resources and Incentives in Federal Student Aid

ERIC Educational Resources Information Center

Burd, Stephen; Carey, Kevin; Delisle, Jason; Fishman, Rachel; Holt, Alex; Laitinen, Amy; McCann, Clare

2013-01-01

The federal financial aid system is no longer up to today's demands. Built in a different era, its haphazard evolution over the decades has made it inefficient, poorly targeted, and overly complicated. With the need for higher education never greater and college growing increasingly unaffordable, students deserve a streamlined aid system that is…
Fertigation - Injecting soluble fertilizers into the irrigation system

Treesearch

Thomas D. Landis; Jeremy R. Pinto; Anthony S. Davis

2009-01-01

Fertigation (fertilization + irrigation) is the newest way for nursery managers to apply fertilizer, and has become a standard practice in container nurseries. Because of the inherent inefficient water distribution patterns in field irrigation systems, fertigation has not been widely used in bareroot nurseries. However, a bareroot nursery with a center-pivot irrigation...
An Investigation of Energy Consumption and Cost in Large Air-Conditioned Buildings. An Interim Report.

ERIC Educational Resources Information Center

Milbank, N. O.

Two similarly large buildings and air conditioning systems are comparatively analyzed as to energy consumption, costs, and inefficiency during certain measured periods of time. Building design and velocity systems are compared to heating, cooling, lighting and distribution capabilities. Energy requirements for pumps, fans and lighting are found to…
Minimizing Losses in a Space Laser Power Beaming System

DTIC Science & Technology

2010-03-01

system was to inefficient for any practical power transfer applications ( Reiman , 1993:2). Shorter wavelengths are easier to direct and have led to the...OH. Winter Quarter 2009 Reiman , D. "Scanning the Past: A History of Electrical Engineering from the Past." n. pag. IEEE (Vol. 81, No. 6, 1993
System for Delivering Student Aid Is Flawed, Many Agree, But What's the Solution?

ERIC Educational Resources Information Center

Burd, Stephen

1997-01-01

Public officials and student aid experts agree that the federal program delivery system is outdated, inefficient, and vulnerable to fraud, but they disagree on how bad the situation is and whether the Education Department has the structure necessary to fix it. A 1995 project to integrate all federal grant and loan programs into one system has not…
The determinants of efficiency in the Canadian health care system.

PubMed

Allin, Sara; Grignon, Michel; Wang, Li

2016-01-01

In spite of the vast number of studies measuring economic efficiency in health care, there has been little take-up of this evidence by policy-makers to date. This study provides an illustration of how a system-level study drawing on best practice in empirical measurement of efficiency may be of practical use to health system decision makers and managers. We make use of the rich data available in Canada to undertake a robust two-stage data envelopment analysis to calculate efficiency at the regional (sub-provincial) level. Decisions about what the health system produces (the outcome to measure efficiency against) and what are the resources it has to produce that outcome were based on interviews and consultation with health system decision makers. Overall, we find large inefficiencies in the Canadian health care system, which could improve outcomes (here, measured as a reduction in treatable causes of death) by between 18 and 35% across our analyses. Also, we find that inefficiencies are the result of three main sets of factors that policy makers could pay attention to: management factors, such as hospital re-admissions; public health factors, such as obesity and smoking rates; and environmental factors such as the population's average income.
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
Exploring the Innate Immune System: Using Complement-Medicated Cell Lysis in the Classroom

ERIC Educational Resources Information Center

Fuller, Kevin G.

2008-01-01

The protein complement pathway comprises an important part of the innate immunity. The use of serum to demonstrate complement-mediated destruction across a series of bacterial dilutions allows an instructor to introduce a number of important biological concepts such as bacterial growth, activation cascades, and adaptive versus innate immunity.
46 CFR 282.21 - Wages of officers and crew.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Definitions. When used in this part. (1) Base period. The first base period under the wage index system, as... employment of the approved manning complement of the subsidized vessel, including payments required by law to... assessments on crew payrolls. (4) Approved manning complement means the complement approved by the Board for...
Complement factor H in host defense and immune evasion.

PubMed

Parente, Raffaella; Clark, Simon J; Inforzato, Antonio; Day, Anthony J

2017-05-01

Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.
A Novel Model to Simulate Flexural Complements in Compliant Sensor Systems

PubMed Central

Tang, Hongyan; Zhang, Dan; Guo, Sheng; Qu, Haibo

2018-01-01

The main challenge in analyzing compliant sensor systems is how to calculate the large deformation of flexural complements. Our study proposes a new model that is called the spline pseudo-rigid-body model (spline PRBM). It combines dynamic spline and the pseudo-rigid-body model (PRBM) to simulate the flexural complements. The axial deformations of flexural complements are modeled by using dynamic spline. This makes it possible to consider the nonlinear compliance of the system using four control points. Three rigid rods connected by two revolute (R) pins with two torsion springs replace the three lines connecting the four control points. The kinematic behavior of the system is described using Lagrange equations. Both the optimization and the numerical fitting methods are used for resolving the characteristic parameters of the new model. An example is given of a compliant mechanism to modify the accuracy of the model. The spline PRBM is important in expanding the applications of the PRBM to the design and simulation of flexural force sensors. PMID:29596377

Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"?

PubMed Central

2011-01-01

Trauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies. PMID:22129197
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
Assessing inefficiency in euro bilateral exchange rates

NASA Astrophysics Data System (ADS)

Tabak, Benjamin M.; Cajueiro, Daniel O.

2006-07-01

This paper assesses inefficiency for 10 euro bilateral exchange rates. We study the dynamics of these time series by estimating Tsallis q entropic index and Hurst exponents using the local Whittle estimator. Empirical results suggest that US, Canadian and Singapore dollar are amongst the most efficient currencies, while Japanese yen and Swedish krona are amongst the most inefficient.
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.
Testing the hospital value proposition: an empirical analysis of efficiency and quality.

PubMed

Huerta, Timothy R; Ford, Eric W; Peterson, Lori T; Brigham, Keith H

2008-01-01

To assess the relationship between hospitals' X-inefficiency levels and overall care quality based on the National Quality Forum's 27 safe practices score and to improve the analytic strategy for assessing X-inefficiency. The 2005 versions of the American Hospital Association and Leapfrog Group's annual surveys were the basis of the study. Additional case mix indices and market variables were drawn from the Centers for Medicare and Medicaid Services data sources and the Area Resource File. Data envelopment analysis was used to determine hospitals' X-inefficiency scores relative to their market-level competitors. Regression was used to assess the relationship between X-inefficiency and quality, controlling for organizational and market characteristics. Expenses (total and labor expenditures), case-mix-adjusted admissions, length of stay, and licensed beds defined the X-inefficiency function. The overall National Quality Forum's safe practice score, health maintenance organization penetration, market share, and teaching status served as independent control variables in the regression. The National Quality Forum's safe practice scores are significantly and positively correlated to hospital X-inefficiency levels (beta = .105, p < or = .05). The analysis of the value proposition had very good explanatory power (adjusted R(2) = .414; p < or = .001; df = 7, 265). Contrary to earlier findings, health maintenance organization penetration and being a teaching hospital were positively related to X-inefficiency. Similar with others' findings, greater market share and for-profit ownership were negatively associated with X-inefficiency. Measurement of overall hospital quality is improving but can still be made better. Nevertheless, the National Quality Forum's measure is significantly related to efficiency and could be used to create differential pay-for-performance programs. A market-segmented analytic strategy for studying hospitals' efficiency yields results with a high degree of explanatory power.
Geosciences In Action Everyday Supporting B2B Partnerships

NASA Astrophysics Data System (ADS)

Glackin, M. M.; Miller, M.

2015-12-01

The weather and climate industry meets the needs of businesses every day providing services and technology that save dollars and protect lives and property. This industry employs thousands of Americans and exports products and services to the benefit of the U.S. economy and the quality of life for all people. It excels in its ability to understand and the rapidly apply the latest research, innovative technology, and business insights to uniquely solve customer needs. These skills complement the expertise of the research community and federal agencies to improve safety and performance. We will review the broad sectors of industry that are served and share insights into partnerships with other industries including an in depth example for the aviation industry. Turbulence is a major safety risk and operational challenge for airline operations, costing airlines hundreds of millions of dollars in injury claims, operational inefficiencies, maintenance costs, and loss revenue. Leveraging research developed under federal grants with latest technology and decision science, the industry provides an innovative solution to the turbulence challenge, proven to improve safety and reduce turbulence-related cost by nearly 50%.
Wholesale Electricity Market Design with Increasing Levels of Renewable Generation: Incentivizing Flexibility in System Operations

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

Ela, Erik; Milligan, Michael; Bloom, Aaron

This paper discusses the importance and challenges of incentivizing flexibility during short-term operations of the bulk power system due to the increasing variability and uncertainty from growing penetrations of variable generation (VG). Operational flexibility can refer to many aspects of a resource's capability to support the power system, such as the speed, range, and duration of power output, as well as the ability to autonomously respond to frequency or voltage changes. Inefficient utilization of existing flexibility, or unwillingness of resources to provide flexibility, can compromise system reliability by not meeting the changing net load, and it can also lead tomore » higher costs when an inefficient use of flexibility resources occurs. There are many existing characteristics of market design that incentivize flexibility in some manner. How they incentivize the provision of flexibility as well as the level of flexibility is still debated. We explore some of these existing market designs, as well as new market mechanisms, such as pay-for-performance regulating reserve and flexible ramping products, that aim to explicitly incentivize the provision of more flexibility to the system, particularly as a result of increasing VG penetration levels.« less
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.
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.
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
Interaction of extremophilic archaeal viruses with human and mouse complement system and viral biodistribution in mice

PubMed Central

Wu, Linping; Uldahl, Kristine Buch; Chen, Fangfang; Benasutti, Halli; Logvinski, Deborah; Vu, Vivian; Banda, Nirmal K.; Peng, Xu; Simberg, Dmitri; Moghimi, Seyed Moein

2017-01-01

Archaeal viruses offer exceptional biophysical properties for modification and exploration of their potential in bionanotechnology, bioengineering and nanotherapeutic developments. However, the interaction of archaeal viruses with elements of the innate immune system has not been explored, which is a necessary prerequisite if their potential for biomedical applications to be realized. Here we show complement activation through lectin (via direct binding of MBL/MASPs) and alternative pathways by two extremophilic archaeal viruses (Sulfolobus monocaudavirus 1 and Sulfolobus spindle-shaped virus 2) in human serum. We further show some differences in initiation of complement activation pathways between these viruses. Since, Sulfolobus monocaudavirus 1 was capable of directly triggering the alternative pathway, we also demonstrate that the complement regulator factor H has no affinity for the viral surface, but factor H deposition is purely C3-dependent. This suggests that unlike some virulent pathogens Sulfolobus monocaudavirus 1 does not acquire factor H for protection. Complement activation with Sulfolobus monocaudavirus 1 also proceeds in murine sera through MBL-A/C as well as factor D-dependent manner, but C3 deficiency has no overall effect on viral clearance by organs of the reticuloendothelial system on intravenous injection. However, splenic deposition was significantly higher in C3 knockout animals compared with the corresponding wild type mice. We discuss the potential application of these viruses in biomedicine in relation to their complement activating properties. PMID:28846925
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.
HPT in a Dot-Com World.

ERIC Educational Resources Information Center

Farrington, Jeanne

2001-01-01

Discusses how human performance technology can help new Internet companies. Highlights include major business goals; using a systems approach to look for gaps in the organization itself, personnel, behavior, performance, feedback, communication, and internal inefficiencies; compensation structures; recruiting; training; rewarding performance; and…
Development of an operationally efficient PTC braking enforcement algorithm for freight trains.

DOT National Transportation Integrated Search

2013-08-01

Software algorithms used in positive train control (PTC) systems designed to predict freight train stopping distance and enforce a penalty brake application have been shown to be overly conservative, which can lead to operational inefficiencies by in...
Report: EPA’s Fleet Management Program Needs Improvement

EPA Pesticide Factsheets

Report #15-P-0001, October 6, 2014. If oversight of the EPA’s fleet is not improved, the $6 million-per-year program could be ineffective and inefficient in supporting the agency’s mission and reporting data to the federal system.
Complement-Mediated Regulation of Metabolism and Basic Cellular Processes.

PubMed

Hess, Christoph; Kemper, Claudia

2016-08-16

Complement is well appreciated as a critical arm of innate immunity. It is required for the removal of invading pathogens and works by directly destroying them through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental cellular processes, such as survival, proliferation, and autophagy. Newly identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription-factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism and the potential implications in infection and other disease settings. Copyright © 2016 Elsevier Inc. All rights reserved.
Nucleic acid encoding a self-assembling split-fluorescent protein system

DOEpatents

Waldo, Geoffrey S.; Cabantous, Stephanie

2014-04-01

The invention provides a protein labeling and detection system based on self-complementing fragments of fluorescent and chromophoric proteins. The system of the invention is exemplified with various combinations of self-complementing fragments derived from Aequorea victoria Green Fluorescent Protein (GFP), which are used to detect and quantify protein solubility in multiple assay formats, both in vitro and in vivo.
Nucleic acid encoding a self-assembling split-fluorescent protein system

DOEpatents

Waldo, Geoffrey S [Santa Fe, NM; Cabantous, Stephanie [Los Alamos, NM

2011-06-07

The invention provides a protein labeling and detection system based on self-complementing fragments of fluorescent and chromophoric proteins. The system of the invention is exemplified with various combinations of self-complementing fragments derived from Aequorea victoria Green Fluorescent Protein (GFP), which are used to detect and quantify protein solubility in multiple assay formats, both in vitro and in vivo.

Nucleic acid encoding a self-assembling split-fluorescent protein system

DOEpatents

Waldo, Geoffrey S.; Cabantous, Stephanie

2015-07-14

The invention provides a protein labeling and detection system based on self-complementing fragments of fluorescent and chromophoric proteins. The system of the invention is exemplified with various combinations of self-complementing fragments derived from Aequorea victoria Green Fluorescent Protein (GFP), which are used to detect and quantify protein solubility in multiple assay formats, both in vitro and in vivo.
Improvements for energy conservation at the Coeur d'Alene Nursery

Treesearch

Aram Eramian

2009-01-01

In 2002, the USDA Forest Service Coeur d'Alene Nursery in Idaho began to evaluate ways to reduce energy consumption in lighting, refrigeration, and heating and cooling of facility workspace. The primary factor leading up to this was the inefficiency of the nursery's Freon(R)-based refrigeration system. Energy costs and maintenance of the system were becoming...
Higher flexibility in input N:P ratios results in more balanced phosphorus budgets in two long-term experimental agroecosystems

USDA-ARS?s Scientific Manuscript database

Inefficient phosphorus (P) use in intensive agriculture is common in both organic and conventional systems, resulting in P overapplication and soil P build-up. Increasing crop P removal and P recycling within farming systems (e.g., via cover crops) and reducing P inputs can improve farm P balances. ...
A Framework for Quantitative Evaluation of Care Coordination Effectiveness

ERIC Educational Resources Information Center

Liu, Wei

2017-01-01

The U.S. healthcare system lacks incentives and quantitative evaluation tools to assess coordination in a patient's care transition process. This is needed because poor care coordination has been identified by many studies as one of the major root causes for the U.S. health system's inefficiency, for poor outcomes, and for high cost. Despite…
Dengue-Immune Humans Have Higher Levels of Complement-Independent Enhancing Antibody than Complement-Dependent Neutralizing Antibody.

PubMed

Yamanaka, Atsushi; Konishi, Eiji

2017-09-25

Dengue is the most important arboviral disease worldwide. We previously reported that most inhabitants of dengue-endemic countries who are naturally immune to the disease have infection-enhancing antibodies whose in vitro activity does not decrease in the presence of complement (complement-independent enhancing antibodies, or CiEAb). Here, we compared levels of CiEAb and complement-dependent neutralizing antibodies (CdNAb) in dengue-immune humans. A typical antibody dose-response pattern obtained in our assay system to measure the balance between neutralizing and enhancing antibodies showed both neutralizing and enhancing activities depending on serum dilution factor. The addition of complement to the assay system increased the activity of neutralizing antibodies at lower dilutions, indicating the presence of CdNAb. In contrast, similar dose-response curves were obtained with and without complement at higher dilutions, indicating higher levels of CiEAb than CdNAb. For experimental support for the higher CiEAb levels, a cocktail of mouse monoclonal antibodies against dengue virus type 1 was prepared. The antibody dose-response curves obtained in this assay, with or without complement, were similar to those obtained with human serum samples when a high proportion of D1-V-3H12 (an antibody exhibiting only enhancing activity and thus a model for CiEAb) was used in the cocktail. This study revealed higher-level induction of CiEAb than CdNAb in humans naturally infected with dengue viruses.
NF-κB and enhancer-binding CREB protein scaffolded by CREB-binding protein (CBP)/p300 proteins regulate CD59 protein expression to protect cells from complement attack.

PubMed

Du, Yiqun; Teng, Xiaoyan; Wang, Na; Zhang, Xin; Chen, Jianfeng; Ding, Peipei; Qiao, Qian; Wang, Qingkai; Zhang, Long; Yang, Chaoqun; Yang, Zhangmin; Chu, Yiwei; Du, Xiang; Zhou, Xuhui; Hu, Weiguo

2014-01-31

The complement system can be activated spontaneously for immune surveillance or induced to clear invading pathogens, in which the membrane attack complex (MAC, C5b-9) plays a critical role. CD59 is the sole membrane complement regulatory protein (mCRP) that restricts MAC assembly. CD59, therefore, protects innocent host cells from attacks by the complement system, and host cells require the constitutive and inducible expression of CD59 to protect themselves from deleterious destruction by complement. However, the mechanisms that underlie CD59 regulation remain largely unknown. In this study we demonstrate that the widely expressed transcription factor Sp1 may regulate the constitutive expression of CD59, whereas CREB-binding protein (CBP)/p300 bridge NF-κB and CREB, which surprisingly functions as an enhancer-binding protein to induce the up-regulation of CD59 during in lipopolysaccharide (LPS)-triggered complement activation, thus conferring host defense against further MAC-mediated destruction. Moreover, individual treatment with LPS, TNF-α, and the complement activation products (sublytic MAC (SC5b-9) and C5a) could increase the expression of CD59 mainly by activating NF-κB and CREB signaling pathways. Together, our findings identify a novel gene regulation mechanism involving CBP/p300, NF-κB, and CREB; this mechanism suggests potential drug targets for controlling various complement-related human diseases.
[The complement system in the pathogenesis of antineutrophil cytoplasm antibodies-associated vasculitis].

PubMed

Flores-Suárez, Luis F

2011-12-01

One of the main characteristics of the vasculitis associated with antineutrophil cytoplasm autoantibodies (AASV) is the absence of immune complex deposition in biopsies of affected tissues as well as a lack of complement depletion. However, in early stages of disease induced in animal models, it has been observed that the complement system may be involved in the generation of these diseases. There are various animal models which have been developed with the aim of knowing which are the pathogenic mechanisms in granulomatosis with polyangiitis (Wegener) (GPA) and microscopic polyangiitis (MPA), the latter being explained using these approaches in a more satisfactory manner, as there is lack of a model which reproduces the changes leading to a granulomatous vasculitis associated with antibodies against proteinase-3, as in GPA. This short review presents recent evidence of the presence of complement in biopsies of patients with AASV and the most recent animal models, which show the participation of complement in their etiology. Copyright © 2011 Elsevier España, S.L. All rights reserved.
Minimization of bacterial size allows for complement evasion and is overcome by the agglutinating effect of antibody

PubMed Central

Dalia, Ankur B.; Weiser, Jeffrey N.

2011-01-01

SUMMARY The complement system, which functions by lysing pathogens directly or by promoting their uptake by phagocytes, is critical for controlling many microbial infections. Here we show that in Streptococcus pneumoniae, increasing bacterial chain length sensitizes this pathogen to complement deposition and subsequent uptake by human neutrophils. Consistent with this, we show that minimizing chain length provides wild-type bacteria with a competitive advantage in vivo in a model of systemic infection. Investigating how the host overcomes this virulence strategy, we find that antibody promotes complement-dependent opsonophagocytic killing of Streptococcus pneumoniae and lysis of Haemophilus influenzae independent of Fc-mediated effector functions. Consistent with the agglutinating effect of antibody, F(ab′)2 but not Fab could promote this effect. Therefore, increasing pathogen size, whether by natural changes in cellular morphology or via antibody-mediated agglutination, promotes complement-dependent killing. These observations have broad implications for how cell size and morphology can affect virulence among pathogenic microbes. PMID:22100164
Technical efficiency of public district hospitals in Madhya Pradesh, India: a data envelopment analysis.

PubMed

Jat, Tej Ram; Sebastian, Miguel San

2013-09-24

Scarcity of resources for healthcare is a well-acknowledged problem. In this context, efficient utilization of existing financial and human resources becomes crucial for strengthening the healthcare delivery. The assessment of efficiency of health facilities can guide decision makers in ensuring the optimum utilization of available resources. The objective of this study was to evaluate the technical efficiency (TE) of the public district hospitals in Madhya Pradesh, India, with special emphasis on maternal healthcare services, using data envelopment analysis (DEA). Data from 40 district hospitals from January to December 2010 were collected from the health management information system and other records of the department of health and family welfare of the state. DEA was performed with input orientation and variable returns to scale assumption. TE and scale efficiency scores of the district hospitals were 0.90 (SD = 0.14) and 0.88 (SD = 0.15), respectively. Of the total district hospitals in the study, 20 (50%) were technically efficient constituting the 'best practice frontier'. The other half were technically inefficient, with an average TE score of 0.79 (SD = 0.12) meaning that these hospitals could produce the same outputs by using 21% less inputs from current input levels. Twenty-six (65%) district hospitals were found to be scale inefficient, manifesting a mean score of 0.81 (SD = 0.16). Half of the district hospitals in the study were operating inefficiently. Decision makers and administrators in the state should identify the causes of the observed inefficiencies and take appropriate measures to increase efficiency of these hospitals.
Controlling costs without compromising quality: paying hospitals for total knee replacement.

PubMed

Pine, Michael; Fry, Donald E; Jones, Barbara L; Meimban, Roger J; Pine, Gregory J

2010-10-01

Unit costs of health services are substantially higher in the United States than in any other developed country in the world, without a correspondingly healthier population. An alternative payment structure, especially for high volume, high cost episodes of care (eg, total knee replacement), is needed to reward high quality care and reduce costs. The National Inpatient Sample of administrative claims data was used to measure risk-adjusted mortality, postoperative length-of-stay, costs of routine care, adverse outcome rates, and excess costs of adverse outcomes for total knee replacements performed between 2002 and 2005. Empirically identified inefficient and ineffective hospitals were then removed to create a reference group of high-performance hospitals. Predictive models for outcomes and costs were recalibrated to the reference hospitals and used to compute risk-adjusted outcomes and costs for all hospitals. Per case predicted costs were computed and compared with observed costs. Of the 688 hospitals with acceptable data, 62 failed to meet effectiveness criteria and 210 were identified as inefficient. The remaining 416 high-performance hospitals had 13.4% fewer risk-adjusted adverse outcomes (4.56%-3.95%; P < 0.001; χ) and 9.9% lower risk-adjusted total costs ($12,773-$11,512; P < 0.001; t test) than all study hospitals. Inefficiency accounted for 96% of excess costs. A payment system based on the demonstrated performance of effective, efficient hospitals can produce sizable cost savings without jeopardizing quality. In this study, 96% of total excess hospital costs resulted from higher routine costs at inefficient hospitals, whereas only 4% was associated with ineffective care.
Complement research in the 18th-21st centuries: Progress comes with new technology.

PubMed

Sim, R B; Schwaeble, W; Fujita, T

2016-10-01

The complement system has been studied for about 120 years. Progress in defining this large and complex system has been dependent on the research technologies available, but since the introduction of protein chromatography, electrophoresis, and antibody-based assay methods in the 1950s and 60s, and sequencing of proteins and DNA in the 70s and 80s, there has been very rapid accumulation of data. With more recent improvements in 3D structure determination (nmr and X-ray crystallography), the structures of most of the complement proteins have now been solved. Complement research since 1990 has been greatly stimulated by the discoveries of the multiple proteins in the lectin pathway, the strong association of Factor H, C3, Factor B allelic variants with adult macular degeneration and atypical haemolytic uremic syndrome, and the introduction of the anti-C5 monoclonal antibody as a therapy for paroxysmal nocturnal hemoglobinuria and atypical haemolytic uremic syndrome. Potential new roles for complement in tissue development and the search for novel therapeutics suggest a very active future for complement research. Copyright © 2016 Elsevier GmbH. All rights reserved.
Losses, inefficiencies and waste in the global food system.

PubMed

Alexander, Peter; Brown, Calum; Arneth, Almut; Finnigan, John; Moran, Dominic; Rounsevell, Mark D A

2017-05-01

Losses at every stage in the food system influence the extent to which nutritional requirements of a growing global population can be sustainably met. Inefficiencies and losses in agricultural production and consumer behaviour all play a role. This paper aims to understand better the magnitude of different losses and to provide insights into how these influence overall food system efficiency. We take a systems view from primary production of agricultural biomass through to human food requirements and consumption. Quantities and losses over ten stages are calculated and compared in terms of dry mass, wet mass, protein and energy. The comparison reveals significant differences between these measurements, and the potential for wet mass figures used in previous studies to be misleading. The results suggest that due to cumulative losses, the proportion of global agricultural dry biomass consumed as food is just 6% (9.0% for energy and 7.6% for protein), and 24.8% of harvest biomass (31.9% for energy and 27.8% for protein). The highest rates of loss are associated with livestock production, although the largest absolute losses of biomass occur prior to harvest. Losses of harvested crops were also found to be substantial, with 44.0% of crop dry matter (36.9% of energy and 50.1% of protein) lost prior to human consumption. If human over-consumption, defined as food consumption in excess of nutritional requirements, is included as an additional inefficiency, 48.4% of harvested crops were found to be lost (53.2% of energy and 42.3% of protein). Over-eating was found to be at least as large a contributor to food system losses as consumer food waste. The findings suggest that influencing consumer behaviour, e.g. to eat less animal products, or to reduce per capita consumption closer to nutrient requirements, offer substantial potential to improve food security for the rising global population in a sustainable manner.
Identifying Inefficient Single-Family Homes With Utility Bill Analysis: Preprint

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

Casey, S.; Krarti, M.; Bianchi, M.

2010-08-01

Differentiating between energy-efficient and inefficient single-family homes on a community scale helps identify and prioritize candidates for energy-efficiency upgrades. Prescreening diagnostic procedures can further retrofit efforts by providing efficiency information before a site-visit is conducted. We applied the prescreening diagnostic to a simulated community of homes in Boulder, Colorado and analyzed energy consumption data to identify energy-inefficient homes.
Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.

PubMed

Mlcochova, Petra; Watters, Sarah A; Towers, Greg J; Noursadeghi, Mahdad; Gupta, Ravindra K

2014-03-21

It is now known that clinically derived viruses are most commonly R5 tropic with very low infectivity in macrophages. As these viruses utilize CD4 inefficiently, defective entry has been assumed to be the dominant restriction. The implication is that macrophages are not an important reservoir for the majority of circulating viruses. Macrophage infection by clinical transmitted/founder isolates was 10-100 and 30-450 fold less efficient as compared to YU-2 and BaL respectively. Vpx complementation augmented macrophage infection by non-macrophage tropic viruses to the level of infectivity observed for YU-2 in the absence of Vpx. Augmentation was evident even when Vpx was provided 24 hours post-infection. The entry defect was measured as 2.5-5 fold, with a further 3.5-10 fold block at strong stop and subsequent stages of reverse transcription as compared to YU-2. The overall block to infection was critically dependent on the mechanism of entry as demonstrated by rescue of infection after pseudotyping with VSV-G envelope. Reverse transcription in macrophages could not be enhanced using a panel of cytokines or lipopolysaccharide (LPS). Although the predominant block to clinical transmitted/founder viruses is post-entry, infectivity is determined by Env-CD4 interactions and can be rescued with VSV-G pseudotyping. This suggests a functional link between the optimal entry pathway taken by macrophage tropic viruses and downstream events required for reverse transcription. Consistent with a predominantly post-entry block, replication of R5 using viruses can be greatly enhanced by Vpx. We conclude therefore that entry is not the limiting step and that macrophages represent clinically relevant reservoirs for 'non-macrophage tropic' viruses.
Xrcc2 deficiency sensitizes cells to apoptosis by MNNG and the alkylating anticancer drugs temozolomide, fotemustine and mafosfamide.

PubMed

Tsaryk, Roman; Fabian, Kerstin; Thacker, John; Kaina, Bernd

2006-08-08

DNA double-strand breaks (DSBs) are potent killing lesions, and inefficient repair of DSBs does not only lead to cell death but also to genomic instability and tumorigenesis. DSBs are repaired by non-homologous end-joining and homologous recombination (HR). A key player in HR is Xrcc2, a Rad51-like protein. Cells deficient in Xrcc2 are hypersensitive to X-rays and mitomycin C and display increased chromosomal aberration frequencies. In order to elucidate the role of Xrcc2 in resistance to anticancer drugs, we compared Xrcc2 knockout (Xrcc2-/-) mouse embryonic fibroblasts with the corresponding isogenic wild-type and Xrcc2 complemented knockout cells. We show that Xrcc2-/- cells are hypersensitive to the killing effect of the simple methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). They undergo apoptosis after MNNG treatment while necrosis is only marginally enhanced. Complementation of Xrcc2 deficient cells by Xrcc2 cDNA transfection conferred resistance to the cytotoxic and apoptosis-inducing effect of MNNG. The hypersensitivity of Xrcc2-/- cells to MNNG prompted us to investigate their killing and apoptotic response to various methylating, chloroethylating and crosslinking drugs used in anticancer therapy. Xrcc2 deficient cells were found to be hypersensitive to temozolomide, fotemustine and mafosfamide. They were also hypersensitive to cisplatin but not to taxol. The data reveal that Xrcc2 plays a role in the protection against a wide range of anticancer drugs and, therefore, suggest Xrcc2 to be a determinant of anticancer drug resistance. They also indicate that HR is involved in the processing of DNA damage induced by simple alkylating agents.
Evaluation plan for the I-95 CC ATIS (Corridor-TravTips) program

DOT National Transportation Integrated Search

1999-03-01

The Boston-to-New York travel corridor is one of the busiest travel corridors in the country and, typical of such developed areas, is experiencing congestion and safety problems and other travel-related inefficiencies along its transportation systems...
Deployment and Evaluation of the Helicopter In-Flight Tracking System (HITS)

DOT National Transportation Integrated Search

2004-12-30

The Gulf of Mexico airspace has two major operating regions: low altitude offshore (below 7,000 ft) and high altitude oceanic (above 18,000 ft). Both regions suffer significant inefficiencies due to the lack of continuous surveillance during Instrume...
Deployment and evaluation of the Helicopter In-flight Tracking System (HITS)

DOT National Transportation Integrated Search

2004-12-31

The Gulf of Mexico airspace has two major operating regions: low altitude offshore (below 7,000 ft) and high altitude oceanic (above 18,000 ft). Both regions suffer significant inefficiencies due to the lack of continuous surveillance during Instrume...
Rationality and Planning: Observations in a Non-Western Country.

ERIC Educational Resources Information Center

Beach, Robert H.

1989-01-01

Discusses several observations related to planning, decision-making, and change within the context of a predominantly norm-based educational system in Malawi. Differing cultural norms are behind observed "inefficiencies" in accessing enrollment information, changing leadership, and planning workshops. Includes 16 references. (MLH)
Potential influences of complement factor H in autoimmune inflammatory and thrombotic disorders.

PubMed

Ferluga, Janez; Kouser, Lubna; Murugaiah, Valarmathy; Sim, Robert B; Kishore, Uday

2017-04-01

Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part. These include systemic lupus erythematosus, rheumatoid arthritis, atypical haemolytic uremic syndrome, anti-phospholipid syndrome and age-related macular degeneration. Such diseases are generally complex - multigenic and heterogeneous in their symptoms and predisposition/susceptibility. They usually need to be triggered by vascular trauma, drugs or infection and non-complement genetic factors also play a part. Underlying events seem to include decline in peripheral regulatory T cells, dendritic cell, and B cell tolerance, associated with alterations in lymphoid organ microenvironment. Factor H is an abundant protein, synthesised in many cell types, and its reported binding to many different ligands, even if not of high affinity, may influence a large number of molecular interactions, together with the accepted role of Factor H within the complement system. Factor H is involved in mesenchymal stem cell mediated tolerance and also contributes to self-tolerance by augmenting iC3b production and opsonisation of apoptotic cells for their silent dendritic cell engulfment via complement receptor CR3, which mediates anti-inflammatory-tolerogenic effects in the apoptotic cell context. There may be co-operation with other phagocytic receptors, such as complement C1q receptors, and the Tim glycoprotein family, which specifically bind phosphatidylserine expressed on the apoptotic cell surface. Factor H is able to discriminate between self and nonself surfaces for self-protection and anti-microbe defence. Factor H, particularly as an abundant platelet protein, may also modulate blood coagulation, having an anti-thrombotic role. Here, we review a number of interaction pathways in coagulation and in immunity, together with associated diseases, and indicate where Factor H may be expected to exert an influence, based on reports of the diversity of ligands for Factor H. Copyright © 2017 Elsevier Ltd. All rights reserved.

Automated quality control in a file-based broadcasting workflow

NASA Astrophysics Data System (ADS)

Zhang, Lina

2014-04-01

Benefit from the development of information and internet technologies, television broadcasting is transforming from inefficient tape-based production and distribution to integrated file-based workflows. However, no matter how many changes have took place, successful broadcasting still depends on the ability to deliver a consistent high quality signal to the audiences. After the transition from tape to file, traditional methods of manual quality control (QC) become inadequate, subjective, and inefficient. Based on China Central Television's full file-based workflow in the new site, this paper introduces an automated quality control test system for accurate detection of hidden troubles in media contents. It discusses the system framework and workflow control when the automated QC is added. It puts forward a QC criterion and brings forth a QC software followed this criterion. It also does some experiments on QC speed by adopting parallel processing and distributed computing. The performance of the test system shows that the adoption of automated QC can make the production effective and efficient, and help the station to achieve a competitive advantage in the media market.
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.
Globalization of health care delivery in the United States through medical tourism.

PubMed

Kumar, Sameer; Breuing, Richard; Chahal, Rajneet

2012-01-01

This study highlights some of the inefficiencies in the U.S. health care system and determines what effect medical tourism has had on the U.S. and global health care supply chains. This study also calls attention to insufficient health communication efforts to inform uninsured or underinsured medical tourists about the benefits and risks and determines the managerial and cost implications of various surgical procedures on the global health care system into the future. This study evaluated 3 years (2005, 2007, and 2011) of actual and projected surgical cost data. The authors selected 3 countries for analysis: the United States, India, and Thailand. The surgeries chosen for evaluation were total knee replacement (knee arthroplasty), hip replacement (hip arthroplasty), and heart bypass (coronary artery bypass graft). Comparisons of costs were made using Monte Carlo simulation with variability encapsulated by triangular distributions. The results are staggering. In 2005, the amount of money lost to India and Thailand on just these 3 surgeries because of cost inefficiencies in the U.S. health care system was between 1.3 to 2 billion dollars. In 2011, because many more Americans are expected to travel overseas for health care, this amount is anticipated to rise to between 20 and 30.2 billion dollars. Therefore, more attention should be paid to health communication efforts that truly illustrate the benefits/risks of medical travel. The challenge of finding reliable data for surgeries performed and associated surgical cost estimates was mitigated by the use of a Monte Carlo simulation of triangular distributions. The implications from this study are clear: If the U.S. health care industry is unable to eliminate waste and inefficiency and thus curb rising costs, it will continue to lose surgical revenue to foreign health providers. Copyright © Taylor & Francis Group, LLC
Genetic testing when there is a mix of compulsory and voluntary health insurance.

PubMed

Hoel, Michael; Iversen, Tor

2002-03-01

When the insurer has access to information about test status, genetic insurance can handle the negative effects of genetic testing on insurance coverage and income distribution. Hence, efficient testing is promoted. When information about prevention and test status is private, two types of social inefficiencies may occur; genetic testing may not be done when it is socially efficient and genetic testing may be done although it is socially inefficient. The first type of inefficiency is shown to be likely for consumers with compulsory insurance only, while the second type of inefficiency is more likely for those who have supplemented the compulsory insurance with substantial voluntary insurance. This second type of inefficiency is more important the less effective prevention is. It is therefore a puzzle that many countries have imposed strict regulation on the genetic information insurers have access to. A reason may be that genetic insurance is not yet a political issue, and the advantage of shared genetic information is therefore not transparent.
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.
Innovative Clinical Trial Designs

PubMed Central

Lavori, Philip W.

2015-01-01

Whereas the 20th-century health care system sometimes seemed to be inhospitable to and unmoved by experimental research, its inefficiency and unaffordability have led to reforms that foreshadow a new health care system. We point out certain opportunities and transformational needs for innovations in study design offered by the 21st-century health care system, and describe some innovative clinical trial designs and novel design methods to address these needs and challenges. PMID:26140056
Protection of host cells by complement regulators.

PubMed

Schmidt, Christoph Q; Lambris, John D; Ricklin, Daniel

2016-11-01

The complement cascade is an ancient immune-surveillance system that not only provides protection from pathogen invasion but has also evolved to participate in physiological processes to maintain tissue homeostasis. The alternative pathway (AP) of complement activation is the evolutionarily oldest part of this innate immune cascade. It is unique in that it is continuously activated at a low level and arbitrarily probes foreign, modified-self, and also unaltered self-structures. This indiscriminate activation necessitates the presence of preformed regulators on autologous surfaces to spare self-cells from the undirected nature of AP activation. Although the other two canonical complement activation routes, the classical and lectin pathways, initiate the cascade more specifically through pattern recognition, their activity still needs to be tightly controlled to avoid excessive reactivity. It is the perpetual duty of complement regulators to protect the self from damage inflicted by inadequate complement activation. Here, we review the role of complement regulators as preformed mediators of defense, explain their common and specialized functions, and discuss selected cases in which alterations in complement regulators lead to disease. Finally, rational engineering approaches using natural complement inhibitors as potential therapeutics are highlighted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Inactivation of complement by Loxosceles reclusa spider venom.

PubMed

Gebel, H M; Finke, J H; Elgert, K D; Cambell, B J; Barrett, J T

1979-07-01

Zymosan depletion of serum complement in guinea pigs rendered them highly resistant to lesion by Loxosceles reclusa spider venom. Guinea pigs deficient in C4 of the complement system are as sensitive to the venom as normal guinea pigs. The injection of 35 micrograms of whole recluse venom intradermally into guinea pigs lowered their complement level by 35.7%. Brown recluse spider venom in concentrations as slight as 0.02 micrograms protein/ml can totally inactivate one CH50 of guinea pig complement in vitro. Bee, scorpion, and other spider venoms had no influence on the hemolytic titer of complement. Fractionation of recluse spider venom by Sephadex G-200 filtration separated the complement-inactivating property of the venom into three major regions which could be distinguished on the basis of heat stability as well as size. None was neutralized by antivenom. Polyacrylamide gel electrophoresis of venom resolved the complement inactivators into five fractions. Complement inactivated by whole venom or the Sephadex fractions could be restored to hemolytic activity by supplements of fresh serum but not by heat-inactivated serum, pure C3, pure C5, or C3 and C5 in combination.
The renaissance of complement therapeutics

PubMed Central

Ricklin, Daniel; Mastellos, Dimitrios C.; Reis, Edimara S.; Lambris, John D.

2018-01-01

The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond. PMID:29199277
21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these...
21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these...
21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these...
21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these...
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
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
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.
Investigation Concerning the Modification of the University of Illinois Computerized Serials Book Catalog to Achieve an Operative System at the University of Colorado Libraries.

ERIC Educational Resources Information Center

Dougherty, Richard M.; Stephens, James G.

The objectives of the study were to record: (1) the problems encountered in interpreting and using the Illinois program documentation; (2) the modifications required to reconcile system incompatibilities and inefficiencies due to different computer configurations; (3) the input instruction modifications made to accommodate local library processing…
Tracking and Treating Mobile Populations. The TB Net System. Migrant Clinicians Network Monograph Series. = El Sistema de Red para la TB.

ERIC Educational Resources Information Center

Migrant Clinicians Network, Inc., Austin, TX.

A comprehensive tracking and referral network that helps provide continuity of care for mobile populations with active tuberculosis (TB) or TB infection is considered essential for effective treatment of TB. However, the interstate referral system that exists between state health departments has been highly inefficient for serving migrant…
Complement system biomarkers in epilepsy.

PubMed

Kopczynska, Maja; Zelek, Wioleta M; Vespa, Simone; Touchard, Samuel; Wardle, Mark; Loveless, Samantha; Thomas, Rhys H; Hamandi, Khalid; Morgan, B Paul

2018-05-24

To explore whether complement dysregulation occurs in a routinely recruited clinical cohort of epilepsy patients, and whether complement biomarkers have potential to be used as markers of disease severity and seizure control. Plasma samples from 157 epilepsy cases (106 with focal seizures, 46 generalised seizures, 5 unclassified) and 54 controls were analysed. Concentrations of 10 complement analytes (C1q, C3, C4, factor B [FB], terminal complement complex [TCC], iC3b, factor H [FH], Clusterin [Clu], Properdin, C1 Inhibitor [C1Inh] plus C-reactive protein [CRP]) were measured using enzyme linked immunosorbent assay (ELISA). Univariate and multivariate statistical analysis were used to test whether combinations of complement analytes were predictive of epilepsy diagnoses and seizure occurrence. Correlation between number and type of anti-epileptic drugs (AED) and complement analytes was also performed. We found: CONCLUSION: This study adds to evidence implicating complement in pathogenesis of epilepsy and may allow the development of better therapeutics and prognostic markers in the future. Replication in a larger sample set is needed to validate the findings of the study. Copyright © 2018. Published by Elsevier Ltd.
Integrated Intermodal Passenger Transportation System

NASA Technical Reports Server (NTRS)

Klock, Ryan; Owens, David; Schwartz, Henry; Plencner, Robert

2012-01-01

Modern transportation consists of many unique modes of travel. Each of these modes and their respective industries has evolved independently over time, forming a largely incoherent and inefficient overall transportation system. Travelers today are forced to spend unnecessary time and efforts planning a trip through varying modes of travel each with their own scheduling, pricing, and services; causing many travelers to simply rely on their relatively inefficient and expensive personal automobile. This paper presents a demonstration program system to not only collect and format many different sources of trip planning information, but also combine these independent modes of travel in order to form optimal routes and itineraries of travel. The results of this system show a mean decrease in inter-city travel time of 10 percent and a 25 percent reduction in carbon dioxide emissions over personal automobiles. Additionally, a 55 percent reduction in carbon dioxide emissions is observed for intra-city travel. A conclusion is that current resources are available, if somewhat hidden, to drastically improve point to point transportation in terms of time spent traveling, the cost of travel, and the ecological impact of a trip. Finally, future concepts are considered which could dramatically improve the interoperability and efficiency of the transportation infrastructure.

Substitution Between Privately and Publicly Supplied Urban Recreational Open Space

ERIC Educational Resources Information Center

Cordell, Harold K.

1976-01-01

Public and private open space should be considered as interrelated components of a singular open-space supply system; ignoring amounts of private space in the development of guidelines for expansion of public open-space supply may lead to inefficiencies in land allocation. (JD)
Analyzing Human Communication Networks in Organizations: Applications to Management Problems.

ERIC Educational Resources Information Center

Farace, Richard V.; Danowski, James A.

Investigating the networks of communication in organizations leads to an understanding of efficient and inefficient information dissemination as practiced in large systems. Most important in organizational communication is the role of the "liaison person"--the coordinator of intercommunication. When functioning efficiently, coordinators maintain…
IMPACT OF AN INDOOR COOK STOVE INTERVENTION ON MEASURES OF SYSTEMIC INFLAMMATION

EPA Science Inventory

Background and Aims: Approximately three billion people use inefficient and poorly-vented indoor cook stoves, which can result in high indoor air pollution concentrations. Few studies have evaluated the cardiovascular effects of indoor biomass burning. Methods: In this pilot s...
Oceanic Flights and Airspace: Improving Efficiency by Trajectory-Based Operations

NASA Technical Reports Server (NTRS)

Fernandes, Alicia Borgman; Rebollo, Juan; Koch, Michael

2016-01-01

Oceanic operations suffer from multiple inefficiencies, including pre-departure planning that does not adequately consider uncertainty in the proposed trajectory, restrictions on the routes that a flight operator can choose for an oceanic crossing, time-consuming processes and procedures for amending en route trajectories, and difficulties exchanging data between Flight Information Regions (FIRs). These inefficiencies cause aircraft to fly suboptimal trajectories, burning fuel and time that could be conserved. A concept to support integration of existing and emerging capabilities and concepts is needed to transition to an airspace system that employs Trajectory Based Operations (TBO) to improve efficiency and safety in oceanic operations. This paper describes such a concept and the results of preliminary activities to evaluate the concept, including a stakeholder feedback activity, user needs analysis, and high level benefits analysis.
Assessing Technical Inefficiency in Private, Not-For-Profit, Bachelor's and Master's Universities in the United States Using Stochastic Frontier Estimation

ERIC Educational Resources Information Center

Refenes, James L.

2017-01-01

This research explored the technical inefficiency of 813 private, not-for-profit, four-year, bachelor's and master's colleges and universities in the U.S. using data from 2006 to 2011. The goal of the study was to describe and explain the level of technical inefficiency in this group of institutions that can be identified using a (SFE) method and…
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
Kinky thresholds revisited: opportunity costs differ in the NE and SW quadrants.

PubMed

Eckermann, Simon

2015-02-01

Historically, a kinked threshold line on the cost-effectiveness plane at the origin was suggested due to differences in willingness to pay (WTP) for health gain with trade-offs in the north-east (NE) quadrant versus willingness to accept (WTA) cost reductions for health loss with trade-offs in the south-west (SW) quadrant. Empirically, WTA is greater than WTP for equivalent units of health, a finding supported by loss aversion under prospect theory. More recently, appropriate threshold values for health effects have been shown to require an endogenous consideration of the opportunity cost of alternative actions in budget-constrained health systems, but also allocative and displacement inefficiency observed in health system practice. Allocative and displacement inefficiency arise in health systems where the least cost-effective program in contraction has a higher incremental cost-effectiveness ratio (ICER = m) than the most cost-effective program in expansion (ICER = n) and displaced services (ICER = d), respectively. The health shadow price derived by Pekarsky, [Formula: see text] reflects the opportunity cost of best alternative adoption and financing actions in reimbursing new technology with expected incremental costs and net effect allowing for allocative (n < m), and displacement, inefficiency (d < m). This provides an appropriate threshold value for the NE quadrant. In this paper, I show that for trade-offs in the SW quadrant, where new strategies have lower expected net cost while lower expected net effect than current practice, the opportunity cost is contraction of the least cost-effective program, with threshold ICER m. That is, in the SW quadrant, the cost reduction per unit of decreased effect should be compared with the appropriate opportunity cost, best alternative generation of funding. Consequently, appropriate consideration of opportunity cost produces a kink in the threshold at the origin, with the health shadow price in the NE quadrant and ICER of the least cost-effective program in contraction (m) in the SW quadrant having the same general shape as that previously suggested by WTP versus WTA. The extent of this kink depends on the degree of allocative and displacement inefficiency, with no kink in the threshold line strictly only appropriate with complete allocative and displacement efficiency, that is n = d = m.
21 CFR 866.5320 - Properdin factor B immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... involvement of the alternative to the classical pathway of activation of complement (a group of plasma... the skin). Other diseases in which the alternate pathway of complement activation has been implicated...
21 CFR 866.5320 - Properdin factor B immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... involvement of the alternative to the classical pathway of activation of complement (a group of plasma... the skin). Other diseases in which the alternate pathway of complement activation has been implicated...
21 CFR 866.5320 - Properdin factor B immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... involvement of the alternative to the classical pathway of activation of complement (a group of plasma... the skin). Other diseases in which the alternate pathway of complement activation has been implicated...
The prognostic performance of the complement system in septic patients in emergency department: a cohort study.

PubMed

Zhao, Xin; Chen, Yun-Xia; Li, Chun-Sheng

2015-01-01

To investigate the prognostic performance of complement components in septic patients, complement 3, membrane attack complex (MAC) and mannose-binding lectin were measured and compared among adult patients with sepsis, severe sepsis and septic shock, as well as between in-hospital nonsurvivors and survivors. The prognostic value of complement components was compared with mortality in emergency department sepsis (MEDS) score. Median complement 3, MAC and mannose-binding lectin increased directly with the sepsis, severe sepsis and septic shock groups, and were significantly higher in nonsurvivors than in survivors. MEDS and MAC independently predicted in-hospital mortality. The prognostic performance of MAC was superior to MEDS as analyzed by receiver operating characteristic curve and area under the curve.
Generalized look-ahead number conversion from signed digit to complement representation with optical logic operations

NASA Astrophysics Data System (ADS)

Qian, Feng; Li, Guoqiang

2001-12-01

In this paper a generalized look-ahead logic algorithm for number conversion from signed-digit to its complement representation is developed. 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 quaternary signed-digit (QSD) to 4's complement. For optical implementation, a parallel logical array module using electron-trapping device is employed, which is suitable for realizing complex logic functions in the form of sum-of-product. The proposed algorithm and architecture are compatible with a general-purpose optoelectronic computing system.
Situational Awareness During Mass-Casualty Events: Command and Control

PubMed Central

Demchak, Barry; Chan, Theordore C.; Griswold, William G.; Lenert, Leslie

2006-01-01

In existing Incident Command systems1, situational awareness is achieved manually through paper tracking systems. Such systems often produce high latencies and incomplete data, resulting in inefficient and ineffective resource deployment. The WIISARD2 system collects much more data than a paper-based system, dramatically reducing latency while increasing the kinds and quality of information available to Incident Commanders. The WIISARD Command Center solves the problem of data overload and uncertainty through the careful use of limited screen area and novel visualization techniques. PMID:17238524
Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor

PubMed Central

Hovingh, Elise S.; de Maat, Steven; Cloherty, Alexandra P. M.; Johnson, Steven; Pinelli, Elena; Maas, Coen; Jongerius, Ilse

2018-01-01

Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Whooping cough is currently re-emerging worldwide and, therefore, still poses a continuous global health threat. B. pertussis expresses several virulence factors that play a role in evading the human immune response. One of these virulence factors is virulence associated gene 8 (Vag8). Vag8 is a complement evasion molecule that mediates its effects by binding to the complement regulator C1 inhibitor (C1-INH). This regulatory protein is a fluid phase serine protease that controls proenzyme activation and enzyme activity of not only the complement system but also the contact system. Activation of the contact system results in the generation of bradykinin, a pro-inflammatory peptide. Here, the activation of the contact system by B. pertussis was explored. We demonstrate that recombinant as well as endogenous Vag8 enhanced contact system activity by binding C1-INH and attenuating its inhibitory function. Moreover, we show that B. pertussis itself is able to activate the contact system. This activation was dependent on Vag8 production as a Vag8 knockout B. pertussis strain was unable to activate the contact system. These findings show a previously overlooked interaction between the contact system and the respiratory pathogen B. pertussis. Activation of the contact system by B. pertussis may contribute to its pathogenicity and virulence. PMID:29915576
Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor.

PubMed

Hovingh, Elise S; de Maat, Steven; Cloherty, Alexandra P M; Johnson, Steven; Pinelli, Elena; Maas, Coen; Jongerius, Ilse

2018-01-01

Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Whooping cough is currently re-emerging worldwide and, therefore, still poses a continuous global health threat. B. pertussis expresses several virulence factors that play a role in evading the human immune response. One of these virulence factors is virulence associated gene 8 (Vag8). Vag8 is a complement evasion molecule that mediates its effects by binding to the complement regulator C1 inhibitor (C1-INH). This regulatory protein is a fluid phase serine protease that controls proenzyme activation and enzyme activity of not only the complement system but also the contact system. Activation of the contact system results in the generation of bradykinin, a pro-inflammatory peptide. Here, the activation of the contact system by B. pertussis was explored. We demonstrate that recombinant as well as endogenous Vag8 enhanced contact system activity by binding C1-INH and attenuating its inhibitory function. Moreover, we show that B. pertussis itself is able to activate the contact system. This activation was dependent on Vag8 production as a Vag8 knockout B. pertussis strain was unable to activate the contact system. These findings show a previously overlooked interaction between the contact system and the respiratory pathogen B. pertussis . Activation of the contact system by B. pertussis may contribute to its pathogenicity and virulence.
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.
Simple method to distinguish between primary and secondary C3 deficiencies.

PubMed

Pereira de Carvalho Florido, Marlene; Ferreira de Paula, Patrícia; Isaac, Lourdes

2003-03-01

Due to the increasing numbers of reported clinical cases of complement deficiency in medical centers, clinicians are now more aware of the role of the complement system in the protection against infections caused by microorganisms. Therefore, clinical laboratories are now prepared to perform a number of diagnostic tests of the complement system other than the standard 50% hemolytic component assay. Deficiencies of alternative complement pathway proteins are related to severe and recurrent infections; and the application of easy, reliable, and low-cost methods for their detection and distinction are always welcome, notably in developing countries. When activation of the alternative complement pathway is evaluated in hemolytic agarose plates, some but not all human sera cross-react to form a late linear lysis. Since the formation of this linear lysis is dependent on C3 and factor B, it is possible to use late linear lysis to routinely screen for the presence of deficiencies of alternative human complement pathway proteins such as factor B. Furthermore, since linear lysis is observed between normal human serum and primary C3-deficient serum but not between normal human serum and secondary C3-deficient serum caused by the lack of factor H or factor I, this assay may also be used to discriminate between primary and secondary C3 deficiencies.
Novel Evasion Mechanisms of the Classical Complement Pathway

PubMed Central

Garcia, Brandon L.; Zwarthoff, Seline A.; Rooijakkers, Suzan H. M.; Geisbrecht, Brian V.

2016-01-01

Complement is a network of soluble and cell surface-associated proteins which gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of ‘non-self’ cells by one of three initiating mechanisms known as the classical, lectin, or alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. While many complement inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review we focus on several recent investigations which have revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules. PMID:27591336
Novel Evasion Mechanisms of the Classical Complement Pathway.

PubMed

Garcia, Brandon L; Zwarthoff, Seline A; Rooijakkers, Suzan H M; Geisbrecht, Brian V

2016-09-15

Complement is a network of soluble and cell surface-associated proteins that gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of nonself cells by one of three initiating mechanisms known as the classical, lectin, and alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. Although many complement-inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review, we focus on several recent investigations that revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules. Copyright © 2016 by The American Association of Immunologists, Inc.
7 CFR 276.4 - Suspension/disallowance of administrative funds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... System reviews, Federal reviews, audits, investigations, corrective action plans, financial management... inefficient or ineffective if the State agency fails to comply with the food stamp requirements established by... ineffective, FNS may warn the State agency that a suspension and/or disallowance of administrative funds is...

MODELING JOINT PRODUCTION OF WILDLIFE AND TIMBER

EPA Science Inventory

Production of marketed commodities and protection of natural systems often conflict. A
focus on only one goal can result in large losses in other goals and may result in inefficient and
unsustainable outcomes. In this paper we develop a method that combines economic and
...
Probabilities of having minimum amounts of available soil water at wheat planting

USDA-ARS?s Scientific Manuscript database

Winter wheat (Triticum aestivum L.)-fallow (WF) remains a prominent cropping system throughout the Central Great Plains despite documentation confirming the inefficiency of precipitation storage during the second summer fallow period. Wheat yield is greatly influenced by available soil water at plan...
Correcting the thermal inefficiencies of a cogeneration and boiler plant by low-pressure steam conversions and hot water thermal energy storage

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

Pals, C.M.

1998-12-31

A liberal arts college in Los Angeles was plagued by inefficient use of low-pressure (LP) steam produced by its two 150 kWe cogeneration units. Poor integration of the LP cogen system into the college`s existing high-pressure (HP) steam boiler plant led to under-utilization of cogenerated steam during the non-space-heating season. Six years of inefficient operation was estimated to have cost the college $750,000 in lost utility and maintenance savings. To improve steam-plant operations, the college`s facilities management staff implemented a plan to convert HP steam loads to LP, replace HP steam boilers with LP equipment, and improve the use ofmore » cogenerated steam through the installation of a hot water thermal energy storage (TES) system. A study was commissioned that identified the plant`s peak winter steam requirements and the typical steam profile for the non-space-heating season. Data from this work helped draw two conclusions: (1) converting HP steam loads to LP would boost demand for cogenerated steam, and (2) a hot water thermal energy storage (TES) system could further utilize a portion of remaining excess cogen steam for the manufacture and storage of the kitchen`s domestic water for use during peak steam demand periods. Combined, these two measures were estimated to improve utilization of cogenerated LP steam by 11,000 pounds (5,000 kg) per day and reduce boiler fuel consumption by 40,000 therms (4,220,000 MJ) each season. In addition to this work, a major plant renovation project was completed, which included the replacement of a 60-year-old, 280 bhp (2,747 kW) HP steam boiler, with two new LP boilers. Conversion to LP and the start-up of the hot water TES was completed in May 1997. During the first year of operation, after the improvement, boiler gas savings exceeded 52,000 therms (5,486,000 MJ). Maintenance savings of $100,000 were also accrued by eliminating licensed HP boiler operators. All construction work described to improve energy efficiency and rehabilitate the steam plant cost $687,000 and is on track to produce a simple payback of 5.5 years. Overall, this paper demonstrates the energy and cost inefficiencies that may result if the opportunities to use waste heat from cogeneration systems are incorrectly identified.« less
AOIPS - An interactive image processing system. [Atmospheric and Oceanic Information Processing System

NASA Technical Reports Server (NTRS)

Bracken, P. A.; Dalton, J. T.; Quann, J. J.; Billingsley, J. B.

1978-01-01

The Atmospheric and Oceanographic Information Processing System (AOIPS) was developed to help applications investigators perform required interactive image data analysis rapidly and to eliminate the inefficiencies and problems associated with batch operation. This paper describes the configuration and processing capabilities of AOIPS and presents unique subsystems for displaying, analyzing, storing, and manipulating digital image data. Applications of AOIPS to research investigations in meteorology and earth resources are featured.
Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation.

PubMed

Paulmurugan, R; Gambhir, S S

2003-04-01

In this study we developed an inducible synthetic renilla luciferase protein-fragment-assisted complementation-based bioluminescence assay to quantitatively measure real time protein-protein interactions in mammalian cells. We identified suitable sites to generate fragments of N and C portions of the protein that yield significant recovered activity through complementation. We validate complementation-based activation of split synthetic renilla luciferase protein driven by the interaction of two strongly interacting proteins, MyoD and Id, in five different cell lines utilizing transient transfection studies. The expression level of the system was also modulated by tumor necrosis factor alpha through NFkappaB-promoter/enhancer elements used to drive expression of the N portion of synthetic renilla luciferase reporter gene. This new system should help in studying protein-protein interactions and when used with other split reporters (e.g., split firefly luciferase) should help to monitor different components of an intracellular network.
Monitoring Protein–Protein Interactions Using Split Synthetic Renilla Luciferase Protein-Fragment-Assisted Complementation

PubMed Central

Paulmurugan, R.; Gambhir, S. S.

2014-01-01

In this study we developed an inducible synthetic renilla luciferase protein-fragment-assisted complementation-based bioluminescence assay to quantitatively measure real time protein–protein interactions in mammalian cells. We identified suitable sites to generate fragments of N and C portions of the protein that yield significant recovered activity through complementation. We validate complementation-based activation of split synthetic renilla luciferase protein driven by the interaction of two strongly interacting proteins, MyoD and Id, in five different cell lines utilizing transient transfection studies. The expression level of the system was also modulated by tumor necrosis factor α through NFκB-promoter/enhancer elements used to drive expression of the N portion of synthetic renilla luciferase reporter gene. This new system should help in studying protein–protein interactions and when used with other split reporters (e.g., split firefly luciferase) should help to monitor different components of an intracellular network. PMID:12705589
Innate inflammatory gene expression profiling in potential brain-dead donors: detailed investigation of the effect of common corticosteroid therapy.

PubMed

Gholamnezhadjafari, Reza; Tajik, Nader; Falak, Reza; Aflatoonian, Reza; Dehghan, Sanaz; Rezaei, Abbas

2017-07-01

Our study aimed to assess the influence of common methylprednisolone therapy on innate inflammatory factors in potential brain-dead organ donors (BDDs). The study groups consisted of 50 potential BDDs who received 15 mg/kg/d methylprednisolone and 25 live organ donors (LDs) as control group. Innate immunity gene expression profiling was performed by RT-PCR array. Soluble serum cytokines and chemokines, complement components, heat shock protein 70 (HSP70) and high mobility group box-1 (HMGB1) were measured by ELISA. Surface expression of TLR2 and TLR4 were determined using flow cytometry. Gene expression profiling revealed up-regulation of TLRs 1, 2, 4, 5, 6, 7 and 8, MYD88, NF-κB, NF-κB1A, IRAK1, STAT3, JAK2, TNF-α, IL-1β, CD86 and CD14 in the BDD group. Remarkably, the serum levels of C-reactive protein and HSP70 were considerably higher in the BDD group. In addition, serum amounts of IL-1β, IL-6, TNF-α, HMGB1, HSP70, C3a and C5a, but not IL-8, sCD86 or monocyte chemoattractant protein-1, were significantly increased in the BDD group. Significant differences were observed in flow cytometry analysis of TLR2 and TLR4 between the two groups. In summary, common methylprednisolone therapy in BDDs did not adequately reduce systemic inflammation, which could be due to inadequate doses or inefficient impact on other inflammatory-inducing pathways, for example oxidative stress or production of damage-associated molecules.
Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: More than a gut feeling

PubMed Central

Severance, Emily G.; Yolken, Robert H.; Eaton, William W.

2014-01-01

Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders. PMID:25034760
Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling.

PubMed

Severance, Emily G; Yolken, Robert H; Eaton, William W

2016-09-01

Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders. Copyright © 2014 Elsevier B.V. All rights reserved.
C1q complement component and -antibodies reflect SLE activity and kidney involvement.

PubMed

Horák, P; Hermanová, Z; Zadrazil, J; Ciferská, H; Ordeltová, M; Kusá, L; Zurek, M; Tichý, T

2006-07-01

The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAM
Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy.

PubMed

Katschke, Kenneth J; Xi, Hongkang; Cox, Christian; Truong, Tom; Malato, Yann; Lee, Wyne P; McKenzie, Brent; Arceo, Rommel; Tao, Jianhua; Rangell, Linda; Reichelt, Mike; Diehl, Lauri; Elstrott, Justin; Weimer, Robby M; Campagne, Menno van Lookeren

2018-05-09

Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA. When exposed to human serum following outer blood-retinal barrier breakdown, POS act as potent activators of the classical and alternative complement pathway. In mouse models of retinal degeneration, classical and alternative pathway complement activation on photoreceptors contributed to the loss of photoreceptor function. This was dependent on C5a-mediated recruitment of peripheral blood monocytes but independent of resident microglia. Genetic or pharmacologic inhibition of both classical and alternative complement C3 and C5 convertases was required to reduce progressive degeneration of photoreceptor rods and cones. Our study implicates systemic classical and alternative complement proteins and peripheral blood monocytes as critical effectors of localized retinal degeneration with potential relevance for the contribution of complement activation to GA.
Contact interaction between a layered foundation and a system of annular punches with complex base shapes

NASA Astrophysics Data System (ADS)

Kazakov, K. E.; Kurdina, S. P.

2018-04-01

We study the contact interaction between a system of rigid annular punches and a viscoelastic two-layer foundation. The upper layer is thin compared with the punch width. We study the case where the punch shapes are described by a rapidly varying functions. We use special methods for constructing the solutions, because the standard methods are inefficient.
Genotypic and phenotypic diversity of Lactobacillus rhamnosus clinical isolates, their comparison with strain GG and their recognition by complement system

PubMed Central

Douillard, François P.; Ritari, Jarmo; Paulin, Lars; Järvinen, Hanna M.; Rasinkangas, Pia; Haapasalo, Karita; Meri, Seppo; Jarva, Hanna; de Vos, Willem M.

2017-01-01

Lactobacillus rhamnosus strains are ubiquitous in fermented foods, and in the human body where they are commensals naturally present in the normal microbiota composition of gut, vagina and skin. However, in some cases, Lactobacillus spp. have been implicated in bacteremia. The aim of the study was to examine the genomic and immunological properties of 16 clinical blood isolates of L. rhamnosus and to compare them to the well-studied L. rhamnosus probiotic strain GG. Blood cultures from bacteremic patients were collected at the Helsinki University Hospital laboratory in 2005–2011 and L. rhamnosus strains were isolated and characterized by genomic sequencing. The capacity of the L. rhamnosus strains to activate serum complement was studied using immunological assays for complement factor C3a and the terminal pathway complement complex (TCC). Binding of complement regulators factor H and C4bp was also determined using radioligand assays. Furthermore, the isolated strains were evaluated for their ability to aggregate platelets and to form biofilms in vitro. Genomic comparison between the clinical L. rhamnosus strains showed them to be clearly different from L. rhamnosus GG and to cluster in two distinct lineages. All L. rhamnosus strains activated complement in serum and none of them bound complement regulators. Four out of 16 clinical blood isolates induced platelet aggregation and/or formed more biofilms than L. rhamnosus GG, which did not display platelet aggregation activity nor showed strong biofilm formation. These findings suggest that clinical L. rhamnosus isolates show considerable heterogeneity but are clearly different from L. rhamnosus GG at the genomic level. All L. rhamnosus strains are still normally recognized by the human complement system. PMID:28493885
Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta

PubMed Central

Banadakoppa, M; Chauhan, M S; Havemann, D; Balakrishnan, M; Dominic, J S; Yallampalli, C

2014-01-01

Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto–maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion. PMID:24802103
Efficiency, cost-effectiveness and need of inversion in nutritional therapy. Importance of detecting and documenting undernutrition.

PubMed

Morán López, Jesús Manuel; Piedra León, María; Beneítez Moralejo, Belén; Enciso Izquierdo, Fidel Jesús; Luengo Pérez, Luis Miguel; Amado Señaris, José Antonio

2016-06-01

Disease Related Malnutrition (DRM) is highly prevalent in Spanish hospitals. WHO estimates that 20-40% of health-associated expenses are lost due to inefficiency. Demonstration that DRM is a component of inefficiency and hiring a specialist physician for its detection and treatment is cost-effective. Comparison between nutritional diagnosis and procedures detected and encoded at discharge using McNemar test. Recoding of 162 discharge reports including nutritional diagnoses and procedures. Determine changes on Case-Mix Index (IC), cost of procedure and cost procedure/DRG index. Comparison using T-student paired test. Only 10 of 162 diagnoses of malnutrition were coded in delivery statements (p < 0.001). After right codification, IC increased in 103,3 DRG points (p < 0.001). Consequently, procedure cost/DRG index was reduced in 978.81 € (p < 0.001). DRM is underdiagnosed in our hospital. DRM and nutritional procedures detection by a doctor specialist in clinical nutrition led to a reduction in cost procedure/DRG index of 16.8% of officially established by the Health System. Loss of 16.8% of health expenses, estimated in 424.785,15 € was described. Proper codification would have justified 343.291,2 € reimbursement just for nutritional diagnoses and processes. Both expenses were lost due to system's inefficiency. Those amounts are much higher than cost associated of hiring a specialist in clinical nutrition. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
[Efficiency, cost-effectiveness and justification of need for investment in nutrition therapy in a hospital of third level; the role of specialists in endocrinology and nutrition and the coding unit].

PubMed

Morán López, Jesús Manuel; Enciso Izquierdo, Fidel Jesús; Beneítez Moralejo, Belén; Luengo Pérez, Luis Miguel; Piedra León, María; Amado Señaris, José Antonio

2015-04-01

Disease Related Malnutrition (DRM) is highly prevalent in Spanish hospitals. WHO estimates that 20-40% of health-associated expenses are lost due to inefficiency. Demonstration that DRM is a component of inefficiency and hiring a specialist physician for its detection and treatment is cost-effective. Comparison between nutritional diagnosis and procedures detected and encoded at discharge using McNemar test. Recoding of 55 discharge reports including nutritional diagnoses and procedures. Determine changes on Case-Mix Index (IC), cost of procedure and cost procedure/GRD index. Comparison using Wilcoxon test. Only 2 of 55 diagnoses of malnutrition were coded in delivery statements (p<0,001). After right codification,IC increased in 42,67 GRD points (p<0,05). Consequently, procedure cost/GRD index was reduced in 976,81€ (p<0,05). DRM is underdiagnosed in our hospital. DRM and nutritional procedures detection by a specialist on endocrinology and nutrition led to a reduction in cost procedure/GRD index of 20% of officially established by the Health System. Loss of 20% of health expenses,estimated in 172690€ was described. Proper codification would have justified 154581€ reimbursement just for nutritional diagnoses and processes. Both expenses were lost due to system's inefficiency. Those amounts are much higher than cost associated of hiring a specialist, so there is no economic reason for denying it. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
Trends in hospital efficiency among metropolitan markets.

PubMed

Wang, B B; Ozcan, Y A; Wan, T T; Harrison, J

1999-04-01

This study evaluates trends in efficiency among American hospital markets. A total of 6010 hospitals were identified for use in the analysis from the American Hospital Association's Annual Surveys for 1989 and 1993. Using data envelopment analysis (DEA), a longitudinal study of hospital efficiency was conducted on all 314 metropolitan markets in the United States. Results suggest that large hospital markets generally demonstrated higher inefficiency. The major inefficiencies exist in the availability of hospital services, the number of operating beds, the utilization of hospital staffing and operating expenses. Consequently, the large hospital market had a significant excess of health manpower that resulted in inefficiency that amounted to approximately $23 billion. From a policy perspective, this study has shed some light on the need to establish more specific policies to address inefficiency in the health care industry.
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.
The Lectin Pathway of Complement and Rheumatic Heart Disease

PubMed Central

Beltrame, Marcia Holsbach; Catarino, Sandra Jeremias; Goeldner, Isabela; Boldt, Angelica Beate Winter; de Messias-Reason, Iara José

2014-01-01

The innate immune system is the first line of host defense against infection and is comprised of humoral and cellular mechanisms that recognize potential pathogens within minutes or hours of entry. The effector components of innate immunity include epithelial barriers, phagocytes, and natural killer cells, as well as cytokines and the complement system. Complement plays an important role in the immediate response against microorganisms, including Streptococcus sp. The lectin pathway is one of three pathways by which the complement system can be activated. This pathway is initiated by the binding of mannose-binding lectin (MBL), collectin 11 (CL-K1), and ficolins (Ficolin-1, Ficolin-2, and Ficolin-3) to microbial surface oligosaccharides and acetylated residues, respectively. Upon binding to target molecules, MBL, CL-K1, and ficolins form complexes with MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2), which cleave C4 and C2 forming the C3 convertase (C4b2a). Subsequent activation of complement cascade leads to opsonization, phagocytosis, and lysis of target microorganisms through the formation of the membrane-attack complex. In addition, activation of complement may induce several inflammatory effects, such as expression of adhesion molecules, chemotaxis and activation of leukocytes, release of reactive oxygen species, and secretion of cytokines and chemokines. In this chapter, we review the general aspects of the structure, function, and genetic polymorphism of lectin-pathway components and discuss most recent understanding on the role of the lectin pathway in the predisposition and clinical progression of Rheumatic Fever. PMID:25654073
SELF-CONTAINED HUMAN AND SOLAR POWERED LED LIGHTING SYSTEM FOR USE IN THE DEVELOPING WORLD

EPA Science Inventory

Approximately 49% of rural households and 14% of urban households in developing nations live without electricity, most of who rely by fuel-based lamps which are inefficient, costly to operate, and produce large amounts of potentially harmful byproducts and green house gas emis...

Thinking about Tax Reform.

ERIC Educational Resources Information Center

Boskin, Michael J.

1985-01-01

Providing pre-college teachers with an analysis of tax reform is the primary goal of this publication. The present tax system is both inefficient and inequitable. Three goals of tax reform proposals are detailed: (1) fairness--the dimensions of horizontal equity, or equal treatment of equals however defined, and vertical equity, reflecting the…
Nitrogen Fertilizer Dependency and Its Contradictions: A Theoretical Exploration of Social-Ecological Metabolism

ERIC Educational Resources Information Center

Mancus, Philip

2007-01-01

The global agro-food system relies heavily on inorganic nitrogenous fertilizers. In addition to consuming enormous amounts of energy, this manufactured input contributes to the accumulation of reactive nitrogen in the biosphere and undermines the biological basis of agricultural production itself. While technological inefficiency and population…
ALTERNATIVE PUBLIC SCHOOL SYSTEMS--A RESPONSE TO AMERICA'S EDUCATIONAL EMERGENCY.

ERIC Educational Resources Information Center

CLARK, KENNETH B.

AMERICAN PUBLIC EDUCATION HAS BEEN INEFFICIENT AND UNEQUAL AND HAS EFFECTIVELY BLOCKED ECONOMIC AND SOCIAL MOBILITY FOR NEGROES. CHANGE AND IMPROVEMENT HAVE BEEN IMPEDED BY DOGMAS ABOUT THE INVIOLABILITY OF THE NEIGHBORHOOD SCHOOL, BY ADMINISTRATIVE BARRIERS, AND BY DEEP-SEATED PSYCHOLOGICAL PREJUDICES. COMPENSATORY EDUCATION PROGRAMS IN…
Improving hospital billing and receivables management: principles for profitability.

PubMed

Hemmer, E

1992-01-01

For many hospitals, billing and receivables management are inefficient and costly. Economic recession, increasing costs for patient and provider alike, and cost-containment strategies will only compound difficulties. The author describes the foundations of an automated billing system that would save hospitals time, error, and, most importantly, money.
An efficient nontraditional method of directly converting a cotton fibrous material into a woven-like hydroentangled nonwoven cotton fabric

USDA-ARS?s Scientific Manuscript database

The traditional technology of producing cotton woven fabrics is comprised of about 20 mechanical and chemical processes that generally are costly, slow, inefficient, and environmentally somewhat unfriendly. A modern system, using fewer preparatory processes, of fabricating hydro-entangled cotton and...
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.
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.
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.
European health policy challenges.

PubMed

Maynard, Alan

2005-09-01

Few countries are immune to the international health care 'virus' of reform, with many countries regularly re-cycling changes that shift costs and benefits in ways that are arbitrary, inefficient and offer short term political palliation. Much of this activity has little evidence base and reveals lack of clarity in defining public policy goals, establishing trade-offs and aligning incentive structures with these objectives. Well established failures in health care delivery systems such as variations in medical practice and continuing absence of systematic outcome measurement, have persisted for decades as nations grapple inefficiently with recurring problems of expenditure inflation and waiting times. The lack of emphasis on evidence to inform the efficient management of chronic disease and the reduction of health inequalities is a product of perverse incentives and managerial inertia that maintains the incomes of powerful interest groups. Copyright (c) 2005 John Wiley & Sons, Ltd.
Toward allocative efficiency in the prescription drug industry.

PubMed

Guell, R C; Fischbaum, M

1995-01-01

Traditionally, monopoly power in the pharmaceutical industry has been measured by profits. An alternative method estimates the deadweight loss of consumer surplus associated with the exercise of monopoly power. Although upper and lower bound estimates for this inefficiency are far apart, they at least suggest a dramatically greater welfare loss than measures of industry profitability would imply. A proposed system would have the U.S. government employing its power of eminent domain to "take" and distribute pharmaceutical patents, providing as "just compensation" the present value of the patent's expected future monopoly profits. Given the allocative inefficiency of raising taxes to pay for the program, the impact of the proposal on allocative efficiency would be at least as good at our lower bound estimate of monopoly costs while substantially improving efficiency at or near our upper bound estimate.
Measuring the efficiency of a healthcare waste management system in Serbia with data envelopment analysis.

PubMed

Ratkovic, Branislava; Andrejic, Milan; Vidovic, Milorad

2012-06-01

In 2007, the Serbian Ministry of Health initiated specific activities towards establishing a workable model based on the existing administrative framework, which corresponds to the needs of healthcare waste management throughout Serbia. The objective of this research was to identify the reforms carried out and their outcomes by estimating the efficiencies of a sample of 35 healthcare facilities engaged in the process of collection and treatment of healthcare waste, using data envelopment analysis. Twenty-one (60%) of the 35 healthcare facilities analysed were found to be technically inefficient, with an average level of inefficiency of 13%. This fact indicates deficiencies in the process of collection and treatment of healthcare waste and the information obtained and presented in this paper could be used for further improvement and development of healthcare waste management in Serbia.
New Milestones Ahead in Complement-Targeted Therapy

PubMed Central

Ricklin, Daniel; Lambris, John D.

2017-01-01

The complement system is a powerful effector arm of innate immunity that typically confers protection from microbial intruders and accumulating debris. In many clinical situations, however, the defensive functions of complement can turn against host cells and induce or exacerbate immune, inflammatory, and degenerative conditions. Although the value of inhibiting complement in a therapeutic context has long been recognized, bringing complement-targeted drugs into clinical use has proved challenging. This important milestone was finally reached a decade ago, yet the clinical availability of complement inhibitors has remained limited. Still, the positive long-term experience with complement drugs and their proven effectiveness in various diseases has reinvigorated interest and confidence in this approach. Indeed, a broad variety of clinical candidates that act at almost any level of the complement activation cascade are currently in clinical development, with several of them being evaluated in phase 2 and phase 3 trials. With antibody-related drugs dominating the panel of clinical candidates, the emergence of novel small-molecule, peptide, protein, and oligonucleotide-based inhibitors offers new options for drug targeting and administration. Whereas all the currently approved and many of the proposed indications for complement-targeted inhibitors belong to the rare disease spectrum, these drugs are increasingly being evaluated for more prevalent conditions. Fortunately, the growing experience from preclinical and clinical use of therapeutic complement inhibitors has enabled a more evidence-based assessment of suitable targets and rewarding indications as well as related technical and safety considerations. This review highlights recent concepts and developments in complement-targeted drug discovery, provides an overview of current and emerging treatment options, and discusses the new milestones ahead on the way to the next generation of clinically available complement therapeutics. PMID:27321574
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.
Exploring the Impact of Fuel Data Acquisition Technology on the USMC Expeditionary Energy Command and Control System

DTIC Science & Technology

2016-09-01

suggested interventions that may reduce inefficient energy practices (Salem & Gallenson, 2014). The E2O selected a commercial-off-the-shelf (COTS) wireless ...IMPACT OF FUEL DATA ACQUISITION TECHNOLOGY ON THE USMC EXPEDITIONARY ENERGY COMMAND AND CONTROL SYSTEM by Jeremy F. Thomas September 2016...ON THE USMC EXPEDITIONARY ENERGY COMMAND AND CONTROL SYSTEM 5. FUNDING NUMBERS 6. AUTHOR(S) Jeremy F. Thomas 7. PERFORMING ORGANIZATION NAME(S
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
On the security flaws in ID-based password authentication schemes for telecare medical information systems.

PubMed

Mishra, Dheerendra

2015-01-01

Telecare medical information systems (TMIS) enable healthcare delivery services. However, access of these services via public channel raises security and privacy issues. In recent years, several smart card based authentication schemes have been introduced to ensure secure and authorized communication between remote entities over the public channel for the (TMIS). We analyze the security of some of the recently proposed authentication schemes of Lin, Xie et al., Cao and Zhai, and Wu and Xu's for TMIS. Unfortunately, we identify that these schemes failed to satisfy desirable security attributes. In this article we briefly discuss four dynamic ID-based authentication schemes and demonstrate their failure to satisfy desirable security attributes. The study is aimed to demonstrate how inefficient password change phase can lead to denial of server scenario for an authorized user, and how an inefficient login phase causes the communication and computational overhead and decrease the performance of the system. Moreover, we show the vulnerability of Cao and Zhai's scheme to known session specific temporary information attack, vulnerability of Wu and Xu's scheme to off-line password guessing attack, and vulnerability of Xie et al.'s scheme to untraceable on-line password guessing attack.
Neuromuscular electrical stimulation induced brain patterns to decode motor imagery.

PubMed

Vidaurre, C; Pascual, J; Ramos-Murguialday, A; Lorenz, R; Blankertz, B; Birbaumer, N; Müller, K-R

2013-09-01

Regardless of the paradigm used to implement a brain-computer interface (BCI), all systems suffer from BCI-inefficiency. In the case of patients the inefficiency can be high. Some solutions have been proposed to overcome this problem, however they have not been completely successful yet. EEG from 10 healthy users was recorded during neuromuscular electrical stimulation (NMES) of hands and feet and during motor imagery (MI) of the same limbs. Features and classifiers were computed using part of these data to decode MI. Offline analyses showed that it was possible to decode MI using a classifier based on afferent patterns induced by NMES and even infer a better model than with MI data. Afferent NMES motor patterns can support the calibration of BCI systems and be used to decode MI. This finding might be a new way to train sensorimotor rhythm (SMR) based BCI systems for healthy users having difficulties to attain BCI control. It might also be an alternative to train MI-based BCIs for users who cannot perform real movements but have remaining afferents (ALS, stroke patients). Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
What does free cash flow tell us about hospital efficiency? A stochastic frontier analysis of cost inefficiency in California hospitals.

PubMed

Pratt, William R

2010-01-01

Hospitals are facing substantial financial and economic pressure as a result of health plan payment restructuring, unfunded mandates, and other factors. This article analyzes the relationship between free cash flow (FCF) and hospital efficiency given these financial challenges. Data from 270 California hospitals were used to estimate a stochastic frontier model of hospital cost efficiency that explicitly takes into account outpatient heterogeneity. The findings indicate that hospital FCF is significantly linked to firm efficiency/inefficiency. The results indicate that higher positive cash flows are related to lower cost inefficiency, but higher negative cash flows are related to higher cost inefficiency. Thus, cash flows not only impact the ability of hospitals to meet current liabilities, they are also related to the ability of the hospitals to use resources effectively.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

PubMed

Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

2015-11-01

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Structure of C3b reveals conformational changes that underlie complement activity.

PubMed

Janssen, Bert J C; Christodoulidou, Agni; McCarthy, Andrew; Lambris, John D; Gros, Piet

2006-11-09

Resistance to infection and clearance of cell debris in mammals depend on the activation of the complement system, which is an important component of innate and adaptive immunity. Central to the complement system is the activated form of C3, called C3b, which attaches covalently to target surfaces to amplify complement response, label cells for phagocytosis and stimulate the adaptive immune response. C3b consists of 1,560 amino-acid residues and has 12 domains. It binds various proteins and receptors to effect its functions. However, it is not known how C3 changes its conformation into C3b and thereby exposes its many binding sites. Here we present the crystal structure at 4-A resolution of the activated complement protein C3b and describe the conformational rearrangements of the 12 domains that take place upon proteolytic activation. In the activated form the thioester is fully exposed for covalent attachment to target surfaces and is more than 85 A away from the buried site in native C3 (ref. 5). Marked domain rearrangements in the alpha-chain present an altered molecular surface, exposing hidden and cryptic sites that are consistent with known putative binding sites of factor B and several complement regulators. The structural data indicate that the large conformational changes in the proteolytic activation and regulation of C3 take place mainly in the first conversion step, from C3 to C3b. These insights are important for the development of strategies to treat immune disorders that involve complement-mediated inflammation.
Complement anaphylatoxins as immune regulators in cancer.

PubMed

Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

2014-08-01

The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediated suppression of immune effector cells responsible for immunosurveillance within the tumor microenvironment. This paradigm accords with models of immune dysregulation, such as autoimmunity and infectious disease, which have defined a pathophysiological role for abnormal complement signaling. Several types of immune cells express the cognate receptors for the complement anaphylatoxins, C3aR and C5aR, and demonstrate functional modulation in response to complement stimulation. In turn, impairment of antitumor immunity has been intimately tied to tumor progression in animal models of cancer. In this article, the literature was systematically reviewed to identify studies that have characterized the effects of the complement anaphylatoxins on the composition and function of immune cells within the tumor microenvironment. The search identified six studies based upon models of lymphoma and ovarian, cervical, lung, breast, and mammary cancer, which collectively support the paradigm of complement as an immune regulator in the tumor microenvironment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Hypothesis tests for the detection of constant speed radiation moving sources

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

Dumazert, Jonathan; Coulon, Romain; Kondrasovs, Vladimir

2015-07-01

Radiation Portal Monitors are deployed in linear network to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal to noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes amore » benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive background, and a vehicle source carrier under the same respectively high and low count rate radioactive background, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm, while guaranteeing the stability of its optimization parameter regardless of signal to noise ratio variations between 2 to 0.8. (authors)« less
Epidemiological monitoring for emerging infectious diseases

NASA Astrophysics Data System (ADS)

Greene, Marjorie

2010-04-01

The Homeland Security News Wire has been reporting on new ways to fight epidemics using digital tools such as iPhone, social networks, Wikipedia, and other Internet sites. Instant two-way communication now gives consumers the ability to complement official reports on emerging infectious diseases from health authorities. However, there is increasing concern that these communications networks could open the door to mass panic from unreliable or false reports. There is thus an urgent need to ensure that epidemiological monitoring for emerging infectious diseases gives health authorities the capability to identify, analyze, and report disease outbreaks in as timely and efficient a manner as possible. One of the dilemmas in the global dissemination of information on infectious diseases is the possibility that information overload will create inefficiencies as the volume of Internet-based surveillance information increases. What is needed is a filtering mechanism that will retrieve relevant information for further analysis by epidemiologists, laboratories, and other health organizations so they are not overwhelmed with irrelevant information and will be able to respond quickly. This paper introduces a self-organizing ontology that could be used as a filtering mechanism to increase relevance and allow rapid analysis of disease outbreaks as they evolve in real time.
Battery model for electrical power system energy balance

NASA Technical Reports Server (NTRS)

Hafen, D. P.

1983-01-01

A model to simulate nickel-cadmium battery performance and response in a spacecraft electrical power system energy balance calculation was developed. The voltage of the battery is given as a function of temperature, operating depth-of-charge (DOD), and battery state-of-charge. Also accounted for is charge inefficiency. A battery is modeled by analysis of the results of a multiparameter battery cycling test at various temperatures and DOD's.
Avoiding Another Hollow Force: Optimizing the Joint Force Despite Sequestration

DTIC Science & Technology

2013-04-01

Vietnam, socio-economic factors and funding decisions that favored the development of advanced weapon systems rather than funding other vital requirements...funding decisions that favored the development of advanced weapon systems rather than funding other vital requirements such as manpower led to the...to factors such as inefficiencies in production, $29.6 billion to quantity changes, and $13.7 billion to research and development (R&D) cost growth
Balancing Hydronic Systems in Multifamily Buildings

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

Ruch, Russell; Ludwig, Peter; Maurer, Tessa

2014-07-01

In multifamily hydronic systems, temperature imbalance may be caused by undersized piping, improperly adjusted balancing valves, inefficient water temperature and flow levels, and owner/occupant interaction with the boilers, distribution, and controls. The imbalance leads to tenant discomfort, higher energy use intensity, and inefficient building operation. This research, conducted by Building America team Partnership for Advanced Residential Retrofit, explores cost-effective distribution upgrades and balancing measures in multifamily hydronic systems, providing a resource to contractors, auditors, and building owners on best practices to improve tenant comfort and lower operating costs. The team surveyed existing knowledge on cost-effective retrofits for optimizing distribution inmore » typical multifamily hydronic systems, with the aim of identifying common situations and solutions, and then conducted case studies on two Chicago area buildings with known balancing issues in order to quantify the extent of temperature imbalance. At one of these buildings a booster pump was installed on a loop to an underheated wing of the building. This study found that unit temperature in a multifamily hydronic building can vary as much as 61°F, particularly if windows are opened or tenants use intermittent supplemental heating sources like oven ranges. Average temperature spread at the building as a result of this retrofit decreased from 22.1°F to 15.5°F.« less
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.
Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

PubMed

Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

2018-01-04

Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.
Visceral perfusion abnormalities following complement activation. Clues to the mediators of organ ischemia in trauma and sepsis. First place winner: Conrad Jobst Award.

PubMed

Schirmer, W J; Schirmer, J M; Naff, G B; Fry, D E

1988-12-01

Complement, activated during infection and injury, has been implicated as a mediator of microvascular injury and obstruction. This study examines how two potent activators of complement, zymosan, and cobra venom factor (CVF), affect systemic and visceral perfusion. Rats were injected with either saline (1 ml/kg), zymosan (5 mg/kg) or CVF (5 units/kg) at t = 0 and 30 minutes. Thermodilution cardiac output, mean arterial pressure, heart rate, systemic vascular resistance, and hematocrit were determined at t = 2 hours. Effective hepatic and renal blood flows, by clearance of galactose and p-aminohippurate respectively, were determined over the next hour. The per cent change in total hemolytic complement from t = 0 to t = 3 hours was determined by immune hemolysis of sheep erythrocytes. There was no difference in systemic hemodynamic parameters between the three groups. Hepatic blood flow was depressed in both the zymosan (3.83 +/- 0.23 ml/min/100 g) and CVF (3.72 +/- 0.20 ml/min/100 g) groups compared with controls (4.62 +/- 0.19 ml/min/100 g, P less than 0.05). Renal blood flow in the zymosan-treated group (6.40 +/- 0.24 ml/min/100 g) increased over control (4.80 +/- 0.40 ml/min/100 g, P less than 0.05) but was unchanged in the CVF group (5.06 +/- 0.23 ml/min/100 g). The amount of complement activated correlated with the change in hepatic (r = -0.419, P less than 0.05) but not renal (r = -0.008, P = 0.917) flow. Complement activation may occupy a proximal position in the pathogenesis of hepatic ischemia associated with trauma and sepsis.
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.
Dimeric, trimeric and tetrameric complexes of immunoglobulin G fix complement.

PubMed Central

Wright, J K; Tschopp, J; Jaton, J C; Engel, J

1980-01-01

The binding of pure dimers, trimers and tetramers of randomly cross-linked non-immune rabbit immunoglobulin G to the first component and subcomponent of the complement system, C1 and C1q respectively, was studied. These oligomers possessed open linear structures. All three oligomers fixed complement with decreasing affinity in the order: tetramer, trimer, dimer. Complement fixation by dimeric immunoglobulin exhibited the strongest concentration-dependence. No clear distinction between a non-co-operative and a co-operative binding mechanism could be achieved, although the steepness of the complement-fixation curves for dimers and trimers was better reflected by the co-operative mechanism. Intrinsic binding constants were about 10(6)M-1 for dimers, 10(7)M-1 for trimers and 3 X 10(9)M-1 for tetramers, assuming non-co-operative binding. The data are consistent with a maximum valency of complement component C1 for immunoglobulin G protomers in the range 6-18. The binding of dimers to purified complement subcomponent C1q was demonstrated by sedimentation-velocity ultracentrifugation. Mild reduction of the complexes by dithioerythritol caused the immunoglobulin to revert to the monomeric state (S20,w = 6.2-6.5S) with concomitant loss of complement-fixing ability. Images Fig. 2. PMID:6985362
More than just immune evasion: Hijacking complement by Plasmodium falciparum.

PubMed

Schmidt, Christoph Q; Kennedy, Alexander T; Tham, Wai-Hong

2015-09-01

Malaria remains one of the world's deadliest diseases. Plasmodium falciparum is responsible for the most severe and lethal form of human malaria. P. falciparum's life cycle involves two obligate hosts: human and mosquito. From initial entry into these hosts, malaria parasites face the onslaught of the first line of host defence, the complement system. In this review, we discuss the complex interaction between complement and malaria infection in terms of hosts immune responses, parasite survival and pathogenesis of severe forms of malaria. We will focus on the role of complement receptor 1 and its associated polymorphisms in malaria immune complex clearance, as a mediator of parasite rosetting and as an entry receptor for P. falciparum invasion. Complement evasion strategies of P. falciparum parasites will also be highlighted. The sexual forms of the malaria parasites recruit the soluble human complement regulator Factor H to evade complement-mediated killing within the mosquito host. A novel evasion strategy is the deployment of parasite organelles to divert complement attack from infective blood stage parasites. Finally we outline the future challenge to understand the implications of these exploitation mechanisms in the interplay between successful infection of the host and pathogenesis observed in severe malaria. Copyright © 2015 Elsevier Ltd. All rights reserved.
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
Possible Economies in Air-Conditioning by Accepting Temperature Swings.

ERIC Educational Resources Information Center

Loudon, A. G.; Petherbridge, P.

Public building air conditioning systems, which use constant and varying heat and cooling loads, are compared and investigated. Experiments indicated that constant temperature controls based on outside air temperature alone were inefficient. Ventilating a building with outside air and the methods of doing so are cited as being the most economical…
Evaluating Educational Efficiency in Texas Schools Utilizing Data Envelopment Analysis

ERIC Educational Resources Information Center

Thompson, Jeremy

2017-01-01

Policymakers and professional educators attempt to be good stewards of public funds while simultaneously raising expectations for student outcomes that reflect academic excellence in the public school system. The purpose of this study was to determine the efficiency of Texas public school districts and the factors influencing the inefficiency of…
Replacing fallow with forage triticale in dryland crop rotations increases profitability

USDA-ARS?s Scientific Manuscript database

A common dryland rotational cropping system in the semi-arid central Great Plains of the U.S. is wheat (Triticum aestivum L.)-corn (Zea mays L.)-fallow (WCF). However, the 12-month fallow period following corn production has been shown to be relatively inefficient in storing precipitation during the...
Cloud-Based Data Storage

ERIC Educational Resources Information Center

Waters, John K.

2011-01-01

The vulnerability and inefficiency of backing up data on-site is prompting school districts to switch to more secure, less troublesome cloud-based options. District auditors are pushing for a better way to back up their data than the on-site, tape-based system that had been used for years. About three years ago, Hendrick School District in…
Thermodynamic Inefficiency of Conversion of Solar Energy to Work.

ERIC Educational Resources Information Center

Adamson, Arthur W.; And Others

1984-01-01

Considers the thermodynamic limitation to the efficiency with which light energy can be converted into work, indicating that no single chemical system converting solar energy into useful work can be very efficient. Also indicates that if solar energy is absorbed as heat for heating purposes, it is almost completely used. (JN)

The Concept of "Talent Loss" in Educational Theory and Research

ERIC Educational Resources Information Center

Sikora, Joanna; Saha, Lawrence J.

2011-01-01

The purpose of this article is to review and revitalize the concept of "talent loss" in educational theory and research. It is our contention that the concept, while it has had a long and varied history among educational researchers, has recently surfaced and is providing useful insights into inefficiencies in educational systems, which…
Two essays on efficiency in the electric power industry: Measurement of technical and allocative efficiency

NASA Astrophysics Data System (ADS)

Gardiner, John Corby

The electric power industry market structure has changed over the last twenty years since the passage of the Public Utility Regulatory Policies Act (PURPA). These changes include the entry by unregulated generator plants and, more recently, the deregulation of entry and price in the retail generation market. Such changes have introduced and expanded competitive forces on the incumbent electric power plants. Proponents of this deregulation argued that the enhanced competition would lead to a more efficient allocation of resources. Previous studies of power plant technical and allocative efficiency have failed to measure technical and allocative efficiency at the plant level. In contrast, this study uses panel data on 35 power plants over 59 years to estimate technical and allocative efficiency of each plant. By using a flexible functional form, which is not constrained by the assumption that regulation is constant over the 59 years sampled, the estimation procedure accounts for changes in both state and national regulatory/energy policies that may have occurred over the sample period. The empirical evidence presented shows that most of the power plants examined have operated more efficiently since the passage of PURPA and the resultant increase of competitive forces. Chapter 2 extends the model used in Chapter 1 and clarifies some issues in the efficiency literature by addressing the case where homogeneity does not hold. A more general model is developed for estimating both input and output inefficiency simultaneously. This approach reveals more information about firm inefficiency than the single estimation approach that has previously been used in the literature. Using the more general model, estimates are provided on the type of inefficiency that occurs as well as the cost of inefficiency by type of inefficiency. In previous studies, the ranking of firms by inefficiency has been difficult because of the cardinal and ordinal differences between different types of inefficiency estimates. However, using the general approach, this study illustrates that plants can be ranked by overall efficiency.
Allocentric but not egocentric visual memory difficulties in adults with ADHD may represent cognitive inefficiency.

PubMed

Brown, Franklin C; Roth, Robert M; Katz, Lynda J

2015-08-30

Attention Deficit Hyperactivity Disorder (ADHD) has often been conceptualized as arising executive dysfunctions (e.g., inattention, defective inhibition). However, recent studies suggested that cognitive inefficiency may underlie many ADHD symptoms, according to reaction time and processing speed abnormalities. This study explored whether a non-timed measure of cognitive inefficiency would also be abnormal. A sample of 23 ADHD subjects was compared to 23 controls on a test that included both egocentric and allocentric visual memory subtests. A factor analysis was used to determine which cognitive variables contributed to allocentric visual memory. The ADHD sample performed significantly lower on the allocentric but not egocentric conditions. Allocentric visual memory was not associated with timed, working memory, visual perception, or mental rotation variables. This paper concluded by discussing how these results supported a cognitive inefficiency explanation for some ADHD symptoms, and discussed future research directions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Inhibitor(s) of the classical complement pathway in mouse serum limit the utility of mice as experimental models of neuromyelitis optica.

PubMed

Ratelade, Julien; Verkman, A S

2014-11-01

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system in which anti-aquaporin-4 (AQP4) autoantibodies (AQP4-IgG) cause damage to astrocytes by complement-dependent cytotoxicity (CDC). Various approaches have been attempted to produce NMO lesions in rodents, some involving genetically modified mice with altered immune cell function. Here, we found that mouse serum strongly inhibits complement from multiple species, preventing AQP4-IgG-dependent CDC. Effects of mouse serum on complement activation were tested in CDC assays in which AQP4-expressing cells were incubated with AQP4-IgG and complement from different species. Biochemical assays and mass spectrometry were used to characterize complement inhibitor(s) in mouse serum. Sera from different strains of mice produced almost no AQP4-IgG-dependent CDC compared with human, rat and guinea pig sera. Remarkably, addition of mouse serum prevented AQP4-IgG-dependent CDC caused by human, rat or guinea pig serum, with 50% inhibition at <5% mouse serum. Hemolysis assays indicated that the inhibitor(s) in mouse serum target the classical and not the alternative complement pathway. We found that the complement inhibitor(s) in mouse serum were contained in a serum fraction purified with protein-A resin; however, the inhibitor was not IgG as determined using serum from IgG-deficient mice. Mass spectrometry on the protein A-purified fraction produced several inhibitor candidates. The low intrinsic complement activity of mouse serum and the presence of complement inhibitor(s) limit the utility of mouse models to study disorders, such as NMO, involving the classical complement pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.
Cell-derived microparticles and complement activation in preeclampsia versus normal pregnancy.

PubMed

Biró, E; Lok, C A R; Hack, C E; van der Post, J A M; Schaap, M C L; Sturk, A; Nieuwland, R

2007-01-01

Inflammation plays a major role in the vascular dysfunction seen in preeclampsia, and several studies suggest involvement of the complement system. To investigate whether complement activation on the surface of microparticles is increased in plasma of preeclamptic patients versus healthy pregnant controls. Microparticles from plasma of preeclamptic (n=10), healthy pregnant (n=10) and healthy nonpregnant (n=10) women were analyzed 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). Fluid phase complement activation products and activator molecules were also determined. Levels of microparticles with bound complement components showed no increase in complement activation on the microparticle surface in preeclamptic women, in line with levels of fluid phase complement activation products. In healthy nonpregnant and pregnant women, bound CRP was associated with classical pathway activation on the microparticle surface, and in healthy pregnant women IgM and IgG molecules also contributed. In preeclamptic women, microparticles with bound SAP and those with IgG seemed to contribute to C1q binding without a clear association to further classical pathway activation. Furthermore, significantly increased levels of microparticles with bound CRP were present in preeclamptic compared with healthy pregnant women (median 178x10(6)/L versus 47x10(6)/L, P<0.01), but without concomitant increases in complement activation. We found no evidence of increased complement activation on the microparticle surface in preeclamptic women. Microparticles with bound CRP were significantly increased, but in contrast to healthy pregnant and nonpregnant women, this was not associated with increased classical pathway activation on the surface of the microparticles.
Differential mechanisms of complement-mediated neutralization of the closely related paramyxoviruses simian virus 5 and mumps virus

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

Johnson, John B.; Capraro, Gerald A.; Parks, Griffith D.

2008-06-20

The complement system is an important component of the innate immune response to virus infection. The role of human complement pathways in the in vitro neutralization of three closely related paramyxoviruses, Simian Virus 5 (SV5), Mumps virus (MuV) and Human Parainfluenza virus type 2 (HPIV2) was investigated. Sera from ten donors showed high levels of neutralization against HPIV2 that was largely complement-independent, whereas nine of ten donor sera were found to neutralize SV5 and MuV only in the presence of active complement pathways. SV5 and MuV neutralization proceeded through the alternative pathway of the complement cascade. Electron microscopy studies andmore » biochemical analyses showed that treatment of purified SV5 with human serum resulted in C3 deposition on virions and the formation of massive aggregates, but there was relatively little evidence of virion lysis. Treatment of MuV with human serum also resulted in C3 deposition on virions, however in contrast to SV5, MuV particles were lysed by serum complement and there was relatively little aggregation. Assays using serum depleted of complement factors showed that SV5 and MuV neutralization in vitro was absolutely dependent on complement factor C3, but was not dependent on downstream complement factors C5 or C8. Our results indicate that even though antibodies exist that recognize both SV5 and MuV, they are mostly non-neutralizing and viral inactivation in vitro occurs through the alternative pathway of complement. The implications of our work for development of paramyxovirus vectors and vaccines are discussed.« less
Anticomplementary activity of horse IgG and F(ab')2 antivenoms.

PubMed

Squaiella-Baptistão, Carla Cristina; Marcelino, José Roberto; Ribeiro da Cunha, Luiz Eduardo; Gutiérrez, José María; Tambourgi, Denise V

2014-03-01

Envenomation by poisonous animals is a neglected condition according to the World Health Organization (WHO). Antivenoms are included in the WHO Essential Medicines List. It has been assumed that immunoglobulin G (IgG) antivenoms could activate the complement system through Fc and induce early adverse reactions (EARs). However, data in the literature indicate that F(ab')2 fragments can also activate the complement system. Herein, we show that several batches of IgG and F(ab')2 antivenoms from the Butantan, Vital Brazil, and Clodomiro Picado Institutes activated the complement classical pathway and induced the production of C3a; however, only those antivenoms from Clodomiro Picado generated C5a. Different protein profiles (IgG heavy chain, protein contaminants, and aggregates) were observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analyses. Our results show that various antivenoms from different producers are able to activate the classical pathway of the complement system and generate anaphylatoxins, and these findings suggest that factors, such as composition, contaminant proteins, and aggregates, may influence the anticomplementary activity of antivenoms in vitro. Therefore, there is a need to further improve antivenom production methods to reduce their anticomplementary activity and potential to cause EARs.
The role of complement system in septic shock.

PubMed

Charchaflieh, Jean; Wei, Jiandong; Labaze, Georges; Hou, Yunfang Joan; Babarsh, Benjamin; Stutz, Helen; Lee, Haekyung; Worah, Samrat; Zhang, Ming

2012-01-01

Septic shock is a critical clinical condition with a high mortality rate. A better understanding of the underlying mechanisms is important to develop effective therapies. Basic and clinical studies suggest that activation of complements in the common cascade, for example, complement component 3 (C3) and C5, is involved in the development of septic shock. The involvement of three upstream complement pathways in septic shock is more complicated. Both the classical and alternative pathways appear to be activated in septic shock, but the alternative pathway may be activated earlier than the classical pathway. Activation of these two pathways is essential to clear endotoxin. Recent investigations have shed light on the role of lectin complement pathway in septic shock. Published reports suggest a protective role of mannose-binding lectin (MBL) against sepsis. Our preliminary study of MBL-associated serine protease-2 (MASP-2) in septic shock patients indicated that acute decrease of MASP-2 in the early phase of septic shock might correlate with in-hospital mortality. It is unknown whether excessive activation of these three upstream complement pathways may contribute to the detrimental effects in septic shock. This paper also discusses additional complement-related pathogenic mechanisms and intervention strategies for septic shock.
Coagulation and complement system in critically ill patients.

PubMed

Helling, H; Stephan, B; Pindur, G

2015-01-01

Activation of coagulation and inflammatory response including the complement system play a major role in the pathogenesis of critical illness. However, only limited data are available addressing the relationship of both pathways and its assessment of a predictive value for the clinical outcome in intense care medicine. Therefore, parameters of the coagulation and complement system were studied in patients with septicaemia and multiple trauma regarded as being exemplary for critical illness. 34 patients (mean age: 51.38 years (±16.57), 15 females, 19 males) were investigated at day 1 of admittance to the intensive care unit (ICU). Leukocytes, complement factors C3a and C5a were significantly (p < 0.0500) higher in sepsis than in trauma, whereas platelet count and plasma fibrinogen were significantly lower in multiple trauma. Activation markers of coagulation were elevated in both groups, however, thrombin-antithrombin-complex was significantly higher in multiple trauma. DIC scores of 5 were not exceeded in any of the two groups. Analysing the influences on mortality (11/34; 32.35% ), which was not different in both groups, non-survivors were significantly older, had significantly higher multiple organ failure (MOF) scores, lactate, abnormal prothrombin times and lower C1-inhibitor activities, even more pronounced in early deaths, than survivors. In septic non-survivors protein C was significantly lower than in trauma. We conclude from these data that activation of the complement system as part of the inflammatory response is a significant mechanism in septicaemia, whereas loss and consumption of blood components including parts of the coagulation and complement system is more characteristic for multiple trauma. Protein C in case of severe reduction might be of special concern for surviving in sepsis. Activation of haemostasis was occurring in both diseases, however, overt DIC was not confirmed in this study to be a leading mechanism in critically ill patients. MOF score, lactate, C1-inhibitor and prothrombin time have been the only statistically significant predictors for lethal outcome suggesting that organ function, microcirculation, haemostasis and inflammatory response are essential elements of the pathomechanism and clinical course of diseases among critically ill patients.
Decreased complement mediated binding of antibody//sup 3/-dsDNA immune complexes to the red blood cells of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies

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

Taylor, R.P.; Horgan, C.; Buschbacher, R.

1983-06-01

The complement mediated binding of prepared antibody//sup 3/H-dsDNA immune complexes to the red blood cells obtained from a number of patient populations has been investigated. Patients with solid tumors have binding activity similar to that seen in a normal group of individuals. However, a significant fraction of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies have lowered binding activity compared with normal subjects. Quantitative studies indicate the lowered activity probably arises due to a decrease in complement receptors on the respective red blood cells. The potential importance and implications of these findings are briefly discussed.
Age-related macular degeneration and modification of systemic complement factor H production through liver transplantation.

PubMed

Khandhadia, Samir; Hakobyan, Svetlana; Heng, Ling Z; Gibson, Jane; Adams, David H; Alexander, Graeme J; Gibson, Jonathan M; Martin, Keith R; Menon, Geeta; Nash, Kathryn; Sivaprasad, Sobha; Ennis, Sarah; Cree, Angela J; Morgan, B Paul; Lotery, Andrew J

2013-08-01

To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD). Multicenter, cross-sectional study. We recruited 223 Western European patients ≥ 55 years old who had undergone LT ≥ 5 years previously. We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor). We evaluated AMD status and recipient and donor CFH Y402H genotype. In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P<0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014). Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation. The authors have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Characterization of a Gene Coding for the Complement System Component FB from Loxosceles laeta Spider Venom Glands.

PubMed

Myamoto, Daniela Tiemi; Pidde-Queiroz, Giselle; Gonçalves-de-Andrade, Rute Maria; Pedroso, Aurélio; van den Berg, Carmen W; Tambourgi, Denise V

2016-01-01

The human complement system is composed of more than 30 proteins and many of these have conserved domains that allow tracing the phylogenetic evolution. The complement system seems to be initiated with the appearance of C3 and factor B (FB), the only components found in some protostomes and cnidarians, suggesting that the alternative pathway is the most ancient. Here, we present the characterization of an arachnid homologue of the human complement component FB from the spider Loxosceles laeta. This homologue, named Lox-FB, was identified from a total RNA L. laeta spider venom gland library and was amplified using RACE-PCR techniques and specific primers. Analysis of the deduced amino acid sequence and the domain structure showed significant similarity to the vertebrate and invertebrate FB/C2 family proteins. Lox-FB has a classical domain organization composed of a control complement protein domain (CCP), a von Willebrand Factor domain (vWFA), and a serine protease domain (SP). The amino acids involved in Mg2+ metal ion dependent adhesion site (MIDAS) found in the vWFA domain in the vertebrate C2/FB proteins are well conserved; however, the classic catalytic triad present in the serine protease domain is not conserved in Lox-FB. Similarity and phylogenetic analyses indicated that Lox-FB shares a major identity (43%) and has a close evolutionary relationship with the third isoform of FB-like protein (FB-3) from the jumping spider Hasarius adansoni belonging to the Family Salcitidae.
Characterization of a Gene Coding for the Complement System Component FB from Loxosceles laeta Spider Venom Glands

PubMed Central

Myamoto, Daniela Tiemi; Pidde-Queiroz, Giselle; Gonçalves-de-Andrade, Rute Maria; Pedroso, Aurélio; van den Berg, Carmen W.; Tambourgi, Denise V.

2016-01-01

The human complement system is composed of more than 30 proteins and many of these have conserved domains that allow tracing the phylogenetic evolution. The complement system seems to be initiated with the appearance of C3 and factor B (FB), the only components found in some protostomes and cnidarians, suggesting that the alternative pathway is the most ancient. Here, we present the characterization of an arachnid homologue of the human complement component FB from the spider Loxosceles laeta. This homologue, named Lox-FB, was identified from a total RNA L. laeta spider venom gland library and was amplified using RACE-PCR techniques and specific primers. Analysis of the deduced amino acid sequence and the domain structure showed significant similarity to the vertebrate and invertebrate FB/C2 family proteins. Lox-FB has a classical domain organization composed of a control complement protein domain (CCP), a von Willebrand Factor domain (vWFA), and a serine protease domain (SP). The amino acids involved in Mg2+ metal ion dependent adhesion site (MIDAS) found in the vWFA domain in the vertebrate C2/FB proteins are well conserved; however, the classic catalytic triad present in the serine protease domain is not conserved in Lox-FB. Similarity and phylogenetic analyses indicated that Lox-FB shares a major identity (43%) and has a close evolutionary relationship with the third isoform of FB-like protein (FB-3) from the jumping spider Hasarius adansoni belonging to the Family Salcitidae. PMID:26771533
Parasitic scabies mites and associated bacteria joining forces against host complement defence.

PubMed

Swe, P M; Reynolds, S L; Fischer, K

2014-11-01

Scabies is a ubiquitous and contagious skin disease caused by the parasitic mite Sarcoptes scabiei Epidemiological studies have identified scabies as a causative agent for secondary skin infections caused by Staphylococcus aureus and Streptococcus pyogenes. This is an important notion, as such bacterial infections can lead to serious downstream life-threatening complications. As the complement system is the first line of host defence that confronts invading pathogens, both the mite and bacteria produce a large array of molecules that inhibit the complement cascades. It is hypothesised that scabies mite complement inhibitors may play an important role in providing a favourable micro-environment for the establishment of secondary bacterial infections. This review aims to bring together the current literature on complement inhibition by scabies mites and bacteria associated with scabies and to discuss the proposed molecular link between scabies and bacterial co-infections. © 2014 John Wiley & Sons Ltd.
Transcriptome Analysis of the Innate Immunity-Related Complement System in Spleen Tissue of Ctenopharyngodon idella Infected with Aeromonas hydrophila

PubMed Central

Dang, Yunfei; Xu, Xiaoyan; Shen, Yubang; Hu, Moyan; Zhang, Meng; Li, Lisen; Lv, Liqun; Li, Jiale

2016-01-01

The grass carp (Ctenopharyngodon idella) is an important commercial farmed herbivorous fish species in China, but is susceptible to Aeromonas hydrophila infections. In the present study, we performed de novo RNA-Seq sequencing of spleen tissue from specimens of a disease-resistant family, which were given intra-peritoneal injections containing PBS with or without a dose of A. hydrophila. The fish were sampled from the control group at 0 h, and from the experimental group at 4, 8, 12, 24, 48 and 72 h. 122.18 million clean reads were obtained from the normalized cDNA libraries; these were assembled into 425,260 contigs and then 191,795 transcripts. Of those, 52,668 transcripts were annotated with the NCBI Nr database, and 41,347 of the annotated transcripts were assigned into 90 functional groups. 20,569 unigenes were classified into six main categories, including 38 secondary KEGG pathways. 2,992 unigenes were used in the analysis of differentially expressed genes (DEGs). 89 of the putative DEGs were related to the immune system and 41 of them were involved in the complement and coagulation cascades pathway. This study provides insights into the complement and complement-related pathways involved in innate immunity, through expression profile analysis of the genomic resources in C. idella. We conclude that complement and complement-related genes play important roles during defense against A. hydrophila infection. The immune response is activated at 4 h after the bacterial injections, indicating that the complement pathways are activated at the early stage of bacterial infection. The study has improved our understanding of the immune response mechanisms in C. idella to bacterial pathogens. PMID:27383749
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
Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency

PubMed Central

Shen, Siming; Sandoval, Juan; Swiss, Victoria A; Li, Jiadong; Dupree, Jeff; Franklin, Robin J M; Casaccia-Bonnefil, Patrizia

2009-01-01

The efficiency of remyelination decreases with age, but the molecular mechanisms responsible for this decline remain only partially understood. In this study, we show that remyelination is regulated by age-dependent epigenetic control of gene expression. In demyelinated young brains, new myelin synthesis is preceded by downregulation of oligodendrocyte differentiation inhibitors and neural stem cell markers, and this is associated with recruitment of histone deacetylases (HDACs) to promoter regions. In demyelinated old brains, HDAC recruitment is inefficient, and this allows the accumulation of transcriptional inhibitors and prevents the subsequent surge in myelin gene expression. Defective remyelination can be recapitulated in vivo in mice receiving systemic administration of pharmacological HDAC inhibitors during cuprizone treatment and is consistent with in vitro results showing defective differentiation of oligodendrocyte progenitors after silencing specific HDAC isoforms. Thus, we suggest that inefficient epigenetic modulation of the oligodendrocyte differentiation program contributes to the age-dependent decline in remyelination efficiency. PMID:19160500
Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta.

PubMed

Banadakoppa, M; Chauhan, M S; Havemann, D; Balakrishnan, M; Dominic, J S; Yallampalli, C

2014-09-01

Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto-maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion. © 2014 British Society for Immunology.
The lectin pathway in renal disease: old concept and new insights.

PubMed

Gaya da Costa, Mariana; Poppelaars, Felix; Berger, Stefan P; Daha, Mohamed R; Seelen, Marc A

2018-04-26

The complement system is composed of a network of at least 40 proteins, which significantly contributes to health and disease. The lectin pathway (LP) is one of three pathways that can activate the complement system. Next to protection of the host against pathogens, the LP has been shown to play a crucial role in multiple renal diseases as well as during renal replacement therapy. Therefore, several complement-targeted drugs are currently being explored in clinical trials. Among these complement inhibitors, specific LP inhibitors are also being tested in renal abnormalities such as in immunoglobulin A nephropathy and lupus nephritis. Using various in vitro models, Yaseen et al. (Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement component 3 (C3) in absence of C4 and/or C2. FASEB J 2017; 31: 2210-2219) showed that Mannan-associated serine protease2 can directly activate C3 thereby bypassing C2 and C4 in the activation of the LP. These new findings broaden our understanding of the mechanisms of complement activation and could potentially impact our strategies to inhibit the LP in renal diseases. In support of these findings, we present data of human renal biopsies, demonstrating the occurrence of the LP bypass mechanism in vivo. In conclusion, this review provides a detailed overview of the LP and clarifies the recently described bypass mechanism and its relevance. Finally, we speculate on the role of the C4 bypass mechanism in other renal diseases.
Towards a Totalitarian Education System in England: Looking at the Academy Question in a Longer Policy Context

ERIC Educational Resources Information Center

Newsam, Peter

2013-01-01

In this opinion piece, the author writes that England is now well on the way to having the most totalitarian as well as one of the most inefficiently managed schools system in Europe. He states that in the much maligned 1960s, people came from all over the world to learn from what was being achieved in the best of England's publicly-funded, local…

Modeling efficiency at the process level: an examination of the care planning process in nursing homes.

PubMed

Lee, Robert H; Bott, Marjorie J; Gajewski, Byron; Taunton, Roma Lee

2009-02-01

To examine the efficiency of the care planning process in nursing homes. We collected detailed primary data about the care planning process for a stratified random sample of 107 nursing homes from Kansas and Missouri. We used these data to calculate the average direct cost per care plan and used data on selected deficiencies from the Online Survey Certification and Reporting System to measure the quality of care planning. We then analyzed the efficiency of the assessment process using corrected ordinary least squares (COLS) and data envelopment analysis (DEA). Both approaches suggested that there was considerable inefficiency in the care planning process. The average COLS score was 0.43; the average DEA score was 0.48. The correlation between the two sets of scores was quite high, and there was no indication that lower costs resulted in lower quality. For-profit facilities were significantly more efficient than not-for-profit facilities. Multiple studies of nursing homes have found evidence of inefficiency, but virtually all have had measurement problems that raise questions about the results. This analysis, which focuses on a process with much simpler measurement issues, finds evidence of inefficiency that is largely consistent with earlier studies. Making nursing homes more efficient merits closer attention as a strategy for improving care. Increasing efficiency by adopting well-designed, reliable processes can simultaneously reduce costs and improve quality.
Iron Requirement and Iron Uptake from Various Iron Compounds by Different Plant Species

PubMed Central

Christ, Rudolf A.

1974-01-01

The Fe requirements of four monocotyledonous plant species (Avena sativa L., Triticum aestivum L., Oryza sativa L., Zea mays L.) and of three dicotyledonous species (Lycopersicum esculentum Mill., Cucumis sativus L., Glycine maxima (L.) Merr.) in hydroponic cultures were ascertained. Fe was given as NaFe-EDDHA chelate (Fe ethylenediamine di (O-hydroxyphenylacetate). I found that the monocotyledonous species required a substantially higher Fe concentration in the nutrient solution in order to attain optimum growth than did the dicotyledonous species. Analyses showed that the process of iron uptake was less efficient with the monocotyledonous species. When the results obtained by using chelated Fe were compared with those using ionic Fe, it was shown that the inefficient species were equally inefficient in utilizing Fe3+ ions. However, the differences between the efficient and the inefficient species disappeared when Fe2+ was used. This confirms the work of others who postulated that Fe3+ is reduced before uptake of chelated iron by the root. In addition, it was shown that reduction also takes place when Fe is used in ionic form. The efficiency of Fe uptake seems to depend on the efficiency of the root system of the particular plant species in reducing Fe3+. The removal of Fe from the chelate complex after reduction to Fe2+ seems to present no difficulties to the various plant species. PMID:16658933
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.
Management of the Student Aid Delivery System. Hearing on Examining Proposed Legislation Authorizing Funds for Programs of the Higher Education Act, Focusing on Student Aid Delivery Systems, of the Committee on Labor and Human Resources. United States Senate, One Hundred Fifth Congress, First Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

This seventh hearing in a series related to the reauthorization of the Higher Education Act focused on the management structure of the Office of Postsecondary Education and the financial aid delivery system. In the opening statement, Chairman James M. Jeffords reported that the current system is outdated and inefficient and indicated that the…
Advanced spacecraft thermal control techniques

NASA Technical Reports Server (NTRS)

Fritz, C. H.

1977-01-01

The problems of rejecting large amounts of heat from spacecraft were studied. Shuttle Space Laboratory heat rejection uses 1 kW for pumps and fans for every 5 kW (thermal) heat rejection. This is rather inefficient, and for future programs more efficient methods were examined. Two advanced systems were studied and compared to the present pumped-loop system. The advanced concepts are the air-cooled semipassive system, which features rejection of a large percentage of the load through the outer skin, and the heat pipe system, which incorporates heat pipes for every thermal control function.
Role of the ruminal microbiome in the production and composition of milk

USDA-ARS?s Scientific Manuscript database

Environmental problems associated with animal agriculture arise primarily from inherent inefficiencies in converting energy in feeds to useful products. Attenuating these inefficiencies provides substantial potential to improve both the economics and environmental footprint of animal agriculture, pa...
A Graphical Teaching Tool for Understanding Two's Complement.

ERIC Educational Resources Information Center

Luck, Carlos L.

As part of the Electrical Engineering program at the Univesity of Southern Maine, students are typically introduced to Two's Complement algebra and representation, a method to include negative numbers in the binary representation of integers that is widely used in microprocessors and related digital systems. The traditional, procedural method to…
Microfibrillar associated protein 4 mfap4 genes in catfish play a novel role in innate immune responses

USDA-ARS?s Scientific Manuscript database

The lectin pathway of the complement system is characterized by two groups of soluble pattern recognition molecules, mannose-binding lectins (MBLs) and ficolins. These molecules recognize and bind carbohydrates in pathogens and activate complement leading to opsonization, leukocyte activation, and d...
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.
PASSIVE HEMOLYSIS BY SERUM AND COBRA VENOM FACTOR: A NEW MECHANISM INDUCING MEMBRANE DAMAGE BY COMPLEMENT*

PubMed Central

Pickering, R. J.; Wolfson, M. R.; Good, R. A.; Gewurz, H.

1969-01-01

The studies presented here indicate that activation of the complement (C′) system by a foreign protein will cause membrane injury and passive lysis of unsensitized erythrocytes present at the time of the reaction. These observations suggest that in addition to the classical antibody-C′-induced cytolysis, there are alternative pathways or mechanisms for activation and participation of the terminal C′ components in the production of cell membrane injury. We have shown that a substance derived from cobra venom and eluted from a single protein band on polyacrylamide can promote lysis of unsensitized autologous or heterologous erythrocytes in the presence of fresh guinea pig serum and that this lysis-inducing activity and C′-inhibiting activity appear to reside in the same fractions. The lytic activity is prevented by several agents known to impair classical C′3 activity, but is unaffected by certain procedures which interfere with the function of C′ components C′1 and C′2, a suggestion that this reaction involves chiefly C′3-C′9. Further, the cobra venom (CV) factor depletes C′ activity in cobra serum, and the CV factor (with its 5S serum cofactor) converts purified C′3 to its inactive form,1 indicating that the reaction of this complex with the complement system occurs without participation of antibody. Therefore, since the lysis-inducing and C′-inhibiting activity of the CV factor appear to result from similar interactions with the complement system, these observations suggest that cell membrane damage and cell lysis can be accomplished through activation of the complement system by a mechanism involving little or no participation of classical antibody or C′ components C′1, 4, or 2. Images PMID:4978744
Evaluation of serum levels of C3 and C4 complement factors in patients with beta thalassemia major in Khuzestan Province, Southwest Iran.

PubMed

Ghafourian, Mehri; Esmaeili, Mehrnosh; Dashti-Gerdabi, Nader; Sadeghi, Alireza; Malekei Naseri, Ali; Kazemi, Akhtar

2017-01-01

Thalassemia syndrome is the most common genetic disorder in the world and infection is the second cause of death in these patients. Measurement of serum C3 and C4 complement factors in serum was done in 60 patients with beta thalassemia major in comparison with 30 healthy subjects as control group. The serum level of C3 and C4 complement factors in 60 patients with beta thalassemia major who were randomly selected from among the patients referred to Shafa Hospital of Ahvaz was evaluated and compared with 30 samples from healthy individuals with no history of recent infectious or autoimmune diseases. It should be noted that single-radial-immunodiffusion assay was used in this study. This study has shown a significant reduction in serum levels of C3 and C4 in patients compared to controls (P value < 0.05). Decreased synthesis or increased consumption of complement factors in patients receiving multiple blood transfusions might lead to continuous contact between the immune system and various antigens, causing nonstop use of complement factors, recurrent infections, changes in parameters of the immune system due to iron overload as well as exposure to infectious factors such as HBV, HCV, HIV, and HTLV through blood transfusion.
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.
Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy.

PubMed

Xu, Jijun; Zhang, Lingjun; Xie, Mian; Li, Yan; Huang, Ping; Saunders, Thomas L; Fox, David A; Rosenquist, Richard; Lin, Feng

2018-06-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and debilitating side effect of cancer chemotherapy with an unclear pathogenesis. Consequently, the available therapies for this neuropathic pain syndrome are inadequate, leading to a significantly reduced quality of life in many patients. Complement, a key component of the innate immune system, has been associated with neuroinflammation, a potentially important trigger of some types of neuropathic pain. However, the role of complement in CIPN remains unclear. To address this issue, we developed a C3 knockout (KO) rat model and induced CIPN in these KO rats and wild-type littermates via the i.p. administration of paclitaxel, a chemotherapeutic agent associated with CIPN. We then compared the severity of mechanical allodynia, complement activation, and intradermal nerve fiber loss between the groups. We found that 1) i.p. paclitaxel administration activated complement in wild-type rats, 2) paclitaxel-induced mechanical allodynia was significantly reduced in C3 KO rats, and 3) the paclitaxel-induced loss of intradermal nerve fibers was markedly attenuated in C3 KO rats. In in vitro studies, we found that paclitaxel-treated rat neuronal cells activated complement, leading to cellular injury. Our findings demonstrate a previously unknown but pivotal role of complement in CIPN and suggest that complement may be a new target for the development of novel therapeutics to manage this painful disease. Copyright © 2018 by The American Association of Immunologists, Inc.
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
Acquired granulocyte abnormality during drug allergic reactions: possible role of complement activation.

PubMed

Bowers, T K; Craddock, P R; Jacob, H S

1977-01-01

A profound defect in granulocyte chemotaxis was documented in an otherwise healthy 21-yr-old man who failed to localize granulocytes to an area of cellulitis during an allergic reaction to cephalothin. During the period of drug allergy, characterized by urticaria, eosinophilia, and profound hypocomplementemia, in vitro migration of the patient's granulocytes in the Boyden chamber was markedly impaired. Although devoid of hemolytic complement activity, the patient's serum possessed supranormal chemotactic activity, even following heat inactivation, suggesting the presence of chemotactically active complement split products. Chemotactic function improved concomitantly with steroid therapy and normalization of serum complement levels, and was entirely normal following clinical recovery and cessation of steroid therapy. The chemotactic abnormality noted in the patient's cells was reproduced in normal granulocytes by preincubation either with patient serum or with cobra venom-activated fresh (but not heated) normal serum, suggesting that in vivo exposure of granulocytes to activated complement was responsible for the patient's abnormal chemotactic response. This mechanism may contribute to the increased infection propensity noted in other conditions characterized by in vivo complement activation, such as rheumatoid arthritis and systemic lupus erythematosis.
How Ecosystem Services Knowledge and Values Influence Farmers' Decision-Making

PubMed Central

Lamarque, Pénélope; Meyfroidt, Patrick; Nettier, Baptiste; Lavorel, Sandra

2014-01-01

The ecosystem services (ES) concept has emerged and spread widely recently, to enhance the importance of preserving ecosystems through global change in order to maintain their benefits for human well-being. Numerous studies consider various dimensions of the interactions between ecosystems and land use via ES, but integrated research addressing the complete feedback loop between biodiversity, ES and land use has remained mostly theoretical. Few studies consider feedbacks from ecosystems to land use systems through ES, exploring how ES are taken into account in land management decisions. To fill this gap, we carried out a role-playing game to explore how ES cognition mediates feedbacks from environmental change on farmers' behaviors in a mountain grassland system. On a close to real landscape game board, farmers were faced with changes in ES under climatic and socio-economic scenarios and prompted to plan for the future and to take land management decisions as they deemed necessary. The outcomes of role-playing game were complemented with additional agronomic and ecological data from interviews and fieldwork. The effects of changes in ES on decision were mainly direct, i.e. not affecting knowledge and values, when they constituted situations with which farmers were accustomed. For example, a reduction of forage quantity following droughts led farmers to shift from mowing to grazing. Sometimes, ES cognitions were affected by ES changes or by external factors, leading to an indirect feedback. This happened when fertilization was stopped after farmers learned that it was inefficient in a drought context. Farmers' behaviors did not always reflect their attitudes towards ES because other factors including topographic constraints, social value of farming or farmer individual and household characteristics also influenced land-management decisions. Those results demonstrated the interest to take into account the complete feedback loop between ES and land management decisions to favor more sustainable ES management. PMID:25268490
How ecosystem services knowledge and values influence farmers' decision-making.

PubMed

Lamarque, Pénélope; Meyfroidt, Patrick; Nettier, Baptiste; Lavorel, Sandra

2014-01-01

The ecosystem services (ES) concept has emerged and spread widely recently, to enhance the importance of preserving ecosystems through global change in order to maintain their benefits for human well-being. Numerous studies consider various dimensions of the interactions between ecosystems and land use via ES, but integrated research addressing the complete feedback loop between biodiversity, ES and land use has remained mostly theoretical. Few studies consider feedbacks from ecosystems to land use systems through ES, exploring how ES are taken into account in land management decisions. To fill this gap, we carried out a role-playing game to explore how ES cognition mediates feedbacks from environmental change on farmers' behaviors in a mountain grassland system. On a close to real landscape game board, farmers were faced with changes in ES under climatic and socio-economic scenarios and prompted to plan for the future and to take land management decisions as they deemed necessary. The outcomes of role-playing game were complemented with additional agronomic and ecological data from interviews and fieldwork. The effects of changes in ES on decision were mainly direct, i.e. not affecting knowledge and values, when they constituted situations with which farmers were accustomed. For example, a reduction of forage quantity following droughts led farmers to shift from mowing to grazing. Sometimes, ES cognitions were affected by ES changes or by external factors, leading to an indirect feedback. This happened when fertilization was stopped after farmers learned that it was inefficient in a drought context. Farmers' behaviors did not always reflect their attitudes towards ES because other factors including topographic constraints, social value of farming or farmer individual and household characteristics also influenced land-management decisions. Those results demonstrated the interest to take into account the complete feedback loop between ES and land management decisions to favor more sustainable ES management.

Strong Performers and Successful Reformers in Education: Education Policy Advice for Greece

ERIC Educational Resources Information Center

OECD Publishing (NJ1), 2011

2011-01-01

The future of Greece's well-being will depend on improving educational performance to boost productivity and improve social outcomes. In the current economic context, with the need to get best value for spending, Greece must and can address inefficiencies in its education system. The challenges are significant. For example, Greece lags behind many…
The Interpretation and Implementation of the Bologna Process in Serbia

ERIC Educational Resources Information Center

Despotovic, Miomir

2011-01-01

This paper neither attacks nor defends the Bologna Declaration; rather, it attempts a critical assessment of its implementation in Serbia. Review of the available data shows that the higher education system in Serbia is inefficient and in profound need of reform. Analysis of some of the reform processes shows that the Bologna Declaration as a…
Desalination as Groundwater Conservation: The Cost of Protecting Cultural and Environmental Resources in Chile's Region II

NASA Astrophysics Data System (ADS)

Edwards, E. C.; Cristi, O.; Libecap, G. D.

2012-12-01

There is a substantial body of evidence that groundwater overdraft is occurring worldwide. Economists argue that the cause of this overdraft is the open-access nature of the resource, which results in a "tragedy of the commons." Sustainable water management requires that some institution control the resource to limit this overdraft by reducing water extraction. This reduction creates scarcity and requires a method of rationing. The economically efficient outcome occurs when the lowest value uses of water are eliminated. This allocation, though, may have undesirable social consequences, such as the loss of small-scale farming, and political ramifications that make such an allocation unpopular to implement. This paper explores the economic cost of leaving water in low-value uses. The policy we explore is a moratorium on voluntary water sales to mining firms to protect the groundwater resource in northern Chile. This policy has accelerated the use of expensive desalinated water, whose cost is primarily driven by its heavy use of carbon-based electricity. Chile has a strong system of water property rights that economists argue ration water in a way that leads to the efficient allocation through water markets. This paper first explores the potential inefficiency of a water market when groundwater and surface water are linked, as well as when different users vary in their intensity of use. This theoretical background provides a framework for determining the economically efficient allocation of water and the losses associated with the moratorium in northern Chile. The policy does protect some environmental and cultural public goods, which potentially offset some or all of this cost. We provide a perspective on the magnitude of these public goods but do not attempt to value them explicitly. Instead, we demonstrate what their value must be so that the moratorium policy has a cost-to-benefit ratio of one. While the estimate of lost income from inefficiency is the main focus of the empirical work, the theoretical development provides an important perspective into groundwater management and the important role of understanding the physical system in water marketing. Worldwide, subsidized and scarce water is allocated to farmers for social and political reasons. The losses from this type of allocation are often ignored or marginalized. The Chilean case demonstrates that the losses due to economically inefficient allocation are real, because the alternative is greater consumption of other resources (fossil fuels in this case), not conservation. The Chilean case also demonstrates the difficulty of adequately defining water rights for efficient markets due to the physical properties of hydrologic systems. Because groundwater and surface water systems are linked and water is partially recycled, water markets may over allocate water to consumptive users or those with preferable extraction locations. This paper provides a theoretical exposition of how water rights that fail incorporate important properties of the physical system may lead to inefficient water markets.
Energy Management for Automatic Monitoring Stations in Arctic Regions

NASA Astrophysics Data System (ADS)

Pimentel, Demian

Automatic weather monitoring stations deployed in arctic regions are usually installed in hard to reach locations. Most of the time they run unsupervised and they face severe environmental conditions: very low temperatures, ice riming, etc. It is usual practice to use a local energy source to power the equipment. There are three main ways to achieve this: (1) a generator whose fuel has to be transported to the location at regular intervals (2) a battery and (3) an energy harvesting generator that exploits a local energy source. Hybrid systems are very common. Polar nights and long winters are typical of arctic regions. Solar radiation reaching the ground during this season is very low or non-existent, depending on the geographical location. Therefore, solar power generation is not very effective. One straightforward, but expensive and inefficient solution is the use of a large bank of batteries that is recharged during sunny months and discharged during the winter. The main purpose of the monitoring stations is to collect meteorological data at regular intervals; interruptions due to a lack of electrical energy can be prevented with the use of an energy management subsystem. Keeping a balance between incoming and outgoing energy flows, while assuring the continuous operation of the station, is the delicate task of energy management strategies. This doctoral thesis explores alternate power generation solutions and intelligent energy management techniques for equipment deployed in the arctic. For instance, harvesting energy from the wind to complement solar generation is studied. Nevertheless, harvested energy is a scarce resource and needs to be used efficiently. Genetic algorithms, fuzzy logic, and common sense are used to efficiently manage energy flows within a simulated arctic weather station.
SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

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

Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee

Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3{sup +} apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver ofmore » SIGN-R1 KO mice, followed by a significant increase of CD11b{sup +} cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1{sup +} macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver.« less
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
Complement is activated in progressive multiple sclerosis cortical grey matter lesions.

PubMed

Watkins, Lewis M; Neal, James W; Loveless, Sam; Michailidou, Iliana; Ramaglia, Valeria; Rees, Mark I; Reynolds, Richard; Robertson, Neil P; Morgan, B Paul; Howell, Owain W

2016-06-22

The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression. We analysed complement expression and activation by immunocytochemistry and in situ hybridisation in frozen or formalin-fixed paraffin-embedded post-mortem tissue blocks from 22 progressive MS cases and made comparisons to inflammatory central nervous system disease and non-neurological disease controls. Expression of the transcript for C1qA was noted in neurons and the activation fragment and opsonin C3b-labelled neurons and glia in the MS cortical and deep grey matter. The density of immunostained cells positive for the classical complement pathway protein C1q and the alternative complement pathway activation fragment Bb was significantly increased in cortical grey matter lesions in comparison to control grey matter. The number of cells immunostained for the membrane attack complex was elevated in cortical lesions, indicating complement activation to completion. The numbers of classical (C1-inhibitor) and alternative (factor H) pathway regulator-positive cells were unchanged between MS and controls, whilst complement anaphylatoxin receptor-bearing microglia in the MS cortex were found closely apposed to cortical neurons. Complement immunopositive neurons displayed an altered nuclear morphology, indicative of cell stress/damage, supporting our finding of significant neurodegeneration in cortical grey matter lesions. Complement is activated in the MS cortical grey matter lesions in areas of elevated numbers of complement receptor-positive microglia and suggests that complement over-activation may contribute to the worsening pathology that underlies the irreversible progression of MS.
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.
The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity.

PubMed

Kieslich, Chris A; Morikis, Dimitrios

2012-01-01

The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the divergence of jawless fish.
The Two Sides of Complement C3d: Evolution of Electrostatics in a Link between Innate and Adaptive Immunity

PubMed Central

Kieslich, Chris A.; Morikis, Dimitrios

2012-01-01

The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of −1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic “hot-spots”. Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic “hot-spots” at the two functional sites of C3d, while the surface of CR2 lacks electrostatic “hot-spots” despite its excessively positive nature. We propose that the electrostatic “hot-spots” of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the divergence of jawless fish. PMID:23300422
Tanker avionics and aircrew complement evaluation.

PubMed

Moss, R W; Barbato, G J

1982-11-01

This paper describes an effort to determine control and display criteria for operating SAC's KC-135 tanker with a reduced crew complement. The Tanker Avionics and Aircrew Complement Evaluation (TAACE) Program was a four-phase effort addressing the control and display design issues associated with operating the tanker without the navigator position. Discussed are: the mission analysis phase, during which the tanker's operational responsibilities were defined and documented; the design phase, during which alternative crew station design concepts were developed; the mockup evaluation phase, which accomplished initial SAC crew member assessment of cockpit designs; and the simulation phase, which validated the useability of the crew system redesign. The paper also describes a recommended crew station configuration and discusses some of the philosophy underlying the selection of cockpit hardware and systems.
Crew procedures for microwave landing system operations

NASA Technical Reports Server (NTRS)

Summers, Leland G.

1987-01-01

The objective of this study was to identify crew procedures involved in Microwave Landing System (MLS) operations and to obtain a preliminary assessment of crew workload. The crew procedures were identified for three different complements of airborne equipment coupled to an autopilot. Using these three equipment complements, crew tasks were identified for MLS approaches and precision departures and compared to an ILS approach and a normal departure. Workload comparisons between the approaches and departures were made by using a task-timeline analysis program that obtained workload indexes, i.e., the radio of time required to complete the tasks to the time available. The results showed an increase in workload for the MLS scenario for one of the equipment complements. However, even this workload was within the capacity of two crew members.
Governance and Territory - Case of the Jaizkibel’s Corridor: An Approach to a Proposal for Urban, Economic and Social Regeneration

NASA Astrophysics Data System (ADS)

Izkeaga, Jose Ramon

2017-10-01

The Bay of Biscay is located in the heart of district known as Donostialdea (San Sebastian). Together with the towns of Donostia-San Sebastian, Lezo, Errenteria and Oiartzun, it makes up the so-called Oarsoaldea region, a supramunicipal area of common interest. A urban continuum peculiar to the region, than may be better understood as an area of shared territorially with several elements in common and as a community where individual interests intersect with common interests. The importance of the geographical location of this region is more than notable. It is on the Bay of Biscay right where Spain curves northward to meet France; it is the only natural point of passage on the west end of the Pyrenees Mountains, with La Junquera in Catalonia at the east end, thus communicating the Iberian Peninsula with the rest of Europe. This is the strategic point for each and every known means of transport. The rail system consists of three different types of track gauge; the road network includes major motorways and the national road system; the airports at Hondarribia and Biarritz and the natural port of Pasaia complements this transportation node. All of this takes place in a small space, a natural corridor at the foot of Mount Jaizkibel. What was once considered modern infrastructures sufficient to meet transportation needs is today absolutely insufficient, obsolete and in operative. A set of partial solutions lacking an overall vision cannot be considered an integrated system. Therein lies the origin of the problem. Here is the diagnosis: The Port of Pasaia is obsolete. Pressure is felt from urban growth in the surrounding cities and from the restrictions of the Hondarribia airport. The roads are completely saturated and traffic continues to increase. The railway service is inefficient owing to three different types of track gauge. And each of these infrastructures is subject to its own restrictions and management. This forces us to think about the current state of these services and to come up with a new way of organizing this “infrastructures complex” that can efficiently solve the problems of mobility, based on the different services complementing each other. The system must be understood as a “whole”, a system made up of individual parts which are effective in their relationship with the rest of the parts, a single way of understanding and dealing with the problem. The complexity involved in managing this situation and in developing common interest’s calls for the creation of a powerful and competent administrator and management entity. Governance is a fundamental ‘factor’ in achieving the objectives put forward by the community through its managers, as a goal for the transformation, improvement and development of the conditions in its territory and of its inhabitants. The ‘social’ character that any type of initiative means in this area takes on an unusual dimension due to the effect it reaches on this territorial scale. Hence, the importance of a territory-wide vision regarding local positions, and the need for an appropriate instrument.
The misnomer of attention-deficit hyperactivity disorder.

PubMed

Wasserman, Theodore; Wasserman, Lori Drucker

2015-01-01

We propose that attention-deficit disorder represents an inefficiency of an integrated system designed to allocate working memory to designated tasks rather than the absence or dysfunction of a particular form of attention. A significant portion of this inefficiency in the allocation of working memory represents poor engagement of the reward circuit with distinct circuits of learning and performance that control instrumental conditioning (learning). Efficient attention requires the interaction of these circuits. For a significant percentage of individuals who present with attention-deficit disorder, their problems represent the engagement, or lack thereof, of the motivational and reward circuit as opposed to problems, or disorders of attention traditionally defined as problems with orienting, focusing, and sustaining. We demonstrate that there is an integrated system of working-memory allocation that responds by recruiting relevant aspects of both cortex and subcortex to the demands of the task being encountered. In this model, attention is viewed as a gating function determined by novelty, flight-or-fight response, and reward history/valence affecting motivation. We view the traditional models of attention, rather than describe specific types of attention per se, as representing the description of the behavioral output of this integrated orienting and engagement system designed to allocate working memory to task-specific stimuli.
Phylogeny and immune evasion: a putative correlation for cerebral Pseudallescheria/Scedosporium infections.

PubMed

Rainer, Johannes; Rambach, Günter; Kaltseis, Josef; Hagleitner, Magdalena; Heiss, Silvia; Speth, Cornelia

2011-10-01

Representatives of the genus Pseudallescheria (anamorph: Scedosporium) are saprobes and the aetiologic agent of invasive mycosis in humans. After dissemination, the central nervous system (CNS) is one of the most affected organs. Prerequisites for the survival of Pseudallescheria/Scedosporium in the host are the ability to acquire nutrients and to evade the immune attack. The cleavage of complement compounds via the secretion of fungal proteases might meet both challenges since proteolytic degradation of proteins can provide nutrients and destroy the complement factors, a fast and effective immune weapon in the CNS. Therefore, we studied the capacity of different Pseudallescheria/Scedosporium species to degrade key elements of the complement cascade in the cerebrospinal fluid and investigated a correlation with the phylogenetic background. The majority of the Pseudallescheria apiosperma isolates tested were demonstrated to efficiently eliminate proteins like complement factors C3 and C1q, thus affecting two main components of a functional complement cascade, presumably by proteolytic degradation, and using them as nutrient source. In contrast, the tested strains of Pseudallescheria boydii have no or only weak capacity to eliminate these complement proteins. We hypothesise that the ability of Pseudallescheria/Scedosporium strains to acquire nutrients and to undermine the complement attack is at least partly phylogenetically determined. © 2011 Blackwell Verlag GmbH.
Lack of association of CFD polymorphisms with advanced age-related macular degeneration.

PubMed

Zeng, Jiexi; Chen, Yuhong; Tong, Zongzhong; Zhou, Xinrong; Zhao, Chao; Wang, Kevin; Hughes, Guy; Kasuga, Daniel; Bedell, Matthew; Lee, Clara; Ferreyra, Henry; Kozak, Igor; Haw, Weldon; Guan, Jean; Shaw, Robert; Stevenson, William; Weishaar, Paul D; Nelson, Mark H; Tang, Luosheng; Zhang, Kang

2010-11-03

Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss worldwide. Research has linked AMD susceptibility with dysregulation of the complement cascade. Typically, complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3) are associated with AMD. In this paper, we investigated the association between complement factor D (CFD), another factor of the complement system, and advanced AMD in a Caucasian population. Six single nucleotide polymorphisms (SNPs), rs1683564, rs35186399, rs1683563, rs3826945, rs34337649, and rs1651896, across the region covering CFD, were chosen for this study. One hundred and seventy-eight patients with advanced AMD and 161 age-matched normal controls were genotyped. Potential positive signals were further tested in another independent 445 advanced AMD patients and 190 controls. χ2 tests were performed to compare the allele frequencies between case and control groups. None of the six SNPs of CFD was found to be significantly associated with advanced AMD in our study. Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD.
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
Financing Education: Overcoming Inefficiency and Inequity.

ERIC Educational Resources Information Center

McMahon, Walter W., Ed.; Geske, Terry G., Ed.

Fiscal inefficiency in education is addressed in this book and ideas for achieving increased efficiency while more effectively using resources to maintain reasonable equality of opportunity in higher education are examined. Fourteen articles and authors that consider social efficiency, equity, and policy implications are as follows: "Efficiency…
Energy conservation and analysis and evaluation. [specifically at Slidell Computer Complex

NASA Technical Reports Server (NTRS)

1976-01-01

The survey assembled and made recommendations directed at conserving utilities and reducing the use of energy at the Slidell Computer Complex. Specific items included were: (1) scheduling and controlling the use of gas and electricity, (2) building modifications to reduce energy, (3) replacement of old, inefficient equipment, (4) modifications to control systems, (5) evaluations of economizer cycles in HVAC systems, and (6) corrective settings for thermostats, ductstats, and other temperature and pressure control devices.

Could Wind or Solar Energy Replace Diesel Generators for Aviation Ground Maintenance Operations?

DTIC Science & Technology

2013-04-17

power. Both of these systems depend on the sun to produce energy. Wind turbines depend on wind which results from the uneven heating of the earth...inefficient. In addition to these limitations, both systems are costly and their installation brings a number of challenges. For the wind turbines ...these challenges include: the obstruction created by the height of the turbines near airfields, the amount of land necessary for a 7 turbines wind farm
Balancing Hydronic Systems in Multifamily Buildings

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

Ruch, R.; Ludwig, P.; Maurer, T.

2014-07-01

In multifamily hydronic systems, temperature imbalance may be caused by undersized piping, improperly adjusted balancing valves, inefficient water temperature and flow levels, and owner/occupant interaction with the boilers, distribution and controls. The effects of imbalance include tenant discomfort, higher energy use intensity and inefficient building operation. This paper explores cost-effective distribution upgrades and balancing measures in multifamily hydronic systems, providing a resource to contractors, auditors, and building owners on best practices to improve tenant comfort and lower operating costs. The research was conducted by The Partnership for Advanced Residential Retrofit (PARR) in conjunction with Elevate Energy. The team surveyed existingmore » knowledge on cost-effective retrofits for optimizing distribution in typical multifamily hydronic systems, with the aim of identifying common situations and solutions, and then conducted case studies on two Chicago area buildings with known balancing issues in order to quantify the extent of temperature imbalance. At one of these buildings a booster pump was installed on a loop to an underheated wing of the building. This study found that unit temperature in a multifamily hydronic building can vary as much as 61 degrees F, particularly if windows are opened or tenants use intermittent supplemental heating sources like oven ranges. Average temperature spread at the building as a result of this retrofit decreased from 22.1 degrees F to 15.5 degrees F.« less
Building America Case Study: Balancing Hydronic Systems in Multifamily Buildings, Chicago, Illinois (Fact Sheet)

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

Not Available

2014-09-01

In multifamily hydronic systems, temperature imbalance may be caused by undersized piping, improperly adjusted balancing valves, inefficient water temperature and flow levels, and owner/occupant interaction with the boilers, distribution and controls. The effects of imbalance include tenant discomfort, higher energy use intensity and inefficient building operation. This paper explores cost-effective distribution upgrades and balancing measures in multifamily hydronic systems, providing a resource to contractors, auditors, and building owners on best practices to improve tenant comfort and lower operating costs. The research was conducted by The Partnership for Advanced Residential Retrofit (PARR) in conjunction with Elevate Energy. The team surveyed existingmore » knowledge on cost-effective retrofits for optimizing distribution in typical multifamily hydronic systems, with the aim of identifying common situations and solutions, and then conducted case studies on two Chicago area buildings with known balancing issues in order to quantify the extent of temperature imbalance. At one of these buildings a booster pump was installed on a loop to an underheated wing of the building. This study found that unit temperature in a multifamily hydronic building can vary as much as 61 degrees F, particularly if windows are opened or tenants use intermittent supplemental heating sources like oven ranges. Average temperature spread at the building as a result of this retrofit decreased from 22.1 degrees F to 15.5 degrees F.« less
Protective responses to sublytic complement in the retinal pigment epithelium

PubMed Central

Tan, Li Xuan; Toops, Kimberly A.; Lakkaraju, Aparna

2016-01-01

The retinal pigment epithelium (RPE) is a key site of injury in inherited and age-related macular degenerations. Abnormal activation of the complement system is a feature of these blinding diseases, yet how the RPE combats complement attack is poorly understood. The complement cascade terminates in the cell-surface assembly of membrane attack complexes (MACs), which promote inflammation by causing aberrant signal transduction. Here, we investigated mechanisms crucial for limiting MAC assembly and preserving cellular integrity in the RPE and asked how these are compromised in models of macular degeneration. Using polarized primary RPE and the pigmented Abca4−/− Stargardt disease mouse model, we provide evidence for two protective responses occurring within minutes of complement attack, which are essential for maintaining mitochondrial health in the RPE. First, accelerated recycling of the membrane-bound complement regulator CD59 to the RPE cell surface inhibits MAC formation. Second, fusion of lysosomes with the RPE plasma membrane immediately after complement attack limits sustained elevations in intracellular calcium and prevents mitochondrial injury. Cholesterol accumulation in the RPE, induced by vitamin A dimers or oxidized LDL, inhibits these defense mechanisms by activating acid sphingomyelinase (ASMase), which increases tubulin acetylation and derails organelle traffic. Defective CD59 recycling and lysosome exocytosis after complement attack lead to mitochondrial fragmentation and oxidative stress in the RPE. Drugs that stimulate cholesterol efflux or inhibit ASMase restore both these critical safeguards in the RPE and avert complement-induced mitochondrial injury in vitro and in Abca4−/− mice, indicating that they could be effective therapeutic approaches for macular degenerations. PMID:27432952
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
From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage

PubMed Central

Mastellos, Dimitrios C.; Reis, Edimara S.; Yancopoulou, Despina; Hajishengallis, George; Ricklin, Daniel; Lambris, John D.

2016-01-01

Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3-directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID:27353192
Deletion of Crry and DAF on murine platelets stimulates thrombopoiesis and increases factor H-dependent resistance of peripheral platelets to complement attack.

PubMed

Barata, Lidia; Miwa, Takashi; Sato, Sayaka; Kim, David; Mohammed, Imran; Song, Wen-Chao

2013-03-15

Complement receptor 1-related gene/protein y (Crry) and decay-accelerating factor (DAF) are two murine membrane C3 complement regulators with overlapping functions. Crry deletion is embryonically lethal whereas DAF-deficient mice are generally healthy. Crry(-/-)DAF(-/-) mice were viable on a C3(-/-) background, but platelets from such mice were rapidly destroyed when transfused into C3-sufficient mice. In this study, we used the cre-lox system to delete platelet Crry in DAF(-/-) mice and studied Crry/DAF-deficient platelet development in vivo. Rather than displaying thrombocytopenia, Pf4-Cre(+)-Crry(flox/flox) mice had normal platelet counts and their peripheral platelets were resistant to complement attack. However, chimera mice generated with Pf4-Cre(+)-Crry(flox/flox) bone marrows showed platelets from C3(-/-) but not C3(+/+) recipients to be sensitive to complement activation, suggesting that circulating platelets in Pf4-Cre(+)-Crry(flox/flox) mice were naturally selected in a complement-sufficient environment. Notably, Pf4-Cre(+)-Crry(flox/flox) mouse platelets became complement susceptible when factor H function was blocked. Examination of Pf4-Cre(+)-Crry(flox/flox) mouse bone marrows revealed exceedingly active thrombopoiesis. Thus, under in vivo conditions, Crry/DAF deficiency on platelets led to abnormal platelet turnover, but peripheral platelet count was compensated for by increased thrombopoiesis. Selective survival of Crry/DAF-deficient platelets aided by factor H protection and compensatory thrombopoiesis demonstrates the cooperation between membrane and fluid phase complement inhibitors and the body's ability to adaptively respond to complement regulator deficiencies.
Diprosopus tetraophthalmus: CT as a complement to autopsy.

PubMed

Laor, T; Stanek, J; Leach, J L

2012-01-01

Diprosopus is the rarest form of conjoined twinning. This anomaly is characterised by craniofacial duplication to varying degrees and is associated with anomalies of the central nervous, cardiac, respiratory and musculoskeletal systems. We present an infant characterised as diprosopus tetraophthalmus who underwent post-mortem CT, which served as a highly useful complement to autopsy.
[An adult case of haemophilus parainfluenzae bacteremia and meningitis].

PubMed

Kangas, Ida

2010-01-04

A case of bacteremia and meningitis caused by Haemophilus parainfluenzae in an adult patient without known immunodeficiency and normal complement system is presented. H. parainfluenzae has not previously been reported as the cause of meningitis in Denmark. Patients with invasive H. parainfluenzae infection should be examined for complement factor 7 defect.
[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.
Multicentre physiological reference intervals for serum concentrations of immunoglobulins A, G and M, complement C3c and C4 measured with Tina-Quant reagents systems.

PubMed

Fuentes-Arderiu, Xavier; Alonso-Gregorio, Eduardo; Alvarez-Funes, Virtudes; Ambrós-Marigómez, Carmen; Coca-Fábregas, Lluís; Cruz-Placer, Marta; Díaz-Fernández, Julián; Pinel-Julián, María Pilar; Gutiérrez-Cecchini, Beatriz; Herrero-Bernal, Pilar; Sempere-Alcocer, Marcos; García-Caballero, Francisca; Del Mar Larrea-Ortiz-Quintana, María; La-Torre-Marcellán, Pedro; Del Señor López-Vélez, María; Mar-Medina, Carmen; Martín-Oncina, Javier; Rodríguez-Hernández, María Victoria; Romero-Sotomayor, María Victoria; Serrano-López, Cándido; Sicilia-Enríquez-de-Salamanca, Adolfo; Velasco-Romero, Ana María; Juvé-Cuxart, Santiago

2007-01-01

Clinical laboratories seeking accreditation for compliance with ISO 15189:2003 need to demonstrate that the physiological reference intervals communicated to all users of the laboratory service are appropriate for the patient population served and for the measurement systems used. In the case of immunological quantities, few articles have been published in peer-reviewed journals. A total of 21 clinical laboratories in different regions of Spain collaborated in identifying reference individuals and determining adult reference intervals for some immunological quantities measured using RD/Hitachi Modular Analytics analysers and Tina-Quant reagent systems. These immunological quantities are the mass concentrations of immunoglobulin A, immunoglobulin G, immunoglobulin M, complement C3c and complement C4 in serum. All the logistic work was carried out in co-operation with the supplier of the reagents and analysers (Roche Diagnostics España, S.L., Sant Cugat del Vallès, Catalonia, Spain). From the set of reference values obtained by each laboratory, multicentre reference limits were estimated non-parametrically. The reference intervals estimated in this study for concentrations of serum components under consideration are: complement C3c, 0.62-1.64 g/L for women and men; complement C4, 0.14-0.72 g/L for women and men; immunoglobulin A, 0.89-4.80 g/L for women and men; immunoglobulin G, 6.5-14.3 g/L for women and men; and immunoglobulin M, 0.48-3.38 g/L for women and 0.41-2.46 g/L for men.
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.
Role of capsule and suilysin in mucosal infection of complement-deficient mice with Streptococcus suis.

PubMed

Seitz, Maren; Beineke, Andreas; Singpiel, Alena; Willenborg, Jörg; Dutow, Pavel; Goethe, Ralph; Valentin-Weigand, Peter; Klos, Andreas; Baums, Christoph G

2014-06-01

Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3(-/-) mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal S. suis infection. S. suis WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3(-/-) mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3(-/-) mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT and C3(-/-) blood depended on capsule but not suilysin expression. Interestingly, S. suis invasion of inner organs was also detectable in C5aR(-/-) mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal S. suis infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal S. suis serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity.
Deposition of mannose-binding lectin and ficolins and activation of the lectin pathway of complement on the surface of polyurethane tubing used for cardiopulmonary bypass.

PubMed

Eppa, Łukasz; Pągowska-Klimek, Izabela; Świerzko, Anna S; Moll, Maciej; Krajewski, Wojciech R; Cedzyński, Maciej

2018-04-01

The artificial surface used for cardiopulmonary bypass (CPB) is a crucial factor activating the complement system and thus contributing to the generation of a systemic inflammatory response. The activation of classical and alternative pathways on this artificial surface is well known. In contrast, lectin pathway (LP) activation has not been fully investigated, although noted during CPB in several studies. Moreover, we have recently proved the contribution of the LP to the generation of the systemic inflammatory response syndrome after pediatric cardiac surgery. The aim of this study was to assess LP-mediated complement activation on the surface of polyurethane CPB circuit tubing (noncoated Chalice ® ), used for CPB procedures in children with congenital heart disease. We found deposition of mannose-binding lectin, ficolin-1, -2, and -3 on the surface of unused tubing and on tubing used for CPB from a small minority of patients. Furthermore, we observed deposition of complement C4 activation products on tubing used for CPB and previously unused tubing after incubation with normal serum. The latter finding indicates LP activation in vitro on the polyurethane surface. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1202-1208, 2018. © 2017 Wiley Periodicals, Inc.
Beneficial effects of Houttuynia cordata polysaccharides on "two-hit" acute lung injury and endotoxic fever in rats associated with anti-complementary activities.

PubMed

Lu, Yan; Jiang, Yun; Ling, Lijun; Zhang, Yunyi; Li, Hong; Chen, Daofeng

2018-03-01

Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins, and has also been used for the treatment of severe acute respiratory syndrome (SARS). In vitro, the crude H. cordata polysaccharides (CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury (ALI) induced by hemorrhagic shock plus lipopolysaccharide (LPS) instillation (two-hit) and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the "two-hit" ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid (BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidant-antioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heat-clearing function of H. cordata .
The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth

PubMed Central

Dunn, Alexis B.; Dunlop, Anne L.; Hogue, Carol J.; Miller, Andrew; Corwin, Elizabeth J.

2018-01-01

Preterm Birth (PTB, < 37 completed weeks' gestation) is one of the leading obstetrical problems in the United States affecting approximately 1 of every 9 births. Even more concerning are the persistent racial disparities in PTB with particularly high rates in African Americans. There are several recognized pathophysiologic pathways to PTB, including infection and/or exaggerated systemic or local inflammation. Intrauterine infection is a causal factor linked to PTB, thought to result most commonly from inflammatory processes triggered by microbial invasion of bacteria ascending from the vaginal microbiome. Trials to treat various infections have shown limited efficacy in reducing PTB risk, suggesting that other complex mechanisms, including those associated with inflammation, may be involved in the relationship between microbes, infection, and PTB. A key mediator of the inflammatory response, and recently shown to be associated with PTB, is the complement system, an innate defense mechanism involved in both normal physiologic processes that occur during pregnancy implantation, as well as processes that promote the elimination of pathogenic microbes. The purpose of this paper is to present a mechanistic model of inflammation-associated PTB, which hypothesizes a relationship between the microbiome and dysregulation of the complement system. Exploring the relationships between the microbial environment and complement biomarkers may elucidate a potentially modifiable biological pathway to preterm birth. PMID:28073296
COMPLEMENT DEVIATION IN SCARLET FEVER WITH COMPARATIVE STUDIES OF THE WASSERMANN AND NOGUCHI SYSTEMS

PubMed Central

Kolmer, John A.

1911-01-01

The Wassermann reaction in scarlet fever per se is uniformly negative. The antigen of scarlet fever liver yields practically the same results as that of luetic liver, and both fail to deviate complement with scarlet fever antibodies. The Noguchi reaction in scarlet fever is practically negative. Sixteen cases, or 6.4 per cent. of 250 cases, were positive when active serum was used; with inactivated serum, but eleven, or 4.4 per cent., remained positive. Five of these eleven cases were also positive with the Wassermann system. In other words, sixteen cases, or 6.4 per cent., were positive according to the Noguchi system with active or inactivated serum or both, whereas with the Wassermann system only 2 per cent. were positive. The presence of anti-sheep hemolysin normally in human serum is one of the main disturbing factors in the Wassermann system; for this reason, complement and hemolysin (made by immunization of rabbits) require careful titration. A positive Wassermann reaction usually indicates the presence of syphilitic antibodies, and a negative Noguchi reaction, their absence, and both systems should be used in the examination of all cases. PMID:19867467
Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

PubMed Central

Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

2016-01-01

The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032
Are Public Enterprises Inefficient?: Viewpoints of Western Scholars

ERIC Educational Resources Information Center

Fuqian, Fang

2006-01-01

People who advocate the privatization of public enterprises generally maintain that these enterprises, compared with private enterprises, have the following shortcomings: (1) public enterprises do not produce in response to consumer needs; (2) they use too much capital on inefficient production; (3) production often experiences breakdowns and…
Inefficient Self-Selection into Education and Wage Inequality

ERIC Educational Resources Information Center

Ordine, Patrizia; Rose, Giuseppe

2011-01-01

This paper proposes a theoretical framework where "within graduates" wage inequality is related to overeducation/educational mismatch in the labor market. We show that wage inequality may arise because of inefficient self-selection into education in the presence of ability-complementary technological progress and asymmetric information…

A Production System Version of the Hearsay-II Speech Understanding System

DTIC Science & Technology

1978-04-01

synchronization mechanisms turn out to be adequate with a rull complement of KSs. Finally, HSP is found to aid solution of the Small Address Problem, as it...much greater than that if HSP’s less powerful synchronization mechanisms turn out to be adequate with a full complement of KSs. Finally, HSP is...earlier version of HSII which had a limited set of KSs. With a richer set of KSs and/or a reduction (or elimination) of synchronization overheads, the
Transonic propulsion system integration analysis at McDonnell Aircraft Company

NASA Technical Reports Server (NTRS)

Cosner, Raymond R.

1989-01-01

The technology of Computational Fluid Dynamics (CFD) is becoming an important tool in the development of aircraft propulsion systems. Two of the most valuable features of CFD are: (1) quick acquisition of flow field data; and (2) complete description of flow fields, allowing detailed investigation of interactions. Current analysis methods complement wind tunnel testing in several ways. Herein, the discussion is focused on CFD methods. However, aircraft design studies need data from both CFD and wind tunnel testing. Each approach complements the other.
Complement-Related Regulates Autophagy in Neighboring Cells.

PubMed

Lin, Lin; Rodrigues, Frederico S L M; Kary, Christina; Contet, Alicia; Logan, Mary; Baxter, Richard H G; Wood, Will; Baehrecke, Eric H

2017-06-29

Autophagy degrades cytoplasmic components and is important for development and human health. Although autophagy is known to be influenced by systemic intercellular signals, the proteins that control autophagy are largely thought to function within individual cells. Here, we report that Drosophila macroglobulin complement-related (Mcr), a complement ortholog, plays an essential role during developmental cell death and inflammation by influencing autophagy in neighboring cells. This function of Mcr involves the immune receptor Draper, suggesting a relationship between autophagy and the control of inflammation. Interestingly, Mcr function in epithelial cells is required for macrophage autophagy and migration to epithelial wounds, a Draper-dependent process. This study reveals, unexpectedly, that complement-related from one cell regulates autophagy in neighboring cells via an ancient immune signaling program. Copyright © 2017 Elsevier Inc. All rights reserved.
The Impact of Early Design Phase Risk Identification Biases on Space System Project Performance

NASA Technical Reports Server (NTRS)

Reeves, John D., Jr.; Eveleigh, Tim; Holzer, Thomas; Sarkani, Shahryar

2012-01-01

Risk identification during the early design phases of complex systems is commonly implemented but often fails to result in the identification of events and circumstances that truly challenge project performance. Inefficiencies in cost and schedule estimation are usually held accountable for cost and schedule overruns, but the true root cause is often the realization of programmatic risks. A deeper understanding of frequent risk identification trends and biases pervasive during space system design and development is needed, for it would lead to improved execution of existing identification processes and methods.
Prepregnancy obesity and complement system activation in early pregnancy and the subsequent development of preeclampsia.

PubMed

Lynch, Anne M; Eckel, Robert H; Murphy, James R; Gibbs, Ronald S; West, Nancy A; Giclas, Patricia C; Salmon, Jane E; Holers, V Michael

2012-05-01

We hypothesized that women who are obese before they become pregnant and also have elevations of complement Bb and C3a in the top quartile in early pregnancy would have the highest risk of preeclampsia compared with a referent group of women who were not obese and had levels of complement less than the top quartile. This was a prospective study of 1013 women recruited at less than 20 weeks' gestation. An EDTA-plasma sample was obtained, and complement fragments were measured using enzyme-linked immunosorbent assays. The data were analyzed using univariable and multivariable logistic regression analysis. Women who were obese with levels of Bb or C3a in the top quartile were 10.0 (95% confidence interval, 3.3-30) and 8.8 (95% confidence interval, 3-24) times, respectively, more likely to develop preeclampsia compared with the referent group. We demonstrate a combined impact of obesity and elevated complement on the development of preeclampsia. Copyright © 2012. Published by Mosby, Inc.
A versatile assay to determine bacterial and host factors contributing to opsonophagocytotic killing in hirudin-anticoagulated whole blood.

PubMed

van der Maten, Erika; de Jonge, Marien I; de Groot, Ronald; van der Flier, Michiel; Langereis, Jeroen D

2017-02-08

Most bacteria entering the bloodstream will be eliminated through complement activation on the bacterial surface and opsonophagocytosis. However, when these protective innate immune systems do not work optimally, or when bacteria are equipped with immune evasion mechanisms that prevent killing, this can lead to serious infections such as bacteremia and meningitis, which is associated with high morbidity and mortality. In order to study the complement evasion mechanisms of bacteria and the capacity of human blood to opsonize and kill bacteria, we developed a versatile whole blood killing assay wherein both phagocyte function and complement activity can easily be monitored and modulated. In this assay we use a selective thrombin inhibitor hirudin to fully preserve complement activity of whole blood. This assay allows controlled analysis of the requirements for active complement by replacing or heat-inactivating plasma, phagocyte function and bacterial immune evasion mechanisms that contribute to survival in human blood.
A versatile assay to determine bacterial and host factors contributing to opsonophagocytotic killing in hirudin-anticoagulated whole blood

PubMed Central

van der Maten, Erika; de Jonge, Marien I.; de Groot, Ronald; van der Flier, Michiel; Langereis, Jeroen D.

2017-01-01

Most bacteria entering the bloodstream will be eliminated through complement activation on the bacterial surface and opsonophagocytosis. However, when these protective innate immune systems do not work optimally, or when bacteria are equipped with immune evasion mechanisms that prevent killing, this can lead to serious infections such as bacteremia and meningitis, which is associated with high morbidity and mortality. In order to study the complement evasion mechanisms of bacteria and the capacity of human blood to opsonize and kill bacteria, we developed a versatile whole blood killing assay wherein both phagocyte function and complement activity can easily be monitored and modulated. In this assay we use a selective thrombin inhibitor hirudin to fully preserve complement activity of whole blood. This assay allows controlled analysis of the requirements for active complement by replacing or heat-inactivating plasma, phagocyte function and bacterial immune evasion mechanisms that contribute to survival in human blood. PMID:28176849
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.
Investigating the Complex Chemistry of Functional Energy Storage Systems: The Need for an Integrative, Multiscale (Molecular to Mesoscale) Perspective.

PubMed

Abraham, Alyson; Housel, Lisa M; Lininger, Christianna N; Bock, David C; Jou, Jeffrey; Wang, Feng; West, Alan C; Marschilok, Amy C; Takeuchi, Kenneth J; Takeuchi, Esther S

2016-06-22

Electric energy storage systems such as batteries can significantly impact society in a variety of ways, including facilitating the widespread deployment of portable electronic devices, enabling the use of renewable energy generation for local off grid situations and providing the basis of highly efficient power grids integrated with energy production, large stationary batteries, and the excess capacity from electric vehicles. A critical challenge for electric energy storage is understanding the basic science associated with the gap between the usable output of energy storage systems and their theoretical energy contents. The goal of overcoming this inefficiency is to achieve more useful work (w) and minimize the generation of waste heat (q). Minimization of inefficiency can be approached at the macro level, where bulk parameters are identified and manipulated, with optimization as an ultimate goal. However, such a strategy may not provide insight toward the complexities of electric energy storage, especially the inherent heterogeneity of ion and electron flux contributing to the local resistances at numerous interfaces found at several scale lengths within a battery. Thus, the ability to predict and ultimately tune these complex systems to specific applications, both current and future, demands not just parametrization at the bulk scale but rather specific experimentation and understanding over multiple length scales within the same battery system, from the molecular scale to the mesoscale. Herein, we provide a case study examining the insights and implications from multiscale investigations of a prospective battery material, Fe3O4.
Renewing VET Provision: Understanding Feedback Mechanisms between Initial VET and the Labour Market. Research Paper No 37

ERIC Educational Resources Information Center

Cedefop - European Centre for the Development of Vocational Training, 2013

2013-01-01

A strong VET system is increasingly seen as essential to overcoming the current economic crisis in Europe. VET is seen as a powerful tool to assist in balancing labour market inefficiencies, increasing youth employment possibilities, and reducing skills mismatch. Its inherent flexibility and closeness to the labour market place VET in a good…
What Is the Real Efficiency of Bulbs?

ERIC Educational Resources Information Center

Polacek, Lubos

2012-01-01

Bulbs are considered to be very inefficient sources of light. Bulbs give light and heat. As we use them for a long time, especially in winter, a large part of the heat produced by bulbs lowers the power consumption of the heating system. In this paper the problem of the real efficiency of a bulb is solved when both the lighting and heating effects…
The Challenges for Physicians of Demonstrating Continuing Competence in the Changing World of Medical Regulation: Osteopathic Pediatrician Case Report

ERIC Educational Resources Information Center

Langenau, Erik E.; Gimpel, John R.

2012-01-01

The current system of continuing medical education, maintenance of certification, and renewal of medical licenses can be quite burdensome and inefficient for all practicing physicians: medical doctors (M.D.s) and doctors of osteopathic medicine (D.O.s). D.O.s have opportunities for residency training and specialty certification which are not…
Translating Policy into Practice: The Role of Intermediary Agents in a Fully Centralized and Highly Hierarchical Educational System

ERIC Educational Resources Information Center

Syed Anuar, Sarifah Norazah

2013-01-01

Variations in educational policy outcomes have always been perceived as policy failures, and they are often associated with policymakers insensitivity to what is happening down at the grass roots level, and with implementers' inefficiency and non-compliance. Based on institutional theory, the nested layers theory in particular, and the Four…
The Impact of Managerialism on the Strategy Work of University Middle Managers

ERIC Educational Resources Information Center

Davis, Annemarie; Jansen van Rensburg, Mari; Venter, Peet

2016-01-01

In an attempt to understand the effects of managerialism on university managers in a developing country, we set out to gather rich data on the strategy work of middle managers through a single case study at a South African university. Managerialism has the potential to solve inefficiencies in university systems and processes, as it could help to…
JPRS Report, China.

DTIC Science & Technology

1992-08-03

to the outside economic system, truly placing plans on a conscious world, we need a peaceful international environment basis and a foundation of the...the permanently. The "Government Work Report" also international environment is favorable. We have all the went on to clarify several important...inefficient and wasteful consumption of capital goods outside the plan dropped. Between January coal also has exacerbated environmental pollution, and
Responsibility Factors of Reducing Inefficiencies in Information System Processes and Their Role on Intention to Acquire Six Sigma Certification

ERIC Educational Resources Information Center

Hejazi, Sara

2009-01-01

Organizations worldwide have been turning to Six Sigma program (SSP) to eliminate the defects in their products or drive out the variability in their processes to attain a competitive advantage in their marketplace. An effective certification program has been touted as a major contributor to successful implementation of SSP. An effective…
Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.

PubMed

Zhang, Jie; Niu, Na; Li, Bingjie; McNutt, Michael A

2013-12-01

Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.
Artificial neural network models: A decision support tool for enhancing seedling selection in sugarcane

USDA-ARS?s Scientific Manuscript database

Currently, sugarcane selection begins at the seedling stage with visual selection for cane yield and other yield-related traits. Although subjective and inefficient, visual selection remains the primary method for selection. Visual selection is inefficient because of the confounding effect of genoty...
Deconstructing the Myth of American Public Schooling Inefficiency

ERIC Educational Resources Information Center

Baker, Bruce D.; Weber, Mark

2016-01-01

In this paper, the authors begin by classifying the arguments that assert American schools are relatively inefficient into two categories: the "long-term trend argument" and the "international comparison argument." Their focus herein is on the latter of these two. They then describe two frameworks for approaching either of…
The promise of air cargo: System aspects and vehicle design

NASA Technical Reports Server (NTRS)

Whitehead, A. H., Jr.

1976-01-01

The current operation of the air cargo system is reviewed. An assessment of the future of air cargo is provided by: (1) analyzing statistics and trends, (2) by noting system problems and inefficiencies, (3) by analyzing characteristics of 'air eligible' commodities, and (4) by showing the promise of new technology for future cargo aircraft with significant improvements in costs and efficiency. The following topics are discussed: (1) air cargo demand forecasts; (2) economics of air cargo transport; (3) the integrated air cargo system; (4) evolution of airfreighter design; and (5) the span distributed load concept.

Fault-tolerant software - Experiment with the sift operating system. [Software Implemented Fault Tolerance computer

NASA Technical Reports Server (NTRS)

Brunelle, J. E.; Eckhardt, D. E., Jr.

1985-01-01

Results are presented of an experiment conducted in the NASA Avionics Integrated Research Laboratory (AIRLAB) to investigate the implementation of fault-tolerant software techniques on fault-tolerant computer architectures, in particular the Software Implemented Fault Tolerance (SIFT) computer. The N-version programming and recovery block techniques were implemented on a portion of the SIFT operating system. The results indicate that, to effectively implement fault-tolerant software design techniques, system requirements will be impacted and suggest that retrofitting fault-tolerant software on existing designs will be inefficient and may require system modification.
[Construction of enterohemorrhagic Escherichia coli O157:H7 strains with espF gene deletion and complementation].

PubMed

Hua, Ying; Sun, Qi; Wang, Xiangyu; DU, Yanli; Shao, Na; Zhang, Qiwei; Zhao, Wei; Wan, Chengsong

2015-11-01

To construct enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains with delection espF gene and its nucleotide fragment and with espF gene complementation. A pair of homologous arm primers was designed to amplify the gene fragment of kanamycin resistance, which was transformed into EHEC O157:H7 EDL933w strain via the PKD46 plasmid by electroporation. The replacement of the espF gene by kanamycin resistance gene through the PKD46-mediated red recombination system was confirmed by PCR and sequencing. The entire coding region of espF along with its nucleotide fragment was amplified by PCR and cloned into pBAD33 plasmid, which was transformed into a mutant strain to construct the strain with espF complementation. RT-PCR was used to verify the transcription of espF and its nucleotide fragment in the complemented mutant strain. We established EHEC O157:H7 EDL933w strains with espF gene deletion and with espF gene complementation. Both espF and its nucleotide fragment were transcribed in the complemented mutant strain. The two strains provide a basis for further study of the regulatory mechanism of espF.
Increasing value and reducing waste in biomedical research regulation and management

PubMed Central

Salman, Rustam Al-Shahi; Beller, Elaine; Kagan, Jonathan; Hemminki, Elina; Phillips, Robert S; Savulescu, Julian; Macleod, Malcolm; Wisely, Janet; Chalmers, Iain

2014-01-01

After identification of an important research question and selection of an appropriate study design, waste can arise from the regulation, governance, and management of biomedical research. Obtaining regulatory and governance approval has become increasingly burdensome and disproportionate to the conceivable risks to research participants. Regulation and governance involve interventions that are assumed to be justified in the interests of patients and the public, but they can actually compromise these interests. Inefficient management of the procedural conduct of research is wasteful, especially if it results in poor recruitment and retention of participants in well designed studies addressing important questions. These sources of waste can be minimised if the following four recommendations are addressed. First, regulators should use their influence to reduce other causes of waste and inefficiency in research. Second, regulators and policy makers should work with researchers, patients, and health professionals to streamline and harmonise the laws, regulations, guidelines, and processes that govern whether and how research can be done, and ensure that they are proportionate to the plausible risks associated with the research. Third, researchers and research managers should increase the efficiency of recruitment, retention, data monitoring, and data sharing in research through use of research designs known to reduce inefficiencies, and further research should be done to learn how efficiency can be increased. Finally, everyone, particularly those responsible for health-care systems, should promote integration of research into everyday clinical practice. Regulators and researchers should monitor adherence to each of these recommendations and publish metrics. PMID:24411646
Diprosopus tetraophthalmus: CT as a complement to autopsy

PubMed Central

Laor, T; Stanek, J; Leach, J L

2012-01-01

Diprosopus is the rarest form of conjoined twinning. This anomaly is characterised by craniofacial duplication to varying degrees and is associated with anomalies of the central nervous, cardiac, respiratory and musculoskeletal systems. We present an infant characterised as diprosopus tetraophthalmus who underwent post-mortem CT, which served as a highly useful complement to autopsy. PMID:22190755
Development of a portable teleoperated robot for the manipulation of a backhoe shovel for the restoration of disaster-stricken sites

NASA Astrophysics Data System (ADS)

Tanaka, Toshihiko; Sakai, Yosiharu; Konomi, Yosiyuki; Chayama, Kazuhiro; Minamoto, Masahiko; Matsunaga, Katsuya

1999-11-01

Restoration activities after disasters such as landslides or rock avalanches require rapid action, but in fact, in most cases these activities are very inefficient because of the danger of secondary disasters. A system which can operate reconstruction machinery by remote control was therefore developed, and it was installed on general-purpose construction machines (backhoe shovels). Control performance experiments and field experiments on this developed system were carried out, and its effectiveness was confirmed.
Resonance-shifting luminescent solar concentrators

DOEpatents

Giebink, Noel Christopher; Wiederrecht, Gary P; Wasielewski, Michael R

2014-09-23

An optical system and method to overcome luminescent solar concentrator inefficiencies by resonance-shifting, in which sharply directed emission from a bi-layer cavity into a glass substrate returns to interact with the cavity off-resonance at each subsequent reflection, significantly reducing reabsorption loss en route to the edges. In one embodiment, the system comprises a luminescent solar concentrator comprising a transparent substrate, a luminescent film having a variable thickness; and a low refractive index layer disposed between the transparent substrate and the luminescent film.
Resonance-shifting luminescent solar concentrators

DOEpatents

Giebink, Noel Christopher; Wiederrecht, Gary P.; Wasielewski, Michael R.

2018-01-23

An optical system and method to overcome luminescent solar concentrator inefficiencies by resonance-shifting, in which sharply directed emission from a bi-layer cavity into a glass substrate returns to interact with the cavity off-resonance at each subsequent reflection, significantly reducing reabsorption loss en route to the edges. In one embodiment, the system comprises a luminescent solar concentrator comprising a transparent substrate, a luminescent film having a variable thickness; and a low refractive index layer disposed between the transparent substrate and the luminescent film.
Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response

PubMed Central

Ramos-Sevillano, Elisa; Urzainqui, Ana; Campuzano, Susana; Moscoso, Miriam; González-Camacho, Fernando; Domenech, Mirian; Rodríguez de Córdoba, Santiago; Sánchez-Madrid, Francisco; Brown, Jeremy S.; García, Ernesto

2014-01-01

The complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to S. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the lytA ply double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia. PMID:25404032
A robust hypothesis test for the sensitive detection of constant speed radiation moving sources

NASA Astrophysics Data System (ADS)

Dumazert, Jonathan; Coulon, Romain; Kondrasovs, Vladimir; Boudergui, Karim; Moline, Yoann; Sannié, Guillaume; Gameiro, Jordan; Normand, Stéphane; Méchin, Laurence

2015-09-01

Radiation Portal Monitors are deployed in linear networks to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal-to-noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes a benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive backgrounds, and a vehicle source carrier under the same respectively high and low count rate radioactive backgrounds, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm. It also guarantees that the optimal coverage factor for this compromise remains stable regardless of signal-to-noise ratio variations between 2 and 0.8, therefore allowing the final user to parametrize the test with the sole prior knowledge of background amplitude.
In-situ, In-Memory Stateful Vector Logic Operations based on Voltage Controlled Magnetic Anisotropy.

PubMed

Jaiswal, Akhilesh; Agrawal, Amogh; Roy, Kaushik

2018-04-10

Recently, the exponential increase in compute requirements demanded by emerging applications like artificial intelligence, Internet of things, etc. have rendered the state-of-art von-Neumann machines inefficient in terms of energy and throughput owing to the well-known von-Neumann bottleneck. A promising approach to mitigate the bottleneck is to do computations as close to the memory units as possible. One extreme possibility is to do in-situ Boolean logic computations by using stateful devices. Stateful devices are those that can act both as a compute engine and storage device, simultaneously. We propose such stateful, vector, in-memory operations using voltage controlled magnetic anisotropy (VCMA) effect in magnetic tunnel junctions (MTJ). Our proposal is based on the well known manufacturable 1-transistor - 1-MTJ bit-cell and does not require any modifications in the bit-cell circuit or the magnetic device. Instead, we leverage the very physics of the VCMA effect to enable stateful computations. Specifically, we exploit the voltage asymmetry of the VCMA effect to construct stateful IMP (implication) gate and use the precessional switching dynamics of the VCMA devices to propose a massively parallel NOT operation. Further, we show that other gates like AND, OR, NAND, NOR, NIMP (complement of implication) can be implemented using multi-cycle operations.
Fast time-domain measurements on telecom single photons

NASA Astrophysics Data System (ADS)

Allgaier, Markus; Vigh, Gesche; Ansari, Vahid; Eigner, Christof; Quiring, Viktor; Ricken, Raimund; Brecht, Benjamin; Silberhorn, Christine

2017-09-01

Direct measurements on the temporal envelope of quantum light are a challenging task and not many examples are known because most classical pulse characterisation methods do not work on the single-photon level. Knowledge of both spectrum and timing can, however, give insights on properties that cannot be determined by the spectral intensity alone. While temporal measurements on single photons on timescales of tens of picoseconds are possible with superconducting photon detectors, and picosecond measurements have been performed using streak cameras, there are no commercial single-photon sensitive devices with femtosecond resolution available. While time-domain sampling using sum-frequency generation has already been exploited for such a measurement, inefficient conversion has necessitated long integration times to build the temporal profile. We demonstrate a highly efficient waveguided sum-frequency generation process in Lithium Niobate to measure the temporal envelope of single photons with femtosecond resolution with short enough acquisition time to provide a live-view of the measurement. We demonstrate the measurement technique and combine it with spectral measurements using a dispersive-fibre time-of-flight spectrometer to determine upper and lower bounds for the spectral purity of heralded single photons. The approach complements the joint spectral intensity measurements as a measure on the purity can be given without knowledge of the spectral phase.
Human Properdin Opsonizes Nanoparticles and Triggers a Potent Pro-inflammatory Response by Macrophages without Involving Complement Activation

PubMed Central

Kouser, Lubna; Paudyal, Basudev; Kaur, Anuvinder; Stenbeck, Gudrun; Jones, Lucy A.; Abozaid, Suhair M.; Stover, Cordula M.; Flahaut, Emmanuel; Sim, Robert B.; Kishore, Uday

2018-01-01

Development of nanoparticles as tissue-specific drug delivery platforms can be considerably influenced by the complement system because of their inherent pro-inflammatory and tumorigenic consequences. The complement activation pathways, and its recognition subcomponents, can modulate clearance of the nanoparticles and subsequent inflammatory response and thus alter the intended translational applications. Here, we report, for the first time, that human properdin, an upregulator of the complement alternative pathway, can opsonize functionalized carbon nanotubes (CNTs) via its thrombospondin type I repeat (TSR) 4 and 5. Binding of properdin and TSR4+5 is likely to involve charge pattern/polarity recognition of the CNT surface since both carboxymethyl cellulose-coated carbon nanotubes (CMC-CNT) and oxidized (Ox-CNT) bound these proteins well. Properdin enhanced the uptake of CMC-CNTs by a macrophage cell line, THP-1, mounting a robust pro-inflammatory immune response, as revealed by qRT-PCR, multiplex cytokine array, and NF-κB nuclear translocation analyses. Properdin can be locally synthesized by immune cells in an inflammatory microenvironment, and thus, its interaction with nanoparticles is of considerable importance. In addition, recombinant TSR4+5 coated on the CMC-CNTs inhibited complement consumption by CMC-CNTs, suggesting that nanoparticle decoration with TSR4+5, can be potentially used as a complement inhibitor in a number of pathological contexts arising due to exaggerated complement activation. PMID:29483907
The role of complement in myasthenia gravis: serological evidence of complement consumption in vivo.

PubMed

Romi, Fredrik; Kristoffersen, Einar K; Aarli, Johan A; Gilhus, Nils Erik

2005-01-01

Antibodies to the acetylcholine receptor (AChR) titin and the ryanodine receptor (RyR) occur in myasthenia gravis (MG). These antibodies are capable of complement activation in vitro. The involvement of the complement system should cause consumption of complement components such as C3 and C4 in vivo. Complement components C3 and C4 were assayed in sera from 78 AChR antibody-positive MG patients and 52 healthy controls. Forty-eight of the patient sera contained titin antibodies as well, and 20 were also RyR antibody-positive. MG patients with AChR antibody concentrations above the median (11.2 nmol/l) had significantly lower mean C3 and C4 concentrations in serum compared to those with AChR antibody concentrations below the median. Titin antibody-positive MG patients, titin antibody-negative early-onset MG patients, titin antibody-negative late-onset MG patients, and controls had similar C3 and C4 concentrations. Nor did mean C3 and C4 concentrations differ in MG patients with RyR antibodies. Patients with severe MG (grades 4 and 5) had similar C3 and similar C4 levels compared to those with mild MG (grades 1 and 2). An increased in vivo complement consumption was detected in MG patients with high AChR antibody concentrations, unrelated to MG severity and non-AChR muscle antibodies.
Analysis of space systems for the space disposal of nuclear waste follow-on study. Volume 2: Technical report

NASA Technical Reports Server (NTRS)

1982-01-01

The space option for disposal of certain high-level nuclear wastes in space as a complement to mined geological repositories is studied. A brief overview of the study background, scope, objective, guidelines and assumptions, and contents is presented. The determination of the effects of variations in the waste mix on the space systems concept to allow determination of the space systems effect on total system risk benefits when used as a complement to the DOE reference mined geological repository is studied. The waste payload system, launch site, launch system, and orbit transfer system are all addressed. Rescue mission requirements are studied. The characteristics of waste forms suitable for space disposal are identified. Trajectories and performance requirements are discussed.
Alternative complement pathway activation increases mortality in a model of burn injury in mice.

PubMed Central

Gelfand, J A; Donelan, M; Hawiger, A; Burke, J F

1982-01-01

We have studied the role of the complement system in burn injury in an experimental model in mice. A 25% body surface area, full-thickness scald wound was produced in anesthetized animals. Massive activation of the alternative complement pathway, but not the classical pathway, was seen. This activation was associated with the generation of neutrophil aggregating activity in the plasma, neutrophil aggregates in the lungs, increased pulmonary vascular permeability, and increased lung edema formation. Decomplementation with cobra venom factor (CVF) or genetic C5 deficiency diminished these pathologic changes, and CVF pretreatment substantially reduced burn mortality in the first 24 h. Preliminary data show that human burn patients have a similar pattern of complement activation involving predominantly the alternative pathway, indicating the possible relevance of the murine model to human disease. Images PMID:7174787
Role of Capsule and Suilysin in Mucosal Infection of Complement-Deficient Mice with Streptococcus suis

PubMed Central

Seitz, Maren; Beineke, Andreas; Singpiel, Alena; Willenborg, Jörg; Dutow, Pavel; Goethe, Ralph; Valentin-Weigand, Peter; Klos, Andreas

2014-01-01

Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3−/− mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal S. suis infection. S. suis WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3−/− mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3−/− mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT and C3−/− blood depended on capsule but not suilysin expression. Interestingly, S. suis invasion of inner organs was also detectable in C5aR−/− mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal S. suis infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal S. suis serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity. PMID:24686060
Marked central nervous system pathology in CD59 knockout rats following passive transfer of Neuromyelitis optica immunoglobulin G.

PubMed

Yao, Xiaoming; Verkman, Alan S

2017-02-17

Neuromyelitis optica spectrum disorders (herein called NMO) is an inflammatory demyelinating disease of the central nervous system in which pathogenesis involves complement-dependent cytotoxicity (CDC) produced by immunoglobulin G autoantibodies targeting aquaporin-4 (AQP4-IgG) on astrocytes. We reported evidence previously, using CD59 -/- mice, that the membrane-associated complement inhibitor CD59 modulates CDC in NMO (Zhang and Verkman, J. Autoimmun. 53:67-77, 2014). Motivated by the observation that rats, unlike mice, have human-like complement activity, here we generated CD59 -/- rats to investigate the role of CD59 in NMO and to create NMO pathology by passive transfer of AQP4-IgG under conditions in which minimal pathology is produced in normal rats. CD59 -/- rats generated by CRISPR/Cas9 technology showed no overt phenotype at baseline except for mild hemolysis. CDC assays in astrocyte cultures and cerebellar slices from CD59 -/- rats showed much greater sensitivity to AQP4-IgG and complement than those from CD59 +/+ rats. Intracerebral administration of AQP4-IgG in CD59 -/- rats produced marked NMO pathology, with astrocytopathy, inflammation, deposition of activated complement, and demyelination, whereas identically treated CD59 +/+ rats showed minimal pathology. A single, intracisternal injection of AQP4-IgG in CD59 -/- rats produced hindlimb paralysis by 3 days, with inflammation and deposition of activated complement in spinal cord, optic nerves and brain periventricular and surface matter, with most marked astrocyte injury in cervical spinal cord. These results implicate an important role of CD59 in modulating NMO pathology in rats and demonstrate amplification of AQP4-IgG-induced NMO disease with CD59 knockout.
Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response.

PubMed

van Vollenhoven, Ronald F; Petri, Michelle A; Cervera, Ricard; Roth, David A; Ji, Beulah N; Kleoudis, Christi S; Zhong, Z John; Freimuth, William

2012-08-01

To identify factors that predict response to belimumab treatment in the phase 3 BLISS trials of autoantibody-positive systemic lupus erythematosus (SLE) and further analyse clinical efficacy in various patient subsets. The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo, all plus standard SLE therapy, over 52 or 76 weeks. Pooled subgroup analyses of week 52 SLE responder index rates (the primary endpoint in both trials) were performed based on demographic characteristics and baseline disease activity indicators. Pooled multivariate analysis was performed to determine predictors of response and treatment effect. Pooled univariate and multivariate analyses (N=1684) identified baseline factors associated with an increased benefit of belimumab versus placebo. These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) ≥10, low complement, anti-dsDNA positivity and corticosteroid use. Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA-SLEDAI ≥10 subgroups. Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7%, 41.5% (p=0.002) and 51.5% (p<0.001) with placebo and belimumab 1 mg/kg and 10 mg/kg, respectively; corresponding rates in the SELENA-SLEDAI ≥10 subgroup were 44.3%, 58.0% (p<0.001) and 63.2% (p<0.001). Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo, belimumab produced greater benefits regarding severe flares, corticosteroid use and health-related quality of life. These findings suggest that belimumab has greater therapeutic benefit than standard therapy alone in patients with higher disease activity, anti-dsDNA positivity, low complement or corticosteroid treatment at baseline. CLINICALTRIALS.GOV: identifiers NCT00424476 and NCT00410384.
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
Installation-Wide Energy Conservation Demonstration at Fort McClellan, Alabama

DTIC Science & Technology

1988-11-01

Inefficient Electrical Motors 12 Dispensary Chiller Installation 12 Combustion Optimization of Gas-fired Heating Equipment 12 Infiltration Study of Family... Chiller Installation 34 5 FAMILY HOUSING .................................................... 37 Combustion Optimization of Gas-fired Heating...in Outdoor Air Ventilation 59 Replacement of Inefficient Electric Motors 59 Dispensary Chiller Installation 60 Combustion Optimization of Gas-fired

Effect of Food Regulation on the Spanish Food Processing Industry: A Dynamic Productivity Analysis.

PubMed

Kapelko, Magdalena; Oude Lansink, Alfons; Stefanou, Spiro E

2015-01-01

This article develops the decomposition of the dynamic Luenberger productivity growth indicator into dynamic technical change, dynamic technical inefficiency change and dynamic scale inefficiency change in the dynamic directional distance function context using Data Envelopment Analysis. These results are used to investigate for the Spanish food processing industry the extent to which dynamic productivity growth and its components are affected by the introduction of the General Food Law in 2002 (Regulation (EC) No 178/2002). The empirical application uses panel data of Spanish meat, dairy, and oils and fats industries over the period 1996-2011. The results suggest that in the oils and fats industry the impact of food regulation on dynamic productivity growth is negative initially and then positive over the long run. In contrast, the opposite pattern is observed for the meat and dairy processing industries. The results further imply that firms in the meat processing and oils and fats industries face similar impacts of food safety regulation on dynamic technical change, dynamic inefficiency change and dynamic scale inefficiency change.
Value for money of changing healthcare services? Economic evaluation of quality improvement

PubMed Central

Severens, J

2003-01-01

   There are many instances of perceived or real inefficiencies in health service delivery. Both healthcare providers and policy makers need to know the impact and cost of applying strategies to change the behaviour of individuals or organisations. Quality improvement or implementation research is concerned with evaluating the methods of behavioural change. Addressing inefficiencies in healthcare services raises a series of issues, beginning with how inefficiency itself should be defined. The basic concepts of cost analysis and economic evaluations are explained and a model for working through the economic issues of quality improvement is discussed. This model combines the costs and benefits of corrected inefficiency with the costs and degree of behavioural change achieved by a quality improvement method in the policy maker's locality. It shows why it may not always be cost effective for policy makers to address suboptimal behaviour. Both the interpretation of quality improvement research findings and their local application need careful consideration. The limited availability of applicable quality improvement research may make it difficult to provide robust advice on the value for money of many behavioural quality improvement strategies. PMID:14532369
Effect of Food Regulation on the Spanish Food Processing Industry: A Dynamic Productivity Analysis

PubMed Central

Kapelko, Magdalena; Lansink, Alfons Oude; Stefanou, Spiro E.

2015-01-01

This article develops the decomposition of the dynamic Luenberger productivity growth indicator into dynamic technical change, dynamic technical inefficiency change and dynamic scale inefficiency change in the dynamic directional distance function context using Data Envelopment Analysis. These results are used to investigate for the Spanish food processing industry the extent to which dynamic productivity growth and its components are affected by the introduction of the General Food Law in 2002 (Regulation (EC) No 178/2002). The empirical application uses panel data of Spanish meat, dairy, and oils and fats industries over the period 1996-2011. The results suggest that in the oils and fats industry the impact of food regulation on dynamic productivity growth is negative initially and then positive over the long run. In contrast, the opposite pattern is observed for the meat and dairy processing industries. The results further imply that firms in the meat processing and oils and fats industries face similar impacts of food safety regulation on dynamic technical change, dynamic inefficiency change and dynamic scale inefficiency change. PMID:26057878
Aggregation in organic light emitting diodes

NASA Astrophysics Data System (ADS)

Meyer, Abigail

Organic light emitting diode (OLED) technology has great potential for becoming a solid state lighting source. However, there are inefficiencies in OLED devices that need to be understood. Since these inefficiencies occur on a nanometer scale there is a need for structural data on this length scale in three dimensions which has been unattainable until now. Local Electron Atom Probe (LEAP), a specific implementation of Atom Probe Tomography (APT), is used in this work to acquire morphology data in three dimensions on a nanometer scale with much better chemical resolution than is previously seen. Before analyzing LEAP data, simulations were used to investigate how detector efficiency, sample size and cluster size affect data analysis which is done using radial distribution functions (RDFs). Data is reconstructed using the LEAP software which provides mass and position data. Two samples were then analyzed, 3% DCM2 in C60 and 2% DCM2 in Alq3. Analysis of both samples indicated little to no clustering was present in this system.
Evaluation of operating room suite efficiency in the Veterans Health Administration system by using data-envelopment analysis.

PubMed

Basson, Marc D; Butler, Timothy

2006-11-01

Operating room (OR) activity transcends single ratios such as cases/room, but weighting multiple inputs and outputs may be arbitrary. Data-envelopment analysis (DEA) is a novel technique by which each facility is analyzed by the weightings that optimize its score. We performed DEA analysis of 23 Veterans Health Administration annual OR activity; 87,180 cases were performed, 24 publications generated, and 560 trainee-years of education delivered, in 168 ORs over 166,377 hours by 1,384 full-time equivalents of surgical and anesthesia providers and 523 nonproviders. Varying analyzed parameters produced similar efficiency rankings, with individual differences suggesting possible inefficiencies. We characterized returns to scale for efficient sites, suggesting whether patient flow might be efficiently further increased through these sites. We matched inefficient sites to similar efficient sites for comparison and suggested resource alterations to increase efficiency. Broader DEA application might characterize OR efficiency more informatively than conventional single-ratio rank ordering.
A study of the efficiency of hydrogen liquefaction

NASA Technical Reports Server (NTRS)

Baker, C. R.; Shaner, R. L.

1976-01-01

The use of liquid hydrogen as a jet aircraft fuel has a number of environmental and technological advantages over conventional fuels. The liquefaction of hydrogen requires a large expenditure of energy. There are many inefficiencies that are a part of any practical liquefaction process. Current technology was investigated for the best available system. Parametric studies were made to identify where inefficiencies occur and to optimize and integrate the component parts. Flowsheets are presented for a module that produces 250 tons per day of liquid hydrogen. Approximately ten of these modules is needed for a major airport in the 1990's. The advantages of producing a product with a minimum amount of ortho to para hydrogen conversion are pointed out. The optimum degree of conversion was determined for a liquid hydrogen product that will be used within a given time. An assessment was made regarding the potentials for improvement of the processing schemes and equipment over the next 10 to 25 years.
Multifuel industrial steam generation

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

Mesko, J.E.

An inefficient, unreliable steam generation and distribution system at the Red River Army Depot (Texarkana, Tex.), a major industrial facility of the federal government, was replaced with a modern, multifuel-burning steam plant. In the new plant, steam is generated by three high-pressure field-erected boilers burning 100 percent coal, 100 percent refuse, or any combination of the two, while maintaining particulate emissions, SO{sub 2} concentration, and NO{sub x} and chlorine levels at or better than clean air standards. The plant, which has been in operation since 1986, is now part of the Army's Energy/Environment Showcase for demonstrating innovative technology to publicmore » and private operators. When the project began, the Red River depot faced several operational problems. Existing No. 2 oil- and gas- fired boilers in three separate boiler plants were inefficient, unreliable, and difficult to maintain. Extra boilers often had to be leased to provide for needed capacity. In addition, the facility had large quantities of waste to dispose of.« less
Stewardship to tackle global phosphorus inefficiency: The case of Europe.

PubMed

Withers, Paul J A; van Dijk, Kimo C; Neset, Tina-Simone S; Nesme, Thomas; Oenema, Oene; Rubæk, Gitte H; Schoumans, Oscar F; Smit, Bert; Pellerin, Sylvain

2015-03-01

The inefficient use of phosphorus (P) in the food chain is a threat to the global aquatic environment and the health and well-being of citizens, and it is depleting an essential finite natural resource critical for future food security and ecosystem function. We outline a strategic framework of 5R stewardship (Re-align P inputs, Reduce P losses, Recycle P in bioresources, Recover P in wastes, and Redefine P in food systems) to help identify and deliver a range of integrated, cost-effective, and feasible technological innovations to improve P use efficiency in society and reduce Europe's dependence on P imports. Their combined adoption facilitated by interactive policies, co-operation between upstream and downstream stakeholders (researchers, investors, producers, distributors, and consumers), and more harmonized approaches to P accounting would maximize the resource and environmental benefits and help deliver a more competitive, circular, and sustainable European economy. The case of Europe provides a blueprint for global P stewardship.
Molecular characterization of the rhesus rhadinovirus (RRV) ORF4 gene and the RRV complement control protein it encodes.

PubMed

Mark, Linda; Spiller, O Brad; Okroj, Marcin; Chanas, Simon; Aitken, Jim A; Wong, Scott W; Damania, Blossom; Blom, Anna M; Blackbourn, David J

2007-04-01

The diversity of viral strategies to modulate complement activation indicates that this component of the immune system has significant antiviral potential. One example is the Kaposi's sarcoma-associated herpesvirus (KSHV) complement control protein (KCP), which inhibits progression of the complement cascade. Rhesus rhadinovirus (RRV), like KSHV, is a member of the subfamily Gammaherpesvirinae and currently provides the only in vivo model of KSHV pathobiology in primates. In the present study, we characterized the KCP homologue encoded by RRV, RRV complement control protein (RCP). Two strains of RRV have been sequenced to date (H26-95 and 17577), and the RCPs they encode differ substantially in structure: RCP from strain H26-95 has four complement control protein (CCP) domains, whereas RCP from strain 17577 has eight CCP domains. Transcriptional analyses of the RCP gene (ORF4, referred to herein as RCP) in infected rhesus macaque fibroblasts mapped the ends of the transcripts of both strains. They revealed that H26-95 encodes a full-length, unspliced RCP transcript, while 17577 RCP generates a full-length unspliced mRNA and two alternatively spliced transcripts. Western blotting confirmed that infected cells express RCP, and immune electron microscopy disclosed this protein on the surface of RRV virions. Functional studies of RCP encoded by both RRV strains revealed their ability to suppress complement activation by the classical (antibody-mediated) pathway. These data provide the foundation for studies into the biological significance of gammaherpesvirus complement regulatory proteins in a tractable, non-human primate model.
Molecular Characterization of the Rhesus Rhadinovirus (RRV) ORF4 Gene and the RRV Complement Control Protein It Encodes▿

PubMed Central

Mark, Linda; Spiller, O. Brad; Okroj, Marcin; Chanas, Simon; Aitken, Jim A.; Wong, Scott W.; Damania, Blossom; Blom, Anna M.; Blackbourn, David J.

2007-01-01

The diversity of viral strategies to modulate complement activation indicates that this component of the immune system has significant antiviral potential. One example is the Kaposi's sarcoma-associated herpesvirus (KSHV) complement control protein (KCP), which inhibits progression of the complement cascade. Rhesus rhadinovirus (RRV), like KSHV, is a member of the subfamily Gammaherpesvirinae and currently provides the only in vivo model of KSHV pathobiology in primates. In the present study, we characterized the KCP homologue encoded by RRV, RRV complement control protein (RCP). Two strains of RRV have been sequenced to date (H26-95 and 17577), and the RCPs they encode differ substantially in structure: RCP from strain H26-95 has four complement control protein (CCP) domains, whereas RCP from strain 17577 has eight CCP domains. Transcriptional analyses of the RCP gene (ORF4, referred to herein as RCP) in infected rhesus macaque fibroblasts mapped the ends of the transcripts of both strains. They revealed that H26-95 encodes a full-length, unspliced RCP transcript, while 17577 RCP generates a full-length unspliced mRNA and two alternatively spliced transcripts. Western blotting confirmed that infected cells express RCP, and immune electron microscopy disclosed this protein on the surface of RRV virions. Functional studies of RCP encoded by both RRV strains revealed their ability to suppress complement activation by the classical (antibody-mediated) pathway. These data provide the foundation for studies into the biological significance of gammaherpesvirus complement regulatory proteins in a tractable, non-human primate model. PMID:17287274
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
Technical efficiency of selected hospitals in Eastern Ethiopia.

PubMed

Ali, Murad; Debela, Megersa; Bamud, Tewfik

2017-12-01

This study examines the relative technical efficiency of 12 hospitals in Eastern Ethiopia. Using six-year-round panel data for the period between 2007/08 and 2012/13, this study examines the technical efficiency, total factor productivity, and determinants of the technical inefficiency of hospitals. Data envelopment analysis (DEA) and DEA- based Malmquist productivity index used to estimate relative technical efficiency, scale efficiency, and total factor productivity index of hospitals. Tobit model used to examine the determinants of the technical inefficiency of hospitals. The DEA Variable Returns to Scale (VRS) estimate indicated that 6 (50%), 5 (42%), 3 (25%), 3 (25%), 4 (33%), and 3 (25%) of the hospitals were technically inefficient while 9 (75%), 9 (75%), 7 (58%), 7 (58%), 7 (58%) and 8 (67%) of hospitals were scale inefficient between 2007/08 and 2012/13, respectively. On average, Malmquist Total Factor Productivity (MTFP) of the hospitals decreased by 3.6% over the panel period. The Tobit model shows that teaching hospital is less efficiency than other hospitals. The Tobit regression model further shows that medical doctor to total staff ratio, the proportion of outpatient visit to inpatient days, and the proportion of inpatients treated per medical doctor were negatively related with technical inefficiency of hospitals. Hence, policy interventions that help utilize excess capacity of hospitals, increase doctor to other staff ratio, and standardize number of inpatients treated per doctor would contribute to the improvement of the technical efficiency of hospitals.
Immune functions of the garment workers.

PubMed

Sultana, R; Ferdous, K J; Hossain, M; Zahid, M S H; Islam, L N

2012-10-01

Occupational exposure to cotton dust, fibers, metal fumes and different chemicals used in the aparrel manufacturing industries cause a wide range of physical and psychological health problems in the garment workers that may also affect their immune function. To assess the immune system function in garment workers. A total of 45 workers of a garment factory, and 41 control subjects, not exposed to the garment working environment were enrolled in this study. In the study subjects, the complement system function was assessed as bactericidal activity on Escherichia coli DH5α cells using the standard plate count method. Serum complement components C3 and C4 were measured by immunoprecipitation, and IgG was measured by immunonephelometry. The bactericidal activity of serum complement in the garment workers (range: 93.5%-99.9%) was significantly (p<0.01) lower than that in the controls (range: 98.6%-100%). The heat-inactivated serum of the workers showed a significantly enhanced bactericidal activity. In the garment workers, the mean levels of complement C3, and C4 were 1.75 and 0.26 g/L, respectively that were close to those of the controls. The mean IgG level in the garment workers was 13.5 g/L that was significantly (p<0.001) higher than that in the controls. Working in a garment factory may affect the immune system.
Role of the endocannabinoid system in brain functions relevant for schizophrenia: an overview of human challenge studies with cannabis or ∆9-tetrahydrocannabinol (THC).

PubMed

Bossong, Matthijs G; Jansma, J Martijn; Bhattacharyya, Sagnik; Ramsey, Nick F

2014-07-03

Accumulating evidence suggests involvement of the endocannabinoid system in the pathophysiology of schizophrenia, which signifies a potential application for this system in the treatment of this disorder. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of schizophrenia. Here we review human studies that investigated acute effects of cannabis or ∆9-tetrahydrocannabinol (THC) on brain functions that are implicated in schizophrenia. Results suggest that the impact of THC administration depends on the difficulty of the task performed. Impaired performance of cognitive paradigms is reported on more challenging tasks, which is associated with both activity deficits in temporal and prefrontal areas and a failure to deactivate regions of the default mode network. Comparable reductions in prefrontal activity and impairments in deactivation of the default mode network are seen in patients during performance of cognitive paradigms. Normal performance levels after THC administration demonstrated for less demanding tasks are shown to be related to either increased neural effort in task-specific regions ('neurophysiological inefficiency'), or recruitment of alternative brain areas, which suggests a change in strategy to meet cognitive demands. Particularly a pattern of performance and brain activity corresponding with an inefficient working memory system is consistently demonstrated in patients. These similarities in brain function between intoxicated healthy volunteers and schizophrenia patients provide an argument for a role of the endocannabinoid system in symptoms of schizophrenia, and further emphasize this system as a potential novel target for treatment of these symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.
Modular supramolecular approach for co-crystallization of donors and acceptors into ordered networks

DOEpatents

Stupp, Samuel I.; Stoddart, J. Fraser; Shveyd, Alex K.; Tayi, Alok S.; Sue, Andrew C. H.; Narayanan, Ashwin

2016-09-20

Organic charge-transfer (CT) co-crystals in a mixed stack system are disclosed, wherein a donor molecule (D) and an acceptor molecule (A) occupy alternating positions (DADADA) along the CT axis. A platform is provided which amplifies the molecular recognition of donors and acceptors and produces co-crystals at ambient conditions, wherein the platform comprises (i) a molecular design of the first constituent (.alpha.-complement), (ii) a molecular design of the second compound (.beta.-complement), and (iii) a solvent system that promotes co-crystallization.
Modular supramolecular approach for co-crystallization of donors and acceptors into ordered networks

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

Stupp, Samuel I.; Stoddart, J. Fraser; Shveyd, Alexander K.

Organic charge-transfer (CT) co-crystals in a mixed stack system are disclosed, wherein a donor molecule (D) and an acceptor molecule (A) occupy alternating positions (DADADA) along the CT axis. A platform is provided which amplifies the molecular recognition of donors and acceptors and produces co-crystals at ambient conditions, wherein the platform comprises (i) a molecular design of the first constituent (.alpha.-complement), (ii) a molecular design of the second compound (.beta.-complement), and (iii) a solvent system that promotes co-crystallization.
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.
The effects of phytase supplementation on performance and phosphorus excretion from broiler chickens fed low phosphorus-containing diets based on normal or low-phytic acid barley

USDA-ARS?s Scientific Manuscript database

: Long term application of poultry manure can lead to soil phosphorus (P) accumulation and the potential P transport into waterbodies which can contribute to eutrophication of freshwater systems. One reason for this accumulation of soil P is due to the inefficiency of poultry to utilize the P in f...
Modulation of post-stroke degenerative and regenerative processes and subacute protection by site-targeted inhibition of the alternative pathway of complement.

PubMed

Alawieh, Ali; Elvington, Andrew; Zhu, Hong; Yu, Jin; Kindy, Mark S; Atkinson, Carl; Tomlinson, Stephen

2015-12-30

Complement promotes neuroinflammation and injury in models of stroke. However, complement is also being increasingly implicated in repair and regeneration after central nervous system (CNS) injury, and some complement deficiencies have been shown to provide acute, but not subacute, protection after murine stroke. Here, we investigate the dual role of complement in injury and repair after cerebral ischemia and reperfusion. We used complement-deficient mice and different complement inhibitors in a model of transient middle cerebral artery occlusion to investigate complement-dependent cellular and molecular changes that occur through the subacute phase after stroke. C3 deficiency and site-targeted complement inhibition with either CR2-Crry (inhibits all pathways) or CR2-fH (inhibits alternative pathway) significantly reduced infarct size, reduced apoptotic cell death, and improved neurological deficit score in the acute phase after stroke. However, only in CR2-fH-treated mice was there sustained protection with no evolution of injury in the subacute phase. Whereas both inhibitors significantly reduced microglia/macrophage activation and astrogliosis in the subacute phase, only CR2-fH improved neurological deficit and locomotor function, maintained neurogenesis markers, enhanced neuronal migration, and increased VEGF expression. These findings in CR2-fH-treated mice correlated with improved performance in spatial learning and passive avoidance tasks. The complement anaphylatoxins have been implicated in repair and regenerative mechanisms after CNS injury, and in this context CR2-fH significantly reduced, but did not eliminate the generation of C5a within the brain, unlike CR2-Crry that completely blocked C5a generation. Gene expression profiling revealed that CR2-fH treatment downregulated genes associated with apoptosis, TGFβ signaling, and neutrophil activation, and decreased neutrophil infiltration was confirmed by immunohistochemistry. CR2-fH upregulated genes for neural growth factor and mediators of neurogenesis and neuronal migration. Live animal imaging demonstrated that following intravenous injection, CR2-fH targeted specifically to the post-ischemic brain, with a tissue half-life of 48.5 h. Finally, unlike C3 deficiency, targeted complement inhibition did not increase susceptibility to lethal post-stroke infection, an important consideration for stroke patients. Ischemic brain tissue-targeted and selective inhibition of alternative complement pathway provide self-limiting inhibition of complement activation and reduces acute injury while maintaining complement-dependent recovery mechanisms into the subacute phase after stroke.
Eliminating Factor H-Binding Activity of Borrelia burgdorferi CspZ Combined with Virus-Like Particle Conjugation Enhances Its Efficacy as a Lyme Disease Vaccine.

PubMed

Marcinkiewicz, Ashley L; Lieknina, Ilva; Kotelovica, Svetlana; Yang, Xiuli; Kraiczy, Peter; Pal, Utpal; Lin, Yi-Pin; Tars, Kaspars

2018-01-01

The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the US and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H (FH). To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds FH to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because FH-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating FH binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating FH-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents.

Characterization and expression analysis of a complement component gene in sea cucumber ( Apostichopus japonicus)

NASA Astrophysics Data System (ADS)

Chen, Zhong; Zhou, Zunchun; Yang, Aifu; Dong, Ying; Guan, Xiaoyan; Jiang, Bei; Wang, Bai

2015-12-01

The complement system plays a crucial role in the innate immune system of animals. It can be activated by distinct yet overlapping classical, alternative and lectin pathways. In the alternative pathway, complement factor B (Bf) serves as the catalytic subunit of complement component 3 (C3) convertase, which plays the central role among three activation pathways. In this study, the Bf gene in sea cucumber ( Apostichopus japonicus), termed AjBf, was obtained by rapid amplification of cDNA ends (RACE). The full-length cDNA of AjBf was 3231 bp in length barring the poly (A) tail. It contained an open reading frame (ORF) of 2742 bp encoding 913 amino acids, a 105 bp 5'-UTR (5'-terminal untranslated region) and a 384 bp 3'-UTR. AjBf was a mosaic protein with six CCP (complement control protein) domains, a VWA (von Willebrand factor A) domain, and a serine protease domain. The deduced molecular weight of AjBf protein was 101 kDa. Quantitative real time PCR (qRT-PCR) analysis indicated that the expression level of AjBf in A. japonicus was obviously higher at larval stage than that at embryonic stage. Expression detection in different tissues showed that AjBf expressed higher in coelomocytes than in other four tissues. In addation, AjBf expression in different tissues was induced significantly after LPS or PolyI:C challenge. These results indicated that AjBf plays an important role in immune responses to pathogen infection.
Steroids and triterpenes from the fruit bodies of Ganoderma lucidum and their anti-complement activity.

PubMed

Seo, Hyo Won; Hung, Tran Manh; Na, MinKyun; Jung, Hyun Ju; Kim, Jin Cheol; Choi, Jae Sue; Kim, Jung Hee; Lee, Hyeong-Kyu; Lee, IkSoo; Bae, KiHwan; Hattori, Masao; Min, Byung Sun

2009-11-01

To determine the anti-complement activity of natural triterpenes, chromatographic separation of the EtOAc-soluble fraction from the fruiting body of Ganoderma lucidum led to the isolation of three steroids and five triterpenoids. They were identified as ergosterol peroxide (1), ergosterol (2), genoderic acid Sz (3), stella sterol (4), ganoderic aic C1 (5), ganoderic acid A (6), methyl ganoderate A (7), and lucidenic acid A (8) based on spectroscopic evidence and physicochemical properties. These compounds were examined for their anti-complement activity against the classical pathway of the complement system. Compounds 2 and 3 showed potent anti-complement activity with IC50 values of 52.0 and 44.6 microM, respectively. Compound 1 exhibited significant inhibitory activity with an IC50 value of 126.8 microM, whereas compounds 4-8 were inactive. Our findings suggested that in addition to the ketone group at C-3, the delta7(8), delta9(11)-lanostadiene type triterpene also plays an important role in inhibiting the hemolytic activity of human serum against erythrocytes.
Homocores, Cores and Operational Inefficiency in Superadditive N-Person Games.

DTIC Science & Technology

1983-02-01

MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS -963-A ’I .. . Re,, arch Report CCS 456 HOMOCO.S S, WOkLS AND OPLP AI [OW \\l INEFFICIENCY...modifications were made in L. Johanssen’s working papers at The Econometric Institute of The University of Oslo in 1981 and in Aumann [1981]. Yet we know
33 CFR 55.11 - How are child development center fees established?

Code of Federal Regulations, 2010 CFR

2010-07-01

... each Command with responsibility for a center-based program, according to the following total family income chart: Total Family Income $0 to $23,000 $23,001 to $34,000 $34,001 to $44,000 $44,001 to $55,000... care, unless it is uneconomical and inefficient. If uneconomical and inefficient, then the fees may be...
Bachelor's Degree Productivity X-Inefficiency: The Role of State Higher Education Policy

ERIC Educational Resources Information Center

Titus, Marvin A.

2010-01-01

Using stochastic frontier analysis and dynamic fixed-effects panel modeling, this study examines how changes in the x-inefficiency of bachelor's degree production are influenced by changes in state higher education policy. The findings from this research show that increases in need-based state financial aid help to mitigate the convergence among…
Modeling cross-correlations and efficiency of Islamic and conventional banks from Saudi Arabia: Evidence from MF-DFA and MF-DXA approaches

NASA Astrophysics Data System (ADS)

Mensi, Walid; Hamdi, Atef; Shahzad, Syed Jawad Hussain; Shafiullah, Muhammad; Al-Yahyaee, Khamis Hamed

2018-07-01

This paper analyzes the dynamic efficiency and interdependence of Islamic and conventional banks of Saudi Arabia. This analysis applies the Multifractal Detrended Fluctuation Analysis (MF-DFA) and Multifractal Detrended Cross-Correlation Analysis (MF-DXA) approaches. The MF-DFA results show strong multifractality in the daily returns of Saudi banks. Moreover, all eight banks studied exhibit persistence correlation, which demonstrates inefficiency. The rolling window results show significant change in the inefficiency levels over the time. The cross-correlation analysis between bank-pairs exhibits long term interdependence between most of them. These findings indicate that the banking sector in Saudi Arabia suffers from inefficiency and exhibits long term memory.
Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi.

PubMed

Bhattacharjee, Arnab; Oeemig, Jesper S; Kolodziejczyk, Robert; Meri, Taru; Kajander, Tommi; Lehtinen, Markus J; Iwaï, Hideo; Jokiranta, T Sakari; Goldman, Adrian

2013-06-28

Borrelia burgdorferi spirochetes that cause Lyme borreliosis survive for a long time in human serum because they successfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is needed for this because it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis. To understand this process at the molecular level, we used a structural approach. First, we solved the solution structure of OspE by NMR, revealing a fold that has not been seen before in proteins involved in complement regulation. Next, we solved the x-ray structure of the complex between OspE and the FH C-terminal domains 19 and 20 (FH19-20) at 2.83 Å resolution. The structure shows that OspE binds FH19-20 in a way similar to, but not identical with, that used by endothelial cells to bind FH via glycosaminoglycans. The observed interaction of OspE with FH19-20 allows the full function of FH in down-regulation of complement activation on the bacteria. This reveals the molecular basis for how B. burgdorferi evades innate immunity and suggests how OspE could be used as a potential vaccine antigen.
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.
Targeted complement inhibition as a promising strategy for preventing inflammatory complications in hemodialysis

PubMed Central

DeAngelis, Robert A.; Reis, Edimara S.; Ricklin, Daniel; Lambris, John D.

2012-01-01

Hemodialysis is the most common method used to remove waste and hazardous products of metabolism in patients suffering from renal failure. Hundreds of thousands of people with end-stage renal disease undergo hemodialysis treatment in the United States each year. Strikingly, the 5-year survival rate for all dialysis patients is only 35%. Most of the patients succumb to cardiovascular disease that is exacerbated by the chronic induction of inflammation caused by contact of the blood with the dialysis membrane. The complement system, a strong mediator of pro-inflammatory networks, is a key contributor to such biomaterial-induced inflammation. Though only evaluated in experimental ex vivo settings, specific targeting of complement activation during hemodialysis has uncovered valuable information that points towards the therapeutic use of complement inhibitors as means to control the unwelcomed inflammatory responses and consequent pathologies in hemodialysis patients. PMID:22964235
Harvesting of novel polyhydroxyalkanaote (PHA) synthase encoding genes from a soil metagenome library using phenotypic screening.

PubMed

Schallmey, Marcus; Ly, Anh; Wang, Chunxia; Meglei, Gabriela; Voget, Sonja; Streit, Wolfgang R; Driscoll, Brian T; Charles, Trevor C

2011-08-01

We previously reported the construction of metagenomic libraries in the IncP cosmid vector pRK7813, enabling heterologous expression of these broad-host-range libraries in multiple bacterial hosts. Expressing these libraries in Sinorhizobium meliloti, we have successfully complemented associated phenotypes of polyhydroxyalkanoate synthesis mutants. DNA sequence analysis of three clones indicates that the complementing genes are homologous to, but substantially different from, known polyhydroxyalkanaote synthase-encoding genes. Thus we have demonstrated the ability to isolate diverse genes for polyhydroxyalkanaote synthesis by functional complementation of defined mutants. Such genes might be of use in the engineering of more efficient systems for the industrial production of bioplastics. The use of functional complementation will also provide a vehicle to probe the genetics of polyhydroxyalkanaote metabolism and its relation to carbon availability in complex microbial assemblages. 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
An ecoimmunological approach to study evolutionary and ancient links between coagulation, complement and Innate immunity

PubMed Central

Kasetty, Gopinath; Alyafei, Saud; Smeds, Emanuel; Salo-Ahen, Outi M. H.; Hansson, Stefan R.; Egesten, Arne; Herwald, Heiko

2018-01-01

ABSTRACT Coagulation, complement, and innate immunity are tightly interwoven and form an alliance that can be traced back to early eukaryotic evolution. Here we employed an ecoimmunological approach using Tissue Factor Pathway Inhibitor (TFPI)-1-derived peptides from the different classes of vertebrates (i.e. fish, reptile, bird, and mammals) and tested whether they can boost killing of various human bacterial pathogens in plasma. We found signs of species-specific conservation and diversification during evolution in these peptides that significantly impact their antibacterial activity. Though all peptides tested executed bactericidal activity in mammalian plasma (with the exception of rodents), no killing was observed in plasma from birds, reptiles, and fish, pointing to a crucial role for the classical pathway of the complement system. We also observed an interference of these peptides with the human intrinsic pathway of coagulation though, unlike complement activation, this mechanism appears not to be evolutionary conserved. PMID:29473457
A pore-forming protein implements VLR-activated complement cytotoxicity in lamprey.

PubMed

Wu, Fenfang; Feng, Bo; Ren, Yong; Wu, Di; Chen, Yue; Huang, Shengfeng; Chen, Shangwu; Xu, Anlong

2017-01-01

Lamprey is a basal vertebrate with a unique adaptive immune system, which uses variable lymphocyte receptors (VLRs) for antigen recognition. Our previous study has shown that lamprey possessed a distinctive complement pathway activated by VLR. In this study, we identified a natterin family member-lamprey pore-forming protein (LPFP) with a jacalin-like lectin domain and an aerolysin-like pore-forming domain. LPFP had a high affinity with mannan and could form oligomer in the presence of mannan. LPFP could deposit on the surface of target cells, form pore-like complex resembling a wheel with hub and spokes, and mediate powerful cytotoxicity on target cells. These pore-forming proteins along with VLRs and complement molecules were essential for the specific cytotoxicity against exogenous pathogens and tumor cells. This unique cytotoxicity implemented by LPFP might emerge before or in parallel with the IgG-based classical complement lytic pathway completed by polyC9.
Dual-Color Click Beetle Luciferase Heteroprotein Fragment Complementation Assays

PubMed Central

Villalobos, Victor; Naik, Snehal; Bruinsma, Monique; Dothager, Robin S.; Pan, Mei-Hsiu; Samrakandi, Mustapha; Moss, Britney; Elhammali, Adnan; Piwnica-Worms, David

2010-01-01

Summary Understanding the functional complexity of protein interactions requires mapping biomolecular complexes within the cellular environment over biologically-relevant time scales. Herein we describe a novel set of reversible, multicolored heteroprotein complementation fragments based on various firefly and click beetle luciferases that utilize the same substrate, D-luciferin. Luciferase heteroprotein fragment complementation systems enabled dual-color quantification of two discreet pairs of interacting proteins simultaneously or two distinct proteins interacting with a third shared protein in live cells. Using real-time analysis of click beetle green and click beetle red luciferase heteroprotein fragment complementation applied to β-TrCP, an E3-ligase common to the regulation of both β-catenin and IκBα, GSK3β was identified as a novel candidate kinase regulating IκBα processing. These dual-color protein interaction switches may enable directed dynamic analysis of a variety of protein interactions in living cells. PMID:20851351
Subglacial Hydrology Model Intercomparison Project (SHMIP)

NASA Astrophysics Data System (ADS)

Werder, Mauro A.; de Fleurian, Basile; Creyts, Timothy T.; Damsgaard, Anders; Delaney, Ian; Dow, Christine F.; Gagliardini, Olivier; Hoffman, Matthew J.; Seguinot, Julien; Sommers, Aleah; Irarrazaval Bustos, Inigo; Downs, Jakob

2017-04-01

The SHMIP project is the first intercomparison project of subglacial drainage models (http://shmip.bitbucket.org). Its synthetic test suites and evaluation were designed such that any subglacial hydrology model producing effective pressure can participate. In contrast to ice deformation, the physical processes of subglacial hydrology (which in turn impacts basal sliding of glaciers) are poorly known. A further complication is that different glacial and geological settings can lead to different drainage physics. The aim of the project is therefore to qualitatively compare the outputs of the participating models for a wide range of water forcings and glacier geometries. This will allow to put existing studies, which use different drainage models, into context and will allow new studies to select the most suitable model for the problem at hand. We present the results from the just completed intercomparison exercise. Twelve models participated: eight 2D and four 1D models; nine include both an efficient and inefficient system, the other three one of the systems; all but two models use R-channels as efficient system, and/or a linked-cavity like inefficient system, one exception uses porous layers with different characteristic for each of the systems, the other exception is based on canals. The main variable used for the comparison is effective pressure, as that is a direct proxy for basal sliding of glaciers. The models produce large differences in the effective pressure fields, in particular for higher water input scenarios. This shows that the selection of a subglacial drainage model will likely impact the conclusions of a study significantly.
Attention mechanisms in visual search -- an fMRI study.

PubMed

Leonards, U; Sunaert, S; Van Hecke, P; Orban, G A

2000-01-01

The human visual system is usually confronted with many different objects at a time, with only some of them reaching consciousness. Reaction-time studies have revealed two different strategies by which objects are selected for further processing: an automatic, efficient search process, and a conscious, so-called inefficient search [Treisman, A. (1991). Search, similarity, and integration of features between and within dimensions. Journal of Experimental Psychology: Human Perception and Performance, 17, 652--676; Treisman, A., & Gelade, G. (1980). A feature integration theory of attention. Cognitive Psychology, 12, 97--136; Wolfe, J. M. (1996). Visual search. In H. Pashler (Ed.), Attention. London: University College London Press]. Two different theories have been proposed to account for these search processes. Parallel theories presume that both types of search are treated by a single mechanism that is modulated by attentional and computational demands. Serial theories, in contrast, propose that parallel processing may underlie efficient search, but inefficient searching requires an additional serial mechanism, an attentional "spotlight" (Treisman, A., 1991) that successively shifts attention to different locations in the visual field. Using functional magnetic resonance imaging (fMRI), we show that the cerebral networks involved in efficient and inefficient search overlap almost completely. Only the superior frontal region, known to be involved in working memory [Courtney, S. M., Petit, L., Maisog, J. M., Ungerleider, L. G., & Haxby, J. V. (1998). An area specialized for spatial working memory in human frontal cortex. Science, 279, 1347--1351], and distinct from the frontal eye fields, that control spatial shifts of attention, was specifically involved in inefficient search. Activity modulations correlated with subjects' behavior best in the extrastriate cortical areas, where the amount of activity depended on the number of distracting elements in the display. Such a correlation was not observed in the parietal and frontal regions, usually assumed as being involved in spatial attention processing. These results can be interpreted in two ways: the most likely is that visual search does not require serial processing, otherwise we must assume the existence of a serial searchlight that operates in the extrastriate cortex but differs from the visuospatial shifts of attention involving the parietal and frontal regions.
Runoff production from intercrater plains on Mars

NASA Astrophysics Data System (ADS)

Irwin, R. P., III; Matsubara, Y.; Cawley, J. C.

2016-12-01

Ancient fluvial paleochannels and paleolakes constrain the hydrology of a wetter epoch in the early history of Mars. The cross-sectional dimensions of fluvial channels scale with discharge, watershed topography is generally well preserved, and adjustments can be made for gravity. These factors have supported conservative estimates of runoff production during event floods more than 3.5 billion years ago. Assuming weak channel banks, such that discharge is low per unit channel width, event floods in smaller watersheds had estimated runoff production of 1 cm/day. Highland surfaces generated runoff inefficiently, such that channel width increases with only the 0.3 power of watershed area. Inefficient runoff production on Mars is also suggested by new landscape evolution modeling. In long-term simulations that accurately reproduce the present landscape, forming and degrading all of the Middle and Late Noachian impact craters in selected study areas, inefficient runoff production is needed to degrade craters without intensely dissecting intercrater surfaces. The model shows that discharge generally cannot increase at more than the 0.3 power of watershed area. Paleolakes provide useful constraints on paleohydrology over intermediate timescales of years to millennia. Most local highland basins were never integrated into regional drainage systems, but some have both a contributing valley network and an outlet valley, indicating that they overflowed. Paleolake overflows require a medium-term water supply that exceeds losses to evaporation. Reasonable evaporation of 0.1 to 1 m/yr and watersheds that are mostly >10 times the area of overflowed paleolakes suggest runoff production of <0.1 m per year. Event floods were both moderate and rare during peak fluvial conditions on Mars. Over the bulk of the Middle and Late Noachian Epochs, the loss of small craters, scarp retreat, and basin infilling suggest less intense fluvial activity along with weathering, impact gardening, and lesser aeolian erosion. Low drainage density is an obvious explanation for inefficient runoff production, but it may be the consequence of moderate rainfall or snowmelt, as well as incision of valley networks over a finite timescale.
Air traffic management as principled negotiation between intelligent agents

NASA Technical Reports Server (NTRS)

Wangermann, J. P.

1994-01-01

The major challenge facing the world's aircraft/airspace system (AAS) today is the need to provide increased capacity, while reducing delays, increasing the efficiency of flight operations, and improving safety. Technologies are emerging that should improve the performance of the system, but which could also introduce uncertainty, disputes, and inefficiency if not properly implemented. The aim of our research is to apply techniques from intelligent control theory and decision-making theory to define an Intelligent Aircraft/Airspace System (IAAS) for the year 2025. The IAAS would make effective use of the technical capabilities of all parts of the system to meet the demand for increased capacity with improved performance.
Laser-SPS systems analysis and environmental impact assessment

NASA Technical Reports Server (NTRS)

Beverly, R. E., III

1980-01-01

The systems feasibility and environmental impact of replacing the microwave transmitters on the Satellite Power System with laser transmitters are examined. The lasers suggested are two molecular-gas electric-discharge lasers (EDL's), namely the CO and CO2 lasers. Calculations are made on system efficiency, atmospheric transmission efficiency, and laser beam spreading. It is found that the present satellite concept using lasers is far too inefficient and massive to be economically viable. However, the safety issues associated with laser power transmission appear tractable, and no effects could be identified which present a real danger of serious injury to the environment, although certain phenomena deserve closer scrutiny.
The Complement System in Flavivirus Infections

PubMed Central

Conde, Jonas N.; Silva, Emiliana M.; Barbosa, Angela S.; Mohana-Borges, Ronaldo

2017-01-01

The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein. This polyprotein is further processed by viral and host proteases into three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) that are involved in viral replication and pathogenicity. The complement system has been described to play an important role in flavivirus infection either by protecting the host and/or by influencing disease pathogenesis. In this mini-review, we will explore the role of complement system inhibition and/or activation against infection by the Flavivirus genus, with an emphasis on dengue and West Nile viruses. PMID:28261172
Split luciferase complementation assay for the analysis of G protein-coupled receptor ligand response in Saccharomyces cerevisiae.

PubMed

Fukutani, Yosuke; Ishii, Jun; Kondo, Akihiko; Ozawa, Takeaki; Matsunami, Hiroaki; Yohda, Masafumi

2017-06-01

The budding yeast Saccharomyces cerevisiae is equipped with G protein-coupled receptors (GPCR). Because the yeast GPCR signaling mechanism is partly similar to that of the mammalian system, S. cerevisiae can be used for a host of mammalian GPCR expression and ligand-mediated activation assays. However, currently available yeast systems require several hours to observe the responses because they depend on the expression of reporter genes. In this study, we attempted to develop a simple GPCR assay system using split luciferase and β-arrestin, which are independent of the endogenous S. cerevisiae GPCR signaling pathways. We applied the split luciferase complementation assay method to S. cerevisiae and found that it can be used to analyze the ligand response of the human somatostatin receptor in S. cerevisiae. On the contrary, the response of the pheromone receptor Ste2 was not observed by the assay. Thus, the split luciferase complementation should be free from the effect of the endogenous GPCR signaling. Biotechnol. Bioeng. 2017;114: 1354-1361. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.
[Complement deficiencies and meningococcal disease in The Netherlands].

PubMed

Swart, A G; Fijen, C A; te Bulte, M T; Daha, M R; Dankert, J; Kuijper, E J

1993-06-05

To determine the prevalence of complement system deficiencies in patients who have survived a Neisseria meningitidis infection. Retrospective. Reference laboratory for bacterial meningitis of the University of Amsterdam and the National Institute of Public Health and Environmental Protection. Out of the files of the laboratory 187 patients who had experienced a meningococcal infection in the Netherlands between 1959-1990 were selected in two groups according to the infecting bacterial strain: 97 patients with a serogroup X, Y, Z, W135, 29E, or non-groupable strains and 90 patients with an infection due to serogroup A or C. The patients were asked for their cooperation by their family doctor and one of us visited the patients at home to take blood samples. The complement activity was studied with a haemolysis in gel test and with an assay of haemolytic activity in free solution. Complement deficiency was present in 18% of the 187 patients who had experienced a meningococcal infection. The highest prevalence was found in patients older than 10 years who had developed infections due to serogroups X, Y, W135, or non-groupable strains (45%). Of the patients with a serogroup A or C infection, 3% had an complement deficiency. Of the complement deficiencies, 42% concerned a component of the alternative pathway, 12% a deficiency of C3, and 46% a component of the terminal route. The most commonly found deficiencies were properdin deficiency (39%) and C8 deficiency (18%). 30% of the complement deficient patients reported other family members having experienced meningitis. Recurrent meningitis was only observed in patients with terminal route deficiencies. We recommend that patients with a meningococcal infection due to serogroups X, Y, W135 or non-groupable strains should be screened for complement deficiency.
How efficiently do corn- and soybean-based cropping systems use water? A systems modeling analysis.

PubMed

Dietzel, Ranae; Liebman, Matt; Ewing, Robert; Helmers, Matt; Horton, Robert; Jarchow, Meghann; Archontoulis, Sotirios

2016-02-01

Agricultural systems are being challenged to decrease water use and increase production while climate becomes more variable and the world's population grows. Low water use efficiency is traditionally characterized by high water use relative to low grain production and usually occurs under dry conditions. However, when a cropping system fails to take advantage of available water during wet conditions, this is also an inefficiency and is often detrimental to the environment. Here, we provide a systems-level definition of water use efficiency (sWUE) that addresses both production and environmental quality goals through incorporating all major system water losses (evapotranspiration, drainage, and runoff). We extensively calibrated and tested the Agricultural Production Systems sIMulator (APSIM) using 6 years of continuous crop and soil measurements in corn- and soybean-based cropping systems in central Iowa, USA. We then used the model to determine water use, loss, and grain production in each system and calculated sWUE in years that experienced drought, flood, or historically average precipitation. Systems water use efficiency was found to be greatest during years with average precipitation. Simulation analysis using 28 years of historical precipitation data, plus the same dataset with ± 15% variation in daily precipitation, showed that in this region, 430 mm of seasonal (planting to harvesting) rainfall resulted in the optimum sWUE for corn, and 317 mm for soybean. Above these precipitation levels, the corn and soybean yields did not increase further, but the water loss from the system via runoff and drainage increased substantially, leading to a high likelihood of soil, nutrient, and pesticide movement from the field to waterways. As the Midwestern United States is predicted to experience more frequent drought and flood, inefficiency of cropping systems water use will also increase. This work provides a framework to concurrently evaluate production and environmental performance of cropping systems. © 2015 John Wiley & Sons Ltd.
Military Hybrid Vehicle Survey

DTIC Science & Technology

2011-08-03

III Composite 4.3% Integrated starter generator for engine shut down, regenerative braking and avoidance of inefficient engine operation [28]. FMTV...eliminating the inefficiencies associated with idling, vehicle braking and low engine speed part load efficiency, many improvements can be realized...literature. They can be divided into the following two categories : (1) Time dependent speed profiles, shown in Figure 4, usually defined by the federal
Current State of Military Hybrid Vehicle Development

DTIC Science & Technology

2011-08-31

Integrated starter generator for engine shut down, regenerative braking and avoidance of inefficient engine operation [28]. FMTV VI Composite 6-9% Fuel...and eliminating the inefficiencies associated with idling, vehicle braking and low engine speed part load efficiency, many improvements could be...different drive cycles were being used to evaluate vehicle performance. These cycles can be divided into the following two categories : (1) Time
A Study on the Reasons for the Inefficiency of College English Teaching and Some Tentative Countermeasures

ERIC Educational Resources Information Center

Wang, Zhaogang

2014-01-01

On the basis of a survey, the reasons for the inefficiency of current College English teaching are examined. First, the traditional learning methodology is entrenched and the concepts and ideology of language teaching are outdated. Second, the social and learning environment resulted in the conflicts between the purpose of English teaching and the…
Energy Technology Investments: Maximizing Efficiency Through a Maritime Energy Portfolio Interface and Decision Aid

DTIC Science & Technology

2012-02-09

Investment (ROI) and Break Even Point ( BEP ). These metrics are essential for determining whether an initiative would be worth pursuing. Balanced...is Unlimited Energy Decision Framework Identify Inefficiencies 2. Perform Analyses 3. Examine Technology Candidates 1. Improve Energy...Unlimited Energy Decision Framework Identify Inefficiencies 2. Perform Analyses 3. Examine Technology Candidates 1. Improve Energy Efficiency 4
The Technical Efficiency of Specialised Milk Farms: A Regional View

PubMed Central

Špička, Jindřich; Smutka, Luboš

2014-01-01

The aim of the article is to evaluate production efficiency and its determinants of specialised dairy farming among the EU regions. In the most of European regions, there is a relatively high significance of small specialised farms including dairy farms. The DEAVRS method (data envelopment analysis with variable returns to scale) reveals efficient and inefficient regions including the scale efficiency. In the next step, the two-sample t-test determines differences of economic and structural indicators between efficient and inefficient regions. The research reveals that substitution of labour by capital/contract work explains the variability of the farm net value added per AWU (annual work unit) income indicator by more than 30%. The significant economic determinants of production efficiency in specialised dairy farming are farm size, herd size, crop output per hectare, productivity of energy, and capital (at α = 0.01). Specialised dairy farms in efficient regions have significantly higher farm net value added per AWU than inefficient regions. Agricultural enterprises in inefficient regions have a more extensive structure and produce more noncommodity output (public goods). Specialised dairy farms in efficient regions have a slightly higher milk yield, specific livestock costs of feed, bedding, and veterinary services per livestock unit. PMID:25050408
A micro-UAS to start prescribed fires

USGS Publications Warehouse

Beachly, Evan; Higgins, James; Laney, Christian; Elbaum, Sebastian; Detweiler, Carrick; Allen, Craig R.; Twidwell, Dirac

2017-01-01

Prescribed fires have many benefits, but existing ignition methods are dangerous, costly, or inefficient. This paper presents the design and evaluation of a micro-UAS that can start a prescribed fire from the air, while being operated from a safe distance and without the costs associated with aerial ignition from a manned aircraft. We evaluate the performance of the system in extensive controlled tests indoors. We verify the capabilities of the system to perform interior ignitions, a normally dangerous task, through the ignition of two prescribed fires alongside wildland firefighters.
The economics of stone disease.

PubMed

Canvasser, Noah E; Alken, Peter; Lipkin, Michael; Nakada, Stephen Y; Sodha, Hiren S; Tepeler, Abdulkadir; Lotan, Yair

2017-09-01

The rising prevalence of kidney stone disease is associated with significant costs to healthcare systems worldwide. This is in part due to direct procedural and medical management costs, as well as indirect costs to health systems, patients, and families. A number of manuscripts evaulating the economics of stone disease have been published since the 2008s International Consultation on Stone Disease. These highlight costs associated with stone disease, including acute management, surgical management, and medical management. This work hopes to highlight optimization in care by reducing inefficient treatments and maximizing cost-efficient preventative strategies.
Nebulized C1-Esterase Inhibitor does not Reduce Pulmonary Complement Activation in Rats with Severe Streptococcus Pneumoniae Pneumonia.

PubMed

de Beer, Friso; Lagrand, Wim; Glas, Gerie J; Beurskens, Charlotte J P; van Mierlo, Gerard; Wouters, Diana; Zeerleder, Sacha; Roelofs, Joris J T H; Juffermans, Nicole P; Horn, Janneke; Schultz, Marcus J

2016-12-01

Complement activation plays an important role in the pathogenesis of pneumonia. We hypothesized that inhibition of the complement system in the lungs by repeated treatment with nebulized plasma-derived human C1-esterase inhibitor reduces pulmonary complement activation and subsequently attenuates lung injury and lung inflammation. This was investigated in a rat model of severe Streptococcus pneumoniae pneumonia. Rats were intra-tracheally challenged with S. pneumoniae to induce pneumonia. Nebulized C1-esterase inhibitor or saline (control animals) was repeatedly administered to rats, 30 min before induction of pneumonia and every 6 h thereafter. Rats were sacrificed 20 or 40 h after inoculation with bacteria. Brochoalveolar lavage fluid and lung tissue were obtained for measuring levels of complement activation (C4b/c), lung injury and inflammation. Induction of pneumonia was associated with pulmonary complement activation (C4b/c at 20 h 1.24 % [0.56-2.59] and at 40 h 2.08 % [0.98-5.12], compared to 0.50 % [0.07-0.59] and 0.03 % [0.03-0.03] in the healthy control animals). The functional fraction of C1-INH was detectable in BALF, but no effect was found on pulmonary complement activation (C4b/c at 20 h 0.73 % [0.16-1.93] and at 40 h 2.38 % [0.54-4.19]). Twenty hours after inoculation, nebulized C1-esterase inhibitor treatment reduced total histology score, but this effect was no longer seen at 40 h. Nebulized C1-esterase inhibitor did not affect other markers of lung injury or lung inflammation. In this negative experimental animal study, severe S. pneumoniae pneumonia in rats is associated with pulmonary complement activation. Repeated treatment with nebulized C1-esterase inhibitor, although successfully delivered to the lungs, does not affect pulmonary complement activation, lung inflammation or lung injury.
East Europe Report

DTIC Science & Technology

1987-01-07

technically advanced, high quality product, but also to the perceived economic impact of a given innova- tion. This is defined for exported products...chronic woe of all socialist systems is economic inefficiency. This is apparently the one thing about which there was no disagreement at the ...International Round Table on "Socialism and Economics ," which was held from 20 through 24 October in Cavtata. In fact, if not the very existence of , then at
Acquisition Reform: DOD Should Streamline Its Decision-Making Process for Weapon Systems to Reduce Inefficiencies

DTIC Science & Technology

2015-02-01

WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) U.S. Government Accountability Office,441 G Street NW,Washington,DC,20548 8...milestone decision process; and (3) alternative processes used by some DOD programs and leading commercial firms. To perform this work , GAO...Decision Makers 27 Abbreviations ACAT Acquisition Category DOD Department of Defense This is a work of the U.S
Chile, 1964-74: The Successes and Failures of Reformism

DTIC Science & Technology

1975-09-22

upon mining for a majur portion or government revenue, saddled with an agricultural system characterized by the inequities and inefficiencies of...the most votes Allende and Alessandri. The Alessandri forces , in a gambit to upset traditional practice and invalidate the election, attempted a...and Alknde’s contradictory "peaceful transition to socialism" bring the country to the brink of civil war, the Armed Forces decided to dispense with
Educational Choice: Answers to the Most Frequently Asked Questions about Mediocrity in American Education and What Can Be Done about It. Wisconsin Policy Research Institute Report, Volume 2, No. 3.

ERIC Educational Resources Information Center

Chubb, John E.; Moe, Terry M.

Parental choice represents a promising approach to school improvement; it eliminates the excessive regulation, inefficient operation, and ineffective service that characterize the public monopolies that American schools and school systems have become. However, school reformers should bear in mind the following key points: (1) school performance…
An Analysis of Implementation of the Defense Travel System at the Naval Postgraduate School

DTIC Science & Technology

2002-03-01

processing called the Shared Services Office. The justification for this reorganization decision was to eliminate some inefficiency in the travel process...Table 2 shows the pros, cons, and issues surrounding the decision to create a Shared Services Office. Travel Manager was also modified to submit...service Location/space issues Expertise is centralized Travelers waiting for shared services concept to fail Coordinating the best order for
Quantum Tomography Protocols with Positivity are Compressed Sensing Protocols (Open Access)

DTIC Science & Technology

2015-12-08

ARTICLE OPEN Quantum tomography protocols with positivity are compressed sensing protocols Amir Kalev1, Robert L Kosut2 and Ivan H Deutsch1...Characterising complex quantum systems is a vital task in quantum information science. Quantum tomography, the standard tool used for this purpose, uses a well...designed measurement record to reconstruct quantum states and processes. It is, however, notoriously inefficient. Recently, the classical signal
Universalization of Primary Education in Colombia: The New School Programme. Notes, Comments... No. 191 = Colombie: L'enseignement primaire pour tous le programme "Ecole nouvelle."

ERIC Educational Resources Information Center

Colbert, Vicky; Arboleda, Jairo

For the first time, Colombia is in a position to comply with the article of her constitution which guarantees a primary education to all citizens. The country now has the technical, political and financial conditions necessary to universalize primary education, particularly in rural areas where low coverage and inefficiency of the system have…
Automation-induced monitoring inefficiency: role of display location.

PubMed

Singh, I L; Molloy, R; Parasuraman, R

1997-01-01

Operators can be poor monitors of automation if they are engaged concurrently in other tasks. However, in previous studies of this phenomenon the automated task was always presented in the periphery, away from the primary manual tasks that were centrally displayed. In this study we examined whether centrally locating an automated task would boost monitoring performance during a flight-simulation task consisting of system monitoring, tracking and fuel resource management sub-tasks. Twelve nonpilot subjects were required to perform the tracking and fuel management tasks manually while watching the automated system monitoring task for occasional failures. The automation reliability was constant at 87.5% for six subjects and variable (alternating between 87.5% and 56.25%) for the other six subjects. Each subject completed four 30 min sessions over a period of 2 days. In each automation reliability condition the automation routine was disabled for the last 20 min of the fourth session in order to simulate catastrophic automation failure (0 % reliability). Monitoring for automation failure was inefficient when automation reliability was constant but not when it varied over time, replicating previous results. Furthermore, there was no evidence of resource or speed accuracy trade-off between tasks. Thus, automation-induced failures of monitoring cannot be prevented by centrally locating the automated task.

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